Ординатура / Офтальмология / Английские материалы / The Neurology of Eye Movements_Leigh, Zee_2006

pometria if the vermis alone is involved, and hypermetria if the deep nuclei are involved (see VIDEO: "Saccadic hypermetria") (Fig. 10-22). Lesions of the fastigial nuclei generally cause marked saccadic hypermetria. The pattern of saccadic dysmetria that occurs in cerebellar disease, as well as whether or not corrective saccades occur, may also vary with the type of visual stimulus.195 Memory-guided saccades are dys-

metric, especially if the target moves during the memory period.716'789 In some

patients with cerebellar disease, only corrective saccades are dysmetric.162 Saccadic dysmetria may be present for externally

triggered movements to a visual target but not for internally triggered saccades during scanning of a visual scene.223 Large torsional "blips" that occur during voluntary saccades constitute violations of Listing's law (see Chap. 9) and have been reported in patients with lesions involving the vermis and fastigial nuclei.607 Dorsal vermal le-

sions may also produce mild deficits of pur- suit,756-1079'1412 as well as defects in motion

perception.1002 Bilateral symmetric lesions of the fastigial nuclei do not lead to pursuit deficits,223 though unilateral lesions lead to a contralateral deficit,1161 probably because of an imbalance in eye acceleration signals.

Other Disorders of Eye Movements Attributed to Cerebellar Disease

Disorders of ocular alignment encountered in association with cerebellar disease include esotropia, especially for distance

viewing (divergence paralysis); alternating skew deviations1427'1527; disconjugate

(poorly yoked) saccades; and disconjugate gaze-evoked nystagmus.1427

Fixation is commonly disrupted in patients with cerebellar disease, either by nystagmus or saccadic intrusions. In addition to the forms of nystagmus that are part of the three principal cerebellar syndromes, divergent nystagmus (Fig. 10-6),1509 centripetal nystagmus (Display 10-7),824 central position upbeating nys-

tagmus (see VIDEO: "Upbeat nystagmus"),322 seesaw nystagmus (Fig. 10-8),1547 and ac-

quired pendular nystagmus (see VIDEOS: "Acquired nystagmus impairing vision")62 have all been reported in patients with cerebellar disease. Hyperventilation-in- duced downbeat nystagmus may occur in some patients with cerebellar disease, perhaps reflecting abnormalities of calcium channels that are known to occur in some forms of cerebellar degeneration.1452 A variety of saccadic intrusions occur commonly in association with cerebellar dis-

10-16A), which are a common finding in patients with Friedreich's ataxia.1117'1312

A singular disturbance of smooth pursuit is the presence of torsional nystagmus during vertical tracking.461 This has been described in patients with cavernous angiomas in the middle cerebellar peduncle. The direction of such torsional nystagmus changes with the direction of the pursuit, with the eye velocity of the slow phase of the torsional nystagmus being directly proportional to the eye velocity of the slow phase of pursuit. This sign may occur because smooth pursuit is programmed in, or superimposed upon, aphylogenetically old, vertical "labyrinthine-optokinetic" coordinate system so that for a pure vertical pursuit movement to occur opposite torsional components must cancel (as is the case for a pure vertical vestibular nys-

tagmus). The middle cerebellar peduncle carries information to the cerebellum from the pontine nuclei, including the nucleus reticularis tegmenti pontis (NRTP), which may contain vertical pursuit signals encoded with a torsional component.

Other vestibular abnormalities are reported in patients with cerebellar disease, including vestibular hyperresponsiveness (increased VOR gain),1372 increased responsiveness of the cervico-ocular reflex,189 abnormalities of off-vertical axis rotation (OVAR) with an increase in the modulation component and a decrease in the bias component,313 and impaired responses to linear translation (L-VOR).89

The cerebellum is also important in long-term adaptive functions that keep eye movements appropriate to the visual stimulus. For example, adaptive properties of the VOR are impaired in patients with cerebellar lesions.1502 This adaptive or "repair shop" function of the cerebellum probably accounts for both the enduring nature of the ocular motor deficits that accompany diffuse cerebellar lesions and, perhaps, the somewhat variable effects of cerebellar lesions. Thus, inherent, idiosyncratic abnormalities in brain stem or peripheral ocular motor mechanisms that are normally "repaired" by the cerebellum may reappear after cerebellar lesions. For example, some patients with cerebellar disease may not be able to adapt to a phoria induced by wearing prisms.568'944 Children with cerebellar lesions often make better recoveries than do adults.832'1456 If cerebellar ablation is performed in neonatal monkeys, almost complete recovery occurs, provided that the deep cerebellar nuclei are left intact; if they are not, gaze holding and smooth pursuit never fully recover.413

Developmental Anomalies of the

Hindbrain and Cerebellum

Arnold-Chiari malformation is an anomaly of the hindbrain involving the caudal cerebellum (including the vestibulocerebellum, flocculus, paraflocculus [tonsils], uvula, and nodulus) and the caudal me-

492 The Diagnosis of Disorders of Eye Movements

dulla. In Chiari type I malformation, the cerebellar tonsils are displaced caudally into the foramen magnum, the medulla is elongated, and a meningomyelocele is only rarely present. Such patients often present with symptoms in adult life. In Chiari type II malformation, both the fourth ventricle and inferior vermis extend below the foramen magnum, the brain stem and spinal cord are thin, and a lumbar meningomyelocele is usually present. Patients with type II malformation usually present in childhood, but, in milder cases, onset of symptoms is delayed until adulthood. Presenting symptoms include oscillopsia (brought on or exacerbated by head movements) and Valsalvainduced dizziness, vertigo, cervical pain, and headaches.1487 A variety of ocular motor abnormalities, especially downbeat nystagmus (both spontaneous and positional), has been reported in patients with Arnold-Chiari malformation (Table 10-12). Many of these signs are reproduced by vestibulocerebellar lesions in

monkeys.1538 The positional nystagmus of posterior fossa lesions548'731-1460 must be

differentiated from the more common benign paroxysmal positional nystagmus of the labyrinth. Diagnosis is by MRI, with

sagittal views of the craniocervical junction (Fig. 10-23).157-1113 Patients often im-

prove after suboccipital decompression, although it may take months for the

eye movement abnormalities to dimin-

ish.1073'1313

The Dandy-Walker syndrome consists of malformation of the cerebellar vermis, a membranous cyst of the fourth ventricle, and malformations of the cerebellar cortex and deep cerebellar nuclei. Patients may show a mild saccadic dysmetria, though eye movements may be normal.832 Ocular motor abnormalities, including nystagmus and strabismus, have also been reported in patients with agenesis of the vermis227 or hypoplasia of the entire cerebellum.1218 Other rare syndromes associated with anomalous cerebellar development include Coffin-Siris syndrome (developmental delay, hypotonia, cutaneous changes, and abnormalities of the roof of the fourth ventricle)341 and Joubert's syndrome (a variable combination of episodic

Table 10-12. Disturbances in Eye

Movements Encountered in

Arnold-Chiari Syndrome

Downbeat nystagmus (occasionally with a torsional component), worse on lateral

gaze267,580,731,1313,1509,1532

Divergence nystagmus1509 Convergence nystagmus972

Horizontal nystagmus (unidirectional, present with eyes in central position—see Fig. 10-7)

Periodic alternating nystagmus492 Gaze-evoked nystagmus23

Rebound nystagmus including torsional rebound1337

Seesaw nystagmus1547

Impaired pursuit (andVOR cancellation)1532

Impaired OKN with slow buildup of eye

velocity in response to a constant-velocity stimulus1509

Strabismus20'247*-864 Divergence paralysis864

Skew deviation accentuated or alternating on lateral gaze1527

Saccadic dysmetria47

Internuclear ophthalmoplegia47 Increased VOR gain1532

Shortened VOR time constant and impaired tilt suppression569

Positional nystagmus86

tachypnea, psychomotor retardation, retinal dystrophy, torsional nystagmus, skew deviation, ocular motor apraxia, agenesis

of the cerebellar vermis, and fibrosis of the extraocular muscles).508'764'807'903'1216

Ocular Motor Findings in the

Hereditary Ataxias

With the identification of several genes responsible for the hereditary ataxias has come an attempt to link phenotype with genotype. Substantial efforts have been made to achieve this goal by identifying distinctive syndromes of abnormal eye movements. Some results of these studies are summarized in Table 10-13. While it appears that certain findings are quite distinctive for one gene mutation, there is enough overlap to advise caution in trying

to assign an individual to one group on the basis of eye movements findings alone. So, for example, the presence of very slow saccades is suggestive of spinocerebellar ataxia type 2 (SCA2) (see VIDEO: "Slow horizontal saccades") formerly called olivopontocerebellar degeneration of Wadia and Swami,

in which pontine saccadic burst cells are also involved.649'1443 Similarly, the pres-

ence of prominent downbeat, gaze-evoked, and rebound nystagmus, with normal velocity saccades, is typical of SCA6,525'1539 which may also correspond to late-onset, Holmes-type cerebellar degeneration and to the autosomal dominant "pure" cerebellar ataxia (autosomal dominant cerebellar ataxia—ADCA3—of Harding) (see VIDEOS: "Gaze-evoked, rebound and downbeat nystagmus").586 However, saccades may also be slow in patients with SCA1,211 and we have recorded slow saccades and downbeat nystagmus in members of a

family with SCA3 (Machado-Joseph disease).789 The clinical picture changes as the disease develops.774 Another factor may be that the severity of the disturbance in any one individual may correlate with the number of trinucleotide repeats, although only a small number of repeats (fewer than 30) may be associated with certain diseases, such as SCA6.1548 Furthermore, there is some suggestion of overlap between certain syndromes, such as SCA6 and familial episodic vertigo and ataxia type 2 (EA-2), both of which affect the calcium channel (CACNL1A4) gene.90'175'509 Features of the episodic ataxias are summarized in Table 10-13. Finally, some patients with genetically confirmed SCA1 have been reported to show clinical and neuropathologic findings indistinguishable from multiple system atrophy.515 Thus, the clinician must keep in mind a broad spectrum of differential di-

Table 10-13. Ocular Motor Findings in Hereditary Ataxias*

Other Distinguishing

Features

Pyramidal tract signs; dysphagia; optic nerve pallor

Cerebellar dysarthria; hypoactive tendon reflexes

Faciolingual myokymia;dystonia; parkinsonism

Sensory axonal neuropathy

Mild ataxia

Late onset; "Pure" cerebellar atrophy with loss of Purkinje cells

Pigmentary maculopathy and visual loss; hearing loss; extrapyramidal signs

Epilepsy, myoclonus, choreoathetosis, dementia

Brief attacks of ataxia; interictal myokymia

Prolonged attacks; may show progressive ataxia; possible overlap with SCA6

Recessive; onset usuallybefore 20 years; sensory loss; areflexia; Babinski responses; cardiomyopathy; diabetes

Recessive; Friedreich-like picture; retinitis pigmentosa may be associated

Ataxia telangiectasia (Louis-Barsyndrome) 1 Iq

Ocular motor apraxia: hypometria, increased latency, normal velocity of saccades; head thrusts; GEN;PAN;

SWJ

Recessive; oculocutaneous telangiectasia; radiosensitivity; immunological disorders; cancer; elevated alphafetoprotein

496 The Diagnosisof Disordersof Eye Movements

agnoses when confronted by a patient with progressive ataxia and abnormal eye movements. Progress in understanding the underlying molecular genetics of these disorders may clarify the pathogenesis of the phenotypes.

Paraneoplastic Cerebcllar

Degeneration

This is a rare "remote effect" of cancer, usually occurring in association with small-cell lung cancer and breast and ovarian carcinoma.36'910'1100 The onset of symptoms is usually acute or subacute, with the development of severe midline and appendicular ataxia, dysarthria, and downbeat nystagmus (see VIDEO: "Downbeat nystagmus"). Many patients will show Yo or Hu antineuronal antibodies. Since pathologic studies indicate total loss of Purkinje cells, such patients have effectively lost all output from the cerebellar cortex. The common finding of primaryposition downbeat nystagmus, therefore, is of interest because it tends to confirm that asymmetric, inhibitory projections of the cerebellum to the central connections of the semicircular canals can cause this nystagmus (see Pathogenesis of Central Vestibular Nystagmus). Treatment is presently unsatisfactory.1102'1437 A cerebellar syndrome may also complicate treatment of cancer or leukemia with cytosine arabinoside.144

Cerebellar Infarction

Three branches of the posterior circulation supply the cerebellum: the poste- rior-inferior cerebellar artery, the ante- rior-inferior cerebellar artery, and the superior cerebellar artery.1358 Occlusion in these vessels often produces concurrent brain stem infarction, making precise clinicopathologic correlation difficult.

The posterior-inferior cerebellar artery (PICA) arises from the vertebral artery and supplies the lateral medulla, the inferior cerebellar peduncle, and the nodulus and uvula. Thus, occlusion of the PICA may cause Wallenberg's syndrome. Infarc-

tion in the distribution of the distal PICA may cause acute vertigo and nystagmus that often simulates an acute peripheral vestibular lesion.410'897'1192 These symptoms are probably due to a central vestibular imbalance created by asymmetric infarction in the vestibulocerebellum, which normally has a tonic inhibitory effect upon the vestibular nuclei. Such patients may have prominent gaze-evoked nystagmus, which helps differentiate this cerebellar lesion from an acute peripheral vestibulopathy.

The anterior-inferior cerebellar artery (AICA) is usually the most caudal large vessel arising from the basilar artery. It supplies portions of the vestibular nuclei, adjacent dorsolateral brain stem, and inferior lateral cerebellum (often including the flocculus). In addition, the AICA is the origin of the labyrinthine artery in most individuals and also sends a twig to the cerebellar flocculus in the cerebellopontine angle. Consequently, ischemia in the AICA distribution (Fig. 10-21) may cause vertigo, vomiting, hearing loss, facial palsy, and ipsilateral limb ataxia. Unilateral loss of vestibular function may cause asymmetric responses with rapid head turns [see VIDEO: "Anterior inferior cerebellar artery (AICA) distribution infarction"]. In addition, there may be gaze-evoked nystagmus, impaired smooth pursuit, and spontaneous vestibular nystagmus.27-541'1028

The superior cerebellar artery (SCA) arises from the rostral basilar artery and supplies the superior surface of the cerebellar hemisphere and vermis and the superior cerebellar peduncle. Infarction in the territory of the superior cerebellar artery causes ataxia of gait and limbs, and vertigo.115'1120'1409 A characteristic abnormality is saccadic contrapulsion. This consists of an overshooting of contralateral saccades and an undershooting of ipsilateral saccades; attempted vertical saccades are oblique, with a horizontal component away from the side of the lesion. Thus, the disorder is the opposite of the saccadic ipsipulsion seen in Wallenberg's syndrome and probably reflects interruption of outputs from the fastigial nucleus running in the uncinate fasciculus next to the superior cerebellar peduncle.1332'1448 Infarction restricted to the posterior-inferior vermis

has been reported to selectively impair pursuit and optokinetic eye movements.1079

Cerebellar Mass Lesions

Cerebellar hemorrhage, tumors, infarction, abscesses, cysts, and extraaxial hematomas may all cause cerebellar eye signs by direct involvement of cerebellar parenchyma. However, acutely expanding or large cerebellar mass lesions, such as hemorrhage, often also compress the brain stem and produce additional signs (see VIDEO: "Ocular bobbing"). Either vertical or horizontal gaze disorders can occur depending upon whether the direction of compression is rostral or forward, respectively. Acute cerebellar hemorrhage frequently causes nystagmus, horizontal gaze palsy (usually toward the side of the lesion), and skew deviation. These signs are, in part, due to brain stem compression. The third, fourth, and sixth cranial nerves may also be affected. Ocular motor dysfunction may also be caused by secondary obstructive hydrocephalus and increased intracranial pressure.

Medulloblastoma arising in the posterior medullary velum frequently causes positional nystagmus, presumably due to involvement of the nodulus and uvula.543 Such involvement may also account for

the inability to suppress postrotational nystagmus by tilting the head.569 Tumors

and dorsal medulla, sometimes producing upbeat or downbeat nystagmus.

Acoustic schwannoma may compress the cerebellar flocculus and paraflocculus, which lie in the cerebellopontine angle, and so cause the flocculo-nodular syndrome (Display 10-17). In addition, patients may show Bruns' nystagmus, in which there is a "coarse" gaze-evoked nystagmus beating toward the side of the lesion and a "fine" vestibular nystagmus

beating away from the side of the lesion.80'200'1004 Asymmetry of the caloric re-

sponses and of rotational testing may be observed,119'954 but the most sensitive and

specific method used to detect small tumors is MRI with gadolinium.1109

OCULAR MOTOR SYNDROMES CAUSED BY DISEASE OF THE PONS

Lesions of the Abducens Nucleus

Lesions of the abducens nucleus (see Display 6-1) cause an ipsilateral palsy of horizontal conjugate gaze (Display10-20).

498 The Diagnosis of Disorders of Eye Movements

Movements of both eyes are affected because the abducens nucleus contains two main groups of neurons: abducens motoneurons, which innervate the ipsilateral lateral rectus muscle, and abducens internuclear neurons, which cross the midline and ascend in the medial longitudinal fasciculus to innervate the contralateral medial rectus motoneurons (see Fig. 6-1, Chap. 6). Vergence movements of the eyes are spared, so some adduction of the contralateral eye may be possible with a near stimulus. These movements are spared because vergence depends mainly on inputs passing directly to medial rectus motoneurons in the oculomotor nucleus. Saccadic, pursuit, optokinetic, and vestibular movements are still present in the contralateral hemifield but are impaired when directed toward the side of the lesion. Thus, in the case of a left abducens nucleus lesion, saccades from center to right gaze are preserved because they depend on projections to the intact abducens nucleus from the excitatory burst neurons of the right paramedian pontine reticular formation (PPRF). Saccades from right gaze to center are slow because they depend solely on

projections to the intact, right abducens nucleus from the inhibitory burst neurons

of the left medullary reticular formation; thus eye velocityis a function of antagonist muscle relaxation rather than agonist contraction. Another factor in asymmetry of residual movements may be horizontal gaze-evoked nystagmus on looking contralaterally (to the right, in the above example). Such nystagmus is probably due to interruption of fibers of passage from the medial vestibular nucleus, which provide an eye position signal to the con-

tralateral abducens nucleus,30 or due to interruption of fibers from cell groups of

the paramedian tracts (PMT), which lie at the rostral end of the abducens nucleus (see Display 6-4).988 Clinical lesions re-

stricted to the abducens nucleus are rare. 116,629,933,988,1083 More commonly, the

abducens nucleus is affected in association with adjacent tegmental structures, especially the medial longitudinal fasciculus and the paramedian reticular formation. An ipsilateral facial palsy usually occurs with abducens nucleus lesions, owing to

involvement of the adjacent genu of the seventh cranial nerve. Mobius syndrome, a congenital brain stem anomaly with horizontal gaze disturbances often with an associated facial palsy,29 may represent congenital hypoplasia of the abducens and facial nuclei. Failure of development of the abducens motoneurons, but not the internuclear neurons, accounts for some of the findings in Duane's syndrome. Both Mobius and Duane's syndromes are discussed in Chap. 9.

Lesions of the Paramedian Pontine

Reticular Formation (PPRF)

Although the predominant effect of destructive lesions of the paramedian pontine reticular formation (PPRF) falls on ipsilateral horizontal saccades (Display 10-21), other horizontal and vertical eye movements may be affected because the PPRF contains several different populations of neurons that are important for generating saccades (see Display 6-3), as well as fibers of passage. Excitatory burst neurons, which are important in the gen-

eration of horizontal saccades, lie in dorsomedial portions of the nucleus pontis centralis caudalis (see Fig. 6-2, Chap. 6), rostral to the abducens nucleus.649 Excitatory burst neurons project to the ipsilateral abducens nucleus. At the level of the abducens nucleus lies the nucleus raphe interpositus, which contains omnipause neurons that inhibit all burst neurons (horizontal and vertical) except during saccades. Caudal to the abducens nucleus, in the dorsomedial tegmentum, lie the inhibitory burst neurons, which receive inputs from the ipsilateral excitatory burst neurons but project to the contralateral abducens nucleus. Additional cell groups involved in the control of eye movements lie within the PPRF, such as the nucleus pararaphales, a member of the cell groups of the paramedian tracts (PMT) (see Display 6-4) that project to the cerebellar flocculus.217 Finally, the PPRF and adjacent pons contain fibers of passage that carry vestibular, pursuit, and gaze-holding signals to the abducens nucleus.

Unilateral lesions of the PPRF, such as infarction, cause an ipsilateral, conjugate, horizontal gaze palsy that may involve all classes of eye movements, but vestibular

and even pursuit eye movements are sometimes spared.707'785'1084 Acutely, the

eyes may be deviated contralaterally. Nystagmus occurs when gaze is directed into the intact contralateral field of movement, with quick phases directed away from the lesioned side; this is usuallyaccentuated in

darkness. Ipsilaterally directed saccades and quick phases are small and slow and

do not carry the eye past the midline.

The degree of slowing of saccades directed toward the lesioned side, when made in the intact field of gaze, may depend upon whether or not inhibitory burst neurons, which project to the contralateral abducens nucleus, are involved. Recall that excitatory saccadic inputs reach the abducens nucleus from the ipsilateral population of excitatory burst cells in the PPRF, whereas inhibitory saccadic inputs originate from contralateral inhibitory burst cells in the medulla (Fig. 6-1, Chap. 6). Thus, if the lesion is restricted to the ipsilateral abducens nucleus, saccades from the opposite field of gaze to the midline may be present but slow, since inhibition of the antagonists (i.e., the ipsilateral medial rectus and con-

tralateral lateral rectus) is intact. However, if the PPRF is extensively involved, particularly in its more caudal part, inhibition is also affected, so saccades directed toward the lesioned side are absent.988 Rapid eye movements directed to the side opposite the lesion appear normal. Vertical saccades may be slightly slow and misdirected obliquely away from the side of the lesion, owing to an inappropriate horizontal component.710

Smooth-pursuit movements and slow phases of optokinetic nystagmus may be preserved, in both directions, within the intact field of movement, but usually they cannot bring the eyes across the midline. Sometimes, horizontal pursuit or optokinetic responses are asymmetrically impaired. It has been suggested that more rostral brain stem lesions tend to cause ipsilateral smooth-pursuit deficits, whereas caudal brain stem lesions lead to contralateral deficits.708 More basal lesions in the

pons, however, tend to impair ipsilateral or bilateral pursuit.505'1368'1444 Because of

the confluence of pursuit pathways in the brain stem and its cerebellar connections, the direction of a pursuit deficit with a brain stem lesion is not reliable for determining the side of the lesion.490 In some patients vestibular stimuli drive the eyes past the midline.319 Presumably, either the