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

410 The Diagnosisof Disordersof Eye Movements

Figure 10-1. Four common slow-phase waveforms of nystagmus. (A) Constant velocity drift of the eyes. This occurs in nystagmus caused by peripheral or central vestibular disease and also with lesions of the cerebral hemispheres. The added quick phases give a "sawtooth" appearance. (B) Drift of the eyes back from an eccentric orbital position toward the midline (gaze-evoked nystagmus). The drift shows a negative exponential time course, with decreasing velocity. This waveform reflects an unsustained eye position signal caused by an impaired neural integrator. (C) Drift of the eyes away from the central position with a positive exponential time course (increasing velocity). This waveform suggests an unstable neural integrator and is encountered in the horizontal plane in congenital nystagmus and in the vertical plane in cerebellar disease. (D) Pendular nystagmus, which is encountered as a type of congenital nystagmus and with acquired disease.

separate mechanisms collaborate to prevent deviation of the line of sight from the object of regard. The first mechanism is the vestibulo-ocular reflex, by which eye movements compensate for head perturbations at short latency, and so maintain

clear vision during natural activities, especially locomotion. The second mechanism is the brain's ability to hold the eye at an eccentric position in the orbit against the elastic pull of the globe's suspensory ligaments and muscles, which tend to return it toward central position. The third mechanism is "fixation," which has two distinct components: the visual system's ability to detect retinal image drift and program corrective eye movements, and the suppression of unwanted saccades that would take the eye away from the target.

For all three gaze-holding mechanisms to work effectively, their performance must be honed. This requires continuous "recalibration" by adaptive mechanisms, which monitor the visual consequences of eye movements.

Disorders of these mechanisms disrupt steady gaze and lead to nystagmus; often the characteristics of the slow-phase drift indicate the ocular motor subsystem that is at fault. For example, imbalance of vestibular drives may cause constant velocity drifts (see Fig. 10-1A). If the gaze-holding mechanism is deficient, the eyes cannot be held steadily in an eccentric orbital position but drift back to the midline with a decreasing-velocity waveform (gazeevoked nystagmus—Fig. 10-1B). Because the gaze-holding mechanism depends, in part, upon the vestibular nuclei, nystagmus due to brain stem lesions often manifests the properties of both vestibular imbalance and disturbed gaze holding. Instability in the gaze-holding mechanism may lead to a slow-phase drift that increases in velocity (Fig. 10-1C). Disorders of the visual pathways may interfere with the ability to suppress nystagmus (of vestibular origin, for example) during fixation, and also lead to drifts of the eyes—including pendular oscillations (Fig. 10-ID)—because adaptive mechanisms cannot null such imbalances if deprived of visual inputs.

Thus, disorders of the vestibular system, the gaze-holding mechanism, and visual stabilization may each lead to nystagmus. First, we will discuss nystagmus due to each of these disorders in turn. We will then consider other forms of nystagmus that are either due to different causes or

for which no satisfactory pathophysiologic basis is known. Finally, we will discuss saccadic abnormalities that disrupt steady gaze and are frequently mistaken for nystagmus.

Nystagmus due to

Vestibular Imbalance

NYSTAGMUS CAUSED BY PERIPHERAL VESTIBULAR IMBALANCE

Disease affecting the vestibular labyrinth or nerve (including the root entry zone) causes nystagmus with linear slow-phase drifts (Display 10-1). The alternation of linear slow phases and corrective quick phases creates a "saw-tooth" pattern of nystagmus (see Fig. 10-1A). Such unidirectional slow-phase drifts reflect an imbalance in the level of tonic neural activity

in the vestibular nuclei. If labyrinthine disease leads to reduced activity in, for example, the right vestibular nuclei, then the left vestibular nuclei will drive the eyes, in a slow phase, to the right. In this example, quick phases will be directed to the left—away from the side of the lesion. Such imbalance of vestibular tone also causes vertigo and a tendency to fall and "past-point" toward the side of the lesion. Paradoxically, some patients will show nystagmus beating toward the side of the lesion; this may be recovery nystagmus that represent the effects of vestibular adaptation.919 Two features are helpful in identifying nystagmus as being of peripheral vestibular origin: its trajectory (direction) and whether it is suppressed by visualfixation.

The trajectory of nystagmus can be related to the geometric relationships of the semicircular canals and to the finding that experimental stimulation of an individual

412 The Diagnosis of Disorders of Eye Movements

canal produces nystagmus in the plane of that canal. Thus, complete unilateral labyrinthine destruction leads to a mixed horizontal-torsional nystagmus (the sum of canal directions from one ear—see Fig. 2-2). In benign paroxysmal positional vertigo, a mixed upbeat-torsional nystagmus reflects posterior semicircular canal stimulation (see VIDEO: "Nystagmus with benign paroxysmal positional vertigo"). Pure vertical or pure torsional nystagmus, however, almost never occurs with peripheral vestibular disease because this would require selective lesions of individual canals from both ears, an unlikely event.

Nystagmus due to disease of the vestibular periphery is more prominent, or may only become more apparent, when visual fixation is prevented. The reason for this is that visually mediated eye movements are working normally and will slow or stop the eyes from drifting due to vestibular imbalance. Fixation suppresses the horizontal and vertical components of nystagmus more than the torsional component. The effects of visual fixation on nystagmus can be evaluated at the bedside with Frenzel goggles or during ophthalmoscopy, if the fixating eye is transiently covered.1526

Another common, but not specific, feature of nystagmus caused by disease of the vestibular periphery is that its intensity increases when the eyes are turned in the di-

rection of the quick phase—Alexander's /aw.24'622-1159 This phenomenon implies an

adaptive mechanism developed to counteract the drift of the vestibular nystagmus and so establish an orbital position, in the direction of the slow phases, at which the eyes are quiet and vision is clear. Because the vestibular nuclei contribute to the gaze-holding network (neural integrator), peripheral or central lesions can cause both imbalance of the vestibular nuclei and impairment of gaze holding. Alexander's law provides the basis for a common classification of unidirectional nystagmus.

First-degree nystagmus is present only on looking in the direction of the quick phases; second-degree nystagmus is also present in the central position; third-degree nystagmus is present on looking in all directions of gaze. In some patients, a horizontal vestibular nystagmus may be-

come evident in up gaze, with convergence, or during vertical smooth pursuit movements.

Several bedside maneuvers can be employed to bring out nystagmus in patients with peripheral vestibular disease. First, a change of head position may exacerbate nystagmus or induce it in the syndrome of benign paroxysmal positional vertigo (see VIDEO: "Nystagmus with benign paroxysmal positional vertigo"). Second, in patients who have symptomatically recovered from a unilateral, peripheral, vestibular lesion, nystagmus can usually be induced following a period of vigorous

head shaking in the horizontal or the vertical plane for 15 to 20 seconds.567'1353 Af-

ter horizontal head shaking, patients may show horizontal nystagmus with quick phases directed away from the side of the lesion (see VIDEO: "Head-shaking nystagmus"). After vertical head shaking, patients with unilateral peripheral vestibular lesions may show less prominent nystagmus with horizontal quick phases directed toward the side of the lesion. Development of vertical nystagmus following horizontal head shaking suggests a central, not a peripheral, cause. Third, a Valsalva maneuver may induce nystagmus. Fourth, vibration of the mastoid bone may induce nystagmus in patients with perilymph fistula, superior canal dehiscence, unilateral loss of labyrinthine function, and with some central lesions, including cerebellar degeneration. Fifth, hyperventilation may

precipitate an acute vestibular imbalance.91a>947a with nystagmus, as the follow-

ing case illustrates.

CASE HISTORY: Hyperventilationinduced nystagmus

A freshman college student developed hemifacial spasms and dizziness precipitated by exercise. On examination, the sole findings were a minimal right facial paresis, as reflected in a decreased spontaneous blink, and strong hy- perventilation-induced nystagmus with slow phases directed toward the left and clockwise (see VIDEO: "Hyperventilation-induced nystagmus"). Laboratory tests initially showed a slightly decreased caloric response on the right

side, but hearing was normal. Computed tomography, angiography, and electroencephalography were normal. The patient's symptoms progressed over several years to a considerable loss of hearing on the right side, absent caloric responses on the right side, and moderate right facial paresis with aberrant regeneration. The hyperventilation-induced nystagmus, however, resolved. A CT, repeated with magnification views of the petrous bone, revealed a lytic lesion that proved to be a congenital epidermoid tumor (Fig. 10-2).

Comment: The unusual feature of this patient's clinical examination was his hyperventi- lation-induced nystagmus with slow phases directed away from the side of the lesion (an excitatory nystagmus). We considered four possible explanations. Two of these, seizures

and ischemia (due to decreased cerebral blood flow), seemed improbable. More plausible were a perilymph fistula and a recovery nystagmus. The former could have occurred because of erosion of the tumor through the bony labyrinth and into the subarachnoid space. Changes in cerebrospinal fluid pressure (as occur with hyperventilation) can be transmitted via the cochlear aqueduct to the perilymph space or directly via the destroyed petrous bone. If this was the mechanism, a Valsalvamaneuver should have produced nystagmus. Unfortunately, this maneuver was not attempted.

Alternatively, hyperventilation, by virtue of its effects upon serum pH and free calcium concentration, is known to improve nerve conduction in marginally functional, often demyelinated, fibers, as found in multiple sclerosis. In our patient, hyperventilation may have

414 The Diagnosis of Disorders of EyeMovements

improved nerve conduction and thereby increased the level of tonic discharge emanating from the right peripheral labyrinth. Because of a moderate degree of vestibular loss on the right side (which was reflected in the caloric response), central adaptation had occurred beforehand to rebalance the level of activity within the vestibular nuclei. Now, with the improved peripheral function due to the hyperventilation, central adaptation became inappropriate (excessive) and a recovery nystagmus ensued with slow phases directed away from the lesioned side. Changes of serum pH may also affect central adaptive mechanisms1206 or calcium channel function.1452

Hyperventilation-induced nystagmus also occurs in patients with acoustic schwannoma and after vestibular neuritis. The nystagmus may be directed with slow phases away from the side of the lesion, and a torsional component is often prominent.1206

Rarely, noises induce peripheral vestibular nystagmus—the Tullio phenomenon (Fig. 10-3) (see VIDEO: "Tullio phenome- non").947-1188 Auditory stimulation of the vestibular organ occurs when there is a leak of perilymph due to a breach in the bony labyrinth (e.g., the roof of the anterior canal, the oval or round windows) or pathologic transduction of sound by the ossicular chain.392

Whether or not an imbalance of proprioceptive inputs from neck muscles can produce a cervical nystagmus akin to that from peripheral vestibular disease is uncertain. In normal human subjects, cervical proprioception—the COR—plays little

role in the stabilization of gaze during natural head movements.190'1223 Although the

COR does assume more importance in in-

dividuals who have lost vestibular function,191'724'1501 the evidence that cervical

disease can induce nystagmus and vertigo is sparse. In human subjects, injection of local anesthetic into the neck has failed to produce nystagmus although slight gait instability or ataxia results.333'393 However, patients who have undergone radical neck surgery may show reduced vestibular responses.705 Vibration of the neck may induce nystagmus in patients with labyrinthine disease.1501 Conversely, a cerebellar lesion has been reported to cause an increase in the COR.189

NYSTAGMUS CAUSED BY CENTRAL

VESTIBULAR IMBALANCE

Here we discuss three forms of nystagmus thought to be caused by central vestibular imbalance: downbeat, upbeat, and torsional nystagmus. We also discuss how central lesions may rarely produce nystagmus with trajectories that are horizontal, or in the plane of a single semicircular canal. After describing the clinical features of each form of nystagmus, we summarize possible pathogenesis. Although periodic alternating nystagmus and seesaw nystagmus may also be viewed as forms of central vestibular nystagmus, they will be dealt with separately, below.

Clinical Features of

Downbeat Nystagmus

Table 10-1 summarizes some of the clinical disorders with which downbeat nystagmus has been reported. Commonly it occurs with degenerations affecting the vestibulocerebellum, lesion near the craniocervical junction, and with drug intoxication. Downbeat nystagmus is usually

Table 10-1. Etiology of Downbeat

Nystagmus86'193'580'1506

Cerebellar Degeneration,86'193'580 including Familial Episodic Ataxia,175'1524 and Paraneoplastic Degeneration36'1452'1534

Craniocervical Anomalies, including Arnold-

Chiari Malformation, Paget's Disease, Basilar Imagination11'1073'1313'1508

Infarction of Brain Stem or Cerebellum86'1294

Dolichoectasia of the Vertebrobasilar

Artery628'694 or Compression of the Vertebral Artery1176

Multiple Sclerosis86'193'912

Cerebellar Tumor, Including Hemangioblastoma1230

Syringobulbia1095 Encephalitis631 Head Trauma86

Increased Intracranial Pressure and Hydro- cephalus1077-1294

Toxic-Metabolic

Anticonvulsant medication26'121'250'671'1134 Lithium intoxication295'577'1488

Alcohol intoxication1174 and induced cerebellar degeneration1523

Wernicke's encephalopathy297'819 Magnesium depletion1219 Amiodarone45a

Vitamin B]2 deficiency916 Toluene abuse901

Tetanus1048 Congenital139'185

Transient Finding in Infants659'1467

present with the eyes in central position, although its amplitude may be so small that it is only detected during ophthalmoscopy (Display 10-2). A low-velocity upward drift of the eyes (downward drift of the optic disc) may occasionally be seen during ophthalmoscopy in normal subjects, but it is not present with a fixation target. Downbeat nystagmus may occur intermittently and, in some patients, only becomes evident during convergence or in lateral gaze (see VIDEO: "Gaze-evoked, rebound, and downbeat nystagmus"). In most patients with downbeat nystagmus, Alexander's law is obeyed and slow-phase

velocity (and nystagmus intensity) is greatest in down gaze and least in up gaze. Hence, asking patients to look down and laterally is often the best way to bring out downbeat nystagmus. In some patients, however, downbeat nystagmus is greatest on up gaze. In these cases, the slow phases may not be linear but are, instead, increasing in velocity (see Figure 10-1C and Figure 10-4) (see VIDEO: "Downbeat nystagmus");11'1534 this finding indicates an instability of the vertical gaze-holding network. A similar pattern of downbeat nystagmus has also been observed following removal of the vestibulocerebellum (flocculus and paraflocculus) in monkeys.1538 Downbeat nystagmus is occasionally disjunctive, being more vertical in one eye and torsional in the other. In these circumstances, it may be accompanied by internuclear ophthalmoplegia.501'1024 Some patients may show combined divergentdownbeat nystagmus.1509

In most patients, removal of fixation (e.g., by Frenzel goggles) does not substantially influence slow-phase velocity, although quick-phase frequency may diminish. Downbeat nystagmus may also be

accentuated or brought on by placing the patient in a head-hanging position or by convergence. In some patients, downbeat nystagmus is converted to upbeat nystag-

mus by convergence, or vice versa.297-435 A variety of ocular motor abnormalities

often accompanies downbeat nystagmus and usually reflects coincident cerebellar involvement. Vertical smooth pursuit and the vertical vestibulo-ocular reflex are usually abnormal in patients with downbeat nystagmus. There is impaired ability to generate downward pursuit eye movements, which cannot simply be attributed to superimposed nystagmus.86 Often the

gain of the vestibulo-ocular reflex for upward eye movements exceeds l.O.1532 Im-

pairment of horizontal gaze holding, smooth pursuit, and combined eye-head tracking (vestibulo-ocular cancellation) also commonly coexist. The consequences of retinal slip produced by the slow phases are oscillopsia, postural instability, and an

increased threshold for egocentric detection of object motion.210'392a Some patients

with downbeat nystagmus also report diplopia, perhaps reflecting coexistent skew deviation.

Clinical Features of

Upbeat Nystagmus

Upbeat nystagmus that is present with the eyes close to the central position may be regarded as a form of central vestibular nystagmus (Display 10-3). The more common disorders with which it is associated are summarized in Table 10-2. Upbeat nystagmus is less well localized than downbeat nystagmus, being reported with lesions from the medulla to midbrain. Upbeat nystagmus with the eyes close to central position should be differentiated from nystagmus evoked exclusively on up gaze, which occurs in general gaze-holding failure, with peripheral ocular motor disorders including myasthenia gravis, and in some normal subjects. It should also be differentiated from the transient, mixed upbeat-torsional nystagmus that is induced by positional testing in patients with benign paroxysmal positional vertigo of the posterior canal type (see VIDEO: "Nystagmus with benign paroxysmal positional vertigo"). Upbeat nystagmus that is present in central posi-

tion usually follows Alexander's law, becoming greatest in up gaze. Sometimes, however, the nystagmus is accentuated on looking down, and then the slow phase is more likely to be increasing velocity rather than linear (Fig. 10-5). Unlike downbeat nystagmus, upbeat nystagmus usually does not increase on lateral gaze. Removal of visual fixation may alter the frequency of quick phases, but it does not influence slow-phase velocity. Convergence enhances the nystagmus in some patients, suppresses it in others, and occasionally converts it to downbeat nystagmus.297'435 Placing the patient in a head-hanging position increases the nystagmus in some individuals. The vertical vestibulo-ocular reflex (VOR) and smooth pursuit are usually abnormal. Some patients show a combined upbeat-di- vergent form of nystagmus (Fig. 10-6) (see VIDEO: "Upbeat nystagmus"). Other patients may show quick phases that have small horizontal components that alternate to the right or left; these trajectories

create the pattern of a bow-tie nystagmus (Fig.lO-5D).1470