Category Archive Neurology

Manual Test and Examination of Spine

Manual Test and Examination of Spine is an essential skill to master that will benefit you throughout your medical and surgical career. This article describes the basic anatomy and surface markings of the spine that will aid your examination and also discusses diagnostic tests for common pathologies. The special tests in the spine examination allow clinicians to tailor the examination to the pathology that they are trying to confirm or refute. Details of the tests for scoliosis, myelopathy, cervical and lumbar radiculopathy are also included.

A good physical examination is an art that improves with more exposure and experiences. That being said, as with any art form, having an appropriate resource to reference and guide one’s experience is vital to success. “Physical Examination of the Spine” is that guide.

Examination of the spine is an essential skill to master that will benefit you throughout your medical and surgical career. This article describes the basic anatomy and surface markings of the spine that will aid your examination and also discusses diagnostic tests for common pathologies. The special tests in the spine examination allow clinicians to tailor the examination to the pathology that they are trying to confirm or refute

Examination of Spine

The purpose of clinical examination is many.  First and foremost, the identification of patients who need emergent or urgent care and treatment, and then, identify the cause of the patient’s symptoms, its impact on the patient, and the needs and expectations of the patient. Any associated medical conditions that have an impact on the treatment of the primary condition should also be identified. Proper physical examination achieves these objectives and allows the clinician to develop a healthy rapport with the patient as well.

The information generated from the history and examination must differentiate normal from abnormal, provide a reliable measure of the abnormality, and permit a valid interpretation. It should fulfill the criteria of normality, reliability, validity, utility, compliance, and cost-effectiveness. (Waddell 1982)

Examination of the spine involves 2 steps: history taking and physical examination. A detailed and chronological history and a structured clinical examination are essential for diagnosis. History taking provides information about the past and the present health status of the patient, his symptoms, and the disease. It helps in the assessment of disability caused by the disease. History provides the foundation for making decisions regarding the working diagnosis,  investigations needed for workup, treatment options, follow-up, outcome analysis, prognostication, and prevention.

History taking

History taking is an art. The clinician should learn to talk less and listen more. It should be detailed and chronological. History taking is divided into various components such as presenting complaint, history of presenting complaint, treatment history, past history, personal history, family history, occupational history, nutritional history etc. Depending on the setting of the patient interview, either some or all these components may have to be gone into.

History taking starts with simple, open-ended questions that allow the patient to communicate her perception of the problem and to let the surgeon understand the treatment goals. Later more focussed questions should be asked to get specific details about various aspects of the symptoms. The questions should be simple, clear, unambiguous and phrased in the patient’s own everyday language. It should avoid medical terminology and inappropriate cultural assumptions (Waddell 1982). The information sought should be within the patient’s knowledge.

History taking helps in the localization of the symptoms to the diseased part, discern the evolution of symptoms, identify the underlying pathology and elucidate the effect of the disease on the patient. It helps in identifying the associations and co-morbidities. The root cause of symptoms in spine patients may be vertebral, paravertebral, or referred. It may be musculoskeletal, neurological, or combined. Vertebral causes may present with pain, deformity, limitation of movement, swelling, or functional limitation. Neurological causes may present with upper motor or lower motor neuron symptoms. Neurological symptoms may be sensory, motor or sphincter related.

The most common presenting complaint is pain. Pain may be somatic, visceral, neurogenic, or psychosomatic. Somatic pain is due to local causes which can be mechanical or non-mechanical. Mechanical pain may be discogenic, capsuloligamentous, or stenotic in origin. Discogenic pain may be disco-dural or disco-radicular. Disco-dural pain presents with acute lumbago, chronic backache, or sciatica. Disco-radicular symptoms pain that radiating pain or neurological deficit in the body area supplied by the roots affected and occur when the neuronal cell bodies in the dorsal root ganglion situated within the intervertebral foramen are chemically or mechanically irritated by various causes; most commonly by a prolapsed disc. Mechanical causes of pain may be herniated nucleus pulposus, osteoarthritis, spinal canal stenosis, spondylolisthesis, or compression fracture. Non-mechanical causes may be inflammatory spondylarthritis, infective spondylitis, tumors, osteoporotic fractures, or visceral causes.

Pain due to spinal canal stenosis presents with unilateral or bilateral neurogenic claudication. Neurogenic claudication is worsened by standing or walking and is relieved by sitting, squatting, or stooping forwards. It is often associated with neurological symptoms such as weakness, numbness, or sphincter disturbance. Dural and root symptoms and signs are generally absent.

The cause of the pain may be identified from patient history based on the site of pain, onset, duration, radiation, relation to activity, and posture. Somatic pain is sharp, localized, and worsened by activity. Visceral pain is poorly localized and not affected by activity or rest. Neurogenic pain is burning or pricking the type of pain felt along the involved dermatomes. Psychosomatic pain is due to underlying psychological diseases and is a diagnosis by exclusion of other causes by detailed evaluation.

The site of pain is described as per the anatomic borders delineated by the International Society for Study of Pain (IASP). Low back pain as the site may be lumbar, sacral, coccygeal, loin, or gluteal pain.

According to the duration of symptoms, pain of duration less than 5 weeks is considered as acute, 5 weeks to 3 months as subacute, and more than 3 months as chronic pain. Radiculopathy is defined by IASP as “Pain perceived as arising in a limb or the trunk wall caused by ectopic activation of nociceptive afferent fibers in a spinal nerve or its roots or other neuropathic mechanisms.”

Pain history

  • Duration – How long the pain is present?
  • Onset – How did it start?
  • Progress – What happened afterward?
  • Site – Where do you feel the pain, point it out with a single finger?
  • Character – What is the nature of pain? Is it throbbing, pricking, or burning type of pain?
  • The intensity of pain – What is the severity of pain at present, at rest, and during activity? How severe was the worst pain you experienced?
  • Temporal factors – Continuous or intermittent, diurnal variation.
    • Is the pain continuous or intermittent?
    • If intermittent, how long does each episode last?
    • If intermittent, is it colicky in nature?
    • Is there any relation between the severity of pain and the time of day?
    • Is there any sleep disturbance due to pain?
  • Aggravating factors.
    • Is it aggravated by activity? Suggestive of mechanical pain.
    • Is it aggravated when getting up in the morning? If yes, how long does the increased pain last? Morning stiffness is present if the pain lasts for more than one hour. Morning stiffness is suggestive of inflammatory spondyloarthropathy.
    • Is it aggravated by walking? Suggestive of vascular or neurogenic claudication.
    • Is it aggravated by standing? Suggestive of neurogenic claudication.
  • Relieving factors.
    • Is it relieved by activity? Suggestive of inflammatory spondyloarthropathy.
    • Is it relieved by rest? Suggestive of mechanical pain.
    • If aggravated by walking, is it relieved by standing? Suggestive of vascular claudication.
    • If aggravated by standing and walking, is it relieved by sitting down or stooping forwards? Suggestive of neurogenic claudication.
  • Associated symptoms.

History taking in spinal deformity

  • When was the deformity noticed?
  • How was the deformity noticed?
  • What happened to the severity of deformity after it was noticed?
  • Is it painful?
  • Is there any difficulty in walking?
  • Is there any weakness or numbness in the upper or lower limbs?
  • Is there any urinary retention or urinary incontinence?
  • Is there any bowel complaints?
  • Is there any exercise intolerance or exertional dyspnoea?
  • Are there any associated symptoms?
  • In girls presenting with spinal deformity, ask about age of menarche.

In history, red flag and yellow flag signs which suggest serious underlying disease should be specifically looked for.

Red flag symptoms

  • Age > 50 years
  • Duration of symptoms > 1month
  • Rest pain
  • Night pain
  • Bilateral sciatica
  • Significant neurological deficit
  • Progressive neurological deficit
  • Bowel or bladder disturbance
  • Unexplained weight loss
  • Fever
  • History of significant trauma
  • History of malignancy
  • History of steroid intake

Yellow flag symptoms

  • Denotes negative psychosocial factors that are associated with chronicity and long term disability. It may be related to work, beliefs, behaviour or affective disorders.

General Examination

Development of secondary sexual characteristics using  Tanner stages should be done in children with spinal deformity.

Tanner stages

  • Used to assess sexual age by assessing the onset and progression of pubertal changes.
  • Boys and girls assessed on a 5-point scale.
  • Boys are assessed by genital development and pubic hair growth, and girls by breast development and pubic hair growth.
  • Girls
    • Pubertal hair development
      • Stage I (Preadolescent) – Vellos hair develops over mons pubis similar to that over the anterior abdominal wall. There is no sexual hair.
      • Stage II – Appearance of sparse, long, pigmented, downy, straight or only slightly curled hair mainly along the labia.
      • Stage III – Appearance of darker, coarser, and curlier sexual hair appears sparsely over the junction of the pubes.
      • Stage IV – The hair distribution similar to adult but decreased in total quantity. No spread to the medial surface of the thigh.
      • Stage V – Pubic hair similar to adults in quantity and appearance.  Distribution have an inverse triangle and extends to the medial surface of the thighs. No extension above the base of the inverse triangle.
    • Breast development
      • Stage I (Preadolescent) – Only the papilla is elevated above the level of the chest wall.
      • Stage II – (Breast Budding) – Elevation of the breasts and papillae above the level of chest wall may as small mounds along with increase in the diameter of the areolae.
      • Stage III – The breasts and areolae continue to enlarge, and show no difference in contour.
      • Stage IV – The areolae and papillae form secondary mounds above the level of the breast.
      • Stage V – Mature female breasts have developed. The papillae project due to recession of the areolae.
  • Boys
    • Pubertal hair development
      • Stage I (Preadolescent) – Only vellos hair over the pubes similar to that over the abdominal wall is present.
      • Stage II – Sparse long pigmented, slightly curved or straight, downy hair begins to appear.
      • Stage III –  Darker, coarser, and curlier pubic hair with its distribution spread over the junction of the pubes.
      • Stage IV – Adult type hair distribution but quantity less. No spread to the medial surface of the thighs.
      • Stage V – Adult-type hair distribution in an inverse triangle shape with extension to the medial thigh. Quantity and type are similar to adult.
    • Male genitalia development
      • Stage I (Preadolescent)- The testes, scrotal sac, and penis similar to early childhood in size and proportion.
      • Stage II – Enlargement of the scrotum and testes with changes in the texture of the scrotal skin.
      • Stage III – Along with increased growth of the testes and scrotum, there is the growth of the penis mainly in length, with some increase in diameter.
      • Stage IV – Penis and glans penis significantly enlarged in length and diameter. Testes and scrotum enlarge further with darkening of the scrotal skin.
      • Stage V – Similar to adult in size and shape.
  • Facial hair
  • Voice change
  • Signs of generalised ligamentous laxity
  • Neurocutaneous markers should be looked for in patients with scoliosis to rule out neurofibromatosis 1.
  • Height
  • Sitting height
  • Upper segment: lower segment ratio
  • Arm span

Inspection

Inspection starts with an assessment of the patient as a whole with the observation of his posture, demeanour,  and gait. Next inspect the entire vertebral column from the front, sides and back. Inspection should be done with the patient standing, sitting, supine and prone. First assess the surface anatomy of the spine.

Surface markings

  • First palpable spinous process – C2
  • Hyoid – C3
  • Adam’s apple – C4/5
  • Cricoid cartilage – C6
  • Carotid tubercles (Chassaignac tubercle) – C6
  • Most prominent spinous process- C7
  • Longest spinous process – T1
  • Sternal notch – T3/4
  • The spine of the scapula – T3
  • Inferior angle of scapula – T7
  • The highest point of the iliac crest – L4/5
  • Posterior superior iliac spine – S2

Assessment of posture

Spinal deformity is defined as a deviation from normal spinal alignment. Deformity should be defined in relation to the ‘neutral upright spinal alignment’ in asymptomatic individuals. Neutral upright spinal alignment (NUSA) position in asymptomatic individuals is determined with the patient standing with the knees and hips comfortably extended, the shoulders neutral or flexed, the neck neutral, and the gaze horizontal. If there is a limb length discrepancy of >2cm, it should be corrected by using blocks.

Assess the posture first and then look for deformities and how it is compensated. The deformity is assessed by asking the patient to stand in the NUSA position and in the forward bend position. Look for any deviation from normal and for asymmetry. In addition to deformity, look for how it is compensated either fully or partially. If alignment changes in one region, then the region above and below will develop compensatory changes to maintain global spinal alignment. Alterations and compensations can happen in the sagittal and coronal planes. Compensatory movements can occur at the hip also.

Stand on the side of the patient at a distance to get a lateral view of the patient. Drop an imaginary plumb line from the ear of the patient; the following is the normal alignment in the sagittal plane on the lateral view with regard to the plumb line.

  • Head – Through the ear lobes
  • Shoulders – Through the acromion.
  • Thorax – Bisects the chest anteroposteriorly.
  • Lumbar area – Midway between the lumbar spine and abdomen and slightly anterior to the sacroiliac joint.
  • Hips – Posterior to the hip, through the greater trochanter.
  • Knee – slightly anterior to the centre of the knee.
  • Ankle – Just in front of lateral malleolus through the tuberosity of 5th metatarsal.

Stand behind the patient to have a posterior view. On the posterior view, the plumb line passes normally as follows.

  • Head – Bisects the head through the external occipital protuberance
  • Shoulders – Midway between the shoulders.
  • Trunk – Bisects the trunk
  • Pelvis – Through the gluteal cleft.
  • Knee – Equidistant from both knees.
  • Ankle – Equidistant from both malleoli.

From the front

To assess the posture and symmetry of the spine ask the following questions.

  • Are the eyes at the same level?
  • Are the ears at the same level?
  • Is the nose in the midline?
  • Is there tilting of the head?
  • Is the head turned to one side?
  • Is the prominence of both sternocleidomastoids identical?
  • Is the concavity of both supraclavicular and infraclavicular fossa comparable?
  • Are the shoulders level?
  • Are the nipples at the same level?
  • Is the shape of the thorax comparable on both sides?
  • Is there abnormal prominence or concavity of the sternum?
  • Is the distance between the arms and trunk on both sides identical?
  • Are the anterior superior iliac spines at the same level?

From the sides

  • Is the head tilted anteriorly or posteriorly?
  • Is the head held anteriorly or posteriorly?
  • Is the neck curvature normal in the sagittal plane?
  • Does the ear lobes and acromion lie in the same line?
  • Is there anteroposterior widening or narrowing of the thorax?
  • Is the normal kyphosis of the thoracic spine maintained?
  • Is the normal lumbar lordosis present?
  • Is there anterior or posterior tilting of the pelvis?
  • How does the plumb line drop from the ear pass in relation to the shoulder, trunk and lower limb joints?

From the back

  • Is there tilting of the head?
  • Is the head turned to one side?
  • Is the prominence of paravertebral muscles identical?
  • Is there periscapular wasting?
  • Are the scapulae level?
  • Are the iliac crests at the same level?
  • Is there a rib hump?
  • Is there abnormal prominence of spinous processes?
  • Is the distance between the arms and trunk on both sides identical?
  • Is the normal curvature of the spine maintained?
  • How does the plumb line drop from the external occipital protuberance pass in relation to the shoulders, trunk and gluteal cleft?

Florence Peterson Kendall author of ‘Muscles: Testing and Function with Posture and Pain described Kendall’s postural types. 

  • Kyphosis-lordosis posture– Head held forwards, neck hyperextended, thoracic spine in long kyphosis, lumbar spine lordotic, pelvis tilted anteriorly, hips flexed and knees hyperextended.
  • Swayback posture– Head held forwards, neck hyperextended, thoracic spine in long kyphosis, lumbar spine flattened or slightly flexed, pelvis tilted posteriorly, hips hyperextended, knees hyperextended and ankle in neutral.
  • Military type posture– Head neutral, neck straight, thoracic spine neutral or flattened, lumbar spine hyperextended, pelvis tilted anteriorly, knees hyperextended and ankles slightly plantarflexed.
  • Flatback posture– Head held forwards, neck slightly extended, upper thoracic spine flexed, lower thoracic spine and lumbar spine flattened, pelvis tilted posteriorly, hips extended, knees hyperextended with plantarflexed ankles or knee flexed with ankle in dorsiflexion.

Swelling

Muscle wasting

Cutaneous abnormalities

  • Spinal dysraphism is classified into occult (occult) and open (opera). In the open type, there is a defect in the skin and posterior elements that exposes the neural elements. It includes myelomeningocele, myelocoele, hemimyelomeningocoele and hemimyelocoele. Closed spinal dysraphism with subcutaneous mass are lipomas with subcutaneous mass such as lipomeningocoele, lipomyelomeningocoele etc. The most common site is the lumbosacral.
  • A combination of 2 or more congenital midline cutaneous lesions is taken as a strong sign of spinal dysraphism. Cutaneous lesions can be subcutaneous lipomas, dermal sinuses, tails and local hypertrichosis. The most common cutaneous sign is a sacral dimple. Sacral dimple can be simple or atypical. Simple dimple is <0.5mm in diameter and <2.5cm closer to the anus. Atypical dimple is >5mm in size and >2.5cm from the anus. A flame-shaped hairy patch may be seen which is called faun tail.

Palpation

Palpation helps to narrow down the cause of pain. Tenderness on palpation of specific structures helps in the identification of pain generators. Palpation starts with a feeling for the local rise of temperature with the dorsal aspect of fingers. Palpate the superficial structures first and then the deeper structures. Identify the bony landmarks. During palpation, look for tenderness, bony abnormalities or bone defects.

Deformities

Note the following points

Kyphosis

  • Location of apex
  • Extent
  • Compensatory lordosis above and below
  • Knuckle type – Prominence of a single spinous process due to collapse of a single vertebra.
  • Angular type- Collapse of 2-3 vertebra.
  • Rounded type- Collapse of several vertebrae.

Scoliosis

  • Location of apex
  • Side of convexity
  • Extent
  • Largest curve
  • Symmetry
    • Shoulder level
    • Adams forward bending test
  • Rib hump
  • Loin hump
  • Waist asymmetry
  • Pelvic obliquity
    • Decompensation
      • Head- Plumb line dropped from C7
      • Trunk- Plumb line dropped from apex of the curve
  • Flexibility of curve
    • Push-prone test
    • Side bending
    • Traction
  • Tenderness
  • Skin
  • Range of movements

Movements

Assess the range of movements in the whole of spine. Aggravation of pain in the lower limbs during extension and relief with flexion indicates spinal stenosis. Aggravation of pain during flexion and relief with extension indicates disc disease.

Measurements

  • Inter-pupillary angle– Angle between the inter-pupillary line drawn between the pupils and the horizontal reference line. Measures tilting of the head due to coronal malalignment.
  • Shoulder tilt angle – Angle between the line drawn between the right and left coracoid processes and the horizontal line. Measures the tilting of the shoulder due to coronal malalignment.
  • The angle of trunk inclination– Measured with the patient in forwarding bent position using an inclinometer. It is the angle between the horizontal reference line and the plane of the greatest rib or lumbar hump. Measures the trunk asymmetry due to axial malrotation of the vertebra.
  • Chin-Brow vertical angle– Measures the angle between a line connecting the chin to the forehead with the vertical line when the patient is viewed from the side. it assesses the coronal malalignment. Normally the lines are parallel.
  • Pelvic Obliquity– The angle subtended between the horizontal reference line and the line connecting the top of iliac crests or the ASIS on boot sides.
  • Lumbar Lordosis– Keep a tape-measure tensed between thoracic and sacral prominences when the patient is standing erect. If the maximum distance between the tape measure and the concavity of the lumbar spine is less than 2cm then the lumbar lordosis is reduced. (Waddell 1982)
  • Sciatic list– Drop a plumb line from the lower thoracic convexity and measure the offset from the gluteal cleft. (Waddell 1982)
  • Lateral flexion– Mark the point in the midaxillary line at the level of a dimple of Venus. Mark the second pint in the midaxillary line 10cm above the first mark. Ask the patient to lateral flex to the opposite side. The normal range is at least 3 cm increase in the distance between the 2 lines. (Waddell 1982)

Modified Schober test (Moll 1971)

Schober described the test in 1937. It was modified by Moll and Wright of the Arthritis research unit of Leeds in 1971 as follows.

  • Patient position – Standing.
  • Examiner position – On the back of the patient.
  • Instruments required – Measuring tap, skin marking pen.
  • Procedure – 3 marks are made. First, at the lumbosacral junction represented by a line connecting the dimple of Venus on either side. Second, 5 cm below the first line and third, 10 cm above the first line. Keep the measuring tape at the uppermost mark. Make sure that the distance between the uppermost and lowermost markings is 15cm. Ask the patient to touch the toes without bending the knee. Measure the distance between the uppermost and lowermost lines.
  • Interpretation – Normal excursion should be more than 5 cm.

Rib-pelvis distance test

  • Patient position – Standing with the upper limbs raised in front to the horizontal position.
  • Examiner position – Standing behind the patient with his hands insinuated between the inferior margin of ribs and superior edge of the iliac crest in the midaxillary line.
  • Instruments required – None.
  • Procedure – Measure the distance between the inferior margin of ribs and the superior edge of the iliac crest in fingerbreadths.
  • Interpretation – Distance of two fingerbreadths or less is considered positive for kyphosis due to osteoporotic vertebral compression fractures.  Distance less than one fingerbreadth is 88% sensitive and 46% specific for osteoporotic vertebral compression fractures.

Wall-occiput distance test

  • Patient position – Standing with the back to the wall and the heels touching the wall .
  • Examiner position – Standing on the side.
  • Instruments required – Measuring tape.
  • Procedure – Ask the patient to put the back of their head against the wall, straightening up as much as possible with the eyes level. Measure the distance between external occipital protuberance and the wall.
  • Interpretation – Inability to touch the wall is positive for kyphosis due to osteoporotic vertebral compression fractures. WO-Distance increases by 1.3cm for every osteoporotic vertebral compression fracture. WOD of 4cm had a specificity of 92% and a sensitivity of 41% for osteoporotic vertebral compression fracture. WOD of more than 6 cm had an odds ratio of 17.8 for osteoporotic vertebral compression fracture.

Kyphotic index

  • Patient position – Standing in the best upright position.
  • Examiner position – Standing behind the patient.
  • Instruments required – Skin marking pen, flexible ruler, graph paper.
  • Procedure  – Mark C7 and the lumbosacral junction. Mould the flexible ruler to the spine. Place the ruler on the graph paper and trace the outline. Measure the length and width of the thorax.
  • Interpretation – Kyphotic index is equal to thoracic width divided by thoracic length multiplied by 100. Clinical kyphosis is present if KI is > 13.

Special Tests

Neck pain maneuvers

  • Spurling’s maneuver – By turning your head and gently applying pressure, your doctor may reproduce radiating, nerve-related neck pain.
  • Manual neck distraction test – This test will help identify nerve pain in your neck. Your doctor will ask you to lift your head, which may relieve pressure on compressed nerves.

Low back and leg pain maneuvers

  • Femoral stretch test – While lying face down, your doctor will flex each knee to determine if you feel pain in your thigh. If you do, this indicates nerve compression in your lumbar spine.
  • Schober test – This test examines the range of motion in your lumbar spine. During this test, you will bend over, as if you are trying to touch your toes.
  • Trendelenburg test – This test can identify weakness in the muscles that support the hip. In this test, you’ll stand straight on one leg for 30 seconds. Your doctor will observe if your pelvis stays level.

Provocative Tests in a Spinal Examination

  • Shoulder Abduction (Relief) sign Active abduction of symptomatic arm achieved by patient placing their ipsilateral hand on their head. A positive test results in relief (or reduction) of cervical radicular symptoms.
  • Neck Distraction test Active distractive force is applied by examiner while grasping patient’s head under the occiput and chin. A positive test results in relief (or reduction) of cervical radicular symptoms.
  • L’hermitte’s sign Examiner passively flexes patient’s cervical spine. A positive test result is an electric shock-like sensation down spine or extremities.
  • Hoffman’s sign Passive snapping flexion of distal phalanx of patient’s middle finger. A positive test results in flexion-adduction of ipsilateral thumb and index finger.
  • Adson’s test Patient is instructed to inspire with chin elevated, and head rotated to the affected side. A positive test results in obliteration of radial pulse.
  • The Spurling Test – is designed to reproduce symptoms by compression of the affected nerve root. The cervical extension is used to induce/reproduce posterior bulging of the intervertebral disk. Rotation of the head causes narrowing of the neuroforamina in the cervical spine. Finally, axial compression is applied to amplify these effects with the aim of exaggerating the preexisting nerve root compression.
  • The prone instability test – The patient starts by standing on one end of the examination couch. While continuing to stand on the foot end of the couch, the patient lowers his / her torso on to the couch.  The patient can hold onto the couch’s sides for support. The examiner then palpates the lower lumbar spine to elicit tenderness. The patient then holds onto the couch and lifts his / her feet off the ground tensing the paraspinal muscles. Less pain and tenderness on repeat palpation of the lower lumbar spine while the feet are off the floor is considered positive.
  • Prone Plank/Bridge – The patient is prone and elevates his / her entire body off the couch/mat on forearms and tips of toes. The body should be parallel to the couch/mat. With adequate muscle strength, men should maintain this position for 124 +/- 72s and Women for 83 +/- 63s.
  • Supine Bridge – The patient is supine and flexes the hip and knee to keep the feet flat on the couch/mat. The arms are flexed to position the hands beside the ears. The lower part of the torso and pelvis is lifted off the couch/mat, to maintain the trunk and the thigh in a straight line. With adequate muscle strength, men should maintain this position for 188 +/- 45s and Women for 152 +/- 30s.

Clinical Tests for Instability

  • Aberrant movement on flexion-extension – The standard examination involves documenting the range of movement. The quantitative range of movement may not be as significant as the qualitative range of movement. The important feature of spinal instability is the aberrant motion that occurs when flexing and extending the spine. A catch, a painful arc, supporting the arms on the thighs, or a reversal of the lumbopelvic rhythm when standing from the flexed posture indicates instability.
  • Passive lumbar extension test – The subject lies on the examination couch. The examiner passively lifts the lower limbs to a height of 30 cm from the coach while maintaining the knee in extension and applying gentle traction on the legs. A positive test is recorded if the patient complains of “pain in the lower back region” or complains of “heaviness in the lower back” or complains that, “the lower back is coming off.” These experiences should return to normal when the leg returned to the couch. The passive lumbar extension test has the highest combined sensitivity and specificity and may be comparable to radiological findings to identify lumbosacral structural instability.
  • The prone instability test – The patient stands at the foot end of the examination couch. The patient then lowers his/her upper body to rest on the examination couch. The iliac crest should rest on the edge of the examination couch. The patient holds the sides of the examination couch for increased stability. In the first part of the test, the feet of the patient is resting on the ground. The examiner with the heel of his/her hand creates a small posterior to anterior trust at each segment of the lumbar spine. Pain, if experienced by the patient, is recorded. In the second part of the test, the patient is asked to lift the feet of the floor and steady himself /herself by holding onto the sides of the examination couch. The examiner again repeats the posterior to anterior trust with the heel of his/her hand at each lumbar segment. The test is positive if the pain created in the initial part of the test subsides when the extensor muscles of the spine are tensed by lifting the feet of the floor.

Clinical tests for endurance

  • Sorensen test – The legs of the patient are strapped onto a low platform, which is only 25 cms above the floor.  The upper end of the iliac crest is aligned to the edge of the table. The upper torso rests on the floor. At the commencement of the test, the patient extends the spine and lifts the upper torso off the floor with the arms crossed across the chest and is asked to maintain the horizontal position. The record of the time, the patient can maintain this position is documented.  Normative values: Men 146 +/- 51. Women 189 +/- 60.
  • Prone isometric chest raise – The patient lies prone on the examination couch with a pad underneath the abdomen and the arms along the sides. The patient is instructed to lift the upper trunk about 30 degrees from the table while keeping the neck flexed, and the intention is to hold the sternum of the surface of the couch. The clinician records the maximum time that the patient can hold this position. Normative values: Men 40 +/- 9. Women 52 +/- 18.
  • Prone double straight leg raise – The patient lies prone on the examination couch with the hips extended and the hands underneath the forehead. The arms are perpendicular to the body. The patient is then requested to lift both the legs off the couch until the knee is cleared off the couch. The patient should maintain normal breathing during the entire test procedure. The examiner can monitor the knee clearance by sliding a hand under the knee. The clinician records the maximum time that the patient can hold this position. Normative values: Men 38 +/- 6. Women 35 +/- 5. The prone double straight leg raise has shown to have great sensitivity and specificity.
  • Supine static chest raise – The patient lies supine on the couch with the legs extended. The hands are placed on the temples with the elbows pointing to the ceiling.  The patient is then instructed to lift the head, the arms and the upper trunk of the couch. The patient should maintain normal breathing during the entire test procedure. The clinician records the maximum time that the patient can hold this position. Normative values: Men 43 +/- 9. Women 32 +/- 5.
  • Supine double straight leg raise – The patient lies supine with the legs extended, and the arms crossed in front of the chest. The pelvis is tilted forward to increase the lumbar lordosis. The patient is then requested to lift both the legs of the floor for 30 degrees while maintaining normal breathing during the entire test procedure. To monitor the pelvic tilt, the examiner can place one hand under the lumbar spine.  The clinician records the maximum time that the patient can hold this position. Normative values: Men 28 +/- 4. Women 28 +/- 4.
  • Flexor endurance test – The patient is supine on the couch with the upper part of the body propped up on a support. The support is at an angle of 60 degrees. The legs are flexed so that the knee is at a 90-degree angle with the foot flat on the couch. The toes and feet are strapped to the couch to provide a counterbalance. In a modified procedure, the examiner sits on the edge of the couch and over the toes of the patient to provide a counterbalance. The arms are crossed across the chest towards the opposite shoulder. The support is moved back by 10 cms, and the patient is instructed to maintain the original position. The clinician records the maximum time that the patient can hold this position. Normal values: Men 144 +/- 76, Women 149 +/- 99 in normal subjects.
  • Prone Plank/Bridge – The patient lies prone on a mat. Initially, the patient lifts his / her upper torso off the mat and steadies on the elbows and forearms. The elbow is directly below the shoulder, and the forearms are straight with hands in front of the elbow. The patient then lifts the pelvis off the mat. The body is now supported on the elbow/forearm and the tips of the toes. The patient maintains a rigid horizontal position parallel to the floor. The clinician records the maximum time that the patient can hold this position. Normative values: Men 124 +/- 72s, Women 83 +/- 63s.
  • Supine Bridge – The patient lies supine with the legs flexed so that the knee is at a 90-degree angle, and the foot is flat on the couch but not touching each other. The elbows are bent, and the hands are placed on the ears. The patient then lifts the pelvis so that the shoulders, hips, and knees are in a straight line. A rigid position is maintained, and the clinician records the maximum time that the patient can hold this position. Normative values: Men 188 +/- 45s, Women 152 +/- 30s.
  • Side Plank/Bridge – The patient lies on the side on a mat. The upper part of the body is lifted off the mat and supported on the elbow of the arm below. The opposite (upper) arm crosses across the chest onto the lower shoulder. The top foot is positioned in front of the lower foot. The patient is then instructed to lift the pelvis off the floor and to maintain the trunk and the legs in a straight line. A rigid position is maintained, and the clinician records the maximum time that the patient can hold this position. Normative values: Men 95 +/- 35s, Women 74 +/- 33s.:

Waddell signs include

  • Superficial tenderness – The patient’s skin over a wide area of the lumbar skin is tender to light touch or pinch.
  • Non-anatomical tenderness – The patient experiences deep tenderness over a wide area that is not localized to one structure and crosses over non-anatomical boundaries.
  • Axial loading – Downward pressure on the top of the patient’s head elicits lumbar pain.
  • Acetabular rotation – Lumbar pain is elicited while the provider passively and simultaneously externally rotates the patient’s shoulder and pelvis together in the same plane as the patient stands. It is considered a positive test if pain occurs within the first 30 degrees of rotation.
  • Distracted straight leg raise discrepancy – The patient complains of pain during a straight leg raise during formal testing, such as when supine, but does not on distraction when the examiner extends the knee with the patient in a seated position.
  • Regional sensory disturbance –The patient experiences decreased sensation fitting a stocking-like distribution rather than a dermatomal pattern.
  • Regional weakness – Weakness, cogwheeling, or the giving way of many muscle groups that are not explained on a neuroanatomical basis.
  • Overreaction – A disproportionate and exaggerated painful response to a stimulus that is not reproduced when the same provocation is given later. These responses can include verbalization, facial expression, muscle tension, or tremor.,

Straight leg raising test

  • The straight leg raising test was described by JJ First in his doctoral thesis in 1881. He attributed the test to his teacher Charles Lasègue, hence called the Lasègue sign. He attributed the sign to be due to compression of the sciatic nerve by the hamstrings. In 1884, de Beurmann in a cadaveric study identified the stretching of the sciatic nerve by straight leg raising and attributed the pain to the stretching of the sciatic nerve.
  • Done with the patient supine. Raise the affected side with the knee in extension. Positive if the patient complains of pain in the back of thigh radiating into the calf.
  • True positive SLR is exacerbation or reproduction of pain radiating along the back of the thigh into the calf in the symptomatic side at 0-700 of limb elevation. It is a test of nerve root irritation. If a patient complains of pain in the back or gluteal region, then the test is a false positive.
  • It is highly sensitive for lower lumbosacral root compressions (0.80-0.97) but low specificity (0.40). Hence a negative SLR is more important clinically than a positive SLR.

Verification of SLR

  • Verification of SLR done to differentiate between pain due to hamstring tightness and sciatica. Verification manoeuvre Do SLR. Flex the knee slightly when pain is produced, pain disappears the limb can be raised further. Pain persists if false positive.

Variants of SLR test

  • Crossed SLR – Described by Fajersztan.  Raising of straightened contralateral limb produced symptoms on the symptomatic side. Has a high specificity of 0.90.
  • Bragaard’s test– Described by Fajersztan. Do SLR. Lower the limb slightly when pain is produced, dorsiflex the ankle. Pain reproduced if positive.
  • Bowstring test– Do SLR. Lower the limb slightly when pain is produced, Pain disappears. Press on the popliteal fossa. Pain reproduced if positive.
  • Cross-over sign– Do SLR. pain radiates into the affected limb and the opposite limb. Indicates a midline lesion, severe enough to compress nerve roots on both sides.

Slump test

  • Position of patient- Seated upright.
  • Position of examiner- Standing on the side of the patient
  • Procedure- Ask the patient to slump first. If pain is not produced then ask the patient to bring his head onto the chest, extend his knee and dorsiflex his ankle one step at a time.
  • Interpretation- Provocative sciatica is taken as a sign of neuromenigeal irritation.
  • Use- Used as an alternative for the SLR test.

Quadrant test

  • Position of patient- Standing
  • Position of examiner- Standing behind the patient
  • Procedure- Keep one hand over the patient’s contralateral shoulder and apply axial pressure. Ask the patient to hyperextend, rotate and laterally flex to the contralateral side.
  • Interpretation- Provocative pain is taken as a sign of lumbar instability.
  • Use- Used if pain cannot be produced by forwarding flexion, lateral flexion etc.

Adams forward bending test

  • Position of patient- Standing with feet together, knee extended.
  • Position of examiner- Standing behind the patient first then in front of the patient.
  • Procedure- Rule out limb length discrepancy. Ask the patient to bend forwards at the waist till the back is in the horizontal plane. Palms should be held together.
  • Interpretation- If there is a rib or loin hump present, then there is structural scoliosis with rotation.
  • Use- To differentiate between structural and non-structural scoliosis.
  • Validity of test-  For a patient with 400 structural scolioses, the test has a sensitivity of 0.83 and a specificity of 0.99.

Background- Described by William Adams in the 10th lecture of 12 lectures delivered in the Grosvenor Place School of Medicine in 1860-61 called “Lectures on the pathology and treatment of lateral and other forms of curvature of the spine”. His attention was first drawn into the rotation of vertebral bodies in scoliosis in the post mortem he conducted in 1852 on Gideon Algernon Mantell: a surgeon, geologist and palaeontologist who was one of the first to describe the dinosaur fossils.

Waddell’s nonorganic signs

Described by Prof Gordon Waddell in 1980 to identify the nonorganic or psychological component of chronic back pain. Consist of 5 categories and 8 signs

Category 1- Tenderness

  • Sign 1- Superficial tenderness: Skin over a wide area is tender to touch.
  • Sign 2- Non-anatomical tenderness: Deep tenderness over a large area that is not localized to one anatomical structure and crossing into non-anatomical areas.

Category 2- Simulation tests

  • Sign 3- Back pain on simulated tests for axial loading: Downward pressure over the top of the head elicits lumbar pain
  • Sign 4- Back pain on simulated rotation of the hips: The shoulder and hip passively rotated together in the same plane with the patient standing. Considered positive if pain appears within 300 of rotation.

Category 3- Distraction 

  • Sign 5- Straight leg raise improves when the patient is distracted: Straight leg raising painful when in supine, but not positive when the knee is extended in the seated position when the patient is distracted.

Category 4- Regional disturbances

  • Sign 6- Non-dermatomal sensory changes: Sensory loss over an area that is not in the dermatomal pattern.
  • Sign 7- Non-anatomical distribution of weakness: Weakness that cannot be explained on a neuroanatomical basis.

Category 5- Overreaction

  • Sign 8- Disproportionate and exaggerated painful response that cannot be reproduced when done later.

If three or more categories are positive then the finding is considered clinically significant. It suggests only symptom magnification or pain behavior but doesn’t rule out organic causes. Positive Waddell signs should not be considered as malingering or for secondary gain. It just indicates that in addition to treatment, the psychosocial and behavioral aspects of the illness also should be addressed. Waddell signs are associated with poorer treatment outcomes.

Tips for Success During Your Physical Exam

You may think your doctor is solely responsible for diagnosing the cause of your back or neck pain, but you also play an essential role. Think of the diagnostic process as a partnership between you and your medical team. The following tips will help ensure you’re upholding your end of the bargain:

  • If you’re in pain, say it  Don’t try to hide it, downplay it, or view it as complaining. If a maneuver during your physical exam creates pain, describe it to your doctor.
  • Get detailed – Does your pain get better when you rest? Does it radiate down your leg when you walk for more than 5 minutes? There’s no such thing as too much information, so consider writing down specific facets of your pain and bringing the list to your appointment to give your doctor the full picture of your pain.
  • Mention all your symptoms – Even if you think they are minor, subtle, or completely disconnected to your back or neck pain, mention any painful or out-of-the-ordinary symptoms to your doctor.
  • Answer your doctor’s questions honestly – Telling your doctor the truth about your medical history and symptoms will help your doctor correctly identify the cause of your pain and craft a safe, effective treatment plan.

References

Crossed Brainstem Syndromes – Causes, Symptoms, Treatment

Crossed Brainstem Syndromes/Brainstem stroke syndromes, also known as crossed brainstem syndromes, refer to a group of syndromes that occur secondary to lesions, most commonly infarcts, of the brainstem. A brainstem infarction (BSI) is a stroke that happens when blood cannot flow to your brainstem. When oxygen cannot get to an area of the brain, tissue in that area may be damaged. Your brainstem allows you to speak, hear, and swallow. It also controls your breathing, heartbeat, blood pressure, balance, and eye movements.

Brainstem infarcts are a collection of difficult-to-diagnose syndromes affecting the midbrain, the pons, and the medulla oblongata. They can cause a varied range of symptoms ranging from impairment of cranial nerves III to XII, to respiratory and cardiac dysfunction, locked-in syndrome, sleep-wake cycle alteration, and decreased consciousness and death. Early diagnosis is a must as brainstem infarction is associated with high mortality and morbidity. An adequate understanding of anatomy, physical exam, and pathophysiology is required for evaluating and managing the disease. This activity reviews the evaluation and treatment of brainstem infarction and highlights the role of the interprofessional team in assessing and treating patients with this condition.

The brainstem is composed of the midbrain, the pons, and the medulla oblongata, situated in the posterior part of the brain. It is a connection between the cerebrum, the cerebellum, and the spinal cord. Embryologically, it develops from the mesencephalon and part of the rhombencephalon, all of which originate from the neural ectoderm. The brainstem is organized internally in three laminae: tectum, tegmentum, and basis. Gray matter in the brainstem is found in clusters all along the brainstem to forming mostly the cranial nerve nuclei, the pontine nuclei, and the reticular formation. White matter in the form of various ascending and descending tracts can be found mainly in the basis lamina, which is the most anterior part. The brainstem is responsible for multiple critical functions, including respiration, cardiac rhythm, blood pressure control, consciousness, and sleep-wake cycle. The cranial nerve nuclei that are present in the brainstem have a crucial role in vision, balance, hearing, swallowing, taste, speech, motor, and sensory supply to the face. The white matter of the brainstem carries most of the signals between the brain and the spinal cord and helps with its relay and processing.

Brainstem stroke syndromes are most commonly classified anatomically.

  • Benedikt syndrome
  • Claude syndrome
  • Nothnagel syndrome
  • Weber syndrome
  • Wernekink commissure syndrome
  • Brissaud-Sicard syndrome
  • facial colliculus syndrome
  • Gasperini syndrome
  • Gellé syndrome
  • Grenet syndrome
  • inferior medial pontine syndrome (Foville syndrome)
  • lateral pontine syndrome (Marie-Foix syndrome)
  • locked-in syndrome
  • Millard-Gubler syndrome
  • Raymond syndrome
  • Raymond-Cestan syndrome
  • Avellis syndrome
  • Babinski-Nageotte syndrome
  • Cestan-Chenais syndrome
  • hemimedullary syndrome (Reinhold syndrome)
  • Jackson syndrome
  • lateral medullary syndrome (Wallenberg syndrome)
  • medial medullary syndrome (Dejerine syndrome)
  • Schmidt syndrome
  • Spiller syndrome
  • Tapia syndrome
  • Vernet syndrome (often not caused by a brainstem lesion)

The blood supply to the brainstem is mostly from the vertebrobasilar system. The blood supply can be divided into a group of arteries supplying each region:

  • Midbrain

    • Anteromedial: supplied by the posterior cerebral artery.
    • Anterolateral: supplied by the posterior cerebral artery and branches of the anterior choroidal artery.
    • Lateral: supplied by the posterior cerebellar artery, the choroidal artery, and the collicular artery.
    • Posterior: supplied by the superior cerebellar artery, the posteromedial choroidal artery.
  • Pons

    • Anteromedial: supplied by the pontine perforating arteries, branches of the basilar artery.
    • Anterolateral: supplied by the anterior inferior cerebellar artery.
    • Lateral: supplied by the lateral pontine perforating arteries, branches of the basilar artery, anterior inferior cerebellar artery, or the superior cerebellar artery.
  • Medulla oblongata

    • Anteromedial: supplied by the anterior spinal artery and vertebral artery.
    • Anterolateral: supplied by the anterior spinal artery and vertebral artery.
    • Lateral: supplied by the posterior inferior cerebellar artery.
    • Posterior: supplied by the posterior spinal artery.

Brainstem infarction is an area of tissue death resulting from a lack of oxygen supply to any part of the brainstem. The knowledge of anatomy, vascular supply, and physical examination can be life-saving in the setting of an acute infarct and provide precise diagnosis and management. Time becomes an essential factor in management. Early intervention has shown to dramatically reduced morbidity and mortality.

Causes of Brainstem Stroke Syndromes

Brainstem infarction refers to the sequelae of ischemia to any part of the brainstem, due to the loss of blood supply or bleeding. Occlusion and stenosis of the posterior circulation cause significant hypoperfusion in the brainstem. The most common etiologies for brainstem infarction are atherosclerosis, thromboembolism, lipohylanosis, tumor, arterial dissection, and trauma. In medulla oblongata infarcts, 73% are due to stenosis of the vertebral artery, 26% due to arterial dissection, and rest being caused by other causes like cardioembolic. However, the number of infarcts due to cardioembolic etiology increase to 8% in pontine infarcts and 20% to 46% in midbrain infarcts.

Risk factors for stroke, in general, include hypertension, diabetes mellitus, metabolic syndromes, hyperlipidemia, tobacco use, obesity, history of ischemic heart disease, atrial fibrillation, sleep apnea, lack of physical activity, use of oral contraceptives, fibromuscular dysplasia, trauma, and spinal manipulation.

Symptoms of Crossed Brainstem Syndromes

The following signs and symptoms may be a warning that you are about to have a stroke in your brainstem:

  • Dizziness, loss of balance, nausea, or vomiting
  • Slurred speech, or trouble speaking or swallowing
  • Blurred or double vision, or eye pain
  • Numbness and weakness on 1 side of your body or face
  • Drowsiness or unconsciousness
  • Jerky eye movements, or pupils that are not the same size
  • Sudden headache or hearing loss

Diagnosis of Crossed Brainstem Syndromes

A loss of about 1.9 million neurons in the brain happens each minute in an untreated stroke. Hence a targeted approach must be followed with clear objectives. Assessment of airway, breathing and circulation, and its stabilization as a patient with brainstem stroke can present with trauma, altered mental status, altered respiratory drive, hypoxia, vomiting, and or mechanical airway obstruction.

Establishing the time of ischemic insult is critical. Patients, family members, attenders, co-workers, first responders, or any reliable witness can determine the time the patient was last known normal. If in the case of deficits arising in one’s sleep, last known normal is the time the patient went to bed. A clinician needs to distinguish between ischemia and its differential diagnosis, causing various neurological deficits. Reliable information about the patient’s current medication, especially with regards to oral hypoglycemic, insulin, anti-epileptics, neurological or psychological drugs, anti-platelets or blood thinners, drug abuse or overdose, and sleep apnea must be established. Co-morbidities and risk factors need to be assessed. Evaluation of signs and symptoms for hemorrhagic stroke is life-saving. Any history of uncontrolled hypertension, sudden onset of headache, vomiting, signs of raised intracranial pressure must raise high suspicion of hemorrhage and warrants an immediate non-contrast computed tomographic (CT) scan of the head.

Brainstem lesions can be divided into three broad categories to identify the affected region or function of the brainstem.

  • Ascending and descending pathways: Weakness, loss of pain and temperature sensation, ataxia, Horner syndrome, loss of position and vibration sensation, gaze palsy
  • Nuclei and cranial nerves: Ocular and extraocular muscle weakness, loss of sensation over the face, autonomic dysregulation, dysphagia, dysarthria, dysphonia, vertigo, alteration in taste and hearing
  • Integrative and other functions: Choreoathetosis, tremors, ataxia, central dysautonomia, gaze paresis, lethargy, locked-in syndrome

A concise physical examination should evaluate any signs suggestive of trauma, meningeal irritation, or neurological deficits. Neurological examination of a brainstem infarct must include the following assessment:

  • Levels of consciousness and higher mental function
  • Complete evaluation of cranial nerves and its functions
  • Motor and sensory system examination, including reflexes, neglect, speech, and language
  • Cerebellar signs, coordination, and gait
  • Autonomic system

Evaluation

The initial evaluation of patients presenting with a suspected stroke of the brainstem includes vital signs, oxygen saturation, blood pressure, pulse rate, respiratory rate, fingerstick blood glucose levels, non-contrast CT scan of the head or brain magnetic resonance imaging (MRI). Non-contrast CT scan of the head is a quick and widely available imaging modality, and it is highly sensitive for acute hemorrhage. On a head CT scan, blood can be seen as a hyper-dense lesion. Infarction of brain tissue can be detected by brain MRI diffusion-weighted images and fluid-attenuated inversion recovery images, which are highly sensitive in the hyper-acute setting.

Blood workup should including complete blood count, coagulation profile, serum electrolytes, renal function, lipid panel, hemoglobin-A1c level, thyroid function, vitamin B12 level, and vitamin D levels. Other blood investigation for hypercoagulability states, autoimmune conditions, liver pathologies, and genetic tests can be obtained. Cardiovascular workup for atrial fibrillation with either an electrocardiogram or Holter monitor, echocardiogram, cardiac enzyme levels, chest X-ray should be obtained. A multi-phase CT angiography can establish the state of vertebral and carotid arteries, along with assessment for any endovascular management. Sleep study or polysomnography is diagnostic for various sleep disorders and must be suspected in stroke cases with unknown etiologies. Evaluation of both modifiable and non-modifiable risk factors for cardiovascular disease must be done.

Due to the high density of nuclei and fibers running through the brainstem, the lesion in various structures gives rise to different signs and symptoms. Variously named stroke and stroke syndromes have been described in the literature.

  • The ‘top-of-the-basilar’ syndrome –  Also known as the rostral brainstem infarction. It results in alternating disorientation, hypersomnolence, unresponsiveness, hallucination, and behavioral abnormalities along with visual, oculomotor deficits, and cortical blindness. Occurs due to occlusion of the distal basilar artery and its perforators.
  • Ondine’s syndrome –  Affects the brainstem response centers for automatic breathing. It results in complete breathing failure during sleep but normal ventilation when awake. The blood supply affected is the pontine perforating arteries, branches of the basilar artery, anterior inferior cerebellar artery, or the superior cerebellar artery.
  • One-and-a-half syndrome –  Affects the paramedian pontine reticular formation and medial longitudinal fasciculus. It results in ipsilateral conjugate gaze palsy and internuclear ophthalmoplegia. The blood supply affected is the pontine perforating arteries and branches of the basilar artery.

Midbrain syndromes

  • Claude syndrome – Affects the fibers from CN III, the rubrodentate fibers, corticospinal tract fibers, and corticobulbar fibers. It results in ipsilateral CN III palsy, contralateral hemiplegia of lower facial muscles, tongue, shoulder, upper and lower limb along with contralateral ataxia. The blood supply involved is from the posterior cerebral artery.
  • Dorsal midbrain syndrome (Benedikt) – Also known as paramedian midbrain syndrome, affects the fibers from CN III and the red nucleus. It results in ipsilateral CN III palsy, contralateral choreoathetosis, tremor, and ataxia. The blood supply involved comes from the posterior cerebral artery and paramedian branches of the basilar artery.
  • Nothnagel syndrome – Affects the fibers from CN III and the superior cerebellar peduncle. It results in ipsilateral CN III palsy and ipsilateral limb ataxia. It can be due to quadrigeminal neoplasms and is often bilateral.
  • Ventral midbrain syndrome (Weber) – Affects the fibers from CN III, cerebral peduncle (corticospinal and corticobulbar tract), and substantia nigra. It results in ipsilateral CN III palsy, contralateral hemiplegia of lower facial muscles, tongue, shoulder, upper and lower limb. The involvement of a substantial nigra is present can result in a contralateral movement disorder. The blood supply affected is the paramedian branches of the posterior cerebral artery.

Pontine syndromes

  • Brissaud-Sicard syndrome: Affects the CN VII nucleus and corticospinal tract. It results in ipsilateral facial cramps and contralateral upper and lower limb hemiparesis. The blood supply affected is the posterior circulation. Rarely, the syndrome can arise due to brainstem glioma.
  • Facial colliculus syndrome: Affects the CN VI nucleus, the CN VII nucleus, and fibers and the medial longitudinal fasciculus. It results in lower motor neuron CN VII palsy, diplopia, and horizontal conjugate. It can occur due to neoplasm, multiple sclerosis, or viral infection.
  • Gasperini syndrome: Affects the nuclei of CN V, VI, VII, VIII, and the spinothalamic tract. It results in ipsilateral facial sensory loss, ipsilateral impaired eye abduction, ipsilateral impaired eye abduction, ipsilateral nystagmus, vertigo, and contralateral hemi-sensory impairment. The blood supply involved derives from the pontine branches of the basilar artery and the long circumferential artery of the anterior inferior cerebellar artery.
  • Gellé syndrome: Affects the CN VII, VIII, and corticospinal tract. It results in ipsilateral facial palsy, ipsilateral hearing loss, and contralateral hemiparesis.
  • Grenet syndrome: Affects CN V lemniscus, CN VII fibers, and spinothalamic tract. It results in altered sensation in the ipsilateral face, contralateral upper, and contralateral lower limbs. It can arise due to neoplasm.
  • Inferior medial pontine syndrome (Fonville syndrome): Also known as the lower dorsal pontine syndrome, affects the corticospinal tract, medial lemniscus, middle cerebellar peduncle, and the nucleus of CN VI and VII. It results in contralateral hemiparesis, contralateral loss of proprioception & vibration, ipsilateral ataxia, ipsilateral facial palsy, lateral gaze paralysis, and diplopia. The blood supply affected is from branches of the basilar artery.
  • Lateral pontine syndrome (Marie-Foix syndrome): Affects the nuclei of CN VII, & VIII, corticospinal tract, spinothalamic tract, and cerebellar tracts. It results in contralateral hemiparesis, contralateral loss of proprioception & vibration, ipsilateral limb ataxia, ipsilateral facial palsy, lateral hearing loss, vertigo, and nystagmus. The blood supply affected is the perforating branches of the basilar artery and the anterior inferior cerebellar artery.
  • Locked-in syndrome: Affects upper ventral pons, including corticospinal tract, corticobulbar tract, and CN VI nuclei. It results in quadriplegia, bilateral facial palsy, and horizontal eye palsy. The patient can move the eyes vertically, blink, and has an intact consciousness. The blood supply affected is the middle and proximal segments of the basilar artery.
  • Raymond syndrome: Affects the CN VI fibers, corticospinal tract, and cervicofacial fibers. It results in an ipsilateral lateral gaze palsy, contralateral hemiparesis, and facial palsy. The blood supply involved is from the branches of the basilar artery.
  • Upper dorsal pontine syndrome (Raymond-Cestan): Affects the longitudinal medial fasciculus, medial lemniscus, spinothalamic tract, CN V fibers and nuclei, superior and middle cerebellar peduncle. It results in ipsilateral ataxia, coarse intension tremors, sensory loss in the face, weakness of mastication, contralateral loss of all sensory modalities. The blood supply involved is from the circumferential branches of the basilar artery.
  • Ventral pontine syndrome (Millard-Gubler): Affects the CN VI & VII and corticospinal tract. It results in ipsilateral lateral rectus palsy, diplopia, ipsilateral facial palsy, and contralateral hemiparesis of upper and lower limbs. The blood supply involved derives from the branches from the basilar artery.

Medulla oblongata

  • Allis syndrome: Affects the pyramidal tract and nucleus ambiguous. It results in ipsilateral palatopharyngeal palsy, contralateral hemiparesis, and contralateral Hemi-sensory impairment. The blood supply affected is the vertebral arteries.
  • Babinski-Nageotte syndrome: Also known as the Wallenberg with hemiparesis, affects the spinal fiber and nucleus of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, afferent spinocerebellar tracts, and corticospinal tract. It results in ipsilateral facial loss of pain & temperature, ipsilateral palsy of the soft palate, larynx &  pharynx, ipsilateral Horner syndrome, ipsilateral cerebellar Hemi-ataxia, contralateral hemiparesis, and contralateral loss of body pain and temperature. The blood supply involved is from the intracranial portion of the vertebral artery and branches from the posterior inferior cerebellar artery.
  • Cestan-Chenais syndrome: It affects the spinal fiber and nucleus of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, and corticospinal tract. It results in ipsilateral facial loss of pain and temperature, ipsilateral palsy of the soft palate, larynx & pharynx, ipsilateral Horner’s syndrome, contralateral hemiparesis, contralateral loss of body pain & temperature, and contralateral tactile hypesthesia. The blood supply affected is the intracranial portion of the vertebral artery and branches from the posterior inferior cerebellar artery.
  • Hemimedullary syndrome (Reinhold syndrome): Affects the nucleus & fiber of CN V, CN XII nucleus ambiguous, lateral spinothalamic tract, sympathetic fibers, afferent spinocerebellar tracts, corticospinal tract, and medial lemniscus. It results in ipsilateral Horner’s syndrome, ipsilateral facial loss of pain & temperature, ipsilateral palsy of soft palate, larynx & pharynx, ipsilateral tongue weakness, ipsilateral cerebellar Hemi-ataxia, contralateral hemiparesis, and contralateral face sparing hemihypesthesia. The blood supply involved is from the ipsilateral vertebral artery, the posterior inferior cerebellar artery, and branches from the anterior spinal artery.
  • Jackson syndrome: Affects CN XII and pyramidal tract. It results in ipsilateral palsy of the tongue and contralateral hemiparesis. The blood supply involved is from the branches of the anterior spinal artery.
  • Lateral medullary syndrome (Wallenberg syndrome): Affects the spinal nucleus & fiber of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, inferior cerebellar peduncle, and vestibular nuclei. It results in ipsilateral Horner’s syndrome, ipsilateral facial loss of pain & temperature, ipsilateral palsy of soft palate, larynx & pharynx, ipsilateral cerebellar Hemi-ataxia, contralateral loss of body pain & temperature, nystagmus, dysarthria, dysphagia, and hyperacusis. The blood supply affected is the vertebral artery and branches from the posterior inferior cerebellar artery.
  • Medial medullary syndrome (Dejerine syndrome): Affects the fibers of CN XII, corticospinal tract, and medial lemniscus spinal. Results in ipsilateral tongue weakness, ipsilateral loss of proprioception & vibration, contralateral hemiparesis, and contralateral face sparing hemihypesthesia. The blood supply affected is the branches from the vertebral artery and the anterior spinal artery.
  • Schmidt syndrome: Affects the fibers and nuclei of CN IX, X, XI, and pyramidal system. It results in ipsilateral palsy of the vocal cords, soft palate, trapezius, & sternocleidomastoid muscle, and contralateral spastic hemiparesis. The blood supply involved involves branches from the vertebral artery, the posterior inferior cerebellar artery the anterior spinal artery.
  • Spiller syndrome: Affects the fibers and nucleus of CN XII, corticospinal tract, and medial lemniscus spinal along with medial Hemi-medulla. Results in ipsilateral tongue weakness, ipsilateral loss of proprioception & vibration, contralateral hemiparesis, and contralateral face sparing hemihypesthesia. The blood supply involved is from the branches from the vertebral artery and the anterior spinal artery.
  • Tapia syndrome: Affects the nucleus ambiguous, CN XII, and pyramidal tract. It results in ipsilateral palsy of the trapezius, sternocleidomastoid muscle, & half of the tongue, dysphagia, dysphonia, and contralateral spasmodic hemiparesis. The blood supply involved is from the branches from the vertebral artery, the posterior inferior cerebellar artery the anterior spinal artery.
  • Vernet syndrome: Affects the CN IX, X, and XI. It occurs due to compression in the jugular foramen

Treatment of Crossed Brainstem Syndromes

After the patient’s airway, breathing and circulation have been stabilized, a timeframe of the patient’s symptoms is obtained. Vitals and fluid status must be stabilized. Hypo or hyperglycemia must be corrected. Fever, if present, should be managed accordingly. Blood pressure must not be aggressively controlled to allow permissive hypertension only in the case of ischemic injury. Patients with last known normal within 4.5 hours can be considered as candidates for thrombolysis, whereas a 24 hour last known normal can be candidates for mechanical thrombectomy. If it is a case presenting earlier than 4.5 hours of onset, thrombolysis with intravenous recombinant tissue plasminogen activator significantly improves the clinical outcome.

Tissue plasminogen activator (tPA)

Inclusion criteria for tPA:

  • Clinical diagnosis of ischemic stroke
  • <4.5 hours of the onset of symptoms
  • Age >18 and <80 years
  • Symptoms of stroke presenting for more than 30 minutes

Excision criteria for tPA:

  • Unknown timeline of onset of patient symptoms
  • Intracranial hemorrhage or any active bleeding
  • Persistently elevated blood pressure ≥ 185 mmHg systolic and ≥ 110 mmHg diastolic
  • Low platelets <100,000/mm3, altered INR >1.7, PT >15 sec or aPTT >40sec
  • Current use of anti-coagulant
  • Severe hypoglycemia <50mg/dL
  • History of previous intracranial hemorrhage
  • History of gastrointestinal bleeding in the past 21 days
  • History of intracranial or intraspinal surgery in the past 90 days
  • History of intra-axial intracranial neoplasm or gastrointestinal malignancy

Intravenous alteplase (recombinant tissue plasminogen activator) should be given at the dose of 0.9 mg/kg (maximum dose of 90 mg/kg) with 10% as the loading dose in the first minute. The patient must be under continuous observation. Anti-platelet therapy must be withheld for at least 24 hours post thrombolysis and restarted after a head CT scan without evidence of bleeding.

Mechanical endovascular thrombectomy in patients with large anterior circulation occlusion is well documented; however, most strokes affecting the brainstem arise from posterior circulation perforating branches. For those cases where the occlusion is at the main vertebral or basilar artery, endovascular thrombectomy is recommended for successful revascularization and favorable outcome. Other studies have shown no evidence of a difference in favorable outcomes between endovascular therapy when compared to standard medical therapy alone.

Antiplatelet therapy: The usage of acetylsalicylic acid as monotherapy or dual therapy along with clopidogrel within 24 – 48 hours after the onset of symptoms significantly improved patient outcomes.

Management of risk factors like hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, thyroid abnormalities, sleep apnea, malignancies, and hypercoagulable states should be treated accordingly.  Dietary and lifestyle modification must be explained and discussed. Supplementation with vitamin B12 and vitamin D3 should also be considered. Physiotherapy, along with speech therapy, can be used if physical deficits arise due to infarct. Treatments must start at the earliest and must be aggressively pursued as the brain losses its plasticity within 90 days.

The differential diagnosis of brainstem infarction includes the following:

  • Transient ischemic attack
  • Metastatic disease of the brain
  • Central pontine demyelination
  • Subarachnoid hemorrhage
  • Seizures
  • Basilar migraine
  • Basilar meningitis
  • Cerebellopontine angle tumors
  • Supratentorial hemispheric mass effect with herniation and brainstem compression
  • Hypoglycemia
  • Electrolyte imbalance
  • Conversion disorder

Complications

  • Hemorrhagic transformation
  • Seizures
  • Aspiration pneumonia
  • Myocardial infarction, arrhythmias, and heart failure
  • Dysphagia and dysphonia
  • Depression and anxiety
  • Blackouts and falls
  • Sleep disorders
  • Urinary tract infection
  • Deep vein thrombosis
  • Pulmonary embolism
  • Dehydration and malnutrition
  • Pressure sores and skin lesions
  • Orthopedic complications and contractures
  • Post-stroke fatigue

Patient Education

ACT FAST is an acronym suggested by the American Stroke Association to recognize the early symptoms of a stroke. It has the following components:

  • F-Face drooping
  • A-Arm Weakness
  • S-Speech
  • T-Time to call 9-1-1

Along with the above symptoms, if the patient experiences any of the following, emergency medical services must be activated

  • Sudden confusion
  • Sudden trouble seeing
  • Sudden numbness
  • Sudden trouble walking
  • Sudden severe headache

Control of risk factors can significantly reduce future strokes:

  • Smoking cessation
  • Alcohol use
  • Drug addiction and abuse
  • Hypertension and diabetes control
  • Obesity and sedentary lifestyle
  • Sleep apnea
  • Regular follow with primary care physician

Stroke and intracranial hemorrhage

  • stroke and intracranial hemorrhage
    • code stroke CT (an approach)
    • ischemic stroke
      • general discussions
        • CT perfusion
          • infarct core
          • ischemic penumbra
          • luxury perfusion
        • multiphase CT angiography
        • fogging phenomenon
        • calcified cerebral embolus
        • DWI in acute stroke
          • early DWI reversal
          • ADC pseudonormalization
          • T2 shine-through
          • T2 washout
          • T2 blackout
        • acute vs chronic ischemic stroke (CT)
        • transient ischemic attack (TIA)
        • intracranial atherosclerotic disease (ICAD)
      • scoring and classification systems
        • Alberta stroke program early CT score (ASPECTS)
          • CT angiography source image ASPECTS
        • Canadian Neurological Scale
        • NIH Stroke Scale
        • Mathew Stroke Scale
        • modified Rankin scale
        • Orgogozo Stroke Scale
        • Scandinavian Stroke Scale
        • thrombolysis in cerebral infarction (TICI)
          • modified treatment in cerebral infarction (mTICI)
        • TOAST classification
        • collateral vessel scores
          • single-phase CTA collateral scores
          • multiphase CTA collateral score
      • signs
        • carotid pseudo-occlusion
        • hyperdense MCA sign
        • MCA dot sign
        • salted pretzel sign
        • tandem lesion
      • by region
        • hemispheric infarcts
          • frontal lobe infarct
          • parietal lobe infarct
            • Gerstmann syndrome
          • temporal lobe infarct
          • occipital lobe infarct
            • alexia without agraphia syndrome: PCA
            • cortical blindness syndrome (Anton syndrome): top of basilar or bilateral PCA
            • Balint syndrome: bilateral PCA
        • lacunar infarct
          • lacunar stroke syndromes
          • lenticulostriate infarct
        • thalamic infarct
          • Déjerine-Roussy syndrome (thalamic pain syndrome): thalamoperforators of PCA
          • top of the basilar syndrome
        • striatocapsular infarct
        • cerebellar infarct
        • brainstem infarct
          • midbrain infarct
            • Benedikt syndrome: PCA
            • Claude syndrome: PCA
            • Nothnagel syndrome: PCA
            • Weber syndrome: PCA
          • pontine infarct
            • Brissaud-Sicard syndrome
            • facial colliculus syndrome
            • Gasperini syndrome: basilar artery or AICA
            • inferior medial pontine syndrome (Foville syndrome): basilar artery
            • lateral pontine syndrome (Marie-Foix syndrome): basilar artery or AICA
            • locked-in syndrome: basilar artery
            • Millard-Gubler syndrome: basilar artery
            • Raymond syndrome: basilar artery
          • medullary infarct
            • Babinski-Nageotte syndrome
            • hemimedullary syndrome (Reinhold syndrome)
            • lateral medullary stroke syndrome (Wallenberg syndrome)
            • medial medullary syndrome (Déjerine syndrome)
        • acute spinal cord ischemia syndrome
          • anterior spinal artery syndrome
          • sulcal artery syndrome
          • posterior spinal artery syndrome
      • by vascular territory
        • anterior circulation infarction
          • anterior cerebral artery infarct
          • anterior choroidal artery infarct
          • middle cerebral artery infarct
            • hyperdense MCA sign
            • MCA dot sign
        • posterior circulation infarction
          • basilar artery infarct
          • posterior cerebral artery infarct
            • artery of Percheron infarct
          • brainstem infarct
            • midbrain infarct
            • pontine infarct
            • medullary infarct
          • cerebellar infarction
            • superior cerebellar artery infarct
            • anterior cerebellar artery infarct
            • posterior inferior cerebellar artery infarct
      • treatment options
        • mechanical thrombectomy
      • complications
        • crossed cerebellar diaschisis
        • hemorrhagic transformation of an ischemic infarct
          • cerebral intraparenchymal hyperattenuations post thrombectomy
    • intracranial hemorrhage
      • intra-axial hemorrhage
        • signs and formulas
          • ABC/2 (volume estimation)
          • CTA spot sign
          • swirl sign
        • by region or type
          • basal ganglia hemorrhage
          • cerebellar hemorrhage
            • remote cerebellar hemorrhage
          • cerebral contusions
          • cerebral microhemorrhage
          • ​hemorrhagic venous infarct
          • hemorrhagic transformation of an ischemic infarct
            • cerebral intraparenchymal hyperattenuations post thrombectomy
          • hypertensive intracranial hemorrhage
          • intraventricular hemorrhage (IVH)
          • jet hematoma
          • lobar hemorrhage
            • cerebral amyloid angiopathy
          • pontine hemorrhage
            • Duret hemorrhage
      • extra-axial hemorrhage
        • extradural versus subdural hemorrhage
        • extradural hemorrhage (EDH)
          • venous extradural hemorrhage
        • intralaminar dural hemorrhage
        • subdural hemorrhage (SDH)
          • calcified chronic subdural hemorrhage
        • subarachnoid hemorrhage (SAH)
          • types
            • ruptured berry aneurysm
              • berry aneurysm
              • fusiform aneurysm
              • mycotic aneurysm
            • convexal subarachnoid hemorrhage
            • traumatic subarachnoid hemorrhage (TSAH)
            • perimesencephalic subarachnoid hemorrhage (PMSAH)
          • vasospasm following SAH
          • grading systems
            • Hunt and Hess grading system
            • Fisher scale
            • modified Fisher scale
            • SDASH score
            • WFNS grading system
        • subpial hemorrhage

References

Brainstem Stroke Syndromes – Causes, Symptoms, Treatment

Brainstem stroke syndromes, also known as crossed brainstem syndromes, refer to a group of syndromes that occur secondary to lesions, most commonly infarcts, of the brainstem. A brainstem infarction (BSI) is a stroke that happens when blood cannot flow to your brainstem. When oxygen cannot get to an area of the brain, tissue in that area may be damaged. Your brainstem allows you to speak, hear, and swallow. It also controls your breathing, heartbeat, blood pressure, balance, and eye movements.

Brainstem infarcts are a collection of difficult-to-diagnose syndromes affecting the midbrain, the pons, and the medulla oblongata. They can cause a varied range of symptoms ranging from impairment of cranial nerves III to XII, to respiratory and cardiac dysfunction, locked-in syndrome, sleep-wake cycle alteration, and decreased consciousness and death. Early diagnosis is a must as brainstem infarction is associated with high mortality and morbidity. An adequate understanding of anatomy, physical exam, and pathophysiology is required for evaluating and managing the disease. This activity reviews the evaluation and treatment of brainstem infarction and highlights the role of the interprofessional team in assessing and treating patients with this condition.

The brainstem is composed of the midbrain, the pons, and the medulla oblongata, situated in the posterior part of the brain. It is a connection between the cerebrum, the cerebellum, and the spinal cord. Embryologically, it develops from the mesencephalon and part of the rhombencephalon, all of which originate from the neural ectoderm. The brainstem is organized internally in three laminae: tectum, tegmentum, and basis. Gray matter in the brainstem is found in clusters all along the brainstem to forming mostly the cranial nerve nuclei, the pontine nuclei, and the reticular formation. White matter in the form of various ascending and descending tracts can be found mainly in the basis lamina, which is the most anterior part. The brainstem is responsible for multiple critical functions, including respiration, cardiac rhythm, blood pressure control, consciousness, and sleep-wake cycle. The cranial nerve nuclei that are present in the brainstem have a crucial role in vision, balance, hearing, swallowing, taste, speech, motor, and sensory supply to the face. The white matter of the brainstem carries most of the signals between the brain and the spinal cord and helps with its relay and processing.

Brainstem stroke syndromes are most commonly classified anatomically.

  • Benedikt syndrome
  • Claude syndrome
  • Nothnagel syndrome
  • Weber syndrome
  • Wernekink commissure syndrome
  • Brissaud-Sicard syndrome
  • facial colliculus syndrome
  • Gasperini syndrome
  • Gellé syndrome
  • Grenet syndrome
  • inferior medial pontine syndrome (Foville syndrome)
  • lateral pontine syndrome (Marie-Foix syndrome)
  • locked-in syndrome
  • Millard-Gubler syndrome
  • Raymond syndrome
  • Raymond-Cestan syndrome
  • Avellis syndrome
  • Babinski-Nageotte syndrome
  • Cestan-Chenais syndrome
  • hemimedullary syndrome (Reinhold syndrome)
  • Jackson syndrome
  • lateral medullary syndrome (Wallenberg syndrome)
  • medial medullary syndrome (Dejerine syndrome)
  • Schmidt syndrome
  • Spiller syndrome
  • Tapia syndrome
  • Vernet syndrome (often not caused by a brainstem lesion)

The blood supply to the brainstem is mostly from the vertebrobasilar system. The blood supply can be divided into a group of arteries supplying each region:

  • Midbrain

    • Anteromedial: supplied by the posterior cerebral artery.
    • Anterolateral: supplied by the posterior cerebral artery and branches of the anterior choroidal artery.
    • Lateral: supplied by the posterior cerebellar artery, the choroidal artery, and the collicular artery.
    • Posterior: supplied by the superior cerebellar artery, the posteromedial choroidal artery.
  • Pons

    • Anteromedial: supplied by the pontine perforating arteries, branches of the basilar artery.
    • Anterolateral: supplied by the anterior inferior cerebellar artery.
    • Lateral: supplied by the lateral pontine perforating arteries, branches of the basilar artery, anterior inferior cerebellar artery, or the superior cerebellar artery.
  • Medulla oblongata

    • Anteromedial: supplied by the anterior spinal artery and vertebral artery.
    • Anterolateral: supplied by the anterior spinal artery and vertebral artery.
    • Lateral: supplied by the posterior inferior cerebellar artery.
    • Posterior: supplied by the posterior spinal artery.

Brainstem infarction is an area of tissue death resulting from a lack of oxygen supply to any part of the brainstem. The knowledge of anatomy, vascular supply, and physical examination can be life-saving in the setting of an acute infarct and provide precise diagnosis and management. Time becomes an essential factor in management. Early intervention has shown to dramatically reduced morbidity and mortality.

Causes of Brainstem Stroke Syndromes

Brainstem infarction refers to the sequelae of ischemia to any part of the brainstem, due to the loss of blood supply or bleeding. Occlusion and stenosis of the posterior circulation cause significant hypoperfusion in the brainstem. The most common etiologies for brainstem infarction are atherosclerosis, thromboembolism, lipohylanosis, tumor, arterial dissection, and trauma. In medulla oblongata infarcts, 73% are due to stenosis of the vertebral artery, 26% due to arterial dissection, and rest being caused by other causes like cardioembolic. However, the number of infarcts due to cardioembolic etiology increase to 8% in pontine infarcts and 20% to 46% in midbrain infarcts.

Risk factors for stroke, in general, include hypertension, diabetes mellitus, metabolic syndromes, hyperlipidemia, tobacco use, obesity, history of ischemic heart disease, atrial fibrillation, sleep apnea, lack of physical activity, use of oral contraceptives, fibromuscular dysplasia, trauma, and spinal manipulation.

Symptoms of Brainstem Stroke Syndromes

The following signs and symptoms may be a warning that you are about to have a stroke in your brainstem:

  • Dizziness, loss of balance, nausea, or vomiting
  • Slurred speech, or trouble speaking or swallowing
  • Blurred or double vision, or eye pain
  • Numbness and weakness on 1 side of your body or face
  • Drowsiness or unconsciousness
  • Jerky eye movements, or pupils that are not the same size
  • Sudden headache or hearing loss

Diagnosis of Brainstem Stroke Syndromes

A loss of about 1.9 million neurons in the brain happens each minute in an untreated stroke. Hence a targeted approach must be followed with clear objectives. Assessment of airway, breathing and circulation, and its stabilization as a patient with brainstem stroke can present with trauma, altered mental status, altered respiratory drive, hypoxia, vomiting, and or mechanical airway obstruction.

Establishing the time of ischemic insult is critical. Patients, family members, attenders, co-workers, first responders, or any reliable witness can determine the time the patient was last known normal. If in the case of deficits arising in one’s sleep, last known normal is the time the patient went to bed. A clinician needs to distinguish between ischemia and its differential diagnosis, causing various neurological deficits. Reliable information about the patient’s current medication, especially with regards to oral hypoglycemic, insulin, anti-epileptics, neurological or psychological drugs, anti-platelets or blood thinners, drug abuse or overdose, and sleep apnea must be established. Co-morbidities and risk factors need to be assessed. Evaluation of signs and symptoms for hemorrhagic stroke is life-saving. Any history of uncontrolled hypertension, sudden onset of headache, vomiting, signs of raised intracranial pressure must raise high suspicion of hemorrhage and warrants an immediate non-contrast computed tomographic (CT) scan of the head.

Brainstem lesions can be divided into three broad categories to identify the affected region or function of the brainstem.

  • Ascending and descending pathways: Weakness, loss of pain and temperature sensation, ataxia, Horner syndrome, loss of position and vibration sensation, gaze palsy
  • Nuclei and cranial nerves: Ocular and extraocular muscle weakness, loss of sensation over the face, autonomic dysregulation, dysphagia, dysarthria, dysphonia, vertigo, alteration in taste and hearing
  • Integrative and other functions: Choreoathetosis, tremors, ataxia, central dysautonomia, gaze paresis, lethargy, locked-in syndrome

A concise physical examination should evaluate any signs suggestive of trauma, meningeal irritation, or neurological deficits. Neurological examination of a brainstem infarct must include the following assessment:

  • Levels of consciousness and higher mental function
  • Complete evaluation of cranial nerves and its functions
  • Motor and sensory system examination, including reflexes, neglect, speech, and language
  • Cerebellar signs, coordination, and gait
  • Autonomic system

Evaluation

The initial evaluation of patients presenting with a suspected stroke of the brainstem includes vital signs, oxygen saturation, blood pressure, pulse rate, respiratory rate, fingerstick blood glucose levels, non-contrast CT scan of the head or brain magnetic resonance imaging (MRI). Non-contrast CT scan of the head is a quick and widely available imaging modality, and it is highly sensitive for acute hemorrhage. On a head CT scan, blood can be seen as a hyper-dense lesion. Infarction of brain tissue can be detected by brain MRI diffusion-weighted images and fluid-attenuated inversion recovery images, which are highly sensitive in the hyper-acute setting.

Blood workup should including complete blood count, coagulation profile, serum electrolytes, renal function, lipid panel, hemoglobin-A1c level, thyroid function, vitamin B12 level, and vitamin D levels. Other blood investigation for hypercoagulability states, autoimmune conditions, liver pathologies, and genetic tests can be obtained. Cardiovascular workup for atrial fibrillation with either an electrocardiogram or Holter monitor, echocardiogram, cardiac enzyme levels, chest X-ray should be obtained. A multi-phase CT angiography can establish the state of vertebral and carotid arteries, along with assessment for any endovascular management. Sleep study or polysomnography is diagnostic for various sleep disorders and must be suspected in stroke cases with unknown etiologies. Evaluation of both modifiable and non-modifiable risk factors for cardiovascular disease must be done.

Due to the high density of nuclei and fibers running through the brainstem, the lesion in various structures gives rise to different signs and symptoms. Variously named stroke and stroke syndromes have been described in the literature.

  • The ‘top-of-the-basilar’ syndrome –  Also known as the rostral brainstem infarction. It results in alternating disorientation, hypersomnolence, unresponsiveness, hallucination, and behavioral abnormalities along with visual, oculomotor deficits, and cortical blindness. Occurs due to occlusion of the distal basilar artery and its perforators.
  • Ondine’s syndrome –  Affects the brainstem response centers for automatic breathing. It results in complete breathing failure during sleep but normal ventilation when awake. The blood supply affected is the pontine perforating arteries, branches of the basilar artery, anterior inferior cerebellar artery, or the superior cerebellar artery.
  • One-and-a-half syndrome –  Affects the paramedian pontine reticular formation and medial longitudinal fasciculus. It results in ipsilateral conjugate gaze palsy and internuclear ophthalmoplegia. The blood supply affected is the pontine perforating arteries and branches of the basilar artery.

Midbrain syndromes

  • Claude syndrome – Affects the fibers from CN III, the rubrodentate fibers, corticospinal tract fibers, and corticobulbar fibers. It results in ipsilateral CN III palsy, contralateral hemiplegia of lower facial muscles, tongue, shoulder, upper and lower limb along with contralateral ataxia. The blood supply involved is from the posterior cerebral artery.
  • Dorsal midbrain syndrome (Benedikt) – Also known as paramedian midbrain syndrome, affects the fibers from CN III and the red nucleus. It results in ipsilateral CN III palsy, contralateral choreoathetosis, tremor, and ataxia. The blood supply involved comes from the posterior cerebral artery and paramedian branches of the basilar artery.
  • Nothnagel syndrome – Affects the fibers from CN III and the superior cerebellar peduncle. It results in ipsilateral CN III palsy and ipsilateral limb ataxia. It can be due to quadrigeminal neoplasms and is often bilateral.
  • Ventral midbrain syndrome (Weber) – Affects the fibers from CN III, cerebral peduncle (corticospinal and corticobulbar tract), and substantia nigra. It results in ipsilateral CN III palsy, contralateral hemiplegia of lower facial muscles, tongue, shoulder, upper and lower limb. The involvement of a substantial nigra is present can result in a contralateral movement disorder. The blood supply affected is the paramedian branches of the posterior cerebral artery.

Pontine syndromes

  • Brissaud-Sicard syndrome: Affects the CN VII nucleus and corticospinal tract. It results in ipsilateral facial cramps and contralateral upper and lower limb hemiparesis. The blood supply affected is the posterior circulation. Rarely, the syndrome can arise due to brainstem glioma.
  • Facial colliculus syndrome: Affects the CN VI nucleus, the CN VII nucleus, and fibers and the medial longitudinal fasciculus. It results in lower motor neuron CN VII palsy, diplopia, and horizontal conjugate. It can occur due to neoplasm, multiple sclerosis, or viral infection.
  • Gasperini syndrome: Affects the nuclei of CN V, VI, VII, VIII, and the spinothalamic tract. It results in ipsilateral facial sensory loss, ipsilateral impaired eye abduction, ipsilateral impaired eye abduction, ipsilateral nystagmus, vertigo, and contralateral hemi-sensory impairment. The blood supply involved derives from the pontine branches of the basilar artery and the long circumferential artery of the anterior inferior cerebellar artery.
  • Gellé syndrome: Affects the CN VII, VIII, and corticospinal tract. It results in ipsilateral facial palsy, ipsilateral hearing loss, and contralateral hemiparesis.
  • Grenet syndrome: Affects CN V lemniscus, CN VII fibers, and spinothalamic tract. It results in altered sensation in the ipsilateral face, contralateral upper, and contralateral lower limbs. It can arise due to neoplasm.
  • Inferior medial pontine syndrome (Fonville syndrome): Also known as the lower dorsal pontine syndrome, affects the corticospinal tract, medial lemniscus, middle cerebellar peduncle, and the nucleus of CN VI and VII. It results in contralateral hemiparesis, contralateral loss of proprioception & vibration, ipsilateral ataxia, ipsilateral facial palsy, lateral gaze paralysis, and diplopia. The blood supply affected is from branches of the basilar artery.
  • Lateral pontine syndrome (Marie-Foix syndrome): Affects the nuclei of CN VII, & VIII, corticospinal tract, spinothalamic tract, and cerebellar tracts. It results in contralateral hemiparesis, contralateral loss of proprioception & vibration, ipsilateral limb ataxia, ipsilateral facial palsy, lateral hearing loss, vertigo, and nystagmus. The blood supply affected is the perforating branches of the basilar artery and the anterior inferior cerebellar artery.
  • Locked-in syndrome: Affects upper ventral pons, including corticospinal tract, corticobulbar tract, and CN VI nuclei. It results in quadriplegia, bilateral facial palsy, and horizontal eye palsy. The patient can move the eyes vertically, blink, and has an intact consciousness. The blood supply affected is the middle and proximal segments of the basilar artery.
  • Raymond syndrome: Affects the CN VI fibers, corticospinal tract, and cervicofacial fibers. It results in an ipsilateral lateral gaze palsy, contralateral hemiparesis, and facial palsy. The blood supply involved is from the branches of the basilar artery.
  • Upper dorsal pontine syndrome (Raymond-Cestan): Affects the longitudinal medial fasciculus, medial lemniscus, spinothalamic tract, CN V fibers and nuclei, superior and middle cerebellar peduncle. It results in ipsilateral ataxia, coarse intension tremors, sensory loss in the face, weakness of mastication, contralateral loss of all sensory modalities. The blood supply involved is from the circumferential branches of the basilar artery.
  • Ventral pontine syndrome (Millard-Gubler): Affects the CN VI & VII and corticospinal tract. It results in ipsilateral lateral rectus palsy, diplopia, ipsilateral facial palsy, and contralateral hemiparesis of upper and lower limbs. The blood supply involved derives from the branches from the basilar artery.

Medulla oblongata

  • Allis syndrome: Affects the pyramidal tract and nucleus ambiguous. It results in ipsilateral palatopharyngeal palsy, contralateral hemiparesis, and contralateral Hemi-sensory impairment. The blood supply affected is the vertebral arteries.
  • Babinski-Nageotte syndrome: Also known as the Wallenberg with hemiparesis, affects the spinal fiber and nucleus of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, afferent spinocerebellar tracts, and corticospinal tract. It results in ipsilateral facial loss of pain & temperature, ipsilateral palsy of the soft palate, larynx &  pharynx, ipsilateral Horner syndrome, ipsilateral cerebellar Hemi-ataxia, contralateral hemiparesis, and contralateral loss of body pain and temperature. The blood supply involved is from the intracranial portion of the vertebral artery and branches from the posterior inferior cerebellar artery.
  • Cestan-Chenais syndrome: It affects the spinal fiber and nucleus of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, and corticospinal tract. It results in ipsilateral facial loss of pain and temperature, ipsilateral palsy of the soft palate, larynx & pharynx, ipsilateral Horner’s syndrome, contralateral hemiparesis, contralateral loss of body pain & temperature, and contralateral tactile hypesthesia. The blood supply affected is the intracranial portion of the vertebral artery and branches from the posterior inferior cerebellar artery.
  • Hemimedullary syndrome (Reinhold syndrome): Affects the nucleus & fiber of CN V, CN XII nucleus ambiguous, lateral spinothalamic tract, sympathetic fibers, afferent spinocerebellar tracts, corticospinal tract, and medial lemniscus. It results in ipsilateral Horner’s syndrome, ipsilateral facial loss of pain & temperature, ipsilateral palsy of soft palate, larynx & pharynx, ipsilateral tongue weakness, ipsilateral cerebellar Hemi-ataxia, contralateral hemiparesis, and contralateral face sparing hemihypesthesia. The blood supply involved is from the ipsilateral vertebral artery, the posterior inferior cerebellar artery, and branches from the anterior spinal artery.
  • Jackson syndrome: Affects CN XII and pyramidal tract. It results in ipsilateral palsy of the tongue and contralateral hemiparesis. The blood supply involved is from the branches of the anterior spinal artery.
  • Lateral medullary syndrome (Wallenberg syndrome): Affects the spinal nucleus & fiber of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, inferior cerebellar peduncle, and vestibular nuclei. It results in ipsilateral Horner’s syndrome, ipsilateral facial loss of pain & temperature, ipsilateral palsy of soft palate, larynx & pharynx, ipsilateral cerebellar Hemi-ataxia, contralateral loss of body pain & temperature, nystagmus, dysarthria, dysphagia, and hyperacusis. The blood supply affected is the vertebral artery and branches from the posterior inferior cerebellar artery.
  • Medial medullary syndrome (Dejerine syndrome): Affects the fibers of CN XII, corticospinal tract, and medial lemniscus spinal. Results in ipsilateral tongue weakness, ipsilateral loss of proprioception & vibration, contralateral hemiparesis, and contralateral face sparing hemihypesthesia. The blood supply affected is the branches from the vertebral artery and the anterior spinal artery.
  • Schmidt syndrome: Affects the fibers and nuclei of CN IX, X, XI, and pyramidal system. It results in ipsilateral palsy of the vocal cords, soft palate, trapezius, & sternocleidomastoid muscle, and contralateral spastic hemiparesis. The blood supply involved involves branches from the vertebral artery, the posterior inferior cerebellar artery the anterior spinal artery.
  • Spiller syndrome: Affects the fibers and nucleus of CN XII, corticospinal tract, and medial lemniscus spinal along with medial Hemi-medulla. Results in ipsilateral tongue weakness, ipsilateral loss of proprioception & vibration, contralateral hemiparesis, and contralateral face sparing hemihypesthesia. The blood supply involved is from the branches from the vertebral artery and the anterior spinal artery.
  • Tapia syndrome: Affects the nucleus ambiguous, CN XII, and pyramidal tract. It results in ipsilateral palsy of the trapezius, sternocleidomastoid muscle, & half of the tongue, dysphagia, dysphonia, and contralateral spasmodic hemiparesis. The blood supply involved is from the branches from the vertebral artery, the posterior inferior cerebellar artery the anterior spinal artery.
  • Vernet syndrome: Affects the CN IX, X, and XI. It occurs due to compression in the jugular foramen

Treatment of Brainstem Stroke Syndromes

After the patient’s airway, breathing and circulation have been stabilized, a timeframe of the patient’s symptoms is obtained. Vitals and fluid status must be stabilized. Hypo or hyperglycemia must be corrected. Fever, if present, should be managed accordingly. Blood pressure must not be aggressively controlled to allow permissive hypertension only in the case of ischemic injury. Patients with last known normal within 4.5 hours can be considered as candidates for thrombolysis, whereas a 24 hour last known normal can be candidates for mechanical thrombectomy. If it is a case presenting earlier than 4.5 hours of onset, thrombolysis with intravenous recombinant tissue plasminogen activator significantly improves the clinical outcome.

Tissue plasminogen activator (tPA)

Inclusion criteria for tPA:

  • Clinical diagnosis of ischemic stroke
  • <4.5 hours of the onset of symptoms
  • Age >18 and <80 years
  • Symptoms of stroke presenting for more than 30 minutes

Excision criteria for tPA:

  • Unknown timeline of onset of patient symptoms
  • Intracranial hemorrhage or any active bleeding
  • Persistently elevated blood pressure ≥ 185 mmHg systolic and ≥ 110 mmHg diastolic
  • Low platelets <100,000/mm3, altered INR >1.7, PT >15 sec or aPTT >40sec
  • Current use of anti-coagulant
  • Severe hypoglycemia <50mg/dL
  • History of previous intracranial hemorrhage
  • History of gastrointestinal bleeding in the past 21 days
  • History of intracranial or intraspinal surgery in the past 90 days
  • History of intra-axial intracranial neoplasm or gastrointestinal malignancy

Intravenous alteplase (recombinant tissue plasminogen activator) should be given at the dose of 0.9 mg/kg (maximum dose of 90 mg/kg) with 10% as the loading dose in the first minute. The patient must be under continuous observation. Anti-platelet therapy must be withheld for at least 24 hours post thrombolysis and restarted after a head CT scan without evidence of bleeding.

Mechanical endovascular thrombectomy in patients with large anterior circulation occlusion is well documented; however, most strokes affecting the brainstem arise from posterior circulation perforating branches. For those cases where the occlusion is at the main vertebral or basilar artery, endovascular thrombectomy is recommended for successful revascularization and favorable outcome. Other studies have shown no evidence of a difference in favorable outcomes between endovascular therapy when compared to standard medical therapy alone.

Antiplatelet therapy: The usage of acetylsalicylic acid as monotherapy or dual therapy along with clopidogrel within 24 – 48 hours after the onset of symptoms significantly improved patient outcomes.

Management of risk factors like hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, thyroid abnormalities, sleep apnea, malignancies, and hypercoagulable states should be treated accordingly.  Dietary and lifestyle modification must be explained and discussed. Supplementation with vitamin B12 and vitamin D3 should also be considered. Physiotherapy, along with speech therapy, can be used if physical deficits arise due to infarct. Treatments must start at the earliest and must be aggressively pursued as the brain losses its plasticity within 90 days.

The differential diagnosis of brainstem infarction includes the following:

  • Transient ischemic attack
  • Metastatic disease of the brain
  • Central pontine demyelination
  • Subarachnoid hemorrhage
  • Seizures
  • Basilar migraine
  • Basilar meningitis
  • Cerebellopontine angle tumors
  • Supratentorial hemispheric mass effect with herniation and brainstem compression
  • Hypoglycemia
  • Electrolyte imbalance
  • Conversion disorder

Complications

  • Hemorrhagic transformation
  • Seizures
  • Aspiration pneumonia
  • Myocardial infarction, arrhythmias, and heart failure
  • Dysphagia and dysphonia
  • Depression and anxiety
  • Blackouts and falls
  • Sleep disorders
  • Urinary tract infection
  • Deep vein thrombosis
  • Pulmonary embolism
  • Dehydration and malnutrition
  • Pressure sores and skin lesions
  • Orthopedic complications and contractures
  • Post-stroke fatigue

Patient Education

ACT FAST is an acronym suggested by the American Stroke Association to recognize the early symptoms of a stroke. It has the following components:

  • F-Face drooping
  • A-Arm Weakness
  • S-Speech
  • T-Time to call 9-1-1

Along with the above symptoms, if the patient experiences any of the following, emergency medical services must be activated

  • Sudden confusion
  • Sudden trouble seeing
  • Sudden numbness
  • Sudden trouble walking
  • Sudden severe headache

Control of risk factors can significantly reduce future strokes:

  • Smoking cessation
  • Alcohol use
  • Drug addiction and abuse
  • Hypertension and diabetes control
  • Obesity and sedentary lifestyle
  • Sleep apnea
  • Regular follow with primary care physician

Stroke and intracranial hemorrhage

  • stroke and intracranial hemorrhage
    • code stroke CT (an approach)
    • ischemic stroke
      • general discussions
        • CT perfusion
          • infarct core
          • ischemic penumbra
          • luxury perfusion
        • multiphase CT angiography
        • fogging phenomenon
        • calcified cerebral embolus
        • DWI in acute stroke
          • early DWI reversal
          • ADC pseudonormalization
          • T2 shine-through
          • T2 washout
          • T2 blackout
        • acute vs chronic ischemic stroke (CT)
        • transient ischemic attack (TIA)
        • intracranial atherosclerotic disease (ICAD)
      • scoring and classification systems
        • Alberta stroke program early CT score (ASPECTS)
          • CT angiography source image ASPECTS
        • Canadian Neurological Scale
        • NIH Stroke Scale
        • Mathew Stroke Scale
        • modified Rankin scale
        • Orgogozo Stroke Scale
        • Scandinavian Stroke Scale
        • thrombolysis in cerebral infarction (TICI)
          • modified treatment in cerebral infarction (mTICI)
        • TOAST classification
        • collateral vessel scores
          • single-phase CTA collateral scores
          • multiphase CTA collateral score
      • signs
        • carotid pseudo-occlusion
        • hyperdense MCA sign
        • MCA dot sign
        • salted pretzel sign
        • tandem lesion
      • by region
        • hemispheric infarcts
          • frontal lobe infarct
          • parietal lobe infarct
            • Gerstmann syndrome
          • temporal lobe infarct
          • occipital lobe infarct
            • alexia without agraphia syndrome: PCA
            • cortical blindness syndrome (Anton syndrome): top of basilar or bilateral PCA
            • Balint syndrome: bilateral PCA
        • lacunar infarct
          • lacunar stroke syndromes
          • lenticulostriate infarct
        • thalamic infarct
          • Déjerine-Roussy syndrome (thalamic pain syndrome): thalamoperforators of PCA
          • top of the basilar syndrome
        • striatocapsular infarct
        • cerebellar infarct
        • brainstem infarct
          • midbrain infarct
            • Benedikt syndrome: PCA
            • Claude syndrome: PCA
            • Nothnagel syndrome: PCA
            • Weber syndrome: PCA
          • pontine infarct
            • Brissaud-Sicard syndrome
            • facial colliculus syndrome
            • Gasperini syndrome: basilar artery or AICA
            • inferior medial pontine syndrome (Foville syndrome): basilar artery
            • lateral pontine syndrome (Marie-Foix syndrome): basilar artery or AICA
            • locked-in syndrome: basilar artery
            • Millard-Gubler syndrome: basilar artery
            • Raymond syndrome: basilar artery
          • medullary infarct
            • Babinski-Nageotte syndrome
            • hemimedullary syndrome (Reinhold syndrome)
            • lateral medullary stroke syndrome (Wallenberg syndrome)
            • medial medullary syndrome (Déjerine syndrome)
        • acute spinal cord ischemia syndrome
          • anterior spinal artery syndrome
          • sulcal artery syndrome
          • posterior spinal artery syndrome
      • by vascular territory
        • anterior circulation infarction
          • anterior cerebral artery infarct
          • anterior choroidal artery infarct
          • middle cerebral artery infarct
            • hyperdense MCA sign
            • MCA dot sign
        • posterior circulation infarction
          • basilar artery infarct
          • posterior cerebral artery infarct
            • artery of Percheron infarct
          • brainstem infarct
            • midbrain infarct
            • pontine infarct
            • medullary infarct
          • cerebellar infarction
            • superior cerebellar artery infarct
            • anterior cerebellar artery infarct
            • posterior inferior cerebellar artery infarct
      • treatment options
        • mechanical thrombectomy
      • complications
        • crossed cerebellar diaschisis
        • hemorrhagic transformation of an ischemic infarct
          • cerebral intraparenchymal hyperattenuations post thrombectomy
    • intracranial hemorrhage
      • intra-axial hemorrhage
        • signs and formulas
          • ABC/2 (volume estimation)
          • CTA spot sign
          • swirl sign
        • by region or type
          • basal ganglia hemorrhage
          • cerebellar hemorrhage
            • remote cerebellar hemorrhage
          • cerebral contusions
          • cerebral microhemorrhage
          • ​hemorrhagic venous infarct
          • hemorrhagic transformation of an ischemic infarct
            • cerebral intraparenchymal hyperattenuations post thrombectomy
          • hypertensive intracranial hemorrhage
          • intraventricular hemorrhage (IVH)
          • jet hematoma
          • lobar hemorrhage
            • cerebral amyloid angiopathy
          • pontine hemorrhage
            • Duret hemorrhage
      • extra-axial hemorrhage
        • extradural versus subdural hemorrhage
        • extradural hemorrhage (EDH)
          • venous extradural hemorrhage
        • intralaminar dural hemorrhage
        • subdural hemorrhage (SDH)
          • calcified chronic subdural hemorrhage
        • subarachnoid hemorrhage (SAH)
          • types
            • ruptured berry aneurysm
              • berry aneurysm
              • fusiform aneurysm
              • mycotic aneurysm
            • convexal subarachnoid hemorrhage
            • traumatic subarachnoid hemorrhage (TSAH)
            • perimesencephalic subarachnoid hemorrhage (PMSAH)
          • vasospasm following SAH
          • grading systems
            • Hunt and Hess grading system
            • Fisher scale
            • modified Fisher scale
            • SDASH score
            • WFNS grading system
        • subpial hemorrhage

References

Frontotemporal Neurocognitive Disorder – Symptoms, Treatment

Frontotemporal Neurocognitive Disorder is a progressive, neurodegenerative, heterogeneous group of non-Alzheimer dementias disorder characterized by loss of intellectual functions, such as memory problems, impaired abstract thinking, reasoning, behavioral changes, and language deficits with frontal and temporal cortical degeneration and executive function, severe enough to hamper activities of daily living. It requires a multidisciplinary approach to improve patient outcomes. The clinical manifestation includes behavior changes, dietary changes, loss of empathy, apathy, and executive function.

Frontotemporal Disorders /Few people have heard of frontotemporal disorders, which lead to dementias that affect personality, behavior, language, and movement. These disorders are little known outside the circles of researchers, clinicians, patients, and caregivers who study and live with them. Although frontotemporal disorders remain puzzling in many ways, researchers are finding new clues that will help them solve this medical mystery and better understand other common dementias.

Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the frontal and temporal lobes.[rx] FTDs are broadly presented as behavioral or language disorders.[rx] The three main subtypes or variant syndromes are a behavioral variant (bvFTD) previously known as Pick’s disease, and two variants of primary progressive aphasia – semantic variant (svPPA), and nonfluent variant (nfvPPA).[rx][rx] Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID), and basophilic inclusion body disease. Other related disorders include corticobasal syndrome and FTD with amyotrophic lateral sclerosis (ALS) FTD-ALS also called FTD-MND.[rx]

Synonyms of Frontotemporal Degeneration

  • frontotemporal dementia
  • frontotemporal lobar degeneration
  • FTD
  • FTLD
  • Pick’s disease (limited, see below)

Subdivisions of Frontotemporal Degeneration

  • behavioral variant frontotemporal degeneration (bvFTD)
  • primary progressive aphasia (PPA)
  • semantic variant primary progressive aphasia (svPPA)
  • nonfluent variant primary progressive aphasia (naPPA)
  • logopenic variant primary progressive aphasia (lvPPA)
  • progressive supranuclear palsy (PSP) syndrome
  • corticobasal syndrome (CBS)
  • FTD with motor neuron disease (FTD-MND)
  • frontotemporal lobar degeneration
  • behavioral variant frontotemporal dementia
  • semantic dementia
  • progressive non-fluent aphasia

The Basics of Frontotemporal Neurocognitive Disorder

Frontotemporal disorders are the result of damage to neurons (nerve cells) in parts of the brain called the frontal and temporal lobes. As neurons die in the frontal and temporal regions, these lobes atrophy, or shrink. Gradually, this damage causes difficulties in thinking and behaviors normally controlled by these parts of the brain. Many possible symptoms can result, including unusual behaviors, emotional problems, trouble communicating, difficulty with work, or difficulty with walking.

A Form of Dementia

Frontotemporal disorders are forms of dementia caused by a family of brain diseases known as frontotemporal lobar degeneration (FTLD). Dementia is a severe loss of thinking abilities that interferes with a person’s ability to perform daily activities such as working, driving, and preparing meals. Other brain diseases that can cause dementia include Alzheimer’s disease and multiple strokes. Scientists estimate that FTLD may cause up to 10 percent of all cases of dementia and may be about as common as Alzheimer’s among people younger than age 65. Roughly 60 percent of people with FTLD are 45 to 64 years old.

People can live with frontotemporal disorders for up to 10 years, sometimes longer, but it is difficult to predict the time course for an individual patient. The disorders are progressive, meaning symptoms get worse over time. In the early stages, people may have just one type of symptom. As the disease progresses, other types of symptoms appear as more parts of the brain are affected.

No cure or treatments that slow or stop the progression of frontotemporal disorders are available today. However, research is improving awareness and understanding of these challenging conditions. This progress is opening doors to better diagnosis, improved care, and, eventually, new treatments.

FTD? FTLD? Understanding Terms

One of the challenges shared by patients, families, clinicians, and researchers is confusion about how to classify and label frontotemporal disorders. A diagnosis by one doctor may be called something else by a second, and the same condition or syndrome referred to by another name by a pathologist who examines the brain after death.

For many years, scientists and physicians used the term frontotemporal dementia (FTD) to describe this group of illnesses. After further research, FTD is now understood to be just one of several possible variations and is more precisely called behavioral variant frontotemporal dementia, or bvFTD.

This booklet uses the term frontotemporal disorders to refer to changes in behavior and thinking that are caused by underlying brain diseases collectively called frontotemporal lobar degeneration (FTLD). FTLD is not a single brain disease but rather a family of neurodegenerative diseases, any one of which can cause a frontotemporal disorder. Frontotemporal disorders are diagnosed by physicians and psychologists based on a person’s symptoms and results of brain scans and genetic tests. With the exception of known genetic causes, the type of FTLD can be identified definitively only by brain autopsy after death.

Changes in the Brain

Frontotemporal disorders affect the frontal and temporal lobes of the brain. They can begin in the frontal lobe, the temporal lobe, or both. Initially, frontotemporal disorders leave other brain regions untouched, including those that control short-term memory.

The frontal lobes, situated above the eyes and behind the forehead both on the right and left sides of the brain, direct executive functioning. This includes planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and monitoring and correcting errors.

When functioning well, the frontal lobes also help manage emotional responses. They enable people to avoid inappropriate social behaviors, such as shouting loudly in a library or at a funeral. They help people make decisions that make sense for a given situation. When the frontal lobes are damaged, people may focus on insignificant details and ignore important aspects of a situation or engage in purposeless activities. The frontal lobes are also involved in language, particularly linking words to form sentences, and in motor functions, such as moving the arms, legs, and mouth.

The temporal lobes, located below and to the side of each frontal lobe on the right and left sides of the brain, contain essential areas for memory but also play a major role in language and emotions. They help people understand words, speak, read, write, and connect words with their meanings. They allow people to recognize objects and to relate appropriate emotions to objects and events. When the temporal lobes are dysfunctional, people may have difficulty recognizing emotions and responding appropriately to them.

Which lobe—and part of the lobe—is affected first determines which symptoms appear first. For example, if the disease starts in the part of the frontal lobe responsible for decision-making, then the first symptom might be trouble managing finances. If it begins in the part of the temporal lobe that connects emotions to objects, then the first symptom might be an inability to recognize potentially dangerous objects—a person might reach for a snake or plunge a hand into boiling water, for example.

Types of Frontotemporal Neurocognitive Disorder

Frontotemporal disorders can be grouped into three types, defined by the earliest symptoms physicians identify when they examine patients.

  • Progressive behavior/personality decline—characterized by changes in personality, behavior, emotions, and judgment (called
    behavioral variant frontotemporal dementia).
  • Progressive language decline—marked by early changes in language ability, including speaking, understanding, reading, and writing (called primary progressive aphasia).
  • Progressive motor decline—characterized by various difficulties with physical movement, including the use of one or more limbs, shaking, difficulty walking, frequent falls, and poor coordination (called a corticobasal syndrome, supranuclear palsy, or amyotrophic lateral sclerosis).

Based on anatomic, genetic, and neuropathologic categorizations, the six clinical subtypes of FTD or related disorders are

  • (1) behavioral variant of FTD,
  • (2) semantic variant primary progressive aphasia,
  • (3) nonfluent agrammatic variant primary progressive aphasia,
  • (4) corticobasal syndrome,
  • (5) progressive supranuclear palsy, and
  • (6) FTD associated with motor neuron disease. Recognition and accurate diagnoses of FTD subtypes will aid the neurologist in the management of patients with FTD.

In the early stages it can be hard to know which of these disorders a person has because symptoms and the order in which they appear can vary widely from one person to the next. Also, the same symptoms can appear later in different disorders. For example, language problems are most typical of primary progressive aphasia but can also appear later in the course of behavioral variant frontotemporal dementia. The table on page 6 summarizes the three types of frontotemporal disorders and lists the various terms that could be used when clinicians diagnose these disorders.

Behavioral Variant Frontotemporal Dementia

The most common frontotemporal disorder, behavioral variant frontotemporal dementia (bvFTD), involves changes in personality, behavior, and judgment. People with this dementia can act strangely around other people, resulting in embarrassing social situations. Often, they don’t know or care that their behavior is unusual and don’t show any consideration for the feelings of others. Over time, language and/or movement problems may occur, and the person needs more care and supervision.

In the past, bvFTD was called Pick’s disease, named after Arnold Pick, the German scientist who first described it in 1892. The term Pick’s disease is now used to describe abnormal collections in the brain of the protein tau, called “Pick bodies.” Some patients with bvFTD have Pick bodies in the brain, and some do not.

Primary Progressive Aphasia

Primary progressive aphasia (PPA) involves changes in the ability to communicate—to use language to speak, read, write, and understand what others are saying. Problems with memory, reasoning, and judgment are not apparent at first but can develop over time. In addition, some people with PPA may experience significant behavioral changes, similar to those seen in bvFTD, as the disease progresses.

There are three types of PPA, categorized by the kind of language problems seen at first. Researchers do not fully understand the biological basis of the different types of PPA. But they hope one day to link specific language problems with the abnormalities in the brain that cause them.

In semantic PPA, also called semantic dementia, a person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.

In agrammatic PPA, also called progressive nonfluent aphasia, a person has more and more trouble producing speech. Eventually, the person may no longer be able to speak at all. He or she may eventually develop movement symptoms similar to those seen in corticobasal syndrome.

In logopenic PPA, a person has trouble finding the right words during the conversation but can understand words and sentences. The person does not have problems with grammar.

Movement Disorders

Two rare neurological disorders associated with FTLD, corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), occur when the parts of the brain that control movement is affected. The disorders may affect thinking and language abilities, too.

CBS can be caused by corticobasal degeneration—gradual atrophy and loss of nerve cells in specific parts of the brain. This degeneration causes progressive loss of the ability to control movement, typically beginning around age 60. The most prominent symptom may be the inability to use the hands or arms to perform a movement despite normal strength (called apraxia). Symptoms may appear first on one side of the body, but eventually, both sides are affected. Occasionally, a person with CBS first has language problems or trouble orienting objects in space and later develops movement symptoms.

PSP causes problems with balance and walking. People with the disorder typically move slowly, experience unexplained falls, lose facial expression, and have body stiffness, especially in the neck and upper body—symptoms similar to those of Parkinson’s disease. A hallmark sign of PSP is trouble with eye movements, particularly looking down. These symptoms may give the face a fixed stare. Behavior problems can also develop.

Other movement-related frontotemporal disorders include frontotemporal dementia with parkinsonism and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS).

Frontotemporal dementia with parkinsonism can be an inherited disease caused by a genetic tau mutation. Symptoms include movement problems similar to those of Parkinson’s disease, such as slowed movement, stiffness, and balance problems, and changes in behavior or language.

FTD-ALS is a combination of bvFTD and ALS, commonly called Lou Gehrig’s disease. Symptoms include the behavioral and/or language changes seen in bvFTD as well as the progressive muscle weakness seen in ALS. Symptoms of either disease may appear first, with other symptoms developing over time. Mutations in certain genes have been found in some patients with FTD-ALS.

Causes of Frontotemporal Neurocognitive Disorder

Frontotemporal lobar degeneration (FTLD) is not a single brain disease but rather a family of brain diseases that share some common molecular features. Scientists are beginning to understand the biological and genetic basis for the changes observed in brain cells that lead to FTLD.

Scientists describe FTLD in terms of patterns of change in the brain seen in an autopsy after death. These changes include loss of neurons and abnormal amounts or forms of proteins called tau and TDP-43. These proteins occur naturally in the body and help cells function properly. When the proteins don’t work properly and accumulate in cells, for reasons not yet fully understood, neurons in specific brain regions are damaged.

In most cases, the cause of a frontotemporal disorder is unknown. In about 15 to 40 percent of people, a genetic (hereditary) cause can be identified. Individuals with a family history of frontotemporal disorders are more likely to have a genetic form of the disease than those without such a history.

Familial and inherited forms of frontotemporal disorders are often related to mutations (permanent changes) in certain genes. Genes are basic units of heredity that tell cells how to make the proteins the body needs to function. Even small changes in a gene may produce an abnormal protein, which can lead to changes in the brain and, eventually, disease.

Scientists have discovered several different genes that, when mutated, can lead to frontotemporal disorders:

  • Tau gene (also called the MAPT gene)—A mutation in this gene causes abnormalities in a protein called tau, which forms tangles inside neurons and ultimately leads to the destruction of brain cells. Inheriting a mutation in this gene means a person will almost surely develop a frontotemporal disorder, usually the bvFTD form, but the exact age of onset and symptoms cannot be predicted.
  • PGRN gene— A mutation in this gene can lead to lower production of the protein progranulin, which in turn causes TDP-43, a cellular protein, to go awry in brain cells. Many frontotemporal disorders can result, though bvFTD is the most common. The PRGRN gene can cause different symptoms in different family members and cause the disease to begin at different ages.
  • VCP, CHMP2B, TARDBP, and FUS genes— Mutations in these genes lead to very rare familial types of frontotemporal disorders. TARDBP and FUS gene mutations are more often associated with hereditary ALS.
  • C9ORF72 gene— An unusual mutation in this gene appears to be the most common genetic abnormality in familial frontotemporal disorders and familial ALS. It also occurs in some cases of sporadic ALS. This mutation can cause a frontotemporal disorder, ALS, or both conditions in a person.

Scientists are continuing to study these genes and to search for other genes and proteins, as well as nongenetic risk factors, that may play a role in frontotemporal disorders. They are trying to understand, for example, how mutations in a single gene lead to different frontotemporal disorders in members of the same family. Environmental factors that may influence the risk for developing the disorders are also being examined.

Families affected by inherited and familial forms of frontotemporal disorders can help scientists further research by participating in clinical studies and trials. For more information, talk with a health care professional, contact any of the research centers listed at the end of this booklet or search www.clinicaltrials.gov.

Symptoms of Frontotemporal Neurocognitive Disorder

Symptoms of frontotemporal disorders vary from person to person and from one stage of the disease to the next as different parts of the frontal and temporal lobes are affected. In general, changes in the frontal lobe are associated with behavioral symptoms, while changes in the temporal lobe lead to language and emotional disorders.

Symptoms are often misunderstood. Family members and friends may think that a person is misbehaving, leading to anger and conflict. For example, a person with bvFTD may neglect personal hygiene or start shoplifting. It is important to understand that people with these disorders cannot control their behaviors and other symptoms. Moreover, they lack any awareness of their illness, making it difficult to get help.

Behavioral Symptoms

  • Problems with executive functioning—Problems with planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and self-monitoring and correcting behavior.
  • Perseveration—A tendency to repeat the same activity or to say the same word over and over, even when it no longer makes sense.
  • Social disinhibition—Acting impulsively without considering how others perceive the behavior. For example, a person might hum at a business meeting or laugh at a funeral.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Utilization behavior—Difficulty resisting impulses to use or touch objects that one can see and reach. For example, a person picks up the telephone receiver while walking past it when the phone is not ringing and the person does not intend to place a call.
  • Inappropriate social behavior and lack of social tact/manners. Examples include touching or kissing strangers, urinating in public, making rude or offensive comments, arguing, rashly overspending, and/or doing or saying things that others would find embarrassing or disgusting.
  • Lack of empathy (interest in, or understanding of, what others feel), loss of interest in other people or activities, reduced affection, neglect of personal grooming and hygiene. People with FTD are not aware of the changes that are happening and do not know how hurtful they are to close family members.
  • Changes in food preferences, overstuffing mouth with food, binge eating, eating food quickly, attempting to eat non-food items.
  • Becoming very obsessive or developing rituals, repeating things, collecting/hoarding items.

Language Symptoms

  • Aphasia—A language disorder in which the ability to use or understand words is impaired but the physical ability to speak properly is normal.
  • Dysarthria—A language disorder in which the physical ability to speak properly is impaired (e.g., slurring) but the message is normal. People with PPA may have only problems using and understanding words or also problems with the physical ability to speak. People with both kinds of problems have trouble speaking and writing. They may become mute, or unable to speak. Language problems usually get worse, while other thinking and social skills may remain normal for longer before deteriorating.

Emotional Symptoms

  • Apathy—A lack of interest, drive, or initiative. Apathy is often confused with depression, but people with apathy may not be sad. They often have trouble starting activities but can participate if others do the planning.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Emotional changes—Emotions are flat, exaggerated, or improper. Emotions may seem completely disconnected from a situation or are expressed at the wrong times or in the wrong circumstances. For example, a person may laugh at sad news.
  • Social-interpersonal changes—Difficulty “reading” social signals, such as facial expressions, and understanding personal relationships. People may lack empathy—the ability to understand how others are feeling—making them seem indifferent, uncaring, or selfish. For example, the person may show no emotional reaction to illnesses or accidents that occur to family members.

Movement Symptoms

  • Dystonia—Abnormal postures of body parts such as the hands or feet. A limb may be bent stiffly or not used when performing activities that are normally done with two hands.
  • Gait disorder—Abnormalities in walking, such as walking with a shuffle, sometimes with frequent falls.
  • Tremor—Shakiness, usually of the hands.
  • Clumsiness—Dropping of small objects or difficulty manipulating small items like buttons or screws.
  • Apraxia—Loss of ability to make common motions, such as combing one’s hair or using a knife and fork, despite normal strength.
  • Neuromuscular weakness—Severe weakness, cramps, and rippling movements in the muscles.

Diagnosis of Frontotemporal Neurocognitive Disorder

Consensus criteria for FTD

  1. Core diagnostic features

    A. Insidious onset and gradual progression

    B. Early decline in social interpersonal conduct

    C. Early impairment in regulation of personal conduct

    D. Early emotional blunting

    E. Early loss of insight

  2. Supportive diagnostic features

    A. Behavioral disorder

    1. Decline in personal hygiene and grooming

    2. Mental rigidity and inflexibility

    3. Distractibility and impersistence

    4. Hyperorality and dietary changes

    5. Perseverative and stereotyped behavior

    6. Utilization behavior

    B. Speech and language

    1. Altered speech output

    a. Aspontaneity and economy of speech

    b. Pressure of speech

    2. Stereotypy of speech

    3. Echolalia

    4. Perseveration

    5. Mutism

    C. Physical signs

    1. Primitive reflexes

    2. Incontinence

    3. Akinesia, rigidity, and tremor

    4. Low and labile blood pressure

    D. Investigations

    1. Neuropsychology: impairment on frontal lobe tests without severe amnesia, aphasia, or perceptuospatial disorder

    2. Electroencephalography: normal on conventional EEG despite clinically evident dementia

    3. Brain imaging (structural and/or functional): predominant frontal and/or anterior temporal abnormality

No single test, such as a blood test, can be used to diagnose a frontotemporal disorder. A definitive diagnosis can be confirmed only by a genetic test in familial cases or a brain autopsy after a person dies. To diagnose a probable frontotemporal disorder in a living person, a doctor— usually a neurologist, psychiatrist, or psychologist—will:

  • record a person’s symptoms, often with the help of family members or friends
  • compile a personal and family medical history
  • perform a physical exam and order blood tests to help rule out other similar conditions
  • if appropriate, order testing to uncover genetic mutations
  • conduct a neuropsychological evaluation to assess behavior, language, memory, and other cognitive functions
  • use brain imaging to look for changes in the frontal and temporal lobes.

In all forms of FTD, functional ability and activities of daily living are compromised.

  • Behavior variant type FTD (bvFTD) – It is the most common phenotype. Patients suffering from bvFTD may present with a cluster of altered behavior and personality changes earlier in the disease process, which include disinhibition, loss of emotional reactivity and disease insight, apathy, impaired abstract thinking and executive function that gradually worsens over time. Additionally, it may demonstrate a change in dietary behavior and loss of fundamental emotions and empathy but with intact memory until late in the disease.
  • Semantic variant FTD – In this form of FTD, patients manifest language difficulties characterized by paraphasia (impaired word-finding ability or loss of vocabulary), difficulty in understanding the meaning of words, impaired comprehension, and difficulty in recognizing unfamiliar objects or faces. Their speech is fluent but not making any sense. Memory is affected late in the disease.
  • Non-fluent variant Primary Progressive Aphasia (nfvPPA) – Patients with this type of FTD presents clinically with effortful halted speech and paraphasia (jumbled words), difficulty in understanding complex sentences and naming objects. Their memory, abstract thinking, and calculating abilities are spared earlier in the disease course.

Various bedside tests can be performed if clinical suspicion for FTD is high.

  • Go-no-go test – In this test, the patient is asked to perform an action in response to a particular stimulus and inhibit that action in response to different stimuli.
  • Letter fluency test – In this test, the patient is asked to say as many words (except proper nouns), starting with a single letter in one minute.
  • Attention test – It is used to evaluate the attention span. It is done either by serial seven subtractions from 100 or spells the word “world” backward.
  • Similarities and differences – It is done to evaluate abstract thinking. The patient is instructed to compare items (table and chair, apple, and orange).

Patients with frontotemporal dementia should be evaluated as follows:

  • Laboratory –  Neural and axonal cytoskeletons are mainly composed of neurofilaments, which are further made up of small subunits called neurofilament light chains. Neurofilament light chain, among other biomarkers, can be increasingly seen in blood and cerebrospinal fluid of FTD patients.
  • Radiographic tests – Magnetic resonance imaging, computed tomography scan, or single-photon emission tomography can be used to demonstrate atrophy and hypoperfusion in the frontal and temporal lobes. However, the findings are not specific. Imaging may aid in the diagnosis or to rule out other etiologies.
  • Electroencephalography (EEG) – It is not very helpful for FTD as it is for Alzheimer’s disease; however, in comparison to the healthy group, a typical EEG pattern was observed in several FTD patients and was marked by the reduction of fast activities (alpha, beta1- beta3), but no difference in slow activities (delta & theta waves).
  • Neurocognitive exams – Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, and Functional Cognitive Assessment. For primary care, the Cochrane dementia and cognitive improvement group supports the utilization of two tests; MMSE (the most commonly used test in primary care) and the Informant Questionnaire for Cognitive Disorders in the Elderly. MMSE assesses different domains of dementia, including but not limited to memory, cognition, language, attention/orientation, and executive functions.
  • A magnetic resonance imaging (MRI) – scan shows changes in the size and shape of the brain, including the frontal and temporal lobes. It may reveal other potentially treatable causes of the person’s symptoms, such as a stroke or tumor. In the early stage of the disease, the MRI may appear normal. In this case, other types of imaging, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), may be useful. PET and SPECT scan to measure activity in the brain by monitoring blood flow, glucose usage, and oxygen usage. Other PET scans can help rule out a diagnosis of Alzheimer’s.
  • Cerebrospinal fluid – and serum protein biomarkers are presently utilized to exclude Alzheimer’s disease in the assessment of frontotemporal dementia and are under appraisal for prospective diagnostic indications and monitoring pathologic progression and response to potential therapies. Elevated CSF tau proteins and decreased beta-amyloid 42 protein concentrations can accurately confirm Alzheimer’s dementia and are validated for eliminating frontotemporal dementia from the differential.
  • Neurofilament light chain (NFL) – proteins are increased in serum and CSF samples of patients with frontotemporal dementia and other neurodegenerative disorders and have promising applications in future frontotemporal dementia assays. Gene-specific biomarkers such as progranulin and poly (GP) have the potential for investigating the expression of GRN and C9orf72 frontotemporal dementia mutations, respectively. As with potential imaging techniques, more data is needed to implement fluid biomarkers into a comprehensive frontotemporal dementia evaluation strategy.
  • Neuropsychological Testing – Performance patterns on cognitive testing may vary according to the subtype. Many patients with CBS will demonstrate deficits on tasks of executive function, writing, visuospatial, and construction tasks. Patients presenting with dominant frontal lobe involvement may show word-finding deficits, agrammatism, and spelling errors similar to patients with nonfluent agrammatic PPA.[
  • Neuroimaging – Structural brain imaging in patients with CBS may show asymmetric frontal and parietal lobe atrophy, although imaging findings may overlap with those seen in other FTDs and AD. Thus, diagnosis at present is based on clinical criteria, with neuroimaging performed to rule out other structural causes of symptoms.

Treatment of Frontotemporal Neurocognitive Disorder

So far, there is no cure for frontotemporal disorders and no way to slow down or prevent them. However, there are ways to manage symptoms. A team of specialists—doctors, nurses, and speech, physical, and occupational therapists—familiar with these disorders can help guide treatment.

Non-Pharmacologic Treatment

It includes a multidisciplinary approach, such as social support services, physical therapy & occupational therapy, speech therapy, cognitive behavior therapy, rehabilitation services, and caregivers’ education. Regular monitoring of the behavior of both the patient and caregiver for assessing activities of daily living, such as financial account managing, driving, environmental modification, and eating, is mandatory.

Pharmacological Treatment

Acetylcholinesterase inhibitors and N-methyl-D-Aspartate inhibitors have no proven benefit. Similarly, selective serotonin reuptake inhibitors (SSRI) have a limited role. It can improve certain behaviors, but not cognition. Antipsychotics have mixed results but comes with a price of severe extrapyramidal side effects to which the FTD patients are susceptible; therefore, they are not approved by the US food and drug administration as a treatment for FTD. Selective dopaminergic antagonists can improve motivation and apathy. Several disease-modifying drugs like Salsalate (tau acetylation inhibitor) and Gosuraneb (anti-tau monoclonal antibodies) targeting different biomarkers are being studied, but no recommendations yet have been made. Several other promising disease-modifying drugs are currently under clinical trials.

Managing Behavior

The behaviors of a person with bvFTD can upset and frustrate family members and other caregivers. It is natural to grieve for the “lost person,” but it is also important to learn how to best live with the person he or she has become. Understanding changes in personality and behavior and knowing how to respond can reduce caregivers’ frustration and help them cope with the challenges of caring for a person with a frontotemporal disorder.

Managing behavioral symptoms can involve several approaches. To ensure the safety of a person and his or her family, caregivers may have to take on new responsibilities or arrange care that was not needed before. For example, they may have to drive the person to appointments and errands, care for young children, or arrange for help at home.

It is helpful, though often difficult, to accept rather than challenge people with behavioral symptoms. Arguing or reasoning with them will not help because they cannot control their behaviors or even see that they are unusual or upsetting to others. Instead, be as sensitive as possible and understand that it’s the illness “talking.”

Frustrated caregivers can take a “timeout”—take deep breaths, count to 10, or leave the room for a few minutes.

To deal with apathy, limit choices and offer specific choices. Open-ended questions (“What would you like to do today?”) are more difficult to answer than specific ones (“Do you want to go to the movies or the shopping center today?”).

Maintaining the person’s schedule and modifying the environment can also help. A regular schedule is less confusing and can help people sleep better. If compulsive eating is an issue, caregivers may have to supervise eating, limit food choices, lock food cabinets and the refrigerator, and distract the person with other activities. To deal with other compulsive behaviors, caregivers may have to change schedules or offer new activities.

Medications are available to treat certain behavioral symptoms. Antidepressants called selective serotonin reuptake inhibitors are commonly prescribed to treat social disinhibition and impulsive behavior. Patients with aggression or delusions sometimes take low doses of antipsychotic medications. The use of Alzheimer’s disease medications to improve behavioral and cognitive symptoms in people with bvFTD and related disorders is being studied, though results so far have been mixed, with some medications making symptoms worse. If a particular medication is not working, a doctor may try another. Always consult a doctor before changing, adding, or stopping a drug.

Treating Language Problems

Treatment of primary progressive aphasia (PPA) has two goals—maintaining language skills and using new tools and other ways to communicate. Treatment tailored to a person’s specific language problem and stage of PPA generally works best. Since language ability declines over time, different strategies may be needed as the illness progresses.

To communicate without talking, a person with PPA may use a communication notebook (an album of photos labeled with names of people and objects), gestures, and drawings. Some people find it helpful to use or point to lists of words or phrases stored in a computer or personal digital assistant.

Caregivers can also learn new ways of talking to someone with PPA. For example, they can speak slowly and clearly, use simple sentences, wait for responses, and ask for clarification if they don’t understand something.

A speech-language pathologist who knows about PPA can test a person’s language skills and determine the best tools and strategies to use. Note that many speech-language pathologists are trained to treat aphasia caused by stroke, which requires different strategies from those used with PPA. (See the Resources section starting on page 27 to find speech-language pathologists and other experts who know about frontotemporal disorders.)

Managing Movement Problems

No treatment can slow down or stop frontotemporal-related movement disorders, though medications and physical and occupational therapy may provide modest relief.

For people with corticobasal syndrome (CBS), movement difficulties are sometimes treated with medications for Parkinson’s disease. But these medicines offer only minimal or temporary improvement. Physical and occupational therapy may help people with CBS move more easily. Speech therapy may help them manage language symptoms.

For people with progressive supranuclear palsy (PSP), sometimes Parkinson’s disease drugs provide temporary relief for slowness, stiffness, and balance problems. Exercises can keep the joints limber, and weighted walking aids— such as a walker with sandbags over the lower front rung—can help maintain balance. Speech, vision, and swallowing difficulties usually do not respond to any drug treatment. Antidepressants have shown modest success. For people with abnormal eye movements.

People with FTD-ALS typically decline quickly over the course of 2 to 3 years. During this time, physical therapy can help treat muscle symptoms, and a walker or wheelchair may be useful. Speech therapy may help a person speak more clearly at first. Later on, other ways of communicating, such as a speech synthesizer, can be used. The ALS symptoms of the disorder ultimately make it impossible to stand, walk, eat, and breathe on one’s own.

For any movement disorder caused by FTLD, a team of experts can help patients and their families address difficult medical and caregiving issues. Physicians, nurses, social workers, and physical, occupational, and speech therapists who are familiar with frontotemporal disorders can ensure that people with movement disorders get appropriate medical treatment and that their caregivers can help them live as well as possible.

The Future of Treatment

Researchers are continuing to explore the genetic and biological actions in the body that lead to frontotemporal disorders. In particular, they seek more information about genetic mutations that cause FTLD, as well as the disorders’ natural history and disease pathways. They also want to develop better ways, such as specialized brain imaging, to track its progression, so that treatments, when they become available, can be directed to the right people. The ultimate goal is to identify possible new drugs and other treatments to test.

Researchers are also looking for better treatments for frontotemporal disorders. Possible therapies that target the abnormal proteins found in the brain are being tested in the laboratory and in animals. Clinical trials and studies are testing a number of possible treatments in humans.

Clinical trials for individuals with frontotemporal disorders will require many participants. People with frontotemporal disorders and healthy people may be able to take part. To find out more about clinical trials, talk to your health care provider or visit www.clinicaltrials.gov.

Caring for a Person with a Frontotemporal Disorder

In addition to managing the medical and day-to-day care of people with frontotemporal disorders, caregivers can face a host of other challenges. These challenges may include changing family relationships, loss of work, poor health, decisions about long-term care, and end-of-life concerns.

Family Issues

People with frontotemporal disorders and their families often must cope with changing relationships, especially as symptoms get worse. For example, the wife of a man with bvFTD not only becomes her husband’s caregiver, but takes on household responsibilities he can no longer perform. Children may suffer the gradual “loss” of a parent at a critical time in their lives. The symptoms of bvFTD often embarrass family members and alienate friends. Life at home can become very stressful.

Work Issues

Frontotemporal disorders disrupt basic work skills, such as organizing, planning, and following through on tasks. Activities that were easy before the illness began might take much longer or become impossible. People lose their jobs because they can no longer perform them. As a result, the caregiver might need to take a second job to make ends meet—or reduce hours or even quit work to provide care and run the household. An employment attorney can offer information and advice about employee benefits, family leave, and disability if needed.

Workers diagnosed with any frontotemporal disorder can qualify quickly for Social Security disability benefits through the “compassionate allowances” program. For more information, see www.socialsecurity.gov/ compassionate allowances or call 1-800-772-1213.

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Caregiver Health and Support

Caring for someone with a frontotemporal disorder can be very hard, both physically and emotionally. To stay healthy, caregivers can do the following:

  • Get regular health care.
  • Ask family and friends for help with child care, errands, and other tasks.
  • Spend time doing enjoyable activities, away from the demands of caregiving. Arrange for respite care—short-term caregiving services
    that give the regular caregiver a break—or take the person to an adult daycare center, a safe, supervised environment for adults with
    dementia or other disabilities.
  • Join a support group for caregivers of people with frontotemporal disorders. Such groups allow caregivers to learn coping strategies and share feelings with others in the same position.

The organizations listed in the Resources section can help with information about caregiver services and support.

For many caregivers, there comes a point when they can no longer take care of the person with a frontotemporal disorder without help. The caregiving demands are simply too great, perhaps requiring around-the-clock care. As the disease progresses, caregivers may want to get home health care services or look for a residential care facility, such as a group home, assisted living facility, or nursing home. The decision to move the person with a frontotemporal disorder to a care facility can be difficult, but it can also give caregivers peace of mind to know that the person is safe and getting good care. The decreased level of stress may also improve the caregivers’ relationship with his or her loved one.

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End-of-Life Concerns

People with frontotemporal disorders typically live 6 to 8 years with their conditions, sometimes longer, sometimes less. Most people die of problems related to advanced disease. For example, as movement skills decline, a person can have trouble swallowing, leading to aspiration pneumonia, in which food or fluid gets into the lungs and causes infection. People with balance problems may fall and seriously injure themselves.

It is difficult, but important, to plan for the end of life. Legal documents, such as a will, living will, and durable powers of attorney for health care and finances should be created or updated as soon as possible after a diagnosis of bvFTD, PPA, or a related disorder. Early on, many people can understand and participate in legal decisions. But as their illness progresses, it becomes harder to make such decisions.

A physician who knows about frontotemporal disorders can help determine the person’s mental capacity. An attorney who specializes in elder law, disabilities, or estate planning can provide legal advice, prepare documents, and make financial arrangements for the caregiving spouse or partner and dependent children. If necessary, the person’s access to finances can be reduced or eliminated.

Next steps

Tips to help you get the most from a visit to your healthcare provider:

  • Know the reason for your visit and what you want to happen.
  • Before your visit, write down questions you want answered.
  • Bring someone with you to help you ask questions and remember what your provider tells you.
  • At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
  • Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
  • Ask if your condition can be treated in other ways.
  • Know why a test or procedure is recommended and what the results could mean.
  • Know what to expect if you do not take the medicine or have the test or procedure.
  • If you have a follow-up appointment, write down the date, time, and purpose for that visit.
  • Know how you can contact your provider if you have questions.

References

Child Cerebral Palsy – Causes, Symptoms, Treatment

Child Cerebral Palsy (CP) is a group of disorders that affect a person’s ability to move and maintain balance and posture. CP is the most common motor disability in childhood. Cerebral means having to do with the brain. Palsy means weakness or problems with using the muscles. CP is caused by abnormal brain development or damage to the developing brain that affects a person’s ability to control his or her muscles.

What is Cerebral Palsy?/Cerebral palsy refers to a group of neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination Cerebral palsy (CP) is caused by damage to or abnormalities inside the developing brain that disrupt the brain’s ability to control movement and maintain posture and balance. The term cerebral refers to the brain; palsy refers to the loss or impairment of motor function.

Cerebral palsy affects the motor area of the brain’s outer layer (called the cerebral cortex), the part of the brain that directs muscle movement.

Types of Child Cerebral Palsy

The specific forms of cerebral palsy are determined by the extent, type, and location of a child’s abnormalities. Doctors classify CP according to the type of movement disorder involved — spastic (stiff muscles), athetoid (writhing movements), or ataxic (poor balance and coordination) — plus any additional symptoms, such as weakness (paresis) or paralysis (plegia). For example, hemiparesis (hemi = half) indicates that only one side of the body is weakened. Quadriplegia (quad = four) means all four limbs are affected.

Spastic cerebral palsy is the most common type of disorder. People have stiff muscles and awkward movements. Forms of spastic cerebral palsy include:

  • Spastic hemiplegia/hemiparesis typically affects the arm and hand on one side of the body, but it can also include the leg. Children with spastic hemiplegia generally walk later and on tip-toe because of tight heel tendons. The arm and leg of the affected side are frequently shorter and thinner. Some children will develop an abnormal curvature of the spine (scoliosis). A child with spastic hemiplegia may also have seizures. The speech will be delayed and, at best, maybe competent, but intelligence is usually normal.
  • Spastic diplegia/diparesis involves muscle stiffness that is predominantly in the legs and less severely affects the arms and face, although the hands may be clumsy. Tendon reflexes in the legs are hyperactive. Toes point up when the bottom of the foot is stimulated. Tightness in certain leg muscles makes the legs move like the arms of a scissor. Children may require a walker or leg braces. Intelligence and language skills are usually normal.
  • Spastic quadriplegia/quadriparesis is the most severe form of cerebral palsy and is often associated with moderate-to-severe intellectual disability. It is caused by widespread damage to the brain or significant brain malformations. Children will often have severe stiffness in their limbs but a floppy neck. They are rarely able to walk. Speaking and being understood are difficult. Seizures can be frequent and hard to control.

Dyskinetic cerebral palsy (also includes athetoid, choreoathetoid, and dystonic cerebral palsies) is characterized by slow and uncontrollable writhing or jerky movements of the hands, feet, arms, or legs. Hyperactivity in the muscles of the face and tongue makes some children grimace or drool. They find it difficult to sit straight or walk. Some children have problems hearing, controlling their breathing, and/or coordinating the muscle movements required for speaking. Intelligence is rarely affected in these forms of cerebral palsy.

Ataxic cerebral palsy affects balance and depth perception. Children with ataxic CP will often have poor coordination and walk unsteadily with a wide-based gait. They have difficulty with quick or precise movements, such as writing or buttoning a shirt, or a hard time controlling voluntary movement such as reaching for a book.

Mixed types of cerebral palsy refer to symptoms that don’t correspond to any single type of CP but are a mix of types. For example, a child with mixed CP may have some muscles that are too tight and others that are too relaxed, creating a mix of stiffness and floppiness.

What other conditions are associated with cerebral palsy?

  • Intellectual disability. Approximately 30 – 50 percent of individuals with CP will be intellectually impaired. Mental impairment is more common among those with spastic quadriplegia than in those with other types of cerebral palsy.
  • Seizure disorder.  As many as half of all children with CP have one or more seizures. Children with both cerebral palsy and epilepsy are more likely to have intellectual disabilities.
  • Delayed growth and development.  Children with moderate to severe CP, especially those with spastic quadriparesis, often lag behind in growth and development. In babies, this lag usually takes the form of too little weight gain. In young children, it can appear as abnormal shortness, and in teenagers, it may appear as a combination of shortness and lack of sexual development. The muscles and limbs affected by CP tend to be smaller than normal, especially in children with spastic hemiplegia, whose limbs on the affected side of the body may not grow as quickly or as long as those on the normal side.
  • Spinal deformities and osteoarthritis. Deformities of the spine—curvature (scoliosis), humpback (kyphosis), and saddleback (lordosis) — are associated with CP. Spinal deformities can make sitting, standing, and walking difficult and cause chronic back pain. Pressure on and misalignment of the joints may result in osteoporosis (a breakdown of cartilage in the joints and bone enlargement).
  • Impaired vision. Many children with CP have strabismus, commonly called “cross eyes,” which left untreated can lead to poor vision in one eye and can interfere with the ability to judge distance. Some children with CP have difficulty understanding and organizing visual information. Other children may have defective vision or blindness that blurs the normal field of vision in one or both eyes.
  • Hearing loss. Impaired hearing is also more frequent among those with CP than in the general population.  Some children have partial or complete hearing loss, particularly as the result of jaundice or lack of oxygen to the developing brain.
  • Speech and language disorders.  Speech and language disorders, such as difficulty forming words and speaking clearly, are present in more than a third of persons with CP. Poor speech impairs communication and is often interpreted as a sign of cognitive impairment, which can be very frustrating to children with CP, especially the majority who have average to above-average intelligence,
  • Drooling.  Some individuals with CP drool because they have poor control of the muscles of the throat, mouth, and tongue.
  • Incontinence.  A possible complication of CP is incontinence, caused by poor control of the muscles that keep the bladder closed.
  • Abnormal sensations and perceptions.  Some individuals with CP experience pain or have difficulty feeling simple sensations, such as touch.
  • Learning difficulties. Children with CP may have difficulty processing particular types of spatial and auditory information. Brain damage may affect the development of language and intellectual functioning.
  • Infections and long-term illnesses. Many adults with CP have a higher risk of heart and lung disease, and pneumonia (often from inhaling bits of food into the lungs), than those without the disorder.
  • Contractures.  Muscles can become painfully fixed into abnormal positions, called contractures, which can increase muscle spasticity and joint deformities in people with CP.
  • Malnutrition. Swallowing, sucking, or feeding difficulties can make it difficult for many individuals with CP, particularly infants, to get proper nutrition and gain or maintain weight.
  • Dental problems. Many children with CP are at risk of developing gum disease and cavities because of poor dental hygiene. Certain medications, such as seizure drugs, can exacerbate these problems.
  • Inactivity. Childhood inactivity is magnified in children with CP due to impairment of the motor centers of the brain that produce and control voluntary movement. While children with CP may exhibit increased energy expenditure during activities of daily living, movement impairments make it difficult for them to participate in sports and other activities at a level of intensity sufficient to develop and maintain strength and fitness. Inactive adults with disabilities exhibit increased severity of disease and reduced overall health and well-being.

Causes of Child Cerebral Palsy

Cerebral palsy is caused by abnormal development of part of the brain or by damage to parts of the brain that control movement. This damage can occur before, during, or shortly after birth. The majority of children have congenital cerebral palsy CP (that is, they were born with it), although it may not be detected until months or years later. A small number of children have acquired cerebral palsy, which means the disorder begins after birth. Some causes of acquired cerebral palsy include brain damage in the first few months or years of life, brain infections such as bacterial meningitis or viral encephalitis, problems with blood flow to the brain, or head injury from a motor vehicle accident, a fall, or child abuse.

In many cases, the cause of cerebral palsy is unknown. Possible causes include genetic abnormalities, congenital brain malformations, maternal infections or fevers, or fetal injury, for example. The following types of brain damage may cause its characteristic symptoms:

Damage to the white matter of the brain (periventricular leukomalacia, or PVL). The white matter of the brain is responsible for transmitting signals inside the brain and to the rest of the body.  Damage from PVL looks like tiny holes in the white matter of an infant’s brain. These gaps in brain tissue interfere with the normal transmission of signals. Researchers have identified a period of selective vulnerability in the developing fetal brain, a period of time between 26 and 34 weeks of gestation, in which periventricular white matter is particularly sensitive to insults and injury.

Abnormal development of the brain (cerebral dysgenesis).  Any interruption of the normal process of brain growth during fetal development can cause brain malformations that interfere with the transmission of brain signals. Mutations in the genes that control brain development during this early period can keep the brain from developing normally. Infections, fevers, trauma, or other conditions that cause unhealthy conditions in the womb also put an unborn baby’s nervous system at risk.

Bleeding in the brain (intracranial hemorrhage).  Bleeding inside the brain from blocked or broken blood vessels is commonly caused by fetal stroke.   Some babies suffer a stroke while still in the womb because of blood clots in the placenta that block blood flow in the brain.  Other types of fetal stroke are caused by malformed or weak blood vessels in the brain or by blood-clotting abnormalities.  Maternal high blood pressure (hypertension) is a common medical disorder during pregnancy and is more common in babies with fetal stroke.  Maternal infection, especially pelvic inflammatory disease, has also been shown to increase the risk of fetal stroke.

Severe lack of oxygen in the brain.   Asphyxia, a lack of oxygen in the brain caused by an interruption in breathing or poor oxygen supply, is common for a brief period of time in babies due to the stress of labor and delivery.  If the supply of oxygen is cut off or reduced for lengthy periods, an infant can develop a type of brain damage called hypoxic-ischemic encephalopathy, which destroys tissue in the cerebral motor cortex and other areas of the brain.   This kind of damage can also be caused by severe maternal low blood pressure, rupture of the uterus, detachment of the placenta, or problems involving the umbilical cord, or severe trauma to the head during labor and delivery.

Common causes of cerebral palsy include:

  • Bacterial and viral infections such as meningitis
  • Bleeding in the brain (hemorrhaging)
  • Head injuries sustained during birth or within the first few years of infancy
  • Lack of oxygen to the brain before, during, or after birth (asphyxia)
  • Mercury poisoning from fish
  • Prenatal exposure to drugs and alcohol
  • Toxoplasmosis from raw/undercooked meat

What are the risk factors?

There are some medical conditions or events that can happen during pregnancy and delivery that may increase a baby’s risk of being born with cerebral palsy. These risks include:

  • Low birth weight and premature birth. Premature babies (born less than 37 weeks into pregnancy) and babies weighing less than 5 ½ pounds at birth have a much higher risk of developing cerebral palsy than full-term, heavier-weight babies.  Tiny babies born at very early gestational ages are especially at risk.
  • Multiple births.  Twins, triplets, and other multiple births — even those born at term — are linked to an increased risk of cerebral palsy. The death of a baby’s twin or triplet further increases the risk.
  • Infections during pregnancy.  Infections such as toxoplasmosis, rubella (German measles), cytomegalovirus, and herpes, can infect the womb and placenta. Inflammation triggered by infection may then go on to damage the developing nervous system in an unborn baby. Maternal fever during pregnancy or delivery can also set off this kind of inflammatory response.
  • Blood type incompatibility between mother and child.   Rh incompatibility is a condition that develops when a mother’s Rh blood type (either positive or negative) is different from the blood type of her baby. The mother’s system doesn’t tolerate the baby’s different blood type and her body will begin to make antibodies that will attack and kill her baby’s blood cells, which can cause brain damage.
  • Exposure to toxic substances.  Mothers who have been exposed to toxic substances during pregnancy, such as methyl mercury, are at a heightened risk of having a baby with cerebral palsy.
  • Mothers with thyroid abnormalities, intellectual disability, excess protein in the urine, or seizures.  Mothers with any of these conditions are slightly more likely to have a child with CP. There are also medical conditions during labor and delivery, and immediately after delivery that act as warning signs for an increased risk of CP. However, most of these children will not develop CP. Warning signs include:
  • Breech presentation.  Babies with cerebral palsy are more likely to be in a breech position (feet first) instead of head first at the beginning of labor. Babies who are unusually floppy as fetuses are more likely to be born in the breech position.
  • Complicated labor and delivery.  A baby who has vascular or respiratory problems during labor and delivery may already have suffered brain damage or abnormalities.
  • Small for gestational age.  Babies born smaller than normal for their gestational age are at risk for cerebral palsy because of factors that kept them from growing naturally in the womb.
  • Low Apgar score.   The Apgar score is a numbered rating that reflects a newborn’s physical health. Doctors periodically score a baby’s heart rate, breathing, muscle tone, reflexes, and skin color during the first minutes after birth. A low score at 10-20 minutes after delivery is often considered an important sign of potential problems such as CP.
  • Jaundice. More than 50 percent of newborns develop jaundice (yellowing of the skin or whites of the eyes) after birth when bilirubin, a substance normally found in bile, builds up faster than their livers can break it down and pass it from the body. Severe, untreated jaundice can kill brain cells and can cause deafness and CP.
  • Seizures.  An infant who has seizures faces a higher risk of being diagnosed later in childhood with CP.

Symptoms of Child Cerebral Palsy

In some cases, the cerebral motor cortex hasn’t developed normally during fetal growth. In others, the damage is a result of injury to the brain either before, during, or after birth. In either case, the damage is not repairable and the disabilities that result are permanent.

Children with CP exhibit a wide variety of symptoms, including:

  • lack of muscle coordination when performing voluntary movements (ataxia);
  • stiff or tight muscles and exaggerated reflexes (spasticity);
  • weakness in one or more arm or leg;
  • walking on the toes, a crouched gait, or a “scissored” gait;
  • variations in muscle tone, either too stiff or too floppy;
  • excessive drooling or difficulties swallowing or speaking;
  • shaking (tremor) or random involuntary movements;
  • delays in reaching motor skill milestones; and
  • difficulty with precise movements such as writing or buttoning a shirt.

The symptoms of CP differ in type and severity from one person to the next, and may even change in an individual over time. Symptoms may vary greatly among individuals, depending on which parts of the brain have been injured. All people with cerebral palsy have problems with movement and posture, and some also have some level of intellectual disability, seizures, and abnormal physical sensations or perceptions, as well as other medical disorders. People with CP also may have impaired vision or hearing, and language, and speech problems.

CP is the leading cause of childhood disabilities, but it doesn’t always cause profound disabilities.  While one child with severe CP might be unable to walk and need extensive, lifelong care, another child with mild CP might be only slightly awkward and require no special assistance. The disorder isn’t progressive, meaning it doesn’t get worse over time. However, as the child gets older, certain symptoms may become more or less evident.

A study by the Centers for Disease Control and Prevention shows the average prevalence of cerebral palsy is 3.3 children per 1,000 live births. There is no cure for cerebral palsy, but supportive treatments, medications, and surgery can help many individuals improve their motor skills and ability to communicate with the world.

What are the early signs?

The signs of cerebral palsy usually appear in the early months of life, although specific diagnoses may be delayed until age two years or later. Infants with CP frequently have developmental delays, in which they are slow to reach developmental milestones such as learning to roll over, sit, crawl, or walk. Some infants with CP have abnormal muscle tone. Decreased muscle tone (hypotonia) can make them appear relaxed, even floppy. Increased muscle tone (hypertonia) can make them seem stiff or rigid. In some cases, an early period of hypotonia will progress to hypertonia after the first 2 to 3 months of life. Children with CP may also have unusual posture or favor one side of the body when they reach, crawl, or move. It is important to note that some children without CP also might have some of these signs.

Physical Symptoms

  • Contractures (shortening of muscles)
  • Drooling
  • Exaggerated or jerky reflexes
  • Floppy muscle tone
  • Gastrointestinal problems
  • Incontinence
  • Involuntary movements or tremors
  • Lack of coordination and balance
  • Problems swallowing or sucking
  • Problems with movement on one side of the body
  • Stiff muscles (spasticity)

Neurological Symptoms

  • The buildup of cranial pressure due to fluid imbalance (hydrocephalus)
  • Behavioral problems
  • Delayed motor skill development
  • Difficulty with speech and language (dysarthria)
  • Sensory impairments
  • Visual/hearing impairments

Parents and caregivers should monitor the timeline of their child’s developmental milestones, as babies with cerebral palsy may have developmental delays that go unnoticed.

Some early warning signs:

In a Baby Younger Than 6 Months of Age

  • His head lags when you pick him up while he’s lying on his back
  • He feels stiff
  • He feels floppy
  • When you pick him up, his legs get stiff and they cross or scissor

In a Baby Older Than 6 Months of Age

  • She doesn’t roll over in either direction
  • She cannot bring her hands together
  • She has difficulty bringing her hands to her mouth
  • She reaches out with only one hand while keeping the other fisted

In a Baby Older Than 10 Months of Age

  • He crawls in a lopsided manner, pushing off with one hand and leg while dragging the opposite hand and leg
  • He cannot stand holding onto support

How is cerebral palsy diagnosed?

Most children with cerebral palsy are diagnosed during the first 2 years of life.  But if a child’s symptoms are mild, it can be difficult for a doctor to make a reliable diagnosis before the age of 4 or 5.

Doctors will order a series of tests to evaluate the child’s motor skills. During regular visits, the doctor will monitor the child’s development, growth, muscle tone, age-appropriate motor control, hearing and vision, posture, and coordination, in order to rule out other disorders that could cause similar symptoms. Although symptoms may change over time, CP is not progressive. If a child is continuously losing motor skills, the problem more likely is a condition other than CP—such as a genetic or muscle disease, metabolism disorder, or tumors in the nervous system.

Lab tests can identify other conditions that may cause symptoms similar to those associated with CP. Neuroimaging techniques that allow doctors to look into the brain (such as an MRI scan) can detect abnormalities that indicate a potentially treatable movement disorder. Neuroimaging methods include:

  • Cranial ultrasound uses high-frequency sound waves to produce pictures of the brains of young babies. It is used for high-risk premature infants because it is the least intrusive of the imaging techniques, although it is not as successful as computed tomography or magnetic resonance imaging at capturing subtle changes in white matter—the type of brain tissue that is damaged in CP.
  • Computed tomography (CT) uses x-rays to create images that show the structure of the brain and the areas of damage.
  • Magnetic resonance imaging (MRI) uses a computer, a magnetic field, and radio waves to create an anatomical picture of the brain’s tissues and structures. MRI can show the location and type of damage and offers finer levels of details than CT.
  • Electroencephalogram – uses a series of electrodes that are either taped or temporarily pasted to the scalp to detect electrical activity in the brain. Changes in the normal electrical pattern may help to identify epilepsy. Some metabolic disorders can masquerade as CP. Most of childhood metabolic disorders have characteristic brain abnormalities or malformations that will show up on an MRI.
  • Cranial ultrasound – This must be performed during infancy. Cranial ultrasound is very useful in high-frequency sound waves to produce images of the brain. Ultrasound doesn’t produce a detailed image only, but it may be used because it’s a quick and inexpensive test or diagnosis, and it can provide a valuable preliminary assessment of the brain.
  • Electroencephalogram (EEG) – If your child is suspected of having seizures, convulsion, an EEG can evaluate the condition further. Seizures can develop in a child with epilepsy and others associate problems. In an EEG test, a series of electrodes are placed or attached to your child’s scalp. The EEG records the electrical activity of your child’s brain and counts records. It’s most common for there to be changes in normal brain wave patterns in epilepsy.
  • Cranial ultrasound – It uses high-frequency sound waves to produce pictures of the brains of young babies in most cases. It is used for high-risk infants because it is the least intrusive of the imaging techniques to find an abnormality, although it is not as successful as computed tomography (CT scan) or magnetic resonance imaging at capturing subtle changes in white matter—the type of brain tissue that is damaged in cerebral palsy.

Other types of disorders can also be mistaken for CP or can cause specific types of CP. For example, coagulation disorders (which prevent blood from clotting or lead to excessive clotting) can cause prenatal or perinatal strokes that damage the brain and produce symptoms characteristic of CP, most commonly hemiparetic CP. Referrals to specialists such as a child neurologist, developmental pediatrician, ophthalmologist, or otologist aid in a more accurate diagnosis and help doctors develop a specific treatment plan.

Treatment of Child Cerebral Palsy

Non-Pharmacological

Cerebral palsy can’t be cured, but treatment will often improve a child’s capabilities.  Many children go on to enjoy near-normal adult lives if their disabilities are properly managed. In general, the earlier treatment begins, the better chance children have of overcoming developmental disabilities or learning new ways to accomplish the tasks that challenge them.

  • Physical therapy – usually begun in the first few years of life or soon after the diagnosis is made, is a cornerstone of CP treatment. Specific sets of exercises (such as resistive, or strength training programs) and activities can maintain or improve muscle strength, balance, and motor skills, and prevent contractures. Special braces (called orthotic devices) may be used to improve mobility and stretch spastic muscles.
  • Occupational therapy – focuses on optimizing upper body function, improving posture, and making the most of a child’s mobility. Occupational therapists help individuals address new ways to meet everyday activities such as dressing, going to school, and participating in day-to-day activities.
  • Recreation therapy – encourages participation in art and cultural programs, sports, and other events that help an individual expand physical and cognitive skills and abilities. Parents of children who participate in recreational therapies usually notice an improvement in their child’s speech, self-esteem, and emotional well-being.
  • Speech and language therapy – can improve a child’s ability to speak, more clearly, help with swallowing disorders, and learn new ways to communicate—using sign language and/or special communication devices such as a computer with a voice synthesizer, or a special board covered with symbols of everyday objects and activities to which a child can point to indicate his or her wishes.
  • Treatments for problems with eating and drooling – are often necessary when children with CP have difficulty eating and drinking because they have little control over the muscles that move their mouth, jaw, and tongue. They are also at risk for breathing food or fluid into the lungs, as well as for malnutrition, recurrent lung infections, and progressive lung disease.
  • Assistive devices – Different kinds of equipment may be helpful for children with cerebral palsy. Leg braces can support their legs as they learn to walk. Arm braces can support arms or hands in a normal position. Other types of assistive devices include communication keyboards, special wheelchairs, and chairs to help with sitting.
  • Alternative therapy – helps children focus on themselves as an individual and lets them overcome physical and mental obstacles. Alternative therapy includes hippotherapy, music therapy, aquatic therapy, acupuncture, and more.
  • Functional electrical stimulation (FES) – It is the therapeutic use of low-level electrical current to stimulate muscle movement, posture, restore useful movements such as standing or stepping is the most effective way to target and strengthen spastic muscles. Researchers are evaluating how FES-assisted stationary cycling also improves physical conditioning with general lower extremity muscle strength adolescents age.
  • Robotic therapy – It is applies controlled force to the leg during the swing phase of gait is may improve the efficacy of body weight-supported treadmill training in children with cerebral palsy. The results from this NICHD study will lead to an innovative clinical therapy aimed at improving locomotor function in children with CP.
  • Stem cell therapy – It is being investigated as a treatment for cerebral palsy, but research is in the early stages and large-scale clinical trials are needed to learn if stem cell therapy is safe and effective in humans in near future. Stem cells are capable of becoming other types of cells in the body. Scientists are hopeful that stem cells may be able to repair damaged nerves, central nervous system, and brain tissues. Studies in the U.S. hopefully examining the safety and tolerability of umbilical cord blood stem cell infusion in children for cerebral palsy.
  • Deep brain stimulation (DBS) – It has been used increasingly in those types of dyskinetic cerebral palsy. It is often used to decrease dystonia. Though it does decrease dystonia, hemiplagiain those  DCP, there is less benefit in quality of life and functionality compared to that seen in patients with primary (inherited) dystonia.

Stem cell therapy is being investigated as a treatment for cerebral palsy, but research is in the early stages and large-scale clinical trials are needed to learn if stem cell therapy is safe and effective in humans. Stem cells are capable of becoming other cell types in the body. Scientists are hopeful that stem cells may be able to repair damaged nerves and brain tissues. Studies in the U.S. are examining the safety and tolerability of umbilical cord blood stem cell infusion in children with CP.

Drug Treatments

Common classes of medications for children with cerebral palsy include

  • Anticholinergics (neurotransmitter blockers)

  • Anticonvulsants (suppress neurons that cause seizures)

  • Antidepressants (relieve symptoms of depression)

  • Anti-inflammatories (reduce pain and inflammation)

  • Baclofen (muscle relaxer)

  • Benzodiazepines (treats anxiety, seizures, and insomnia)

  • Botox (treats spasticity)

  • Muscle relaxants

  • Nerve blocks

  • Stool softeners

Medication may also be used to treat secondary disorders caused by cerebral palsy such as incontinence, acid reflux, behavioral disorders, and more.

  • Oral medications such as diazepam, baclofen, dantrolene sodium, and tizanidine are usually used as the first line of treatment to relax stiff, contracted, or overactive muscles. Some drugs have some risky side effects such as drowsiness, changes in blood pressure, and risk of liver damage that require continuous monitoring. Oral medications are most appropriate for children who need an only mild reduction in muscle tone or who have widespread spasticity.
  • Botulinum toxin (BT-A), injected locally, has become a standard treatment for overactive muscles in children with spastic movement disorders such as CP. BT-A relaxes contracted muscles by keeping nerve cells from over-activating muscle. The relaxing effect of a BT-A injection lasts approximately 3 months. Undesirable side effects are mild and short-lived, consisting of pain upon injection and occasionally mild flu-like symptoms. BT-A injections are most effective when followed by a stretching program including physical therapy and splinting. BT-A injections work best for children who have some control over their motor movements and have a limited number of muscles to treat, none of which is fixed or rigid.
  • Intrathecal baclofen therapy uses an implantable pump to deliver baclofen, a muscle relaxant, into the fluid surrounding the spinal cord. Baclofen decreases the excitability of nerve cells in the spinal cord, which then reduces muscle spasticity throughout the body. The pump can be adjusted if muscle tone is worse at certain times of the day or night. The baclofen pump is most appropriate for individuals with chronic, severe stiffness or uncontrolled muscle movement throughout the body

Surgery

  • Orthopedic surgery is often recommended when spasticity and stiffness are severe enough to make walking and moving about difficult or painful. For many people with CP, improving the appearance of how they walk – their gait – is also important. Surgeons can lengthen muscles and tendons that are proportionately too short, which can improve mobility and lessen pain. Tendon surgery may help the symptoms for some children with CP but could also have negative long-term consequences. Orthopedic surgeries may be staggered at times appropriate to a child’s age and level of motor development. Surgery can also correct or greatly improve spinal deformities in people with CP. Surgery may not be indicated for all gait abnormalities and the surgeon may request a quantitative gait analysis before surgery.
  • Surgery to cut nerves.  Selective dorsal rhizotomy (SDR) is a surgical procedure recommended for cases of severe spasticity when all of the more conservative treatments – physical therapy, oral medications, and intrathecal baclofen — have failed to reduce spasticity or chronic pain. A surgeon locates and selectively severs overactivated nerves at the base of the spinal column. SDR is most commonly used to relax muscles and decrease chronic pain in one or both of the lower or upper limbs. It is also sometimes used to correct an overactive bladder. Potential side effects include sensory loss, numbness, or uncomfortable sensations in limb areas once supplied by the severed nerve.

Assistive devices

Assistive devices such devices as computers, computer software, voice synthesizers, and picture books can greatly help some individuals with CP improve communications skills. Other devices around the home or workplace make it easier for people with CP to adapt to activities of daily living.

Orthotic devices help to compensate for muscle imbalance and increase independent mobility. Braces and splints use external force to correct muscle abnormalities and improve function such as sitting or walking. Other orthotics help stretch muscles or the positioning of a joint. Braces, wedges, special chairs, and other devices can help people sit more comfortably and make it easier to perform daily functions. Wheelchairs, rolling walkers, and powered scooters can help individuals who are not independently mobile. Vision aids include glasses, magnifiers, and large-print books and computer typeface. Some individuals with CP may need surgery to correct vision problems. Hearing aids and telephone amplifiers may help people hear more clearly.

Complementary and Alternative Therapies

Many children and adolescents with CP use some form of complementary or alternative medicine. Controlled clinical trials involving some of the therapies have been inconclusive or showed no benefit and the therapies have not been accepted in mainstream clinical practice. Although there are anecdotal reports of some benefit in some children with CP, these therapies have not been approved by the U.S. Food and Drug Administration for the treatment of CP. Such therapies include hyperbaric oxygen therapy, special clothing worn during resistance exercise training, certain forms of electrical stimulation, assisting children in completing certain motions several times a day, and specialized learning strategies. Also, dietary supplements, including herbal products, may interact with other products or medications a child with CP may be taking or have unwanted side effects on their own. Families of children with CP should discuss all therapies with their doctor.

Cerebral palsy surgery may be recommended to:

  • Correct fixed joints and tendons
  • Correct foot deformities
  • Correct muscle contractures
  • Correct spinal curvatures (scoliosis)
  • Improve posture
  • Improve balance and coordination
  • Prevent hip dislocation
  • Prevent spinal deformities
  • Reduce tremors
  • Relieve pain
  • Relieve stiff muscles
  • Treat co-occurring conditions

Assistive Devices

Specialized assistive devices can help individuals with cerebral palsy that experienced issues with communication, hearing, and vision.

Types of assistive devices include:

  • Cochlear implants
  • Electronic communication boards
  • Eye-tracking devices
  • Typing aids
  • Writing aids

Mobility Aids

Children with mobility limitations may benefit from assistive technology that can be adjusted to their individual needs. Mobility aids aim to help children with cerebral palsy move freely and can greatly improve their quality of life and independence.

Types of mobility aids include:

  • Canes
  • Crutches
  • Lifts
  • Power scooters
  • Orthotic devices
  • Standers
  • Walkers
  • Walking sticks
  • Wheelchairs

Are there treatments for other conditions associated with cerebral palsy?

  • Epilepsy. Many children with intellectual disability and CP also have epilepsy. In general, drugs are prescribed based on the type of seizures an individual experiences, since no one drug controls all types. Some individuals may need a combination of two or more drugs to achieve good seizure control.
  • Incontinence. Medical treatments for incontinence include special exercises, biofeedback, prescription drugs, surgery, or surgically implanted devices to replace or aid muscles.
  • Osteopenia. Children with CP who are unable to walk risk developing poor bone density (osteopenia), which makes them more likely to break bones. In a study of older Americans funded by the National Institutes of Health (NIH), a family of drugs called bisphosphonates, which has been approved by the FDA to treat mineral loss in elderly patients, also appeared to increase bone mineral density Doctors may choose to selectively prescribe the drug off-label to children to prevent osteopenia.
  • Pain. Pain can be a problem for people with CP due to spastic muscles and the stress and strain on parts of the body that are compensating for muscle abnormalities. Some individuals may also have frequent and irregular muscle spasms that can’t be predicted or medicated in advance. Diazepam can reduce the pain associated with muscle spasms and gabapentin has been used successfully to decrease the severity and frequency of painful spasms. Botulinum toxin injections have also been shown to decrease spasticity and pain. Intrathecal baclofen has shown good results in reducing pain. Some children and adults have been able to decrease pain by using noninvasive and drug-free interventions such as distraction, relaxation training, biofeedback, and therapeutic massage.

Do adults with cerebral palsy face special health challenges?

  • Premature aging. The majority of individuals with CP will experience some form of premature aging by the time they reach their 40s because of the extra stress and strain the disease puts upon their bodies. The developmental delays that often accompany CP keep some organ systems from developing to their full capacity and level of performance. As a consequence, organ systems such as the cardiovascular system (the heart, veins, and arteries) and pulmonary system (lungs) have to work harder and they age prematurely.
  • Functional issues at work.  The day-to-day challenges of the workplace are likely to increase as an employed individual with CP reaches middle age.  Some individuals will be able to continue working with accommodations such as an adjusted work schedule, assistive equipment, or frequent rest periods.
  • Depression.  Mental health issues can also be of concern as someone with cerebral palsy grows older.  The rate of depression is three to four times higher in people with disabilities such as cerebral palsy.  It appears to be related not so much to the severity of their disabilities, but to how well they cope with them.  The amount of emotional support someone has, how successful they are at coping with disappointment and stress, and whether or not they have an optimistic outlook about the future all have a significant impact on mental health.
  • Post-impairment syndrome.  This syndrome is marked by a combination of pain, fatigue, and weakness due to muscle abnormalities, bone deformities, overuse syndromes (sometimes also called repetitive motion injuries), and arthritis.   Fatigue is often a challenge, since individuals with CP may use up to three to five times the amount of energy that able-bodied people use when they walk and move about.
  • Osteoarthritis and degenerative arthritis.  Musculoskeletal abnormalities that may not produce discomfort during childhood can cause pain in adulthood.  For example, the abnormal relationships between joint surfaces and excessive joint compression can lead to the early development of painful osteoarthritis and degenerative arthritis.  Individuals with CP also may have limited strength and restricted patterns of movement, which puts them at risk for overuse syndromes and nerve entrapments.
  • Pain. Individuals with CP may have pain that can be acute (usually comes on quickly and lasts a short while) or chronic and is experienced most commonly in the hips, knees, ankles, and the upper and lower back. Individuals with spastic CP may have an increased number of painful sites and worse pain than those with other types of cerebral palsy. Preventive treatment aimed at correcting skeletal and muscle abnormalities early in life may help to avoid the progressive accumulation of stress and strain that causes pain. Dislocated hips, which are particularly likely to cause pain, can be surgically repaired.
  • Other medical conditions. Adults have higher than normal rates of other medical conditions secondary to their cerebral palsy, such as hypertension, incontinence, bladder dysfunction, and swallowing difficulties. Scoliosis is likely to progress after puberty when bones have matured into their final shape and size. People with CP also have a higher incidence of bone fractures, occurring most frequently during physical therapy sessions.

What research is being done?

The National Institute of Neurological Disorders and Stroke, (NINDS), a part of the National Institutes of Health (NIH), is the nation’s leading funder of basic, clinical, and translational research on brain and nervous system disorders.  Another NIH agency, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), also conducts and supports research on cerebral palsy.

Much of what we now know about CP came from research sponsored by the NINDS, including the identification of new causes and risk factors for cerebral palsy, the discovery of drugs to control stiff and spastic muscles and more precise methods to deliver them, refined surgical techniques to correct abnormalities in muscle and bone, and a greater understanding of how and why brain damage at critical stages of fetal development causes CP.

Many scientists think that a significant number of children develop CP because of mishaps early in

brain development. They are examining how neurons (nerve cells) in the brain specialize and form the right connections with other brain cells, and they are looking for ways to prevent the factors that disrupt the normal processes of brain development.

Genetic defects are sometimes responsible for the brain malformations and abnormalities that cause cerebral palsy.  Scientists are searching for the genes responsible for these abnormalities by collecting DNA samples from people with cerebral palsy and their families and using genetic screening techniques to discover linkages between individual genes and specific types of abnormality – primarily those associated with the process in the developing brain in which neurons migrate from where they are born to where they settle into neural circuits (called neural migration).

Scientists are scrutinizing events in newborn babies’ brains, such as bleeding, epileptic seizures, and breathing and circulation problems, which can cause the

abnormal release of chemicals that triggers the kind of damage that causes cerebral palsy.  For example, research has shown that bleeding in the brain unleashes dangerously high amounts of glutamate, a chemical that helps neurons communicate.  However, too much glutamate overexcites and kills neurons.  By learning how brain chemicals that are normally helpful become dangerously toxic, scientists will have opportunities to develop new drugs to block their harmful effects.

Researchers are using

imaging techniques and neurobehavioral tests to predict those preterm infants who will develop cerebral palsy. If these screening techniques are successful, doctors will be able to identify infants at risk for cerebral palsy before they are born.

Periventricular

white matter damage—the most common cause of CP—is characterized by the death of the white matter around the fluid-filled ventricles in the brain. The periventricular area contains nerve fibers that carry messages from the brain to the body’s muscles. NINDS-sponsored researchers are hoping to develop preventative strategies for white matter damage. For example, researchers are examining the role brain chemicals play on white matter development in the brain. Another NINDS-funded project involves the development of a novel mouse model and cell-based therapies for perinatal white matter injury.  Researchers funded by NINDS are studying a chemical found naturally in the body, called erythropoietin to see if it decreases the risk of CP in prematurely born infants.

NIH-funded scientists continue to look at new therapies and novel ways to use existing options to treat individuals with CP, including:

Constraint-induced therapy (CIT) is a promising therapy for CP. CIT typically involves restraining the stronger limb (such as the “good” arm in a person who has been affected by a stroke on one side of the body) in a cast and forcing the weaker arm to perform intensive activities every day over a period of weeks.  A clinical study sponsored by the NICHD is examining the use of different dosage levels of daily training using either full-time cast immobilization vs. part-time splint restraint in improving upper body extremity skills in children with weakness on both sides of their body. Study findings will establish evidence-based practice standards to improve lifelong neuromotor capacity in individuals with CP.

Functional electrical stimulation (FES)—the therapeutic use of low-level electrical current to stimulate muscle movement and restore useful movements such as standing or stepping—is an effective way to target and strengthen spastic muscles. Researchers are evaluating how FES-assisted stationary cycling can improve physical conditioning and general lower extremity muscle strength in adolescents.

Robotic therapy that applies controlled force to the leg during the swing phase of gait is may improve the efficacy of body weight-supported treadmill training in children with CP. The results from this NICHD study will lead to an innovative clinical therapy aimed at improving locomotor function in children with CP.

Botulinum toxin (Botox), injected locally, has become a standard treatment in children with spastic movement disorders such as CP. Recent animal studies suggest Botox degrades bone but there are no studies of its skeletal consequences in humans. Other research shows a low-intensity vibration treatment can improve bone structure in the lower extremity leg bones of children with CP. In a novel clinical study being conducted by NICHD, researchers are determining the effect of Botox treatment in conjunction with a daily vibration treatment on bone mass and bone structure in children with spastic CP.

Systemic hypothermia—the controlled medical cooling of the body’s core temperature—appears to protect the brain and decrease the rate of death and disability from certain disorders and brain injuries. Previous studies have shown that hypothermia is effective in treating neurologic symptoms in term or late preterm babies less than the one-month old that is attributed to hypoxic-ischemia (HIE, brain injury due to a severe decrease in the oxygen supply to the body), which can cause quadriplegic CP, with or without movement disorder. In an effort to determine the most effective cooling strategies, NICHD-funded researchers are studying different cooling treatments to improve the chance of survival and neurodevelopment outcomes 18-22 months post-treatment in infants with neurologic symptoms attributed to HIE. Other researchers are examining if combined therapy using hypothermia and recombinant erythropoietin (a hormone that promotes the growth of new red blood cells and increases oxygen levels in the blood) is more effective than either therapy alone in treating neurodevelopmental handicaps in an animal model involving a lack of oxygen before, during, or just after birth.

Preventing CP

In many cases, the cause or causes of congenital CP aren’t fully known, which means that currently little can be done to prevent it. CP related to genetics is not preventable. However, there are actions people can take before and during pregnancy, as well as after birth that might help reduce the risk of developmental problems, including CP.

Taking steps to help ensure a healthy pregnancy can help prevent developmental problems, including CP. Acquired CP often is related to an infection or injury, and some of these cases can be prevented.

Before Pregnancy
  • Be as healthy as possible before pregnancy. Make sure that any infections in the mother are treated and health conditions are in control, ideally before pregnancy occurs.
  • Get vaccinated for certain diseases (such as chickenpox and rubella) that could harm a developing baby. It is important to have many of these vaccinations before becoming pregnant.
  • If assistive reproductive technology (ART) infertility treatments are used to get pregnant, consider ways to reduce the chance of a multiple pregnancy (twins, triplets, or more), such as transferring only one embryo at a time.
During Pregnancy
  • Learn how to have a healthy pregnancy.
  • Get early and regular prenatal care, both for your health and for that of your developing baby.
  • Wash your hands often with soap and water to help reduce the risk of infections that might harm your developing baby.
  • Contact your health care provider if you get sick, have a fever, or have other signs of infection during pregnancy.
  • A flu shot is your best protection against serious illness from the flu. A flu shot can protect pregnant women and their unborn babies, both before and after birth. Flu shots have not been shown to cause harm to pregnant women or their babies.
  • If there is a difference in the blood type or Rh incompatibility between mother and baby it can cause Jaundice and kernicterus. Women should know their blood type and talk to their doctor about ways to prevent problems. Doctors can treat the mother with Rh immune globulin (“Rhogam”) when she is 28 weeks pregnant and again shortly after giving birth to prevent kernicterus from occurring.
  • Talk to your doctor about ways to prevent problems if you are at risk for preterm delivery. Research has shown that taking magnesium sulfate before anticipated early preterm birth reduces the risk of CP among surviving infants. (rx,rx,rx,rx)
After the Baby is Born
  • Learn how to help keep your baby healthy and safe after birth.
  • Any baby can get jaundice. Severe jaundice that is not treated can cause brain damage, called kernicterus. Kernicterus is a cause of CP that potentially can be prevented. Your baby should be checked for jaundice in the hospital and again within 48 hours after leaving the hospital. Ask your doctor or nurse about a jaundice bilirubin test. In addition, steps can be taken to prevent kernicterus that is caused by Rh blood type incompatibility between the mother and baby.
  • Make sure your child is vaccinated against infections that can cause meningitis and encephalitis, including Haemophilus influenzae type B (HiB vaccine) and Streptococcus pneumoniae (pneumococcal vaccine).
  • Take steps to prevent injuries:
    • Buckle your child in the car using an infant or child car seat, booster seat, or seat belt (according to the child’s height, weight, and age).
    • Make living areas safer for children by using window guards to keep young children from falling out of open windows and using safety gates at the top and bottom of stairs.
    • Make sure the surface on your child’s playground is made of a shock-absorbing material, such as hardwood mulch or sand.
    • Carefully watch young children at all times around bathtubs, swimming or wading pools, and natural bodies of water. Adults watching kids near water should avoid distracting activities like using a computer or handheld device, reading, or talking on the phone.
    • Make sure your child wears a helmet for activities like riding a bike.
    • Never hit, throw, shake, or hurt a child.

Cerebral Palsy Frequently Asked Questions

Is there a cure for cerebral palsy?

Unfortunately, there is no cure for cerebral palsy. That said, there are many treatment options available to treat symptoms such as therapy, medication, surgery, assistive technology, and more.

What are the risk factors for cerebral palsy?

There are several risk factors before, during, and after pregnancy that can lead to cerebral palsy at birth.

Risk Factors During Pregnancy

  • Bacterial and viral infections
  • Exposure to toxins
  • Incompatible blood type between mother and fetus
  • Maternal health issues such as bleeding, blood clotting, seizures, and thyroid problems

Risk Factors During Labor and Delivery

  • Breech birth (baby delivered feet or rear-end first)
  • High birth weight (more than 8 pounds, 13 ounces)
  • Inability of placenta to provide nutrients and oxygen
  • Improper use of vacuum extractors or forceps
  • Low birth weight (less than 5 pounds, 7.5 ounces)
  • Loss of oxygen to the infant brain (hypoxia)
  • Premature birth (child born before start of 37th week of pregnancy)

Risk Factors After Childbirth

  • Head trauma
  • Infections
  • Lack of oxygen (asphyxiation)
  • Severe jaundice
  • Vascular problems shortly after birth

How does cerebral palsy affect the brain?

Cerebral palsy affects the cerebral cortex area of the brain. The cerebral cortex is the outer layer of the brain that controls muscle movement. Damage to this area can cause disruption in messages sent from the brain to the body, resulting in movement issues.

How does cerebral palsy affect the body?

Cerebral palsy can cause issues with motor function control. Individuals with cerebral palsy may have issues with voluntary and/or involuntary movement which can result in jerky or floppy movements.

Cerebral palsy also affects muscle tone. Some individuals may suffer from contractures due to stiff muscles, whereas others may experience floppy or loose muscles.

How do I know if my child has cerebral palsy?

There are several common signs and symptoms that present themselves in children with cerebral palsy. It is important to note any signs of delayed or missed developmental milestones within the first year of life.

That said, the only way to know for sure that your child has cerebral palsy is to consult with a doctor who will be able to run diagnostic testing.

Is cerebral palsy genetic?

Although cerebral palsy itself is not hereditary and is generally caused by birth trauma, there are potential genetic factors that may lead to the development of cerebral palsy.

According to a 2020 study by the National Institute of Neurological Disorders and Stroke (NINDS), about 14% of cerebral palsy cases may be tied to genes.

What should I do if I think my child has cerebral palsy?

It is important to consult with a cerebral palsy specialist as soon as possible if you think your child has cerebral palsy. Specialized doctors will be able to conduct tests to diagnose your child and create a treatment plan.

Getting diagnosed and starting treatment early can help improve cerebral palsy signs and symptoms in a timely manner and can improve their overall quality of life.

References

What Is Dementia? – Causes, Symptoms, Treatment

Dementia is a syndrome of chronic progressive cognitive decline, a neurodegenerative brain disorder that is characterized by cognitive decline involving memory and at least 1 of the other domains, including personality, praxis, abstract thinking, language, executive functioning, complex attention, social, visuospatial skills language, memory, comprehension, attention, judgment, and reasoning usually affects people over the age of 65 with the involvement of.

Dementia is a collective term used to describe various symptoms of cognitive decline, such as forgetfulness. It is a symptom of several underlying diseases and brain disorders. Dementia is not a single disease in itself, but a general term to describe symptoms of impairment in memory, communication, and thinking.

A diagnosis of dementia can be frightening for those affected by the syndrome, their family members, and caretakers. Unfortunately, there is a stigma associated with this term. Learning more about this medical condition can help.

Dementia types

There are several types of dementia, including:

  • Alzheimer’s disease – is characterized by “plaques” between the dying cells in the brain and “tangles” within the cells (both are due to protein abnormalities). The brain tissue in a person with Alzheimer’s has progressively fewer nerve cells and connections, and the total brain size shrinks.
  • Dementia with Lewy bodies – is a neurodegenerative condition linked to abnormal structures in the brain. The brain changes involve a protein called alpha-synuclein.
  • Mixed dementia – refers to a diagnosis of two or three types occurring together. For instance, a person may show both Alzheimer’s disease and vascular dementia at the same time.
  • Parkinson’s disease – is also marked by the presence of Lewy bodies. Although Parkinson’s is often considered a disorder of movement, it can also lead to dementia symptoms.
  • Huntington’s disease – is characterized by specific types of uncontrolled movements but also includes dementia.
  • Frontotemporal dementia – is also known as Pick’s disease.
  • Normal-pressure hydrocephalus – when excess cerebrospinal fluid accumulates in the brain.
  • Posterior cortical atrophy – resembles changes seen in Alzheimer’s disease but in a different part of the brain.
  • Down syndrome – increases the likelihood of young-onset Alzheimer’s.

The Basics of Dementia and Cognitive Impairment

Dementia is the loss of cognitive functioning—the ability to think, remember, or reason—to such an extent that it interferes with a person’s daily life and activities. These functions include memory, language skills, visual perception, problem solving, self-management, and the ability to focus and pay attention. Some people with dementia cannot control their emotions, and their personalities may change. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a person’s functioning, to the most severe stage, when the person must depend completely on others for basic activities of daily living.

Age is the primary risk factor for developing dementia. For that reason, the number of people living with dementia could double in the next 40 years as the number of Americans age 65 and older increases from 48 million today to more than 88 million in 2050. Regardless of the form of dementia, the personal, economic, and societal demands can be devastating.

Dementia is not the same as age-related cognitive decline—when certain areas of thinking, memory, and information processing slow with age, but intelligence remains unchanged. Unlike dementia, age-related memory loss isn’t disabling. Occasional lapses of forgetfulness are normal in elderly adults. While dementia is more common with advanced age (as many as half of all people age 85 or older may have some form of dementia), it is not an inevitable part of aging. Many people live into their 90s and beyond without any signs of dementia.

Dementia is also not the same as delirium, which is usually a short-term complication of a medical condition and most often can be treated successfully. Signs and symptoms of dementia result when once-healthy neurons (nerve cells) in the brain stop working, lose connections with other brain cells, and die. While everyone loses some neurons as they age, people with dementia experience far greater loss.

Mild cognitive impairment (MCI) is a stage between normal cognitive changes that may occur with age and more serious symptoms that indicate dementia. Symptoms of MCI can include problems with thinking, judgment, memory, and language, but the loss doesn’t significantly interfere with the ability to handle everyday activities. Symptoms of MCI include mild memory loss; difficulty with planning or organization; trouble finding words; frequently losing or misplacing things; and forgetting names, conversations, and events. Someone who has MCI may be at greater risk of eventually developing Alzheimer’s or another type of dementia, particularly if the degree of memory impairment is significant, but MCI does not always progress to dementia. Symptoms may remain stable for several years, and even improve over time in some people.

It is common to have more than one cause of dementia. Many people with dementia have both Alzheimer’s disease and one or more closely related disorders that share brain scanning or clinical features (and sometimes both) with Alzheimer’s disease. When a person is affected by more than one dementia disorder, dementia can be referred to as a mixed dementia.

Autopsy studies of the brains of people who had dementia suggest that a majority of those age 80 and older probably had mixed dementia caused by Alzheimer’s-related neurodegenerative processes, vascular disease-related processes, or another neurodegenerative condition. In fact, some studies indicate that mixed vascular-degenerative dementia is the most common cause of dementia in the elderly.

Researchers are still trying to understand the underlying disease processes involved in dementia. Scientists have some theories about mechanisms that may lead to different forms of dementia, but more research is needed to better understand if and how these mechanisms are involved.

Dementias Associated with Aging and Neurodegeneration

Various disorders and factors contribute to dementia, resulting in a progressive and irreversible loss of neurons and brain functions. Currently, there are no cures for these neurodegenerative disorders.

Some specific causes of dementia disorders are explained below.

Alzheimer’s disease (AD) is the most common cause of dementia in older adults. As many as 5 million Americans age 65 and older may have the disease. In most neurodegenerative diseases, certain proteins abnormally clump together and are thought to damage healthy neurons, causing them to stop functioning and die. In Alzheimer’s, fragments of a protein called amyloid form abnormal clusters called plaques between brain cells, and a protein called tau forms tangles inside nerve cells.

It seems likely that damage to the brain starts a decade or more before memory and other cognitive problems appear. The damage often initially appears in the hippocampus, the part of the brain essential in forming memories. Ultimately, the abnormal plaques and tangles spread throughout the brain, and brain tissue significantly shrinks.

As Alzheimer’s disease progresses, people experience greater memory loss and other cognitive difficulties. Problems can include wandering and getting lost, trouble handling money and paying bills, repeating questions, taking longer to complete normal daily tasks, and personality and behavior changes.

People are often diagnosed in this stage. Memory loss and confusion worsen, and people begin to have problems recognizing family and friends. They may be unable to learn new things, carry out multi-step tasks such as getting dressed, or cope with new situations. In addition, people at this stage may have hallucinations, delusions, and paranoia and may behave impulsively.

People with severe Alzheimer’s cannot communicate and are completely dependent on others for their care. Near the end, the person may be in bed most or all of the time as body functions shut down. Certain drugs can temporarily slow some symptoms of Alzheimer’s from getting worse, but currently there are no treatments that stop the progression of the disease. For more information on Alzheimer’s disease, visit the Alzheimer’s and related Dementias Education and Referral (ADEAR) Center at www.alzheimers.gov.

Researchers have not found a single gene solely responsible for Alzheimer’s disease; rather, multiple genes are likely involved. One genetic risk factor— having one form of the apolipoprotein E (APOE) gene on chromosome 19—does increase a person’s risk for developing Alzheimer’s. People who inherit one copy of this APOE ε4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. (An allele is a variant form of a pair of genes that are located on a particular chromosome and control the same trait.) The APOE ε4 allele may also be associated with an earlier onset of memory loss and other symptoms. Researchers have found that this allele is associated with an increased number of amyloid plaques in the brain tissue of affected people.

Frontotemporal disorders are forms of dementia caused by a family of neurodegenerative brain diseases collectively called frontotemporal lobar degeneration. They primarily affect the frontal and temporal lobes of the brain, rather than the widespread shrinking and wasting away (atrophy) of brain tissue seen in Alzheimer’s disease. In these disorders, changes to nerve cells in the brain’s frontal lobes affect the ability to reason and make decisions, prioritize and multitask, act appropriately, and control movement. Changes to the temporal lobes affect memory and how people understand words, recognize objects, and recognize and respond to emotions. Some people decline rapidly over 2 to 3 years, while others show only minimal changes for many years. People can live with frontotemporal disorders for 2 to 10 years, sometimes longer, but it is difficult to predict the time course for an affected individual. The signs and symptoms may vary greatly among individuals as different parts of the brain are affected. No treatment that can cure or reverse frontotemporal disorders is currently available.

Clinically, FTD is classified into two main types of syndromes:

  • Behavioral variant frontotemporal dementia (bvFTD) involves changes in behavior, judgment, and personality. People with this disorder may have problems with cognition, but their memory may stay relatively intact. They may do impulsive things that are out of character or may engage in repetitive, unusual behaviors. People with bvFTD also may say or do inappropriate things or become uncaring. Over time, language and/or movement problems may occur.
  • Primary progressive aphasia (PPA) involves changes in the ability to speak, understand, and express thoughts and/or words and to write and read. Many people with PPA, though not all, develop symptoms of dementia. Problems with memory, reasoning, and judgment are not apparent at first but can develop and progress over time. Sometimes a person with PPA cannot recognize the faces of familiar people and common objects (called semantic PPA). Other individuals have increasing trouble producing speech and may eventually be unable to speak at all (called agrammatic PPA). PPA is a language disorder that is not the same as the problems with speech and ability to read and write (called aphasia) that can result from a stroke.
  • Corticobasal degeneration (CBD) involves progressive nerve-cell loss and atrophy of specific areas of the brain, which can affect memory, behavior, thinking, language, and movement. The disease is named after parts of the brain that are affected—the cerebral cortex (the outer part of the brain) and the basal ganglia (structures deep in the brain involved with movement). Not everyone who has CBD has problems with memory, cognition, language, or behavior. The disease tends to progress gradually, with early symptoms beginning around age 60. Some of the movement symptoms of CBD are similar to those seen in Parkinson’s disease.
  • Frontotemporal dementia with motor neuron disease (FTD/MND, also called FTD-ALS) is a combination of behavioral variant frontotemporal dementia and the progressive neuromuscular weakness typically seen in amyotrophic lateral sclerosis (ALS). ALS is a neurodegenerative disease that attacks nerve cells responsible for controlling voluntary muscles (muscle action that can be controlled, such as that in the arms, legs, and face). Symptoms of either disease may appear first, with other symptoms developing over time.
  • Pick’s disease is characterized by Pick bodies—masses comprised of the protein tau that accumulate inside nerve cells, causing them to appear enlarged or balloon-like. It is usually seen with bvFTD but sometimes with PPA. Some symptoms are similar to those of Alzheimer’s disease, including loss of speech, changes in behavior, and trouble with thinking. However, while inappropriate behavior characterizes the early stages of Pick’s disease, memory loss is often the first symptom of Alzheimer’s. Antidepressants and antipsychotics can control some of the behavioral symptoms of Pick’s disease, but no treatment is available to stop the disease from progressing.
  • Progressive supranuclear palsy (PSP) is a brain disease that can cause problems with thinking, memory, behavior, problem solving, and judgment. It also affects the control of eye movements, mood, speech, swallowing, vision, concentration, and language. Because certain parts of the brain that control movement are damaged, this disease shares some of the problems with movement seen in people with corticobasal degeneration and Parkinson’s disease.
  • Lewy body dementia (LBD) is one of the most common causes of dementia after Alzheimer’s disease and vascular disease. It typically begins after age 50, but can occur earlier. It involves abnormal protein deposits called Lewy bodies, which are balloon-like structures that form inside nerve cells. The abnormal buildup of the protein alpha-synuclein and other proteins causes neurons to work less effectively and die. Initial symptoms may vary, but over time, people with these disorders develop similar cognitive, behavioral, physical, and sleep-related symptoms. Lewy body dementia includes two related conditions—dementia with Lewy bodies and Parkinson’s disease dementia. In dementia with Lewy bodies, the cognitive symptoms are seen within a year of movement symptoms called parkinsonism (including tremor, difficulty with walking and posture, and rigid muscles). In Parkinson’s disease dementia, the cognitive symptoms develop more than a year after movement problems begin.
  • Dementia with Lewy bodies (DLB) is one of the more common forms of progressive dementia. Neurons in the outer layer of the brain (cortex) and in the substantia nigra (a region involved with the production of dopamine) degenerate. Many neurons that remain contain Lewy bodies. Symptoms such as difficulty sleeping, loss of smell, and visual hallucinations often precede movement and other problems by as many as 10 years. Later in the course of DLB, some signs and symptoms are similar to Alzheimer’s disease and may include memory loss, poor judgment, and confusion. Other signs and symptoms of DLB are similar to those of Parkinson’s disease, including difficulty with movement and posture, a shuffling walk, and changes in alertness and attention. There is no cure for DLB, but there are drugs that control some symptoms.
  • Parkinson’s disease dementia (PDD) can occur in people with Parkinson’s disease, but not all people with Parkinson’s disease will develop dementia. PDD may affect memory, social judgment, language, or reasoning. Autopsy studies show that people with PDD often have Lewy bodies in the cortex and other brain areas, and many have amyloid plaques and tau tangles like those found in people with Alzheimer’s disease, though it is not understood what these similarities mean. The time from the onset of movement symptoms to the onset of dementia symptoms varies greatly from person to person. Risk factors for developing PDD include the onset of Parkinson’s-related movement symptoms followed by mild cognitive impairment and REM sleep behavior disorder, which involves having frequent nightmares and hallucinations.
  • Vascular contributions to cognitive impairment and dementia (VCID) cause significant changes to memory, thinking, and behavior. Cognition and brain function can be significantly affected by the size, location, and number of brain injuries. Vascular dementia and vascular cognitive impairment arise as a result of risk factors that similarly increase the risk for cerebrovascular disease (stroke), including atrial fibrillation, hypertension, diabetes, and high cholesterol. Symptoms of VCID can begin suddenly and progress or subside during one’s lifetime. VCID can occur along with Alzheimer’s disease. Persons with VCID almost always have abnormalities in the brain on magnetic resonance imaging scans. These include evidence of prior strokes, often small and asymptomatic, as well as diffuse changes in the brain’s “white matter”—the connecting “wires” of the brain that are critical for relaying messages between brain regions. Microscopic brain examination shows the thickening of blood vessel walls called arteriosclerosis and thinning or loss of components of the white matter.

Forms of VCID include:

  • Vascular dementia refers to progressive loss of memory and other cognitive functions caused by vascular injury or disease within the brain. Symptoms of vascular dementia may sometimes be difficult to distinguish from Alzheimer’s disease. Problems with organization, attention, slowed thinking, and problem-solving are all more prominent in VCID, while memory loss is more prominent in Alzheimer’s.
  • Vascular cognitive impairment involves changes in language, attention, and the ability to think, reason, and remember that are noticeable but are not significant enough to greatly impact daily life. These changes, caused
    by vascular injury or disease within the brain, progress slowly over time.
  • Post-stroke dementia can develop months after a major stroke. Not everyone who has had a major stroke will develop vascular dementia, but the risk for dementia is significantly higher in someone who has had a stroke.
  • Multi-infarct dementia is the result of many small strokes (infarcts) and mini-strokes. Language or other functions may be impaired, depending on the region of the brain that is affected. The risk for dementia is significantly higher in someone who has had a stroke. Dementia is more likely when strokes affect both sides of the brain. Even strokes that don’t show any noticeable symptoms can increase the risk of dementia.
  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an extremely rare inherited disorder caused by a thickening of the walls of small- and medium-sized blood vessels,
    which reduces the flow of blood to the brain. CADASIL is associated with multi-infarct dementia, stroke, and other disorders. The first symptoms can appear in people between ages 20 and 40. CADASIL may have symptoms that can be confused with multiple sclerosis. Many people with CADASIL are undiagnosed.
  • Subcortical vascular dementia, previously called Binswanger’s disease, involves extensive microscopic damage to the small blood vessels and nerve fibers that make up the white matter. Some consider it an aggressive form of multi-infarct dementia. Cognitive changes include problems with short-term memory, organization, attention, decision making, and behavior. Symptoms tend to begin after age 60, and they progress in a stepwise manner. People with the subcortical vascular disease often have high blood pressure, a history of stroke, or evidence of disease of the large blood vessels in the neck or heart valves.
  • Cerebral amyloid angiopathy is a buildup of amyloid plaques in the walls of blood vessels in the brain. It is generally diagnosed when multiple tiny bleeds in the brain are discovered using magnetic resonance imaging.

Neuropathology of Neurodegenerative Disorders

The different forms of age-related dementia, as well as many age-related neurodegenerative diseases, are thought to be caused by changes in various proteins. These diseases are called proteinopathies because they involve the abnormal buildup of specific proteins in the brain. Mutations in genes that provide instructions for making these proteins have been found to cause dementia in families. However, in the vast majority of affected individuals, dementia is not inherited, and the cause is unknown. Alzheimer’s disease, frontotemporal disorders, and Lewy body dementia are proteinopathies.

In some dementias, changes in the protein tau cause it to form clumps inside nerve cells in the brain, which is believed to make the cells stop functioning properly and die. Disorders that are associated with the abnormal buildup of tau are called tauopathies.

In Alzheimer’s disease, the tau protein aggregates (accumulates into abnormal clumps) and becomes twisted and tangled, forming fibers— called neurofibrillary or tau tangles—inside neurons. Abnormal clumps (plaques) of another protein, called beta-amyloid, are prominent in spaces between brain cells. Both plaques and tangles are thought to contribute to reduced function and nerve-cell death in Alzheimer’s and are the hallmarks of the disease.

Beta-amyloid plaques are also seen in some forms of LBD, cerebral amyloid angiopathy, and Parkinson’s disease dementia. They are also common in elderly individuals who do not have dementia.

Some, but not all, forms of frontotemporal disorders are tauopathies. Other forms of these disorders are associated with the buildup of the protein TDP-43. A mutation in a gene called progranulin, and another in a gene called C9orf72, can cause frontotemporal disorders with accumulation of TDP-43 in nerve cells.

In other dementias and some brain disorders, the protein synuclein becomes misshapen and forms harmful clumps inside neurons in different brain regions. Disorders in which synuclein builds up inside neurons are called synucleinopathies. Changes in synuclein and/or its function are the basis of LBD and other disorders such as multiple system atrophy. Multiple system atrophy is a progressive neurodegenerative disorder characterized by a combination of symptoms that affect both the autonomic nervous system (the part of the nervous system that controls involuntary action such as blood pressure or digestion) and movement. These changes cause parkinsonism, a condition resembling Parkinson’s disease.

Reversible Dementia-like Disorders and Conditions

Many conditions that cause dementia-like symptoms can be halted or even reversed with the appropriate treatment.

  • Normal-pressure hydrocephalus is an abnormal buildup of cerebrospinal fluid in the brain. Elderly individuals with the condition usually have trouble with walking and with bladder control before the onset of dementia. Normal-pressure hydrocephalus can be treated or even reversed by implanting a shunt system to divert fluid from the brain.
  • Nutritional deficiencies of vitamin B1 (thiamine), caused by chronic alcoholism, and of vitamin B12 can be reversed with treatment. People who have abused substances such as alcohol and recreational drugs sometimes display signs of dementia even after the substance abuse has stopped.
  • Side effects of medications or drug combinations may cause cognitive impairment that looks like degenerative or vascular dementia but which could reverse upon stopping these medications.
  • Vasculitis, an inflammation of brain blood vessels, can cause dementia after multiple strokes and may be treated with immunosuppressive medications.
  • Subdural hematoma, or bleeding between the brain’s surface and its outer covering (the dura), is common after a fall. Subdural hematomas can cause dementia-like symptoms and changes in mental function. With treatment, some symptoms can be reversed.
  • Some non-malignant brain tumors can cause symptoms resembling dementia and recovery occurs following their removal by neurosurgery.
  • Some chronic infections around the brain, so-called chronic meningitis, can cause dementia and may be treatable by drugs that kill the infectious agent.

Progressive dementias

Types of dementias that progress and aren’t reversible include:

  • Alzheimer’s disease. Alzheimer’s disease is the most common cause of dementia. Although not all causes of Alzheimer’s disease are known, experts do know that a small percentage are related to mutations of three genes, which can be passed down from parent to child. While several different genes are probably involved in Alzheimer’s disease, one important gene that increases risk is apolipoprotein E4 (APOE). Alzheimer’s disease patients have plaques and tangles in their brains. Plaques are clumps of a protein called beta-amyloid, and tangles are fibrous tangles made up of tau protein. It’s thought that these clumps damage healthy neurons and the fibers connecting them.
  • Vascular dementia. This second most common type of dementia is caused by damage to the vessels that supply blood to your brain. Blood vessel problems can cause strokes or damage the brain in other ways, such as by damaging the fibers in the white matter of the brain. The most common symptoms of vascular dementia include difficulties with problem-solving, slowed thinking, focus and organization. These tend to be more noticeable than memory loss.
  • Lewy body dementia. Lewy bodies are abnormal balloonlike clumps of protein that have been found in the brains of people with Lewy body dementia, Alzheimer’s disease and Parkinson’s disease. This is one of the more common types of progressive dementia. Common signs and symptoms include acting out one’s dreams in sleep, seeing things that aren’t there (visual hallucinations), and problems with focus and attention. Other signs include uncoordinated or slow movement, tremors, and rigidity (parkinsonism).
  • Frontotemporal dementia. This is a group of diseases characterized by the breakdown (degeneration) of nerve cells and their connections in the frontal and temporal lobes of the brain, the areas generally associated with personality, behavior and language. Common symptoms affect behavior, personality, thinking, judgment, and language and movement.
  • Mixed dementia. Autopsy studies of the brains of people 80 and older who had dementia indicate that many had a combination of several causes, such as Alzheimer’s disease, vascular dementia, and Lewy body dementia. Studies are ongoing to determine how having mixed dementia affects symptoms and treatments.
  • Huntington’s disease. Caused by a genetic mutation, this disease causes certain nerve cells in your brain and spinal cord to waste away. Signs and symptoms, including a severe decline in thinking (cognitive) skills, usually appear around age 30 or 40.
  • Traumatic brain injury (TBI). This condition is most often caused by repetitive head trauma. People such as boxers, football players, or soldiers might experience TBI. Depending on the part of the brain that’s injured, this condition can cause dementia signs and symptoms such as depression, explosiveness, memory loss, and impaired speech. TBI may also cause parkinsonism. Symptoms might not appear until years after the trauma.
  • Creutzfeldt-Jakob disease. This rare brain disorder usually occurs in people without known risk factors. This condition might be due to deposits of infectious proteins called prions. Creutzfeldt-Jakob disease usually has no known cause but can be inherited. It may also be caused by exposure to diseased brain or nervous system tissue, such as from a cornea transplant. Signs and symptoms of this fatal condition usually appear after age 60.
  • Parkinson’s disease. Many people with Parkinson’s disease eventually develop dementia symptoms (Parkinson’s disease dementia).

Dementia-like conditions that can be reversed

Some causes of dementia or dementia-like symptoms can be reversed with treatment. They include:

  • Infections and immune disorders. Dementia-like symptoms can result from fever or other side effects of your body’s attempt to fight off an infection. Multiple sclerosis and other conditions caused by the body’s immune system attacking nerve cells also can cause dementia.
  • Metabolic problems and endocrine abnormalities. People with thyroid problems, low blood sugar (hypoglycemia), too little or too much sodium or calcium, or problems absorbing vitamin B-12 can develop dementia-like symptoms or other personality changes.
  • Nutritional deficiencies. Not drinking enough liquids (dehydration); not getting enough thiamin (vitamin B-1), which is common in people with chronic alcoholism; and not getting enough vitamins B-6 and B-12 in your diet can cause dementia-like symptoms. Copper and vitamin E deficiencies also can cause dementia symptoms.
  • Medication side effects. Side effects of medications, a reaction to a medication or an interaction of several medications can cause dementia-like symptoms.
  • Subdural hematomas. Bleeding between the surface of the brain and the covering over the brain, which is common in the elderly after a fall, can cause symptoms similar to those of dementia.
  • Poisoning. Exposure to heavy metals, such as lead, and other poisons, such as pesticides, as well as recreational drug or heavy alcohol use can lead to symptoms of dementia. Symptoms might resolve with treatment.
  • Brain tumors. Rarely, dementia can result from damage caused by a brain tumor.
  • Anoxia. This condition, also called hypoxia, occurs when organ tissues aren’t getting enough oxygen. Anoxia can occur due to severe sleep apneas, asthma, heart attack, carbon monoxide poisoning or other causes.
  • Normal-pressure hydrocephalus. This condition, which is caused by enlarged ventricles in the brain, can cause walking problems, urinary difficulty and memory loss.

Risk factors

Many factors can eventually contribute to dementia. Some factors, such as age, can’t be changed. Others can be addressed to reduce your risk.

Risk factors that can’t be changed

  • Age. The risk rises as you age, especially after age 65. However, dementia isn’t a normal part of aging, and dementia can occur in younger people.
  • Family history. Having a family history of dementia puts you at greater risk of developing the condition. However, many people with a family history never develop symptoms, and many people without a family history do. There are tests to determine whether you have certain genetic mutations.
  • Down syndrome. By middle age, many people with Down syndrome develop early-onset Alzheimer’s disease.

Risk factors you can change

You might be able to control the following risk factors for dementia.

  • Diet and exercise. Research shows that lack of exercise increases the risk of dementia. And while no specific diet is known to reduce dementia risk, research indicates a greater incidence of dementia in people who eat an unhealthy diet compared with those who follow a Mediterranean-style diet rich in produce, whole grains, nuts and seeds.
  • Heavy alcohol use. If you drink large amounts of alcohol, you might have a higher risk of dementia. While some studies have shown that moderate amounts of alcohol might have a protective effect, results are inconsistent. The relationship between moderate amounts of alcohol and dementia risk isn’t well-understood.
  • Cardiovascular risk factors. These include high blood pressure (hypertension), high cholesterol, buildup of fats in your artery walls (atherosclerosis) and obesity.
  • Depression. Although not yet well-understood, late-life depression might indicate the development of dementia.
  • Diabetes. Having diabetes may increase your risk of dementia, especially if it’s poorly controlled.
  • Smoking. Smoking might increase your risk of developing dementia and blood vessel (vascular) diseases.
  • Sleep apnea. People who snore and have episodes where they frequently stop breathing while asleep may have reversible memory loss.
  • Vitamin and nutritional deficiencies. Low levels of vitamin D, vitamin B-6, vitamin B-12 and folate may increase your risk of dementia.

Symptoms of Dementia

Doctors have identified many other conditions that can cause dementia or dementia-like symptoms. The diseases have different symptoms that involve body and brain functions and affect mental health and cognition.

  • Argyrophilic grain disease is a common, late-onset degenerative disease that affects brain regions involved in memory and emotion. It causes cognitive decline and changes in memory and behavior, with difficulty finding words. The disease’s signs and symptoms are indistinguishable from late-onset AD. Confirmation of the diagnosis can be made only at autopsy.
  • Creutzfeldt-Jakob disease is a rare brain disorder that is characterized by rapidly progressing dementia. Scientists found that infectious proteins called prions become misfolded and tend to clump together, causing the brain damage. Initial symptoms include impaired memory, judgment, and thinking, along with loss of muscle coordination and impaired vision. Some symptoms of CJD can be similar to symptoms of other progressive neurological disorders, such as Alzheimer’s disease.
  • Chronic traumatic encephalopathy (CTE) is caused by repeated traumatic brain injury (TBI) in some people who suffered multiple concussions. People with CTE may develop dementia, poor coordination, slurred speech, and other symptoms similar to those seen in Parkinson’s disease 20 years or more after the injury. Late-stage CTE is also characterized by brain atrophy and widespread deposits of tau in nerve cells. In some people, even just 5 to 10 years beyond the traumatic brain injury, behavioral and mood changes may occur. Dementia may not yet be present and the brain may not have started to shrink, but small deposits of tau are seen in specific brain regions at autopsy.
  • Huntington’s disease is an inherited, progressive brain disease that affects a person’s judgment, memory, ability to plan and organize, and other cognitive functions. Symptoms typically begin around age 30 or 40 years and include abnormal and uncontrollable movements called chorea, as well as problems with walking and lack of coordination. Cognitive problems worsen as the disease progresses, and problems controlling movement lead to complete loss of ability for self-care.
  • HIV-associated dementia (HAD) can occur in people who have human immunodeficiency virus, the virus that causes AIDS. HAD damages the brain’s white matter and leads to a type of dementia associated with memory problems, social withdrawal, and trouble concentrating. People with HAD may develop movement problems as well. The incidence of HAD has dropped dramatically with the availability of effective antiviral therapies for managing the underlying HIV infections.
  • Secondary dementias occur in people with disorders that damage brain tissue. Such disorders may include multiple sclerosis, meningitis, and encephalitis, as well as Wilson’s disease (in which excessive amounts of copper build up to cause brain damage). People with malignant brain tumors may develop dementia or dementia-like symptoms because of damage to their brain circuits or a buildup of pressure inside the skull.

In addition to symptoms of dementia, the following atypical symptoms may be seen in the following conditions:

  • In patients with LBD, symptoms of well-formed visual hallucinations, delusions, sleep disturbances, and trouble processing visual information can be seen.
  • In patients with CJD, symptoms of muscle stiffness, twitches, muscle jerks, visual hallucinations, and double vision may be seen.
  • In patients with Huntington’s disease, symptoms of chorea, irritability, and obsessive-compulsive behavior may be seen.
  • In patients with vascular dementia, symptoms of imbalance, headache, sensorimotor deficits, and speech difficulties may be seen.
  • In patients with FTD, behavior changes, problems with spatial orientation, and speech difficulties may be seen.
  • In patients with PDD, symptoms of parkinsonism characterized by muffled speech, slow movement, tremors may be seen. In addition, visual hallucinations and delusions may also be seen, especially in the late stages.

Symptom By specific category

Early-stage: the early stage of dementia is often overlooked because the onset is gradual. Common symptoms include:

  • forgetfulness
  • losing track of the time
  • becoming lost in familiar places.

Middle stage: as dementia progresses to the middle stage, the signs and symptoms become clearer and more restricting. These include:

  • becoming forgetful of recent events and people’s names
  • becoming lost at home
  • having increasing difficulty with communication
  • needing help with personal care
  • experiencing behavior changes, including wandering and repeated questioning.

Late-stage: the late stage of dementia is one of near-total dependence and inactivity. Memory disturbances are serious and the physical signs and symptoms become more obvious. Symptoms include:

  • becoming unaware of the time and place
  • having difficulty recognizing relatives and friends
  • having an increasing need for assisted self-care
  • having difficulty walking
  • experiencing behavior changes that may escalate and include aggression.

Risk Factors for Dementia and Vascular Cognitive Impairment

The following risk factors may increase a person’s chance of developing one or more kinds of dementia. Some of these factors can be modified, while others cannot.

  • Age. Advancing age is the best known risk factor for developing dementia.
  • Hypertension. High blood pressure has been linked to cognitive decline, stroke, and types of dementia that damage the white matter regions of the brain. High blood pressure causes “wear-and-tear” to brain blood vessel walls called arteriosclerosis.
  • Stroke. A single major stroke or a series of smaller strokes increases a person’s risk of developing vascular dementia. A person who has had a stroke is at an increased risk of having additional strokes, which further increases the risk of developing dementia.
  • Alcohol use. Most studies suggest that regularly drinking large amounts of alcohol increases the risk of dementia. Specific dementias are associated with alcohol abuse, such as Wernicke-Korsakoff syndrome.
  • Atherosclerosis. The accumulation of fats and cholesterol in the lining of arteries, coupled with an inflammatory process that leads to a thickening of the vessel walls (known as atherosclerosis), can lead to stroke, which raises the risk for vascular dementia.
  • Diabetes. People with diabetes appear to have a higher risk for dementia. Poorly controlled diabetes is a risk factor for stroke and cardiovascular disease, which in turn increase the risk for vascular dementia.
  • Down syndrome. Many people with Down syndrome develop symptoms of Alzheimer’s disease by the time they reach middle age.
  • Genetics. The chance of developing a genetically linked form of dementia increases when more than one family member has the disorder. In many dementias, there can be a family history of a similar disease. In some cases, such as with the FTDs, having just one parent who carries a mutation increases the risk of inheriting the condition. A very small proportion of dementia is inherited.
  • Head injury. An impact to the head can cause a traumatic brain injury, or TBI. Certain types of TBI, or repeated TBIs, can cause dementia and other severe cognitive problems.
  • Parkinson’s disease. The degeneration and death of nerve cells in the brain in people with Parkinson’s disease can cause dementia and significant memory loss.
  • Smoking. Smoking increases the risk of developing cardiovascular diseases that slow or stop blood from getting to the brain.

The National Academies of Sciences, Engineering, and Medicine recently released a report of the evidence on preventing dementia: www.ncbi.nlm.nih.gov/books/NBK436397.

Diagnosis of Dementia

To diagnose dementia, doctors first assess whether an individual has an underlying treatable condition such as abnormal thyroid function, vitamin deficiency, or normal pressure hydrocephalus that may relate to cognitive difficulties. Early detection of symptoms is important, as some causes can be treated. In many cases, the specific type of dementia may not be confirmed until after the person has died and the brain is examined.

An assessment generally includes:

  • Medical history and physical exam. Assessing a person’s medical and family history, current symptoms and medication, and vital signs can help the doctor detect conditions that might cause or occur with dementia. Some conditions may be treatable.

  • Neurological evaluations. Assessing balance, sensory response, reflexes, and other functions helps the doctor identify signs of conditions that may affect the diagnosis or are treatable with drugs. Doctors also might use an electroencephalogram, a test that records patterns of electrical activity in the brain, to check for abnormal electrical brain activity.

  • Brain scans. Computed tomography (CT) and magnetic resonance imaging (MRI) can detect structural abnormalities and rule out other causes of dementia.  Positron-emission tomography (PET) can look for patterns of altered brain activity that are common in dementia. Recent advances in PET can detect amyloid plaques and tau tangles in AD.

  • Cognitive and neuropsychological tests. These tests are used to assess memory, language skills, math skills, problem-solving, and other abilities related to mental functioning.

  • Laboratory tests. Testing a person’s blood and other fluids, as well as checking levels of various chemicals, hormones, and vitamin levels can identify or rule out conditions that may contribute to dementia.

  • Presymptomatic tests. Genetic testing can help some people who have a strong family history of dementia identify risk for dementia with a known gene defect.

  • Psychiatric evaluation. This evaluation will help determine if depression or another mental health condition is causing or contributing to a person’s symptoms.

Guidelines prepared by the National Institute on Aging and the Alzheimer’s Association focus on three stages of Alzheimer’s disease: (1) dementia due to Alzheimer’s, (2) mild cognitive impairment (MCI) due to Alzheimer’s, and (3) preclinical (presymptomatic) Alzheimer’s. (Presymptomatic identification is exclusively used as a research diagnosis at this point and has no relevance to routine clinical practice.) The guidelines also include biomarker tests used in studies to measure biological changes in the brain associated with Alzheimer’s disease and criteria for documenting and reporting Alzheimer’s-related changes observed during an autopsy.

Treatment and Management

There are currently no treatments to stop or slow dementia in neurodegenerative diseases.  Some diseases that occur at the same time as dementia (such as diabetes and depression) can be treated. Other symptoms that may occur in dementia-like conditions can also be treated, although some symptoms may only respond to treatment for a period of time. A team of specialists—doctors, nurses, and speech, physical, and other therapists—familiar with these disorders can help guide patient care.

Medications are available to treat certain behavioral symptoms, as well as delusions, depression, muscle stiffness, and risk factors for vascular cognitive impairment such as high blood pressure. Always consult with a doctor, as some medications may make symptoms worse.

Cholinesterase inhibitors prevent the breakdown of acetylcholine and can slow or delay the worsening of symptoms. Memantine is an NMDA agonist and decreases the activity of glutamine. Donepezil is approved for all stages of Alzheimer’s disease, galantamine, and rivastigmine for mild to moderate stage and memantine for moderate to severe stage.

Behavior symptoms include irritability, anxiety, and depression. Antidepressants like SSRI, antipsychotics, and anxiolytics can help with these symptoms. In addition, non-drug approaches like supportive care, memory training, physical exercise programs, mental and social stimulation must be employed in symptom control.

Treatment of sleep symptoms must be an important consideration in patients with dementia. Medication options include amitriptyline, lorazepam, zolpidem, temazepam, quetiapine, etc., Non-drug approaches include daily exercise, light therapy, sleep routine, avoiding caffeine and alcohol, pain control, biofeedback, and multicomponent cognitive-behavioral therapy.

Alzheimer’s disease. Most drugs for dementia are used to treat symptoms in AD. One class of drugs, called cholinesterase inhibitors, can temporarily improve or stabilize memory and thinking skills in some people by increasing the activity of the cholinergic brain network—a subsystem in the brain that is highly involved with memory and learning.  These drugs include donepezil, rivastigmine, and galantamine. The drug memantine is in another class of medications called NMDA receptor antagonists, which prevent declines in learning and memory. Memantine may be combined with a cholinesterase inhibitor for added benefits. These drugs are sometimes used to treat other dementias in which Alzheimer’s disease is believed to co-occur.

Frontotemporal disorders. There are no medications approved to treat or prevent FTD and most other types of progressive dementia. Sedatives, antidepressants, and other drugs used to treat Parkinson’s and Alzheimer’s symptoms may help manage certain symptoms and behavioral problems associated with the disorders.

Dementia with Lewy bodies. Medicines available for managing DLB are aimed at relieving symptoms such as gait and balance disturbances, stiffness, hallucinations, and delusions.  Studies suggest that the cholinesterase inhibitor drugs for Alzheimer’s disease may offer some benefit to people with DLB.

Parkinson’s disease dementia. Some studies suggest that the cholinesterase inhibitors used to treat people with AD might improve cognitive, behavioral, and psychotic symptoms in people with Parkinson’s disease dementia. Unfortunately, many of the medications used to treat the motor symptoms of PD worsen cognitive problems. The U.S. Food and Drug Administration has approved rivastigmine (an Alzheimer’s drug) to treat cognitive symptoms in PDD.

Vascular contributions to cognitive impairment and dementia. This type of dementia is often managed with drugs to prevent strokes or reduce the risk of additional brain damage. Some studies suggest that drugs that improve memory in AD might benefit people with early vascular dementia. Treating the modifiable risk factors can help prevent additional stroke.

A team of therapists can help with maintaining physical movement, address speech, and swallowing issues, and help people learn new ways to handle the loss of skills with everyday tasks such as feeding oneself.

It is important to educate family, friends, and caregivers about a loved one’s medical issues. Also, in-person and online support groups available through many disease awareness and caregiver advocacy organizations can give families and other caregivers additional resources, as well as opportunities to share experiences and express concerns.

WHO response

WHO recognizes dementia as a public health priority. In May 2017, the World Health Assembly endorsed the Global action plan on the public health response to dementia 2017-2025. The Plan provides a comprehensive blueprint for action – for policy-makers, international, regional and national partners, and WHO as in the following areas: addressing dementia as a public health priority; increasing awareness of dementia and establishing dementia-friendly initiatives; reducing the risk of dementia; diagnosis, treatment and care; information systems for dementia; support for dementia carers; and, research and innovation

An international surveillance platform, the Global Dementia Observatory (GDO), has been established for policy-makers and researchers to facilitate monitoring and sharing of information on dementia policies, service delivery, epidemiology, and research. WHO is also developing a knowledge exchange platform to facilitate the exchange of good practices in the area of dementia.

WHO has developed Towards a dementia plan: a WHO guide, which provides guidance to the Member States in creating and operationalizing a dementia plan. The guide is closely linked to WHO’s GDO and includes associated tools such as a checklist to guide the preparation, development, and implementation of a dementia plan. It can also be used for stakeholder mapping and priority setting.

WHO’s Guidelines on risk reduction of cognitive decline and dementia provide evidence-based recommendations on interventions for reducing modifiable risk factors for dementia, such as physical inactivity and unhealthy diets, as well as controlling medical conditions linked to dementia, including hypertension and diabetes.

Dementia is also one of the priority conditions in the WHO Mental Health Gap Action Programme (mhGAP), which is a resource for generalists, particularly in low- and middle-income countries, to help them provide first-line care for mental, neurological, and substance use disorders.

WHO has developed iSupport, a knowledge and skills training program for carers of people living with dementia. support is available as a hard copy manual and is already being implemented in several countries. The online version of support will be available soon.

What are the Epilepsies? – Causes, Symptoms, Treatment

Epilepsies are chronic neurological disorders in which clusters of nerve cells, or neurons, in the brain sometimes signal abnormally and cause seizures. Neurons normally generate electrical and chemical signals that act on other neurons, glands, and muscles to produce human thoughts, feelings, and actions. During a seizure, many neurons fire (signal) at the same time – as many as 500 times a second, much faster than normal. This surge of excessive electrical activity happening at the same time causes involuntary movements, sensations, emotions, and behaviors and the temporary disturbance of normal neuronal activity may cause a loss of awareness.

Epilepsy can be considered a spectrum disorder because of its different causes, different seizure types, its ability to vary in severity and impact from person to person, and its range of co-existing conditions. Some people may have convulsions (sudden onset of repetitive general contraction of muscles) and lose consciousness. Others may simply stop what they are doing, have a brief lapse of awareness, and stare into space for a short period. Some people have seizures very infrequently, while other people may experience hundreds of seizures each day. There also are many different types of epilepsy, resulting from a variety of causes. The recent adoption of the term “the epilepsies” underscores the diversity of types and causes.

In general, a person is not considered to have epilepsy until he or she has had two or more unprovoked seizures separated by at least 24 hours. In contrast, a provoked seizure is one caused by a known precipitating factor such as high fever, nervous system infections, acute traumatic brain injury, or fluctuations in blood sugar or electrolyte levels.

Anyone can develop epilepsy.  About 2.3 million adults and more than 450,000 children and adolescents in the United States currently live with epilepsy. Each year, an estimated 150,000 people are diagnosed with epilepsy. Epilepsy affects both males and females of all races, ethnic backgrounds, and ages. In the United States alone, the annual costs associated with epilepsies are estimated to be $15.5 billion in direct medical expenses and lost or reduced earnings and productivity.

The majority of those diagnosed with epilepsy have seizures that can be controlled with drug therapies and surgery. However, as much as 30 to 40 percent of people with epilepsy continue to have seizures because available treatments do not completely control their seizures (called intractable or medication-resistant epilepsy).

While many forms of epilepsy require lifelong treatment to control the seizures, for some people the seizures eventually go away. The odds of becoming seizure-free are not as good for adults or for children with severe epilepsy syndromes, but it is possible that seizures may decrease or even stop over time. This is more likely if the epilepsy starts in childhood, has been well-controlled by medication, or if the person has had surgery to remove the brain focus of the abnormal cell firing.

Many people with epilepsy lead productive lives, but some will be severely impacted by their epilepsy. Medical and research advances in the past two decades have led to a better understanding of epilepsies and seizures. More than 20 different medications and a variety of dietary treatments and surgical techniques (including two devices) are now available and may provide good control of seizures.  Devices can modulate brain activity to decrease seizure frequency. Advance neuroimaging can identify brain abnormalities that give rise to seizures which can be cured by neurosurgery. Even dietary changes can effectively treat certain types of epilepsy. Research on the underlying causes of epilepsies, including the identification of genes for some forms of epilepsy, has led to a greatly improved understanding of these disorders that may lead to more effective treatments or even to new ways of preventing epilepsy in the future.

What causes the epilepsies?

Epilepsies have many possible causes, but for up to half of people with epilepsy a cause is not known. In other cases, epilepsies are clearly linked to genetic factors, developmental brain abnormalities, infection, traumatic brain injury, stroke, brain tumors, or other identifiable problems. Anything that disturbs the normal pattern of neuronal activity – from illness to brain damage to abnormal brain development – can lead to seizures.

The epilepsies may develop because of an abnormality in brain wiring, an imbalance of nerve signaling in the brain (in which some cells either over-excited or over-inhibit other brain cells from sending messages), or some combination of these factors. In some pediatric conditions, abnormal brain wiring causes other problems such as intellectual impairment.

In other persons, the brain’s attempts to repair itself after a head injury, stroke, or other problem may inadvertently generate abnormal nerve connections that lead to epilepsy. Brain malformations and abnormalities in brain wiring that occur during brain development also may disturb neuronal activity and lead to epilepsy.

Seizures may be either provoked or unprovoked. Provoked seizures, also known as acute symptomatic seizures, may result from electrolyte disorders, toxins, head injury, infectious processes, vascular anomalies, tumors or other mass lesions, and many other causes. A listing of provoked causes of seizures is lengthy and could include complications of almost any disease process. Some common causes are listed below:

  • Electrolyte disturbances (hypoglycemia, hyponatremia, hypernatremia, hypocalcemia, others)
  • Acute toxic effects (antidepressants, sympathomimetics, others)
  • Withdrawal syndromes (ethanol, benzodiazepines, others)
  • Irregularity with prescribed antiepileptic medications
  • Sepsis
  • CNS infections
  • Hypoxic brain injury
  • Traumatic brain injury
  • Stroke ischemic or hemorrhagic
  • Neoplasm
  • Inflammatory (lupus cerebritis, anti-NMDA receptor encephalitis, others)
  • Fever
  • Sleep deprivation

Geneticsyoclonus

Genetic mutations may play a key role in the development of certain epilepsies. Many types of epilepsy affect multiple blood-related family members, pointing to a strong inherited genetic component. In other cases, gene mutations may occur spontaneously and contribute to the development of epilepsy in people with no family history of the disorder (called “de novo” mutations). Overall, researchers estimate that hundreds of genes could play a role in the disorders.

Several types of epilepsy have been linked to mutations in genes that provide instructions for ion channels, the “gates” that control the flow of ions in and out of cells to help regulate neuronal signaling. For example, most infants with Dravet syndrome, a type of epilepsy associated with seizures that begin before the age of one year, carry a mutation in the SCN1A gene that causes seizures by affecting sodium ion channels.

Genetic mutations also have been linked to disorders known as progressive myoclonic epilepsies, which are characterized by ultra-quick muscle contractions (m) and seizures over time. For example, Lafora disease, a severe, progressive form of myoclonic epilepsy that begins in childhood, has been linked to a gene that helps to break down carbohydrates in brain cells.

Mutations in genes that control neuronal migration – a critical step in brain development – can lead to areas of misplaced or abnormally formed neurons, called cortical dysplasia, in the brain that can cause these miswired neurons to misfire and lead to epilepsy.

Other genetic mutations may not cause epilepsy but may influence the disorder in other ways. For example, one study showed that many people with certain forms of epilepsy have an abnormally active version of a gene that results in resistance to anti-seizure drugs. Genes also may control a person’s susceptibility to seizures, or seizure threshold, by affecting brain development.

Other Disorders

Epilepsies may develop as a result of brain damage associated with many types of conditions that disrupt normal brain activity. Seizures may stop once these conditions are treated and resolved. However, the chances of becoming seizure-free after the primary disorder is treated are uncertain and vary depending on the type of disorder, the brain region that is affected, and how much brain damage occurred prior to treatment. Examples of conditions that can lead to epilepsy include:

  • Brain tumors, including those associated with neurofibromatosis or tuberous sclerosis complex, two inherited conditions that cause benign tumors called hamartomas to grow in the brain
  • Head trauma
  • Alcoholism or alcohol withdrawal
  • Alzheimer’s disease
  • Strokes, heart attacks, and other conditions that deprive the brain of oxygen (a significant portion of new-onset epilepsy in elderly people is due to stroke or another cerebrovascular disease)
  • Abnormal blood vessel formation (arteriovenous malformations) or bleeding in the brain (hemorrhage)
  • Inflammation of the brain
  • Infections such as meningitis, HIV, and viral encephalitis

Cerebral palsy or other developmental neurological abnormalities may also be associated with epilepsy. About 20 percent of seizures in children can be attributed to developmental neurological conditions. Epilepsies often co-occur in people with abnormalities of brain development or other neurodevelopmental disorders. Seizures are more common, for example, among individuals with an autism spectrum disorder or intellectual impairment. In one study, fully a third of children with autism spectrum disorder had treatment-resistant epilepsy.

Seizure Triggers

Seizure triggers do not cause epilepsy but can provoke first seizures in those who are susceptible or can cause seizures in people with epilepsy who otherwise experience good seizure control with their medication.  Seizure triggers include alcohol consumption or alcohol withdrawal, dehydration or missing meals, stress, and hormonal changes associated with the menstrual cycle. In surveys of people with epilepsy, stress is the most commonly reported seizure trigger. Exposure to toxins or poisons such as lead or carbon monoxide, street drugs, or even excessively large doses of antidepressants or other prescribed medications also can trigger seizures.

Sleep deprivation is a powerful trigger of seizures. Sleep disorders are common among people with epilepsies and appropriate treatment of co-existing sleep disorders can often lead to improved control of seizures. Certain types of seizures tend to occur during sleep, while others are more common during times of wakefulness, suggesting to physicians how to best adjust a person’s medication.

For some people, visual stimulation can trigger seizures in a condition known as photosensitive epilepsy. Stimulation can include such things as flashing lights or moving patterns.

What are the different kinds of seizures?

Seizures are divided into two major categories – focal seizures and generalized seizures. However, there are many different types of seizures in each of these categories. In fact, doctors have described more than 30 different types of seizures.

Focal Seizures

Focal seizures originate in just one part of the brain. About 60 percent of people with epilepsy have focal seizures. These seizures are frequently described by the area of the brain in which they originate. Many people are diagnosed with focal frontal lobe or medial temporal lobe seizures.

In some focal seizures, the person remains conscious but may experience motor, sensory, or psychic feelings (for example, intense dejà vu or memories) or sensations that can take many forms. The person may experience sudden and unexplainable feelings of joy, anger, sadness, or nausea. He or she also may hear, smell, taste, see, or feel things that are not real and may have movements of just one part of the body, for example, just one hand.

In other focal seizures, the person has a change in consciousness, which can produce a dreamlike experience. The person may display strange, repetitious behaviors such as blinks, twitches, mouth movements (often like chewing or swallowing, or even walking in a circle). These repetitious movements are called automatisms. More complicated actions, which may seem purposeful, can also occur involuntarily. Individuals may also continue activities they started before the seizure began, such as washing dishes in a repetitive, unproductive fashion. These seizures usually last just a minute or two.

Some people with focal seizures may experience auras – unusual sensations that warn of an impending seizure. Auras are usually focal seizures without interruption of awareness ( e.g., dejà vu, or an unusual abdominal sensation) but some people experience a true warning before an actual seizure. An individual’s symptoms, and the progression of those symptoms, tend to be similar every time. Other people with epilepsy report experiencing a prodrome, a feeling that a seizure is imminent lasting hours or days.

The symptoms of focal seizures can easily be confused with other disorders. The strange behavior and sensations caused by focal seizures also can be mistaken for symptoms of narcolepsy, fainting, or even mental illness. Several tests and careful monitoring may be needed to make the distinction between epilepsy and these other disorders.

Generalized Seizures

Generalized seizures are a result of abnormal neuronal activity that rapidly emerges on both sides of the brain. These seizures may cause loss of consciousness, falls, or a muscle’s massive contractions. The many kinds of generalized seizures include:

  • Absence seizures – may cause the person to appear to be staring into space with or without slight twitching of the muscles.
  • Tonic seizures  cause stiffening of muscles of the body, generally those in the back, legs, and arms.
  • Clonic seizures cause repeated jerking movements of muscles on both sides of the body.
  • Myoclonic seizures cause jerks or twitches of the upper body, arms, or legs.
  • Atonic seizures – cause a loss of normal muscle tone, which often leads the affected person to fall down or drop the head involuntarily.
  • Tonic-clonic seizures – cause a combination of symptoms, including stiffening of the body and repeated jerks of the arms and/or legs as well as loss of consciousness.
  • Secondarily generalized seizures.

Not all seizures can be easily defined as either focal or generalized. Some people have seizures that begin as focal seizures but then spread to the entire brain. Other people may have both types of seizures but with no clear pattern.

What are the different kinds of epilepsy?

Just as there are many different kinds of seizures, there are many different kinds of epilepsy. Hundreds of different epilepsy syndromes – disorders characterized by a specific set of symptoms that include epilepsy as a prominent symptom – have been identified. Some of these syndromes appear to be either hereditary or caused by de Novo mutations. For other syndromes, the cause is unknown. Epilepsy syndromes are frequently described by their symptoms or by where in the brain they originate.

  • Absence epilepsy – is characterized by repeated seizures that cause momentary lapses of consciousness. These seizures almost always begin in childhood or adolescence and tend to run in families, suggesting that they may be at least partially due to genetic factors. Individuals may show purposeless movements during their seizures, such as a jerking arm or rapidly blinking eyes, while others may have no noticeable symptoms except for brief times when they appear to be staring off into space. Immediately after a seizure, the person can resume whatever he or she was doing. However, these seizures may occur so frequently (in some cases up to 100 or more a day) that the person cannot concentrate in school or other situations. Childhood absence epilepsy usually stops when the child reaches puberty. Although most children with childhood absence epilepsy have a good prognosis, there may be long-lasting negative consequences and some children will continue to have absence seizures into adulthood and/or go on to develop other seizure types.
  • Frontal lobe epilepsy is a common epilepsy syndrome that features brief focal seizures that may occur in clusters.  It can affect the part of the brain that controls movement and involves seizures that can cause muscle weakness or abnormal, uncontrolled movement such as twisting, waving the arms or legs, eye deviation to one side, or grimacing, and are usually associates with some loss of awareness.  Seizures usually occur when the person is asleep but also may occur while awake.
  • Temporal lobe epilepsy or TLE, is the most common epilepsy syndrome with focal seizures. These seizures are often associated with auras of nausea, emotions (such as déjà vu or fear), or unusual smell or taste. The seizure itself is a brief period of impaired consciousness which may appear as a staring spell, dream-like state, or repeated automatisms. TLE often begins in childhood or teenage years. Research has shown that repeated temporal lobe seizures are often associated with shrinkage and scarring (sclerosis) of the hippocampus. The hippocampus is important for memory and learning. It is not clear whether localized asymptomatic seizure activity over years causes hippocampal sclerosis.
  • Neocortical epilepsy is characterized by seizures that originate from the brain’s cortex or outer layer. The seizures can be either focal or generalized. Symptoms may include unusual sensations, visual hallucinations, emotional changes, muscle contractions, convulsions, and a variety of other symptoms, depending on where in the brain the seizures originate.
  • Lennox-Gastaut syndrome have several different types of seizures, including atonic seizures, which cause sudden falls and are also called drop attacks. Seizure onset is usually before age four years. This severe form of epilepsy can be very difficult to treat effectively. Rasmussen’s encephalitis is a progressive form of epilepsy in which half the brain shows chronic inflammation. Some childhood epilepsy syndromes, such as childhood absence epilepsy, tend to go into remission or stop entirely during adolescence, whereas other syndromes such as juvenile myoclonic epilepsy (which features jerk-like motions upon waking) and Lennox-Gastaut syndrome are usually present for life once they develop. Children with Dravet syndrome have seizures that start before age one and later in infancy develop into other seizure types.
  • A hypothalamic hamartoma is a rare form of epilepsy that first occurs during childhood and is associated with malformations of the hypothalamus at the base of the brain. People with hypothalamic hamartoma have seizures that resemble laughing or crying. Such seizures frequently go unrecognized and are difficult to diagnose.
  • Tonic seizures: Your arms and legs become rigid and stiff. This kind of seizure usually passes quite quickly and doesn’t always affect your state of consciousness.
  • Atonic seizures (“drop attacks”): Here the muscles in one part of your body suddenly become limp. As a result, your chin might drop down towards your chest, or your legs might give way, for instance. You may also briefly become unconscious and fall.
  • Clonic seizures: Large muscle groups – for instance in the arms or legs – jerk in a slow rhythm. This is usually accompanied by loss of consciousness.
  • Myoclonic seizures: Individual muscle groups twitch rapidly. Your state of consciousness is usually not affected.
  • Tonic-clonic seizures (sometimes called “grand mal seizures”): Your whole body convulses and twitches, and you become unconscious.
  • Absence seizures (sometimes called “petit mal seizures”): In this mild type of seizure, people suddenly lose awareness (appear to “zone out”) for a brief moment.

When are seizures not epilepsy?

While any seizure is cause for concern, having a seizure does not by itself mean a person has epilepsy. First seizures, febrile seizures, nonepileptic events, and eclampsia (a life-threatening condition that can occur in pregnant women) are examples of conditions involving seizures that may not be associated with epilepsy. Regardless of the type of seizure, it’s important to inform your doctor when one occurs.

First Seizures

Many people have a single seizure at some point in their lives, and it can be provoked or unprovoked, meaning that they can occur with or without any obvious triggering factor. Unless the person has suffered brain damage or there is a family history of epilepsy or other neurological abnormalities, the majority of single seizures usually are not followed by additional seizures. Medical disorders which can provoke a seizure include low blood sugar, very high blood sugar in diabetics, disturbances in salt levels in the blood (sodium, calcium, magnesium), eclampsia during or after pregnancy, impaired function of the kidneys, or impaired function of the liver. Sleep deprivation, missing meals, or stress may serve as seizure triggers in susceptible people.

Many people with a first seizure will never have a second seizure, and physicians often counsel against starting antiseizure drugs at this point.  In some cases where additional epilepsy risk factors are present, drug treatment after the first seizure may help prevent future seizures. Evidence suggests that it may be beneficial to begin antiseizure medication once a person has had a second unprovoked seizure, as the chance of future seizures increases significantly after this occurs. A person with a pre-existing brain problem, for example, a prior stroke or traumatic brain injury, will have a higher risk of experiencing a second seizure. In general, the decision to start antiseizure medication is based on the doctor’s assessment of many factors that influence how likely it is that another seizure will occur in that person.

In one study that followed individuals for an average of 8 years, 33 percent of people had a second seizure within 4 years after an initial seizure. People who did not have a second seizure within that time remained seizure-free for the rest of the study. For people who did have a second seizure, the risk of a third seizure was about 73 percent by the end of 4 years. Among those with a third unprovoked seizure, the risk of a fourth was 76 percent.

Febrile Seizures

Not infrequently a child will have a seizure during the course of an illness with a high fever. These seizures are called febrile seizures. Antiseizure medications following a febrile seizure are generally not warranted unless certain other conditions are present: a family history of epilepsy, signs of nervous system impairment prior to the seizure, or a relatively prolonged or complicated seizure. The risk of subsequent non-febrile seizures is low unless one of these factors is present.

Results from a study funded by the National Institute of Neurological Disorders and Stroke (NINDS) suggested that certain findings using diagnostic imaging of the hippocampus may help identify which children with prolonged febrile seizures are subsequently at increased risk of developing epilepsy.

Researchers also have identified several different genes that influence the risks associated with febrile seizures in certain families. Studying these genes may lead to new understandings of how febrile seizures occur and perhaps point to ways of preventing them.

Nonepileptic Events

An estimated 5 to 20 percent of people diagnosed with epilepsy actually have non-epileptic seizures (NES), which outwardly resemble epileptic seizures, but are not associated with a seizure-like electrical discharge in the brain. Non-epileptic events may be referred to as psychogenic non-epileptic seizures or PNES, which do not respond to antiseizure drugs. Instead, PNES are often treated by cognitive behavioral therapy to decrease stress and improve self-awareness.

A history of traumatic events is among the known risk factors for PNES. People with PNES should be evaluated for underlying psychiatric illness and treated appropriately. Two studies together showed a reduction in seizures and fewer coexisting symptoms following treatment with cognitive behavioral therapy. Some people with epilepsy have psychogenic seizures in addition to their epileptic seizures.

Other nonepileptic events may be caused by narcolepsy (sudden attacks of sleep), Tourette syndrome (repetitive involuntary movements called tics), cardiac arrhythmia (irregular heartbeat), and other medical conditions with symptoms that resemble seizures. Because symptoms of these disorders can look very much like epileptic seizures, they are often mistaken for epilepsy.

Are there special risks associated with epilepsy?

Although most people with epilepsy lead full, active lives, there is an increased risk of death or serious disability associated with epilepsy. There may be an increased risk of suicidal thoughts or actions related to some antiseizure medications that are also used to treat mania and bipolar disorder. Two life-threatening conditions associated with epilepsies are status epilepticus and sudden unexpected death in epilepsy (SUDEP).

Status Epilepticus

Status epilepticus is a potentially life-threatening condition in which a person either has an abnormally prolonged seizure or does not fully regain consciousness between recurring seizures. Status epilepticus can be convulsive (in which outward signs of a seizure are observed) or nonconvulsive (which has no outward signs and is diagnosed by an abnormal EEG). Nonconvulsive status epilepticus may appear as a sustained episode of confusion, agitation, loss of consciousness, or even coma.

Any seizure lasting longer than 5 minutes should be treated as though it was status epilepticus. There is some evidence that 5 minutes is sufficient to damage neurons and that seizures are unlikely to end on their own, making it necessary to seek medical care immediately.  One study showed that 80 percent of people in status epilepticus who received medication within 30 minutes of seizure onset eventually stopped having seizures, whereas only 40 percent recovered if 2 hours had passed before they received medication. The mortality rate can be as high as 20 percent if treatment is not initiated immediately.

Researchers are trying to shorten the time it takes for antiseizure medications to be administered. A key challenge has been establishing an intravenous (IV) line to deliver injectable antiseizure drugs in a person having convulsions. An NINDS-funded study on status epilepticus found that when paramedics delivered the medication midazolam to the muscles using an autoinjector, similar to the EpiPen drug delivery system used to treat serious allergic reactions, seizures could be stopped significantly earlier compared to when paramedics took the time to give lorazepam intravenously. In addition, drug delivery by autoinjector was associated with a lower rate of hospitalization compared with IV delivery.

Sudden Unexplained Death in Epilepsy (SUDEP)

For reasons that are poorly understood, people with epilepsy have an increased risk of dying suddenly for no discernible reason. Some studies suggest that each year approximately one case of SUDEP occurs for every 1,000 people with epilepsies. For some, this risk can be higher, depending on several factors. People with more difficult to control seizures tend to have a higher incidence of SUDEP.

SUDEP can occur at any age. Researchers are still unsure why SUDEP occurs, although some research points to abnormal heart and respiratory function due to gene abnormalities (ones that cause epilepsy and also affect heart function). People with epilepsy may be able to reduce the risk of SUDEP by carefully taking all antiseizure medication as prescribed. Not taking the prescribed dosage of medication on a regular basis may increase the risk of SUDEP in individuals with epilepsy, especially those who are taking more than one medication for their epilepsy.

Symptoms of Epilepsies

Symptoms depend on the area involved.

  • Temporal lobe focal aware seizures can cause autonomic and/or psychological symptoms. The most common symptom is an epigastric rising sensation. Sometimes sensory symptoms like auditory and olfactory hallucinations can be present.
  • Frontal lobe simple partial seizures are usually short but can have a rapid generalization. They have prominent motor manifestations like twitching or stiffness in one muscle group on one side.
  • Parietal lobe Focal aware seizures present with predominantly sensory symptoms. They may have a feeling of tingling or numbness that may or may not spread in a Jacksonian manner. Head, arm, and face are most commonly involved. They can also present with visual metamorphopsia, loss of awareness of a body part, vertigo, and sometimes language disturbances.
  • Occipital lobe seizures usually have visual manifestations like scotoma, amaurosis, or flashing lights. They also can have visual hallucinations and perceptive illusions in which objects appear distorted.   

Diagnosis of Epilepsies

A number of tests are used to determine whether a person has a form of epilepsy and, if so, what kind of seizures the person has.

Imaging and Monitoring

An electroencephalogram, or EEG, can assess whether there are any detectable abnormalities in the person’s brain waves and may help to determine if antiseizure drugs would be of benefit.  This most common diagnostic test for epilepsy records electrical activity detected by electrodes placed on the scalp. Some people who are diagnosed with a specific syndrome may have abnormalities in brain activity, even when they are not experiencing a seizure. However, some people continue to show normal electrical activity patterns even after they have experienced a seizure. These occur if the abnormal activity is generated deep in the brain where the EEG is unable to detect it. Many people who do not have epilepsy also show some unusual brain activity on an EEG. Whenever possible, an EEG should be performed within 24 hours of an individual’s first seizure. Ideally, EEGs should be performed while the person is drowsy as well as when he or she is awake because brain activity during sleep and drowsiness is often more revealing of activity resembling epilepsy.  Video monitoring may be used in conjunction with EEG to determine the nature of a person’s seizures and to rule out other disorders such as psychogenic non-epileptic seizures, cardiac arrhythmia, or narcolepsy that may look like epilepsy.

A magnetoencephalogram (MEG) detects the magnetic signals generated by neurons to help detect surface abnormalities in brain activity. MEG can be used in planning a surgical strategy to remove focal areas involved in seizures while minimizing interference with brain function.

The most commonly used brain scans include CT (computed tomography), PET (positron emission tomography), and MRI (magnetic resonance imaging). CT and MRI scans reveal structural abnormalities of the brain such as tumors and cysts, which may cause seizures. A type of MRI called functional MRI (fMRI) can be used to localize normal brain activity and detect abnormalities in functioning. SPECT (single-photon emission computed tomography) is sometimes used to locate seizure foci in the brain.  A modification of SPECT, called ictal SPECT, can be very helpful in localizing the brain area generating seizures. In a person admitted to the hospital for epilepsy monitoring, the SPECT blood flow tracer is injected within 30 seconds of a seizure, then the images of brain blood flow at the time of the seizure are compared with blood flow images taken in between seizures. The seizure onset area shows a high blood flow region on the scan. PET scans can be used to identify brain regions with lower than normal metabolism, a feature of the epileptic focus after the seizure has stopped.

Medical History

Taking a detailed medical history, including symptoms and duration of the seizures, is still one of the best methods available to determine what kind of seizures a person has had and to determine any form of epilepsy.  The medical history should include details about any past illnesses or other symptoms a person may have had, as well as any family history of seizures. Since people who have suffered a seizure often do not remember what happened, caregiver or other accounts of seizures are vital to this evaluation. The person who experienced the seizure is asked about any warning experiences. The observers will be asked to provide a detailed description of events in the timeline they occurred.

Blood Tests

Blood samples may be taken to screen for metabolic or genetic disorders that may be associated with seizures. They also may be used to check for underlying health conditions such as infections, lead poisoning, anemia, and diabetes that may be causing or triggering the seizures. In the emergency department, it is standard procedure to screen for exposure to recreational drugs in anyone with a first seizure.

Developmental, Neurological, and Behavioral Tests

Tests devised to measure motor abilities, behavior, and intellectual ability are often used as a way to determine how epilepsy is affecting an individual. These tests also can provide clues about what kind of epilepsy the person has.

Can epilepsies be prevented?

At this time there are no medications or other therapies that have been shown to prevent epilepsy. In some cases, the risk factors that lead to epilepsy can be modified. Good prenatal care, including treatment of high blood pressure and infections during pregnancy, may prevent brain injury in the developing fetus that may lead to epilepsy and other neurological problems later. Treating cardiovascular disease, high blood pressure, and other disorders that can affect the brain during adulthood and aging also may prevent some cases of epilepsy. Prevention or early treatment of infections such as meningitis in high-risk populations may also prevent cases of epilepsy. Also, the wearing of seatbelts and bicycle helmets, and correctly securing children in car seats, may avert some cases of epilepsy associated with head trauma.

Treatment of Epilepsies

An accurate diagnosis of the type of epilepsy a person has is crucial for finding an effective treatment. There are many different ways to successfully control seizures. Doctors who treat epilepsies come from many different fields of medicine and include neurologists, pediatricians, pediatric neurologists, internists, and family physicians, as well as neurosurgeons. An epileptologist is someone who has completed advanced training and specializes in treating epilepsies.

Once epilepsy is diagnosed, it is important to begin treatment as soon as possible. Research suggests that medication and other treatments may be less successful once seizures and their consequences become established. There are several treatment approaches that can be used depending on the individual and the type of epilepsy. If seizures are not controlled quickly, referral to an epileptologist at a specialized epilepsy center should be considered, so that careful consideration of treatment options, including dietary approaches, medication, devices, and surgery, can be performed in order to gain optimal seizure treatment.

Medications

The most common approach to treating epilepsies is to prescribe antiseizure drugs.  More than 20 different antiseizure medications are available today, all with different benefits and side effects. Most seizures can be controlled with one drug (called monotherapy).  Deciding on which drug to prescribe, and at what dosage, depends on many different factors, including seizure type, lifestyle and age, seizure frequency, drug side effects, medicines for other conditions, and, for a woman, whether she is pregnant or will become pregnant.  It may take several months to determine the best drug and dosage.  If one treatment is unsuccessful, another may work better.

Seizure medications include:

Generic Brand Name (United States)
Carbamazepine Carbatrol, Tegretol
Clobazam Frisium, Onfi
Clonazepam Klonopin
Diazepam Diastat, Diazepam, Valium
Divalproex Sodium Depakote, Depakote ER
Eslicarbazepine Acetate Options
Ezogabine Potiga
Felbamate Felbatol
Gabapentin Neurontin
Lacosamide Vimpat
Lamotrigine Lamictal
Levetiracetam Keppra, Keppra XR
Lorazepam Ativan
Oxcarbazepine Oxtellar, Oxtellar XR, Trileptal
Perampanel Fycompa
Phenobarbital
Phenytoin Dilantin, Phenytek,
Pregabalin Lyrica
Primidone Mysoline
Rufinamide Daniel
Tiagabine Hydrochloride Gabitril
Topiramate Topamax, Topamax XR
Valproic Acid Depakene
Vigabatrin Sabril

In June 2018 the U.S. Food and Drug Administration approved cannabidiol (Epidolex, derived from marijuana) for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome for children age 2 and older.  The drug contains only a small amount of the psychoactive element in marijuana and does not induce euphoria associated with the drug. In November 2019 the FDA approved cenobamate tablets to treat adults with partial-onset seizures. FDA also has approved the drug fenfluramine to reduce the frequency of convulsive seizures associated with Dravet syndrome in children ages 2 years and older.

Start drug therapy, many medications are options to treat a chronic seizure disorder or epilepsy as first-line medication or adjunctive medications. Selection may be guided by side effects and in consultation with a neurologist. They can be grouped based on their mechanism of action and include sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine, phenytoin, fosphenytoin, lamotrigine, lacosamide, and zonisamide), and agonists of GABA receptor (benzodiazepine and barbiturates). Other drugs with associated mechanisms include GABA reuptake inhibitors (tiagabine), inhibitors of GABA-transaminase (vigabatrin), glutamate antagonists (topiramate, felbamate, perampanel), medications with binding to synaptic vesicle 2A protein (levetiracetam, brivaracetam), and drugs with multiple mechanisms (gabapentin, pregabalin, valproic acid).

For the patient with generalized convulsive status epilepticus, immediate treatment of the seizures should begin while stabilization and other diagnostic procedures commence. Supportive care with attention to airway, breathing, and circulation issues are vital. Benzodiazepines such as diazepam, midazolam, or lorazepam are acceptable as the first-line medications for continuing seizures. Recommended dosage varies, but accepted regimens for adults are listed below. Respiratory depression is a common side effect, and patients will need careful monitoring. Underdosing of benzodiazepines is common, and the provider should be certain that there has been an adequate dose of a benzodiazepine given before adding additional medications.

  • Lorazepam 4 mg IV; repeat once in 5 to 10 minutes if seizures continue
  • Midazolam 10 mg IM or IV; repeat once in 5 to 10 minutes if seizures continue
  • Diazepam 10 mg IV; repeat once in 10 minutes if seizures continue

The best second-line medication is unclear even after completing a highly anticipated randomized trial of benzodiazepine refractory status epilepticus- the established status epilepticus treatment trial (ESETT). Second-line medications include fosphenytoin, valproate, levetiracetam, and others. Doses used in the ESETT study are listed below, given with an infusion time of ten minutes. The dosing of these medications in this study was higher than doses typically used in clinical practice. Clinicians have noted similar incidences of adverse effects with these medications, and no one drug was superior to the others.

  • Fosphenytoin 20PE/kg (up to 1500 phenytoin equivalents)
  • Valproate 40mg/kg (up to 300 mg)
  • Levetiracetam 60/mg (up to 4500 mg)

Should generalized convulsive status epilepticus continue, often advanced airway management is necessary? Blood pressure support may be necessary. The best treatment for refractory status epilepticus is unknown, but options include propofol, barbiturates (pentobarbital), or continuous benzodiazepine infusions in addition to other anesthetic medications. ICU admission will be necessary with continuous EEG monitoring.

For many people with epilepsy, seizures can be controlled with monotherapy at the optimal dosage.  Combining medications may amplify side effects such as fatigue and dizziness, so doctors usually prescribe just one drug whenever possible. Combinations of drugs, however, are still sometimes necessary for some forms of epilepsy that do not respond to monotherapy.

When starting any new antiseizure medication, a low dosage will usually be prescribed initially followed by incrementally higher dosages, sometimes with blood-level monitoring, to determine when the optimal dosage has been reached. It may take time for the dosage to achieve optimal seizure control while minimizing side effects. The latter are usually worse when first starting a new medicine.

Most side effects of antiseizure drugs are relatively minor, such as fatigue, dizziness, or weight gain. Antiseizure medications have different effects on mood: some may worsen depression, where others may improve depression or stabilize mood. However, severe and life-threatening reactions such as allergic reactions or damage to the liver or bone marrow can occur. Antiseizure medications can interact with many other drugs in potentially harmful ways. Some antiseizure drugs can cause the liver to speed the metabolism of other drugs and make the other drugs less effective, as may be the case with oral contraceptives. Since people can become more sensitive to medications as they age, blood levels of medication may need to be checked occasionally to see if dosage adjustments are necessary.  The effectiveness of a medication can diminish over time, which can increase the risk of seizures.  Some citrus fruit and products, in particular grapefruit juice, may interfere with the breakdown of many drugs, including antiseizure medications – causing them to build up in the body, which can worsen side effects.

Some people with epilepsy may be advised to discontinue their antiseizure drugs after 2-3 years have passed without a seizure. Others may be advised to wait for 4 to 5 years. Discontinuing the medication should always be done with the supervision of a health care professional. It is very important to continue taking antiseizure medication for as long as it is prescribed. Discontinuing medication too early is one of the major reasons people who have been seizure-free start having new seizures and can lead to status epilepticus. Some evidence also suggests that uncontrolled seizures may trigger changes in the brain that will make it more difficult to treat the seizures in the future.

The chance that a person will eventually be able to discontinue medication varies depending on the person’s age and his or her type of epilepsy. More than half of children who go into remission with medication can eventually stop their medication without having new seizures. One study showed that 68 percent of adults who had been seizure-free for 2 years before stopping medication were able to do so without having more seizures and 75 percent could successfully discontinue medication if they had been seizure-free for 3 years. However, the odds of successfully stopping medication are not as good for people with a family history of epilepsy, those who need multiple medications, those with focal seizures, and those who continue to have abnormal EEG results while on medication.

There are specific syndromes in which certain antiseizure medications should not be used because they may make the seizures worse.  For example, carbamazepine can worsen epilepsy in children diagnosed with Dravet syndrome.

Diet

Dietary approaches and other treatments may be more appropriate depending on the age of the individual and the type of epilepsy. A high-fat, very low carbohydrate ketogenic diet is often used to treat medication-resistant epilepsies. The diet induces a state known as ketosis, which means that the body shifts to breaking down fats instead of carbohydrates to survive.  A ketogenic diet effectively reduces seizures for some people, especially children with certain forms of epilepsy. Studies have shown that more than 50 percent of people who try the ketogenic diet have a greater than 50 percent improvement in seizure control and 10 percent experience seizure freedom. Some children are able to discontinue the ketogenic diet after several years and remain seizure-free, but this is done with strict supervision and monitoring by a physician.

The ketogenic diet is not easy to maintain, as it requires strict adherence to a limited range of foods. Possible side effects include impaired growth due to nutritional deficiency and a buildup of uric acid in the blood, which can lead to kidney stones.

Researchers are looking at modified versions of and alternatives to the ketogenic diet. For example, studies show promising results for a modified Atkins diet and for a low-glycemic-index treatment, both of which are less restrictive and easier to follow than the ketogenic diet, but well-controlled randomized controlled trials have yet to assess these approaches.

Surgery

Evaluation of persons for surgery is generally recommended only  after focal seizures persist despite the person having tried at least two appropriately chosen and well-tolerated medications, or if there is an identifiable brain lesion (a dysfunctional part of the brain) believed to cause the seizures. When someone is considered to be a good candidate for surgery experts generally agree that it should be performed as early as possible.

Surgical evaluation takes into account the seizure type, the brain region involved, and the importance of the area of the brain where seizures originate (called the focus) for everyday behavior. Prior to surgery, individuals with epilepsy are monitored intensively in order to pinpoint the exact location in the brain where seizures begin. Implanted electrodes may be used to record activity from the surface of the brain, which yields more detailed information than an external scalp EEG. Surgeons usually avoid operating in areas of the brain that are necessary for speech, movement, sensation, memory and thinking, or other important abilities.  fMRI can be used to locate such “eloquent” brain areas involved in an individual.

While surgery can significantly reduce or even halt seizures for many people, any kind of surgery involves some level of risk. Surgery for epilepsy does not always successfully reduce seizures and it can result in cognitive or personality changes as well as physical disability, even in people who are excellent candidates for it. Nonetheless, when medications fail, several studies have shown that surgery is much more likely to make someone seizure-free compared to attempts to use other medications. Anyone thinking about surgery for epilepsy should be assessed at an epilepsy center experienced in surgical techniques and should discuss with the epilepsy specialists the balance between the risks of surgery and desire to become seizure-free.

Even when surgery completely ends a person’s seizures, it is important to continue taking antiseizure medication for some time. Doctors generally recommend continuing medication for at least two years after a successful operation to avoid recurrence of seizures.

Surgical procedures for treating epilepsy disorders include:

  • Surgery to remove a seizure focus involves removing the defined area of the brain where seizures originate.  It is the most common type of surgery for epilepsy, which doctors may refer to as a lobectomy or laminectomy, and is appropriate only for focal seizures that originate in just one area of the brain. In general, people have a better chance of becoming seizure-free after surgery if they have a small, well-defined seizure focus. The most common type of lobectomy is a temporal lobe resection, which is performed for people with medial temporal lobe epilepsy.  In such individuals, one hippocampus (there are two, one on each side of the brain) is seen to be shrunken and scarred on an MRI scan.
  • Multiple subpial transactions may be performed when seizures originate in part of the brain that cannot be removed. It involves making a series of cuts that are designed to prevent seizures from spreading into other parts of the brain while leaving the person’s normal abilities intact.
  • Corpus callosotomy, or severing the network of neural connections between the right and left halves (hemispheres) of the brain, is done primarily in children with severe seizures that start in one half of the brain and spread to the other side. Corpus callosotomy can end drop attacks and other generalized seizures. However, the procedure does not stop seizures in the side of the brain where they originate, and these focal seizures may even worsen after surgery.
  • Hemispherectomy and hemispherectomy involve removing half of the brain’s cortex, or outer layer. These procedures are used predominantly in children who have seizures that do not respond to medication because of damage that involves only half the brain, as occurs with conditions such as Rasmussen’s encephalitis. While this type of surgery is very excessive and is performed only when other therapies have failed, with intense rehabilitation, children can recover many abilities.
  • Thermal ablation for epilepsy, also called laser interstitial thermal therapy, directs a set amount of energy to a specific, targeted brain region causing the seizures (the seizure focus). The energy, which is changed to thermal energy, destroys the brain cells causing the seizures. Laser ablation is less invasive than open brain surgery for treating epilepsy.

Devices

Electrical stimulation of the brain remains a therapeutic strategy of interest for people with medication-resistant forms of epilepsy who are not candidates for surgery.

The vagus nerve stimulation device for the treatment of epilepsy was approved by the U.S. Food and Drug Administration (FDA) in 1997. The vagus nerve stimulator is surgically implanted under the skin of the chest and is attached to the vagus nerve in the lower neck. The device delivers short bursts of electrical energy to the brain via the vagus nerve. On average, this stimulation reduces seizures by about 20 – 40 percent. Individuals usually cannot stop taking epilepsy medication because of the stimulator, but they often experience fewer seizures and they may be able to reduce the dosage of their medication.

Responsive stimulation involves the use of an implanted device that analyzes brain activity patterns to detect a forthcoming seizure. Once detected, the device administers an intervention, such as electrical stimulation or a fast-acting drug to prevent the seizure from occurring.  These devices also are known as closed-loop systems. NeuroPace, one of the first responsive stimulation, closed-loop devices, received premarket approval by the FDA in late 2013 and is available for adults with refractory epilepsy (hard to treat epilepsy that does not respond well to trials of at least two medicines).

Experimental devices:  not approved by the FDA for use in the United States (as of March 2015)

  • Deep brain stimulation using mild electrical impulses has been tried as a treatment for epilepsy in several different brain regions. It involves surgically implanting an electrode connected to an implanted pulse generator – similar to a heart pacemaker – to deliver electrical stimulation to specific areas in the brain to regulate electrical signals in neural circuits. Stimulation of an area called the anterior thalamic nucleus has been particularly helpful in providing at least partial relief from seizures in people who had medication-resistant forms of the disorder.
  • A report on trigeminal nerve stimulation (using electrical signals to stimulate parts of the trigeminal nerve and affected brain regions) showed efficacy rates similar to those for vagal nerve stimulation, with responder rates hovering around 50 percent. (A responder is defined as someone having greater than a 50 percent reduction in seizure frequency.) Freedom from seizures, although reported, remains rare for both methods. At the time of this writing, a trigeminal nerve stimulation device was available for use in Europe, but it had not yet been approved in the United States.
  • Transcutaneous magnetic stimulation involves a device being placed outside the head to produce a magnetic field to induce an electrical current in nearby areas of the brain. It has been shown to reduce cortical activity associated with specific epilepsy syndromes.

What is the impact of epilepsies on daily life?

The majority of people with epilepsy can do the same things as people without the disorder and have successful and productive lives.  In most cases, it does not affect job choice or performance.  One-third or more of people with epilepsy, however, may have cognitive or neuropsychiatric co-concurring symptoms that can negatively impact their quality of life. Many people with epilepsy are significantly helped by available therapies, and some may go months or years without having a seizure. However, people with treatment-resistant epilepsy can have as many as hundreds of seizures a day or they can have one seizure a year with sometimes disabling consequences. On average, having treatment-resistant epilepsy is associated with an increased risk of cognitive impairment, particularly if the seizures developed in early childhood. These impairments may be related to the underlying conditions associated with epilepsy rather than to epilepsy itself.

Mental Health and Stigmatization

Depression is common among people with epilepsy. It is estimated that one of every three persons with epilepsy will have depression in the course of his or her lifetime, often with accompanying symptoms of anxiety disorder. In adults, depression and anxiety are the two most frequent mental health-related diagnoses. In adults, a depression screening questionnaire specifically designed for epilepsy helps health care professions identify people who need treatment. Depression or anxiety in people with epilepsy can be treated with counseling or most of the same medications used in people who don’t have epilepsy. People with epilepsy should not simply accept that depression is part of having epilepsy and should discuss symptoms and feelings with health care professionals.

Children with epilepsy also have a higher risk of developing depression and/or attention deficit hyperactivity disorder compared with their peers. Behavioral problems may precede the onset of seizures in some children.

Children are especially vulnerable to the emotional problems caused by ignorance or the lack of knowledge among others about epilepsy.  This often results in stigmatization, bullying, or teasing of a child who has epilepsy. Such experiences can lead to behaviors of avoidance in school and other social settings. Counseling services and support groups can help families cope with epilepsy in a positive manner.

Driving and Recreation

Most states and the District of Columbia will not issue a driver’s license to someone with epilepsy unless the person can document that she/he has been seizure-free for a specific amount of time (the waiting period varies from a few months to several years). Some states make exceptions for this policy when seizures don’t impair consciousness, occur only during sleep, or have long auras or other warning signs that allow the person to avoid driving when a seizure is likely to occur. Studies show that the risk of having a seizure-related accident decreases as the length of time since the last seizure increases. Commercial drivers’ licenses have additional restrictions. In addition, people with epilepsy should take extra care if a job involves the operation of machinery or vehicles.

The risk of seizures also limits people’s recreational choices. Individuals may need to take precautions with activities such as climbing, sailing, swimming, or working on ladders. Studies have not shown any increase in seizures due to sports, although these studies have not focused on any activity in particular. There is some evidence that regular exercise may improve seizure control in some people, but this should be done under a doctor’s supervision. The benefits of sports participation may outweigh the risks and coaches or other leaders can take appropriate safety precautions. Steps should be taken to avoid dehydration, overexertion, and hypoglycemia, as these problems can increase the risk of seizures.

Education and Employment

By law, people with epilepsy (or disabilities) in the United States cannot be denied employment or access to any educational, recreational, or other activity because of their epilepsy. However, significant barriers still exist for people with epilepsy in school and work. Antiseizure drugs may cause side effects that interfere with concentration and memory. Children with epilepsy may need extra time to complete schoolwork, and they sometimes may need to have instructions or other information repeated for them. Teachers should be told what to do if a child in their classroom has a seizure, and parents should work with the school system to find reasonable ways to accommodate any special needs their child may have.

Pregnancy and Motherhood

Women with epilepsy are often concerned about whether they can become pregnant and have a healthy child. Epilepsy itself does not interfere with the ability to become pregnant. With the right planning, supplemental vitamin use, and medication adjustments prior to pregnancy, the odds of a woman with epilepsy having a healthy pregnancy and a healthy child are similar to a woman without a chronic medical condition.

Children of parents with epilepsy have about 5 percent risk of developing the condition at some point during life, in comparison to about a 1 percent risk in a child in the general population. However, the risk of developing epilepsy increases if a parent has a clearly hereditary form of the disorder. Parents who are worried that their epilepsy may be hereditary may wish to consult a genetic counselor to determine their risk of passing on the disorder.

Other potential risks to the developing child of a woman with epilepsy or on antiseizure medication include increased risk for major congenital malformations (also known as birth defects) and adverse effects on the developing brain. The types of birth defects that have been most commonly reported with antiseizure medications include cleft lip or cleft palate, heart problems, abnormal spinal cord development (spina bifida), urogenital defects, and limb-skeletal defects. Some antiseizure medications, particularly valproate, are known to increase the risk of having a child with birth defects and/or neurodevelopmental problems, including learning disabilities, general intellectual disabilities, and autism spectrum disorder. It is important that a woman work with a team of providers that includes her neurologist and her obstetrician to learn about any special risks associated with her epilepsy and the medications she may be taking.

Although planned pregnancies are essential to ensuring a healthy pregnancy, effective birth control is also essential. Some antiseizure medications that induce the liver’s metabolic capacity can interfere with the effectiveness of hormonal contraceptives (e.g., birth control pills, vaginal ring). Women who are on these enzyme-inducing antiseizure medications and using hormonal contraceptives may need to switch to a different kind of birth control that is more effective (such as different intrauterine devices, progestin implants, or long-lasting injections).

Prior to a planned pregnancy, a woman with epilepsy should meet with her health care team to reassess the current need for antiseizure medications and to determine a) the optimal medication to balance seizure control and avoid birth defects and b) the lowest dose for going into a planned pregnancy. Any transitions to either a new medication or dosage should be phased in prior to the pregnancy, if possible. If a woman’s seizures are controlled for the 9 months prior to pregnancy, she is more likely to continue to have seizure control during pregnancy. For all women with epilepsy during pregnancy, approximately 15-25 percent will have seizure worsening, but another 15-25 percent will have seizure improvement. As a woman’s body changes during pregnancy, the dose of seizure medication may heed to be increased. For most medicines, monthly monitoring of blood levels of the antiseizure medicines can help to assure continued seizure control. Many of the birth defects seen with antiseizure medications occur in the first six weeks of pregnancy, often before a woman is aware she is pregnant. In addition, up to 50 percent of pregnancies in the U.S. are unplanned. For these reasons, the discussion about the medications should occur early between the health care professional and any woman with epilepsy who is in her childbearing years.

For all women thinking of becoming pregnant, using supplemental folic acid beginning prior to conception and continuing the supplement during pregnancy is an important way to lower the risk for birth defects and developmental delays. Prenatal multivitamins should also be used prior to the beginning of pregnancy. Pregnant women with epilepsy should get plenty of sleep and avoid other triggers or missed medications to avoid worsening of seizures.

Most pregnant women with epilepsy can deliver with the same choices as women without any medical complications. During the labor and delivery, it is important that the woman be allowed to take her same formulations and doses of antiseizure drugs at her usual times; it is often helpful for her to bring her medications from home. If a seizure does occur during labor and delivery, intravenous short-acting medications can be given if necessary. It is unusual for the newborns of women with epilepsy to experience symptoms of withdrawal from the mother’s antiseizure medication (unless she is on phenobarbital or a standing dose of benzodiazepines), but the symptoms resolve quickly and there are usually no serious or long-term effects.

The use of antiseizure medications is considered safe for women who choose to breastfeed their child. On very rare occasions, the baby may become excessively drowsy or feed poorly, and these problems should be closely monitored. However, experts believe the benefits of breastfeeding outweigh the risks except in rare circumstances. One large study showed that the children who were breastfed by mothers with epilepsy on antiseizure medications performed better on learning and developmental scales than the babies who were not breastfed. It is common for the antiseizure medication dosing to be adjusted again in the postpartum setting, especially if the dose was altered during pregnancy.

With the appropriate selection of safe antiseizure medicines during pregnancy, use of supplemental folic acid, and ideally, with pre-pregnancy planning, most women with epilepsy can have a healthy pregnancy with good outcomes for themselves and their developing child.

What research is being done on the epilepsies by the NINDS?

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use the knowledge to reduce the burden of neurological disease.  The NINDS is a component of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world.  The NINDS conducts and supports research to better understand and diagnose epilepsy, develop new treatments, and ultimately, prevent epilepsy.  Researchers hope to learn the epileptogenesis of these disorders – how the epilepsies develop, and how, where, and why neurons begin to display the abnormal firing patterns that cause epileptic seizures.

Mechanisms

Researchers are learning more about the fundamental processes – known as mechanisms – that lead to epileptogenesis. With every mechanism that is discovered come new potential targets for drug therapies to interrupt the processes that lead to the development of epilepsy. Basic science studies continue to investigate how neurotransmitters (chemicals which carry signals from one nerve cell to another) interact with brain cells to control nerve firing and how non-neuronal cells in the brain contribute to seizures.  For example, studies are focusing on the role of gamma-aminobutyric acid (GABA), a key neurotransmitter that inhibits activity in the central nervous system. Research on GABA has led to drugs that alter the amount of this neurotransmitter in the brain or change how the brain responds to it. Researchers also are studying the role of excitatory neurotransmitters such as glutamate. In some cases, the epilepsies may result from changes in the ability of supportive brain cells called glia to regulate glutamate levels.  Researchers have found that when astrocytes – a type of glial cell that play a critical housekeeping role by removing excessive levels of glutamate – are impaired, levels of glutamate rise excessively in the spaces between brain cells, which may contribute to the onset of seizures.

The blood-brain barrier plays in important protective role between the circulatory systems and the fluid surrounding the brain, as it keeps toxins in the blood from reaching the brain. However, this protective layer of cells and other components can also block potentially beneficial medications from reaching the brain. Scientists are looking for ways to overcome this barrier for the sake of expanding therapeutic options. For example, in one study people with drug-resistant epilepsy are receiving infusions of neurotransmitter-specific agents directly into the epileptic focus.

In another study, researchers are looking at a protein that is part of the blood-brain barrier, called P-glycoprotein (P-gp). Levels of P-gp are higher in people with epilepsy than in people without it. These different levels of P-gp may explain why some people have seizures that do not respond well to medications. NINDS-funded researchers want to see if manipulating P-gp levels can affect the response to epilepsy medications.

The brain chemical serotonin helps neurons communicate. Previous research suggests that serotonin activity may be lower in brain areas where seizures start, and that increasing activity at the serotonin receptor site on nerve cells may help prevent seizures. NINDS-funded researchers are studying an experimental medication aimed at increasing the activity of serotonin receptors to see if it can reduce seizure frequency in people whose seizures are not well controlled on antiseizure medication.

Research has shown that the cell membrane that surrounds each neuron plays an important role in epilepsy because it allows neurons to generate electrical impulses. Scientists are studying details of the membrane structure, how molecules move in and out of membranes, and how the cell nourishes and repairs the membrane. A disruption in any of these processes may lead to seizures.

Ongoing research is focused on developing better animal models that more closely reflect the mechanisms that cause epilepsy in humans so that they can be used to more effectively screen potential treatments for the epilepsies.

Improving treatments

The NINDS Epilepsy Therapy Screening Program (ETSP) provides a free compound screening service to identify candidate drugs to treat the epilepsies. The ASP annually has screened hundreds of new chemical agents from academic, industrial, and government participants using a battery of models of potential efficacy and side-effect liability. Results are compared to those obtained with standard marketed antiepileptic drugs. The ASP has played a role in the identification and development of numerous marketed antiseizure drugs, including felbamate, topiramate, lacosamide, and retigabine. Current efforts emphasize unmet medical needs in epilepsy, such as treatments for refractory epilepsies, the development of epilepsy in previously unaffected individuals, and disease progression.

NINDS-funded researchers are looking at drug combinations that would help boost the effectiveness of medication therapy. For example, one trial is looking at the ability of an antianxiety medication to increase brain activity in specific regions, which could in turn decrease epileptic seizures.

Neonatal seizures frequently lead to epilepsy as well as to significant cognitive and motor disabilities. At the same time, safe and completely effective antiseizure medications for these newborns are lacking. Current treatment options are generally ineffective and have significant side effects. NINDS-funded investigators are working to identify better treatment options for neonates and to test them in randomized controlled trials.

Researchers continue to engineer technological advances to assist in the diagnosis of epilepsies and to identify the source (focus) of the seizures in the brain. For example, electrode arrays that are flexible enough to mold to the brain’s complex surface provide unprecedented access for recording and stimulating brain activity and possibly provide a way to deliver treatment. While these arrays have not yet been used in humans, they are a promising advance toward expanded options for epilepsy diagnosis and treatment.

Researchers are striving to make surgery for epilepsy safer by minimizing the language deficits that can occur afterward.  Using functional magnetic resonance imaging (fMRI) as well as other imaging technologies, researchers are helping to improve preoperative planning by more accurately mapping areas of the brain that are important for the ability to understand and speak the language – which will help surgeons to preserve those areas during surgery. Doctors also are experimenting with brain scans called functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS) that can detect abnormalities in the brain’s biochemical processes, and near-infrared spectroscopy, a technique that can detect oxygen levels in brain tissue.

Researchers also continue to develop minimally-invasive approaches to treat epilepsy focus via heat (thermoablation), transcranial ultrasound, or high-powered x-rays (stereotactic radiosurgery). For example, minimally invasive MRI-guided laser surgery is being studied for the treatment of the epilepsies associated with tumors such as hypothalamic hamartomas and tuberous sclerosis complex. The technique involves drilling a very small hole in the skull through which a thermal laser is inserted to ablate an epileptogenic zone under MRI guidance.

Genetics

Advances in understanding the human genome have spurred continued efforts to identify genes responsible for epileptic conditions. NINDS is a large supporter of research investigating genes responsible for epilepsies and disorders of human cognition that gain a foothold during early brain development. Continued progress in the identification of genetic causes of epilepsies could guide the care and medical management of individuals and, in the case of heritable mutations, will help affected families understand their risks.

NINDS established its Epilepsy Centers without Walls Program in 2010 to address challenges and gaps in epilepsy research. The innovative program encourages collaborations, including sharing of data and resources, between researchers from a variety of disciplines and institutions regardless of geographic location, that may lead to advances in prevention, diagnosis, or treatment of epilepsies and related comorbidities.

Epi4K is an NINDS-funded Epilepsy Center without Walls aimed at determining the genetic basis of various epilepsies. Epi4K investigators are analyzing the genomes of at least 4,000 people with well-characterized epilepsies. Through this work, researchers have successfully identified mutations associated with Dravet syndrome, infantile spasms, and Lennox-Gastaut syndrome. Most important, these discoveries will give researchers the basis for screening agents for their potential therapeutic effects.

The discovery of genetic mutations that are linked to specific epilepsy syndromes suggests the possibility of using gene-directed therapies to counter the effects of these mutations. Gene therapies remain the subject of many studies in animal models of epilepsy, and the number of potential approaches continues to expand.  A common approach in gene therapy research uses viruses modified to be harmless to introduce new genes into brain cells, which then act as “factories” to produce potentially therapeutic proteins.

Pick Disease – Causes, Symptoms, Diagnosis, Treatment

Pick disease, also known as frontotemporal dementia is a progressive, neurodegenerative, heterogeneous group of non-Alzheimer dementias disorder characterized by loss of intellectual functions, such as memory problems, impaired abstract thinking, reasoning, behavioral changes, and language deficits with frontal and temporal cortical degeneration and executive function, severe enough to hamper activities of daily living. It requires a multidisciplinary approach to improve patient outcomes. The clinical manifestation includes behavior changes, dietary changes, loss of empathy, apathy, and executive function.

Frontotemporal Disorders /Few people have heard of frontotemporal disorders, which lead to dementias that affect personality, behavior, language, and movement. These disorders are little known outside the circles of researchers, clinicians, patients, and caregivers who study and live with them. Although frontotemporal disorders remain puzzling in many ways, researchers are finding new clues that will help them solve this medical mystery and better understand other common dementias.

Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the frontal and temporal lobes.[rx] FTDs are broadly presented as behavioral or language disorders.[rx] The three main subtypes or variant syndromes are a behavioral variant (bvFTD) previously known as Pick’s disease, and two variants of primary progressive aphasia – semantic variant (svPPA), and nonfluent variant (nfvPPA).[rx][rx] Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID), and basophilic inclusion body disease. Other related disorders include corticobasal syndrome and FTD with amyotrophic lateral sclerosis (ALS) FTD-ALS also called FTD-MND.[rx]

Synonyms of Frontotemporal Degeneration

  • frontotemporal dementia
  • frontotemporal lobar degeneration
  • FTD
  • FTLD
  • Pick’s disease (limited, see below)

Subdivisions of Frontotemporal Degeneration

  • behavioral variant frontotemporal degeneration (bvFTD)
  • primary progressive aphasia (PPA)
  • semantic variant primary progressive aphasia (svPPA)
  • nonfluent variant primary progressive aphasia (naPPA)
  • logopenic variant primary progressive aphasia (lvPPA)
  • progressive supranuclear palsy (PSP) syndrome
  • corticobasal syndrome (CBS)
  • FTD with motor neuron disease (FTD-MND)
  • frontotemporal lobar degeneration
  • behavioral variant frontotemporal dementia
  • semantic dementia
  • progressive non-fluent aphasia

The Basics of Pick Disease

Frontotemporal disorders are the result of damage to neurons (nerve cells) in parts of the brain called the frontal and temporal lobes. As neurons die in the frontal and temporal regions, these lobes atrophy, or shrink. Gradually, this damage causes difficulties in thinking and behaviors normally controlled by these parts of the brain. Many possible symptoms can result, including unusual behaviors, emotional problems, trouble communicating, difficulty with work, or difficulty with walking.

A Form of Dementia

Frontotemporal disorders are forms of dementia caused by a family of brain diseases known as frontotemporal lobar degeneration (FTLD). Dementia is a severe loss of thinking abilities that interferes with a person’s ability to perform daily activities such as working, driving, and preparing meals. Other brain diseases that can cause dementia include Alzheimer’s disease and multiple strokes. Scientists estimate that FTLD may cause up to 10 percent of all cases of dementia and may be about as common as Alzheimer’s among people younger than age 65. Roughly 60 percent of people with FTLD are 45 to 64 years old.

People can live with frontotemporal disorders for up to 10 years, sometimes longer, but it is difficult to predict the time course for an individual patient. The disorders are progressive, meaning symptoms get worse over time. In the early stages, people may have just one type of symptom. As the disease progresses, other types of symptoms appear as more parts of the brain are affected.

No cure or treatments that slow or stop the progression of frontotemporal disorders are available today. However, research is improving awareness and understanding of these challenging conditions. This progress is opening doors to better diagnosis, improved care, and, eventually, new treatments.

FTD? FTLD? Understanding Terms

One of the challenges shared by patients, families, clinicians, and researchers is confusion about how to classify and label frontotemporal disorders. A diagnosis by one doctor may be called something else by a second, and the same condition or syndrome referred to by another name by a pathologist who examines the brain after death.

For many years, scientists and physicians used the term frontotemporal dementia (FTD) to describe this group of illnesses. After further research, FTD is now understood to be just one of several possible variations and is more precisely called behavioral variant frontotemporal dementia, or bvFTD.

This booklet uses the term frontotemporal disorders to refer to changes in behavior and thinking that are caused by underlying brain diseases collectively called frontotemporal lobar degeneration (FTLD). FTLD is not a single brain disease but rather a family of neurodegenerative diseases, any one of which can cause a frontotemporal disorder (see “Causes,” page 11). Frontotemporal disorders are diagnosed by physicians and psychologists based on a person’s symptoms and results of brain scans and genetic tests. With the exception of known genetic causes, the type of FTLD can be identified definitively only by brain autopsy after death.

Changes in the Brain

Frontotemporal disorders affect the frontal and temporal lobes of the brain. They can begin in the frontal lobe, the temporal lobe, or both. Initially, frontotemporal disorders leave other brain regions untouched, including those that control short-term memory.

The frontal lobes, situated above the eyes and behind the forehead both on the right and left sides of the brain, direct executive functioning. This includes planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and monitoring and correcting errors.

When functioning well, the frontal lobes also help manage emotional responses. They enable people to avoid inappropriate social behaviors, such as shouting loudly in a library or at a funeral. They help people make decisions that make sense for a given situation. When the frontal lobes are damaged, people may focus on insignificant details and ignore important aspects of a situation or engage in purposeless activities. The frontal lobes are also involved in language, particularly linking words to form sentences, and in motor functions, such as moving the arms, legs, and mouth.

The temporal lobes, located below and to the side of each frontal lobe on the right and left sides of the brain, contain essential areas for memory but also play a major role in language and emotions. They help people understand words, speak, read, write, and connect words with their meanings. They allow people to recognize objects and to relate appropriate emotions to objects and events. When the temporal lobes are dysfunctional, people may have difficulty recognizing emotions and responding appropriately to them.

Which lobe—and part of the lobe—is affected first determines which symptoms appear first. For example, if the disease starts in the part of the frontal lobe responsible for decision-making, then the first symptom might be trouble managing finances. If it begins in the part of the temporal lobe that connects emotions to objects, then the first symptom might be an inability to recognize potentially dangerous objects—a person might reach for a snake or plunge a hand into boiling water, for example.

Types of Frontotemporal Dementia/Pick Disease

Frontotemporal disorders can be grouped into three types, defined by the earliest symptoms physicians identify when they examine patients.

  • Progressive behavior/personality decline—characterized by changes in personality, behavior, emotions, and judgment (called
    behavioral variant frontotemporal dementia).
  • Progressive language decline—marked by early changes in language ability, including speaking, understanding, reading, and writing (called primary progressive aphasia).
  • Progressive motor decline—characterized by various difficulties with physical movement, including the use of one or more limbs, shaking, difficulty walking, frequent falls, and poor coordination (called a corticobasal syndrome, supranuclear palsy, or amyotrophic lateral sclerosis).

Based on anatomic, genetic, and neuropathologic categorizations, the six clinical subtypes of FTD or related disorders are

  • (1) behavioral variant of FTD,
  • (2) semantic variant primary progressive aphasia,
  • (3) nonfluent agrammatic variant primary progressive aphasia,
  • (4) corticobasal syndrome,
  • (5) progressive supranuclear palsy, and
  • (6) FTD associated with motor neuron disease. Recognition and accurate diagnoses of FTD subtypes will aid the neurologist in the management of patients with FTD.

In the early stages it can be hard to know which of these disorders a person has because symptoms and the order in which they appear can vary widely from one person to the next. Also, the same symptoms can appear later in different disorders. For example, language problems are most typical of primary progressive aphasia but can also appear later in the course of behavioral variant frontotemporal dementia. The table on page 6 summarizes the three types of frontotemporal disorders and lists the various terms that could be used when clinicians diagnose these disorders.

Behavioral Variant Frontotemporal Dementia

The most common frontotemporal disorder, behavioral variant frontotemporal dementia (bvFTD), involves changes in personality, behavior, and judgment. People with this dementia can act strangely around other people, resulting in embarrassing social situations. Often, they don’t know or care that their behavior is unusual and don’t show any consideration for the feelings of others. Over time, language and/or movement problems may occur, and the person needs more care and supervision.

In the past, bvFTD was called Pick’s disease, named after Arnold Pick, the German scientist who first described it in 1892. The term Pick’s disease is now used to describe abnormal collections in the brain of the protein tau, called “Pick bodies.” Some patients with bvFTD have Pick bodies in the brain, and some do not.

Primary Progressive Aphasia

Primary progressive aphasia (PPA) involves changes in the ability to communicate—to use language to speak, read, write, and understand what others are saying. Problems with memory, reasoning, and judgment are not apparent at first but can develop over time. In addition, some people with PPA may experience significant behavioral changes, similar to those seen in bvFTD, as the disease progresses.

There are three types of PPA, categorized by the kind of language problems seen at first. Researchers do not fully understand the biological basis of the different types of PPA. But they hope one day to link specific language problems with the abnormalities in the brain that cause them.

In semantic PPA, also called semantic dementia, a person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.

In agrammatic PPA, also called progressive nonfluent aphasia, a person has more and more trouble producing speech. Eventually, the person may no longer be able to speak at all. He or she may eventually develop movement symptoms similar to those seen in corticobasal syndrome.

In logopenic PPA, a person has trouble finding the right words during the conversation but can understand words and sentences. The person does not have problems with grammar.

Movement Disorders

Two rare neurological disorders associated with FTLD, corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), occur when the parts of the brain that control movement is affected. The disorders may affect thinking and language abilities, too.

CBS can be caused by corticobasal degeneration—gradual atrophy and loss of nerve cells in specific parts of the brain. This degeneration causes progressive loss of the ability to control movement, typically beginning around age 60. The most prominent symptom may be the inability to use the hands or arms to perform a movement despite normal strength (called apraxia). Symptoms may appear first on one side of the body, but eventually, both sides are affected. Occasionally, a person with CBS first has language problems or trouble orienting objects in space and later develops movement symptoms.

PSP causes problems with balance and walking. People with the disorder typically move slowly, experience unexplained falls, lose facial expression, and have body stiffness, especially in the neck and upper body—symptoms similar to those of Parkinson’s disease. A hallmark sign of PSP is trouble with eye movements, particularly looking down. These symptoms may give the face a fixed stare. Behavior problems can also develop.

Other movement-related frontotemporal disorders include frontotemporal dementia with parkinsonism and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS).

Frontotemporal dementia with parkinsonism can be an inherited disease caused by a genetic tau mutation. Symptoms include movement problems similar to those of Parkinson’s disease, such as slowed movement, stiffness, and balance problems, and changes in behavior or language.

FTD-ALS is a combination of bvFTD and ALS, commonly called Lou Gehrig’s disease. Symptoms include the behavioral and/or language changes seen in bvFTD as well as the progressive muscle weakness seen in ALS. Symptoms of either disease may appear first, with other symptoms developing over time. Mutations in certain genes have been found in some patients with FTD-ALS.

Causes of Frontotemporal Dementia/Pick Disease

Frontotemporal lobar degeneration (FTLD) is not a single brain disease but rather a family of brain diseases that share some common molecular features. Scientists are beginning to understand the biological and genetic basis for the changes observed in brain cells that lead to FTLD.

Scientists describe FTLD in terms of patterns of change in the brain seen in an autopsy after death. These changes include loss of neurons and abnormal amounts or forms of proteins called tau and TDP-43. These proteins occur naturally in the body and help cells function properly. When the proteins don’t work properly and accumulate in cells, for reasons not yet fully understood, neurons in specific brain regions are damaged.

In most cases, the cause of a frontotemporal disorder is unknown. In about 15 to 40 percent of people, a genetic (hereditary) cause can be identified. Individuals with a family history of frontotemporal disorders are more likely to have a genetic form of the disease than those without such a history.

Familial and inherited forms of frontotemporal disorders are often related to mutations (permanent changes) in certain genes. Genes are basic units of heredity that tell cells how to make the proteins the body needs to function. Even small changes in a gene may produce an abnormal protein, which can lead to changes in the brain and, eventually, disease.

Scientists have discovered several different genes that, when mutated, can lead to frontotemporal disorders:

  • Tau gene (also called the MAPT gene)—A mutation in this gene causes abnormalities in a protein called tau, which forms tangles inside neurons and ultimately leads to the destruction of brain cells. Inheriting a mutation in this gene means a person will almost surely develop a frontotemporal disorder, usually the bvFTD form, but the exact age of onset and symptoms cannot be predicted.
  • PGRN gene— A mutation in this gene can lead to lower production of the protein progranulin, which in turn causes TDP-43, a cellular protein, to go awry in brain cells. Many frontotemporal disorders can result, though bvFTD is the most common. The PRGRN gene can cause different symptoms in different family members and cause the disease to begin at different ages.
  • VCP, CHMP2B, TARDBP, and FUS genes— Mutations in these genes lead to very rare familial types of frontotemporal disorders. TARDBP and FUS gene mutations are more often associated with hereditary ALS.
  • C9ORF72 gene— An unusual mutation in this gene appears to be the most common genetic abnormality in familial frontotemporal disorders and familial ALS. It also occurs in some cases of sporadic ALS. This mutation can cause a frontotemporal disorder, ALS, or both conditions in a person.

Scientists are continuing to study these genes and to search for other genes and proteins, as well as nongenetic risk factors, that may play a role in frontotemporal disorders. They are trying to understand, for example, how mutations in a single gene lead to different frontotemporal disorders in members of the same family. Environmental factors that may influence the risk for developing the disorders are also being examined.

Families affected by inherited and familial forms of frontotemporal disorders can help scientists further research by participating in clinical studies and trials. For more information, talk with a health care professional, contact any of the research centers listed at the end of this booklet or search www.clinicaltrials.gov.

Symptoms of Frontotemporal Dementia/Pick Disease

Symptoms of frontotemporal disorders vary from person to person and from one stage of the disease to the next as different parts of the frontal and temporal lobes are affected. In general, changes in the frontal lobe are associated with behavioral symptoms, while changes in the temporal lobe lead to language and emotional disorders.

Symptoms are often misunderstood. Family members and friends may think that a person is misbehaving, leading to anger and conflict. For example, a person with bvFTD may neglect personal hygiene or start shoplifting. It is important to understand that people with these disorders cannot control their behaviors and other symptoms. Moreover, they lack any awareness of their illness, making it difficult to get help.

Behavioral Symptoms

  • Problems with executive functioning—Problems with planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and self-monitoring and correcting behavior.
  • Perseveration—A tendency to repeat the same activity or to say the same word over and over, even when it no longer makes sense.
  • Social disinhibition—Acting impulsively without considering how others perceive the behavior. For example, a person might hum at a business meeting or laugh at a funeral.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Utilization behavior—Difficulty resisting impulses to use or touch objects that one can see and reach. For example, a person picks up the telephone receiver while walking past it when the phone is not ringing and the person does not intend to place a call.
  • Inappropriate social behavior and lack of social tact/manners. Examples include touching or kissing strangers, urinating in public, making rude or offensive comments, arguing, rashly overspending, and/or doing or saying things that others would find embarrassing or disgusting.
  • Lack of empathy (interest in, or understanding of, what others feel), loss of interest in other people or activities, reduced affection, neglect of personal grooming and hygiene. People with FTD are not aware of the changes that are happening and do not know how hurtful they are to close family members.
  • Changes in food preferences, overstuffing mouth with food, binge eating, eating food quickly, attempting to eat non-food items.
  • Becoming very obsessive or developing rituals, repeating things, collecting/hoarding items.

Language Symptoms

  • Aphasia—A language disorder in which the ability to use or understand words is impaired but the physical ability to speak properly is normal.
  • Dysarthria—A language disorder in which the physical ability to speak properly is impaired (e.g., slurring) but the message is normal. People with PPA may have only problems using and understanding words or also problems with the physical ability to speak. People with both kinds of problems have trouble speaking and writing. They may become mute, or unable to speak. Language problems usually get worse, while other thinking and social skills may remain normal for longer before deteriorating.

Emotional Symptoms

  • Apathy—A lack of interest, drive, or initiative. Apathy is often confused with depression, but people with apathy may not be sad. They often have trouble starting activities but can participate if others do the planning.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Emotional changes—Emotions are flat, exaggerated, or improper. Emotions may seem completely disconnected from a situation or are expressed at the wrong times or in the wrong circumstances. For example, a person may laugh at sad news.
  • Social-interpersonal changes—Difficulty “reading” social signals, such as facial expressions, and understanding personal relationships. People may lack empathy—the ability to understand how others are feeling—making them seem indifferent, uncaring, or selfish. For example, the person may show no emotional reaction to illnesses or accidents that occur to family members.

Movement Symptoms

  • Dystonia—Abnormal postures of body parts such as the hands or feet. A limb may be bent stiffly or not used when performing activities that are normally done with two hands.
  • Gait disorder—Abnormalities in walking, such as walking with a shuffle, sometimes with frequent falls.
  • Tremor—Shakiness, usually of the hands.
  • Clumsiness—Dropping of small objects or difficulty manipulating small items like buttons or screws.
  • Apraxia—Loss of ability to make common motions, such as combing one’s hair or using a knife and fork, despite normal strength.
  • Neuromuscular weakness—Severe weakness, cramps, and rippling movements in the muscles.

Diagnosis of Pick Disease

Consensus criteria for FTD

  1. Core diagnostic features

    A. Insidious onset and gradual progression

    B. Early decline in social interpersonal conduct

    C. Early impairment in regulation of personal conduct

    D. Early emotional blunting

    E. Early loss of insight

  2. Supportive diagnostic features

    A. Behavioral disorder

    1. Decline in personal hygiene and grooming

    2. Mental rigidity and inflexibility

    3. Distractibility and impersistence

    4. Hyperorality and dietary changes

    5. Perseverative and stereotyped behavior

    6. Utilization behavior

    B. Speech and language

    1. Altered speech output

    a. Aspontaneity and economy of speech

    b. Pressure of speech

    2. Stereotypy of speech

    3. Echolalia

    4. Perseveration

    5. Mutism

    C. Physical signs

    1. Primitive reflexes

    2. Incontinence

    3. Akinesia, rigidity, and tremor

    4. Low and labile blood pressure

    D. Investigations

    1. Neuropsychology: impairment on frontal lobe tests without severe amnesia, aphasia, or perceptuospatial disorder

    2. Electroencephalography: normal on conventional EEG despite clinically evident dementia

    3. Brain imaging (structural and/or functional): predominant frontal and/or anterior temporal abnormality

No single test, such as a blood test, can be used to diagnose a frontotemporal disorder. A definitive diagnosis can be confirmed only by a genetic test in familial cases or a brain autopsy after a person dies. To diagnose a probable frontotemporal disorder in a living person, a doctor— usually a neurologist, psychiatrist, or psychologist—will:

  • record a person’s symptoms, often with the help of family members or friends
  • compile a personal and family medical history
  • perform a physical exam and order blood tests to help rule out other similar conditions
  • if appropriate, order testing to uncover genetic mutations
  • conduct a neuropsychological evaluation to assess behavior, language, memory, and other cognitive functions
  • use brain imaging to look for changes in the frontal and temporal lobes.

In all forms of FTD, functional ability and activities of daily living are compromised.

  • Behavior variant type FTD (bvFTD) – It is the most common phenotype. Patients suffering from bvFTD may present with a cluster of altered behavior and personality changes earlier in the disease process, which include disinhibition, loss of emotional reactivity and disease insight, apathy, impaired abstract thinking and executive function that gradually worsens over time. Additionally, it may demonstrate a change in dietary behavior and loss of fundamental emotions and empathy but with intact memory until late in the disease.
  • Semantic variant FTD – In this form of FTD, patients manifest language difficulties characterized by paraphasia (impaired word-finding ability or loss of vocabulary), difficulty in understanding the meaning of words, impaired comprehension, and difficulty in recognizing unfamiliar objects or faces. Their speech is fluent but not making any sense. Memory is affected late in the disease.
  • Non-fluent variant Primary Progressive Aphasia (nfvPPA) – Patients with this type of FTD presents clinically with effortful halted speech and paraphasia (jumbled words), difficulty in understanding complex sentences and naming objects. Their memory, abstract thinking, and calculating abilities are spared earlier in the disease course.

Various bedside tests can be performed if clinical suspicion for FTD is high.

  • Go-no-go test – In this test, the patient is asked to perform an action in response to a particular stimulus and inhibit that action in response to different stimuli.
  • Letter fluency test – In this test, the patient is asked to say as many words (except proper nouns), starting with a single letter in one minute.
  • Attention test – It is used to evaluate the attention span. It is done either by serial seven subtractions from 100 or spells the word “world” backward.
  • Similarities and differences – It is done to evaluate abstract thinking. The patient is instructed to compare items (table and chair, apple, and orange).

Patients with frontotemporal dementia should be evaluated as follows:

  • Laboratory –  Neural and axonal cytoskeletons are mainly composed of neurofilaments, which are further made up of small subunits called neurofilament light chains. Neurofilament light chain, among other biomarkers, can be increasingly seen in blood and cerebrospinal fluid of FTD patients.
  • Radiographic tests – Magnetic resonance imaging, computed tomography scan, or single-photon emission tomography can be used to demonstrate atrophy and hypoperfusion in the frontal and temporal lobes. However, the findings are not specific. Imaging may aid in the diagnosis or to rule out other etiologies.
  • Electroencephalography (EEG) – It is not very helpful for FTD as it is for Alzheimer’s disease; however, in comparison to the healthy group, a typical EEG pattern was observed in several FTD patients and was marked by the reduction of fast activities (alpha, beta1- beta3), but no difference in slow activities (delta & theta waves).
  • Neurocognitive exams – Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, and Functional Cognitive Assessment. For primary care, the Cochrane dementia and cognitive improvement group supports the utilization of two tests; MMSE (the most commonly used test in primary care) and the Informant Questionnaire for Cognitive Disorders in the Elderly. MMSE assesses different domains of dementia, including but not limited to memory, cognition, language, attention/orientation, and executive functions.
  • A magnetic resonance imaging (MRI) – scan shows changes in the size and shape of the brain, including the frontal and temporal lobes. It may reveal other potentially treatable causes of the person’s symptoms, such as a stroke or tumor. In the early stage of the disease, the MRI may appear normal. In this case, other types of imaging, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), may be useful. PET and SPECT scan to measure activity in the brain by monitoring blood flow, glucose usage, and oxygen usage. Other PET scans can help rule out a diagnosis of Alzheimer’s.
  • Cerebrospinal fluid – and serum protein biomarkers are presently utilized to exclude Alzheimer’s disease in the assessment of frontotemporal dementia and are under appraisal for prospective diagnostic indications and monitoring pathologic progression and response to potential therapies. Elevated CSF tau proteins and decreased beta-amyloid 42 protein concentrations can accurately confirm Alzheimer’s dementia and are validated for eliminating frontotemporal dementia from the differential.
  • Neurofilament light chain (NFL) – proteins are increased in serum and CSF samples of patients with frontotemporal dementia and other neurodegenerative disorders and have promising applications in future frontotemporal dementia assays. Gene-specific biomarkers such as progranulin and poly (GP) have the potential for investigating the expression of GRN and C9orf72 frontotemporal dementia mutations, respectively. As with potential imaging techniques, more data is needed to implement fluid biomarkers into a comprehensive frontotemporal dementia evaluation strategy.
  • Neuropsychological Testing – Performance patterns on cognitive testing may vary according to the subtype. Many patients with CBS will demonstrate deficits on tasks of executive function, writing, visuospatial, and construction tasks. Patients presenting with dominant frontal lobe involvement may show word-finding deficits, agrammatism, and spelling errors similar to patients with nonfluent agrammatic PPA.[
  • Neuroimaging – Structural brain imaging in patients with CBS may show asymmetric frontal and parietal lobe atrophy, although imaging findings may overlap with those seen in other FTDs and AD. Thus, diagnosis at present is based on clinical criteria, with neuroimaging performed to rule out other structural causes of symptoms.

Treatment of Pick Disease

So far, there is no cure for frontotemporal disorders and no way to slow down or prevent them. However, there are ways to manage symptoms. A team of specialists—doctors, nurses, and speech, physical, and occupational therapists—familiar with these disorders can help guide treatment.

Non-Pharmacologic Treatment

It includes a multidisciplinary approach, such as social support services, physical therapy & occupational therapy, speech therapy, cognitive behavior therapy, rehabilitation services, and caregivers’ education. Regular monitoring of the behavior of both the patient and caregiver for assessing activities of daily living, such as financial account managing, driving, environmental modification, and eating, is mandatory.

Pharmacological Treatment

Acetylcholinesterase inhibitors and N-methyl-D-Aspartate inhibitors have no proven benefit. Similarly, selective serotonin reuptake inhibitors (SSRI) have a limited role. It can improve certain behaviors, but not cognition. Antipsychotics have mixed results but comes with a price of severe extrapyramidal side effects to which the FTD patients are susceptible; therefore, they are not approved by the US food and drug administration as a treatment for FTD. Selective dopaminergic antagonists can improve motivation and apathy. Several disease-modifying drugs like Salsalate (tau acetylation inhibitor) and Gosuraneb (anti-tau monoclonal antibodies) targeting different biomarkers are being studied, but no recommendations yet have been made. Several other promising disease-modifying drugs are currently under clinical trials.

Managing Behavior

The behaviors of a person with bvFTD can upset and frustrate family members and other caregivers. It is natural to grieve for the “lost person,” but it is also important to learn how to best live with the person he or she has become. Understanding changes in personality and behavior and knowing how to respond can reduce caregivers’ frustration and help them cope with the challenges of caring for a person with a frontotemporal disorder.

Managing behavioral symptoms can involve several approaches. To ensure the safety of a person and his or her family, caregivers may have to take on new responsibilities or arrange care that was not needed before. For example, they may have to drive the person to appointments and errands, care for young children, or arrange for help at home.

It is helpful, though often difficult, to accept rather than challenge people with behavioral symptoms. Arguing or reasoning with them will not help because they cannot control their behaviors or even see that they are unusual or upsetting to others. Instead, be as sensitive as possible and understand that it’s the illness “talking.”

Frustrated caregivers can take a “timeout”—take deep breaths, count to 10, or leave the room for a few minutes.

To deal with apathy, limit choices and offer specific choices. Open-ended questions (“What would you like to do today?”) are more difficult to answer than specific ones (“Do you want to go to the movies or the shopping center today?”).

Maintaining the person’s schedule and modifying the environment can also help. A regular schedule is less confusing and can help people sleep better. If compulsive eating is an issue, caregivers may have to supervise eating, limit food choices, lock food cabinets and the refrigerator, and distract the person with other activities. To deal with other compulsive behaviors, caregivers may have to change schedules or offer new activities.

Medications are available to treat certain behavioral symptoms. Antidepressants called selective serotonin reuptake inhibitors are commonly prescribed to treat social disinhibition and impulsive behavior. Patients with aggression or delusions sometimes take low doses of antipsychotic medications. The use of Alzheimer’s disease medications to improve behavioral and cognitive symptoms in people with bvFTD and related disorders is being studied, though results so far have been mixed, with some medications making symptoms worse. If a particular medication is not working, a doctor may try another. Always consult a doctor before changing, adding, or stopping a drug.

Treating Language Problems

Treatment of primary progressive aphasia (PPA) has two goals—maintaining language skills and using new tools and other ways to communicate. Treatment tailored to a person’s specific language problem and stage of PPA generally works best. Since language ability declines over time, different strategies may be needed as the illness progresses.

To communicate without talking, a person with PPA may use a communication notebook (an album of photos labeled with names of people and objects), gestures, and drawings. Some people find it helpful to use or point to lists of words or phrases stored in a computer or personal digital assistant.

Caregivers can also learn new ways of talking to someone with PPA. For example, they can speak slowly and clearly, use simple sentences, wait for responses, and ask for clarification if they don’t understand something.

A speech-language pathologist who knows about PPA can test a person’s language skills and determine the best tools and strategies to use. Note that many speech-language pathologists are trained to treat aphasia caused by stroke, which requires different strategies from those used with PPA. (See the Resources section starting on page 27 to find speech-language pathologists and other experts who know about frontotemporal disorders.)

Managing Movement Problems

No treatment can slow down or stop frontotemporal-related movement disorders, though medications and physical and occupational therapy may provide modest relief.

For people with corticobasal syndrome (CBS), movement difficulties are sometimes treated with medications for Parkinson’s disease. But these medicines offer only minimal or temporary improvement. Physical and occupational therapy may help people with CBS move more easily. Speech therapy may help them manage language symptoms.

For people with progressive supranuclear palsy (PSP), sometimes Parkinson’s disease drugs provide temporary relief for slowness, stiffness, and balance problems. Exercises can keep the joints limber, and weighted walking aids— such as a walker with sandbags over the lower front rung—can help maintain balance. Speech, vision, and swallowing difficulties usually do not respond to any drug treatment. Antidepressants have shown modest success. For people with abnormal eye movements.

People with FTD-ALS typically decline quickly over the course of 2 to 3 years. During this time, physical therapy can help treat muscle symptoms, and a walker or wheelchair may be useful. Speech therapy may help a person speak more clearly at first. Later on, other ways of communicating, such as a speech synthesizer, can be used. The ALS symptoms of the disorder ultimately make it impossible to stand, walk, eat, and breathe on one’s own.

For any movement disorder caused by FTLD, a team of experts can help patients and their families address difficult medical and caregiving issues. Physicians, nurses, social workers, and physical, occupational, and speech therapists who are familiar with frontotemporal disorders can ensure that people with movement disorders get appropriate medical treatment and that their caregivers can help them live as well as possible.

The Future of Treatment

Researchers are continuing to explore the genetic and biological actions in the body that lead to frontotemporal disorders. In particular, they seek more information about genetic mutations that cause FTLD, as well as the disorders’ natural history and disease pathways. They also want to develop better ways, such as specialized brain imaging, to track its progression, so that treatments, when they become available, can be directed to the right people. The ultimate goal is to identify possible new drugs and other treatments to test.

Researchers are also looking for better treatments for frontotemporal disorders. Possible therapies that target the abnormal proteins found in the brain are being tested in the laboratory and in animals. Clinical trials and studies are testing a number of possible treatments in humans.

Clinical trials for individuals with frontotemporal disorders will require many participants. People with frontotemporal disorders and healthy people may be able to take part. To find out more about clinical trials, talk to your health care provider or visit www.clinicaltrials.gov.

Caring for a Person with a Frontotemporal Disorder

In addition to managing the medical and day-to-day care of people with frontotemporal disorders, caregivers can face a host of other challenges. These challenges may include changing family relationships, loss of work, poor health, decisions about long-term care, and end-of-life concerns.

Family Issues

People with frontotemporal disorders and their families often must cope with changing relationships, especially as symptoms get worse. For example, the wife of a man with bvFTD not only becomes her husband’s caregiver, but takes on household responsibilities he can no longer perform. Children may suffer the gradual “loss” of a parent at a critical time in their lives. The symptoms of bvFTD often embarrass family members and alienate friends. Life at home can become very stressful.

Work Issues

Frontotemporal disorders disrupt basic work skills, such as organizing, planning, and following through on tasks. Activities that were easy before the illness began might take much longer or become impossible. People lose their jobs because they can no longer perform them. As a result, the caregiver might need to take a second job to make ends meet—or reduce hours or even quit work to provide care and run the household. An employment attorney can offer information and advice about employee benefits, family leave, and disability if needed.

Workers diagnosed with any frontotemporal disorder can qualify quickly for Social Security disability benefits through the “compassionate allowances” program. For more information, see www.socialsecurity.gov/ compassionate allowances or call 1-800-772-1213.

Caregiver Health and Support

Caring for someone with a frontotemporal disorder can be very hard, both physically and emotionally. To stay healthy, caregivers can do the following:

  • Get regular health care.
  • Ask family and friends for help with child care, errands, and other tasks.
  • Spend time doing enjoyable activities, away from the demands of caregiving. Arrange for respite care—short-term caregiving services
    that give the regular caregiver a break—or take the person to an adult day care center, a safe, supervised environment for adults with
    dementia or other disabilities.
  • Join a support group for caregivers of people with frontotemporal disorders. Such groups allow caregivers to learn coping strategies and share feelings with others in the same position.

The organizations listed in the Resources section can help with information about caregiver services and support.

For many caregivers, there comes a point when they can no longer take care of the person with a frontotemporal disorder without help. The caregiving demands are simply too great, perhaps requiring around-the-clock care. As the disease progresses, caregivers may want to get home health care services or look for a residential care facility, such as a group home, assisted living facility, or nursing home. The decision to move the person with a frontotemporal disorder to a care facility can be difficult, but it can also give caregivers peace of mind to know that the person is safe and getting good care. The decreased level of stress may also improve the caregivers’ relationship with his or her loved one.

End-of-Life Concerns

People with frontotemporal disorders typically live 6 to 8 years with their conditions, sometimes longer, sometimes less. Most people die of problems related to advanced disease. For example, as movement skills decline, a person can have trouble swallowing, leading to aspiration pneumonia, in which food or fluid gets into the lungs and causes infection. People with balance problems may fall and seriously injure themselves.

It is difficult, but important, to plan for the end of life. Legal documents, such as a will, living will, and durable powers of attorney for health care and finances should be created or updated as soon as possible after a diagnosis of bvFTD, PPA, or a related disorder. Early on, many people can understand and participate in legal decisions. But as their illness progresses, it becomes harder to make such decisions.

A physician who knows about frontotemporal disorders can help determine the person’s mental capacity. An attorney who specializes in elder law, disabilities, or estate planning can provide legal advice, prepare documents, and make financial arrangements for the caregiving spouse or partner and dependent children. If necessary, the person’s access to finances can be reduced or eliminated.

Next steps

Tips to help you get the most from a visit to your healthcare provider:

  • Know the reason for your visit and what you want to happen.
  • Before your visit, write down questions you want answered.
  • Bring someone with you to help you ask questions and remember what your provider tells you.
  • At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
  • Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
  • Ask if your condition can be treated in other ways.
  • Know why a test or procedure is recommended and what the results could mean.
  • Know what to expect if you do not take the medicine or have the test or procedure.
  • If you have a follow-up appointment, write down the date, time, and purpose for that visit.
  • Know how you can contact your provider if you have questions.

References

Frontotemporal Dementia – Causes, Symptoms, Treatment

Frontotemporal dementia is a progressive, neurodegenerative, heterogeneous group of non-Alzheimer dementias disorder characterized by loss of intellectual functions, such as memory problems, impaired abstract thinking, reasoning, behavioral changes, and language deficits with frontal and temporal cortical degeneration and executive function, severe enough to hamper activities of daily living. It requires a multidisciplinary approach to improve patient outcomes. The clinical manifestation includes behavior changes, dietary changes, loss of empathy, apathy, and executive function.

Frontotemporal Disorders /Few people have heard of frontotemporal disorders, which lead to dementias that affect personality, behavior, language, and movement. These disorders are little known outside the circles of researchers, clinicians, patients, and caregivers who study and live with them. Although frontotemporal disorders remain puzzling in many ways, researchers are finding new clues that will help them solve this medical mystery and better understand other common dementias.

The symptoms of frontotemporal disorders gradually rob people of basic abilities—thinking, talking, walking, and socializing—that most of us take for granted. They often strike people in the prime of life, when they are working and raising families. Families suffer, too, as they struggle to cope with the person’s daily needs as well as changes in relationships and responsibilities.

This booklet is meant to help people with frontotemporal disorders, their families, and caregivers learn more about these conditions and resources for coping. It explains what is known about the different types of disorders and how they are diagnosed. Most importantly, it describes how to treat and manage these difficult conditions, with practical advice for caregivers.

The Basics of Frontotemporal Dementia

Frontotemporal disorders are the result of damage to neurons (nerve cells) in parts of the brain called the frontal and temporal lobes. As neurons die in the frontal and temporal regions, these lobes atrophy, or shrink. Gradually, this damage causes difficulties in thinking and behaviors normally controlled by these parts of the brain. Many possible symptoms can result, including unusual behaviors, emotional problems, trouble communicating, difficulty with work, or difficulty with walking.

A Form of Dementia

Frontotemporal disorders are forms of dementia caused by a family of brain diseases known as frontotemporal lobar degeneration (FTLD). Dementia is a severe loss of thinking abilities that interferes with a person’s ability to perform daily activities such as working, driving, and preparing meals. Other brain diseases that can cause dementia include Alzheimer’s disease and multiple strokes. Scientists estimate that FTLD may cause up to 10 percent of all cases of dementia and may be about as common as Alzheimer’s among people younger than age 65. Roughly 60 percent of people with FTLD are 45 to 64 years old.

People can live with frontotemporal disorders for up to 10 years, sometimes longer, but it is difficult to predict the time course for an individual patient. The disorders are progressive, meaning symptoms get worse over time. In the early stages, people may have just one type of symptom. As the disease progresses, other types of symptoms appear as more parts of the brain are affected.

No cure or treatments that slow or stop the progression of frontotemporal disorders are available today. However, research is improving awareness and understanding of these challenging conditions. This progress is opening doors to better diagnosis, improved care, and, eventually, new treatments.

FTD? FTLD? Understanding Terms

One of the challenges shared by patients, families, clinicians, and researchers is confusion about how to classify and label frontotemporal disorders. A diagnosis by one doctor may be called something else by a second, and the same condition or syndrome referred to by another name by a pathologist who examines the brain after death.

For many years, scientists and physicians used the term frontotemporal dementia (FTD) to describe this group of illnesses. After further research, FTD is now understood to be just one of several possible variations and is more precisely called behavioral variant frontotemporal dementia, or bvFTD.

This booklet uses the term frontotemporal disorders to refer to changes in behavior and thinking that are caused by underlying brain diseases collectively called frontotemporal lobar degeneration (FTLD). FTLD is not a single brain disease but rather a family of neurodegenerative diseases, any one of which can cause a frontotemporal disorder (see “Causes,” page 11). Frontotemporal disorders are diagnosed by physicians and psychologists based on a person’s symptoms and results of brain scans and genetic tests. With the exception of known genetic causes, the type of FTLD can be identified definitively only by brain autopsy after death.

Changes in the Brain

Frontotemporal disorders affect the frontal and temporal lobes of the brain. They can begin in the frontal lobe, the temporal lobe, or both. Initially, frontotemporal disorders leave other brain regions untouched, including those that control short-term memory.

The frontal lobes, situated above the eyes and behind the forehead both on the right and left sides of the brain, direct executive functioning. This includes planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and monitoring and correcting errors.

When functioning well, the frontal lobes also help manage emotional responses. They enable people to avoid inappropriate social behaviors, such as shouting loudly in a library or at a funeral. They help people make decisions that make sense for a given situation. When the frontal lobes are damaged, people may focus on insignificant details and ignore important aspects of a situation or engage in purposeless activities. The frontal lobes are also involved in language, particularly linking words to form sentences, and in motor functions, such as moving the arms, legs, and mouth.

The temporal lobes, located below and to the side of each frontal lobe on the right and left sides of the brain, contain essential areas for memory but also play a major role in language and emotions. They help people understand words, speak, read, write, and connect words with their meanings. They allow people to recognize objects and to relate appropriate emotions to objects and events. When the temporal lobes are dysfunctional, people may have difficulty recognizing emotions and responding appropriately to them.

Which lobe—and part of the lobe—is affected first determines which symptoms appear first. For example, if the disease starts in the part of the frontal lobe responsible for decision-making, then the first symptom might be trouble managing finances. If it begins in the part of the temporal lobe that connects emotions to objects, then the first symptom might be an inability to recognize potentially dangerous objects—a person might reach for a snake or plunge a hand into boiling water, for example.

Types of Frontotemporal Dementia

Frontotemporal disorders can be grouped into three types, defined by the earliest symptoms physicians identify when they examine patients.

  • Progressive behavior/personality decline—characterized by changes in personality, behavior, emotions, and judgment (called
    behavioral variant frontotemporal dementia).
  • Progressive language decline—marked by early changes in language ability, including speaking, understanding, reading, and writing (called primary progressive aphasia).
  • Progressive motor decline—characterized by various difficulties with physical movement, including the use of one or more limbs, shaking, difficulty walking, frequent falls, and poor coordination (called corticobasal syndrome, supranuclear palsy, or amyotrophic lateral sclerosis).

Based on anatomic, genetic, and neuropathologic categorizations, the six clinical subtypes of FTD or related disorders are

  • (1) behavioral variant of FTD,
  • (2) semantic variant primary progressive aphasia,
  • (3) nonfluent agrammatic variant primary progressive aphasia,
  • (4) corticobasal syndrome,
  • (5) progressive supranuclear palsy, and
  • (6) FTD associated with motor neuron disease. Recognition and accurate diagnoses of FTD subtypes will aid the neurologist in the management of patients with FTD.

In the early stages it can be hard to know which of these disorders a person has because symptoms and the order in which they appear can vary widely from one person to the next. Also, the same symptoms can appear later in different disorders. For example, language problems are most typical of primary progressive aphasia but can also appear later in the course of behavioral variant frontotemporal dementia. The table on page 6 summarizes the three types of frontotemporal disorders and lists the various terms that could be used when clinicians diagnose these disorders.

Behavioral Variant Frontotemporal Dementia

The most common frontotemporal disorder, behavioral variant frontotemporal dementia (bvFTD), involves changes in personality, behavior, and judgment. People with this dementia can act strangely around other people, resulting in embarrassing social situations. Often, they don’t know or care that their behavior is unusual and don’t show any consideration for the feelings of others. Over time, language and/or movement problems may occur, and the person needs more care and supervision.

In the past, bvFTD was called Pick’s disease, named after Arnold Pick, the German scientist who first described it in 1892. The term Pick’s disease is now used to describe abnormal collections in the brain of the protein tau, called “Pick bodies.” Some patients with bvFTD have Pick bodies in the brain, and some do not.

Primary Progressive Aphasia

Primary progressive aphasia (PPA) involves changes in the ability to communicate—to use language to speak, read, write, and understand what others are saying. Problems with memory, reasoning, and judgment are not apparent at first but can develop over time. In addition, some people with PPA may experience significant behavioral changes, similar to those seen in bvFTD, as the disease progresses.

There are three types of PPA, categorized by the kind of language problems seen at first. Researchers do not fully understand the biological basis of the different types of PPA. But they hope one day to link specific language problems with the abnormalities in the brain that cause them.

In semantic PPA, also called semantic dementia, a person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.

In agrammatic PPA, also called progressive nonfluent aphasia, a person has more and more trouble producing speech. Eventually, the person may no longer be able to speak at all. He or she may eventually develop movement symptoms similar to those seen in corticobasal syndrome.

In logopenic PPA, a person has trouble finding the right words during the conversation but can understand words and sentences. The person does not have problems with grammar.

Movement Disorders

Two rare neurological disorders associated with FTLD, corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), occur when the parts of the brain that control movement is affected. The disorders may affect thinking and language abilities, too.

CBS can be caused by corticobasal degeneration—gradual atrophy and loss of nerve cells in specific parts of the brain. This degeneration causes progressive loss of the ability to control movement, typically beginning around age 60. The most prominent symptom may be the inability to use the hands or arms to perform a movement despite normal strength (called apraxia). Symptoms may appear first on one side of the body, but eventually, both sides are affected. Occasionally, a person with CBS first has language problems or trouble orienting objects in space and later develops movement symptoms.

PSP causes problems with balance and walking. People with the disorder typically move slowly, experience unexplained falls, lose facial expression, and have body stiffness, especially in the neck and upper body—symptoms similar to those of Parkinson’s disease. A hallmark sign of PSP is trouble with eye movements, particularly looking down. These symptoms may give the face a fixed stare. Behavior problems can also develop.

Other movement-related frontotemporal disorders include frontotemporal dementia with parkinsonism and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS).

Frontotemporal dementia with parkinsonism can be an inherited disease caused by a genetic tau mutation. Symptoms include movement problems similar to those of Parkinson’s disease, such as slowed movement, stiffness, and balance problems, and changes in behavior or language.

FTD-ALS is a combination of bvFTD and ALS, commonly called Lou Gehrig’s disease. Symptoms include the behavioral and/or language changes seen in bvFTD as well as the progressive muscle weakness seen in ALS. Symptoms of either disease may appear first, with other symptoms developing over time. Mutations in certain genes have been found in some patients with FTD-ALS.

Causes of Frontotemporal Dementia

Frontotemporal lobar degeneration (FTLD) is not a single brain disease but rather a family of brain diseases that share some common molecular features. Scientists are beginning to understand the biological and genetic basis for the changes observed in brain cells that lead to FTLD.

Scientists describe FTLD in terms of patterns of change in the brain seen in an autopsy after death. These changes include loss of neurons and abnormal amounts or forms of proteins called tau and TDP-43. These proteins occur naturally in the body and help cells function properly. When the proteins don’t work properly and accumulate in cells, for reasons not yet fully understood, neurons in specific brain regions are damaged.

In most cases, the cause of a frontotemporal disorder is unknown. In about 15 to 40 percent of people, a genetic (hereditary) cause can be identified. Individuals with a family history of frontotemporal disorders are more likely to have a genetic form of the disease than those without such a history.

Familial and inherited forms of frontotemporal disorders are often related to mutations (permanent changes) in certain genes. Genes are basic units of heredity that tell cells how to make the proteins the body needs to function. Even small changes in a gene may produce an abnormal protein, which can lead to changes in the brain and, eventually, disease.

Scientists have discovered several different genes that, when mutated, can lead to frontotemporal disorders:

  • Tau gene (also called the MAPT gene)—A mutation in this gene causes abnormalities in a protein called tau, which forms tangles inside neurons and ultimately leads to the destruction of brain cells. Inheriting a mutation in this gene means a person will almost surely develop a frontotemporal disorder, usually the bvFTD form, but the exact age of onset and symptoms cannot be predicted.
  • PGRN gene— A mutation in this gene can lead to lower production of the protein progranulin, which in turn causes TDP-43, a cellular protein, to go awry in brain cells. Many frontotemporal disorders can result, though bvFTD is the most common. The PRGRN gene can cause different symptoms in different family members and cause the disease to begin at different ages.
  • VCP, CHMP2B, TARDBP, and FUS genes— Mutations in these genes lead to very rare familial types of frontotemporal disorders. TARDBP and FUS gene mutations are more often associated with hereditary ALS.
  • C9ORF72 gene— An unusual mutation in this gene appears to be the most common genetic abnormality in familial frontotemporal disorders and familial ALS. It also occurs in some cases of sporadic ALS. This mutation can cause a frontotemporal disorder, ALS, or both conditions in a person.

Scientists are continuing to study these genes and to search for other genes and proteins, as well as nongenetic risk factors, that may play a role in frontotemporal disorders. They are trying to understand, for example, how mutations in a single gene lead to different frontotemporal disorders in members of the same family. Environmental factors that may influence the risk for developing the disorders are also being examined.

Families affected by inherited and familial forms of frontotemporal disorders can help scientists further research by participating in clinical studies and trials. For more information, talk with a health care professional, contact any of the research centers listed at the end of this booklet or search www.clinicaltrials.gov.

Symptoms of Frontotemporal Dementia

Symptoms of frontotemporal disorders vary from person to person and from one stage of the disease to the next as different parts of the frontal and temporal lobes are affected. In general, changes in the frontal lobe are associated with behavioral symptoms, while changes in the temporal lobe lead to language and emotional disorders.

Symptoms are often misunderstood. Family members and friends may think that a person is misbehaving, leading to anger and conflict. For example, a person with bvFTD may neglect personal hygiene or start shoplifting. It is important to understand that people with these disorders cannot control their behaviors and other symptoms. Moreover, they lack any awareness of their illness, making it difficult to get help.

Behavioral Symptoms

  • Problems with executive functioning—Problems with planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and self-monitoring and correcting behavior.
  • Perseveration—A tendency to repeat the same activity or to say the same word over and over, even when it no longer makes sense.
  • Social disinhibition—Acting impulsively without considering how others perceive the behavior. For example, a person might hum at a business meeting or laugh at a funeral.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Utilization behavior—Difficulty resisting impulses to use or touch objects that one can see and reach. For example, a person picks up the telephone receiver while walking past it when the phone is not ringing and the person does not intend to place a call.

Language Symptoms

  • Aphasia—A language disorder in which the ability to use or understand words is impaired but the physical ability to speak properly is normal.
  • Dysarthria—A language disorder in which the physical ability to speak properly is impaired (e.g., slurring) but the message is normal. People with PPA may have only problems using and understanding words or also problems with the physical ability to speak. People with both kinds of problems have trouble speaking and writing. They may become mute, or unable to speak. Language problems usually get worse, while other thinking and social skills may remain normal for longer before deteriorating.

Emotional Symptoms

  • Apathy—A lack of interest, drive, or initiative. Apathy is often confused with depression, but people with apathy may not be sad. They often have trouble starting activities but can participate if others do the planning.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Emotional changes—Emotions are flat, exaggerated, or improper. Emotions may seem completely disconnected from a situation or are expressed at the wrong times or in the wrong circumstances. For example, a person may laugh at sad news.
  • Social-interpersonal changes—Difficulty “reading” social signals, such as facial expressions, and understanding personal relationships. People may lack empathy—the ability to understand how others are feeling—making them seem indifferent, uncaring, or selfish. For example, the person may show no emotional reaction to illnesses or accidents that occur to family members.

Movement Symptoms

  • Dystonia—Abnormal postures of body parts such as the hands or feet. A limb may be bent stiffly or not used when performing activities that are normally done with two hands.
  • Gait disorder—Abnormalities in walking, such as walking with a shuffle, sometimes with frequent falls.
  • Tremor—Shakiness, usually of the hands.
  • Clumsiness—Dropping of small objects or difficulty manipulating small items like buttons or screws.
  • Apraxia—Loss of ability to make common motions, such as combing one’s hair or using a knife and fork, despite normal strength.
  • Neuromuscular weakness—Severe weakness, cramps, and rippling movements in the muscles.

Diagnosis of Frontotemporal Dementia

Consensus criteria for FTD

  1. Core diagnostic features

    A. Insidious onset and gradual progression

    B. Early decline in social interpersonal conduct

    C. Early impairment in regulation of personal conduct

    D. Early emotional blunting

    E. Early loss of insight

  2. Supportive diagnostic features

    A. Behavioral disorder

    1. Decline in personal hygiene and grooming

    2. Mental rigidity and inflexibility

    3. Distractibility and impersistence

    4. Hyperorality and dietary changes

    5. Perseverative and stereotyped behavior

    6. Utilization behavior

    B. Speech and language

    1. Altered speech output

    a. Aspontaneity and economy of speech

    b. Pressure of speech

    2. Stereotypy of speech

    3. Echolalia

    4. Perseveration

    5. Mutism

    C. Physical signs

    1. Primitive reflexes

    2. Incontinence

    3. Akinesia, rigidity, and tremor

    4. Low and labile blood pressure

    D. Investigations

    1. Neuropsychology: impairment on frontal lobe tests without severe amnesia, aphasia, or perceptuospatial disorder

    2. Electroencephalography: normal on conventional EEG despite clinically evident dementia

    3. Brain imaging (structural and/or functional): predominant frontal and/or anterior temporal abnormality

No single test, such as a blood test, can be used to diagnose a frontotemporal disorder. A definitive diagnosis can be confirmed only by a genetic test in familial cases or a brain autopsy after a person dies. To diagnose a probable frontotemporal disorder in a living person, a doctor— usually a neurologist, psychiatrist, or psychologist—will:

  • record a person’s symptoms, often with the help of family members or friends
  • compile a personal and family medical history
  • perform a physical exam and order blood tests to help rule out other similar conditions
  • if appropriate, order testing to uncover genetic mutations
  • conduct a neuropsychological evaluation to assess behavior, language, memory, and other cognitive functions
  • use brain imaging to look for changes in the frontal and temporal lobes.

In all forms of FTD, functional ability and activities of daily living are compromised.

  • Behavior variant type FTD (bvFTD) – It is the most common phenotype. Patients suffering from bvFTD may present with a cluster of altered behavior and personality changes earlier in the disease process, which include disinhibition, loss of emotional reactivity and disease insight, apathy, impaired abstract thinking and executive function that gradually worsens over time. Additionally, it may demonstrate a change in dietary behavior and loss of fundamental emotions and empathy but with intact memory until late in the disease.
  • Semantic variant FTD – In this form of FTD, patients manifest language difficulties characterized by paraphasia (impaired word-finding ability or loss of vocabulary), difficulty in understanding the meaning of words, impaired comprehension, and difficulty in recognizing unfamiliar objects or faces. Their speech is fluent but not making any sense. Memory is affected late in the disease.
  • Non-fluent variant Primary Progressive Aphasia (nfvPPA) – Patients with this type of FTD presents clinically with effortful halted speech and paraphasia (jumbled words), difficulty in understanding complex sentences and naming objects. Their memory, abstract thinking, and calculating abilities are spared earlier in the disease course.

Various bedside tests can be performed if clinical suspicion for FTD is high.

  • Go-no-go test – In this test, the patient is asked to perform an action in response to a particular stimulus and inhibit that action in response to different stimuli.
  • Letter fluency test – In this test, the patient is asked to say as many words (except proper nouns), starting with a single letter in one minute.
  • Attention test – It is used to evaluate the attention span. It is done either by serial seven subtractions from 100 or spells the word “world” backward.
  • Similarities and differences – It is done to evaluate abstract thinking. The patient is instructed to compare items (table and chair, apple, and orange).

Patients with frontotemporal dementia should be evaluated as follows:

  • Laboratory –  Neural and axonal cytoskeletons are mainly composed of neurofilaments, which are further made up of small subunits called neurofilament light chains. Neurofilament light chain, among other biomarkers, can be increasingly seen in blood and cerebrospinal fluid of FTD patients.
  • Radiographic tests – Magnetic resonance imaging, computed tomography scan, or single-photon emission tomography can be used to demonstrate atrophy and hypoperfusion in the frontal and temporal lobes. However, the findings are not specific. Imaging may aid in the diagnosis or to rule out other etiologies.
  • Electroencephalography (EEG) – It is not very helpful for FTD as it is for Alzheimer’s disease; however, in comparison to the healthy group, a typical EEG pattern was observed in several FTD patients and was marked by the reduction of fast activities (alpha, beta1- beta3), but no difference in slow activities (delta & theta waves).
  • Neurocognitive exams – Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, and Functional Cognitive Assessment. For primary care, the Cochrane dementia and cognitive improvement group supports the utilization of two tests; MMSE (the most commonly used test in primary care) and the Informant Questionnaire for Cognitive Disorders in the Elderly. MMSE assesses different domains of dementia, including but not limited to memory, cognition, language, attention/orientation, and executive functions.
  • A magnetic resonance imaging (MRI) – scan shows changes in the size and shape of the brain, including the frontal and temporal lobes. It may reveal other potentially treatable causes of the person’s symptoms, such as a stroke or tumor. In the early stage of the disease, the MRI may appear normal. In this case, other types of imaging, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), may be useful. PET and SPECT scan to measure activity in the brain by monitoring blood flow, glucose usage, and oxygen usage. Other PET scans can help rule out a diagnosis of Alzheimer’s.
  • Cerebrospinal fluid – and serum protein biomarkers are presently utilized to exclude Alzheimer’s disease in the assessment of frontotemporal dementia and are under appraisal for prospective diagnostic indications and monitoring pathologic progression and response to potential therapies. Elevated CSF tau proteins and decreased beta-amyloid 42 protein concentrations can accurately confirm Alzheimer’s dementia and are validated for eliminating frontotemporal dementia from the differential.
  • Neurofilament light chain (NFL) – proteins are increased in serum and CSF samples of patients with frontotemporal dementia and other neurodegenerative disorders and have promising applications in future frontotemporal dementia assays. Gene-specific biomarkers such as progranulin and poly (GP) have the potential for investigating the expression of GRN and C9orf72 frontotemporal dementia mutations, respectively. As with potential imaging techniques, more data is needed to implement fluid biomarkers into a comprehensive frontotemporal dementia evaluation strategy.
  • Neuropsychological Testing – Performance patterns on cognitive testing may vary according to the subtype. Many patients with CBS will demonstrate deficits on tasks of executive function, writing, visuospatial, and construction tasks. Patients presenting with dominant frontal lobe involvement may show word-finding deficits, agrammatism, and spelling errors similar to patients with nonfluent agrammatic PPA.[
  • Neuroimaging – Structural brain imaging in patients with CBS may show asymmetric frontal and parietal lobe atrophy, although imaging findings may overlap with those seen in other FTDs and AD. Thus, diagnosis at present is based on clinical criteria, with neuroimaging performed to rule out other structural causes of symptoms.

Treatment of Frontotemporal Dementia

So far, there is no cure for frontotemporal disorders and no way to slow down or prevent them. However, there are ways to manage symptoms. A team of specialists—doctors, nurses, and speech, physical, and occupational therapists—familiar with these disorders can help guide treatment.

Non-Pharmacologic Treatment

It includes a multidisciplinary approach, such as social support services, physical therapy & occupational therapy, speech therapy, cognitive behavior therapy, rehabilitation services, and caregivers’ education. Regular monitoring of the behavior of both the patient and caregiver for assessing activities of daily living, such as financial account managing, driving, environmental modification, and eating, is mandatory.

Pharmacological Treatment

Acetylcholinesterase inhibitors and N-methyl-D-Aspartate inhibitors have no proven benefit. Similarly, selective serotonin reuptake inhibitors (SSRI) have a limited role. It can improve certain behaviors, but not cognition. Antipsychotics have mixed results but comes with a price of severe extrapyramidal side effects to which the FTD patients are susceptible; therefore, they are not approved by the US food and drug administration as a treatment for FTD. Selective dopaminergic antagonists can improve motivation and apathy. Several disease-modifying drugs like Salsalate (tau acetylation inhibitor) and Gosuraneb (anti-tau monoclonal antibodies) targeting different biomarkers are being studied, but no recommendations yet have been made. Several other promising disease-modifying drugs are currently under clinical trials.

Managing Behavior

The behaviors of a person with bvFTD can upset and frustrate family members and other caregivers. It is natural to grieve for the “lost person,” but it is also important to learn how to best live with the person he or she has become. Understanding changes in personality and behavior and knowing how to respond can reduce caregivers’ frustration and help them cope with the challenges of caring for a person with a frontotemporal disorder.

Managing behavioral symptoms can involve several approaches. To ensure the safety of a person and his or her family, caregivers may have to take on new responsibilities or arrange care that was not needed before. For example, they may have to drive the person to appointments and errands, care for young children, or arrange for help at home.

It is helpful, though often difficult, to accept rather than challenge people with behavioral symptoms. Arguing or reasoning with them will not help because they cannot control their behaviors or even see that they are unusual or upsetting to others. Instead, be as sensitive as possible and understand that it’s the illness “talking.”

Frustrated caregivers can take a “timeout”—take deep breaths, count to 10, or leave the room for a few minutes.

To deal with apathy, limit choices and offer specific choices. Open-ended questions (“What would you like to do today?”) are more difficult to answer than specific ones (“Do you want to go to the movies or the shopping center today?”).

Maintaining the person’s schedule and modifying the environment can also help. A regular schedule is less confusing and can help people sleep better. If compulsive eating is an issue, caregivers may have to supervise eating, limit food choices, lock food cabinets and the refrigerator, and distract the person with other activities. To deal with other compulsive behaviors, caregivers may have to change schedules or offer new activities.

Medications are available to treat certain behavioral symptoms. Antidepressants called selective serotonin reuptake inhibitors are commonly prescribed to treat social disinhibition and impulsive behavior. Patients with aggression or delusions sometimes take low doses of antipsychotic medications. The use of Alzheimer’s disease medications to improve behavioral and cognitive symptoms in people with bvFTD and related disorders is being studied, though results so far have been mixed, with some medications making symptoms worse. If a particular medication is not working, a doctor may try another. Always consult a doctor before changing, adding, or stopping a drug.

Treating Language Problems

Treatment of primary progressive aphasia (PPA) has two goals—maintaining language skills and using new tools and other ways to communicate. Treatment tailored to a person’s specific language problem and stage of PPA generally works best. Since language ability declines over time, different strategies may be needed as the illness progresses.

To communicate without talking, a person with PPA may use a communication notebook (an album of photos labeled with names of people and objects), gestures, and drawings. Some people find it helpful to use or point to lists of words or phrases stored in a computer or personal digital assistant.

Caregivers can also learn new ways of talking to someone with PPA. For example, they can speak slowly and clearly, use simple sentences, wait for responses, and ask for clarification if they don’t understand something.

A speech-language pathologist who knows about PPA can test a person’s language skills and determine the best tools and strategies to use. Note that many speech-language pathologists are trained to treat aphasia caused by stroke, which requires different strategies from those used with PPA. (See the Resources section starting on page 27 to find speech-language pathologists and other experts who know about frontotemporal disorders.)

Managing Movement Problems

No treatment can slow down or stop frontotemporal-related movement disorders, though medications and physical and occupational therapy may provide modest relief.

For people with corticobasal syndrome (CBS), movement difficulties are sometimes treated with medications for Parkinson’s disease. But these medicines offer only minimal or temporary improvement. Physical and occupational therapy may help people with CBS move more easily. Speech therapy may help them manage language symptoms.

For people with progressive supranuclear palsy (PSP), sometimes Parkinson’s disease drugs provide temporary relief for slowness, stiffness, and balance problems. Exercises can keep the joints limber, and weighted walking aids— such as a walker with sandbags over the lower front rung—can help maintain balance. Speech, vision, and swallowing difficulties usually do not respond to any drug treatment. Antidepressants have shown modest success. For people with abnormal eye movements.

People with FTD-ALS typically decline quickly over the course of 2 to 3 years. During this time, physical therapy can help treat muscle symptoms, and a walker or wheelchair may be useful. Speech therapy may help a person speak more clearly at first. Later on, other ways of communicating, such as a speech synthesizer, can be used. The ALS symptoms of the disorder ultimately make it impossible to stand, walk, eat, and breathe on one’s own.

For any movement disorder caused by FTLD, a team of experts can help patients and their families address difficult medical and caregiving issues. Physicians, nurses, social workers, and physical, occupational, and speech therapists who are familiar with frontotemporal disorders can ensure that people with movement disorders get appropriate medical treatment and that their caregivers can help them live as well as possible.

The Future of Treatment

Researchers are continuing to explore the genetic and biological actions in the body that lead to frontotemporal disorders. In particular, they seek more information about genetic mutations that cause FTLD, as well as the disorders’ natural history and disease pathways. They also want to develop better ways, such as specialized brain imaging, to track its progression, so that treatments, when they become available, can be directed to the right people. The ultimate goal is to identify possible new drugs and other treatments to test.

Researchers are also looking for better treatments for frontotemporal disorders. Possible therapies that target the abnormal proteins found in the brain are being tested in the laboratory and in animals. Clinical trials and studies are testing a number of possible treatments in humans.

Clinical trials for individuals with frontotemporal disorders will require many participants. People with frontotemporal disorders and healthy people may be able to take part. To find out more about clinical trials, talk to your health care provider or visit www.clinicaltrials.gov.

Caring for a Person with a Frontotemporal Disorder

In addition to managing the medical and day-to-day care of people with frontotemporal disorders, caregivers can face a host of other challenges. These challenges may include changing family relationships, loss of work, poor health, decisions about long-term care, and end-of-life concerns.

Family Issues

People with frontotemporal disorders and their families often must cope with changing relationships, especially as symptoms get worse. For example, the wife of a man with bvFTD not only becomes her husband’s caregiver, but takes on household responsibilities he can no longer perform. Children may suffer the gradual “loss” of a parent at a critical time in their lives. The symptoms of bvFTD often embarrass family members and alienate friends. Life at home can become very stressful.

Work Issues

Frontotemporal disorders disrupt basic work skills, such as organizing, planning, and following through on tasks. Activities that were easy before the illness began might take much longer or become impossible. People lose their jobs because they can no longer perform them. As a result, the caregiver might need to take a second job to make ends meet—or reduce hours or even quit work to provide care and run the household. An employment attorney can offer information and advice about employee benefits, family leave, and disability if needed.

Workers diagnosed with any frontotemporal disorder can qualify quickly for Social Security disability benefits through the “compassionate allowances” program. For more information, see www.socialsecurity.gov/ compassionate allowances or call 1-800-772-1213.

Caregiver Health and Support

Caring for someone with a frontotemporal disorder can be very hard, both physically and emotionally. To stay healthy, caregivers can do the following:

  • Get regular health care.
  • Ask family and friends for help with child care, errands, and other tasks.
  • Spend time doing enjoyable activities, away from the demands of caregiving. Arrange for respite care—short-term caregiving services
    that give the regular caregiver a break—or take the person to an adult day care center, a safe, supervised environment for adults with
    dementia or other disabilities.
  • Join a support group for caregivers of people with frontotemporal disorders. Such groups allow caregivers to learn coping strategies and share feelings with others in the same position.

The organizations listed in the Resources section can help with information about caregiver services and support.

For many caregivers, there comes a point when they can no longer take care of the person with a frontotemporal disorder without help. The caregiving demands are simply too great, perhaps requiring around-the-clock care. As the disease progresses, caregivers may want to get home health care services or look for a residential care facility, such as a group home, assisted living facility, or nursing home. The decision to move the person with a frontotemporal disorder to a care facility can be difficult, but it can also give caregivers peace of mind to know that the person is safe and getting good care. The decreased level of stress may also improve the caregivers’ relationship with his or her loved one.

End-of-Life Concerns

People with frontotemporal disorders typically live 6 to 8 years with their conditions, sometimes longer, sometimes less. Most people die of problems related to advanced disease. For example, as movement skills decline, a person can have trouble swallowing, leading to aspiration pneumonia, in which food or fluid gets into the lungs and causes infection. People with balance problems may fall and seriously injure themselves.

It is difficult, but important, to plan for the end of life. Legal documents, such as a will, living will, and durable powers of attorney for health care and finances should be created or updated as soon as possible after a diagnosis of bvFTD, PPA, or a related disorder. Early on, many people can understand and participate in legal decisions. But as their illness progresses, it becomes harder to make such decisions.

A physician who knows about frontotemporal disorders can help determine the person’s mental capacity. An attorney who specializes in elder law, disabilities, or estate planning can provide legal advice, prepare documents, and make financial arrangements for the caregiving spouse or partner and dependent children. If necessary, the person’s access to finances can be reduced or eliminated.

References

Frontotemporal Disorders – Causes, Symptoms, Treatment

Frontotemporal dementia is a progressive, neurodegenerative, heterogeneous group of non-Alzheimer dementias disorder characterized by loss of intellectual functions, such as memory problems, impaired abstract thinking, reasoning, behavioral changes, and language deficits with frontal and temporal cortical degeneration and executive function, severe enough to hamper activities of daily living. It requires a multidisciplinary approach to improve patient outcomes. The clinical manifestation includes behavior changes, dietary changes, loss of empathy, apathy, and executive function.

Frontotemporal Disorders /Few people have heard of frontotemporal disorders, which lead to dementias that affect personality, behavior, language, and movement. These disorders are little known outside the circles of researchers, clinicians, patients, and caregivers who study and live with them. Although frontotemporal disorders remain puzzling in many ways, researchers are finding new clues that will help them solve this medical mystery and better understand other common dementias.

The symptoms of frontotemporal disorders gradually rob people of basic abilities—thinking, talking, walking, and socializing—that most of us take for granted. They often strike people in the prime of life, when they are working and raising families. Families suffer, too, as they struggle to cope with the person’s daily needs as well as changes in relationships and responsibilities.

This booklet is meant to help people with frontotemporal disorders, their families, and caregivers learn more about these conditions and resources for coping. It explains what is known about the different types of disorders and how they are diagnosed. Most importantly, it describes how to treat and manage these difficult conditions, with practical advice for caregivers.

The Basics of Frontotemporal Disorders

Frontotemporal disorders are the result of damage to neurons (nerve cells) in parts of the brain called the frontal and temporal lobes. As neurons die in the frontal and temporal regions, these lobes atrophy, or shrink. Gradually, this damage causes difficulties in thinking and behaviors normally controlled by these parts of the brain. Many possible symptoms can result, including unusual behaviors, emotional problems, trouble communicating, difficulty with work, or difficulty with walking.

A Form of Dementia

Frontotemporal disorders are forms of dementia caused by a family of brain diseases known as frontotemporal lobar degeneration (FTLD). Dementia is a severe loss of thinking abilities that interferes with a person’s ability to perform daily activities such as working, driving, and preparing meals. Other brain diseases that can cause dementia include Alzheimer’s disease and multiple strokes. Scientists estimate that FTLD may cause up to 10 percent of all cases of dementia and may be about as common as Alzheimer’s among people younger than age 65. Roughly 60 percent of people with FTLD are 45 to 64 years old.

People can live with frontotemporal disorders for up to 10 years, sometimes longer, but it is difficult to predict the time course for an individual patient. The disorders are progressive, meaning symptoms get worse over time. In the early stages, people may have just one type of symptom. As the disease progresses, other types of symptoms appear as more parts of the brain are affected.

No cure or treatments that slow or stop the progression of frontotemporal disorders are available today. However, research is improving awareness and understanding of these challenging conditions. This progress is opening doors to better diagnosis, improved care, and, eventually, new treatments.

FTD? FTLD? Understanding Terms

One of the challenges shared by patients, families, clinicians, and researchers is confusion about how to classify and label frontotemporal disorders. A diagnosis by one doctor may be called something else by a second, and the same condition or syndrome referred to by another name by a pathologist who examines the brain after death.

For many years, scientists and physicians used the term frontotemporal dementia (FTD) to describe this group of illnesses. After further research, FTD is now understood to be just one of several possible variations and is more precisely called behavioral variant frontotemporal dementia, or bvFTD.

This booklet uses the term frontotemporal disorders to refer to changes in behavior and thinking that are caused by underlying brain diseases collectively called frontotemporal lobar degeneration (FTLD). FTLD is not a single brain disease but rather a family of neurodegenerative diseases, any one of which can cause a frontotemporal disorder (see “Causes,” page 11). Frontotemporal disorders are diagnosed by physicians and psychologists based on a person’s symptoms and results of brain scans and genetic tests. With the exception of known genetic causes, the type of FTLD can be identified definitively only by brain autopsy after death.

Changes in the Brain

Frontotemporal disorders affect the frontal and temporal lobes of the brain. They can begin in the frontal lobe, the temporal lobe, or both. Initially, frontotemporal disorders leave other brain regions untouched, including those that control short-term memory.

The frontal lobes, situated above the eyes and behind the forehead both on the right and left sides of the brain, direct executive functioning. This includes planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and monitoring and correcting errors.

When functioning well, the frontal lobes also help manage emotional responses. They enable people to avoid inappropriate social behaviors, such as shouting loudly in a library or at a funeral. They help people make decisions that make sense for a given situation. When the frontal lobes are damaged, people may focus on insignificant details and ignore important aspects of a situation or engage in purposeless activities. The frontal lobes are also involved in language, particularly linking words to form sentences, and in motor functions, such as moving the arms, legs, and mouth.

The temporal lobes, located below and to the side of each frontal lobe on the right and left sides of the brain, contain essential areas for memory but also play a major role in language and emotions. They help people understand words, speak, read, write, and connect words with their meanings. They allow people to recognize objects and to relate appropriate emotions to objects and events. When the temporal lobes are dysfunctional, people may have difficulty recognizing emotions and responding appropriately to them.

Which lobe—and part of the lobe—is affected first determines which symptoms appear first. For example, if the disease starts in the part of the frontal lobe responsible for decision-making, then the first symptom might be trouble managing finances. If it begins in the part of the temporal lobe that connects emotions to objects, then the first symptom might be an inability to recognize potentially dangerous objects—a person might reach for a snake or plunge a hand into boiling water, for example.

Types of Frontotemporal Disorders

Frontotemporal disorders can be grouped into three types, defined by the earliest symptoms physicians identify when they examine patients.

  • Progressive behavior/personality decline—characterized by changes in personality, behavior, emotions, and judgment (called
    behavioral variant frontotemporal dementia).
  • Progressive language decline—marked by early changes in language ability, including speaking, understanding, reading, and writing (called primary progressive aphasia).
  • Progressive motor decline—characterized by various difficulties with physical movement, including the use of one or more limbs, shaking, difficulty walking, frequent falls, and poor coordination (called corticobasal syndrome, supranuclear palsy, or amyotrophic lateral sclerosis).

Based on anatomic, genetic, and neuropathologic categorizations, the six clinical subtypes of FTD or related disorders are

  • (1) behavioral variant of FTD,
  • (2) semantic variant primary progressive aphasia,
  • (3) nonfluent agrammatic variant primary progressive aphasia,
  • (4) corticobasal syndrome,
  • (5) progressive supranuclear palsy, and
  • (6) FTD associated with motor neuron disease. Recognition and accurate diagnoses of FTD subtypes will aid the neurologist in the management of patients with FTD.

In the early stages it can be hard to know which of these disorders a person has because symptoms and the order in which they appear can vary widely from one person to the next. Also, the same symptoms can appear later in different disorders. For example, language problems are most typical of primary progressive aphasia but can also appear later in the course of behavioral variant frontotemporal dementia. The table on page 6 summarizes the three types of frontotemporal disorders and lists the various terms that could be used when clinicians diagnose these disorders.

Behavioral Variant Frontotemporal Dementia

The most common frontotemporal disorder, behavioral variant frontotemporal dementia (bvFTD), involves changes in personality, behavior, and judgment. People with this dementia can act strangely around other people, resulting in embarrassing social situations. Often, they don’t know or care that their behavior is unusual and don’t show any consideration for the feelings of others. Over time, language and/or movement problems may occur, and the person needs more care and supervision.

In the past, bvFTD was called Pick’s disease, named after Arnold Pick, the German scientist who first described it in 1892. The term Pick’s disease is now used to describe abnormal collections in the brain of the protein tau, called “Pick bodies.” Some patients with bvFTD have Pick bodies in the brain, and some do not.

Primary Progressive Aphasia

Primary progressive aphasia (PPA) involves changes in the ability to communicate—to use language to speak, read, write, and understand what others are saying. Problems with memory, reasoning, and judgment are not apparent at first but can develop over time. In addition, some people with PPA may experience significant behavioral changes, similar to those seen in bvFTD, as the disease progresses.

There are three types of PPA, categorized by the kind of language problems seen at first. Researchers do not fully understand the biological basis of the different types of PPA. But they hope one day to link specific language problems with the abnormalities in the brain that cause them.

In semantic PPA, also called semantic dementia, a person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.

In agrammatic PPA, also called progressive nonfluent aphasia, a person has more and more trouble producing speech. Eventually, the person may no longer be able to speak at all. He or she may eventually develop movement symptoms similar to those seen in corticobasal syndrome.

In logopenic PPA, a person has trouble finding the right words during the conversation but can understand words and sentences. The person does not have problems with grammar.

Movement Disorders

Two rare neurological disorders associated with FTLD, corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), occur when the parts of the brain that control movement is affected. The disorders may affect thinking and language abilities, too.

CBS can be caused by corticobasal degeneration—gradual atrophy and loss of nerve cells in specific parts of the brain. This degeneration causes progressive loss of the ability to control movement, typically beginning around age 60. The most prominent symptom may be the inability to use the hands or arms to perform a movement despite normal strength (called apraxia). Symptoms may appear first on one side of the body, but eventually, both sides are affected. Occasionally, a person with CBS first has language problems or trouble orienting objects in space and later develops movement symptoms.

PSP causes problems with balance and walking. People with the disorder typically move slowly, experience unexplained falls, lose facial expression, and have body stiffness, especially in the neck and upper body—symptoms similar to those of Parkinson’s disease. A hallmark sign of PSP is trouble with eye movements, particularly looking down. These symptoms may give the face a fixed stare. Behavior problems can also develop.

Other movement-related frontotemporal disorders include frontotemporal dementia with parkinsonism and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS).

Frontotemporal dementia with parkinsonism can be an inherited disease caused by a genetic tau mutation. Symptoms include movement problems similar to those of Parkinson’s disease, such as slowed movement, stiffness, and balance problems, and changes in behavior or language.

FTD-ALS is a combination of bvFTD and ALS, commonly called Lou Gehrig’s disease. Symptoms include the behavioral and/or language changes seen in bvFTD as well as the progressive muscle weakness seen in ALS. Symptoms of either disease may appear first, with other symptoms developing over time. Mutations in certain genes have been found in some patients with FTD-ALS.

Causes of Frontotemporal Disorders

Frontotemporal lobar degeneration (FTLD) is not a single brain disease but rather a family of brain diseases that share some common molecular features. Scientists are beginning to understand the biological and genetic basis for the changes observed in brain cells that lead to FTLD.

Scientists describe FTLD in terms of patterns of change in the brain seen in an autopsy after death. These changes include loss of neurons and abnormal amounts or forms of proteins called tau and TDP-43. These proteins occur naturally in the body and help cells function properly. When the proteins don’t work properly and accumulate in cells, for reasons not yet fully understood, neurons in specific brain regions are damaged.

In most cases, the cause of a frontotemporal disorder is unknown. In about 15 to 40 percent of people, a genetic (hereditary) cause can be identified. Individuals with a family history of frontotemporal disorders are more likely to have a genetic form of the disease than those without such a history.

Familial and inherited forms of frontotemporal disorders are often related to mutations (permanent changes) in certain genes. Genes are basic units of heredity that tell cells how to make the proteins the body needs to function. Even small changes in a gene may produce an abnormal protein, which can lead to changes in the brain and, eventually, disease.

Scientists have discovered several different genes that, when mutated, can lead to frontotemporal disorders:

  • Tau gene (also called the MAPT gene)—A mutation in this gene causes abnormalities in a protein called tau, which forms tangles inside neurons and ultimately leads to the destruction of brain cells. Inheriting a mutation in this gene means a person will almost surely develop a frontotemporal disorder, usually the bvFTD form, but the exact age of onset and symptoms cannot be predicted.
  • PGRN gene— A mutation in this gene can lead to lower production of the protein progranulin, which in turn causes TDP-43, a cellular protein, to go awry in brain cells. Many frontotemporal disorders can result, though bvFTD is the most common. The PRGRN gene can cause different symptoms in different family members and cause the disease to begin at different ages.
  • VCP, CHMP2B, TARDBP, and FUS genes— Mutations in these genes lead to very rare familial types of frontotemporal disorders. TARDBP and FUS gene mutations are more often associated with hereditary ALS.
  • C9ORF72 gene— An unusual mutation in this gene appears to be the most common genetic abnormality in familial frontotemporal disorders and familial ALS. It also occurs in some cases of sporadic ALS. This mutation can cause a frontotemporal disorder, ALS, or both conditions in a person.

Scientists are continuing to study these genes and to search for other genes and proteins, as well as nongenetic risk factors, that may play a role in frontotemporal disorders. They are trying to understand, for example, how mutations in a single gene lead to different frontotemporal disorders in members of the same family. Environmental factors that may influence the risk for developing the disorders are also being examined.

Families affected by inherited and familial forms of frontotemporal disorders can help scientists further research by participating in clinical studies and trials. For more information, talk with a health care professional, contact any of the research centers listed at the end of this booklet or search www.clinicaltrials.gov.

Common Symptoms

Symptoms of frontotemporal disorders vary from person to person and from one stage of the disease to the next as different parts of the frontal and temporal lobes are affected. In general, changes in the frontal lobe are associated with behavioral symptoms, while changes in the temporal lobe lead to language and emotional disorders.

Symptoms are often misunderstood. Family members and friends may think that a person is misbehaving, leading to anger and conflict. For example, a person with bvFTD may neglect personal hygiene or start shoplifting. It is important to understand that people with these disorders cannot control their behaviors and other symptoms. Moreover, they lack any awareness of their illness, making it difficult to get help.

Behavioral Symptoms

  • Problems with executive functioning—Problems with planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and self-monitoring and correcting behavior.
  • Perseveration—A tendency to repeat the same activity or to say the same word over and over, even when it no longer makes sense.
  • Social disinhibition—Acting impulsively without considering how others perceive the behavior. For example, a person might hum at a business meeting or laugh at a funeral.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Utilization behavior—Difficulty resisting impulses to use or touch objects that one can see and reach. For example, a person picks up the telephone receiver while walking past it when the phone is not ringing and the person does not intend to place a call.

Language Symptoms

  • Aphasia—A language disorder in which the ability to use or understand words is impaired but the physical ability to speak properly is normal.
  • Dysarthria—A language disorder in which the physical ability to speak properly is impaired (e.g., slurring) but the message is normal. People with PPA may have only problems using and understanding words or also problems with the physical ability to speak. People with both kinds of problems have trouble speaking and writing. They may become mute, or unable to speak. Language problems usually get worse, while other thinking and social skills may remain normal for longer before deteriorating.

Emotional Symptoms

  • Apathy—A lack of interest, drive, or initiative. Apathy is often confused with depression, but people with apathy may not be sad. They often have trouble starting activities but can participate if others do the planning.
  • Compulsive eating—Gorging on food, especially starchy foods like bread and cookies, or taking food from other people’s plates.
  • Emotional changes—Emotions are flat, exaggerated, or improper. Emotions may seem completely disconnected from a situation or are expressed at the wrong times or in the wrong circumstances. For example, a person may laugh at sad news.
  • Social-interpersonal changes—Difficulty “reading” social signals, such as facial expressions, and understanding personal relationships. People may lack empathy—the ability to understand how others are feeling—making them seem indifferent, uncaring, or selfish. For example, the person may show no emotional reaction to illnesses or accidents that occur to family members.

Movement Symptoms

  • Dystonia—Abnormal postures of body parts such as the hands or feet. A limb may be bent stiffly or not used when performing activities that are normally done with two hands.
  • Gait disorder—Abnormalities in walking, such as walking with a shuffle, sometimes with frequent falls.
  • Tremor—Shakiness, usually of the hands.
  • Clumsiness—Dropping of small objects or difficulty manipulating small items like buttons or screws.
  • Apraxia—Loss of ability to make common motions, such as combing one’s hair or using a knife and fork, despite normal strength.
  • Neuromuscular weakness—Severe weakness, cramps, and rippling movements in the muscles.

Diagnosis of Frontotemporal Disorders

Consensus criteria for FTD

  1. Core diagnostic features

    A. Insidious onset and gradual progression

    B. Early decline in social interpersonal conduct

    C. Early impairment in regulation of personal conduct

    D. Early emotional blunting

    E. Early loss of insight

  2. Supportive diagnostic features

    A. Behavioral disorder

    1. Decline in personal hygiene and grooming

    2. Mental rigidity and inflexibility

    3. Distractibility and impersistence

    4. Hyperorality and dietary changes

    5. Perseverative and stereotyped behavior

    6. Utilization behavior

    B. Speech and language

    1. Altered speech output

    a. Aspontaneity and economy of speech

    b. Pressure of speech

    2. Stereotypy of speech

    3. Echolalia

    4. Perseveration

    5. Mutism

    C. Physical signs

    1. Primitive reflexes

    2. Incontinence

    3. Akinesia, rigidity, and tremor

    4. Low and labile blood pressure

    D. Investigations

    1. Neuropsychology: impairment on frontal lobe tests without severe amnesia, aphasia, or perceptuospatial disorder

    2. Electroencephalography: normal on conventional EEG despite clinically evident dementia

    3. Brain imaging (structural and/or functional): predominant frontal and/or anterior temporal abnormality

No single test, such as a blood test, can be used to diagnose a frontotemporal disorder. A definitive diagnosis can be confirmed only by a genetic test in familial cases or a brain autopsy after a person dies. To diagnose a probable frontotemporal disorder in a living person, a doctor— usually a neurologist, psychiatrist, or psychologist—will:

  • record a person’s symptoms, often with the help of family members or friends
  • compile a personal and family medical history
  • perform a physical exam and order blood tests to help rule out other similar conditions
  • if appropriate, order testing to uncover genetic mutations
  • conduct a neuropsychological evaluation to assess behavior, language, memory, and other cognitive functions
  • use brain imaging to look for changes in the frontal and temporal lobes.

In all forms of FTD, functional ability and activities of daily living are compromised.

  • Behavior variant type FTD (bvFTD) – It is the most common phenotype. Patients suffering from bvFTD may present with a cluster of altered behavior and personality changes earlier in the disease process, which include disinhibition, loss of emotional reactivity and disease insight, apathy, impaired abstract thinking and executive function that gradually worsens over time. Additionally, it may demonstrate a change in dietary behavior and loss of fundamental emotions and empathy but with intact memory until late in the disease.
  • Semantic variant FTD – In this form of FTD, patients manifest language difficulties characterized by paraphasia (impaired word-finding ability or loss of vocabulary), difficulty in understanding the meaning of words, impaired comprehension, and difficulty in recognizing unfamiliar objects or faces. Their speech is fluent but not making any sense. Memory is affected late in the disease.
  • Non-fluent variant Primary Progressive Aphasia (nfvPPA) – Patients with this type of FTD presents clinically with effortful halted speech and paraphasia (jumbled words), difficulty in understanding complex sentences and naming objects. Their memory, abstract thinking, and calculating abilities are spared earlier in the disease course.

Various bedside tests can be performed if clinical suspicion for FTD is high.

  • Go-no-go test – In this test, the patient is asked to perform an action in response to a particular stimulus and inhibit that action in response to different stimuli.
  • Letter fluency test – In this test, the patient is asked to say as many words (except proper nouns), starting with a single letter in one minute.
  • Attention test – It is used to evaluate the attention span. It is done either by serial seven subtractions from 100 or spells the word “world” backward.
  • Similarities and differences – It is done to evaluate abstract thinking. The patient is instructed to compare items (table and chair, apple, and orange).

Patients with frontotemporal dementia should be evaluated as follows:

  • Laboratory –  Neural and axonal cytoskeletons are mainly composed of neurofilaments, which are further made up of small subunits called neurofilament light chains. Neurofilament light chain, among other biomarkers, can be increasingly seen in blood and cerebrospinal fluid of FTD patients.
  • Radiographic tests – Magnetic resonance imaging, computed tomography scan, or single-photon emission tomography can be used to demonstrate atrophy and hypoperfusion in the frontal and temporal lobes. However, the findings are not specific. Imaging may aid in the diagnosis or to rule out other etiologies.
  • Electroencephalography (EEG) – It is not very helpful for FTD as it is for Alzheimer’s disease; however, in comparison to the healthy group, a typical EEG pattern was observed in several FTD patients and was marked by the reduction of fast activities (alpha, beta1- beta3), but no difference in slow activities (delta & theta waves).
  • Neurocognitive exams – Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, and Functional Cognitive Assessment. For primary care, the Cochrane dementia and cognitive improvement group supports the utilization of two tests; MMSE (the most commonly used test in primary care) and the Informant Questionnaire for Cognitive Disorders in the Elderly. MMSE assesses different domains of dementia, including but not limited to memory, cognition, language, attention/orientation, and executive functions.
  • A magnetic resonance imaging (MRI) – scan shows changes in the size and shape of the brain, including the frontal and temporal lobes. It may reveal other potentially treatable causes of the person’s symptoms, such as a stroke or tumor. In the early stage of the disease, the MRI may appear normal. In this case, other types of imaging, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), may be useful. PET and SPECT scan to measure activity in the brain by monitoring blood flow, glucose usage, and oxygen usage. Other PET scans can help rule out a diagnosis of Alzheimer’s.
  • Cerebrospinal fluid – and serum protein biomarkers are presently utilized to exclude Alzheimer’s disease in the assessment of frontotemporal dementia and are under appraisal for prospective diagnostic indications and monitoring pathologic progression and response to potential therapies. Elevated CSF tau proteins and decreased beta-amyloid 42 protein concentrations can accurately confirm Alzheimer’s dementia and are validated for eliminating frontotemporal dementia from the differential.
  • Neurofilament light chain (NFL) – proteins are increased in serum and CSF samples of patients with frontotemporal dementia and other neurodegenerative disorders and have promising applications in future frontotemporal dementia assays. Gene-specific biomarkers such as progranulin and poly (GP) have the potential for investigating the expression of GRN and C9orf72 frontotemporal dementia mutations, respectively. As with potential imaging techniques, more data is needed to implement fluid biomarkers into a comprehensive frontotemporal dementia evaluation strategy.
  • Neuropsychological Testing – Performance patterns on cognitive testing may vary according to the subtype. Many patients with CBS will demonstrate deficits on tasks of executive function, writing, visuospatial, and construction tasks. Patients presenting with dominant frontal lobe involvement may show word-finding deficits, agrammatism, and spelling errors similar to patients with nonfluent agrammatic PPA.[
  • Neuroimaging – Structural brain imaging in patients with CBS may show asymmetric frontal and parietal lobe atrophy, although imaging findings may overlap with those seen in other FTDs and AD. Thus, diagnosis at present is based on clinical criteria, with neuroimaging performed to rule out other structural causes of symptoms.

Treatment of Frontotemporal Disorders

So far, there is no cure for frontotemporal disorders and no way to slow down or prevent them. However, there are ways to manage symptoms. A team of specialists—doctors, nurses, and speech, physical, and occupational therapists—familiar with these disorders can help guide treatment.

Non-Pharmacologic Treatment

It includes a multidisciplinary approach, such as social support services, physical therapy & occupational therapy, speech therapy, cognitive behavior therapy, rehabilitation services, and caregivers’ education. Regular monitoring of the behavior of both the patient and caregiver for assessing activities of daily living, such as financial account managing, driving, environmental modification, and eating, is mandatory.

Pharmacological Treatment

Acetylcholinesterase inhibitors and N-methyl-D-Aspartate inhibitors have no proven benefit. Similarly, selective serotonin reuptake inhibitors (SSRI) have a limited role. It can improve certain behaviors, but not cognition. Antipsychotics have mixed results but comes with a price of severe extrapyramidal side effects to which the FTD patients are susceptible; therefore, they are not approved by the US food and drug administration as a treatment for FTD. Selective dopaminergic antagonists can improve motivation and apathy. Several disease-modifying drugs like Salsalate (tau acetylation inhibitor) and Gosuraneb (anti-tau monoclonal antibodies) targeting different biomarkers are being studied, but no recommendations yet have been made. Several other promising disease-modifying drugs are currently under clinical trials.

Managing Behavior

The behaviors of a person with bvFTD can upset and frustrate family members and other caregivers. It is natural to grieve for the “lost person,” but it is also important to learn how to best live with the person he or she has become. Understanding changes in personality and behavior and knowing how to respond can reduce caregivers’ frustration and help them cope with the challenges of caring for a person with a frontotemporal disorder.

Managing behavioral symptoms can involve several approaches. To ensure the safety of a person and his or her family, caregivers may have to take on new responsibilities or arrange care that was not needed before. For example, they may have to drive the person to appointments and errands, care for young children, or arrange for help at home.

It is helpful, though often difficult, to accept rather than challenge people with behavioral symptoms. Arguing or reasoning with them will not help because they cannot control their behaviors or even see that they are unusual or upsetting to others. Instead, be as sensitive as possible and understand that it’s the illness “talking.”

Frustrated caregivers can take a “timeout”—take deep breaths, count to 10, or leave the room for a few minutes.

To deal with apathy, limit choices and offer specific choices. Open-ended questions (“What would you like to do today?”) are more difficult to answer than specific ones (“Do you want to go to the movies or the shopping center today?”).

Maintaining the person’s schedule and modifying the environment can also help. A regular schedule is less confusing and can help people sleep better. If compulsive eating is an issue, caregivers may have to supervise eating, limit food choices, lock food cabinets and the refrigerator, and distract the person with other activities. To deal with other compulsive behaviors, caregivers may have to change schedules or offer new activities.

Medications are available to treat certain behavioral symptoms. Antidepressants called selective serotonin reuptake inhibitors are commonly prescribed to treat social disinhibition and impulsive behavior. Patients with aggression or delusions sometimes take low doses of antipsychotic medications. The use of Alzheimer’s disease medications to improve behavioral and cognitive symptoms in people with bvFTD and related disorders is being studied, though results so far have been mixed, with some medications making symptoms worse. If a particular medication is not working, a doctor may try another. Always consult a doctor before changing, adding, or stopping a drug.

Treating Language Problems

Treatment of primary progressive aphasia (PPA) has two goals—maintaining language skills and using new tools and other ways to communicate. Treatment tailored to a person’s specific language problem and stage of PPA generally works best. Since language ability declines over time, different strategies may be needed as the illness progresses.

To communicate without talking, a person with PPA may use a communication notebook (an album of photos labeled with names of people and objects), gestures, and drawings. Some people find it helpful to use or point to lists of words or phrases stored in a computer or personal digital assistant.

Caregivers can also learn new ways of talking to someone with PPA. For example, they can speak slowly and clearly, use simple sentences, wait for responses, and ask for clarification if they don’t understand something.

A speech-language pathologist who knows about PPA can test a person’s language skills and determine the best tools and strategies to use. Note that many speech-language pathologists are trained to treat aphasia caused by stroke, which requires different strategies from those used with PPA. (See the Resources section starting on page 27 to find speech-language pathologists and other experts who know about frontotemporal disorders.)

Managing Movement Problems

No treatment can slow down or stop frontotemporal-related movement disorders, though medications and physical and occupational therapy may provide modest relief.

For people with corticobasal syndrome (CBS), movement difficulties are sometimes treated with medications for Parkinson’s disease. But these medicines offer only minimal or temporary improvement. Physical and occupational therapy may help people with CBS move more easily. Speech therapy may help them manage language symptoms.

For people with progressive supranuclear palsy (PSP), sometimes Parkinson’s disease drugs provide temporary relief for slowness, stiffness, and balance problems. Exercises can keep the joints limber, and weighted walking aids— such as a walker with sandbags over the lower front rung—can help maintain balance. Speech, vision, and swallowing difficulties usually do not respond to any drug treatment. Antidepressants have shown modest success. For people with abnormal eye movements.

People with FTD-ALS typically decline quickly over the course of 2 to 3 years. During this time, physical therapy can help treat muscle symptoms, and a walker or wheelchair may be useful. Speech therapy may help a person speak more clearly at first. Later on, other ways of communicating, such as a speech synthesizer, can be used. The ALS symptoms of the disorder ultimately make it impossible to stand, walk, eat, and breathe on one’s own.

For any movement disorder caused by FTLD, a team of experts can help patients and their families address difficult medical and caregiving issues. Physicians, nurses, social workers, and physical, occupational, and speech therapists who are familiar with frontotemporal disorders can ensure that people with movement disorders get appropriate medical treatment and that their caregivers can help them live as well as possible.

The Future of Treatment

Researchers are continuing to explore the genetic and biological actions in the body that lead to frontotemporal disorders. In particular, they seek more information about genetic mutations that cause FTLD, as well as the disorders’ natural history and disease pathways. They also want to develop better ways, such as specialized brain imaging, to track its progression, so that treatments, when they become available, can be directed to the right people. The ultimate goal is to identify possible new drugs and other treatments to test.

Researchers are also looking for better treatments for frontotemporal disorders. Possible therapies that target the abnormal proteins found in the brain are being tested in the laboratory and in animals. Clinical trials and studies are testing a number of possible treatments in humans.

Clinical trials for individuals with frontotemporal disorders will require many participants. People with frontotemporal disorders and healthy people may be able to take part. To find out more about clinical trials, talk to your health care provider or visit www.clinicaltrials.gov.

Caring for a Person with a Frontotemporal Disorder

In addition to managing the medical and day-to-day care of people with frontotemporal disorders, caregivers can face a host of other challenges. These challenges may include changing family relationships, loss of work, poor health, decisions about long-term care, and end-of-life concerns.

Family Issues

People with frontotemporal disorders and their families often must cope with changing relationships, especially as symptoms get worse. For example, the wife of a man with bvFTD not only becomes her husband’s caregiver, but takes on household responsibilities he can no longer perform. Children may suffer the gradual “loss” of a parent at a critical time in their lives. The symptoms of bvFTD often embarrass family members and alienate friends. Life at home can become very stressful.

Work Issues

Frontotemporal disorders disrupt basic work skills, such as organizing, planning, and following through on tasks. Activities that were easy before the illness began might take much longer or become impossible. People lose their jobs because they can no longer perform them. As a result, the caregiver might need to take a second job to make ends meet—or reduce hours or even quit work to provide care and run the household. An employment attorney can offer information and advice about employee benefits, family leave, and disability if needed.

Workers diagnosed with any frontotemporal disorder can qualify quickly for Social Security disability benefits through the “compassionate allowances” program. For more information, see www.socialsecurity.gov/ compassionate allowances or call 1-800-772-1213.

Caregiver Health and Support

Caring for someone with a frontotemporal disorder can be very hard, both physically and emotionally. To stay healthy, caregivers can do the following:

  • Get regular health care.
  • Ask family and friends for help with child care, errands, and other tasks.
  • Spend time doing enjoyable activities, away from the demands of caregiving. Arrange for respite care—short-term caregiving services
    that give the regular caregiver a break—or take the person to an adult day care center, a safe, supervised environment for adults with
    dementia or other disabilities.
  • Join a support group for caregivers of people with frontotemporal disorders. Such groups allow caregivers to learn coping strategies and share feelings with others in the same position.

The organizations listed in the Resources section can help with information about caregiver services and support.

For many caregivers, there comes a point when they can no longer take care of the person with a frontotemporal disorder without help. The caregiving demands are simply too great, perhaps requiring around-the-clock care. As the disease progresses, caregivers may want to get home health care services or look for a residential care facility, such as a group home, assisted living facility, or nursing home. The decision to move the person with a frontotemporal disorder to a care facility can be difficult, but it can also give caregivers peace of mind to know that the person is safe and getting good care. The decreased level of stress may also improve the caregivers’ relationship with his or her loved one.

End-of-Life Concerns

People with frontotemporal disorders typically live 6 to 8 years with their conditions, sometimes longer, sometimes less. Most people die of problems related to advanced disease. For example, as movement skills decline, a person can have trouble swallowing, leading to aspiration pneumonia, in which food or fluid gets into the lungs and causes infection. People with balance problems may fall and seriously injure themselves.

It is difficult, but important, to plan for the end of life. Legal documents, such as a will, living will, and durable powers of attorney for health care and finances should be created or updated as soon as possible after a diagnosis of bvFTD, PPA, or a related disorder. Early on, many people can understand and participate in legal decisions. But as their illness progresses, it becomes harder to make such decisions.

A physician who knows about frontotemporal disorders can help determine the person’s mental capacity. An attorney who specializes in elder law, disabilities, or estate planning can provide legal advice, prepare documents, and make financial arrangements for the caregiving spouse or partner and dependent children. If necessary, the person’s access to finances can be reduced or eliminated.

References

Headache Disorders – Causes, Symptoms, Treatment

Headache Disorders /These patients may also complain of shoulder or neck muscle tightness as well as sleep disturbances. Symptoms of nausea, vomiting, photophobia or phonophobia are typically absent or are very mild. These features, when present, easily differentiate TTH from migraines. Sometimes the symptoms are overlapping, and confirmation of an exact diagnosis may only occur over time. Medication history is also critical. The type, frequency, and response to analgesic drugs require evaluation in all the patients.

Primary headache disorders

Migraine headache

Tension-type headache

Trigeminal autonomic cephalalgias

Other primary headache disorder

  • Primary cough headache
  • Primary exercise headache
  • Primary headache associated with sexual activity
  • Primary thunderclap headache
  • Cold-stimulus headache
  • Hypnic headache
  • New daily persistent headache (NDPH)
  • Nummular headache
  • Primary stabbing headache
  • Idiopathic trochleitis
  • Supraorbital neuralgia
  • External compression headache
  • Nasociliary neuralgia
  • Occipital neuralgia
  • Auriculotemporal neuralgia

Secondary Headache disorders:

  • Trauma and Injury headache
  • Vascular headache
  • Headache secondary to intracranial disorders
  • Chemical or substance abuse-related headache
  • Headache related to infectious causes in the head and neck regions
  • Headache related to disorders of homeostasis
  • Headache related to hypoxia and hypercapnia
    • High altitude
    • Airplane travel
    • Diving
    • Sleep apnea
  • Dialysis headache
  • Hypertension headache

    • Autonomic dysreflexia
    • Preeclampsia and eclampsia
    • Pheochromocytoma
    • Hypertensive crisis and encephalopathy
  • Fasting headache
  • Cardiac cephalgia
  • Hypothyroidism headache
  • Other disorders of homeostasis

Causes Of Headache Disorders

The International Classification of Headache Disorders (ICHD-III) classifies headaches as either :

  • Primary headache, including tension, migraine, and cluster
  • Secondary headache, including potentially life-threatening etiologies such as traumatic brain injury and vascular disorders
  • Cranial neuropathies, such as trigeminal neuralgia

Headache can be a symptom of many underlying pathologies, some of which can lead to severe disability and mortality. The emergency clinician should be especially familiar with the following conditions:

  • Hypertensive emergencies
  • Idiopathic intracranial hypertension
  • Carotid or vertebrobasilar dissection
  • Space occupying lesions (tumors, abscesses, cysts)
  • Acute hydrocephalus
  • Dural sinus thrombosis
  • Intracranial hemorrhage
  • Giant cell (temporal) arteritis
  • Cerebrovascular accident or stroke
  • Meningitis and encephalitis
  • Carbon monoxide poisoning
  • Toxin exposure or withdrawal
  • Acute angle-closure glaucoma
  • Medication overuse headache

Symptoms Of Headache Disorders

Clinical features of primary headache subtypes

Migraine headache

  • Typically unilateral in adults, bilateral in children
  • Gradual onset, crescendo pattern, pulsating, moderate or severe, aggravated by routine activity
  • Duration 4 to 72 hours
  • Patient most comfortable resting in a dark, quiet room
  • May have associated nausea, vomiting, photophobia, phonophobia, aura (most often visual)

Tension headache

  • Typically bilateral
  • Pressure or tightness, waxing and waning intensity
  • Duration 30 minutes to 7 days
  • The patient may be active or desirous of rest
  • Usually no associated symptoms

Cluster headache

  • Always unilateral, usually beginning near the temple or eye
  • Pain begins quickly, reaching maximal intensity in minutes, quality is deep, constant, excruciating or explosive
  • Duration 15 minutes to 3 hours
  • Patient remains active
  • Associated symptoms include ipsilateral lacrimation and redness to the eye, nasal congestion or rhinorrhea, pallor, diaphoresis, horner syndrome, restlessness

Conversely, if patients have high-risk features or a history and physical not compatible with primary headache, the etiology of secondary headache must be investigated. As is often the case in clinical medicine, pattern recognition is useful.

The following are several of the most important critical diagnoses of secondary headaches to consider and their key clinical features:

Subarachnoid Hemorrhage

  • “Thunderclap” headache that is sudden, with maximal pain at onset and often described as the “worst headache of my life.”
  • Associated with nausea or vomiting, neck pain and/or stiffness, and focal neurological deficits.
  • History may include age greater than 50, loss of consciousness, known vascular aneurysms, connective tissue diseases, polycystic kidney disease, family members with SAH, or history of poorly controlled hypertension.
  • Physical exam findings may include hemotympanum, focal neurological deficits, or nuchal rigidity.

Cervical artery dissection

  • Symptoms include headache, neck pain, dizziness or unsteadiness, double vision, focal weakness, confusion, and stroke-like symptoms in a younger patient.
  • History may include trauma to the head or neck.
  • Physical exam findings may include a carotid bruit, cerebellar deficits, visual field deficits, bulbar deficits, and asymmetric strength or motor findings.

Meningitis and encephalitis

  • Symptoms may include fever, headache, nuchal rigidity, altered mental status, non-specific flu-like prodrome, nausea, vomiting, focal neurological deficits, photophobia, and seizures.
  • History may include non-vaccination, immunocompromised state, close-quarter living, recent travel, tick or mosquito bite,  and sick contacts.
  • Physical exam findings may include Kernig sign (painful knee extension on hip flexion), Brudzinski sign (passive hip flexion on active neck flexion), papilledema, or petechial rash.

Dural sinus thrombosis

  • Symptoms include headache, blurry vision or visual field deficits, nausea, and vomiting. The history may include infection, head trauma, inherited or acquired hypercoagulable disorders of the patient or family members, or other causes of hypercoagulability such as systemic lupus erythematosus (SLE), sickle cell anemia, OCP use, cancer, pregnancy, estrogen use, previous thromboembolic events, antiphospholipid syndrome, and dehydration.
  • The physical exam may reveal papilledema and focal neurological and/or cranial nerve deficits.

Ischemic or hemorrhagic stroke/cerebrovascular accident

  • Symptoms correspond to the anatomic area of the brain affected. Focal neurological deficits are the most common and specific findings. Other symptoms may include headache, nausea, vomiting, vertigo, aphasia, confusion, and visual deficits.
  • History may include previous ischemic or hemorrhagic events, tobacco use, diabetes, hyperlipidemia,  hypertension, and other vascular risk factors.
  • The physical exam may include neurological deficits, altered mental status, and facial droop.

Carbon monoxide poisoning

  • Symptoms may include headache, dizziness, ataxia, confusion, nausea, and vomiting.
  • History may include the use of indoor heaters, house fires, and exposure to car exhaust.
  • The physical exam may reveal pink-tinged skin, wheezing, hyperventilation, singed nares, and an edematous oropharynx.

Acute angle-closure glaucoma

  • Symptoms may include unilateral or bilateral eye pain, photophobia, changes in or loss of vision, and sudden onset of headache.
  • The history may include older age, exacerbation of symptoms in a dark room, and family history.
  • Physical exam findings may include decreased visual acuity, conjunctival injection, increased intraocular pressure (60 to 90 mmHg is diagnostic), a shallow anterior chamber, and a fixed and mid-dilated pupil.

Idiopathic intracranial hypertension

  • Symptoms may include headache not responding to analgesia, changes in vision, nausea, and vomiting, and headache worse when supine.
  • History may include female gender, childbearing age, obesity, and new medication use. Specific medications implicated in IIH include oral contraceptives and tetracycline antibiotics, as well as lithium and vitamin A.
  • Physical exam findings may include papilledema, bradycardia, and visual field deficits.

 Hypertensive emergencies

  • Symptoms include headache, changes in vision, nausea and vomiting, confusion, seizure, and oliguria or anuria.
  • History may include pregnancy (preeclampsia/eclampsia), history of hypertension, and medication noncompliance, Autonomic dysregulation syndromes, including secondary to stroke, pheochromocytoma, and neuromuscular diseases.
  • Physical exam findings may include altered mental status, symptoms of heart failure, bradycardia, papilledema, jaundice, and a renal vein bruit.

Temporal (giant cell) arteritis

  • Symptoms may include unilateral headache, painless monocular vision loss, jaw claudication, and proximal muscle weakness.
  • History may include older age (greater than 65), polymyalgia rheumatic, and female gender.
  • Physical exam findings may include tenderness along the temporal bone, papilledema, and decreased strength of proximal muscle groups.

Diagnosis of Headache Disorders

Physical examination is normal in primary headache disorders, including the TTH. Although the transient trigeminal cranial features of ptosis, conjunctivitis, or orbital swelling may occur with the trigeminal autonomic cephalgias (TACs). Physical examination is vital in excluding the secondary causes, such as nuchal rigidity seen in meningitis and subarachnoid hemorrhage, focal neurological deficits seen in the space-occupying lesion, and/or papilledema in idiopathic intracranial hypertension, etc.

“Red flags” for secondary disorders should always be ruled out during the history and physical examination. These include:

  • Sudden onset of headache
  • Age of onset of headache after 50 years of age
  • Very severe headache
  • New onset of headache with an underlying medical condition
  • Headache with concomitant systemic illness
  • Focal neurologic signs or symptoms
  • Papilledema, and
  • History of head trauma

Secondary headache disorders can also have an evaluation using the acronym: “SNOOP4”.

  • “S” stands for systemic symptoms, fevers, chills, myalgias, and weight loss.
  • “N” is the neurological symptoms, especially the focal neurologic deficits.
  • The first “O” is for older onset, meaning the age of 50 years or greater.
  • The second “O” is onset, particularly that of a sudden onset headache like a subarachnoid hemorrhage.
  • “P1” is papilledema.
  • “P2” is positional.
  • “P3” is precipitated by the Valsalva maneuver or exertion.
  • “P4” is a progressive headache or substantial pattern change.

Evaluation

TTH is a clinical diagnosis using the IHS diagnostic criteria. No laboratory testing or imaging studies are usually necessary for the diagnosis of TTH. However, if one or more red-flags are present, then appropriate investigations, including but not limited to brain imaging, should be performed to rule out secondary causes. A magnetic resonance imaging (MRI) with gadolinium contrast is the recommended imaging study in these patients.

IHS Diagnostic criteria for TTH

IHS has proposed the diagnostic criteria in the third edition of the International Classification of Headache Disorders (ICHD-3). The criteria are as follows:

  • At least ten episodes of headache fulfilling criteria B-D
  • Lasting from 30 minutes to as long as seven days
  • Minimally two of the following four characteristics:

    • Bilaterally located
    • Pressing or tightening (non-pulsating) quality
    • Mild or moderate in intensity
    • Not exacerbated by routine physical activity, e.g., walking or climbing stairs.
  • Both of the following:

    • No nausea or vomiting
    • No more than one of photophobia or homophobia
  • They are not better explained by another ICHD-3 diagnosis.

The above is a general ICHD-3 diagnostic criterion for the TTH. If one of the above ICHD-3 features for TTH is missing and not fulfilling the criteria for another headache disorder, a diagnosis of probable tension-type headache is possible. These patients with probable TTH should undergo evaluation over time, and the clinician usually makes a diagnosis of TTH in these patients. TVs further subdivided into three subtypes based on the frequency of headache episodes.

  • Infrequent episodic TTH: At least ten episodes of headache occurring on <1 day/month on average (<12 days/year).
  • Frequent episodic TTH: At least ten episodes of headache occurring on 1 to 14 days/month on average for over 3 months (≥12 and <180 days/year).
  • Chronic TTH: Headache occurring on ≥15 days/month on average for >3 months (≥180 days/year).

Treatment of Headache Disorders

Treatment of Episodic TTH

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay treatment options to abort episodes of TTH. Recent metanalysis studies suggest that ibuprofen 400 mg and acetaminophen 1000 mg are the best pharmacological agents for acute treatment of TTH. There appears to be a synergistic effect of these two drugs together, as the NNT to treat with ibuprofen alone was greater than that of both aforementioned in combination treatment. While ASA alone is used frequently over the counter for treatment, a 500 mg dose showed to be equivalent to a placebo. Other NSAIDs (e.g. naproxen sodium [375 to 550 mg], ketoprofen [25 to 50 mg], and diclofenac [50 to 100 mg] etc.) are also more effective than placebo in acute TTH. Patients should avoid the overuse of analgesic medicines as it may, ironically, lead to medication overuse headache. Evidence for the efficacy of muscle relaxants in TTH is weak, and there is a risk for habituation.

Treatment of Chronic TTH

Pharmacological Treatment: The goal of chronic TTH therapy is to reduce the frequency of headaches through the use of preventive medications. Among pharmacologic agents, amitriptyline (a tricyclic antidepressant [TCA]), is the most efficacious and well-studied drug in the management of chronic TTH. Amitriptyline should be started on a low dose (10 to 25 mg daily) and slowly titrated (10 to 25 mg weekly) till achieving an appropriate therapeutic response, or the adverse effects appear. The therapeutic response usually occurs in 3 to 4 weeks. In responsive patients, amitriptyline usually continues for at least six months, and then withdrawal may be attempted. In case of recurrence of chronic TTH on withdrawal, amitriptyline may be continued long term.  Adverse effects are common and include dry mouth, drowsiness, urinary retention, cardiac arrhythmias, and glaucoma.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) were not as effective as TCAs.

Evidence for the efficacy of muscle relaxants in TTH is weak, and there is a risk for habituation.

Unlike chronic migraine, botulinum toxin type A has varying efficacy in different studies for chronic TTH prevention and is usually not recommended as a first-line treatment. However, in refractory chronic TTH cases, a trial of botulinum toxin A may be given.

Non-pharmacological Treatment 

The best non-pharmacological therapy for chronic TTH are physical therapy, biofeedback, and cognitive-behavioral therapy. Relaxation, exercise programs, and improvement of posture are critical components of physical therapy. Several other treatments, including massage, manipulation, acupuncture, and osteopathic manipulative medicine, have also shown improvement in both acute and chronic presentations, using measures such as increasing range of motion of the head.


Children and Headache

Headaches are common in children. Headaches that begin early in life can develop into migraines as the child grows older. Migraines in children or adolescents can develop into tension-type headaches at any time. In contrast to adults with migraines, young children often feel migraine pain on both sides of the head and have headaches that usually last less than 2 hours. Children may look pale and appear restless or irritable before and during an attack. Other children may become nauseous, lose their appetite, or feel pain elsewhere in the body during the headache.

Headaches in children can be caused by a number of triggers, including emotional problems such as the tension between family members, stress from school activities, weather changes, irregular eating and sleep, dehydration, and certain foods and drinks. Of special concern among children are headaches that occur after a head injury or those accompanied by rash, fever, or sleepiness.

It may be difficult to identify the type of headache because children often have problems describing where it hurts, how often the headaches occur, and how long they last. Asking a child with a headache to draw a picture of where the pain is and how it feels can make it easier for the doctor to determine the proper treatment.

Migraine in particular is often misdiagnosed in children. Parents and caretakers sometimes have to be detectives to help determine that a child has a migraine. Clues to watch for include sensitivity to light and noise, which may be suspected when a child refuses to watch television or use the computer, or when the child stops playing to lie down in a dark room. Observe whether or not a child is able to eat during a headache. Very young children may seem cranky or irritable and complain of abdominal pain (abdominal migraine).

Headache treatment in children and teens usually includes rest, fluids, and over-the-counter pain relief medicines. Always consult with a physician before giving headache medicines to a child. Most tension-type headaches in children can be treated with over-the-counter medicines that are marked for children with usage guidelines based on the child’s age and weight. Headaches in some children may also be treated effectively using relaxation/behavioral therapy. Children with cluster headaches may be treated with oxygen therapy early in the initial phase of the attacks.

Headache and Sleep Disorders

Headaches are often a secondary symptom of a sleep disorder. For example, tension-type headache is regularly seen in persons with insomnia or sleep-wake cycle disorders. Nearly three-fourths of individuals who suffer from narcolepsy complain of either migraine or cluster headache. Migraines and cluster headaches appear to be related to the number of and transition between rapid eye movement (REM) and other sleep periods an individual has during sleep. Hypnic headache awakens individuals mainly at night but may also interrupt daytime naps. Reduced oxygen levels in people with sleep apnea may trigger early morning headaches.

Getting the proper amount of sleep can ease headache pain. Generally, too little or too much sleep can worsen headaches, as can the overuse of sleep medicines. Daytime naps often reduce deep sleep at night and can produce headaches in some adults. Some sleep disorders and secondary headaches are treated using antidepressants. Check with a doctor before using over-the-counter medicines to ease sleep-associated headaches.

Coping with Headache

Headache treatment is a partnership between you and your doctor, and honest communication is essential. Finding a quick fix to your headache may not be possible. It may take some time for your doctor or specialist to determine the best course of treatment. Avoid using over-the-counter medicines more than twice a week, as they may actually worsen headache pain and the frequency of attacks. Visit a local headache support group meeting (if available) to learn how others with headaches cope with their pain and discomfort. Relax whenever possible to ease stress and related symptoms, get enough sleep, regularly perform aerobic exercises, and eat a regularly scheduled and healthy diet that avoids food triggers. Gaining more control over your headache, stress, and emotions will make you feel better and let you embrace daily activities as much as possible.

What Research is Being Done?

Several studies either conducted or supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, are revealing much about the headache process and may lead to new treatments or perhaps ways to block debilitating headache pain. Studies by other investigators are adding insight to headache etiology and treatment.

Understanding headache mechanisms and underlying causes

The molecular basis for migraine headaches and the aura associated with certain migraines is uncertain. One multi-faceted research study is examining how migraine with aura may affect metabolism and neurophysiological function. Investigators are also studying if particular regions of the visual cortex are unusually susceptible to the events in the brain that cause the aura. Another study component is investigating what happens at the beginning of a headache and how changes in the brain’s meninges may lead to vascular and trigeminal nerve stimulation associated with the painful part of a migraine headache. Results may provide a greater understanding of migraine and assist the development of new therapies.

Mast cells, which are part of the immune system and are involved in the inflammatory allergic response, are activated in some chronic pain conditions, including headache. Researchers are examining the possibility of a relationship between the mast cells’ anti-analgesic properties and their proximity to and enhanced activation of nerve fiber endings that receive and transmit pain signals (nociceptors). Mast cells may release substances that activate nociceptive nerve cells that transmit signals from the linings of the skull and its blood vessels. Findings that link mast cell activation to headache pain may identify drug targets that could lead to new analgesics for headache and other pain syndromes.

Cortical spreading depression (CSD) is a process in migraine with aura in which a wave of increased brain activity, followed by decreased activity, slowly spreads along the brain’s surface. The wave of brain activity often travels across the part of the brain that processes vision and corresponds to the typical visual aura of migraine. Research has shown that migraines with aura may be associated with tiny areas of stroke-like brain damage caused by a short-term drop in oxygen levels (associated with the CSD) which prevents normal cell function and swelling in the brain’s nerve cells. Animal studies have shown that CSD also irritates the trigeminal nerve, causing it to transmit pain signals and trigger inflammation in the membranes that surround the brain. CSD inhibiting drugs such as tonabersat are being tested in clinical trials for their usefulness in treating migraine and other neurological diseases. Other investigators hope to build on initial results showing that estrogen withdrawal makes it easier for CSD to occur in the brains of animals, which may explain the contribution of estrogen fluctuation to menstrual migraines. This research may result in a better understanding of how a migraine starts in the brain and offer new methods of treatment by interrupting this process and preventing the migraine.

Cutaneous allodynia is the feeling of pain or unpleasant sensations in response to normally nonpainful stimuli, such as light touch. Researchers are investigating why it is present on the head or face in people with cluster headaches, to better understand neurological changes that occur with these headaches. Similar research is looking at why some people with migraines have more than the typically restricted allodynia that affects a particular area of the head predicted by the headache (for example, on the same side of the face as the migraine pain). Individuals with extended allodynia may experience unpleasant sensations on the side of the face opposite the headache pain or even on their feet. Previous studies have shown that sensitized nociceptors in the brain’s coverings are involved in the throbbing pain of migraine and that other sensitized neurons found deeper in the brain are involved with restricted allodynia, but it is not certain which cells are responsible for extended allodynia. Future studies will explore whether nerve cells in the thalamus (which is involved in relaying signals between the brain and the body) become more sensitive a result of headache pain and cause extended allodynia. Findings may offer a better understanding of how the nervous system changes and becomes more sensitive after repeated stimulation, resulting in chronic pain.

Social and other factors may impact headaches. Researchers are examining how race and psychiatric conditions are related to headache severity, quality of life, the ability to reliably follow a treatment program, and treatment response in people with migraines, tension-type headache, substance abuse headache, or cluster headache.

Genetics of headache

Genetics may contribute to a predisposition for migraines. Most migraine sufferers have a family member with migraine. Researchers are studying the activity of different genes to see if they make some people more likely to have migraines. One strategy is to test for a gene in several families having members with migraines and then determine if the gene is related to migraine in a broader population.

In April 2008, researchers at the University of Helsinki reported significant evidence for linkage between a gene variant on a specific site on chromosome 10q22-q23 and susceptibility to common types of migraine. The findings were from a study of 1,675 migraine sufferers or their close relatives from 210 Finnish and Australian migraine families. Another study replicated the findings in the two populations and also showed that the site was particularly linked to female migraine sufferers. Although it has been known for some time that genetic factors shared by family members make people more susceptible to migraines, this study is the first to identify convincingly a specific gene locus for common forms of migraine.

Currently under investigation are gene expression patterns (signs of changes in gene activity) in the blood of individuals during migraine attacks and among individuals with chronic daily headaches. Preliminary studies show that children with acute migraines and chronic daily headaches have specific similar gene expression profiles in their blood that are different from healthy individuals and from children with other non-related neurological diseases. Researchers are exploring differences in gene expression profiles among individuals who respond to different types of headache drugs. Study results may indicate a molecular genomic approach using blood samples to detect genes that may be activated during headaches and identify which drugs are best used for each person with migraines.

Scientists are exploring the role of the calcitonin gene-related peptide (CGRP) in migraines. Levels of the CGRP molecule, which is involved in sending signals between neurons, increase during migraine attacks and revert to normal when the pain resolves. Researchers plan to use CGRP as a model and then to use functional magnetic resonance imaging to estimate the pain response in the central nervous system. Evidence from individuals with Familial Hemiplegic Migraine (FHM) with known mutations indicates that migraine pathways in FHM may be different from normal migraine. Investigators are also measuring levels of CGRP during the premonitory, mild, moderate, and severe phases of a single migraine compared to the baseline level when individuals are pain-free. The fluctuations of CGRP during the migraine process will help to define its role in migraine pain and may offer new opportunities for acute treatment.

Clinical studies in headache management

A major focus of headache research is the development of new drugs and other treatment options. Several drug studies seek to identify new drugs to treat various headache disorders and to find safer, more effective doses for medications already being used. Other research is aimed at identifying receptors or drug targets to stop the process of migraine aura in the brain.

Results of three randomized, placebo-controlled clinical trials show the drug topiramate is effective, safe, and generally well-tolerated for treating chronic migraine. Experts agree that treatment with combinations of preventive agents offers maximum relief for the majority of individuals with chronic migraines. An NINDS-funded clinical trial is examining the effectiveness and safety of the drug propranolol combined with topiramate in reducing the frequency of chronic migraine in 250 participants who will be randomly selected to receive treatment with both drugs or topiramate and placebo.

Sleep plays an important role in migraine. Migraine in older adults is sometimes triggered by sleep changes; regulating their sleep may lessen the frequency of migraines. Younger migraine sufferers often report migraine relief after sleep. Researchers are studying the use of the drug ramelteon, which is approved by the U.S. Food and Drug Administration for insomnia, in reducing the number of migraines over a 12-week period.

Headache is the most common symptom after a closed head injury, and it can last for more than 2 months in 60 percent of affected individuals. Unfortunately, individuals with chronic post-traumatic headaches also have cognitive and behavioral problems, and many drugs currently used to treat the headaches also have a negative influence on cognition. Scientists are testing different drugs, such as naratriptan (which acts as a neurotransmitter) and galantamine (used to treat Alzheimer’s disease), to treat both headache and cognitive disturbances in individuals with chronic post-traumatic headaches.

Non-pharmaceutical approaches to treatment and prevention

Historically, very little research has been done on children with headaches. A variety of headache education and drug and/or behavioral management techniques are aimed at improving headache treatment and prevention in children and adolescents. Scientists are testing the effectiveness of combined pain coping skills (including age-appropriate biofeedback, muscle relaxation techniques, imagery, activity pacing, and the use of calming techniques) and the drug amitriptyline in reducing headache frequency, intensity, and depressive symptoms in youth ages 10 to 17 years. Additional studies include the use of alternative approaches such as yoga to decrease headaches in adolescents, a modified diet to treat chronic daily headaches in teenagers, and programs designed to teach very young children how to understand and self-manage their headaches.


Craniosacral therapy (CST) involves gentle massaging of the neck, head, and spine to release constraints in tissue in the head and around the spine. Limited preliminary data shows significant, the sustained benefit of CST in a small group of individuals with migraines. Future research will gather data on the usefulness of CST in preventing migraines and examine the feasibility of a larger, randomized trial.

Electrical stimulation of the occipital nerve has effectively eased the symptoms of painful chronic headache conditions such as cluster headache as well as hard-to-treat migraine in small clinical studies. A tiny battery-powered rechargeable electrode, surgically implanted near the occipital nerve, sends continuous energy pulses to the nerve to ease pain. The use of this non-drug treatment in reducing migraine frequency, intensity, and effect on the quality of life is being tested in larger clinical trials.

References

Chronic Headaches – Causes, Symptoms, Treatment

Chronic headaches are headaches that occur for at least 15 days of a month for at least three months. There are a variety of causes and ways to manage this condition. This activity reviews the evaluation and treatment of chronic headache, and explains the role of the interprofessional team in evaluating, treating, managing, and improving care for patients with this condition.

Chronic headache is not a single disease entity but an umbrella term that encompasses all chronic headaches. The International Headache Society defines chronic daily headaches (CDH) as “15 or more headache episodes per month for at least 3 months.” Chronic headaches are not included as an official class in the International Classification of Headache Disorders (ICHD).

A chronic daily headache can be divided into primary and secondary headache disorders depending upon its etiology. Primary chronic headache disorders do not have secondary organic etiology. Within the primary headache categories, a headache duration of fewer than 4 hours is labeled as a ‘short headache,’ and more than 4 hours is known as a ‘long headache.’ Long headache is more commonly include chronic migraine and chronic tension headaches. Secondary headaches can occur due to secondary causes such as medication overuse, intracranial tumors, central nervous system (CNS) infections, raised intracranial pressure, metabolic abnormalities, post-traumatic, vascular, and structural pathologies. It is important to realize that chronic headaches are often caused by a multifactorial combination of the above-mentioned causes and can occur along a continuum.

Causes of Chronic Headaches

The International Classification of Headache Disorders (ICHD) recognizes over 200 headache disorders and divides them into three groups, which are primary, secondary, and painful cranial neuropathies. The ICHD system is hierarchical with multiple subtypes within each main headache type.

All chronic headaches meet the criteria of occurring at least 15 times a month for at least 3 months, but both primary and secondary chronic headaches have unique characteristics.

Primary headaches lasting greater than four hours include chronic migraines, tension headaches, new daily persistent headaches, and hemicrania continua.

  • Chronic migraine has typical migraine features of being unilateral, pulsatile, and moderate to severe and may or may not have an aura. Episodic migraines may evolve into chronic migraines.
  • Chronic migraine in children and adolescents is often bilateral, and associated symptoms such as photophobia and phonophobia are often inferred from behavior.
  • Chronic headaches, which are bilateral, non-pulsatile, and lack associated symptoms, are classified as chronic tension headaches. Pericranial tenderness is often found on palpation.
  • New persistent daily headache (NDPH) occurs suddenly and becomes unremitting within 24 hours of onset. Patients typically have no prior history of headaches. NDPH is rare and refractory to treatment.
  • Hemicrania continua is unilateral, has autonomic symptoms, and is continuous with exacerbations. Responsiveness to indomethacin helps distinguish this form of headache.

Primary headaches lasting less than four hours include chronic cluster headache, neuralgiform headache attacks, and primary stabbing headache.

  • Chronic cluster headache varies from the acute form in that there are no remissions, and headaches must occur over at least one year. Headaches are unilateral in the trigeminal distribution and associated with unilateral autonomic symptoms. Patients often experience agitation during the headache.
  • The short-lasting neuralgiform headaches include short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). Both types have severe, unilateral pain associated with autonomic symptoms. SUNCT has both lacrimation and conjunctival injection. SUNA may have either but not both of those features and may be accompanied by rhinorrhea or nasal congestion.
  • Primary stabbing headaches may frequently occur throughout the day. Sharp, sudden, jabbing pain occurs in the temporal or peri-orbital regions.

Secondary chronic daily headaches include medication overuse, CNS infection, CNS hematomas, intracranial tumor, raised intracranial pressure, low-pressure headache, vasculitis, aneurysms, and cerebrospinal fluid (CSF) leak.

  • Chronic medication overuse headaches often overlap with other acute and chronic headache types. Analgesics are widely used for symptom control in migraine and tension headaches. Patients inadvertently increase headache frequency by overuse of analgesics. The ICHD further classifies this disorder based on the medications used, including NSAIDs, triptans, ergotamines, non-opioid, and opioid analgesics. Withdrawl of analgesics typically worsens these headaches.
  • The remainder of the secondary chronic headache etiologies is beyond the scope of this article.

Diagnosis of Chronic Headaches

A thorough history and physical exam are indispensable in the diagnosis of chronic daily headaches. As noted above, a chronic headache should have 15 or more episodes per month for at least 3 months. One should determine the frequency, intensity, characteristics of the pain, as well as the aggravating and alleviating factors. Many headache types involve ipsilateral autonomic symptoms such as lacrimation, conjunctival injection, conjunctival edema, ptosis, miosis, nasal congestion, rhinorrhea, etc.

A thorough medication reconciliation, including over-the-counter analgesics, is essential. Patients with medication-overuse headaches often have a primary headache disorder, and they frequently use pain medications. Medication classes may include non-steroidal anti-inflammatory drugs (NSAIDs), triptans, ergotamines, opioids, or a combination of multiple analgesics. Key historical features include morning headaches, the onset of headaches when medication is delayed, and relief when medication is taken.

Comorbidities, sleep history, and family history of headaches should also be noted. A secondary headache disorder should be excluded from the history and examination.

Recognition of headache “red flags” is a critical piece in identifying secondary headaches and ordering additional diagnostic testing. Those “red flags” include:

  • Age above 50
  • Significant change in prior headache pattern
  • Severe, “thunderclap” headache
  • Systemic illness signs such as fever
  • Known illness which increases the risk for secondary headaches such as cancer or HIV
  • Neurologic symptoms
  • Headaches associated with Valsalva maneuvers

Physical exam findings concerning secondary headache causes include focal neurological deficits, papilledema, bitemporal hemianopia, homonymous hemianopia, decrease visual acuity or increased pain with the Valsalva method.

Primary chronic headaches often lack physical findings but may have autonomic activation or muscle tenderness in the occipital or cervical regions.

Evaluation

In a straightforward chronic primary headache disorder, further evaluation may not be warranted, but many clinicians will advise for baseline laboratory testing and brain imaging to exclude the secondary treatable causes.

Laboratory workup includes a complete blood count to look for infection. Erythrocyte sedimentation rate (ESR) is increased in giant cell arteritis and other vasculitides. A metabolic panel to look for metabolic causes of headache, and endocrine testings to look for pituitary gland abnormalities.

Magnetic resonance imaging (MRI) of the brain is the imaging modality of choice. A contrast study is often recommended to increase the sensitivity and specificity to detect structural abnormalities. A need for vascular imaging is based on the differential diagnosis. Further studies may be warranted depending upon the underlying cause. These may include positron emission tomography (PET) scan, magnetic resonance spectroscopy (MRS), and/or biopsy. A lumbar puncture may be required if there is suspicion of a CNS infection or idiopathic intracranial hypertension.

Treatment of Chronic Headaches

Treatment and management of chronic headache disorders depend upon the underlying etiology and may require an interprofessional approach.

A patient should maintain a headache journal that will document their headache episodes and any accompanying triggers. If found, stressors should be avoided or minimized.

Chronic Migraine

  • Chronic migraine treatment should begin with setting the expectation that headache frequency and severity will decrease, but headaches will not be eliminated.
  • The patient should be counseled that high caffeine intake, sleep deprivation, overuse of analgesics, and comorbid conditions can worsen chronic migraines.
  • Prophylactic pharmacologic treatment should be used. First-line therapy includes beta-blockers, anticonvulsants, and antidepressants. The most commonly used medications are propranolol, topiramate, and amitriptyline.
  • Botulinum toxin A is a Food and Drug Administration (FDA) approved treatment for chronic migraines and is considered second-line therapy.
  • Monoclonal antibodies that target calcitonin gene-related peptides (CGRP) are the newest development in chronic migraine treatment. Erenumab, fremanezumab, and galcanezumab are approved for chronic migraines, which have failed to respond to other treatments.
  • Triptans, steroids, NSAIDs, and opioids are often used to abort acute episodes, but routine use of these medications increases the risk of developing a medication-overuse headache.
  • Patients may also benefit from psychological counseling if anxiety or depression is present.
  • Manual medicine, such as spinal manipulation and trigger point treatment, may be used as a complementary or alternative therapy.
  • In drug-resistant cases, invasive procedures such as sphenopalatine ganglion blockade and occipital nerve blockade may be tried with variable results. Deep brain stimulation (DBS) is also used in some treatment-resistant cases.

Chronic Tension Headache

  • Amitriptyline, a tricyclic antidepressant, is recommended as the first-line treatment for chronic tension headaches.
  • Amitriptyline, in addition to inhibiting the reuptake of serotonin and noradrenaline, also reduces tenderness in pericranial muscles.
  • Tricyclic antidepressants increase the risk for cardiac arrhythmia, and patients should be screened for cardiovascular disorders prior to initiating therapy. Patients over 40 should undergo an ECG.
  • Anticonvulsants, such as topiramate and gabapentin, can be considered as second-line treatment.
  • Addressing the potential musculoskeletal causes of tension headache, treatment with physical therapy, acupuncture, trigger point injections, spinal manipulation, or muscle relaxants may be beneficial.
  • Behavioral therapy, including cognitive-behavioral therapy, biofeedback, and relaxation techniques, is particularly helpful for patients with coexisting anxiety or depression.

Medication Overuse Headache

  • Patient education about the potential for overuse of analgesic medication to lead to headache progression is key. Include the use of over-the-counter analgesics in the discussion.
  • The physician initiates a preventative medication while simultaneously assisting the patient in discontinuing the causative medication.
  • Patients may experience withdrawal symptoms of nausea and anxiety for 2 to 10 days when the analgesic medication is discontinued.
  • There is no consensus on the most appropriate medication for use as bridge therapy following discontinuation of the offending drug. Long-acting NSAIDs, prednisone, dihydroergotamine, and antiemetics are options. The medication should not be from the same class as the offending medication.
  • Medications that may be effective for prophylaxis include topiramate, amitryptiline, valproic acid, and beta-blockers. The choice of medication should be based upon comorbidities and the primary headache disorder.

Chronic Autonomic Cephalgia

  • Indomethacin is the drug of choice for paroxysmal hemicrania, hemicrania continua, primary stabbing headache, hypnic headache, and Valsalva-induced headaches (e.g., cough headache, exercise headache).
  • Verapamil is the drug of choice for the prevention of chronic cluster headaches. Verapamil requires titration to become effective, and glucocorticoids or dihydroergotamine can be used for exacerbations.
  • Chronic cluster headaches not responsive to pharmacologic therapy can be treated with a non-invasive vagus nerve stimulator or sphenopalatine ganglion microstimulator.
  • First-line prophylactic therapy for chronic SUNCT and SUNA is lamotrigine. Topiramate and gabapentin are alternatives.

Alternative treatment

  • Changes in lifestyle; must be a commitment from the patient; however, social support is of great importance to improve mental health to help the patient’s involvement.
  • Regular exercise
  • Yoga
  • Relaxation training
  • Cognitive-behavioral therapy
  • Biofeedback
  • Reduction of triggers
  • Detoxification
  • Butterbur
  • Melatonin


Children and Headache

Headaches are common in children. Headaches that begin early in life can develop into migraines as the child grows older. Migraines in children or adolescents can develop into tension-type headaches at any time. In contrast to adults with migraines, young children often feel migraine pain on both sides of the head and have headaches that usually last less than 2 hours. Children may look pale and appear restless or irritable before and during an attack. Other children may become nauseous, lose their appetite, or feel pain elsewhere in the body during the headache.

Headaches in children can be caused by a number of triggers, including emotional problems such as the tension between family members, stress from school activities, weather changes, irregular eating and sleep, dehydration, and certain foods and drinks. Of special concern among children are headaches that occur after a head injury or those accompanied by rash, fever, or sleepiness.

It may be difficult to identify the type of headache because children often have problems describing where it hurts, how often the headaches occur, and how long they last. Asking a child with a headache to draw a picture of where the pain is and how it feels can make it easier for the doctor to determine the proper treatment.

Migraine in particular is often misdiagnosed in children. Parents and caretakers sometimes have to be detectives to help determine that a child has a migraine. Clues to watch for include sensitivity to light and noise, which may be suspected when a child refuses to watch television or use the computer, or when the child stops playing to lie down in a dark room. Observe whether or not a child is able to eat during a headache. Very young children may seem cranky or irritable and complain of abdominal pain (abdominal migraine).

Headache treatment in children and teens usually includes rest, fluids, and over-the-counter pain relief medicines. Always consult with a physician before giving headache medicines to a child. Most tension-type headaches in children can be treated with over-the-counter medicines that are marked for children with usage guidelines based on the child’s age and weight. Headaches in some children may also be treated effectively using relaxation/behavioral therapy. Children with cluster headaches may be treated with oxygen therapy early in the initial phase of the attacks.

Headache and Sleep Disorders

Headaches are often a secondary symptom of a sleep disorder. For example, tension-type headache is regularly seen in persons with insomnia or sleep-wake cycle disorders. Nearly three-fourths of individuals who suffer from narcolepsy complain of either migraine or cluster headache. Migraines and cluster headaches appear to be related to the number of and transition between rapid eye movement (REM) and other sleep periods an individual has during sleep. Hypnic headache awakens individuals mainly at night but may also interrupt daytime naps. Reduced oxygen levels in people with sleep apnea may trigger early morning headaches.

Getting the proper amount of sleep can ease headache pain. Generally, too little or too much sleep can worsen headaches, as can the overuse of sleep medicines. Daytime naps often reduce deep sleep at night and can produce headaches in some adults. Some sleep disorders and secondary headaches are treated using antidepressants. Check with a doctor before using over-the-counter medicines to ease sleep-associated headaches.

Coping with Headache

Headache treatment is a partnership between you and your doctor, and honest communication is essential. Finding a quick fix to your headache may not be possible. It may take some time for your doctor or specialist to determine the best course of treatment. Avoid using over-the-counter medicines more than twice a week, as they may actually worsen headache pain and the frequency of attacks. Visit a local headache support group meeting (if available) to learn how others with headaches cope with their pain and discomfort. Relax whenever possible to ease stress and related symptoms, get enough sleep, regularly perform aerobic exercises, and eat a regularly scheduled and healthy diet that avoids food triggers. Gaining more control over your headache, stress, and emotions will make you feel better and let you embrace daily activities as much as possible.

What Research is Being Done?

Several studies either conducted or supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, are revealing much about the headache process and may lead to new treatments or perhaps ways to block debilitating headache pain. Studies by other investigators are adding insight to headache etiology and treatment.

Understanding headache mechanisms and underlying causes

The molecular basis for migraine headaches and the aura associated with certain migraines is uncertain. One multi-faceted research study is examining how migraine with aura may affect metabolism and neurophysiological function. Investigators are also studying if particular regions of the visual cortex are unusually susceptible to the events in the brain that cause the aura. Another study component is investigating what happens at the beginning of a headache and how changes in the brain’s meninges may lead to vascular and trigeminal nerve stimulation associated with the painful part of a migraine headache. Results may provide a greater understanding of migraine and assist the development of new therapies.

Mast cells, which are part of the immune system and are involved in the inflammatory allergic response, are activated in some chronic pain conditions, including headache. Researchers are examining the possibility of a relationship between the mast cells’ anti-analgesic properties and their proximity to and enhanced activation of nerve fiber endings that receive and transmit pain signals (nociceptors). Mast cells may release substances that activate nociceptive nerve cells that transmit signals from the linings of the skull and its blood vessels. Findings that link mast cell activation to headache pain may identify drug targets that could lead to new analgesics for headache and other pain syndromes.

Cortical spreading depression (CSD) is a process in migraine with aura in which a wave of increased brain activity, followed by decreased activity, slowly spreads along the brain’s surface. The wave of brain activity often travels across the part of the brain that processes vision and corresponds to the typical visual aura of migraine. Research has shown that migraines with aura may be associated with tiny areas of stroke-like brain damage caused by a short-term drop in oxygen levels (associated with the CSD) which prevents normal cell function and swelling in the brain’s nerve cells. Animal studies have shown that CSD also irritates the trigeminal nerve, causing it to transmit pain signals and trigger inflammation in the membranes that surround the brain. CSD inhibiting drugs such as tonabersat are being tested in clinical trials for their usefulness in treating migraine and other neurological diseases. Other investigators hope to build on initial results showing that estrogen withdrawal makes it easier for CSD to occur in the brains of animals, which may explain the contribution of estrogen fluctuation to menstrual migraines. This research may result in a better understanding of how a migraine starts in the brain and offer new methods of treatment by interrupting this process and preventing the migraine.

Cutaneous allodynia is the feeling of pain or unpleasant sensations in response to normally nonpainful stimuli, such as light touch. Researchers are investigating why it is present on the head or face in people with cluster headaches, to better understand neurological changes that occur with these headaches. Similar research is looking at why some people with migraines have more than the typically restricted allodynia that affects a particular area of the head predicted by the headache (for example, on the same side of the face as the migraine pain). Individuals with extended allodynia may experience unpleasant sensations on the side of the face opposite the headache pain or even on their feet. Previous studies have shown that sensitized nociceptors in the brain’s coverings are involved in the throbbing pain of migraine and that other sensitized neurons found deeper in the brain are involved with restricted allodynia, but it is not certain which cells are responsible for extended allodynia. Future studies will explore whether nerve cells in the thalamus (which is involved in relaying signals between the brain and the body) become more sensitive a result of headache pain and cause extended allodynia. Findings may offer a better understanding of how the nervous system changes and becomes more sensitive after repeated stimulation, resulting in chronic pain.

Social and other factors may impact headaches. Researchers are examining how race and psychiatric conditions are related to headache severity, quality of life, the ability to reliably follow a treatment program, and treatment response in people with migraines, tension-type headache, substance abuse headache, or cluster headache.

Genetics of headache

Genetics may contribute to a predisposition for migraines. Most migraine sufferers have a family member with migraine. Researchers are studying the activity of different genes to see if they make some people more likely to have migraines. One strategy is to test for a gene in several families having members with migraines and then determine if the gene is related to migraine in a broader population.

In April 2008, researchers at the University of Helsinki reported significant evidence for linkage between a gene variant on a specific site on chromosome 10q22-q23 and susceptibility to common types of migraine. The findings were from a study of 1,675 migraine sufferers or their close relatives from 210 Finnish and Australian migraine families. Another study replicated the findings in the two populations and also showed that the site was particularly linked to female migraine sufferers. Although it has been known for some time that genetic factors shared by family members make people more susceptible to migraines, this study is the first to identify convincingly a specific gene locus for common forms of migraine.

Currently under investigation are gene expression patterns (signs of changes in gene activity) in the blood of individuals during migraine attacks and among individuals with chronic daily headaches. Preliminary studies show that children with acute migraines and chronic daily headaches have specific similar gene expression profiles in their blood that are different from healthy individuals and from children with other non-related neurological diseases. Researchers are exploring differences in gene expression profiles among individuals who respond to different types of headache drugs. Study results may indicate a molecular genomic approach using blood samples to detect genes that may be activated during headaches and identify which drugs are best used for each person with migraines.

Scientists are exploring the role of the calcitonin gene-related peptide (CGRP) in migraines. Levels of the CGRP molecule, which is involved in sending signals between neurons, increase during migraine attacks and revert to normal when the pain resolves. Researchers plan to use CGRP as a model and then to use functional magnetic resonance imaging to estimate the pain response in the central nervous system. Evidence from individuals with Familial Hemiplegic Migraine (FHM) with known mutations indicates that migraine pathways in FHM may be different from normal migraine. Investigators are also measuring levels of CGRP during the premonitory, mild, moderate, and severe phases of a single migraine compared to the baseline level when individuals are pain-free. The fluctuations of CGRP during the migraine process will help to define its role in migraine pain and may offer new opportunities for acute treatment.

Clinical studies in headache management

A major focus of headache research is the development of new drugs and other treatment options. Several drug studies seek to identify new drugs to treat various headache disorders and to find safer, more effective doses for medications already being used. Other research is aimed at identifying receptors or drug targets to stop the process of migraine aura in the brain.

Results of three randomized, placebo-controlled clinical trials show the drug topiramate is effective, safe, and generally well-tolerated for treating chronic migraine. Experts agree that treatment with combinations of preventive agents offers maximum relief for the majority of individuals with chronic migraines. An NINDS-funded clinical trial is examining the effectiveness and safety of the drug propranolol combined with topiramate in reducing the frequency of chronic migraine in 250 participants who will be randomly selected to receive treatment with both drugs or topiramate and placebo.

Sleep plays an important role in migraine. Migraine in older adults is sometimes triggered by sleep changes; regulating their sleep may lessen the frequency of migraines. Younger migraine sufferers often report migraine relief after sleep. Researchers are studying the use of the drug ramelteon, which is approved by the U.S. Food and Drug Administration for insomnia, in reducing the number of migraines over a 12-week period.

Headache is the most common symptom after a closed head injury, and it can last for more than 2 months in 60 percent of affected individuals. Unfortunately, individuals with chronic post-traumatic headaches also have cognitive and behavioral problems, and many drugs currently used to treat the headaches also have a negative influence on cognition. Scientists are testing different drugs, such as naratriptan (which acts as a neurotransmitter) and galantamine (used to treat Alzheimer’s disease), to treat both headache and cognitive disturbances in individuals with chronic post-traumatic headaches.

Non-pharmaceutical approaches to treatment and prevention

Historically, very little research has been done on children with headaches. A variety of headache education and drug and/or behavioral management techniques are aimed at improving headache treatment and prevention in children and adolescents. Scientists are testing the effectiveness of combined pain coping skills (including age-appropriate biofeedback, muscle relaxation techniques, imagery, activity pacing, and the use of calming techniques) and the drug amitriptyline in reducing headache frequency, intensity, and depressive symptoms in youth ages 10 to 17 years. Additional studies include the use of alternative approaches such as yoga to decrease headaches in adolescents, a modified diet to treat chronic daily headaches in teenagers, and programs designed to teach very young children how to understand and self-manage their headaches.


Craniosacral therapy (CST) involves gentle massaging of the neck, head, and spine to release constraints in tissue in the head and around the spine. Limited preliminary data shows significant, the sustained benefit of CST in a small group of individuals with migraines. Future research will gather data on the usefulness of CST in preventing migraines and examine the feasibility of a larger, randomized trial.

Electrical stimulation of the occipital nerve has effectively eased the symptoms of painful chronic headache conditions such as cluster headache as well as hard-to-treat migraine in small clinical studies. A tiny battery-powered rechargeable electrode, surgically implanted near the occipital nerve, sends continuous energy pulses to the nerve to ease pain. The use of this non-drug treatment in reducing migraine frequency, intensity, and effect on the quality of life is being tested in larger clinical trials.

References

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