Category Archive Health A – Z

Weakness or asthenia is a symptom of a number of different conditions.The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular junction disorders, such as myasthenia gravis.

Spinal Cord Anatomy

Dorsal Column – Medial Lemniscus (fine touch, proprioception)

• Afferent sensory fibers with cell body in DRG
• Ascend in ipsilateral posterior column
• Synapse in medulla, decussate, ascend in contralateral medial lemniscus
• Synapse in thalamus (VPL)
• Synapse in sensory strip of post-central gyrus

Spinothalamic Tract (pain, temperature)

• Afferent sensory fibers with cell body in DRG
• Ascends 1-2 levels
• Synapse in ipsilateral spinal cord, decussate, ascend in contralateral lateral spinothalamic tract\
• Synapse in thalamus (VPL)
• Synapse in sensory strip of post-central gyrus

Lateral Corticospinal Tract (motor)

• Efferent cell body in motor strip of pre-central gyrus
• Descends through internal capsule
• Decussates in pyramid of medulla, descends in contralateral lateral corticospinal tract
• Synapse in anterior horn, lower motor neuron to muscle fiber

Types

Muscle fatigue can be central, neuromuscular, or peripheral muscular. Central muscle fatigue manifests as an overall sense of energy deprivation, and peripheral muscle weakness manifests as a local, muscle-specific inability to do work. Neuromuscular fatigue can be either central or peripheral.

Central weakness

The central fatigue is generally described in terms of a reduction in the neural drive or nerve-based motor command to working muscles that results in a decline in the force output.It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if the work was continued at the same intensity.The exact mechanisms of central fatigue are unknown, though there has been a great deal of interest in the role of serotonergic pathways.

Neuromuscular weakness

Nerves control the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiences synaptic fatigue it becomes unable to stimulate the muscle that it innervates. Most movements require a force far below what a muscle could potentially generate, and barring pathology, neuromuscular fatigue is seldom an issue

Peripheral muscle weakness

Peripheral muscle fatigue during physical work is considered an inability for the body to supply sufficient energy or other metabolites to the contracting muscles to meet the increased energy demand. This is the most common case of physical fatigue—affecting a national average of 72% of adults in the work force in 2002. This causes contractile dysfunction that manifests in the eventual reduction or lack of ability of a single muscle or local group of muscles to do work.

Weakness may be all over the body or in only one area. Weakness is more noticeable when it is in one area. Weakness in one area may occur:

• After a stroke
• After injury to a nerve
• During a flare-up of multiple sclerosis (MS)

Weakness may be caused by diseases or conditions affecting many different body systems, such as the following:

METABOLIC

• Adrenal glands not producing enough hormones (Addison disease)
• Parathyroid glands producing too much parathyroid hormone (hyperparathyroidism)
• Low sodium or potassium
• Overactive thyroid (thyrotoxicosis)

BRAIN/NERVOUS SYSTEM (NEUROLOGIC)

• Disease of the nerve cells in the brain and spinal cord (amyotrophic lateral sclerosis; ALS)
• Weakness of the muscles of the face (Bell palsy)
• Group of disorders involving brain and nervous system functions (cerebral palsy)
• Nerve inflammation causing muscle weakness (Guillain-Barre syndrome)
• Multiple sclerosis
• Pinched nerve (for example, caused by a slipped disk in the spine)
• Stroke

MUSCLE DISEASES

• Becker muscular dystrophy
• Dermatomyositis
• Muscular dystrophy (Duchenne)
• Myotonic dystrophy

POISONING

• Botulism
• Poisoning (insecticides, nerve gas)
• Shellfish poisoning

OTHERS

• Not enough healthy red blood cells (anemia)
• Disorder of the muscles and nerves that control them (myasthenia gravis)
• Polio
• Electrolyte Imbalances
• Malignant Tumors
• Malnutrition
• Muscle Disease Medications
• Muscular Dystrophy
• Myotonic Dystrophy
• Nerve Impingement
• Poisoning (Organophosphates)
• Poliomyelitis
• Thyrotoxicosis
• Trauma

 Symptoms 

• Slow or delayed movement in performing specific task.
• Muscle cramps
• Episodes of tremors or shaking while doing any task.
• Muscle twitching.
• Fever may be a common sign of asthenia affecting whole body.
• Tiredness, loss or reduced energy is a common sign and symptom of asthenia.
• Physical discomfort, loss or absence of muscle strength is also a symptom of asthenia.
• Inability to finish a task or a movement.
• Change in mental state or sometimes confusion.
• Sudden change or reduced vision
• Sudden loss of consciousness
• Difficulty in speech, difficulty swallowing etc.

Weakness over all syndromes 

Unilateral weakness, ipsilateral face

• Lesion: Contralateral cortex, internal capsule
• Causes: Stroke (sudden onset), demyelination/mass (gradual onset)
• Symptoms: Neglect, visual field cut, aphasia
• Findings: UMN signs
• Key features: Association with headache suggests hemorrhage or mass

Unilateral weakness, contralateral face

• Lesion: Brainstem
• Causes: Vertebrobasilar insufficiency, demyelination
• Symptoms: Dysphagia, dysarthria, diplopia, vertigo, nausea/vomiting
• Findings: CN involvement, cerebellar abnormalities

Unilateral weakness, no facial involvement

• Lesion: Contralateral medial cerebral cortex, discrete internal capsule
• Causes: Stroke
• Rare Cause: Brown-Sequard if contralateral hemibody pain and temperature sensory disturbance

Unilateral weakness single limb (monoparesis/plegia)

• Lesion: Spinal cord, peripheral nerve, NMJ
• UMN signs: Brown-Sequard if contralateral pain and temperature sensory disturbance
• LMN signs: Radiculopathy if associated sensory disturbance
• Normal reflexes, normal sensation: Consider NMJ disorder

Bilateral weakness of lower extremities (paraparesis/plegia)

• Lesion: Spinal cord, peripheral nerve
• UMN signs: Anterior cord syndrome (compression, ischemia, demyelination) if contralateral pain and temperature sensory disturbance
• Cauda equina: Loss of perianal sensation, loss of rectal tone, or urinary retentionGBS: If no signs of cauda equina and sensory disturbances paralleling ascending weakness (with hyporeflexia)

Bilateral weakness of upper extremities

• Lesion: Central cord syndrome
• Causes: Syringomyelia, hyperextension injury
• Findings: Pain and temperature sensory disturbances in upper extremities (intact proprioception)

Bilateral weakness of all four extremities (quadriparesis/plegia)

• Lesion: Cervical spinal cord
• Findings: UMN signs below level of injury, strength/sensory testing identifies level

Bilateral weakness, proximal groups

• Lesion: Muscle
• Causes: Rhabdomyolysis, polymyositis, dermatomyositis, myopathies
• Findings: Muscle tenderness to palpation, no UMN signs, no sensory disturbances

Facial weakness, upper and lower face

• Lesion: CNVII
• Causes: Bell’s palsy, mastoiditis, parotitis
• Other CN involvement suggests brainstem lesion, multiple cranial neuropathies, or NMJ.

Migraine is a primary headache disorder characterized by recurrent headaches that are moderate to severe. Typically, the headaches affect one half of the head, are pulsating in nature, and last from two to 72 hours. Associated symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell.

Types of Migraine

There are several types of migraine, including

• Migraine with aura – where there are specific warning signs just before a migraine begins, such as seeing flashing lights
• A migraine without aura – the most common type, where a migraine occurs without the specific warning signs
• Migraine aura without a headache, also known as a silent migraine – where an aura or other migraine symptoms are experienced, but a headache doesn’t develop.
• Lower-half Headache or a Facial Migraine – The term applies to a common migraine that covers one-half of the face involving the nostril, cheek, and jaw.
• Migraine Aura without a Headache – Where the headache of a migraine with aura may become less severe over the years or may not occur at all, the attacks are referred to as migraine aura without a headache.  It is rare for attacks to have always occurred without a headache and a doctor should be consulted if this develops for the first time when over 50.
• Status Migrainosus – This term describes a migraine that may last longer than 72 hours.  Symptoms of nausea and light sensitivity resolve after a couple of days but a headache persists.
• An abdominal Migraine (recurrent stomach pains in childhood) – Symptoms are periodic abdominal pains (experienced by about 20% of migrainous children compared with about 4% of children who do not suffer from a headache).
• A symptom of basilar artery migraine -Symptoms include visual disturbances, giddiness, loss of balance, slurred speech followed by aching mainly in the back of the head.  Fainting can occur at the height of the attack.
• A hemiplegic Migraine (with weakness on one side of the body) – Symptoms resemble a stroke and may progress until the arm and leg on one side are completely paralyzed for a few hours.  Repeated attacks may leave a residual weakness.  Familial hemiplegic migraine occurs where there is a family history of a hemiplegic migraine.
• An ophthalmoplegic Migraine (with double vision) – Symptom is paralysis of one or more of the muscles moving the eyes resulting in the eyes moving out of alignment and the person seeing double.
• A retinal Migraine (with loss of vision in one eye) – Symptom is a loss of sight in one eye and normal vision in the other.  The sight clears leaving an ache behind the eye or a generalized headache.
• Migrainous Infarction – Symptoms range from permanent blind spots to a full stroke occurring during a typical migraine attack.  An infarct is the death of tissue due to an inadequate blood supply.

Causes of Migraine

Migraines may be caused by changes in the brainstem and its interactions with the trigeminal nerve, a major pain pathway.

Imbalances in brain chemicals — including serotonin, which helps regulate pain in your nervous system — also may be involved. Researchers are still studying the role of serotonin in migraines.

Serotonin levels drop during migraine attacks – This may cause your trigeminal nerve to release substances called neuropeptides, which travel to your brain’s outer covering (meninges). The result is migraine pain. Other neurotransmitters play a role in the pain of a migraine, including calcitonin gene-related peptide (CGRP).

A number of factors may trigger migraines, including

• Hormonal changes in women – Fluctuations in estrogen seem to trigger headaches in many women. Women with a history of migraines often report headaches immediately before or during their periods, when they have a major drop in estrogen. Hormonal medications, such as oral contraceptives and hormone replacement therapy, also may worsen migraines. Some women, however, find their migraines occur less often when taking these medications.
• Foods – Aged cheeses, salty foods and processed foods may trigger migraines. Skipping meals or fasting also can trigger attacks.
• Food additives – The sweetener aspartame and the preservative monosodium glutamate (MSG), found in many foods, may trigger migraines.
• Drinks – Alcohol, especially wine, and highly caffeinated beverages may trigger migraines.
• Stress – Stress at work or home can cause migraines.
• Sensory stimuli – Bright lights and sun glare can induce migraines, as can loud sounds. Strong smells — including perfume, paint thinner, secondhand smoke, and others — can trigger migraines in some people.
• Changes in the wake-sleep pattern –  Missing sleep or getting too much sleep may trigger migraines in some people, as can jet lag.
• Physical factors – Intense physical exertion, including sexual activity, may provoke migraines.
• Changes in the environment – A change of weather or barometric pressure can prompt a migraine.
• Medications – Oral contraceptives and vasodilators, such as nitroglycerin, can aggravate migraines.

Symptoms of a Migraine

Common symptoms include

Prodrome

One or two days before a migraine, you may notice subtle changes that warn of an upcoming migraine, including:

• Constipation
• Mood changes, from depression to euphoria
• Food cravings
• Neck stiffness
• Increased thirst and urination
• Frequent yawning
• Eye pain
• Sensitivity to light or sound
• Nausea ,Vomiting
• Severe pain, usually on one side of the head that some individuals describe as “pounding”
• Other types of headaches can also cause severe pain, and not all headaches are migraines. For example, some people describe the pain of cluster headaches as the worst pain they have experienced.

Aura

Aura may occur before or during migraines. Most people experience migraines without aura.Each of these symptoms usually begins gradually, builds up over several minutes and lasts for 20 to 60 minutes. Examples of migraine aura include:

• Visual phenomena, such as seeing various shapes, bright spots or flashes of light
• Vision loss
• Pins and needles sensations in an arm or leg
• Weakness or numbness in the face or one side of the body
• Difficulty speaking
• Hearing noises or music
• Uncontrollable jerking or other movements

Attack

A migraine usually lasts from four to 72 hours if untreated. The frequency with which headaches occur varies from person to person. Migraines may be rare, or strike several times a month. During a migraine, you may experience

• Pain on one side or both sides of your head
• Pain that feels throbbing or pulsing
• Sensitivity to light, sounds, and sometimes smells and touch
• Nausea and vomiting
• Blurred vision
• Lightheadedness, sometimes followed by fainting

Triggers 

Dietary Triggers

Common, well-recognised dietary triggers include:

• missed, delayed or inadequate meals
• caffeine (coffee and tea) withdrawal
• certain wines, beers and spirits
• chocolate, citrus fruits, aged cheeses and cultured products (chocolate and other sugar cravings may be prodomal not triggers)
• monosodium glutamate (MSG)
• dehydration.

Environmental Triggers

Environmental triggers include

• bright or flickering lights, bright sunlight
• strong smells, e.g. perfume, gasoline, chemicals, smoke-filled rooms, various food odours
• travel, travel-related stress, high altitude, flying
• weather changes, changes in barometric pressure (likewise, decompression after deep-sea diving)
• loud sounds
• going to the movies
• computers (overuse, incorrect use).

Hormonal Triggers

Hormonal fluctuations – are implicated as a significant trigger for women as three times as many women suffer from migraine headaches as men, this difference being most apparent during the reproductive years,.  Hormonal triggers may be

• Climacteric (final menstrual period)
• Menstruation (a UK study found 50% of women more likely to have migraine around menstruation)
• Ovulation
• Oral contraceptives
• Pregnancy (may worsen for first few months but in two thirds of women improves in latter part)
• Hormone replacement therapy (HRT)
• Menopause.

Physical and Emotional Triggers

Physical and emotional factors include

• lack of sleep or oversleeping – (even as little as half hour difference in routine, e.g. sleeping in on weekends)
• illness –  such as a viral infection or a cold (if taken cold and migraine medication, remember that many cold remedies contain pain-killers)
• back and neck pain – stiff and painful muscles, especially in scalp, jaw, neck, shoulders, and upper back
• sudden, excessive or vigorous exercise (regular exercise can however prevent migraine, if migraine is triggered by a blow to the head a doctor should be consulted)
• emotional triggers such as arguments, excitement, stress and muscle tension
• relaxation after stress (weekend headache).

Diagnosis of Migraine

The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the “5, 4, 3, 2, 1 criteria”

Five or more attacks—for migraine with aura, two attacks are sufficient for diagnosis.

Four hours to three days in duration

Two or more of the following:

• Unilateral (affecting half the head)
• Pulsating
• Moderate or severe pain intensity
• Worsened by or causing avoidance of routine physical activity

One or more of the following:

• Nausea and/or vomiting;
• Sensitivity to both light (photophobia) and sound (phonophobia)

If someone experiences two of the following

Photophobia, nausea, or inability to work or study for a day, the diagnosis is more likely. In those with four out of five of the following: pulsating headache, duration of 4–72 hours, pain on one side of the head, nausea, or symptoms that interfere with the person’s life, the probability that this is a migraine is 92%.In those with fewer than three of these symptoms the probability is 17%.

Classification of  Migraine

Migraines were first comprehensively classified in 1988.The International Headache Society most recently updated their classification of headaches in 2004.A third version is in preparation as of 2016. According to this classification migraines are primary headaches along with tension-type headaches and cluster headaches, among others.

Migraines are divided into seven subclasses (some of which include further subdivisions)

• A migraine without aura,  – a common migraine”, involves migraine headaches that are not accompanied by an aura.
• A migraine with aura, or a classic migraine – usually involves migraine headaches accompanied by an aura. Less commonly, an aura can occur without a headache, or with a nonmigraine headache. Two other varieties are familial hemiplegic migraine and sporadic hemiplegic migraine, in which a person has migraines with aura and with accompanying motor weakness. If a close relative has had the same condition, it is called “familial”, otherwise, it is called “sporadic”. Another variety is a basilar-type migraine, where a headache and aura are accompanied by difficulty speaking, world spinning, ringing in ears, or a number of other brainstem-related symptoms, but not motor weakness. This type was initially believed to be due to spasms of the basilar artery, the artery that supplies the brainstem. Now that this mechanism is not believed to be primary, the symptomatic term migraine with brainstem aura (MBA) is preferred.
• Childhood periodic syndromes –  that are commonly precursors of a migraine include cyclical vomiting (occasional intense periods of vomiting), abdominal migraine (abdominal pain, usually accompanied by nausea), and benign paroxysmal vertigo of childhood (occasional attacks of vertigo).
• A retinal migraine involves a migraine – headaches accompanied by visual disturbances or even temporary blindness in one eye.
• Complications of a migraine  – describe migraine headaches and/or auras that are unusually long or unusually frequent, or associated with a seizure or brain lesion.
• A probable migraine – describes conditions that have some characteristics of migraines, but where there is not enough evidence to diagnose it as a migraine with certainty (in the presence of concurrent medication overuse).
• A chronic migraine –  is a complication of migraines, and is a headache that fulfills diagnostic criteria for migraine headache and occurs for a greater time interval. Specifically, greater or equal to 15 days/month for longer than 3 months.

Treatment of a Migraine

Infrequent, less severe migraine may respond to over-the-counter medications such as

• aspirin (not recommended for young children, some adults respond well to three tablets)
• paracetamol
• non-steroidal anti-inflammatory drugs such as ibuprofen , naproxen .
  Medications that may be prescribed for more severe migraine include
• triptans such as sumatriptan, naratriptan, zolmitriptan that are based on the serotonin molecule
• ergotamine compounds  that appear to provide relief by constricting cranial blood vessels
• stronger non-steroidal anti-inflammatory drugs
• stronger narcotic-type analgesics.
  Anti-emetic medications often prescribed with other forms of acute therapy to minimise the nausea that often accompanies migraine include
• metoclopramide , prochlorperazine or domperidone  to increase absorption and reduce nausea.
• Prescription medications used to relieve the pain of migraine include triptans (a class of drugs), for example:
  • sumatriptan
  • rizatriptan
  • eletriptan
  • zolmitriptan
  • naratriptan
  • almotriptan
  • frovatriptan
  • Lifestyle changes like eating a healthy diet and getting exercise may help reduce the frequency of your attacks.
  • Try to avoid any foods that trigger your migraines. It also may reduce the frequency of attacks.
  • Some people find that exercises, for example yoga, promote muscle relaxation are helpful in managing severe pain.
  • Most people with migraines usually are able to manage their condition with a combination of medications and lifestyle changes.
  • Some people may need prescription medications to decrease the frequency of headaches.

Complementary Therapies of Migraine

Prevention of Migraine

Prophylactic/preventative medication is taken daily, regardless or whether a headache is present, to reduce the incidence of severe or frequent headaches. These include:

• beta blockers such as propranolol (Inderal), timolol (Blocadren), atenolol (Tenormin) and metoprolol (Lopresor, Betaloc) that block the beta-receptors on which adrenaline works in the nervous system as well as on blood vessels
• serotonin antagonists such as methysergide (Deseril),   pizotifen (Sandomigran) and cyproheptadine (Periactin)
• sodium valproate or valproic acid (eg Epilim), an anti-epileptic drug shown to reduce the intensity of migraine
• calcium-channel blockers such as verapamil (Isoptin) that stop the constriction of blood vessels by preventing the use of calcium necessary for this reaction
• antidepressants such as amitriptyline  (eg. Tryptanol) have an action on headache that is independent of their antidepressant action
• feverfew, a herbal remedy
• riboflavin 200mgm twice daily has been reported as useful.
  All are effective.  All have side effects and, except feverfew and riboflavin, are prescription drugs.  Many were initially introduced for some other problem and were also observed to reduce a headache.

References

Motor Neuron Disease is any of several neurodegenerative disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. A group of related diseases of the nervous system that are characterized by steadily progressive deterioration of the motor neurons in the brain, brain stem, and spinal cord. Abbreviated MND. Motor neurons are the nerve cells along which the brain sends instructions, in the form of electrical impulses, to the muscles. The degeneration of motor neurons leads to weakness and wasting of muscles. MND usually first affects the arms or legs. Then shoulders and other muscles may be affected. Weakness and wasting in the muscles of the face and throat may cause problems with speech, chewing, and swallowing. MND does not affect touch, taste, sight, smell, or hearing, nor does it directly affect bladder, bowel, or sexual function.

Types of Motor Neuron Disease

• Amyotrophic lateral sclerosis (ALS)
• Primary lateral sclerosis (PLS)
• Hereditary spastic paraparesis (HSP)
• Progressive bulbar palsy (PBP), including hereditary forms
• Spinal muscular atrophy (SMA)
• X-linked spinobulbar muscular atrophy (SBMA; Kennedy disease)
• Postpolio syndrome (PPS)
• Progressive muscular atrophy (PMA),
• progressive bulbar palsy (PBP)
• Pseudobulbar palsy.

What are the symptoms of motor neuron diseases

A brief description of the symptoms of some of the more common MNDs follows.

Amyotrophic lateral sclerosis (ALS),

It is also called Lou Gehrig’s disease or classical motor neuron disease, is a progressive, ultimately fatal disorder that disrupts signals to all voluntary muscles.  Many doctors use the terms motor neuron disease and ALS interchangeably.  Both upper and lower motor neurons are affected.  Symptoms are usually noticed first in the arms and hands, legs, or swallowing muscles.  Approximately 75 percent of people with classic ALS will develop weakness and wasting of the bulbar muscles (muscles that control speech, swallowing, and chewing).  Muscle weakness and atrophy occur on both sides of the body.  Affected individuals lose strength and the ability to move their arms and legs, and to hold the body upright.  Other symptoms include spasticity, spasms, muscle cramps, and fasciculations.  Speech can become slurred or nasal.  When muscles of the diaphragm and chest wall fail to function properly, individuals lose the ability to breathe without mechanical support.

Progressive bulbar palsy,

also called progressive bulbar atrophy, involves the brain stem—the bulb-shaped region containing lower motor neurons needed for swallowing, speaking, chewing, and other functions.  Symptoms include pharyngeal muscle weakness (involved with swallowing), weak jaw and facial muscles, progressive loss of speech, and tongue muscle atrophy.  Limb weakness with both lower and upper motor neuron signs is almost always evident but less prominent.  Individuals are at increased risk of choking and aspiration pneumonia, which is caused by the passage of liquids and food through the vocal folds and into the lower airways and lungs.  Affected persons have outbursts of laughing or crying (called emotional lability).  Stroke and myasthenia gravis may have certain symptoms that are similar to those of progressive bulbar palsy and must be ruled out prior to diagnosing this disorder.

Pseudobulbar palsy

which shares many symptoms of progressive bulbar palsy, is characterized by degeneration of upper motor neurons that transmit signals to the lower motor neurons in the brain stem.  Affected individuals have progressive loss of the ability to speak, chew, and swallow.  Progressive weakness in facial muscles leads to an expressionless face.  Individuals may develop a gravelly voice and an increased gag reflex.  The tongue may become immobile and unable to protrude from the mouth.  Individuals may have outbursts of laughing or crying.

Primary lateral sclerosis (PLS) 

It affects the upper motor neurons of the arms, legs, and face.  It occurs when specific nerve cells in the motor regions of the cerebral cortex (the thin layer of cells covering the brain which is responsible for most high-level brain functions) gradually degenerate, causing the movements to be slow and effortful.  The disorder often affects the legs first, followed by the body trunk, arms and hands, and, finally, the bulbar muscles.  Speech may become slowed and slurred.  When affected, the legs and arms become stiff, clumsy, slow and weak, leading to an inability to walk or carry out tasks requiring fine hand coordination.  Difficulty with balance may lead to falls.  Speech may become slow and slurred.

Progressive muscular atrophy

It is marked by slow but progressive degeneration of only the lower motor neurons.  It largely affects men, with onset earlier than in other MNDs.  Weakness is typically seen first in the hands and then spreads into the lower body, where it can be severe.  Other symptoms may include muscle wasting, clumsy hand movements, fasciculations, and muscle cramps.  The trunk muscles and respiration may become affected.  Exposure to cold can worsen symptoms.  The disease develops into ALS in many instances.

Spinal muscular atrophy (SMA)

It is a hereditary disease affecting the lower motor neurons.  It is an autosomal recessive disorder caused by defects in the gene SMN1, which makes a protein that is important for the survival of motor neurons (SMN protein).  In SMA, insufficient levels of the SMN protein lead to degeneration of the lower motor neurons, producing weakness and wasting of the skeletal muscles.

SMA type I, also called Werdnig-Hoffmann disease,

It is evident by the time a child is 6 months old.  Symptoms may include hypotonia (severely reduced muscle tone), diminished limb movements, lack of tendon reflexes, fasciculations, tremors, swallowing and feeding difficulties, and impaired breathing.  Some children also develop scoliosis (curvature of the spine) or other skeletal abnormalities.  Affected children never sit or stand and the vast majority usually die of respiratory failure before the age of 2.  However, the survival in individuals with SMA type I has increased in recent years, in relation to the growing trend toward more proactive clinical care.

Symptoms of SMA type II,

The intermediate form, usually begin between 6 and 18 months of age.  Children may be able to sit but are unable to stand or walk unaided, and may have respiratory difficulties.  The progression of disease is variable.  Life expectancy is reduced but some individuals live into adolescence or young adulthood.

Symptoms of SMA type III (Kugelberg-Welander disease) 

appear between 2 and 17 years of age and include abnormal gait; difficulty running, climbing steps, or rising from a chair; and a fine tremor of the fingers.  The lower extremities are most often affected.  Complications include scoliosis and joint contractures—chronic shortening of muscles or tendons around joints, caused by abnormal muscle tone and weakness, which prevents the joints from moving freely.  Individuals with SMA type III may be prone to respiratory infections, but with care may have a normal lifespan.

Congenital SMA with arthrogryposis 

(persistent contracture of joints with fixed abnormal posture of the limb) is a rare disorder.  Manifestations include severe contractures, scoliosis, chest deformity, respiratory problems, unusually small jaws, and drooping of the upper eyelids.

Kennedy’s disease, also known as progressive spinobulbar muscular atrophy,

It is an X-linked recessive disease caused by mutations in the gene for the androgen receptor.  Daughters of individuals with Kennedy’s disease are carriers and have a 50 percent chance of having a son affected with the disease.  The onset of symptoms is variable and the disease may first be recognized between 15 and 60 years of age.  Symptoms include weakness and atrophy of the facial, jaw, and tongue muscles, leading to problems with chewing, swallowing, and changes in speech.  Early symptoms may include muscle pain and fatigue.  Weakness in arm and leg muscles closest to the trunk of the body develops over time, with muscle atrophy and fasciculations.

Post-polio syndrome (PPS)

It is a condition that can strike polio survivors decades after their recovery from poliomyelitis.  Polio is an acute viral disease that destroys motor neurons.  Many people who are affected early in life recover and develop new symptoms many decades later.  After acute polio, the surviving motor neurons expand the amount of muscle that each controls.  PPS and Post-Polio Muscular Atrophy (PPMA) are thought to occur when the surviving motor neurons are lost in the aging process or through injury or illness.  Many scientists believe PPS is latent weakness among muscles previously affected by poliomyelitis and not a new MND.

Symptoms of Motor Neuron Disease

You may have some or all of the symptoms listed below

• Muscle weakness, with loss of muscle mass (wasting), and movement and mobility problems
• Muscle cramps and spasms, including rippling sensations (known as fasciculation)
• Stiff joints, which may limit range of movement
• Pain or discomfort, as a result of other symptoms (not usually caused by MND directly)
• Speech and communication problems – affecting how you speak, gesture and show expression
• Swallowing difficulties – affecting how you eat and drink
• Saliva problems, where thin saliva pools in the mouth or saliva becomes thick and sticky
• Weakened coughing – which makes it harder to clear the throat
• Breathing problems – which can lead to breathlessness and fatigue
• Emotional lability – with inappropriate emotional responses, such as laughing when feeling sad
• Changes to thinking and behaviour – for about half of those diagnosed with MND.

Avobe all MND can be divided into three stages, early, middle, and advanced.

Early stage signs and symptoms

Symptoms develop slowly and can be confused with symptoms of some other unrelated neurological conditions.

They include

• a weakening grip, making it hard to pick up and hold things
• fatigue
• muscle pains, cramps, and twitches
• slurred and sometimes garbled speech
• weakness in the arms and legs
• increased clumsiness and stumbling
• difficulty swallowing
• trouble breathing or shortness of breath

Middle stage signs and symptoms 

As the condition progresses, symptoms become more severe.

• Muscle pain and weakness increase, and spasms and twinges worsen.
• Limbs become progressively weaker.
• Limb muscles start to shrink.
• Movement in affected limbs becomes more difficult.
• Limb muscles may become abnormally stiff.
• Joint pain grows.
• Eating, drinking, and swallowing become harder.
• Drooling occurs, due to problems controlling saliva.
• Yawning occurs, sometimes in uncontrollable bouts.
• Jaw pain may result from excessive yawning.
• Speech problems worsen, as muscles in the throat and mouth become weaker.

Advanced stage 

Eventually, the patient will be unable to move, eat, or breathe without assistance. Without supportive care, an individual will pass away. Despite the best of care currently available, complications of the respiratory system are the most common causes of death.

Diagnosis of Motor Neuron Disease

• Blood tests – These analyses can rule out other conditions and detect any rise in creatinine kinase. This is produced when muscle breaks down, and it is sometimes be found in the blood of patients with MND.
• An electroencephalogram (EEG) – small electrodes are placed on your scalp, which pick up the electrical signals from your brain and show abnormal brain activity
• Lumbar puncture (spinal tap), this helps determine via a test using the cerebral-spinal fluid, obtained from the lumbar region.
• Spinal fluid analysis – By doing a lumbar puncture (also called a spinal tap), your doctor can check the spinal fluid for an increase in white blood cells and protein. The bacteria, virus, parasite, or fungus causing the encephalitis also may be found in the spinal fluid.
• Urine analysis
• Polymerase chain reaction (PCR) testing of the cerebrospinal fluid, to detect the presence of viral DNA which is a sign of viral encephalitis.
• Blood cultures identify bacteria in the blood – Bacteria can travel from the blood to the brain. N. meningitidis and S. pneumoniae can cause both sepsis and meningitis.
• A complete blood count  – with differential is a general index of health. It checks the number of red and white blood cells in your blood. White blood cells fight infection. The count is usually elevated in meningitis.
• Cerebrospinal fluid (CSF) – CSF is the fluid that surrounds your brain and spinal cord. It helps to support and protect the brain and spinal cord from trauma.
• Chest X-rays –  can reveal the presence of pneumonia, tuberculosis, or fungal infections. Meningitis can occur after pneumonia.
• A CT scan  – of the head may show problems like a brain abscess or sinusitis. Bacteria can spread from the sinuses to the meninges.
• MRI brain scan – This cannot detect an MND, but it can help rule out other conditions, such as stroke, brain tumor, brain circulation problems, or abnormal brain structure.
• Electromyography (EMG) and nerve conduction study (NCS) – These are often performed together. An EMG tests the amount of electrical activity within muscles, while NCS tests the speed at which electricity moves through muscles.
• Muscle biopsy – If the doctor thinks the patient may have a muscle disease, rather than MND, a muscle biopsy may be performed.
• Nerve conduction tests  apply an electrical impulse through a small pad on the skin. This measures the speed at which nerves carry electrical signals.
• Transcranial Magnetic Stimulation (TMS) – measures the activity of the upper motor neurones to help diagnosis.

Treatment of Motor Neuron Disease

Management of the condition will require input from a multi-disciplinary group of health professionals that may include:

• Family doctor and medical specialists (neurology, respiratory, sleep, gastroenterology)
• Physiotherapists
• Occupational therapists
• Speech and language therapists
• Nurse specialists and district nurses
• Dietitians
• Social workers
• Counsellors
• Palliative care specialists and hospice care
• Sleep technologists

Muscle cramps and stiffness

Muscle cramps and stiffness can be treated with physical therapy and medications, such botulinum toxin (BTA) injections. BTA blocks the signals from the brain to the stiff muscles for about 3 months.

Baclofen, a muscle relaxer, may reduce muscle stiffness. A small pump is surgically implanted outside the body and connected to the space around the spinal cord. A regular dose of baclofen is delivered into the nervous system.

Baclofen blocks some of the nerve signals that cause spasticity. It may help with extreme yawning.

Treatment for drooling

Scopolamine, a drug for motion sickness, may help control symptoms of drooling. It is worn as a patch behind the ear.

Uncontrolled laughter or crying

Antidepressants, called serotonin reuptake inhibitors (SSRIs), may help with episodes of uncontrollable laughter or crying, known as emotional lability.

Speech, occupational and physical therapy

Patients with speech and communication difficulties may learn some useful techniques with a qualified speech and language therapist. As the disease advances, patients often need some communication aids.

Physical and occupational therapy can help maintain mobility and function, and reduce stress.

Swallowing difficulties (dysphagia)

As eating and drinking become harder, the patient may need a percutaneous endoscopic gastrostomy (PEG), a feeding tube that is placed on the abdomen, a relatively minor procedure.

Pain

A non-steroidal anti-inflammatory drug (NSAID), such as ibuprofen, will help with mild to moderate pain from muscle cramping as spasms. Drugs such as morphine can help relieve severe joint and muscle pain in the advanced stages.

Breathing problems

Respiratory muscles usually weaken gradually, but a sudden deterioration is possible.

Mechanical ventilation can help with breathing. A machine takes in air, filters it, and pumps it into the lungs often through a tracheostomy, a surgical hole in the neck that allows for assisted breathing.

Some people use complementary therapies, including special diets that are high in vitamins. These will not cure MND, but following a healthful diet can improve overall health and wellbeing.

Stem cell transplant for ALS treatment

Stem cell research and gene therapy have shown promise for treating ALS in the future, but more studies are needed.

References

Agitation can be defined as excessive verbal / motor behavior. It can readily escalate to aggression, which can be either verbal (vicious cursing and threats) or physical (toward objects or people). Technically, violence is defined as physical aggression against other people.  The signs are unintentional and purposeless motions; the symptoms are emotional distress and restlessness. Typical manifestations include pacing around a room, wringing the hands, uncontrolled tongue movement, pulling off clothing and putting it back on, and other similar actions. In more severe cases, the motions may become harmful to the individual, such as ripping, tearing, or chewing at the skin around one’s fingernails, lips, or other body parts to the point of bleeding.

Agitation also means

Agitation (action), putting into motion by shaking or stirring, often to achieve mixing

An emotional state of excitement or restlessness

• Psychomotor agitation, an extreme form of the above, which can be part of a mental illness or a side effect of anti-psychotic medication
• Agitation (dementia), a symptom of dementia

Political agitation or demonstration (protest), political activities in which an agitator urges people to do something

• Agitation and Propaganda against the State, a former criminal offence in communist Albania
• Anti-Soviet agitation, a former criminal offence in the Soviet Union

Causes of Agitation 

• Schizophrenia
• Bipolar disorder
• Excited delirium
• Post-traumatic stress disorder
• Panic attacks
• Anxiety disorder
• Obsessive-compulsive disorder
• Alcohol withdrawal
• Claustrophobia
• Dementia
• Parkinson’s disease
• Traumatic brain injury
• Alzheimer’s disease
• Acute intermittent porphyria
• Hereditary coproporphyria
• Variegate porphyria
• Side effects of drugs like cocaine or methylphenidate
• Side effects of antipsychotics like haloperidol

Causes of Terminal Agitation

Opioid toxicity – High or prolonged opioid administration can lead sedation, neuroexcitation and even agitated delirium.

Pain – Uncontrolled and severe pain can cause agitation; this should be ruled out early. Note that communicating pain is difficult for cognitively impaired patients.

Drug interactions – Many drugs used in palliative care, such as hypnotics, antimuscarinics and anticonvulsants, can cause agitation.

Fever or sepsis – The onset of delirium can occur with fever (which can reduce cerebral oxidative metabolism).

Hypercalcaemia – Hypercalcaemia the most common life-threatening metabolic disorder in cancer patients. It can lead to a confused and agitated state so calcium levels should be monitored.

Raised intracranial pressure – Brain tumours or cerebral metastasis can increase intracranial pressure, leading to an agitated state.

Symptoms of Agitation 

Also, a person will also have experienced at least five of the following symptoms

• Feelings of sadness, hopelessness, or irritability on a nearly daily basis.
• Lack of interest or pleasure in activities almost every day.
• Experiencing significant weight loss or appetite loss that results in weight loss.
• Difficulty sleeping or sleeping excessively.
• Experiencing psychomotor agitation, restlessness, or feelings of being “slowed down.”
• Feeling fatigued or having a lack of energy nearly every day.
• Feeling worthless or having excessive and unexplained guilt almost every day.
• Difficulty thinking clearly, concentrating, or making decisions on a daily basis.
• Experiencing thoughts of death, thinking of harming one’s self, or creating a specific plan for committing suicide.
• Angry outbursts
• Clenching fists
• Disruptive behavior
• Excessive talking
• Feeling as if a person cannot sit still or focus
• Pacing or shuffling feet
• Tension
• Wringing of the hands
• Violent outbursts

Diagnosis of Agitation 

Your doctor will ask you questions and review your medical history. They will also run some tests and perform a physical exam. Your test results will be used to rule out causes of agitation.

Agitation (states of irritability, restlessness and tensions) is an acute, severe and pathological complication of many chronic psychiatric disorders, including schizophrenia and mania. Psychomotor agitation is defined as excess motor activity coupled with a feeling of inner anxiety.

Patients describe agitation as a feeling of inner distress (they feel nervous, restless, overwhelmed, out of control, in fear, in panic). It leads to an externally recognized dysfunctional state and manifests itself in swearing, hostility, lack of impulse controls, uncooperative behavior and a greater propensity to violence

Treatment of Agitation 

In the first instance, a doctor may prescribe medications called sedatives or benzodiazepines.

Examples may include diazepam  or lorazepam . These medications work quickly to help a person feel calmer and can temporarily relieve agitation.

Additional steps include

• Antidepressants – can help if your loved one is depressed and irritable. Options include citalopram , fluoxetine , nortriptyline (, paroxetine , and sertraline . Side effects of these medicines can include drowsiness,xerostomia constipation, and anxiety.
• Anti- anxiety medications – which include alprazolam , buspirone ,lorazepam  and oxazepam , often cause drowsiness.

• Medications to relieve depression – Doctors may prescribe a variety of drugs to relieve depression, including anti-depressants. If a person does not respond to these medicines, a doctor may add another drug or prescribe a different medication type entirely. Examples can include anti-anxiety medications or mood stabilizers.
• Counseling – Seeing a psychiatrist or other mental health professional can help a person identify thoughts and feelings that can signal the start of agitation or depressive symptoms. Therapy can help a person focus on thoughts and behaviors that can help them feel better when they struggle with agitated depression.
• Stress-relieving techniques – Relieving stress and depression through physical activity, meditation, deep breathing, and journaling can all help a person cope with feelings agitated depression.
• Intramuscular – midazolam, lorazepam, or another benzodiazepine can be used to both sedate agitated patients, and control semi-involuntary muscle movements in cases of suspected akathisia.
• Droperidol, haloperidol, or other typical antipsychotics can decrease the duration of agitation caused by acute psychosis, but should be avoided if the agitation is suspected to be akathisia, which can be potentially worsened. Also using promethazine may be useful.
• Recently three atypical antipsychotics, olanzapine, aripiprazole and ziprasidone, have become available and FDA approved as an instant release intramuscular injection formulations to control acute agitation. The IM formulations of these three atypical antipsychotics to be at least as effective or even more effective than the IM administration of haloperidol alone or haloperidol with lorazepam (which is the standard treatment of agitation in most hospitals) and the atypicals have a dramatically improved tolerability due to a milder side-effect profile.
• In those with psychosis causing agitation there is a lack of support for the use of benzodiazepines alone, however they are commonly used in combination with antipsychotics since they can prevent side effects associated with dopamine antagonists.

Pharmacologic Options for Acute Agitation — Intramuscular Agents

Agent	Dose (mg)	Comments
Lorazepam	0.5 to 2.0	Will treat underlying alcohol withdrawal. Caution: respiratory depression.
Haloperidol	0.5 to 10	Caution: akathisia, acute dystonic reaction, seizure threshold decrease.
Droperidol	2.5 to 5.0	No FDA-approved psychiatric indication. Caution: prolongation of the QTc interval (removed from UK market, and new black box warning in United States)
Olanzapine*	10 (2.5 for patients with dementia)	Superiority over haloperidol (schizophrenia) and lorazepam (bipolar disorder) in clinical trials. No EPS. Caution: weight gain over time.
Ziprasidone*	10 to 20	Little or no EPS. Caution: prolongation of the QTc interval.

References