THE NEUROLOGIC EXAMINATION Ralph F



Brainstem – Part 2: Midbrain

DAVID GRIESEMER, MD

Professor of Neurosciences and Pediatrics

Key Concepts:

1. On the ventral surface of the midbrain are the cerebral peduncles, and in the interpeduncular fossa are the oculomotor nerves (CN III).

2. The oculomotor nerve (CN III) innervates all extraocular muscles except the lateral rectus and superior oblique, and it has an autonomic nucleus called the Edinger-Westfal nucleus.

3. The Edinger-Westfal nucleus sends preganglionic parasympathetic fibers to the ciliary ganglion, from which postganglionic fibers travel to innervate the papillary constrictor muscles and the ciliary muscles (which alter the shape of the lens).

4. Pupillary fibers travel on the outside of the oculomotor nerve and are therefore more sensitive to external compression.

5. On the dorsal surface of the midbrain is the quadrigeminal plate, consisting of the superior colliculi and the inferior colliculi.

6. Neurons from the superior colliculus, which are involved in visual processing, project to the lateral geniculate and thalamus.

7. Neurons from the inferior colliculus, which coordinate head and eye movement in response to sound, project to the medial geniculate from which it receives feedback information.

8. The trochlear nerves (CN IV) leave the dorsal surface of the midbrain near the center of the quadrigeminal plate.

9. The trochlear nerve, which is a pure motor nerve that innervates the superior oblique muscle, is the smallest cranial nerve and the only one that decussates before leaving the brainstem.

10. Axons traveling between nuclei of CN III, IV and VI travel in the medial longitudinal fasciculus.

11. The pretectal area (rostral to the quadrigeminal plate) is involved in the pupillary light reflex.

12. The dorsal raphe nucleus is a source of serotonergic neurons which project throughout the brain.

13. The substantia nigra sends dopaminergic projections primarily to the dorsal striatum.

14. The red nucleus, which is primarily concerned with coordinating movement of the arms, receives input from the cerebral cortex and the deep cerebellar nuclei. Its output is to the spinal cord, cerebellum, reticular formation and inferior olive.

15. The periaqueductal gray nuclei modulate pain, respirations, behavior, and vertical gaze.

The midbrain contains many important structures and systems that coordinate eye movements, various reflexes to light, and pathways and function of the basal ganglia.

EXTERNAL VIEW OF THE MIDBRAIN

The ventral surface of the midbrain (mesencephalon) is dominated by two massive, V-shaped columns at the ventrolateral edges. These are the cerebral peduncles that consist mainly of axons originating in the cerebral cortex that descend to synapse on brainstem and spinal cord nuclei. As the columns descend to the level of the pons, they disappear into the prominent brachum pontis, and at the level of the medulla they re-appear as the pyramids. The roughly triangular depression between the cerebral peduncles at the level of the midbrain is called the interpeduncular fossa. From this fossa emanates the oculomotor nerves (CN III). Just above the oculomotor nerves can be seen the mammillary bodies, which are considered part of the diencephalon rather than the midbrain. Note in the cross-section view (on the left) the “disorienting” view of the midbrain; it appears upside down. The traditional anatomic sections of the brainstem are 180 degrees from the standard radiologic view of the brain.[1]

The trochlear nerve (CN IV) emerges from the dorsal surface (tectum) of the midbrain, slightly below the level that the oculomotor nerve emerges on the ventral surface. Rostral to the trochlear nerve is the quadrigeminal plate, which consists of two larger superior colliculi and two smaller inferior colliculi. The former are involved in control of eye and head movements, and the latter participate in ascending pathways that process auditory signals. Also on the dorsal aspect is the brachium conjunctivum (superior cerebellar peduncle)¸ which is the most rostral connection of the cerebellum to the brainstem.

INTERNAL STRUCTURES OF THE MIDBRAIN

A cross section of the midbrain provides an axial view that demonstrates a very distinctive appearance of the midbrain. The ventrolateral cerebral peduncles are massive, creating bulges almost as large as the rest of the midbrain. The small cerebral aqueduct is seen as the later development of the central canal. It is surrounded by periaqueductal gray matter. At the ventral margin of the periaqueductal gray matter lie the trochlear nuclei (CN IV) in a midline position.

Dorsal to the cerebral aqueduct is the midbrain tectum which contains the nuclei of the superior and inferior colliculi (the four together creating the “quadrigeminal plate”). The superior colliculi are slightly higher (more rostral) than the CN IV nuclei, and the inferior colliculi are slightly lower (more caudal). The drawing on the left, while not showing CN IV, demonstrates the relationship of the tectum to the thalamus and lateral geniculate rostrally.

Ventral to the cerebral aqueduct and periaqueductal gray matter are two well-defined, “color coded” nuclei:

• red nucleus – named for its pinkish appearance at autopsy. These are symmetric, large, round nuclei located in the midbrain tegmentum. They fill the space between the periaqueductal gray matter and the substantia nigra. The oculomotor nuclei (CN III) are medial to the red nuclei.

• substantia nigra – named for neurons which contain black-colored melanin. These nuclei are located in the midbrain basis.[2] They are broad flat structures which separate the cerebral peduncles from the rest of the midbrain.

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It is beneficial to consider two cross-sectional (axial) views of the midbrain: one at the level of the inferior colliculus and one at the level of the superior colliculus:

• Level of the inferior colliculus

o In the tectum

▪ nucleus of the inferior colliculus – this receives afferents from the lateral lemniscus, the cerebral (auditory) cortex and the contralateral inferior colliculus. In addition it receives a feedback loop from the ipsilateral medial geniculate body to which it sends efferent axons. It also sends efferents to the superior colliculus to facilitate turning the head and eyes in response to sound.

▪ mesencephalic nucleus of V -- this is homologous to a dorsal root ganglion for the spinal cord, but it is uniquely positioned within the CNS. It is located medial to the inferior colliculi. It processes proprioceptive signals from the gums and muscles of mastication.

▪ locus ceruleus – this nucleus was discussed with structures of the pons, but it extends rostrally to the lower midbrain. It’s noradrenergic projections have a role in the regulation of arousal, sleep and cognitive functions such as attention.

o In the tegmentum

▪ nucleus of the trochlear nerve (CN IV) – these nuclei are midline in location, at the ventral margin of the periaqueductal gray matter. Axons from the nuclei course dorsally around the central gray matter and once in the tectum cross to the opposite side before exiting near the midline at the center of the quadrigeminal plate. The trochlear nerve innervates the superior oblique muscle, which lowers the eye when looking medially.

[pic]

▪ medial longitudinal fasciculus (MLF) – this ascending pathway is located immediately ventral to the CN IV nuclei.

▪ dorsal raphe nucleus -- this nucleus is located directly in the center of the four “spots” created by the CN IV nuclei and the MLF, appearing like a 5-spot on one of two dice. Neurons in this nucleus send serotonergic fibers to the substantia nigra, the caudate and putamen, and throughout the cerebral cortex.

▪ red nucleus – this nucleus receives fibers from deep nuclei of the cerebellum and from the motor and pre-motor cortex of the brain. These latter projections are somatotopically arranged. The corticorubral and rubrospinal tracts are often considered an “indirect” corticospinal system. The red nucleus participates in the control of arm movement. It sends efferents to the spinal cord, cerebellum, reticular formation, and inferior olive.

▪ other nuclei in the tegmentum include the ventral tegmental nucleus (which deals with emotion and behavior), the dorsal tegmental nucleus (which projects to brainstem autonomic nuclei), and the parabigeminal nucleus (which sends cholinergic fibers to the superior colliculus and processes visual information).

▪ pathways that track through the tegmentum include:

• brachium conjunctivum (superior cerebellar peduncle) – these axons originate in the deep nuclei of the cerebellum and project to the midbrain where they cross to the opposite side in the tegmentum. Some of the fibers synapse on neurons of the red nucleus and others continue rostrally to the thalamus (VPL nucleus).

• lemniscal pathways – these include the medial lemniscus (which carries kinesthetic and discriminative touch information), the trigeminal lemniscus (which carries sensation from the contralateral face), and the spinothalamic tract (which carries sensation from the contralateral body). All three originate from levels below the midbrain and are just “passing through” to the thalamus (VPL nucleus). Lateral to the spino-thalamic tract is the lateral lemniscus (which carries auditory fibers).

• medial longitudinal fasciculus (MFL) – in addition to other functions, this pathway provides a conduit of communication between cranial nerve nuclei at different levels involved in the control of eye movements (CN III, IV and VI).

• central tegmental tract – this carries information from basal ganglia and midbrain to the inferior olive

• rubrospinal tract – located between the red nucleus and the substantia nigra, this pathway carries fibers from the red nucleus to the spinal cord and inferior olive

o In the basis

▪ cerebral peduncles -- corticospinal and corticobulbar fibers occupy a mid-position in the cerebral peduncles. Corticopontine fibers that synapse on pontine nuclei are located in the most ventral and dorsal positions. In a rostral direction the cerebral peduncles become the internal capsule.

▪ substantia nigra – this large nucleus has two regions: a dorsal region with melanin-containing dopaminergic neurons (zona compacta) and a ventral region containing iron pigment (zona reticulata). Pigmented neurons are twice as numerous as non-pigmented neurons and project dopaminergic fibers to the striatum of the basal ganglia. Destruction of these neurons leads to Parkinson’s disease. Non-pigmented neurons from the zona reticulate project GABAergic fibers to the thalamus, superior colliculus, and reticular formation. They likely have a role in minimizing epileptic discharges.

▪ Mesencephalic nuclei – there are other dopaminergic neurons at this level in addition to those of the substantia nigra. They occur in lesser known areas: the ventral tegmental area of Tsai and a retrorubral group of neurons close to the red nucleus. Dopaminergic fibers from these cells also project to the striatum and may have a role in reward processing and cognition.

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• Level of the superior colliculus

o In the tectum

▪ nucleus of the superior colliculus – this is a laminated nucleus consisting of alternating layers of gray matter and white matter. It’s highly structured organization mirrors that of visual fields and represents a map of visual space. In addition to the retina, it receives projections from the frontal and occipital cortex, spinal cord, and inferior colliculus – all of which provide input necessary for coordination of rapid visual pursuit and movement. Efferents from the superior colliculus travel to:

• lateral geniculate, pulvinar, and lateral posterior nucleus (LPN) of the thalamus via the tectothalamic tract

• lamina VII and VIII of the cervical spinal cord via the tectospinal tract, which decussates in the midbrain tegmentum

• ipsilateral cerebellum via the tectopontocerebellar tract

• reticular nuclei in the midbrain via the tectoreticular tract

▪ pretectal nucleus – this area is rostral to the superior colliculus at the junction of the midbrain with the diencephalon. It is an important relay station in the pupillary light reflex and vertical gaze. It receives fibers from both retinas and projects to both oculomotor nuclei (CN III).

o Periaqueductal gray – neurons in this region stimulate serotonergic neurons in the medulla, which then project to sensory neurons in the dorsal horn of the spinal cord to decrease pain. Other functions of this region include:

▪ control of vertical gaze

▪ initiation of voiding in response to bladder filling

▪ initiation of penile erection in response to stimuli from hippocampus, amygdala, reticular formation, and spinal cord

▪ modulation of respiratory centers in the medulla

▪ activation of behaviors relating to fear and escape

▪ modulation of aggressive behavior

o In the tegmentum

▪ red nucleus – discussed above

▪ oculomotor nucleus (CN III) -- this nucleus lies dorsal to the MLF. It is composed of a lateral somatic motor column and a medial visceral column, each about 1 cm in length. The latter is called the Edinger-Westfal nucleus, or visceral oculomotor nucleus, and it mediates the light reflex.

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• The oculomotor nerve exits the brainstem between the superior cerebellar artery and the posterior cerebral artery. It then runs anteriorly in the subarachnoid space until it penetrates the dura at the roof of the cavernous sinus. Here it divides into superior and inferior divisions. The superior division provides innervation to the levator palpebrae (which raises the eyelid) and to the superior rectus muscle (which elevates the eye when looking laterally).

• The inferior division innervates the inferior rectus (which lowers the eye when looking laterally), the medial rectus (which adducts the eye), and the inferior oblique (which elevates the eye when looking medially).

• Axons from the Edinger-Westfal nucleus course with other fibers until the orbit where these preganglionic fibers synapse in the ciliary ganglion. Postganglionic fibers innervate the papillary sphincter[3] (which constricts the pupil) and the ciliary muscles (which change the shape of the lens to permit focus at a closer distance).

▪ accessory oculomotor nuclei

• Interstitial nucleus of Cajal – located rostral to Edinger-Westfal nucleus, this group of neurons coordinates vertical gaze and eye-head movement.

• Rostral interstitial nucleus of the MLF – located rostral to the oculomotor nucleus and close to the red nucleus, this groups of “burst” neurons is involved with upward and downward eye movements

• Other nuclei include the Darkschewitsch nucleus and the nucleus of the posterior commissure.

BLOOD SUPPLY TO THE MIDBRAIN

The blood supply to the midbrain is complex, compared to that of the pons and medulla. In general, the midbrain receives its blood supply from the basilar artery via the superior cerebellar artery and branches from the posterior cerebral and posterior communicating arteries.

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[1] CT and MRI studies show the brain as if the patient is lying on his back and the viewer is standing at the foot of the bed. The right side of the brain therefore appears on the left side of the radiographic image.

[2] The cerebral peduncles and the substantia nigra, which are located in the basis of the midbrain, are sometimes called the basis pedunculi. The cerebral peduncles alone are sometimes called the crus cerebri.

[3] Parasympathetic fibers responsible for the papillary light reflex travel on the outside of motor fibers in the oculomotor nerve. This has two important clinical consequences. First, the pupillary fibers are more sensitive to external compression. Thus pupillary reflexes are likely to be lost first in cases of tumors or masses compressing CN III. Second, the oculomotor nerve receives its vascular supply from penetrating arterioles in the center of the nerve. If disease processes (like diabetes) compromise these vessels, the interior of the nerve is likely to infarct. The unmyelinated parasympathetic fibers are relatively resistant to ischemia and they are superficially located. This leads to weakness of muscles of eye movement, with sparing the papillary light reflexes. This is referred to as a “pupil-sparing third nerve palsy.”

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