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Section IV • Neuroscience

Clinical Correlate

Neurons in both the raphe and locus caeruleus degenerate in Alzheimer disease.

Parinaud Syndrome

Parinaud syndrome usually occurs as a result of a pineal tumor compressing the superior colliculi. The most common sign is paralysis of upward or vertical gaze, combined with bilateral pupillary abnormalities (e.g., slightlydilated pupils, which may show an impaired light or accommodation reaction) and signs of el­ evated intracranial pressure. Compression of the cerebral aqueduct can result in noncommunicating hydrocephalus.

RETICULAR FORMATION

The reticular formation is located in the brain stem and functions to coordinate and integrate the actions of different parts of the CNS. It plays an important role in the regulation of muscle and reflex activity and control of respiration, cardio­ vascular responses, behavioral arousal, and sleep.

Reticular Nuclei

Raphe nuclei

The raphe nuclei are a narrow column of cells in the midline ofthe brain stem, ex­ tending from the medulla to the midbrain. Cells in some of the raphe nuclei (e.g., the dorsal raphe nucleus) synthesize serotonin (5-hydroxytryptamine [5-HT]) from L-tryptophan and project to vast areas ofthe CNS. Theyplay a role in mood, aggression, and the induction ofnon-rapid eye movement (non-REM) sleep.

Locuscaeruleus

Cells in the locus caeruleus synthesize norepinephrine and send projections to most brain areas involved in the control of cortical activation (arousal). De­ creased levels ofnorepinephrine are evident in REM (paradoxic) sleep.

Periaqueductal gray

The periaqueductal (central) gray is a collection of nuclei surrounding the ce­ rebral aqueduct in the midbrain. Opioid receptors are present on many periaq­ ueductal gray cells, the projections from which descend to modulate pain at the level ofthe dorsal horn of the spinal cord.

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Chapter 5 • The Brain Stem

ChapterSummary

The brain stem is divided into 3 major subdivisions-the medulla oblongata, pons, and midbrain. The brain stem contains many descending and ascending tracts, the reticular formation, and the sensory and motor cranial nuclei ofCNs Ill-XII. Cranial nerve nuclei forCN Ill and IV are located in the midbrain; cranial nerve nuclei for CN V-Vlll are located in the pons; and cranial nerve nuclei of IX-XII in the medulla. Most ofthe motor nuclei are located medially and the sensory nuclei are located more laterally in the brain stem. Normal functions ofthe cranial nerves and the clinical deficits resulting from lesions ofthe brain stem are listed in Table IV-5-1. Lesions affecting the 3 long tracts to and from the spinal cord will produce contralateral deficits, but lesions ofthe motor or sensory cranial nuclei result in ipsilateral findings.

The motor nuclei of CNs Ill-VII and IX-XII are lower motor neurons that innervate most ofthe skeletal muscles ofthe head. These lower motor neurons are innervated by upper motor neurons (corticobulbar fibers). The cell bodies of the corticobulbar fibers are found primarily in the motor cortex of the frontal lobe. Corticobulbar innervation of lower motor neurons is primarily bilateral from both the right and left cerebral cortex, except for the innervation ofthe lower facial muscles around the mouth, which are derived only from the contralateral motor cortex. Generally, no cranial deficits will be seen with unilateral corticobulbar lesions, except for drooping ofthe corner of the mouth contralateral to the side of the lesion.

CN VIII provides sensory pathways for auditory and vestibular systems.

Auditory input depends on the stimulation of hair cells on the organ of Corti due to movement of endolymph within the membranous labyrinth of the inner ear. Axons from the organ of Corti enterthe pons via CN VIII and

synapse in the cochlear nuclei. From the cochlear nuclei, auditory projections bilaterally ascend the brain stem to the superior olivary nuclei, then via the lateral lemniscus to the inferior colliculus, and then to the medial geniculate body of the thalamus. Final auditory projections connect the thalamus with the primary auditory cortex of both temporal lobes. Thus, each auditory cortex receives input from both ears; however, input from the contralateral ear predominates. Lesions of the inner ear or ofthe cochlear nuclei in the

pons will produce total deafness, whereas other lesions central to the cochlear nuclei will primarily affect the ability to localize sound directi(Continued).

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Section IV • Neuroscience

From medialto lateral, the deep cerebellar nuclei in the internal white matter are the fastigial nucleus, interposed nuclei, and dentate nucleus.

Two kinds ofexcitatoryinput enter the cerebellum in the form ofclimbingfibers and mossy fibers. Both types influence the firingofdeep cerebellar nucleibyaxon collaterals.

Climbingfibers originate exclusively from the inferiorolivarycomplexofnuclei on the contralateral side ofthe medulla. Climbing fibers provide a direct power­ ful monosynaptic excitatoryinput to Purkinje cells.

Mossyfibersrepresentthe axonsfromallothersourcesofcerebellarinput. Mossy

fibers provide an indirect, morediffuseexcitatory input to Purkinje cells.

Allmossyfibers exertan excitatory effect on granule cells. Each granule cell sends its axon into the molecular layer, where it gives offcollaterals at a 90-degree angle thatrun parallelto the cortical surface (i.e.,parallelfibers). These granule cell axons stimulate the apical dendrites of the Purkinje cells. Golgi cells receive excitatory input from mossy fibers and from the parallel fibers ofthe granule cells. The Golgi cell in turn inhibits the granule cell, which activatedit in the firstplace.

The basket and stellate cells, which also receive excitatory input from parallel fibers ofgranule cells, inhibit Purkinje cells.

CIRCUITRY

Thebasic cerebellar circuits beginwith Purkinje cells that receiveexcitatoryinput directly from climbing fibers and from parallel fibers ofgranule cells.

Purkinje cell axons project to and inhibit the deep cerebellar nuclei or the ves­ tibular nuclei in an orderlyfashion (Figure IV-6-3).

Purkinje cells in the flocculonodular lobe project to the lateral vestibular nucleus.

Purkinje cells in the vermis project to the fastigial nuclei.

Purkinje cells in the intermediate hemisphere primarily project to the interposed (globose and emboliform) nuclei.

Purkinje cells in the lateral cerebellar hemisphere project to the dentate nucleus.

Dysfunction

Hemisphere lesions -7 ipsilateral symptoms: intention tremor, dysmet­ ria, dysdiadochokinesia, scanning dysarthria, nystagmus, hypotonia

Vermal lesions -7 truncal ataxia

MajorPathway

Purkinje cells -7 deep cerebellar nucleus; dentate nucleus -7 contralateral VL -7 first-degree motor cortex -7 pontine nuclei -7 contralateral cerebellarcortex

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Section IV • Neuroscience

Clinical Correlate

Anterior vermis lesions are usually the result of degeneration from alcohol abuse and are present with gait ataxia. Posterior vermis lesions result from medulloblastomas or ependymomas and present with truncal ataxia.

Efferents from the deep cerebellar nuclei leave mainlythrough the SCP and influ­ ence allupper motoneurons. In particular, axons from the dentate and interposed nuclei leave through the SCP, cross the midline, and terminate in the ventrolat­ eral (VL) nucleus ofthe thalamus.

The VL nucleus ofthe thalamus projects to primary motor cortex and influences the firing ofcorticospinal and corticobulbar neurons.

Axons from other deep cerebellar nuclei influence uppermotoneurons in the red nucleus and in the reticular formation and vestibular nuclei.

Cerebellar Lesions

The hallmark of cerebellar dysfunction is a tremor with intended movement without paralysis or paresis. Symptoms associated with cerebellar lesions are ex­ pressed ipsilaterally because the major outflow ofthe cerebellum projects to the contralateral motor cortex, and then the corticospinal fibers cross on their wayto the spinal cord. Thus, unilateral lesions ofthe cerebellum willresult in a patient falling toward the side ofthe lesion.

Lesions that include the hemisphere

Lesions that include the hemisphere produce a number of dysfunctions, mostly involving distal musculature.

An intention tremor is seen whenvoluntarymovements are performed. Forexam­ ple, ifa patient with a cerebellar lesion is asked to pick up a penny, a slight tremor of the fingers is evident and increases as the penny is approached. The tremor is barelynoticeable or is absent at rest.

Dysmetria (past pointing) is the inabilityto stop a movement at the proper place. The patient has difficulty performing the finger-to-nose test.

Dysdiadochokinesia (adiadochokinesia) is the reduced ability to perform alter­ nating movements, such as pronation and supination of the forearm, at a mod­ erately quickpace.

Scanning dysarthria is causedby asynergy ofthe muscles responsible for speech. In scanning dysarthria, patients divide words into syllables, thereby disrupting the melody ofspeech.

Gaze dysfunction occurs when the eyes try to fix on a point: They may pass it or stop too soon and then oscillate a few times before they settle on the target. A nystagmus may be present, particularly with acute cerebellar damage. The nys­ tagmus is often coarse, with the fast component usually directed toward the in­ volved cerebellar hemisphere.

Hypotonia usually occurs with an acute cerebellar insult that includes the deep cerebellar nuclei. The muscles feel flabby on palpation, and deep tendon reflexes are usually diminished.

Lesions to the vermal region

Verma! lesions result in difficultymaintaining posture, gait, or balance (an ataxic gait). Patients with vermal damage maybe differentiated from those with a lesion of the dorsal columns by the Romberg sign. In cerebellar lesions, patients will swayor lose their balancewith their eyes open; in dorsal column lesions, patients sway with their eyes closed.

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Chapter 6 • The Cerebellum

ChapterSummary

The cerebellum controls posture, muscle tone, and learning of repeated motor functions, and coordinates voluntary motor activity. Diseases ofthe cerebellum result in disturbances of gait, balance, and coordinated motor actions, but there is no paralysis or inability to start or stop movement.

The cerebellum is functionally divided into (1) the vermis and intermediate

zone, (2) the hemisphere, and (3) the flocculonodular lobe. Each ofthese 3 areas receives afferent inputs mainly from the spinal cord, cortex and inferior olivary nucleus, and vestibular nuclei, respectively. These afferent fibers (mossy and climbing) reach the cerebellum via the inferior and middle cerebellar peduncles, which connect the cerebellum with the brain stem. The afferent fibers are excitatory and project directly or indirectlyvia granule cells to the Purkinje cells ofthe cerebellar cortex. The axons of the Purkinje cells are inhibitory and are the only outflow from the cerebellar cortex. They project to and inhibit the deep cerebellar nuclei (dentate, interposed, and fastigial nuclei) in the medulla. From the deep nuclei, efferents project mainly through the superior cerebellar peduncle and drive the upper motor neurons ofthe motor cortex. The efferents from the hemisphere project through the dentate nucleus, to the contralateral ventral lateral/ventral anterior nuclei of the thalamus, to reach the contralateral precentral gyrus.

These influence contralateral lower motor neurons via the corticospinal tract.

Symptoms associated with cerebellar lesions are expressed ipsilaterally. Unilateral lesions ofthe cerebellum will result in a patient falling toward the side of the lesion. Hallmarks of cerebellar dysfunction include ataxia, intention tremor, dysmetria, and dysdiadochokinesia.

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