CHAPTER 21

Brainstem and Multiple Cranial Nerve Syndromes

he is a compact structure, with cra- the lower motor neurons of the CN nuclei. With a nial nerve (CN) nuclei, nerve fascicles, and few exceptions, CNs innervate structures of the head T long ascending and descending tracts all and neck ipsilaterally. A process affecting the brain- closely juxtaposed. Structures and centers in the reticu- stem long tracts on one side causes clinical abnormal- lar formation control many vital functions. Brainstem ities on the opposite side of the body. For this reason, diseases are serious and often life threatening. focal brainstem lesions are characterized by “crossed” Involvement of the intricate network of neural struc- syndromes of ipsilateral CN dysfunction and contra- tures often causes a plethora of clinical findings. lateral long motor or sensory tract dysfunction. For Brainstem syndromes typically involve dysfunction of instance, in the right side of the pons, the nuclei for one or more CNs. Deficits due to dysfunction of indi- CNs VI and VII lie in proximity to the right corti- vidual nerves are covered in the preceding chapters. cospinal tract, which is destined to decussate in the This chapter discusses conditions that cause dysfunc- medulla to innervate the left side of the body. The tion beyond the distribution of a single CN, involving patient with a lesion in the right pons will have CN more than one CN, or conditions that involve brain- findings on the right, such as a sixth or seventh nerve stem structures in addition to the CN nucleus or fasci- palsy, and a on the left. cles. The first part covers intramedullary disorders of This crossed deficit will often be associated with the brainstem, and the second part covers disorders that symptoms reflecting dysfunction of other brainstem involve multiple CNs in their extramedullary course. structures or their connections. Because of the rich Some may argue it is sufficient to recognize that a vestibular and cerebellar connections, patients with brainstem disorder exists and to define the process more brainstem disease often have dizziness or vertigo, precisely with an imaging study. However, some impor- unsteadiness, imbalance, incoordination, difficulty tant clinical conditions may cause major brainstem dys- walking, nausea, and vomiting. Pharyngeal and laryn- function without dramatically changing the appearance geal muscles are innervated by neurons in the brain- of the imaging study. Examples of processes easily missed stem, and patients often have or . radiographically include Wernicke’s disease, progres- Dysfunction of CNs III, IV, and VI or their connec- sive (PBP), progressive supranuclear palsy, tions may cause ocular motility abnormalities. Unless basilar artery , Whipple’s disease, , the process has impaired the reticular activating sys- olivopontocerebellar atrophy, and Gerstmann-Sträussler- tem, these patients are normal mentally—awake, Scheinker syndrome. With disorders causing multiple alert, able to converse (though perhaps dysarthric), CN deficits, the imaging studies are often not helpful. not demented, not confused, and not aphasic. The fourth ventricle and cerebral aqueduct lie nearby; if these are involved, patients may develop obstructive BRAINSTEM SYNDROMES . Although most pathologic processes that involve the brainstem occur in other parts of the In the brainstem, descending motor tracts prior to brain, some disorders are characterized by primarily decussation, as well as ascending sensory pathways brainstem involvement (e.g., central pontine myelin- that have already crossed, lie in intimate relation to olysis, medulloblastoma, and olivopontocerebellar­

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atrophy). With vascular lesions, the clinical deficit horizontal gaze palsy, internuclear ophthalmoplegia depends on whether the occlusive process has involved (INO), or impaired taste, with contralateral corti- the paramedian perforating, short circumferential, or cospinal weakness and impaired lemniscal sensation. long circumferential branches of the basilar artery. Thrombosis of the lateral pontine branches of the From an anatomical standpoint, brainstem syn- basilar artery produces ischemia that may involve the dromes may be localized by considering the rostral middle and superior cerebellar peduncles, the ves- to caudal level and the medial to lateral level. The tibular and cochlear nuclei, the facial and trigeminal rostral to caudal localization is determined by the motor nuclei, the trigeminal sensory nucleus, and the CN involvement. Abnormality of CN III or IV, or a spinothalamic tract. Findings may include ipsilateral vertical gaze abnormality, indicates a midbrain lesion; cerebellar and dysfunction of CNs V, VII, and CN VI or VII, or a horizontal gaze palsy—a pontine VIII, with contralateral loss of pain and temperature lesion; CN VIII—a pontomedullary junction lesion; sensation on the trunk and extremities. Occlusion of and CNs IX, X, XI, or XII—a medullary lesion. the internal auditory artery causes unilateral deafness Because of the vast longitudinal extent of the spinal and impaired vestibular function. tract of CN V, facial sensory abnormalities can occur with lesions anywhere from the pons to the cervical . CLASSICAL BRAINSTEM SYNDROMES The long motor tracts tend to lie medial, and the long sensory tracts lateral, in the brainstem. Somatic Many of the early neurologic pioneer clinicians motor nuclei (extraocular and hypoglossal) are para- described the clinical findings due to a focal process median; branchiomotor nuclei are more lateral. affecting the brainstem. These physicians practiced in Involvement of descending motor tracts or somatic an era when disorders such as tuberculoma, syphilitic motor nuclei indicates medial lesions; involvement of gumma, and tumor were seen much more often than long sensory tracts, branchiomotor nuclei, and special today. Many of the classical brainstem syndromes sensory nuclei indicates lateral lesions. The cerebel- as originally described were not due to ischemia, lar peduncles also lie laterally. The alar plate–derived and the effects of tuberculoma, gumma, and similar sensory nuclei lie laterally and are separated from the lesions are not limited to vascular distributions. Some basal plate–derived motor nuclei by the sulcus limi- degree of mismatch has therefore resulted between tans (Figures 11.2 and 11.4). Paramedian perforators the classic descriptions and the current environment from the basilar artery perfuse the midline structures; when most brainstem syndromes are due to ischemia. circumferential arteries perfuse the lateral structures. There has also been significant drift of many of the There are therefore medial and lateral medullary eponymic syndromes through failure to honor pre- syndromes; medial and lateral inferior, middle, cisely the original descriptions. Liu et al. pointed out and superior pontine syndromes; and the midbrain the variability in textbook descriptions of Claude’s, syndromes. The posterior inferior cerebellar artery Benedikt’s, and Nothnagel’s syndromes and noted (PICA) supplies the lateral medulla; the anterior the difference in textbook descriptions compared inferior cerebellar artery (AICA) supplies the inferior to the original papers. Box 21.1 contains a discus- lateral pons; and the superior cerebellar artery (SCA) sion of the classical eponymic brainstem syndromes, supplies the superior lateral pons. Paramedian lesions largely from a historical perspective, and Table 21.1 are typically lacunar; lateral lesions are more often summarizes the clinical features. from disease of the larger circumferential vessels. The Wallenberg described the lateral medullary syn- lateral medullary and pontine syndromes are often drome (LMS), the most common form of brainstem referred to by their vascular territory designations: . Wallenberg’s original patient had an occlusion PICA, AICA, and SCA. of the PICA, but LMS is most often due to isch- Occlusion of medial pontine branches of the emia in the PICA distribution­ because of vertebral basilar artery may cause involvement of the nuclei of artery occlusion (Figure 21.1). Typical manifestations CNs VI and VII or their emerging fibers, the medial include vertigo, nausea and vomiting, nystagmus, longitudinal fasciculus (MLF), the corticospinal hoarseness, dysphagia, dysphonia, singultus, ipsi- tract, the medial lemniscus, and the pontine parame- lateral hemiataxia, and numbness of the ipsilateral dian reticular formation. Clinical manifestations may face and contralateral body. Occipital or include ipsilateral palsy, abducens palsy, pain in the back of the neck may occur at the onset;

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BOX 21.1 Classical Brainstem Syndromes Midbrain Syndromes the ­midbrain tectum and is often neoplastic. Weber described a patient with a hematoma of one Nothnagel’s original patient had a pineal sarcoma. cerebral peduncle, which damaged the corticospi- Pontine Syndromes nal and corticobulbar tracts and the exiting third Millard and Gubler separately described patients nerve. The patient had a contralateral hemipare- with an ipsilateral lower facial nerve sis involving face, arm, and leg and an ipsilateral palsy and contralateral hemiparesis due to a lesion complete third nerve palsy. Benedikt described involving the pons. Gubler’s cases included three one patient with a similar peduncular lesion due with a tumor, one with a stroke, and one with a to a midbrain tuberculoma, which extended fur- brownish softening. Millard reported one case due ther into the tegmentum and involved the regions to pontine hemorrhage as a letter to the editor in of the substantia nigra and red nucleus, causing the journal where Gubler reported his cases. In all and involuntary movements of the hemipa- cases, the lesion lay in the lateral pons and did not retic limbs. Two clinically similar patients were not involve CN VI; the patients had no ocular motil- studied pathologically; one probably had meningo- ity disturbance. Nevertheless, it is common to see vascular syphilis. Claude described a patient with included in textbook descriptions a midbrain infarction in whom the corticospinal of Millard-Gubler syndrome. Gubler was a senior pathways were not involved; the clinical picture clinician reporting several cases; Millard had just was ipsilateral third nerve palsy and contralateral graduated from medical school, was essentially a due to involvement of the superior resident, and reported only one. Gubler instructed cerebellar peduncle. Debate remains about how the journal editor to give Millard precedence, hence much red nucleus involvement occurs in Claude’s the eponym. and Benedikt’s syndrome. Seo concluded on the Foville described a patient with an ipsilateral basis of clinical and magnetic resonance imaging facial palsy and a horizontal (MRI) studies that the lesion usually lies just caudal gaze palsy, with a contralateral hemiparesis; there and medial to the red nucleus and that the tremor was no pathology but the onset was apoplectic. and ataxia are due to involvement of the cerebel- Landry, in a letter commenting on Foville’s case, lar outflow pathways in the superior cerebellar described a patient with sixth nerve palsy and peduncle. contralateral hemiplegia, including the face, due These three midbrain syndromes are variations to pontine ischemia in a patient with syphilis. on a theme. The lesion is anterior—in the cerebral Yelloly had described a case of abducens palsy peduncle—in Weber’s syndrome, causing hemipa- with contralateral hemiplegia 50 years previ- resis. It is more posterior—in the tegmentum— ously. Raymond described a patient with sixth in Claude’s syndrome, causing hemiataxia. In nerve palsy and contralateral hemiplegia, but it Benedikt’s syndrome, the lesion is more extensive, is not clear that the hemiplegia was of pontine involving both the tegmentum and the peduncle, origin. causing hemiparesis with tremor and ataxia of the involved limbs; Benedikt’s is essentially Weber’s Medullary Syndromes + Claude’s. Because the fascicles of cranial nerve There are two primary medullary syndromes, the (CN) III are scattered in their course through the lateral (Wallenberg) and the medial (Dejerine). midbrain, the third nerve palsy in any of these syn- The rare medial medullary syndrome is summa- dromes may be partial. rized in Table 21.1. In a study of clinical mag- Nothnagel’s (ophthalmoplegia-ataxia) syn- netic resonance imaging (MRI) correlation in drome is different; it is more a variant of Parinaud’s medial medullary infarction, classical Dejerine’s syndrome, with unilateral or bilateral third nerve syndrome (ipsilateral weakness with con- palsy and ataxia accompanied by vertical gaze defi- tralateral hemiparesis and lemniscal sensory loss) cits and other neurologic signs. The lesion affects was seen in 64% of patients; the remainder had (continued)

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BOX 21.1 Classical Brainstem Syndromes (Continued) partial lesions, which may be less readily recog- bilateral ­medullary infarction. Other syndromes of nized. In a series of 18 patients, the most com- the medulla (Avellis’s, Jackson’s, Schmidt’s, Céstan- mon manifestation of medial medullary stroke was Chenais, and Babinski-Nageotte) are described in a unilateral sensorimotor deficit. The extremely Table 21.1. Except for the occasional upper motor rare bilateral medial medullary syndrome causes neuron facial palsy in Wallenberg’s syndrome, there quadriparesis and other abnormalities. Isolated is sparing of facial motor function in all of the med- tongue weakness has been reported because of ullary syndromes.

prominent pain raises the possibility of ­vertebral penetrating vessels from the rostral basilar artery. The artery dissection. The patient may be unable to talk LMS is discussed in the previous section, and the and swallow initially. Clinical findings are summa- medial medullary syndrome is discussed in Box 21.1. rized in Table 21.1. The vascular pontine syndromes can be divided In a series of MRI-verified LMS, the most com- into medial and lateral and into superior, middle, and mon findings were ipsilateral Horner’s syndrome and inferior. The medial pontine syndromes are due to ataxia and contralateral body hypalgesia. The sponta- disease of the paramedian perforators; the lateral pon- neous nystagmus is usually horizontal or mixed hor- tine syndromes are due to disease of the circumfer- izontal-torsional. Horizontal nystagmus beats away ential arteries. The AICA supplies the lateral inferior from the side of the lesion and may be second or third pons and upper medulla, whereas the SCA supplies degree. Torsional nystagmus with the upper poles beat- the lateral upper pons. The midpons is supplied by ing away from the side of the lesion is also common. a short circumferential artery. Just as PICA ischemia The nystagmus is influenced by head and eye posi- causes the LMS, ischemia in the AICA distribution tion and by fixation. Dysphagia is common. It is often causes the lateral inferior pontine syndrome; and more severe than would be expected simply from a ischemia in the SCA distribution causes the lateral lesion of the nucleus ambiguus, and disruption of con- superior pontine syndrome. The generally recognized nections to a premotor swallowing center in the dorso- pontine syndromes are therefore the medial inferior lateral medulla has been postulated. Partial resolution pontine, lateral inferior pontine (AICA), medial and and survival is the rule; the ability to swallow and talk lateral midpontine, medial superior pontine, and lat- returns, although residual hoarseness, persistent ataxia, eral superior pontine (SCA). The vascular pontine and sensory changes may remain. Aspiration is a major syndromes are summarized in Table 21.2. In a series threat. The presence of dysphonia, dysfunc- of patients with lesions involving the AICA distribu- tion, or facial sensory loss suggests an increased risk. tion, only 29% had the complete AICA syndrome. Although LMS is usually ischemic, it has also been Partial syndromes were characteristic of small vessel described with , abscess, hematoma, arterio- disease; more widespread involvement indicated basi- venous malformation, , and met- lar artery occlusive disease. The SCA syndrome is also astatic neoplasm. The LMS may have many unusual often partial. Basilar branch occlusion may involve manifestations (Box 21.2). any of the branches of the basilar artery. The mecha- nism is atherothrombotic occlusion at the point of origin of the branch, and the infarction typically ANATOMIC BRAINSTEM SYNDROMES extends to the ventral surface of the pons. Vertebrobasilar transient ischemic attacks (verte- The other approach to organizing brainstem syn- brobasilar insufficiency, VBI) are episodes of brain- dromes is by the anatomical area or the major blood stem ischemia due to occlusive disease involving the vessel involved. The midbrain syndromes are variations posterior circulation. Symptoms depend upon which and combinations of an ipsilateral third nerve palsy and region of the brainstem is ischemic. The clinical man- weakness, ataxia, or tremor of the contralateral limbs; ifestations of an attack of VBI are typically bilateral, this is due to ischemia in the distribution of paramedian­ with varying degrees of weakness, numbness, and CN

Chapter 21.indd 348 10/30/2019 4:14:27 PM CHAPTER 21 | Brainstem and Multiple Cranial Nerve Syndromes 349 - (continued) the posterior third ventricle, most often pinealoma, or due to midbrain infarction is inconsistent syndrome; usage is inconsistent ipsilateral facial palsy due to involvement of aberrant CST; facial sensation sometimes preserved; ischemia in PICA distribution but more often due to vertebral artery occlusion occasional involvement of ML and ST with loss of touch and propriocep tion of contralateral body; occasional syndrome occasional ipsilateral Horner’s ­ contralateral hemiparesis paralysis; more likely due to extramedullary multiple cranial nerve palsy more likely due to extramedullary multiple cranial nerve palsy Comment Usually due to mass lesion in the region of Usually vascular Usually vascular Usually vascular Usually neoplastic Usually vascular; CN VI not involved; usage Usually vascular; usage is inconsistent often lumped with Foville’s Usually vascular, Several variants recognized; occasional Usually due to vertebral artery thrombosis; Also known as vago-accessory-hypoglossal Also known as vago-accessory syndrome; - mus; dilated pupils with light near dissociation with ataxia, hyperkinesia, and tremor (“rubral tremor”) tremor (“rubral tremor”) hemiparesis contralateral hemiparesis hemiparesis and contralateral body; decreased ipsilateral corneal ; weakness of ipsilateral soft palate; loss of ipsilateral gag reflex; paralysis of ipsilateral vocal cord; central syndrome; nystagmus; cerebellar Homer’s ataxia of ipsilateral limbs; lateropulsion of pain and temperature contralateral body pharynx, and larynx; flaccid weakness atrophy of SCM and trapezius (partial) the tongue larynx; flaccid weakness and atrophy of SCM and trapezius (partial) Clinical Findings Impaired upgaze; convergence retraction nystag Ipsilateral CN III palsy; contralateral hemiparesis Ipsilateral CN III palsy; contralateral hemiparesis Ipsilateral CN III palsy; contralateral ataxia and Oculomotor palsies; ataxia Ipsilateral peripheral facial palsy; contralateral Ipsilateral facial palsy and horizontal gaze palsy; Ipsilateral abducens palsy; contralateral Loss of pain and temperature ipsilateral face Ipsilateral palatal and vocal cord weakness; loss Ipsilateral of the soft palate, Ipsilateral paralysis of soft palate, pharynx, and periaqueductal gray matter nucleus ambiguus; emerging fibers descending of CNs IX and X; LST; sympathetic fibers; vestibular nuclei; inferior cerebellar peduncle; afferent spinocerebellar tracts; lateral cuneate nucleus XI and XII nuclei of CN XI and/or their radicular fibers Structures Involved Quadrigeminal plate region; pretectum; CN III fibers; cerebral peduncle CN III fibers; red nucleus; CST CN III fibers; red nucleus; SCP Ipsilateral or bilateral CN III CN VII; CST CST CN VII; lateral gaze center, CN VI; CST Spinal tract of CN V and its nucleus; nucleus ambiguus CN X; LST; CN X fibers or nucleus ambiguus; CNs Nucleus ambiguus; bulbar and spinal tegmentum tegmentum Lesion Location Midbrain dorsum Midbrain base Midbrain tegmentum Midbrain tegmentum Midbrain tectum Pons Pons Pons Lateral medullary Medullary tegmentum Medullary tegmentum Lower medullary Summary of the Classical Named Brainstem Syndromes (Raymond-Foville) Landry) medullary syndrome) Syndrome Parinaud’s Weber’s Benedikt’s Claude’s Nothnagel’s Millard-Gubler Foville’s (Yelloly, Raymond’s (lateral Wallenberg’s syndrome Avellis’ syndrome Jackson’s Schmidt’s TABLE 21.1 TABLE

Chapter 21.indd 349 10/30/2019 4:14:28 PM 350 SECTION D | THE CRANIAL NERVES - the origin of PICA; differs from because of CST and ML Wallenberg’s involvement and absence of changes in pain and temperature chiefly in the distribution of vertebral artery; similar to, perhaps the same as, Céstan-Chenais ­ paramedian perforator or the anterior findings may be bilateral spinal artery, and of variable laterality because involvement of the pyramidal decussa tion and variations in the anatomy of anterior spinal artery Comment Due to vertebral artery occlusion below Caused by multiple or scattered lesions, Due to ischemia in the distribution of larynx; cerebellar ataxia; Horner’s syndrome; larynx; cerebellar ataxia; Horner’s contralateral hemiparesis with loss of posterior column function ­ larynx, +/− tongue; loss of taste on posterior third of tongue; impaired facial pain and syndrome; ­ temperature; ataxia; Horner’s contralateral hemiparesis; impaired posterior column function; +/− impaired pain and temperature hemiparesis (sparing the face); +/− impairment of posterior column function; LST functions spared Clinical Findings Ipsilateral weakness of soft palate, pharynx, and Ipsilateral paralysis of soft palate, pharynx, Ipsilateral tongue weakness; contralateral (Continued ) CST; ML CST; ICP; sympathetics; CST; tract of V; ML; +/−XII (at/near decussation); +/−ML Structures Involved Nucleus ambiguus; ICP; sympathetics; Nucleus ambiguus; solitary tract; spinal XII nucleus or fibers; medullary pyramid medulla Lesion Location Medullary tegmentum Medial and lateral Medial medulla - - Summary of the Classical Named Brainstem Syndromes medullary syndrome) syndrome (Dejerine’s anterior bulbar syndrome, pyramid- hypoglossal syndrome, alternating hypoglos sal hemiplegia) Syndrome Céstan-Chenais Babinski-Nageotte (hemi Medial medullary solitary tract. ST, TABLE 21.1 TABLE CN, cranial nerve; CST, corticospinal tract; ICP, inferior cerebellar peduncle; LST, lateral spinothalamic tract; ML, medial lemniscus; PICA, posterior inferior cerebellar artery; SCM, sternocleidomastoid; SCP, superior cerebellar peduncle; lateral spinothalamic tract; ML, medial lemniscus; PICA, posterior inferior cerebellar artery; SCM, sternocleidomastoid; SCP, inferior cerebellar peduncle; LST, corticospinal tract; ICP, CN, cranial nerve; CST,

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Dorsal efferent tract of nerve X

Nucleus solitarius

Med. vestibular nucleus

Inf. vestibular nucleus Lat. cuneate nucleus Restiform body

Nucleus of nerve XII Nucleus & root of nerve V

Nucleus ambiguus Vent. spinocerebellar Med. long. fasc. Roots of nerve X

Lat. spinothalamic tract

Secondary ascending tract of nerve V

Inf. olive

Pyramid Med. lemniscus FIGURE 21.1 Cross section of the medulla illustrating the lesion in the lateral medullary syndrome.

dysfunction. Accompanying symptoms indicative of thrombosis, frequently present at an early stage, brainstem dysfunction include diplopia, dysarthria, when brainstem signs are absent or inconspicuous, dysphagia, vertigo, nausea, and vomiting. There may followed within a few hours by bilateral hemiplegia be impaired vision due to ischemia in the posterior and coma or a locked-in state (Chapter 51). With cerebral artery distribution. Bilateral sensory com- total occlusion, there is either hemiplegia on one side plaints are common, especially circumoral paresthe- and partial hemiplegia on the other, or quadriplegia. sias. Attacks usually last from a few minutes to half Involvement of ascending sensory pathways causes a an hour, sometimes longer. disturbance of both deep and superficial sensations Basilar artery occlusion may have a gradual on the body, the extremities, and sometimes the face. onset or a fluctuating course with prodromata, but The pupils are usually miotic and poorly reactive. often, the symptoms appear apocalyptically; death Ocular bobbing and palatal may occur. may occur within a short period of time. When the The neurologic signs are characteristically variable onset is acute, there is sudden loss of and complex. Coma and decerebrate rigidity with with gradually increasing coma and flaccid extremi- respiratory and circulatory instability are common. ties or decerebrate rigidity. The onset may be sub- Patients with coma at the outset have a grave acute with prodromal vertigo, nausea, headache, and prognosis. The site of occlusion is usually in the lower paresthesias, which may occur up to 2 weeks before third of the basilar artery. The outcome with severe the stroke, followed by bilateral CN and long tract brainstem ischemic disease is usually poor. Death is a abnormalities (progressive basilar thrombosis). Fisher common outcome of complete basilar artery occlusion. described a “herald hemiparesis” in basilar artery Patients may be left in a locked-in state (Chapter 51).

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BOX 21.2 Unusual Manifestations of Lateral Medullary Syndrome Patients may have an ipsilateral upper motor neu- weakness are common and do not imply extension ron facial palsy due to involvement of Dejerine’s of the lesion beyond the lateral medulla. There may aberrant pyramidal tract (see facial nerve chapter). be contralateral hemiparesis due to inferior exten- In the series of Sacco et al., mild ipsilateral facial sion of the zone of ischemia to the medullary pyra- weakness was present in 42% of patients, usu- mid prior to decussation or ipsilateral hemiparesis ally limited to the lower face. The hypalgesia may due to inferior extension to the lateral funiculus of involve only the ipsilateral face or only the contra- the rostral spinal cord (Opalski’s submedullary syn- lateral body; the classical crossed pattern occurs drome, Figure 21.2). Rarely, there is impaired sen- only in a minority. Other patterns of sensory loss sation of the ipsilateral arm and leg due to inferior are discussed in Chapter 15. Ocular motor abnor- extension to the gracile and cuneate nuclei, ipsilat- malities are common, including skew deviation eral loss of taste, or contralateral facial hypalgesia. with ipsilateral hypotropia, ocular tilt reaction, Other unusual manifestations include wild unilat- bizarre environmental tilt illusions including world eral, proximal arm ataxia; neurotrophic ulceration inversion (floor on ceiling phenomenon), ipsilat- of the face; inability to sneeze; paroxysmal sneez- eral gaze deviation with impaired contralateral pur- ing; loss of taste; Ondine’s curse; and weakness suit, saccadic abnormalities, seesaw nystagmus, and of the sternocleidomastoid. Chronic central facial eyelid nystagmus. Ocular abnormalities and facial pain develops in some patients.

FIGURE 21.2 Imaging features of Opalski syndrome. Fluid-attenuated inversion recovery MRI. A. Directionally encoded map with hues reflecting tensor orientation.B. Superimposed images. C,D. A yellow halo represents the infarct and blue lines represent the (coronal); the tracts fuse at the decussation (transverse). Caudal extension of the lesion involves the ipsilateral corticospinal tract (arrows) after the decussation (arrowheads). (Reprinted from Nakamura S, Kitami M, Furukawa Y. Opalski syndrome: ipsilateral hemiplegia due to a lateral-medullary infarction. 2010;75[18]:1658, with permission.)

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TABLE 21.2 Summary of the Vascular Pontine Syndromes Organized by Anatomical Region and Blood Vessel Involved

Syndrome Structures Involved Clinical Findings Comment Medial inferior pontine PRRF; CN VI nucleus or Ipsilateral CN VI or horizontal gaze palsy; ataxia. Due to occlusion of fibers; MCP; CST; ML and impaired lemniscal sensation of paramedian perforat- contralateral limbs ing vessel Lateral inferior pontine CN VII nucleus or fibers; Ipsilateral cerebellar ataxia; loss of pain and Due to occlusion of AICA (AICA syndrome) CN VIII nuclei; MCP; ICP; temperature sensation and diminished CST; principal and spinal light touch sensation of face; impaired nucleus of CN V; LST; taste ­sensation; central Horner’s syndrome; ST; flocculus and inferior deafness; peripheral type of facial palsy. surface of cerebellar Loss of pain and temperature sensation of hemisphere contralateral limbs Medial midpontine MCP; CST; ML Ipsilateral ataxia. Contralateral weakness of Due to occlusion of arm, leg, and face; gaze deviation; paramedian perforating +/− impaired lemniscal sensation vessel Lateral midpontine MCP; CN V motor and Ipsilateral ataxia; weakness of muscles of Due to occlusion of short sensory nuclei or fibers mastication; impaired facial sensation circumferential artery Medial superior SCP and/or MCP; MLF, CTT; Ipsilateral ataxia; INO. Contralateral weakness Due to occlusion of pontine CST; ML of arm, leg, and face; +/− impaired lemniscal paramedian perforating sensation. Palatal myoclonus vessel Lateral superior pontine SCP and MCP; LST; lateral Ipsilateral ataxia; Horner’s syndrome; skew Due to occlusion of (SCA syndrome, part of ML; superior deviation. Contralateral impairment of pain, superior cerebellar or Mills’ syndrome) cerebellar hemisphere temperature, and lemniscal sensation. Vertigo; distal basilar artery dysarthria; lateropulsion to side of lesion

AICA, anterior inferior cerebellar artery; CN, cranial nerve; CST, corticospinal tract; CTT, central tegmental tract; ICP, inferior cerebellar peduncle; INO, internuclear ophthalmoplegia; LST, lateral spinothalamic tract; MCP, middle cerebellar peduncle; ML, medial lemniscus; MLF, medial longitudinal fasciculus; PPRF, pontine paramedian reticular formation; SCA, superior cerebellar artery; SCP, superior cerebellar peduncle; ST, solitary tract.

The “top of the basilar” syndrome is caused by ­corticospinal tract signs, decorticate rigidity, and ischemia in the distribution of the distal basilar artery, progressive impairment of diencephalic, midbrain, usually embolic, involving the rostral brainstem, thal- pontine, and medullary function. Because of the pat- amus, and portions of the cerebral hemispheres fed terns of venous drainage, increased intracranial pres- by the posterior cerebral arteries. A variety of oculo- sure and herniation at either the foramen magnum motor and pupillary abnormalities may occur, along or the tentorium may cause secondary bleeding into with visual and behavioral abnormalities, often with- the midbrain, pons, or medulla. Duret hemorrhages out significant extremity weakness. are secondary hemorrhages into the upper brain- Patients with pontine hemorrhage have a clinical stem that occur with increased picture similar to basilar artery occlusion, but warn- and descending transtentorial herniation. Brainstem ing symptoms are less apt to occur. They are comatose hemorrhage may cause hyperthermia, respiratory and quadriplegic and have bilateral facial paralysis, abnormalities, coma, and finally death in patients bilateral horizontal gaze palsies, and pinpoint poorly with brain tumors, , cere- reactive pupils. Hyperthermia is common. Imaging bral hemorrhage, trauma, rapidly expanding supra- studies often show a large hematoma in the midpons. tentorial mass lesions, or similar conditions causing Few patients survive such an event. The initial level an increase in intracranial pressure. Affected patients of consciousness and the size of the hematoma are rarely survive; Stiver et al. reported an exception in a strongly related to the outcome. young adult patient. Pressure on the brainstem due to supratento- When increased intracranial pressure causes rial mass effect can cause either lateral transtento- tonsillar herniation, the cerebellar tonsils and lower rial herniation (uncal syndrome), with third nerve medulla are forced downward through the foramen involvement and signs of lateral midbrain compres- magnum. Although tonsillar herniation is a feared sion, or central transtentorial herniation, with con- complication of lumbar puncture done in the face stricted pupils, Cheyne-Stokes respirations, bilateral of increased intracranial pressure, it is in fact rare.

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BOX 21.3 Other Brainstem Syndromes The one-and-a-half syndrome is a horizontal gaze hemianesthesia, and due to basilar branch palsy and ipsilateral internuclear ophthalmoplegia, occlusion. Rasdolsky’s syndrome is contracture and or INO (Chapter 14). The association of an ipsi- paresis of the masseter and facial muscles due to neo- lateral lower motor neuron facial nerve palsy and plasm of ipsilateral pontine tegmentum. Marie-Foix a one-and-a-half syndrome has been termed the syndrome is contralateral hemiparesis and hypalgesia eight-and-a-half syndrome. The Brissaud-Sicard with ipsilateral cerebellar ataxia due to a lesion involv- syndrome is ipsilateral hemifacial and con- ing the lateral pons. Other unusual manifestations tralateral hemiparesis due to a pontine lesion. The of brainstem disease include pontine anosognosia, lateral pontomedullary syndrome consists of the cognitive dysfunction, painful isolated Horner’s syn- findings of the lateral medullary syndrome with drome, head shaking nystagmus, jaw opening dysto- additional involvement of CNs VII and VIII consis- nia, hemidystonia, facial pain syndromes, a sensory tent with extension of the lesion to the inferior pons. level on the trunk, unilateral hyper- or hypohidrosis, Raymond-Cestan syndrome is horizontal or vertical upside-down reversal of vision, tonic , and gaze palsy, contralateral hemiparesis or quadriparesis, convulsive-like movements.

Medullary compression causes profound impair- especially pure sensory stroke and ataxic hemiparesis, ment of all vital functions, with bradycardia, either are highly predictive of lacunar infarction, in about a fall or rise in blood pressure, slow or rapid res- one in four patients the etiology involves a nonlacu- pirations, soaring temperature, convulsions, uncon- nar mechanism. sciousness, and death. The Cushing (vasopressor) Other unusual, typically vascular, brainstem syn- reflex (response, reaction, or effect) is hypertension, dromes are briefly described in Box 21.3. increased pulse pressure, bradycardia, and slow, irregular respirations seen in patients with increased Nonvascular Brainstem Disorders intracranial pressure and brainstem compression. The full triad occurs in only about one-third of Brainstem are astrocytomas that diffusely cases, and some patients may have isolated hyper- infiltrate the brainstem. Most involve the pons, but tension. On postmortem examination, a pressure they may affect any level of the brainstem, typically cone may be seen on the medulla. causing a combination of multiple cranial nerve of the basilar or vertebral arter- palsies (MCNPs), gaze palsy, long tract signs, and ies or their branches, and hemangiomas, may cause ataxia. Because of the slow evolution, there is some- extramedullary compression and CN involvement. times a paucity of neurologic signs in spite of the Arteriovenous malformations may cause intramed- size of the tumor. Ventricular obstruction may pro- ullary or extramedullary dysfunction, depending on duce hydrocephalus and increased intracranial pres- their extent and location. Extravasation of blood sure. Ependymomas and medulloblastomas may about the base of the brain from subarachnoid or also involve the brainstem. Extramedullary tumors may affect the CNs as they (neurofibromas, schwannomas, meningiomas, hem- leave the skull. angiomas, metastases) may cause pressure effects. Lacunes are small, deep infarctions in the terri- The course of a brainstem neoplasm is progressive. tory of a deep penetrating arteriole. Hypertension is Increased intracranial pressure may appear late, par- the major predisposing factor. The brainstem, par- ticularly in brainstem gliomas. Extrinsic metasta- ticularly the pons, is a common location for lacunar ses and neoplasms that spread by direct extension infarction. Brainstem lacunar syndromes include pure from the nasopharynx and neighboring sites may motor stroke, dysarthria–clumsy hand syndrome, cause widespread CN involvement and bone erosion and ataxic hemiparesis (homolateral ataxia and cru- with signs of brainstem compression. Tuberculomas, ral paresis). Pure motor stroke is the most common ­sarcoidosis, and other granulomas may produce a pic- lacunar syndrome. Although lacunar syndromes, ture similar to neoplasms.

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Brainstem (Bickerstaff’s encephali- and the neural abnormality are part of the same pro- tis) is a clinical syndrome of acute diffuse or multi- cess. Platybasia, basilar impression, occipitalization focal brainstem dysfunction with of the atlas, and cervical spina bifida are examples of (CSF) pleocytosis and increased protein. Actual viral primary bony abnormalities. Klippel-Feil syndrome infection has seldom, if ever, been documented, and is the congenital fusion of two or more cervical ver- the disease is usually immunologically mediated. tebrae. There may be accompanying craniocervical Patients develop ophthalmoplegia and ataxia fol- junction abnormalities. The associated neurologic lowed by gradual brainstem dysfunction and altered abnormalities may include , radiculopa- consciousness. The illness is usually preceded by a thy, syringomyelia, and mirror movements. viral infection. Some patients have serum anti-GQ1b Arnold-Chiari (or simply Chiari, who made the IgG autoantibodies, the same antibody found in greater contribution) malformation is a congenital Miller Fisher syndrome (ophthalmoplegia, ataxia, maldevelopment of the brainstem and cerebellum. and areflexia). Bickerstaff’s brainstem encephali- The cerebellar tonsils are herniated or displaced down tis is not to be confused with Bickerstaff’s (basilar into the upper cervical spinal canal. With more severe artery) migraine (see below). Brainstem encephali- maldevelopment, the inferior vermis, lower medulla, tis may be paraneoplastic. Rhombencephalitis refers and fourth ventricle may also be displaced below the to inflammatory disease affecting the hindbrain foramen magnum. Clinical manifestations include (brainstem and cerebellum). It has a wide variety of headache, cerebellar ataxia, nystagmus (typically etiologies, including (MS), Behcet’s downbeat), and other brainstem deficits. Three variet- disease, paraneoplastic syndrome, lupus, and viral ies commonly occur. Type 1 is the hindbrain malfor- and tuberculous infection. Listeria monocytogenes mation only; it can present in adulthood. Mild type is particularly likely to cause rhombencephalitis; it 1 Chiari malformations are not uncommonly found accounted for 9% of cases in one series. on MRI imaging done for other reasons and may be Demyelinating disease frequently involves totally asymptomatic. Type 2 is a more severe hind- the brainstem. INO due to a demyelinating lesion brain defect usually associated with a lumbar menin- involving the MLF is a very common clinical mani- gomyelocele. Type 3 is the same as type 2 except that festation of MS. MS can cause lesions elsewhere in the meningomyelocele or encephalocele occurs in the the brainstem and can occasionally simulate one of occipitocervical region. The Dandy-Walker syndrome the vascular syndromes. Acute disseminated encepha- is agenesis of the cerebellar vermis with a massively lomyelitis may affect the brainstem, and the involve- dilated fourth ventricle forming a cystic structure that ment is occasionally limited to the brainstem. occupies most of the posterior fossa. In central pontine myelinolysis (osmotic demy- Syringobulbia is a slit-like cavity in the brain- elination syndrome), there is widespread, symmetric stem. A brainstem syrinx is usually a rostral extension myelin loss in the central portion of the pons. Lesions of a syringomyelic cavity from the cervical spinal cord commonly occur in other sites as well (extrapontine in a patient with a , but syringo- myelinolysis). Central pontine myelinolysis occurs bulbia may rarely occur de novo. In syringobulbia, the especially in alcoholics or other malnourished or syrinx most often involves the lateral medullary teg- debilitated individuals and after correction of severe mentum. The cavity is usually restricted to the lower hyponatremia. It typically begins with diplopia, dys- brainstem but may extend to the pons and rarely phagia, dysarthria, and other evidence of brainstem higher. The cavity and the resultant clinical picture dysfunction, followed by quadriplegia, mutism, and are typically asymmetric, with lower CN dysfunction, extensor rigidity. Central pontine myelinolysis runs a facial numbness, and nystagmus. The facial sensory fulminating course and is often fatal. loss may be in an onion-skin distribution, initially Developmental or congenital anomalies of the sparing the nasal tip and perioral region. Hypoglossal craniocervical junction are frequently associated with weakness and atrophy may occur. Facial is brainstem dysfunction. The bony walls of the fora- an unusual feature. There may be autonomic involve- men magnum and upper spinal canal lie in close ment and respiratory compromise. anatomic relationship to the lower brainstem, upper A strategically placed lesion involving the pyra- spinal cord, and cerebellum. Neurologic abnormali- midal decussation may cause unusual patterns of ties may be produced by mechanical compression by weakness. The corticospinal fibers innervating the the bony abnormality, but often the bony abnormality upper extremities are thought to decussate more

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rostrally and medially than the fibers innervating the loss. Tumors are generally histologically benign and lower extremities, although this concept has been often become large before the diagnosis is made. questioned (Figure 11.12). The term cruciate paraly- Masses usually intrude from posteriorly, so that pos- sis is used in two ways. One refers to weakness of both terior column signs, including pseudoathetosis, are arms, brachial , with relative sparing of the common. Lower CN palsies are uncommon. There legs, due to a lesion involving the rostral portion of may be a fluctuating course simulating MS. the pyramidal decussation. The findings are similar to those of a central cord syndrome of the cervical Bulbar Palsy spine or the man-in-the-barrel syndrome because of watershed . Most cases are due to There are two principal types of bulbar palsy: PBP trauma. The other use refers to corticospinal paralysis and . In both, the outstanding of one arm and the opposite leg (cruciate hemiplegia, symptoms are dysphagia and dysarthria; both run a pyramidal decussation syndrome). This may occur chronic course. Despite the similarities, the etiologies because a lesion involves arm fibers that have already are different (Table 21.3). decussated but leg fibers that have not, which causes PBP is a form of involv- a crossed pattern of weakness. Triparesis, with weak- ing bulbar innervated muscles, causing weakness and ness of one arm and both legs, has been reported after atrophy of muscles supplied by the lower CNs, often unilateral medial medullary infarction. accompanied by . It is closely related Gerstman-Sträussler-Schinker (GSS) syndrome to progressive , in which the is a rare autosomal dominant spongiform encepha- process is limited to the anterior horn cells of the lopathy due to a mutation of the prion protein gene. spinal cord, and amyotrophic lateral sclerosis (ALS), It begins in midlife and runs a progressive course with in which there is involvement of the bulbar nuclei, ataxia, , dysarthria, nystagmus, and demen- the anterior horn cells, and the pyramidal cells in the tia. GSS is genetically and phenotypically heteroge- motor cortex. neous; among the different prion diseases, it has the In PBP, there is a relentlessly progressive degen- longest clinical course and the potential to mimic eration of the neurons of the brainstem motor nuclei, other neurologic disorders, such as cerebellar degen- primarily those in the medulla. It usually occurs in late eration and demyelinating disease. adult life with onset in the sixth and seventh decades. Basilar artery (Bickerstaff’s, basilar type, ver- tebrobasilar, posterior fossa) migraine is an unusual Difference Between Progressive type of complicated migraine with prominent brain- TABLE 21.3 Bulbar Palsy and Pseudobulbar Palsy stem symptoms similar to those of VBI. The disorder occurs primarily in young females and is usually fol- Progressive Bulbar Pseudobulbar lowed by an occipital headache. Palsy Palsy The foramen magnum syndrome can cause some Lesion Bulbar nuclei Lesion in bilateral involvement corticobulbar unusual and puzzling clinical deficits. Lesions in the tracts to the region of the foramen magnum are typically compres- bulbar nuclei sive extramedullary mass lesions (e.g., meningioma). Tongue tone Flaccid Spastic Patients may have crossed hemiparesis, involving one Tongue Present Absent arm and the opposite leg, because of involvement of fasciculations the pyramidal decussation (see above). There may be Tongue atrophy Present Absent weakness and wasting of the small hand muscles for Gag reflex Absent Hyperactive reasons that remain unclear. Such hand muscle wasting Jaw jerk Normal Hyperactive may also occur as a false localizing sign in upper cervi- Frontal release Absent Present cal . Downbeat nystagmus in signs Pseudobulbar Absent Present primary gaze is suggestive of a lesion at the cervicome- affect dullary junction, and the nystagmus is often greatest Conditions Amyotrophic Multiple cerebral in eccentric downgaze. Other symptoms suggestive of lateral sclerosis, infarctions, a foramen magnum lesion include occipital headache, Fazio-Londe multiple disease, Kennedy’s sclerosis, neck pain, and stiffness; Lhermitte’s sign; C2 sensory syndrome encephalitis loss; and shawl distribution upper extremity sensory

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The disease usually starts in the nucleus of the CN the bulbar nuclei. PBP and bulbar ALS cause lower XII and ascends. Typical initial manifestations are motor neuron weakness; pseudobulbar palsy causes atrophy, weakness, and fasciculations of the tongue. upper motor neuron weakness. In patients with bul- Involvement is bilateral from the outset. In advanced bar ALS, both processes may be at work. Because of cases, the patient may be unable to protrude the bilateral supranuclear innervation, unilateral lesions tongue or to manipulate food in the mouth. The lin- of the rarely cause significant gual involvement is followed or accompanied by dys- bulbar dysfunction. But with bilateral supranuclear phagia and dysarthria. Nasal regurgitation of liquids lesions, the bulbar dysfunction may be severe. It is is common and may lead to choking and aspiration. usually accompanied by other upper motor neuron Involvement of the soft palate, larynx, and tongue signs. There may be weakness and spasticity of the causes flaccid dysarthria. Early, the most pronounced muscles of mastication, an exaggerated jaw jerk, and difficulty is with pronunciation of linguals and velars; frontal release signs such as snout and suck . later, the labials are affected. In advanced cases, speech Difficulty with emotional control causing sponta- is reduced to unintelligible laryngeal noises. There is neous, unprovoked laughing and crying (pseudo- often marked drooling of saliva. Patients may keep a bulbar affect, emotional incontinence) is common. tissue or rag at the chin to absorb unswallowed secre- Pathologic laughing (crazy or “fou rire tions. Sometimes, atrophy and fasciculations extend prodromique”) and crying have also been reported to the palate and pharynx, and the condition may with brainstem lesions. Some patients have paresis of eventually ascend to involve the facial and trigemi- the muscles of facial expression causing masking of nal motor nuclei. Occasionally, the sternocleidomas- the facies. There are typically significant neurologic toid and trapezius muscles are affected. There may be abnormalities beyond the distribution of the CN autonomic involvement with tachycardia. The palatal nuclei, with bilateral cortical spinal tract signs. and pharyngeal gag reflexes disappear early. There are The most common cause of pseudobulbar palsy no sensory changes. PBP is aggressive and relentless, is multiple cerebral infarctions. The syndrome may with death usually caused by aspiration pneumonia. also occur in encephalitis, MS, trauma, cerebral PBP may be the first manifestation of ALS. When anoxia, primary lateral sclerosis, or other disease pro- ALS causes prominent bulbar weakness, it is referred cesses that cause bilateral corticobulbar tract lesions. to as bulbar ALS. In bulbar palsy due to ALS, there The lesions may be in the cortex or in the corona are also corticospinal tract manifestations. In a series radiata, internal capsule, cerebral peduncles, or brain- of 32 patients with PBP, all but two progressed to stem rostral to the nuclear centers. Speech is thick ALS, regardless of the presence of upper motor signs and slurred but may have an explosive quality. There or generalized denervation on limb electromyography may be dysphagia, nasal regurgitation, choking, and (EMG). The other two died at the PBP stage. drooling. Patients may keep food in the mouth for Severe bulbar involvement occurs in other motor prolonged periods. There is less of a tendency to choke neuronopathies. It is often the terminal aspect of than in true bulbar palsy because the gag reflexes are Werdnig-Hoffmann disease (hereditary spinal mus- intact and may be hyperactive. Although the tongue cular atrophy type 1). Fazio-Londe disease is PBP may be strikingly immobile, atrophy and fascicula- occurring in children. Kennedy’s disease (X-linked tions do not develop. The prognosis in pseudobulbar recessive bulbospinal neuronopathy) causes a clinical palsy is no more favorable than in PBP. The eventual picture resembling ALS but with slow progression and outcome in both conditions is death, often because other atypical features; dysphagia or dysarthria may be of aspiration. Two types of pseudobulbar palsy have prominent late in the course. Bulbar polioencephalitis been described; one is due to lesions affecting the may occur as part of paralytic poliomyelitis, causing corticobulbar fibers, and the other is due to involve- paralysis of the throat, tongue, and respiratory muscles. ment of the basal ganglia or extrapyramidal pathways. Creutzfeldt-Jakob disease may present as bulbar palsy. In striatal pseudobulbar palsy, there are additional Pseudobulbar palsy also causes marked difficulty signs of basal ganglia involvement, including rigidity, with bulbar function, especially speech and swallow- hyperkinesias, and a parkinsonian picture. ing. Although the clinical manifestations are simi- Other conditions that may cause prominent lar, the underlying mechanism is entirely different. weakness of bulbar muscles or other evidence of brain- Pseudobulbar palsy is caused by bilateral supranuclear stem dysfunction include neuromuscular transmission lesions, which involve the corticobulbar pathways to disorders, some neuropathies and myopathies, and

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certain rare neurologic conditions. The dysarthria and TABLE 21.4 Some Disease Processes That May dysphagia of (MG) may resemble Involve Multiple Cranial Nerves (CNs) bulbar palsy. Early in the course, it may be difficult to distinguish bulbar ALS or PBP from MG. The Acute infectious characteristic eye signs of MG are not always present. Chronic infectious meningitis Bulbar similar to those of MG Syphilis can occur in and Lambert-Eaton syndrome. Patients with MUSK antibody MG tend to have Viral infection (Herpes zoster, herpes simplex, EBV, HIV, HTLV-1, prominent bulbar dysfunction, neck and shoulder CMV) girdle weakness, and respiratory symptoms and may Meningeal neoplasia (leptomeningeal metastases, carcinoma- tous meningitis, lymphomatous meningitis, primary leptomen- develop muscle atrophy. Bulbar muscle weakness can ingeal lymphoma, neurolymphomatosis) occur in muscular dystrophies, especially oculopha- Pituitary apoplexy ryngeal dystrophy, and other myopathies. Bulbar Nasopharyngeal carcinoma (Schmincke tumor) weakness may complicate Guillain-Barré syndrome Primary clivus or skull base neoplasm (glomus tumor, menin- and other polyneuropathies. CN involvement is char- gioma, chordoma, others) acteristic of diphtheritic polyneuropathy. In tetanus, Metastatic clivus or skull base neoplasm (prostate, breast, lung, pharyngeal may accompany . In rabies, head, and neck tumors) spasmodic contractions of the muscles occur on Cavernous sinus disease (Tolosa-Hunt syndrome, mass lesion, others) attempts to swallow. Whipple’s disease involving the Sarcoidosis (special predilection for CNs II, VII, and VIII) central (CNS) may have prominent Granulomatosis with polyangiitis (Wegener’s granulomatosis) brainstem findings. Oculomasticatory myorhyth- Vasculitis (polyarteritis nodosa, Churg-Strauss, lymphomatoid granulomatosis, giant cell arteritis, granulomatous angiitis) mia, a striking involving the eyes Connective tissue disease (systemic lupus erythematosis, Sjögren’s and jaw, is characteristic, perhaps pathognomonic, syndrome, scleroderma, mixed connective tissue disease) of CNS Whipple’s disease. Brainstem involvement Cryoglobulinemia may be a striking feature of Leigh’s disease (subacute Prepontine mass lesion necrotizing encephalomyopathy). The brainstem can Skull base trauma also be damaged by radiation. Aneurysm (carotid dissection, fusiform basilar) Carotid endarterectomy Bony disease of skull base (Paget’s disease, osteopetrosis) MULTIPLE CRANIAL NERVE PALSIES Diabetes mellitus Guillain-Barré syndrome Intracranial-extramedullary or extracranial processes Miller Fisher syndrome may involve more than one CN. A disease may Polyneuritis cranialis involve homologous nerves on the two sides (e.g., Amyloidosis bilateral facial palsy) or different nerves on the same Craniocervical junction anomalies or opposite sides. In some conditions, a cluster of Cranial irradiation nerves is involved in a discrete anatomical region. Idiopathic cranial polyneuropathy The progression may follow some anatomical pattern Idiopathic hypertrophic cranial pachymeningitis or appear capricious. Multiple CNs may be affected from the outset, or the process may begin with one CMV, cytomegalovirus; EBV, Epstein-Barr virus; HTLV-1, human T-cell lymphocy- totrophic virus. nerve and progress to involve others. Pain may or may not be present. Table 21.4 lists some conditions that may cause MCNPs. Table 21.5 covers some of the disease, trauma, infection, and the Guillain-Barré named multiple CN syndromes. and Miller Fisher syndromes. A MCNP variant of In Keane’s series of 979 patients with MCNP, Guillain-Barré has been described. The most com- the most commonly involved nerves were CNs VI, mon causes of recurrent cranial neuropathies were VII, V, and VIII. The most common combinations diabetes and idiopathic. were involvement of CNs III and IV, V and VI, and A major consideration when there is MCNP is V and VII. The most common locations were cav- some process affecting the meninges at the base of the ernous sinus, brainstem, and individual nerve trunks. skull. Although infectious and inflammatory condi- The most common causes were neoplasm, vascular tions are possible, the major consideration when there

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TABLE 21.5 Summary of Syndromes with Involvement of Multiple CNs*

Syndrome Lesion Location Structures Involved Clinical Findings Comment

Superior orbit Superior orbital CNs III; IV; VI; V1 Weakness of CNs III, IV, Usually due to tumor or carotid fissure (Rochon- fissure VI; sensory loss in V1 aneurysm Duvigneau) ­distribution; +/− proptosis Orbital apex Orbital apex Same as superior orbital Same as superior orbital Usually due to tumor, aneurysm, fissure plus CN II fissure plus visual or inflammatory process (orbital ­impairment due to pseudotumor) CN II involvement

Orbital floor Orbital floor Ocular motor nerve or Diplopia, V2 sensory loss, Mass lesion or blowout fracture of (Dejean’s) extraocular muscle, V2 exophthalmos floor of orbit

Cavernous sinus Cavernous sinus CNs III; IV; VI; V1, Weakness of CNs III, IV, Common causes include granulomatous (Foix-Jefferson) +/−V2; pericarotid VI; sensory loss in V1 (Tolosa-Hunt syndrome), sympathetics ­distribution; +/− proptosis tumor, and aneurysm Retrosphenoid space Retrosphenoid CNs II; III; IV; V, VI Dysfunction of listed nerves Usual cause is large middle fossa (Negro-Jacod) space neoplasm Petrous apex Apex of the CNs V; VI Sixth nerve palsy and facial Usual causes are inflammation apex( (Gradenigo’s) petrous bone pain and/or numbness petrositis) and tumor Cerebellopontine Cerebellopontine CN VIII; +/−VII; +/−V; +/− Hearing loss; imbalance; Usual cause is acoustic neuroma; angle angle cerebellar hemisphere facial sensory loss; other mass lesions may produce the large tumors may cause same picture (e.g., meningioma) facial weakness, ataxia, increased ICP Jugular foramen Jugular foramen CN IX; X; XI Weakness in the distribution Usual causes are tumor of jugular (Vernet’s) of involved nerves bulb, aneurysm, and trauma (e.g., basilar skull fracture) Collet-Sicard Posterior lateral CN IX; X; XI; XII Weakness in the distribution Usually due to neoplasm of the (MacKenzie, condylar space of involved nerves skull base, especially glomus Lannois-Jouty) jugulare tumor; occasionally carotid ­aneurysm (including dissection) Villaret’s Retropharyngeal CNs IX; X; XI; XII; Weakness in the ­distribution Usually due to neoplasm of the space carotid sympathetics of involved nerves; skull base, especially glomus Horner’s syndrome jugulare tumor, occasionally carotid ­aneurysm (including dissection) Tapia’s Retroparotid CNs X; XII; +/−XI; Weakness in the ­distribution Usually due to tumor of parotid or space carotid sympathetics of involved nerves; skull base; occasionally carotid Horner’s syndrome aneurysm (including dissection) Garcin’s (half-base) Skull base Variable CNs III–XII Unilateral paralysis of all or Usually due to tumor of the skull base, most of the cranial nerves; nasopharynx, or retropharyngeal occasionally bilateral space; can be due to granuloma or infection

*Most are due to disease extracranially in the region of the skull base. Some are more commonly known by their anatomic description (e.g., ) and some by their eponym (e.g., Collet-Sicard syndrome). In some instances, the anatomic designation is reasonably precise and appropriate (e.g., cavernous sinus syndrome). In others, the anatomical description is cumbersome or obscure, and the eponym is more convenient. The table lists the usage likely to be most familiar to most readers first. CN, cranial nerve; ICP, increased intracranial pressure.

is painless dysfunction of several CNs over a period the meninges but is a common cause of meningeal of days to weeks is neoplastic meningitis, which can neoplasia because of its frequency. be either carcinomatous or lymphomatous (menin- Patients with neoplastic meningitis typically have geal carcinomatosis or lymphomatosis). Neoplastic accompanying headache, meningeal signs, and evi- meningitis occurs in as many as 15% of patients with dence of increased intracranial pressure. Facial numb- systemic malignancy and may be the presenting man- ness in association with a multiple lower CN palsy ifestation in 5% to 10%. The most common neoplas- syndrome is ominous. A combination of CNs VI and tic processes to involve the meninges are small cell XII palsies is particularly suggestive of a neoplastic­ carcinoma of the lung, melanoma, and myeloblastic process involving the clivus. Leptomeningeal meta- leukemia. Carcinoma of the breast seldom spreads to static disease from solid tumors is more likely to

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present with spinal cord or radicular involvement. Infectious disease accounted for 10% of Keane’s Diffuse meningeal involvement from hematologic MCNP cases. Conditions particularly prone to cause malignancies is more likely to present with MCNP. cranial neuropathy include Lyme disease, tuberculo- Obtaining CSF cytologic confirmation is often dif- sis, neurosyphilis, cryptococcosis, and HIV. ficult initially; biochemical markers may be helpful. The nervous system is involved in 5% to 15% Other neoplastic processes and mass lesions at of patients with sarcoidosis. The disease may pres- the base of the skull may also produce an MCNP ent neurologically and rarely remains confined to the syndrome. A skull base neoplasm accounted for 13% nervous system. About half of the patients with neu- of cases in Keane’s MCNP series. Nasopharyngeal rosarcoidosis have CN involvement. The CNs most carcinomas (NPCs), such as lymphoepithelioma commonly involved are II, VII, and VIII. A periph- (Schmincke tumor), occur in younger patients than eral facial palsy is the most common manifestation. do other head and neck cancers; there may be an asso- About half of the patients with CN involvement have ciation with Epstein-Barr virus infection. NPC often a cranial polyneuropathy, most commonly bilateral arises in Rosenmuller’s fossa and spreads laterally to the facial nerve palsy. Other common neurologic compli- paranasopharyngeal space and then to the skull base. cations include chronic meningitis, hydrocephalus, The tumor may infiltrate the pterygopalatine fossa, hypothalamic-pituitary dysfunction, myelopathy, and the maxillary nerve, and may spread to involve myopathy, and peripheral neuropathy. Neurologic the cavernous sinus. About 20% of patients have CN involvement occurs in as many as 20% of patients involvement at the time of the diagnosis of NPC. with Behcet’s disease, including MCNP due to men- Radiotherapy for the tumor may itself cause cranial ingeal or brainstem lesions. The most commonly neuropathy, particularly of CN XII. Distinguishing involved nerves are CN II and CN VIII. radiation-induced neuropathy from tumor recurrence Several forms of systemic vasculitis may cause may be difficult (Case Scenario 21.1). MCNP; the most common is granulomatosis with NPCs may erode the clivus. Other tumors polyangiitis (Wegener’s granulomatosis). In one involving the clivus may also cause MCNP. A chor- series, cranial neuropathies were the most common doma, a rare primary bone tumor, usually presents neurologic abnormality. Giant cell arteritis may cause in males in the sixth decade. The tumor is histo- the combination of optic and extraocular neuropa- logically benign but locally invasive and destruc- thies. Other vasculitic processes of concern include tive. When it extends posteriorly, it may cause CN lymphomatoid granulomatosis, a lymphoreticular palsies or brainstem compression. Other skull base malignancy, and vasculitis due to connective tissue neoplasms include metastasis, meningiomas, lym- disease, especially polyarteritis nodosa. phoma, myeloma, histiocytosis, neurinoma, giant Polyneuritis cranialis is an MCNP syndrome that cell tumor, hemangiopericytoma, and various pri- may represent a variant of Guillain-Barré syndrome mary bone tumors. Osteopetrosis (Albers-Schonberg involving the lower CNs. An acute, painful, steroid- or marble bone disease) causes a generalized increase responsive MCNP syndrome that may be on a con- in bone density and can narrow exit foramina, caus- tinuum with Tolosa-Hunt syndrome (see section on ing MCNP. Other bone disorders that may behave Cavernous Sinus Syndrome) but involving nerves out- similarly include Paget’s disease, fibrous dysplasia, side the cavernous sinus has been described (idiopathic and hyperostosis cranialis interna. cranial polyneuropathy). Bannwarth’s syndrome (men- Mass lesions lying along the clivus, even though ingopolyradiculitis) refers to MCNP and painful poly- not arising from it directly, may cause MCNP. radiculopathies due to Lyme disease. Most patients Vertebrobasilar dolichoectasia may cause cranial have an acute peripheral facial paresis with additional neuropathies because of compression or ischemia. involvement of other nerves and spinal roots. Patients with a tortuous basilar artery of normal cali- CN palsy occurs occasionally in carotid artery ber are more likely to have isolated cranial neuropa- dissection; rarely, it is the dominant or only manifes- thy; those with basilar artery ectasia or with fusiform, tation. Ipsilateral headache, Horner’s syndrome, and giant aneurysm are more likely to have MCNP. Rarely, lower CN palsy are suggestive of carotid dissection hematoma lying along the clivus in the prepontine even in the absence of cerebral ischemic symptoms. region affects multiple CNs. Other processes that may CN XII is invariably affected, and in some patients, affect the prepontine region include exophytic other CNs may be involved as well. The etiology is not and dermoid, epidermoid, and other cystic lesions. certain. There may be compression or stretching by

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CASE SCENARIO 21.1

A 53-year-old female presented with a 2-month lesion in the left extra-axial region in the region history of headache, numbness of face with of cerebellopontine angle. Neuroimaging of brain decreased sensation on the left, and deviation of and base of skull revealed a nasopharyngeal mass angle of mouth to the right. She developed hearing extending into the oropharynx, posteriorly up to impairment on the left side, vertigo, slurring of the left cerebellopontine angle and medially up to speech, and double vision for the past 1 month. the left petrous apex suggestive of nasopharyngeal Examination revealed a conscious, oriented patient. carcinoma (NPC) (Figure 21.3), which was Abduction was restricted on the left side and histopathologically confirmed. The patient was sensation to fine touch and pain reduced in the left treated with concurrent chemoradiotherapy after trigeminal distribution. Left peripheral facial palsy staging. and sensorineural hearing impairment in the left NPC often arises in Rosenmuller’s fossa and ear were noted. Head impulse revealed a catch-up spreads laterally to the paranasopharyngeal space saccade on the left side. Rest of neurological and and then to the skull base. The tumor may infil- systemic examination was normal. trate the pterygopalatine fossa and the maxillary nerve, and may spread to involve the cavernous Comments: The structures involved in the patient sinus. About 20% of patients have cranial nerve described above are trigeminal, abducens, facial, involvement at the time of the diagnosis of NPC. and vestibulocochlear cranial nerves on the left side Radiotherapy for the tumor may itself cause cranial without clinical evidence of long tract signs. Owing neuropathy, particularly of CN XII. Distinguishing to the involvement of multiple cranial nerves on radiation-induced neuropathy from tumor recur- the left side, it is imperative to rule out structural rence may be difficult.

FIGURE 21.3 MRI brain. A. T2WI and B. T1 post-gadolinium contrast showing a nasopharyngeal contrast-enhancing mass extending into the oropharynx, posteriorly up to the left cerebellopontine angle and medially up to the left petrous apex suggestive of nasopharyngeal carcinoma.

the aneurysmal dilatation or ischemia due to involve- DISORDERS OF CRANIAL NERVE ment of the segmental arteries supplying the nerves, GROUPS particularly the ascending pharyngeal artery. CN palsy also occurs as a complication of carotid endarterectomy. In some locations, two or more CNs are bundled in Trauma accounted for 12% of MCNP cases in a common anatomical space, such as the cavernous Keane’s series. Blunt trauma, such as MVA or falling, sinus or jugular foramen. A focal disease process may is twice as common as penetrating trauma. Iatrogenic involve the entire cluster of nerves. Intradural, extra- trauma accounts for a significant minority, especially medullary pathology involves the nerves after they exit radical head or neck dissections. the brainstem but before they exit the skull (e.g., in the

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cerebellopontine angle [CPA]). Extracranial pathol- turcica, extending from the superior orbital fissure to ogy involves a group of nerves just after they exit the the apex of the petrous temporal bone (Figure 21.4). skull but before they disperse (e.g., in the retroparotid The two sides are connected by an anterior and space). As with brainstem syndromes, the many posterior intercavernous sinus. A thin layer of dura, syndromes that involve multiple CNs carry an eponym the pituitary capsule, forms the medial wall of the and an anatomical description. The anatomical regions cavernous sinus. The internal carotid artery with its involved are often so arcane that the eponym serves just pericarotid sympathetic plexus runs through the sinus. as well. Table 21.5 summarizes these syndromes. Most CNs III, IV, and V lie in the wall of the sinus from of the disorders affecting CN groups are due to mass above to below. CN VI lies free in the lumen of the effect. The mass is often neoplastic. Primary neural sinus inferolateral to the carotid artery. The ophthalmic tumors, such as schwannoma or neurofibroma, aris- division of CN V traverses the sinus; the maxillary ing from one CN may cause compression of adjacent division runs for a short distance through its posterior- nerves. Many of these syndromes are rare in neurologic inferior part. practice. The relatively common ones are the cavern- Conditions of the cavernous sinus were recognized ous sinus, CPA, and jugular foramen syndromes. by Gowers in 1888, but some years later, the writ- ings of C. Foix (French neurologist) and G. Jefferson Cavernous Sinus Syndrome (English neurosurgeon, best known for describing C1 fracture) brought wide recognition to the existence of The cavernous sinuses are complex venous channels the cavernous sinus syndrome. The cavernous sinus that lie on either side of the sphenoid bone and sella may be involved by tumor, thrombosis (bland or

Oculomotor nerve Cavernous sinus Pituitary Carotid artery (cavernous part) Ophthalmic nerve

Sphenoid sinus Maxillary nerve

A

Oculomotor nerve Cavernous sinus Trochlear nerve Pituitary Carotid artery Abducens nerve aneurysm Ophthalmic nerve

Maxillary nerve Sphenoid sinus

B FIGURE 21.4 A. The cavernous sinus lies just lateral to the sella turcica. Within it lie the carotid artery and cranial nerves (CNs) III, IV, and VI and branches of CN V. B. Pathologic findings involving the cavern- ous sinus are not rare and can usually be recognized by the pattern of CN involvement.

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septic), carotid aneurysm, carotid-cavernous fistula, steroid responsiveness has been used as a diagnos- inflammation, infection, and other processes. There tic criterion. However, other conditions involving is variable involvement of the CNs crossing the the cavernous sinus, including tumors, infection, sinus. Severe processes may affect all of the nerves, and aneurysm, may also improve with steroids. but isolated sixth nerve palsy also occurs. In Keane’s MRI may show T2 isointense tissue that enhances series of 151 patients, the most common etiolo- with gadolinium. Another condition related to gies were tumor, trauma, self-limited inflammation, cavernous sinus syndrome is Raeder’s paratrigeminal carotid aneurysms and fistulas, and infection. These (or the paratrigeminal oculosympathetic) syndrome accounted for 88% of the cases. Other causes of cav- (Chapter 15). ernous sinus syndrome include pituitary apoplexy, metastasis, lymphoma or leukemia, myeloma, neuro- Cerebellopontine Angle Syndrome blastoma, mucormycosis, aspergillosis, tuberculosis, carotid-cavernous fistula, trauma, and sarcoidosis. A mass lesion in the CPA is usually an acoustic neu- Intracavernous carotid aneurysms may com- roma, but other tumors and masses may arise in the press and distort the contents of the cavernous sinus region (Chapter 17). An acoustic neuroma usually (Figure 21.4B). A carotid-cavernous fistula is a com- arises from the vestibular portion of CN VIII within munication between the carotid artery and the cav- the internal auditory meatus. The initial symptoms ernous sinus. Fistulas may be traumatic or develop are usually hearing loss and tinnitus. Examination spontaneously because of rupture of an intracavern- early in the course shows sensorineural hearing loss ous carotid aneurysm. In addition to CN palsies, and impaired labyrinthine function on the involved patients may have pulsatile proptosis, chemosis, an side. Vertigo is unusual because the tumor grows ocular bruit, and evidence of increased venous pres- slowly and the vestibular system compensates, sure in the eye. Dilated, arteriolized conjunctival and although patients may have impaired balance. As the episcleral blood vessels with a tortuous, corkscrew mass expands, compression of CN V causes ipsilat- shape are characteristic (Figure 21.5). Neoplasms eral facial sensory loss and impairment of the corneal commonly involve the cavernous sinus. Common reflex. Pressure on the cerebellum or its peduncles tumor types include NPC, metastases, lymphoma, causes ataxia and incoordination. There may be pituitary adenoma, and meningioma. involvement of CN VII, with a peripheral facial Two neurosurgeons, E. S. Tolosa (Spanish) palsy, and of CNs VI, IX, and X. Late in the course, and W. E. Hunt (American), described indolent, increased intracranial pressure may cause headache, idiopathic, granulomatous inflammation of the papilledema, and occasional loss of consciousness. cavernous sinus causing pain and ophthalmoplegia. Nystagmus is common; it may be coarse and slow on Pathologically, there is noncaseating, granulomatous gaze toward the side of the lesion (gaze paretic nystag- inflammation similar to that seen in orbital mus) and fine and rapid on gaze away from the lesion pseudotumor. Patients present with severe periorbital (vestibular nystagmus). This unusual combination is headache and dysfunction of one or more of the referred to as Bruns’ nystagmus (for Ludwig Bruns, intracavernous CNs. Tolosa-Hunt syndrome is exqui- German neurologist, see Video Link 21.1). sitely responsive to even small doses of steroids, and Lower Cranial Nerve Syndromes The lower CN syndromes involve CNs IX to XII uni- laterally in various combinations. These nerves exit the skull just above the foramen magnum. CNs IX, X, and XI exit through the jugular foramen along with the jugular vein. CN XII exits through the hypoglossal canal just inferiorly. CNs IX to XII lie close together in their initial course, near the carotid artery, with its pericarotid sympathetic plexus, and the jugular vein in the upper neck. The prototype lower CN syn- FIGURE 21.5 Corkscrew conjunctival and episcleral vessels in a drome is the jugular foramen syndrome (JFS) charac- patient with a carotid-cavernous fistula. terized by ipsilateral paralysis of CNs IX, X, and XI.

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JFS is caused by a lesion at the jugular foramen or when there is intracranial extension, and the pres- in the retroparotid space. Collet-Sicard syndrome is ence of JFS indicates 50% likelihood that the tumor the additional involvement of CN XII. Villaret’s syn- has invaded the posterior fossa. Involvement of CN drome is Collet-Sicard with the addition of Horner’s XII increases the probability to 75%. Other reported syndrome (Table 21.5). Sometimes, the term JFS is causes of JFS include metastasis, trauma, menin- used to refer to any combination of palsies affecting gioma, ectopic glioma, hydatid cyst, plasmacytoma, the last four CNs. chordoma, malignant external otitis, retroparotid Glomus tumors (paragangliomas, chemodecto- abscess, giant cell arteritis, cephalic herpes zoster, mas) arise from the glomera of the chemoreceptor and thrombosis of the jugular bulb. The lower four system. They commonly arise in the jugular bulb CNs also run close together just prior to their exit (glomus jugulare), the middle ear (glomus tympani- from the skull and may be involved in intracranial cum), and the nodose ganglion of the processes such as schwannoma, ependymoma, and (glomus vagale). On examination, a vascular polyp meningioma. may be found in the auditory canal or behind the tympanic membrane. Glomus jugulare tumors are Video Links a common cause of JFS. These tumors grow slowly, Video Link 21.1. Bruns’ nystagmus. http://www.neuroophthalmology. may erode bone, and may extend intracranially. ca/case-of-the-month/eye-movements/diplopia- Glomus tumors are much more difficult to manage and-an-unusual-nystagmus

REVISION PEARLS 1. The brainstem is a compact structure, with 6. The posterior inferior cerebellar artery (PICA) cranial nerve (CN) nuclei, nerve fascicles, supplies the lateral medulla; the anterior inferior and long ascending and descending tracts all cerebellar artery (AICA) supplies the inferior closely juxtaposed. lateral pons; and the superior cerebellar artery 2. A process affecting the brainstem long tracts (SCA) supplies the superior lateral pons. on one side causes clinical abnormalities 7. The clinical manifestations of an attack of on the opposite side of the body. For this vertebrobasilar insufficiency are typically bilat- reason, focal brainstem lesions are character- eral, with varying degrees of weakness, numb- ized by “crossed” syndromes of ipsilateral CN ness, and CN dysfunction. Accompanying dysfunction and contralateral long motor or symptoms indicative of brainstem dysfunction sensory tract dysfunction. include diplopia, dysarthria, dysphagia, 3. Because of the rich vestibular and cerebellar vertigo, nausea, and vomiting. connections, patients with brainstem disease 8. Patients with pontine hemorrhage are often have dizziness or vertigo, unsteadiness, comatose and quadriplegic and have bilateral imbalance, incoordination, difficulty walking, facial paralysis, bilateral horizontal gaze nausea, and vomiting. palsies, and pinpoint poorly reactive pupils. 4. Unless the process has impaired the reticular Hyperthermia is also common. activating system, the patients are normal 9. Duret hemorrhages are secondary hemorrhages mentally—awake, alert, able to converse into the upper brainstem that occur with (though perhaps dysarthric), not demented, increased intracranial pressure and descending not confused, and not aphasic. transtentorial herniation. 5. Involvement of descending motor tracts 10. The Cushing (vasopressor) reflex (response, reac or somatic motor nuclei indicates medial tion, or effect) is hypertension, increased pulse lesions; involvement of long sensory tracts, pressure, bradycardia, and slow, irregular res- branchiomotor nuclei, and special sensory pirations seen in patients with increased intra- nuclei indicates lateral lesions. cranial pressure and brainstem compression.

(Continued )

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(Continued )

REVISION PEARLS 11. Brainstem lacunar syndromes include pure of CN V traverses the sinus; the maxillary motor stroke, dysarthria–clumsy hand division runs for a short distance through its syndrome, and ataxic hemiparesis (homolateral posterior-inferior part. ataxia and crural paresis). 14. An acoustic neuroma usually arises from the 12. A combination of CNs VI and XII palsies is vestibular portion of CN VIII within the internal particularly suggestive of a neoplastic process auditory meatus. The initial symptoms are involving the clivus. usually hearing loss and tinnitus. As the mass 13. In cavernous sinus, CNs III, IV, and V lie in the expands, compression of CN V causes ipsi- wall of the sinus from above to below. CN VI lateral facial sensory loss and impairment of lies free in the lumen of the sinus inferolateral the corneal reflex followed by involvement of to the carotid artery. The ophthalmic division CNs VII, VI, IX, and X and cerebellum.

Multiple Choice Questions 1. Structures that are not involved in lateral 4. Which of the following statements is NOT medullary syndrome are: true? a. Motor nucleus of CN V a. Type 2 Chiari malformation is associated with b. Nucleus ambiguus lumbar meningomyelocele. c. Vestibular nuclei b. Type 3 Chiari malformation is associated with d. Spinal tract of CN V meningomyelocele or encephalocele in the occipitocervical region. 2. Weber’s syndrome is characterized by deficit in c. Dandy-Walker syndrome is associated with which of the following? cerebellar agenesis and small fourth ventricle. a. Cranial nerve III + corticospinal tract d. Klippel-Feil syndrome is the congenital fusion involvement of two or more cervical vertebrae. b. Cranial nerve III + red nucleus involvement c. Cranial nerve III + cerebellar peduncle 5. Which of the following statements is false? involvement a. Vernet’s syndrome occurs with lesion in jugular d. Cranial nerve VII + corticospinal tract foramen. involvement b. CNs IX, X, and XI are involved in jugular foramen syndrome. 3. Which of the following causes c. CNs IX, X, XI, and XII are involved in Collet- rhombencephalitis? Sicard syndrome. a. Bechet’s syndrome d. Sympathetic tract is spared in Villaret’s b. Multiple sclerosis syndrome. c. Systemic lupus erythematosus d. All of the above

Answers 1. a (Page 349); 2. a (Page 349); 3. d (Page 355); 4. c (Page 355); 5. d (Page 359)

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