What Is Brainstem? – Anatomy, Nerve Blood Supply, Function

What Is Brainstem? – Anatomy, Nerve Blood Supply, Function

What Is Brainstem?/Brainstem is the structure that connects the cerebrum of the brain to the spinal cord and cerebellum. It is composed of four sections in descending order: the diencephalon, midbrain, pons, and medulla oblongata. It is responsible for many vital functions of life, such as breathing, consciousness, blood pressure, heart rate, and sleep. The brainstem contains many critical collections of white and grey matter. The grey matter within the brainstem consists of nerve cell bodies and form many important brainstem nuclei. The white matter tracts of the brainstem include axons of nerves traversing their course to different structures; the axons originate from cell bodies located elsewhere within the central nervous system (CNS). Some of the white matter tract cell bodies are located within the brainstem as well. These tracts travel both to the brain (afferent) and from the brain (efferent) such as the somatosensory pathways and the corticospinal tracts, respectively. Ten of the twelve cranial nerves arise from their cranial nerve nuclei in the brainstem. Clinicians can localize lesions of the brainstem with a thorough knowledge of brainstem anatomy and functions. The following activity addresses the nuclei, tracts, and functions of the brainstem.

Anatomy of Brainstem

The brainstem contains many different nuclei and tracts. This section overviews the major structures located in each area of the brainstem, followed by a summary of the course of the major pathways through the brainstem.

Diencephalon

The diencephalon is the most superior portion of the brainstem and connects to the midbrain inferiorly. This structure encompasses the third ventricle, which connects the interventricular foramen of the lateral ventricles to the cerebral aqueduct. The diencephalon is composed of four major portions: the epithalamus, subthalamus, hypothalamus, and thalamus. Some sources state the subthalamus is one of the four components of the diencephalon while others refer to the pretectum in place of the subthalamus; however, both terms refer to the inferior portion of the diencephalon that is continuous with the midbrain. The epithalamus is located in the posterior diencephalon and is composed of the pineal gland, habenular commissure, and posterior commissure. The subthalamus is the upward continuation of the tegmentum of the midbrain and forms the greater part of the inferior portion of the third ventricle. The substantia nigra and red nucleus extend upward from the midbrain into the inferior subthalamus. The acetylcholine-producing neurons of the nucleus of Meynert are located within the subthalamus. The loss of neurons of the nucleus of Meynert occurs in several pathologies that result in dementia. The subthalamus also contains the subthalamic nucleus at the base of the cerebral peduncle. The subthalamic nucleus participates in the regulation of movement with the basal ganglia. The hypothalamus is located in the anterior inferior portion of the diencephalon and includes the infundibulum, mammillary bodies, hypophysis, and many hypothalamic nuclei. The posterior thalamus protrudes and overlaps the superior colliculus of the midbrain, the medial portion of this is the pulvinar. The pulvinar extends laterally to the lateral geniculate bodies which play a role in vision. The medial geniculate bodies are located inferior to the pulvinar and play a role in the auditory pathway.

The thalamus is the most substantial portion of the diencephalon, composing its remainder as two large oval masses flanking the third ventricle. The thalamus serves as a relay point for all sensory input tracts. The thalamus divides into several components composed of different thalamic nuclei and tracts. The anterior thalamus contains the anterior thalamic nuclei that receive communication from the mammillary nuclei via the mammillothalamic tract and play a role in the limbic system. The medial thalamus contains the dorsomedial nucleus and has connections with hypothalamic nuclei and the prefrontal cortex. The medial thalamus integrates an immense amount of sensory data. The lateral thalamus subdivides into dorsal and ventral components. The dorsal portion includes the lateral dorsal nucleus, pulvinar, and the lateral posterior nucleus. The ventral portion contains the ventral anterior and lateral nuclei; these nuclei affect activities of the motor cortex because they have connections to the reticular formation, substantia nigra, and corpus striatum. The ventral portion also contains the ventral posterior medial nuclei which have connections with the ascending trigeminal tracts, as well as the ventral posterior lateral nuclei which serve as the primary sensory relay station for input from the body. The major nuclei have been addressed in this section, but some studies divide the thalamus into 14 major nuclei, and those can be subdivided further into many subnuclei.

Midbrain

The midbrain serves as the connection between the pons and the diencephalon. It also connects posteriorly to the cerebellum via the superior cerebellar peduncles. The anterior part of the midbrain contains the crus cerebri with the interpeduncular fossa located between them. The crus cerebri carry motor cortical spinal fibers, corticonuclear fibers, and pontine fiber tracts. The midbrain contains the cerebral aqueduct centrally which connects the third ventricle superiorly with the fourth ventricle inferiorly. The periaqueductal grey surrounds the cerebral aqueduct. The midbrain is separated relative to the cerebral aqueduct with the posterior portion being the tectum (floor) and anterior to the aqueduct serving as the tegmentum (roof). The posterior surface of the midbrain contains the corpora quadrigemina which are composed of bilateral superior colliculi and bilateral inferior colliculi. The superior colliculi are involved in visual reflexes such as saccadic eye movements. Each superior colliculus sends fibers to the corresponding lateral geniculate body and optic tract through the superior brachium. The inferior colliculi are involved in auditory processing and connect to their corresponding medial geniculate nuclei through the inferior brachium. Just inferior to the inferior colliculi at the posterior midline of the brainstem cranial nerve IV, the trochlear nerve, emerges. The trochlear nerve is unique among cranial nerves as it is the only one to emerge from the posterior surface of the brainstem. The other cranial nerve that arises from the midbrain is cranial nerve III, the oculomotor nerve. The oculomotor nerve arises from the midbrain in the oculomotor sulcus on the medial surface of the crus cerebri, within the interpeduncular cistern.

The midbrain also includes many other important nuclei including but not limited to the substantia nigra at the base of the midbrain, the red nucleus anterior medially at the level of the superior colliculus, and the dorsal raphe nucleus. The largest of the raphe nuclei are in the anterior midline of the periaqueductal grey, and the location of the ventral tegmental area is near the midline medial to the red nucleus. The substantia nigra contains dopaminergic neurons that help to regulate movement associated with the basal ganglia. The ventral tegmental area also contains dopaminergic neurons and plays a role in reward pathways. The raphe nuclei contain serotonergic neurons and project widely throughout the brain. The periaqueductal grey is thought to play a role in pain suppression. The red nucleus is involved with movement and contains many connections with the cerebellum. The medial longitudinal fasciculus lies anterior to the periaqueductal grey and plays a role in coordinating eye movements.

Pons

The pons connects the medulla oblongata inferiorly to the midbrain superiorly. The anterior portion of the pons is convex and can be easily seen as a visible distention when viewing the brainstem anteriorly. The surface of the anterior distention contains the basilar groove, which is where the basilar artery rests. The posterior pons is connected to the cerebellum by the middle cerebellar peduncles which are the largest of the cerebellar peduncles. The posterior portion of the pons forms the superior portion of the floor of the fourth ventricle. A groove is formed inferiorly where the pons meets the medulla from which cranial nerves VI, VII, and VIII emerge medially to laterally. Cranial nerve V, the largest cranial nerve, exits from the superior anterior lateral pons. Important nuclei of the pons include the cranial nerve nuclei covered in the nerves section, the locus coeruleus, and pontine nuclei. The neurons of the locus coeruleus produce norepinephrine and have projections that spread widely throughout the CNS. The locus coeruleus is located in the posterior lateral pons at the lateral border of the periaqueductal grey and is involved in the reticular activating system. The locus coeruleus also suffers compromise in Alzheimer disease.[8] The pontine nuclei are a collection of pontine motor nuclei in the anterior pons that have many connections with the cerebellum via the middle cerebellar peduncle and assist with coordinating movement and help to modulate breathing.

Medulla Oblongata

The most inferior portion of the midbrain is the medulla oblongata, which connects the pons to the spinal cord. It meets the spinal cord at the level of the foramen magnum. The anterior portion of the medulla oblongata contains the pyramids. The pyramids carry motor fibers from the precentral gyrus, or motor cortex, to the grey matter of the spinal cord where they synapse and continue to the muscles of the body through the peripheral nervous system. The pyramids contain a decussation caudally in which the majority of the motor fibers contained cross to the contralateral side of the body. The fibers that decussate become the lateral corticospinal tract in the spinal cord, the fibers that do not decussate become the medial corticospinal tract in the anterior portion of the spinal cord. The pyramids lie on either side of the anterior median fissure, a midline groove that continues caudally along the anterior portion of the spinal cord. Lateral to the pyramids are the olivary bodies that are part of the olivocerebellar system. The hypoglossal nerve, cranial nerve XII, emerges from the anterior surface of the medulla from the sulcus between the olivary bodies and the pyramids. Posterior to the olivary bodies is the postolivary groove. Cranial nerves IX (glossopharyngeal), X (vagus), and XI (accessory) emerge from the postolivary groove in superior to inferior order. Posterior to the postolivary grooves are the inferior cerebellar peduncles that connect the medulla to the cerebellum. The posterior portion of the medulla oblongata inferiorly connects to the spinal cord. The posterior median sulcus is located in the midline on the posterior aspect of the inferior medulla and continues caudally along the posterior spinal cord.  The posterior median sulcus in the posterior midline of the spinal cord is flanked by visible localized prominences called the gracile tubercles. On each side, the gracile tubercle contains the gracile nucleus. Similar bilateral localized prominences called the cuneate tubercles (containing the cuneate nucleus on each side) are just lateral to each of the gracile tubercles on the posterior aspect of the spinal cord. The gracile and cuneate tubercles carry second-order neurons of the dorsal column-medial lemniscus system. The gracile nucleus carries fibers for the lower extremities and trunk, and the cuneate nucleus carries fibers for the upper body above T6 except for the face and ears. The superior area of the posterior medulla oblongata forms a portion of the floor of the fourth ventricle.

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Surface of Brainstem

Ventral Surface

The ventral surface of the medulla is marked by a midline depression known as the anterior median fissure. This is a cranial continuation of the anterior median fissure of the spinal cord, which divides the medulla into symmetrical halves. The most distal end of the anterior median fissure is covered by crisscrossing fibers known as the decussation of the pyramids.

The pyramids contain the corticospinal fibers that start from the motor cortex, pass through the internal capsule, and contribute to the formation of the cerebral peduncles. The fibers then descend to the spinal cord, passing through the pons and the medulla. Their role is to regulate muscle movement. Most of these fibers cross to the opposite side at the level of the caudal medulla and they form the aforementioned decussation of pyramids.

Lateral to the medullary pyramids is a shallow depression that represents the cranial continuation of the ventrolateral sulcus of the spinal cord. It separates the pyramids from another prominent bulge, the olive, which corresponds to the location of the inferior olivary nucleus. Posterolateral to the olives are the inferior cerebellar peduncles. Although these structures lie above the upper limit of the medulla, they are often labeled as medullary structures owing to the fact that they carry fibers from the medulla to the cerebellum.

The lower four cranial nerves also emerge from the anterior surface of the medulla. The hypoglossal nerve (CN XII) rootlets emerge between the pyramids and the olives before they unite to form the trunk of the nerve. The glossopharyngeal nerve (CN IX) rootlets arise between the inferior cerebellar peduncle and the olive (close to the choroid plexus of the fourth ventricle). Caudal to CN IX are the rootlets of the vagus nerve (CN X). The most inferior of the cranial nerves is the accessory nerve (CN XI) whose rootlets ascend the lateral aspect of the medulla to unite as the nerve trunk.

Dorsal Surface

The posterior surface of the medulla can be divided into an upper open area and a lower closed area. The open area is also known as the floor of the fourth ventricle or rhomboid fossa. It has unique raised areas that mark the location of underlying structures. These include the hypoglossal and vagal trigones that are present on either side of the posterior (dorsal) median sulcus. The hypoglossal trigone (location of the nucleus of CN XII) is superior to the vagal trigone (location of CN X nucleus). The vagal trigone is above the obex, which is the most caudal aspect of the fourth ventricle.

The closed part of the posterior surface (outside of the fourth ventricle) of the medulla is also divided into symmetrical halves by the caudal continuation of the dorsal median sulcus. On either side of the sulcus is a raised structure known as the gracile tubercle. Deep to the tubercle is the gracile nucleus, which is the point of termination of the gracile fasciculus of the dorsal column of the spinal cord.

The paired cuneate tubercles, which are raised areas over the cuneate nucleus also marks the point of termination of the cuneate fasciculus. It is laterally related to the gracile tubercle. The cuneate fasciculus is medically related to the lateral funiculus which carries contralateral corticospinal and spinothalamic tracts. Similarly, the trigeminal tubercle is laterally related to the cuneate tubercle. It represents the location of the spinal nucleus of the trigeminal nerve (CN V).

The inferior cerebellar peduncles also form part of the posterior surface of the medulla. It is best seen when the cerebellum is removed. This paired tract carries efferent and afferent impulses between the cerebellum and vestibular nuclei.

There are unique openings (one on either posterolateral surface and one in the posterior midline) on the medulla that facilitate communication between the fourth ventricle and the surrounding cisterns. Those on the posterolateral surfaces of the medulla are called the lateral apertures of the fourth ventricle (lateral apertures of Luschka). The midline opening is called the median aperture of the fourth ventricle (foramen of Magendie).

Read more in our article and then test how much you know about the subarachnoid cisterns by trying this quiz below.

Major Brainstem Tracts of Brainstem

The Reticular Formation

The reticular formation is found in the anterior portion of the brainstem and is composed of multiple tracts that have a large number of connections. The reticular formation extends from the spinal cord through the brainstem to the diencephalon. It receives input from various tracts including, spinothalamic tracts, spinoreticular tracts, the dorsal column medial lemniscus pathway, visual pathways, auditory pathways, vestibular pathways, and cerebelloreticular pathways. The reticular formation sends efferent fibers to the thalamic nuclei, cerebellum, red nucleus, corpus striatum, substantia nigra, hypothalamus, and subthalamic nucleus. The vast connections of the reticular formation allow it to modulate many different functions; some of these include movement coordination, autonomic regulation of blood pressure, heart rate, and respiratory rate, postural reflexes, neuro-vegetative reflexes, and taste. It also plays a role in wakefulness and sleep.

The Motor Tracts

Corticospinal Tracts

The majority of the upper motor neurons of the motor tracts originate in the precentral gyrus. The corticospinal fibers descend through the posterior limb of the internal capsule to the crus cerebri and then down the anterior pons to the pyramids of the medulla. At the pyramids, the majority of the corticospinal fibers decussate and descend the spinal cord as the lateral corticospinal tract and eventually continue to supply motor innervation to the limbs and digits. The majority of corticospinal fibers that do not cross over at the medullary pyramids become the medial corticospinal tracts, located anteriorly in the spinal cord, and provide innervation to the muscles of the trunk.

Corticobulbar Tracts

The corticobulbar tracts descend through the genu of the internal capsule and down through a similar course as the corticospinal fibers; however, the corticobulbar fibers exit this course and synapse at the appropriate cranial nerve nuclei at their respective levels. The majority of corticospinal fibers decussate while only some of the corticobulbar fibers decussate as described in the nerves section of this article. The corticobulbar tracts also contain connections with many of the sensory nuclei of the brainstem.

The Sensory Tracts

Spinothalamic Tract or Anterolateral System

The spinothalamic tract is responsible for conveying pain and temperature information from the body to the brain. Peripheral neurons carry sensory information to the posterior column of the spinal cord. After synapsing in the spinal cord, the axons ascend two to three levels before decussating. After decussating, the fibers ascend as the lateral and anterior spinothalamic tracts in the anterior and lateral portions of the spinal cord. When the tracts ascend through the medulla, they merge to form the spinothalamic tract and course along the lateral portion of the medulla. The tract continues up the lateral portion of the anterior pons and midbrain to the ventral posterior lateral thalamus where the axons synapse and continue up through the posterior limb of the internal capsule to enter the post-central gyrus of the cortex.

Dorsal Column-Medial Lemniscus

The dorsal column-medial lemniscus tract is responsible for carrying afferent proprioception, fine touch, two-point discrimination, and vibration to the cortex from the body. Peripheral neurons carry sensory information to the posterior column of the spinal cord and ascend in the posterior portions of the spinal cord as the gracile fasciculus and cuneate fasciculus. The neurons in these fasciculi will synapse of the gracile nucleus and cuneate nucleus at the level of the inferior medulla respectively. The second order neurons will decussate at the level of the medulla and become the medial lemniscus. The medial lemniscus maintains a medial position within the brainstem as it ascends to the ventral posterior lateral thalamus. After synapsing in the thalamus, the fibers continue through the posterior limb of the internal capsule to the post-central gyrus of the cortex.

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Trigeminal Lemniscus and Spinotrigeminal Tract

Pain and temperature sensory input from the face enters the brainstem via cranial nerve V. The fibers that carry this information enter the brainstem and descend parallel to the spinal trigeminal nucleus before synapsing in it. Their descent forms the spinotrigeminal tract. After these fibers synapse, they decussate to the contralateral side and ascend as a part of the trigeminal lemniscus.

The trigeminal lemniscus carries sensory axons from the second-order neurons of the principal sensory nucleus of the trigeminal nerve, which contain discriminative touch and oral cavity proprioception. These neurons do not descend before synapsing after entering the brainstem. Most of these fibers decussate to the contralateral side on their course to the ventral posterior medial thalamus and then proceed to the post-central gyrus of the cortex. The fibers of the trigeminal lemniscus ascend the pons and midbrain posterior to the medial lemniscus.

Lateral Lemniscus

The lateral lemniscus carries auditory information from the cochlear nuclei at the level of the inferior pons superiorly to the superior olivary complex, nuclei of the lateral lemniscus, inferior colliculi, and eventually to the medial geniculate body which sends the auditory information to the temporal lobes of the cerebral cortex. Some of the fibers of the lateral lemniscus decussate while others do not. The lateral lemniscus travels up the posterior lateral portion of the pons and is important for sensory input to the brain.

Blood Supply of Brainstem

The significant conduits of blood to the CNS are the internal carotid arteries and the vertebral arteries; they give rise to the many arterial branches that perfuse the CNS.  The most inferior portion of the brainstem is the medulla oblongata. Caudally it receives the majority of its blood supply from the anterior spinal artery anterior-medially and the posterior spinal artery posterior laterally. Superiorly it receives the majority of its blood supply from the vertebral artery laterally, basilar artery branches anteriorly, and the posterior inferior cerebellar artery posteriorly.

Moving superiorly, the pons is the next brainstem structure encountered.  Most of its blood supply comes from branches of the basilar artery. Superiorly, it is also perfused on its posterior lateral portion by branches of the superior cerebellar artery and branches of the anterior inferior cerebellar artery.

The next brainstem structure superior to the pons is the midbrain. It is perfused anterior medially by branches of the basilar artery, anterior laterally by branches of the posterior choroidal arteries and quadrigeminal artery originating from the posterior cerebral artery, and posteriorly by the quadrigeminal and superior cerebellar arteries.

The most superior brainstem structure, the diencephalon, is supplied anteriorly by branches of the anterior cerebral artery. Its posterior portions receive supply from branches of the posterior cerebral artery such as thalamogeniculate branches, thalamoperforating branches, and branches of the posterior communicating artery.

The anatomical lymphatic drainage of the central nervous system was described over 100 years ago, but until the last decade, the widely held consensus was that CNS lymphatics do not exist. The lymphatics of the CNS are small channels within the meninges and differ from the basic structure of the peripheral lymphatics. The CNS lymphatic system is still poorly understood but is thought to participate in immune cell transport, cerebrospinal fluid drainage, and interstitial fluid drainage. The lymphatics of the central nervous system continue to be a topic of investigation.

Nerves of Brainstem

The entire brainstem is composed of neural tissue. Ten of the twelve cranial nerves also emerge from the brainstem.

Midbrain

The oculomotor nerve (cranial nerve III)

Arises from the oculomotor sulcus on the medial portion of the crus cerebri. It is a motor nerve that receives inputs from two nuclei. The first nucleus is the oculomotor nucleus; it serves as its main motor nucleus and is in the anterior midline of the periaqueductal grey at the level of the superior colliculus. The second nucleus is the Edinger-Westphal nucleus, which provides parasympathetic motor inputs. The somatic motor fibers from the oculomotor nucleus provide innervation to all the extraocular muscles, with the exceptions of the superior oblique and lateral rectus muscles. The parasympathetic motor fibers of the Edinger-Westphal nucleus provide innervation to the ciliary muscles and constrictor pupillae after passing through the ciliary ganglion.

The Trochlear nerve (cranial nerve IV)

Exits from the posterior surface of the midbrain and is the only cranial nerve to exit posteriorly. It is a motor nerve with its nucleus located in the midline of the brainstem, also in the anterior portion of the periaqueductal grey, but inferior to the oculomotor nucleus. The nerve innervates the superior oblique ocular muscle, which is responsible for moving the eye downward and laterally. A unique feature of the trochlear nerve among the cranial nerves is that it is the only cranial nerve decussating peripherally. The nerve decussates at the superior medullary velum after leaving the brainstem, which causes cranial nerve nuclei deficits to appear as loss of function of the contralateral superior oblique muscle. Injuries that happen to the nerve distal to the decussation result in ipsilateral deficits to the superior oblique muscle.

Pons

The Trigeminal Nerve (cranial nerve V)

Arises from the superior anterior lateral pons as the largest cranial nerve. It contains both motor and sensory fibers. It arises as a smaller motor nerve and a larger sensory nerve. The sensory fibers provide innervation to the face and head. The motor fibers provide innervation to the muscles of mastication, mylohyoid, anterior belly of the digastric, tensor tympani, and tensor veli palatini. The trigeminal motor nucleus situates in the superior posterior lateral pons. The motor nucleus also receives corticobulbar fibers from both hemispheres as well as fibers from the reticular formation, medial longitudinal fasciculus, and red nucleus. The nerve has contributions from three sensory nuclei: The principal sensory nucleus of cranial nerve V, the mesencephalic nucleus, and the spinal trigeminal nucleus. The principal sensory nucleus of cranial nerve V lies directly lateral to the trigeminal motor nucleus and receives inputs from nerves that convey touch and pressure. The mesencephalic nucleus is located on the lateral aspect of the periaqueductal grey, anterior lateral to the fourth ventricle, and ascends to the height of the inferior colliculus.  The mesencephalic nucleus conveys proprioceptive input from the teeth, hard palate, temporomandibular joint, and muscles of mastication. The spinal trigeminal nucleus is located in the inferior posterior lateral pons and extends inferiorly through the medulla into the superior spinal cord. The spinal trigeminal nucleus receives pain and temperature input for the sensory distribution of the trigeminal nerve.

The Abducens nerve (cranial nerve VI)

Is a motor nerve that emerges anteriorly and medially from the junction of the pons and medulla.  The abducens nucleus is in the midline of the inferior tegmentum of the pons just ventral to the fourth ventricular floor. It provides innervation to the lateral rectus muscle, which is responsible for the abduction of the eye.

The facial nerve (cranial nerve VII)

Emerges from the junction of the pons and the medulla lateral to the abducens nerve at the cerebellopontine angle. It is both a motor and a sensory nerve and emerges as two separate roots; these include a medial motor root and a lateral sensory root. The facial motor nucleus situates in the anterior lateral inferior pons just anterior and medial to the spinal trigeminal nucleus. The muscles of facial expression derive innervation from the motor nucleus of the facial nerve. The upper face receives corticobulbar fibers that partially decussate from both hemispheres, which allow sparing of deficits with lesions at the level of the cranial nerve nuclei while the lower muscles corticobulbar fibers fully decussate. The sensory nucleus is the upper portion of the solitary nucleus, which is located posterior and lateral to the facial nerve motor nucleus. It receives afferent fibers for taste from the anterior two-thirds of the tongue and sensation for the skin near the auricle of the ear. Its parasympathetic nucleus is the superior salivatory nucleus and is located laterally to the abducens nucleus but posterior to the facial motor nucleus. It innervates the submandibular and submental salivary glands.

The Vestibulocochlear nerve (cranial nerve VIII)

Arises from the brainstem directly lateral to the sensory root of the facial nerve. Cranial nerve VIII has two distinct portions, the vestibular, responsible for balance, and the cochlear, which is responsible for hearing. Cranial nerve VIII is purely a sensory nerve and both of its portions course together until they reach their nuclei within the brainstem.  The vestibular portion of the nerve provides input to the vestibular nuclei located along the lateral portion of the fourth ventricle in the inferior pons. The vestibular nuclei are composed of four different nuclei (superior, inferior, lateral, and medial.) These nuclei send tracts to three separate areas: the cerebellum via the vestibulocerebellar tract, the spinal cord through the vestibulospinal tract, and the nuclei of cranial nerves III, IV, and VI by the medial longitudinal fasciculus. The cochlear portion provides input to the dorsal and ventral cochlear nuclei. These nuclei are in the anterior lateral portion of the inferior pons. The posterior cochlear nucleus processes high-frequency sounds while the anterior cochlear nucleus processes low-frequency sound. The anterior cochlear nucleus projects fibers to the ipsilateral superior olive and then to the lateral lemniscus. The posterior cochlear nucleus projects to the contralateral lateral lemniscus.

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Medulla Oblongata

The glossopharyngeal nerve (cranial nerve IX)

Emerges from the postolivary groove and contains motor fibers, sensory fibers, and parasympathetic nerves. The nerve shares several cranial nerve nuclei with cranial nerve X (the vagus nerve), the nucleus ambiguous, and the nucleus solitarius. Cranial nerve IX also uses the inferior salivatory nucleus. The superior portion of the nucleus ambiguous is located posterior to the inferior olivary nucleus and contains second-order motor cell nuclei for the glossopharyngeal nerve. The motor fibers from the superior nucleus ambiguous innervate the stylopharyngeus muscle. The cranial nerve IX parasympathetic cranial nerve nucleus is the inferior salivary nucleus; its postganglionic parasympathetic, visceral efferent fibers provide innervation to the parotid gland. The inferior salivary nucleus is located posterior to the nucleus ambiguous and receives afferent input from the hypothalamus, olfactory system, and nucleus solitarius. The last nuclei of the glossopharyngeal nerve are the nucleus solitarius. It is a sensory nucleus that receives taste from the posterior one-third of the tongue from the glossopharyngeal nerve. It also receives afferent impulses from the carotid sinus.

The Vagus nerve (cranial nerve X)

Emerges from the postolivary groove and contains motor fibers, sensory fibers, and parasympathetic fibers. The inferior portion of the nucleus ambiguous provides motor output to the muscles of the pharynx and larynx. The parasympathetic nucleus of the vagus nerve is the dorsal motor nucleus. The dorsal motor nucleus is located lateral to the hypoglossal nucleus and receives afferent fibers from the upper gastrointestinal tract, liver, pancreas, heart, and bronchi. The sensory nucleus for the vagus nerve is also the nucleus solitarius similar to the glossopharyngeal nerve. It receives afferent inputs from the carotid sinus as well.

The accessory nerve (cranial nerve XI)

Arises from the medulla between the olive and inferior cerebellar peduncle and upper cervical spinal cord to C5. It forms from the combination of both cranial and spinal nerve roots. This nerve supplies both the trapezius and sternocleidomastoid muscles with motor innervation. It’s efferent motor fibers arise from the nucleus ambiguous.

The hypoglossal nerve (cranial nerve XII)

Is a motor nerve and arises anteriorly from the medulla, its nucleus sits in the midline of the brainstem anterior to the fourth ventricle. The hypoglossal nerve innervates the muscles of the tongue and the hyoglossus, genioglossus, and styloglossus muscles. It receives innervation via cortico-nuclear fibers from both hemispheres of the brain. However, the genioglossus muscle is innervated only by the contralateral side.

Function of Brainstem

The following brainstem reflexes should be carried out for evaluating the clinical integrity of the brainstem: 

  • The corneal reflex – The blinking of eyelids after touching the cornea with a cotton wisp or small jet of water.
  • The pupillary light reflex  – This constitutes brisk constriction of the pupils after exposure to bright light. However,  precautions are necessary to rule out any previous eye surgeries, concurrent cataract, and use of drugs such as atropine.
  • Oculocephalic reflex – Turning of the eyes in the opposite direction of head movement when the head is turned from the mid position to both sides. This should not be attempted in patients with concern for cervical cord injuries.
  • Oculovestibular reflex – Lack of eye movements after 50 ml of ice-cold water is instilled into the external auditory meatus over one minute after assuring patency of the tympanic membrane.
  • Gag reflex – Pharyngeal contraction after stimulating the pharynx with a spatula or tongue depressor.
  • Cough reflex – Presence of cough after stimulation of the carina by a bronchial catheter.
  • Response to noxious stimuli – along with the distribution of cranial nerves. For-example facial grimace after noxious stimulus applied on the supraorbital ridge supplied by the trigeminal nerve.

However, following confounding factors that can impede upon correct evaluation of the brainstem function must first be ruled out:

  • No concurrent use of central nervous system depressant drugs or neuromuscular blocking agents

    • Must wait for at least five half-lives of the drug to attempt valid evaluation if such agents have been used
  • Normal core body temperature
  • Normal systolic blood pressure
  • No severe electrolyte, acid-base or endocrine disturbances

If the patient fulfills the above criteria and evaluation reveal the absence of brainstem reflexes, the clinician should perform apnea testing per the AAN recommendation.

Apnea Test:

  • Connect a pulse oximeter, pre-oxygenate with 100% oxygen (O2), and disconnect the ventilator.
  • Deliver 100% O2 at 6 L/min through a cannula placed at the level of the carina.
  • If respiratory movements are absent despite arterial partial pressure of carbon dioxide (PCO2) of greater than or equal to 60 mmHg or a 20 mmHg increase in PCO2 over a normal baseline is noted, the apnea test is considered concluded.

The test is terminated in instances wherein there is hypotension, hypoxemia, or cardiac arrhythmias. The absence of brainstem reflexes and an apnea test negative for spontaneous respirations validate the brain death of the patient.

Ancillary tests that can be used to diagnose brain death include:

  • Flat electrical activity on at least a 30-minute electroencephalogram (EEG)
  • Absence of cerebral flow beyond the circle of Willis during angiography
  • No uptake of isotope within the blood vessel or brain parenchyma during a nuclear scan
  • Small systolic peaks in early systole without diastolic flow or reverberating flow on a transcranial doppler

These tests are only justified when apnea testing is inconclusive, or patients are too unstable to proceed with apnea testing, or when brainstem reflexes cannot be carried out (vestibulo-ocular reflex in cervical spine injuries).

Issues of Concern

Brainstem death is a clinical diagnosis made by an examiner. Ancillary tests are not essential for confirming brain death.

Brainstem death has to be certified by certified board members, which include:

  •  Medical superintendent (MS) – in-charge of the hospital
  •  The treating medical or critical care specialist
  •  A neurologist or a neurosurgeon

Members from the organ donation or the transplantation team cannot be involved in this certification.

The clinical diagnosis of brain death should take place in three steps:

  • Establishing the etiology
  • Excluding possible reversible syndromes that may produce signs similar to brain death
  • Demonstration of clinical signs of brain death including coma, brainstem areflexia, and apnea

However, when planning for organ donation, separate complete examinations by two physicians is recommended.

Ethical morality – justifying the use of limited medical resources, adding up the financial burden, and maximizing emotional toll to relatives in a hopeless clinical scenario

The whole-brain death concept- It is more prudent for the application of brainstem death rather than the whole brain death concept. It requires emphasis that though the brain stem is dead, there may still be some cortical and the hypothalamic functions (osmoregulation) intact in the patient. It is also distinct from cortical death (persistent vegetative state) wherein the brainstem functions are intact.

Concerns with the apnea test- There are inherent confounding clinical factors that can invalidate the apnea test, such as hypoxia, hypotension, cervical cord injuries. Moreover, hypercarbia by causing cerebral vasodilation can further impede upon the cascade of impending cerebral herniation, thereby further complication the clinical scenario.

Public belief in brain death and organ procurement- There can be a significant concern among the relatives and the public that organ donation occurs when the patient heart is still beating, and the person is not entirely dead. There can be looming fear that death will be declared prematurely for the sake of organ and tissue retrieval.

Is the brain dead person really dead? – Issues in defining biological death – certain pitfalls merit consideration while evaluating for brainstem death confirmation:

  • The inexperience – of the performing physician
  • Potential confounders – such as hypothermia, drugs, alcohol
  • Inadequate consideration during apnea test– such as low pCO2, ventilator trigger settings
  • False Positive Brain Death Determination – in scenarios such as barbiturate coma, baclofen toxicity
  • False Negative Brain Death Determination – spinal reflexes and automatisms, ventilator auto-triggering during the apnea test
  • Brain Death in Children – From 37 weeks of gestational age to 30 days, two examinations 24 hours apart whereas in 30 days to 18 years child, two examinations 12 hours apart
  • Limitations of Ancillary Tests – artifacts in EEG
  • Concerns relating to families and potential Organ donation – such as personal and religious beliefs
  • Failure to Maintain adequate environment for Organ donation – Systolic blood pressure of 100 mm Hg, urine output of at least 0.5 ml/kg/h; normal serum electrolytes and a tidal volume, not more than 8 ml/kg

References

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