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

Clinical Features of

Torsional Nystagmus

Although peripheral vestibular, congenital, and seesaw nystagmus may all have torsional components—especially on lat-

Table 10-2. Etiology of Upbeat

Nystagmus86-446

Cerebellar degenerations and atrophies493'494

Multiple sclerosis446'1036

Infarction of medulla86'221'630'754'981 or cerebel-

lum and superior cerebellar peduncle115

Tumors of the medulla,446-514 cerebellum,419'1390 or midbrain996'1396

Wernicke'sencephalopathy297-446'1550

Brain stem encephalitis488

Behget's syndrome678 Meningitis640

Leber's congenital amaurosis and other con-

genital disorders of the anterior visual path-

ways529-662

Thalamic arteriovenous malformation1023

Congenital1303

Organophosphate poisoning701 Tobacco1285

Associated with middle ear disease552 Transient finding in infants659

eral gaze, when described in an eye-fixed coordinate system—nystagmus that is purely torsional in central position (like purely vertical nystagmus) bespeaks disease affecting central vestibular connections (Display 10-4). Often it is difficult to detect except by careful observation of conjunctival vessels or by noting the direction of retinal movement on either side of the fovea. This rarer form of central vestibular nystagmus is usually associated with medullary lesions, such as syringobulbia and Wallenberg's syndrome (lateral medullary infarction) (Table 10-3). Torsional nystagmus may show features similar to downbeat and upbeat nystagmus,including modulation by head rotations, variable slow-phase waveforms, and suppression by convergence.1021 It is probably a common finding in patients with the ocular tilt reaction,60 including those with internuclear ophthalmoplegia.343 Torsional nystagmus has also been described during vertical smooth pursuit in patients with lesions involving the middle cerebellar peduncle;461 this phenomenon is discussed further in the section on Ocular Motor Syndromes Caused by Disease of the Cerebellum. Nonrhythmic but continuous torsional eye movements have been reported as a possible paraneoplastic phenome-

non 1178 Episodes of torsional nystagmus, initiated by quick phases that rotated the upper poles of each eye towards the side of a mesodiencephalic lesion, might be due to activation of the ipsilateral riMLF.H6a

Horizontal Nystagmus Due to Central Vestibular Imbalance

Most predominantly horizontal nystagmus is congenital or peripheral vestibular in origin. However, central vestibular disturbances sometimes cause nystagmus that is horizontal (when the eyes are close to central position); often the underlying disorder is an Arnold-Chiari malformation (Fig. 10-7).102 The slow-phase waveform may be increasing velocity, making distinction from congenital nystagmus potentially difficult. However, patients may report recent onset of visual symptoms such as oscillopsia, and measurements may demonstrate an associated vertical component, which is usually absent in congenital nystagmus. Patients with horizontal nystagmus that is present in the central position should always be observed for a period of 2 minutes to exclude the possibility of periodic alternating nystagmus.

Perverted Vestibular Nystagmus

Patients with disease affecting central vestibular connections, including the vestibulocerebellum, sometimes develop nystagmus in a plane other than that being stimulated by either caloric stimulation or head rotation. For example, after horizontal head shaking, downbeat nystagmus may occur—an inappropriate cross-coupling of vestibular nystagmus. Following experimental lesions of the vestibular nuclei, unilateral caloric stimulation sometimes induced vertical responses ("perverted nystagmus").1407 This last finding is not a reliable sign of vestibular nucleus disease, however, because a small vertical component may also be present in normal subjects.94

Pathogenesis of Central

Vestibular Nystagmus

Better understanding of the pathogenesis of central forms of vestibular nystagmus

has been gained from clinicopathological correlation, the development of animal models, and application of modern anatomy and physiology. Downbeat nystagmus is usually associated with lesions of the vestibulocerebellum (flocculus, paraflocculus, nodulus, and uvula) and underlying medulla.86 Upbeat nystagmus is most com-

monly reported with medullary lesions,322'446'514'754'981 which variably involve

the perihypoglossal nuclei and adjacent medial vestibular nucleus (structures important for gaze holding), nucleus intercalatus,630'700a and the ventral tegmentum, which contains projections from the vestibular nuclei that receive inputs from the anterior semicircular canals.1121 Upbeat nystagmus is also reported with lesions involving the anterior vermis of the cerebellum322 or the adjacent brachium conjunctivum and midbrain.115'730'996 This evidence suggests that lesions at several distinct sites can cause upbeat and downbeat nystagmus. However, it is possible to account for these findings by considering the fundamental anatomic fact that, unlike the horizontal vestibular system, which is right-left symmetric, the connections for vertical vestibular responses are dissimilar for upward and downward eye movements. Furthermore, the anatomical orientation of the semicircular canals may be rightleft symmetric, but it lacks symmetry in a craniocaudal direction.160 These up-down asymmetries involve connections subserving (1} the vertical vestibulo-ocular reflex, (2) the otolith-ocular reflexes, (3) the vestibulocerebellum, (4) the network for eccentric gaze holding (neural integrator), and (5} the smooth-pursuit system.

Excitatory projections for the vertical vestibulo-ocular reflex (see Fig. 2-3) from the posterior semicircular canals, which mediate downward eye movements, synapse in the medial vestibular nucleus and then cross dorsally in the medulla, beneath the nucleus prepositus hypoglossi to reach the contralateral medial longitudinal fasciculus. Experimental lesions that presumably involve this pathway cause upward eye drifts and downbeat nystagmus.86 It appears, however, that excitatory connections from the anterior semicircular canals, which mediate upward

eye movements, take different routes,

and more than one pathway may contribute.922,923

It has also been suggested that a central imbalance of otolithic inputs (see Table 2-2) may contribute to vertical nystagmus.551 This hypothesis is based on the observation that downbeat or upbeat nystagmus may

Table 10-3. Etiology of Torsional

Nystagmus*877

Syringobulbia, with or without syringomyelia and Arnold-Chiari malformation1470

Brain stem stroke (e.g., Wallenberg's syndrome)960

Arteriovenous malformation in the brain stem960'1021 or middle cerebellar peduncle461

Brain stem tumor877 Multiple sclerosis877

Oculopalatal tremor ("myoclonus")64 Head trauma877

Congential

*Often occurs in association with the ocular tilt reaction60'1331 and unilateral internuclear ophthalmoplegia.343

be precipitated or exacerbated by a change in head position (e.g., head-hanging position). Furthermore, normal humans and other species may develop vertical drifts in darkness when their heads are not erect.524-1193 While otolithic inputs (including tilt of the head and imposed linear accelerations) can influence vertical nystagmus, there is some debate as to whether an otolithic imbalance is the primary disturbance. For example, in some patients, head tilt does not influence the nystagmus.551 Nevertheless, in one patient with upbeat nystagmus due to a hemorrhage affecting the left brachium conjunctivum and anterior cerebellum, a leftward head tilt suppressed the nystagmus.730 Furthermore, an otolithic influence on vertical nystagmus offers perhaps the only plausible explanation for the effects of convergence. It has been shown that viewing a near target increases the gain of the VOR

and that the otoliths influence this modulation.1432

The case for the cerebellar flocculus (see Display 6-10) rests on the finding that Purkinje cells send inhibitory projections to the central connections of the anterior

canal but not of the posterior canal.84-684 This asymmetry of inhibitory projections accounts for the finding that experimental flocculectomy causes downbeat nystagmus;1538 this lesion disinhibits anterior canal (but not posterior canal) projections and so causes the eyes to drift up, producing downbeat nystagmus. The development of an animal model makes this the strongest hypothesis for downbeat nystagmus.

A neural network that includes the nucleus prepositus hypoglossi and adjacent medial vestibular nuclei (NPH-MVN region) and the vestibulocerebellum is important for the mechanism for holding the eyes steady in eccentric gaze. Consistent with this, a patient with lithium intoxication and downbeat nystagmus had lesions in the nucleus prepositus hypoglossi.295 Disease of the vestibulocerebellum may cause instability of this network (Fig. 5-6), causing the eyes to drift at increasing velocity away from central position in the

vertical or horizontal planes (see VIDEO: "Downbeat nystagmus").11'102'1534 The cell

groups of the paramedian tracts (PMT) (see Display 6-4) also may contribute to neural integrator function by relaying eye movement signals to the vestibulocerebellum.217 One component of the PMT cell groups is the medullary nucleus pararaphales, which receives vertical eye position signals from the interstitial nucleus of Cajal. Thus, medullary lesions that affect this nucleus might lead to upbeat nystagmus.221

Finally, based on the observation that the slow-phase velocity of downbeat nystagmus is unaffected by visual fixation, and vertical smooth pursuit is impaired, it was proposed that the characteristics of downbeat nystagmus could be best explained by a central imbalance in smoothpursuit tone with cerebellar lesions.1532 Although subsequent studies have made it more likely that vestibular or gaze-holding disturbances rather than pursuit imbalance are primarily responsible, the original observation remains valid and thus might reflect coexistent impairment of the smooth pursuit pathway either as it passes through the cerebellum or in the vestibular and prepositus nuclei (see Fig. 6-7).

Resolution of upbeat or downbeat nystagmus after the first few months of life, in otherwise normal infants,659 may reflect "calibration" of pursuit or gaze-holding mechanisms as the visual system becomes fully myelinated.

Periodic Alternating Nystagmus

Acquired periodic alternating nystagmus

minutes (Display 10-5) (see VIDEO: "Periodic alternating nystagmus"). Because the period of oscillation is about 4 minutes, the disorder may be missed unless the examiner observes the nystagmus for several minutes. As the nystagmus finishes one half-cycle (e.g., of right-beating nystagmus), a brief transition period occurs during which there may be upbeating or downbeating nystagmus or square-wave jerks before the next half cycle (e.g., of left-beating nystagmus) starts. Although rare, acquired PANis perhaps the best understood of all forms of nystagmus and

was the first for which an effective treatment was identified.579'835-1447

Several other disorders are characterized by periodic reversals of spontaneous, abnormal eye movements. A congenital form of PAN is usually much less regular in the timing of reversal of direction and shows slow-phase waveforms typical of congenital nystagmus.7'542 PAN should be differentiated from ping-pong gaze, which is encountered in unconscious patients with large bihemispheric lesions and consists of ocular deviations that reverse direction over the course of a few seconds.676 Certain patients with acquired PAN show a "short cycle" of 20 to 30 seconds, and it is uncertain whether their underlying pathophysiology differs from classic acquired PAN.

In most patients with acquired PAN, the nystagmus has the same characteristics in light or in darkness. Some patients, especially children, also show periodic head rotations in the direction of the quick

phases, using Alexander's law to partially or completely null the nystagmus.521'758'1318

Smooth pursuit and optokinetic nystagmus are usually impaired.835 Vestibular stimuli are able to "reset" the oscillations, and critically timed rotational stimuli can stop PAN for several minutes.492'835

Acquired PAN has been reported in association with a number of conditions (Table 10-4), many of which involve the cerebellum. If the neurologic disorder also involves the brain stem mechanism for generating quick phases, patients may progress to periodic alternating gaze deviation.58'544 It has also been reported that PAN develops following visual loss due to vitreous hemorrhage305 or cataract702 and is abolished when vision is restored. The GABAB-ergic drug baclofen abolishes acquired PAN in most patients.579

Insight into the pathogenesis of PAN has come from experimental studies. Ablation of the cerebellar nodulus and uvula in monkeys causes PAN when they are in

darkness; baclofen abolishes this nystagmus.1447 One function of the nodulus and

uvula is to control the time course of rotationally induced nystagmus—the so-called velocity-storage mechanism.276 Thus, following ablation of the nodulus and uvula, the

duration (velocity storage) of rotationally induced nystagmus is prolonged excessively, and it is postulated that normal vestibular "repair mechanisms" act to reverse the direction of this nystagmus, so pro-

Table 10-4. Etiology of Periodic

Alternating Nystagmus492'791'835

Arnold-Chiari malformation and other hindbrain anomalies492'835'934

Multiple sclerosis736'791 Cerebellar degenerations492-534'865

Cerebellar tumor, abscess, cyst, and other mass lesion758-835

Creutzfeldt-Jakob disease544 Ataxia telangiectasia1327 Brain stem infarction492

Anticonvulsant medications228-1246

Infections affecting cerebellum, including syphilis791'835

Hepatic encephalopathy58 Trauma791

Following visual loss (due to vitreous hemorrhage or cataract)305'702

Congenital nystagmus7

426 The Diagnosis of Disorders of Eye Movements

ducing the oscillations of PAN.492'791'835 These oscillations would ordinarily be blocked by visual stabilization mechanisms that tend to suppress nystagmus, but disease of the cerebellum that causes PAN usually also impairs these mechanisms; in rare cases, eye disease (cataract or retinal

detachment) prevents fixation and allows PAN to develop.305-702 Finally, pharmaco-

logical evidence suggests that the nodulus and uvula maintain inhibitory control on the vestibular rotational responses by using GABA.276 Thus, the GABA agonist baclofen is able to abolish PAN caused by either experimental or clinical lesions of the nodulus and uvula.276

Two other unusual disorders may be related to PAN. The first is a variation of PAN—alternating windmill nystagmus— which consists of oscillations in both the horizontal and vertical planes, 90° out of phase.1212 This phenomenon occurred in a blind patient. The second is a patient with paroxysms of mixed torsional-hori- zontal-vertical nystagmus that occurred every 2 minutes in association with nausea.821 In this patient, the initial mechanism was probably paroxysmal hyperactivity in one vestibular nucleus complex, unlike PAN, in which prolongation of the vestibular response is the initial mechanism. However, in both, an "adaptive mechanism" appeared to influence the nystagmus every 2 minutes; this is perhaps the most direct evidence that activation of the ocular motor "recalibration mechanism" can lead to nystagmus.

Seesaw and Hemi-seesaw

Nystagmus

In these forms of nystagmus, one half cycle consists of elevation and intorsion of one eye and synchronous depression and extorsion of the other eye; during the next half cycle, the vertical and torsional movements reverse (Fig. 10-8, Display

10-6). The waveform may be pendular,318,402,406,994 or j^ in which case the

slow phase corresponds to one half-cycle

(hemi-seesaw nystagmus}.^1 A seesaw component is present in many central forms of

nystagmus. Seesaw nystagmus has been reported in association with a variety of disorders (Table 10-5) and may present as a

form of congenital nystagmus (see VIDEO: "Seesaw nystagmus").318'842'1229 One pa-

tient with congenital seesaw nystagmus was reported to show the opposite pattern of vertical-torsional synchrony seen with acquired cases, so elevation occurred with extorsion and depression with intorsion.318

Measurement of horizontal, vertical, and torsional components of these oscillations using the magnetic search coil technique has clarified the characteristics and pathogenesis of hemi-seesaw and seesaw nystagmus. Jerk seesaw nystagmus (hemiseesaw nystagmus) occurs in patients with lesions in the region of the interstitial nucleus of Cajal (INC—see Display 6-6). Such patients often have a contralateral ocular tilt reaction; with a left INC lesion; this would cause right head tilt, skew deviation (left hypertopia), tonic intorsion of the left and extorsion of the right eye, and

the misperception that earth-vertical is tilted to the right.172'571 Rarely, the ocular

tilt reaction is paroxysmal in form, in which case it is ipsilateral to the INC lesion; some such patients also show corresponding paroxysms of jerk seesaw nystagmus.571 The ocular tilt reaction represents an imbalance of central otolithic

projections from vestibular nuclei to the INC.172a Stimulation in the region of INC

in monkeys produces an ocular tilt reaction1478 consisting of extorsion and de-

pression of the eye on the stimulated side and intorsion and elevation of the other eye; somewhat similar results are reported in humans.885-1215 Thus, the various forms of the ocular tilt reaction are similar to the slow phases of jerk seesaw nystagmus. The presence of corrective, ipsilesional quick phases may occur if the adjacent rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) (see Display 6-5) is intact; if the riMLF is also involved, either no quick phases571 or contralesional quick phases608 may be observed. (Recall that each riMLF contributes to upward and downward saccades but only to ipsilaterally directed torsional quick phases, with top poles rotating toward the ipsilateral side—see Display 6-5.)

Pendular seesaw nystagmus has most frequently been described with large parasellar tumors, so these oscillations have been attributed to either secondary midbrain compression or to the effects of commonly associated visual field defects. Pendular seesaw nystagmus has been re-

Figure 10-8. Seesaw nystagmus. (A) Schematic of the oscillation showing that during one half-cyclethe right eye rises and intorts, and the left falls and extorts (top); during the next half-cycle, the opposite movements occur (bottom). (B) Record of 39-year-old woman with congenital seesaw nystagmus shown in the video (see VIDEO: "Seesaw nystagmus").The horizontal component has a conjugate "pseudocycloid"waveform typical for congenital nystagmus. There is a disconjugate vertical component and a large conjugate torsional component. Note that as either eye goes up, it intorts, and as it goes down, it extorts. The single position traces are offset for convenience of display; upward deflections indicate rightward (horizontal), upward (vertical), or clockwise (torsional) eye rotations with respect to the patient. RH, right horizontal; LH, left horizontal; RV, right vertical; LV, left vertical; RT, right torsional; LT,left torsional.

ported with visual loss123 and has been documented to develop in a patient who progressively lost vision due to retinitis pigmentosa.915 It is also reported in patients who have congenital abnormalities of their optic chiasm.40'842 Thus, it is possible that visual loss inactivates the "recali-

bration" mechanism for eye movements that compensate for head rotations in roll (ear-to-shoulder). If the subject looks at an object located off the midsagittal plane during head roll, a seesaw rotation of the eyes is the geometrically appropriate compensation.1253 It seems that normal calibration of this response, which would require that motion-visual information be sent to the cerebellum, could be impaired

Table 10-5. Etiology of Seesaw and

Hemi-Seesaw Nystagmus571

Mesodiencephalic disease, such as stroke571'719 Parasellar masses318'402-406

Lack or loss of crossing fibers in the optic

chiasm (e.g., achiasma and septo-optic dysplasia)40'326

Multiple sclerosis1208 Arnold-Chiari malformation1547 Syringobulbia433

Progressive visual loss (e.g., due to retinitis pigmentosa)123'915

Head trauma479'741'1215 Congenital318'351'662'1229

with parasellar lesions, leading to the pendular variant of seesaw nystagmus.994 Thus, the two variants of seesaw nystagmus probably arise from either imbalance or miscalibration of vestibular responses that normally function to optimize gaze during head rotations in roll. Finally, dissociated vertical deviation (DVD),1415 a form of congenital vertical strabismus in which the covered eye elevates and extorts, is similar to one half-cycle of the variant of congenital seesaw nystagmus described by Daroff,318 and suggests a relationship between these two disorders.

Nystagmus OccurringWhen the

Eyes Are in EccentricGaze

GAZE-EVOKED NYSTAGMUS

Nystagmus induced by moving the eye to an eccentric position in the orbit is called gaze-evoked nystagmus (Display 10-7). It is the commonest form of nystagmus encountered in clinical practice. The term gaze-paretic nystagmus is only accurate in those cases with associated paresis of gaze

due, for example, to a cerebral or brain stem process, or to weaknessof extraocular muscles. Usually gaze-evoked nystagmus occurs on lateral or upward gaze—seldom on looking down. If fixation is impaired or prevented (e.g., in darkness), the slow phases consist of centripetal drifts that may have an exponentially decaying waveform (see Figure 10-1B and Figure 10-9). If visual fixation is possible, however, the slow phases have a more linear profile.

Figure 10-9. Gaze-evoked and rebound nystagmus. The eye movement recording is taken from a patient with familial cerebellar degeneration. On looking to the far left, gaze-evoked nystagmus commences, with some individual slow phases showing declining velocity. After 35 sec of this sustained effort at maintaining eccentric gaze, the slow-phase drift velocity is reduced. When the eyes are returned to the central position, the nystagmus reverses direction (rebound nystagmus) (see VIDEOS: "Gaze-evoked, rebound, and downbeat nystagmus"). (From Zee DS, Yee RD, Cogan DG, Robinson DA, Engel WK. Ocular motor abnormalities in hereditary cerebellar ataxia. Brain 1976;99:207-34, copyright, Oxford University Press.)

In order to understand how gazeevoked nystagmus arises, consider the neural command required to hold the eye steadily at an eccentric position in the orbit (see Fig. 1-3, Chap. 1). When the eye is turned toward a corner of the orbit, the tissues that suspend the eye exert an elastic force to return it toward central position. A tonic contraction of the extraocular muscles is required to overcome this elastic, restoring force. This is achieved by a "step" eye position command from the ocular motoneurons, which is generated by a gaze-holding network (the neural integrator). Gaze-evoked nystagmus is due to a deficient eye position signal: The eyes cannot be maintained at an eccentric orbital position and they are pulled back toward the central position by the elastic forces of the orbital fascia. Then corrective quick phases move the eyes back toward the desired position in the orbit. Frequently, lesions that produce gaze-evoked nystagmus also impair visual fixation and smooth pursuit. Crucial structures for horizontal gaze holding are the nucleus prepositus hypoglossi and medial vestibular nucleus (the NPH-MVN region); for vertical gaze holding the interstitial nucleus of Cajal (INC) (see Display 6-6) plays an important role. In addition, thevestibulocerebellum contributes to this gazeholding function. The mechanism for gaze holding is discussed further in Chap. 5.