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

480 The Diagnosis of Disorders of Eye Movements

Table 10-11. Etiology of Oscillopsia

Oscillopsia With Head Movements: Abnormal

Vestibulo-Ocular Reflex

Peripheral vestibular hypofunction164>621'1141a

Aminoglycoside toxicity574-946'14593 Surgical section of eighth cranial nerve471

Tumors914 Meningitis940

Congenital ear anomalies904'982 Hereditary vestibular areflexia76'1421'1422 Cisplatin therapy772'991'998

Idiopathic77'81'440'1428 Dolichoectatic basilar artery222-1026

Central vestibular dysfunction

Decreased VOR gain558-1122

Increased VOR gain1372'1532 Abnormal VOR phase558

Paresis of extraocular muscles (including ocular motor nerve palsies)

Oscillopsia Due to Nystagmus

Acquired nystagmus (especially pendular nys-

tagmus, upbeat, downbeat, seesaw, dissociated nystagmus)533'829-836'1505

Saccadic oscillations (psychogenic flutter/voluntary nystagmus, ocular flutter, microsaccadic flutter and opsoclonus)

Superior oblique myokymia (monocular oscil- lopsia—see Chap. 9)

Congenital nystagmus (uncommon under natural illumination)829

Central Oscillopsia

With cerebral disorders: seizures, occipital lobe infarction113

With transcutaneous magnetic stimulation of scalp726

and the development of Oscillopsia is less consistent and varies among subjects. For example, individuals with congenital nystagmus, who often have images moving across the retina with speeds exceeding 100°/sec,8 seldom complain of Oscillopsia under normal viewing conditions. Acquired disease affecting eye movements produces Oscillopsia in three main ways: an abnormal VOR, paresis of extraocular muscles, and ocular oscillations—such as nystagmus.

Oscillopsia Due to an Abnormal VOR

An abnormal VOR may lead to Oscillopsia during head movements via three mechanisms: abnormal gain, abnormal phase shift (timing) between eye and head rotations, and a directional mismatch between the vectors of the head rotation and eye rotation (see Quantitative Aspects of the Vestibular-Optokinetic System in Chap. 2). Peripheral or central dysfunction affecting either the angular or the linear VOR can lead to Oscillopsia.377'846 Especially in the acute phase of loss of vestibular sense due, for example, to bilateral eighth nerve section471 or aminoglycoside antibiotic intoxication,686 head rotations will lead to Oscillopsia.

Patients with bilateral vestibular loss may become excessively dependent upon visual inputs for image stabilization and consequently may develop visual discomfort and inappropriate body sway, while standing still and attempting to watch swaying trees on a windy day, for example. This excessive visual dependence can become a problem in any patient with an active labyrinthine disorder, or even a past history of one. It leads to the common complaint of visual discomfort and unsteadiness in such patients when they are walking down shopping aisles in a supermarket, seeing action movies on a large screen, looking out of the car through windshield wipers, or walking or riding by a picket fence.

Typically, Oscillopsia is worse during locomotion (see (Fig. 7-1) but it may be noticed during chewing food and, in the most severe cases, it may occur due to transmitted cardiac pulsation.686 In addition, dynamic visual acuity declines during head movements; this decline can be easily demonstrated at the bedside.208'876 Objectively, using the ophthalmoscope, the optic disc will be seen to move with every head rotation. Patients with essential head tremor and vestibular failure may show abnormal oscillations of the optic disc during ophthalmoscopy.188 Because any residual function of the VOR is preferentially spared for higher-frequency

stimuli,75 the inadequacy of the vestibuloocular reflex may sometimes be more evident during large-amplitude, back-and- forth oscillations of the head at about 1 Hz; during these movements, saccades are necessary to hold gaze steady during attempted fixation. With time, however, compensation takes place, owing to potentiation of the cervico-ocular reflex, preprograming of compensatory eye movements, perceptual changes,560a and other factors (see Table 7-1, Chap. 7). Bilateral

vestibular loss may be the cause of gait imbalance in the elderly,440 in whom the po-

tential for compensation is reduced. Ototoxicity, especially associated with

administration of aminoglycoside antibi-

tamicin is the most common culprit and its toxicity may be insidious.946 It may occur without hearing symptoms and even with normal blood levels and relatively short periods of administration.574 Some patients who develop Ototoxicity may be genetically predisposed to the drug's toxic side effects.445'1110 Topical gentamicin may occasionally lead to unwanted labyrinthine loss when used to treat external ear infections.874 Intratympanic gentamicin is used to purposefully ablate labyrinthine function as part of the treatment of intractable Meniere's syndrome.37'120 Cisplatin is prob-

Dolichoectasia of the vertebral or basilar artery also may lead to bilateral loss, usu-

ally without involvement of hearing.1026'1070 Bilaterally vestibular defi-

ciency may be associated with congenital ear anomalies.982 Often no cause can be

identified for bilateral vestibular defi- ciency.77'164'440-1421'1428 Idiopathic bilateral

vestibular loss is sometimes familial, inherited as a dominant trait, and can be associated with migraine and recurrent attacks of vertigo.76 These patients may have normal hearing. Acetazolamide may help the attacks of vertigo and headaches, but it is

not yet clear if the bilateral loss can be arrested or improved. Baloh and colleagues reported autopsy findings in a patient with isolated progressive loss of labyrinthine function who also had ultrashort vestibular time constants, but preserved amplitude of response.81 They found loss of hair cells and altered mitochondria (and presumably abnormal energy metabolism) and suggested that these factors could account for the pattern of loss of vestibular function.

Oscillopsia may also occur with disor-

ders of the central nervous system that change the gain or phase of the VOR.558

Thus, disease of the vestibulocerebellum may cause vestibular hyper-responsive- ness, particularly in the vertical plane. This is common in patients with ArnoldChiari malformation.1532 Occasionally, pa-

tients are reported with increased gain of both the horizontal and vertical VOR.1372

In some patients with vestibulocerebellar dysfunction, the gain of the VOR is normal, but the phase relationship between head and eye movements is abnormal and causes retinal image slip.558 Lesions of the medial longitudinal fasciculus producing INO may cause a low gain of the vertical

VOR and produce oscillopsia with vertical head movements.533'1122

Oscillopsia due to Paresis of

Extraocular Muscles

Weakness of extraocular muscles beside

causing diplopia may also lead to oscillopsia during head movements.1491 This is be-

cause the VOR is prevented from working adequately in the paretic field of gaze. The cause of the muscle weakness may be a nerve palsy; neuromuscular disease, such as myasthenia gravis; or restrictive diseases of the orbit, such as thyroid ophthalmopathy. Disease of the extraocular muscles themselves also limits ocular motility, but the slow progression of these disorders seems to allow patients time to make perceptual adaptations to the slip of retinal images during head movements. These disorders of the extraocular mus-

482 The Diagnosisof Disordersof Eye Movements

cles are discussed in Chap. 9. Rarely, lens subluxation following head trauma may cause monocular oscillopsia that occurs with each saccade.985

Oscillopsia Due to Nystagmus and Other Abnormal Eye Movements

Oscillopsia may also be caused by ocular oscillations such as nystagmus (see The Nature and Visual Consequences of Abnormal Eye Movements That Prevent Steady Fixa-

tion). In such cases, oscillopsia occurs even when the head is still.1491 Thus, acquired

pendular nystagmus, occurring in multiple sclerosis or in association with palatal tremor; downbeat and upbeat nystagmus; and even gaze-evoked nystagmus may lead to oscillopsia (see VIDEOS: "Acquired nystagmus impairing vision"). In addition, certain saccadic disorders such as ocular flutter and opsoclonus (see VIDEOS: "Opsoclonus") may cause oscillopsia. Superior oblique myokymia may cause monocular oscillopsia (see VIDEO: "Superior oblique myokymia"). One method of bringing out oscillopsia is to ask the patient to fixate on a small light in a dark room and to indicate the direction of the perceived movement of the stationary light. The nystagmus causing oscillopsia is not always obvious on gross examination.113 A sensitive and convenient way to detect instability of gaze is to view the retina with an ophthalmoscope.

The magnitude of oscillopsia is usually less than the magnitude of nystagmus. For example, in patients with downbeat nystagmus, oscillopsia is equivalent to about

one-third of what would be predicted from the amplitude of the nystagmus.210'3923

This finding implies that the brain compensates for the excessive retinal image motion by using an extraretinal signal, such as efference copy, to maintain visual constancy.355-829 As previously mentioned, oscillopsia is rarely a complaint in individuals with congenital nystagmus, though visual acuity may be impaired due to the oscillation. Motion detection may be impaired in some individuals with congenital nystagmus,388 but this cannot be the entire explanation, since artificial stabilization of

images, paradoxically, may cause oscillopsia.355'829 Methods available for treatment of nystagmus are listed in Table 10-8.

Finally, oscillopsia is rarely reported by patients who do not have excessive retinal image motion (i.e., have no nystagmus or vestibular dysfunction) but, rather, seem to have a disorder of those central mechanisms that normally ensure a sense of visual constancy.113

OCULAR MOTOR SYNDROMES CAUSED BY LESIONS IN

THE MEDULLA

Medullary Lesions Impairing

Gaze Holding

The medulla contains a number of structures that are important in the control of eye movements: vestibular nuclei, perihypoglossal nuclei, medullary reticular formation, inferior olivary nuclei, and restiform body. The perihypoglossal nuclei consist of the nucleus prepositus hypoglossi (NPH), which lies in the floor of the fourth ventricle; the nucleus intercalatus, and the nucleus of Roller. These nuclei have rich connections with other ocular motor structures. The NPH and the adjacent medial vestibular nuclei (MVN)— the NPH-MVN region—are critically im-

structures also participate in vertical gaze holding, with contributions from more rostral structures, especially the interstitial nucleus of Cajal (see Display 6-6). With lesions in the paramedian structures of the medulla, nystagmus (commonly upbeat but sometimes horizontal with a gazeevoked component) is the most com-

mon finding (see VIDEO: "Upbeat nystag- mus»).630,7ooa,98U388 Tumor or infarction

involving the paramedian medulla, including the perihypoglossal nuclei, has been described in patients with upbeat nystagmus.514'754 Upbeat nystagmus has also been described with a lesion involving the nucleus intercalates.630 One medullary component of the PMT cell groups (see Display 6-4) 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 cause upbeat nystagmus.221 Involvement of a ventral tegmental pathway for the upward VOR may lead to a downward vestibular bias and a consequent upbeat nystagmus.1121

A patient who died of lithium intoxica-

tion showed selective loss of neurons and gliosis in the NPH-MVN region.295

Wernicke's encephalopathy commonly in-

Effects of Disease Involving the

Inferior Olivary Nucleus

Lesions of the inferior olivary nucleus or its connections may produce the oculopalatal tremor (or myoclonus} syndrome (see VIDEO: "Oculopalatal tremor"). This condition, which usually develops weeks to months after a brain stem or cerebellar infarction, is discussed in the section on Oculopalatal Tremor (Myoclonus). Oculopalatal tremor may also occur with degenerative conditions;381'1311 a patient with cyclovergent pendular eye oscillations and synchronous palatal movements in association with progressive ataxia has been described.64

The main pathologic finding with palatal tremor is hypertrophy of the inferior olivary nucleus, which may be seen during life using MRI.381>1311 Histologically, the olivary nucleus is enlarged, with hypertrophic neurons that contain increased acetylcholinesterase reaction product.777 Guillain and Mollaret postulated that disruption of connections between the dentate and the contralateral olivary nucleus (which run via the red nucleus and central

tegmental tract) is responsible for the syndrome;561 however, the red nucleus has no

known role in eye movements. It has also been proposed that the ocular oscillations are due to an instability arising from the projection from the inferior olive to the

flocculus, which is thought to be important in the adaptive control of the VOR.993 Only rarely does Oculopalatal tremor resolve spontaneously. Gabapentin, ceruletide, and anticholinergic agents may help some patients (see Table 10-8).62>685

Effects of Disease Restricted to the Vestibular Nuclei

Occasionally, the acute manifestation of a generalized disease process may be restricted to the vestibular nuclei. For example, vertigo may be the sole symptom of an exacerbation of multiple sclerosis729 or of brain stem ischemia.451'526'541 Nystagmus caused by disease of the vestibular nuclei may be purely horizontal, vertical, or torsional, or mixed patterns may occur. Moreover, nystagmus from a central vestibular lesion can mimic that caused by peripheral vestibular disease.937 Paroxysmal vertigo with nystagmus has been reported with an arteriovenous malformation near the vestibular nucleus, and close to the middle cerebellar peduncle.821 The attacks were successfully treated with carbamazepine. Dolichoectasia of the basilar artery may produce a variety of combinations of central and peripheral vestibular syn- dromes.221-1070 Microvascular compression of the eighth nerve is reported to cause paroxysmal vertigo.171

Wallenberg's Syndrome (Lateral

Medullary Infarction)

Most commonly, lesions of the vestibular nuclei also affect neighboring structures, in particular the cerebellar peduncles and the perihypoglossal nuclei. The best-rec- ognized syndrome involving the vestibular nuclei is that due to lateral medullary in- farction—Wallenberg's syndrome (Fig. 10-20) (Display 10-16). The typical findings of Wallenberg's syndrome are ipsilateral impairment of pain and temperature sensation over the face, Horner's syndrome,

limb ataxia, and bulbar disturbance causing dysarthria and dysphagia.1199 Con-

tralaterally, pain and temperature sensa-

tion is impaired over the trunk and limbs. The seventh cranial nerve may also be affected if the infarct extends more rostrally. The disorder is most commonly due to occlusion of the ipsilateral vertebral artery; occasionally the posterior inferior cerebellar artery is selectively involved.454 Dissection of the vertebral artery (either spontaneous or traumatic, sometimes following chiropractic manipulation) is occasionally

the cause.624 Rarely, demyelinating disease may produce this syndrome.1297

The symptoms of Wallenberg's syndrome include vertigo and a variety of unusual sensations of body and environmen-

tal tilt, often so bizarre as to be thought to be psychiatric in origin.1383 Patients may report the whole room tilted on its side or even upside down; such misperceptions tend to be transient, whereas smaller tilts of the subjective visual vertical tend to be more persistent.166'1383 Similar symptoms are occasionally reported in patients without signs of lateral medullary infarction and may be due to transient brain stem or cerebellar ischemia.245'878 Such symptoms may also occur with lesions in the cerebral hemispheres.1305

Lateropulsion, a compelling sensation of being pulled toward the side of the lesion,

is often a prominent complaint and is

also evident in the ocular motor findings.88'651'786 If the patient is asked to fixate

straight ahead and then gently close the lids, the eyes deviate conjugately toward the side of the lesion (see VIDEO: "Wallenberg's syndrome"). This is reflected by the corrective saccades that the patient must make on eye opening to reacquire the target. Lateropulsion may appear with a blink.

Saccadic eye movements are also affected by the lateropulsion.88'178'223'1306'1445'1446'1449

Horizontally, saccades directed toward the side of the lesion usually overshoot the target, and saccades directed away from the side of the lesion undershoot the target (see VIDEO: "Wallenberg's syndrome"); this is referred to as ipsipulsion of saccades and should be differentiated from contrapukion

of saccades that occurs with infarcts due to occlusion of the superior cerebellar artery. Quick phases of nystagmus are similarlyaffected, so that in Wallenberg's syndrome those directed away from the side of the lesion are smaller than those toward the lesion. On attempting a purely vertical refixation, an oblique saccade directed toward the side of the lesion is produced (see VIDEO: "Wallenberg's syndrome"). Corrective saccades then bring the eyes back to the target.769 Saccades made in total darkness also show lateropulsion, although in one report the patient was still able to make corrective saccades to the remembered location of a previously seen target, implying that the central nervous system had a knowledge of actual eye position.1037 With time, vertical saccades may become more perverse; S-shaped saccadic trajectories

can appear a week or more after the onset of the illness and may reflect an adaptive strategy to correct the saccadic abnormality. Torsipulsion (inappropriate torsional saccades during attempted horizontal or vertical saccades) may also occur in association with torsional nystagmus,which may be re-

garded as a violation of Listing's law (discussed in Chap. 9).607>960

When present, spontaneous nystagmus in Wallenberg's syndrome is usually horizontal or mixed horizontal-torsional with a small vertical component.960 In central position, the slow phase is usually directed toward the side of the lesion, although it may reverse direction in eccentric posi-

tions, suggesting coexistent involvement of the gaze-holding mechanism. Lid nystagmus (synkineticlid twitcheswith horizontal quick phases) can also occur.321 The ocular tilt reaction commonly occurs in Wallenberg's syndrome.389 The skew deviation manifests as an ipsilateral hypotropia (see VIDEO: "Wallenberg's syndrome").169 The eyes are cyclodeviated toward the side of the lesion, but unequally so that the lower eye is more extorted. The head tilt is ipsilateral.168 The skew deviation and head tilt arise from imbalance in pathways mediating otolith responses. The subjective sensations of tilt or inversion of the world probably also reflect involvement of cen-

tral projections from the gravireceptors, the utricle and the saccule.

Smooth pursuit is usually impaired, par-

ticularly for tracking targets moving away from the side of the lesion.88'1449 Caloric

testing usually shows intact horizontal canal function. During both rotational and caloric testing, there is a directional pre-

ponderance of slow phases, usually toward the side of the lesion.88'423 Head nystag-

mus also occurs in some patients with Wallenberg's syndrome.786

Many of the findings in Wallenberg's syndrome, including the bizarre visual disturbances and the skew deviation, may reflect imbalance of otolith influences due to direct involvement of the caudal aspects of the vestibular nuclei. Involvement of the restiform body, which carries olivocerebellar projections, may also account for some of the ocular motor findings, especially the steady-state deviation of the

eyes toward the side of the lesion and the ipsipulsion of saccades.223'1306'1445'1446-1449

Ipsipulsion of saccades, with deviation of the eyes to the side of the lesion, can be produced experimentally by fastigial nucleus lesions.1160 This finding supports the hypothesis that in Wallenberg's syndrome the interruption of climbing fiber input to the dorsal cerebellar vermis releases Purkinje cell inhibition upon the underlying fastigial nucleus, leading to the equivalent of a lesion in the fastigial nucleus.1449 An analogous increase in Purkinje cell inhibition from the flocculus to the vestibular nucleus may also play a role in the nystagmus that these patients may develop (with the slow phase toward the side of the lesion).

The vestibular nuclei and adjacent dorsolateral brain stem are also supplied by the anterior inferior cerebellar artery (AICA). In addition, the AICA supplies the inferior lateral cerebellum and is the origin of the labyrinthine artery in most individuals. Consequently, ischemia in the distribution of the AICA (Fig. 10-21) may cause vertigo, vomiting, hearing loss, facial palsy, and ipsilateral limb ataxia, along with gaze holding and pursuit deficits, and vestibular imbalance (see VIDEO: "An-

terior inferior cerebellar artery (AICA) distribution infarction").541'1028 The AICA

syndrome is discussed further under Cerebellar Infarction.

OCULAR MOTOR SYNDROMES CAUSED BY DISEASE OF THE CEREBELLUM

Clinicians have been cautious in attributing eye movement abnormalities specifically to cerebellar dysfunction because the brain stem is so frequently involved in patients with lesions of the cerebellum. Holmes638 and Cogan,263 however, recognized specific cerebellar eye signs, and modern clinical and experimental studies have clarified the functional deficits that are caused by specific cerebellar le-

sions<867,1046,1131,1160,1161,1427,1447,1538

Three Principal

Cerebellar Syndromes

Based on discrete lesions and pharmacological inactivation in monkeys, it is possible to define three principal cerebellar syndromes: the syndrome of the flocculus and paraflocculus (see Display 6-10 and Display 10-17), the syndrome of the nodulus and ventral uvula (see Display 6-11 and Display 10-18), and the syndrome of the dorsal vermis (lobules VI and VII) and underlying

caudal fastigial nuclei (see Display 6-12, Display 6-13, Display 10-19). In addition, there is some evidence that the cerebellar hemispheres contribute to the control ofeye movements. Thus, during voluntary saccades made between two visual targets, or remembered target locations in darkness, fMRI demonstrates increased activation in the hemispheres as well as in the midline (vermis and fastigial nuclei), as is shown in Figure 3-10 of Chap. 3. Furthermore, lesions restricted to one cerebellar hemisphere impair ipsilateral smooth pursuit.1336

LESIONS OF THE FLOCCULUS AND PARAFLOCCULUS

Lesions of the flocculus and paraflocculus cause gaze-evoked nystagmus, rebound nystagmus, and downbeat nystag-

mus (see VIDEOS: "Gaze-evoked, rebound, and downbeat nystagmus"); impaired smooth tracking either with eyes alone (smooth pursuit) or with eyes and head; postsaccadic drift; and loss of some adaptive capabilities, such as the ability to adjust the gain and direction of the VOR or the pulse-step match for saccades. Unilat-

eral lesions produce ipsilateral deficits in pursuit and gaze holding.1336'1444'1476 In

patients with cerebellar disease, pursuit defects with the head still, defects in combined eye-head tracking, and gaze-hold- ing deficits frequently occur together, reflecting their common substrate in the flocculus and vestibular nuclei.220 Quantitatively, though, pursuit with the head still is sometimes relatively more impaired.545'1458 Patients with cerebellar disease may show timing errors during track-

ing of a target moving in a periodic fashion,1458 but there is some preservation of a

predictive capability.845 The ability to generate anticipatory smooth eye movements of high speed at the onset of tracking is also impaired in some cerebellar patients.964

LESIONS OF THE NODULUS AND VENTRAL UVULA

Lesions of the nodulus and ventral uvula lead to an increase in the duration of vestibular responses that predisposes the individual to the development of periodic

alternating nystagmus (see VIDEO: "Periodic alternating nystagmus"). Other abnormalities of the velocity-storage mechanism are present, including a failure of tilt-suppression of postrotatory nystagmus,569 and loss of habituation. Positional nystagmus and downbeat nystagmus also occur in patients with nodular lesions.

LESIONS OF THE DORSAL VERMIS AND FASTIGIAL NUCLEI

Lesions of the dorsal vermis and fastigial nuclei (fastigial oculomotor region—FOR) cause saccadic dysmetria, typically hy-