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

lobe involvement, including increased errors on the antisaccade task (Fig. 10-31), increased fixation instability, and increased latencies of saccades, especially vertically.706'942 Some patients may develop acquired ocular motor apraxia.179 Others show signs suggesting cerebellar and brain

stem involvement, including gaze-evoked and dissociated nystagmus,1076 slow sac-

cades,1009 and ocular flutter.715 Decreased

or asymmetric pursuit gain is a common finding.706'1349 In addition, patients with

AIDS may show a number of ocular motor abnormalities, reflecting the effects of op-

portunistic infection or coexistent neopla-

sia.309'582'601'752

EYE MOVEMENT DISORDERS IN PSYCHIATRIC ILLNESSES

Although abnormalities of voluntary gaze have long been associated with insanity, it was Diefendorf and Dodge who, in 1908, first suggested that eye tracking is abnormal in dementia praecox (schizophrenia).387 A substantial research effort has gone into trying to delineate the eye movement abnormalities encountered in psychosis.861 Initial studies were thwarted by poor recording techniques and methods of analysis that bear no relevance to the physiologic properties of eye movements.669 More recent reports agree that smooth pursuit is abnormal in most schizophrenics: Eye acceleration at onset of pursuit is decreased, the gain of sustained pursuit is reduced, and the

number of catch-up saccades is increased.428'478'858'968'1350'1366 Another ab-

normality that interferes with smooth

pursuit in schizophrenics is saccadic intrusions.857'869 These consist of small to-and-

fro square-wave jerks (Fig 10-16A) and larger anticipatory saccades that are also followed, after about 0.5 to 1.5 seconds, by a corrective saccade that brings the eyes back to the target.

How specific for schizophrenia are the abnormalities of eye movements that occur during tests of smooth pursuit? Lowgain pursuit eye movements may occur in some patients with affective disorders, but

it is suggested that the disruption of pursuit by saccades is more specific.428'478 However, square-wave jerks occur in a variety of conditions, and anticipatory saccades are not peculiar to schizophrenics; they also occur in Alzheimer's disease,466 and in normal subjects as they track a target moving across a textured background.733 Furthermore, cigarette smoking—a habit common among schizo- phrenics—is known to induce squarewave jerks1287 and may influence smoothpursuit gain (see Effects of Drugs on Eye Movements).1040 Finally, the possible contribution of neuroleptic medications to the saccadic intrusions is not completely settled, although unmedicated schizophren-

ics do show lower smooth-pursuit gain than controls.478'669'6693'1351 Whether psy-

chiatrically well relatives of schizophrenics show a similar tracking disorder is in dis- pute.641-870 There is some evidence that impaired smooth pursuit may be due to a deficit in motion perception.1342 However, the disorder of smooth pursuit in schizophrenia resembles the disturbance occurring in monkeys after frontal lobe lesions.892 Functional imaging has supported this hypothesis, linking impaired smooth

tracking with hypometabolism in the frontal eye fields.1179

Consonant with this line of reasoning, the most consistent abnormalities in schizophrenia have concerned the voluntary control of saccades, and especially those functions that depend on the frontal lobes. Although simple tests of saccades demonstrate increased saccadic latencies and hy-

pometria compared with control subjects or patients with affective disorders,895-968'1227

the most impressive findings are with tests requiring imagination, memory, or prediction. Thus, schizophrenics show saccade abnormalities similar to those in patients with frontal lobe or basal ganglia disease, including excessive dis-

tractibility in the antisaccade task (Fig. 10-31).300'669a'1365 Such distractibility is

present in schizophrenics who have received no neuroleptic drugs for 6 months and is not a feature of bipolar affective disorder or obsessive-compulsive states.924 Schizophrenics also show defects in mem- ory-guided saccades, suggesting dysfunc-

tion of dorsolateral prefrontal cortex.1061 However, schizophrenics are able to generate express saccades, depending on the length of the gap between the disappearance of the fixation light and the appearance of the target.258 Taken together with results from patients with cortical lesions, these findings suggest that in schizophrenia there is impaired frontal lobe influence on the programming of saccades.484 Evidence has also been presented from tests of saccadic eye movements that suggests disturbed frontal lobe function in pa-

tients with obsessive-compulsive disorde^ 1170,1376

EYE MOVEMENTSIN STUPOR AND COMA

The ocular motor examination is especially useful for evaluating the unconscious patient because both arousal and eye movement are controlled by neurons in the brain stem reticular formation. Comatose patients do not make eye movements that depend upon cortical visual processing; voluntary saccades and smooth pursuit are in abeyance. Quick phases of nystagmus, too, may be absent. The ocular motor examination of the unconscious patient, therefore, consists of observing the resting position of the eyes, looking for

any spontaneous movements, and reflexively inducing eye movements.206'452'831'1098

Resting Position of the Eyes in

Unconscious Patients

Conjugate, horizontal deviation of the eyes is common in coma (Display 10-33). If this is due to lesions above the brain stem ocular motor decussation (between the midbrain and pons), then the eyes are usually directed toward the side of the lesion and away from the hemiparesis. A vestibular stimulus, though, can usually drive the eyes across the midline. If the conjugate deviation is due to a lesion below the ocular motor decussation, then the eyes will be directed away from the side of the lesion and toward the hemiparesis.

This situation is typically seen with pontine lesions but also in some patients with thalamic lesions,450 and rarely with hemispheric disease above the thalamus (socalled wrong-waydeviation).1075'1264

Intermittent deviation of the eyes and head turning are usually due to seizure activity. At the onset of each attack, gaze is usually deviated contralateral to the side of the seizure focus; it may be followed by nystagmus with contralaterally directed quick phases. Toward the end of the seizure, gaze drifts to an ipsilateral (paretic) position (see Eye Movements During EpilepticSeizures).

Tonic downward gaze deviation of the eyes, often accompanied by convergence, occurs in thalamic hemorrhage447'448 and with lesions affecting the dorsal midbrain. It may be induced by unilateral caloric stimulation, after the initial horizontal deviation subsides, in patients with coma due to sedative drugs.1288 Forced downward deviation of the eyes has also been reported in patients feigning coma or seizures.1172

Tonic upward gaze deviation of the eyes occurs following a hypoxic-ischemic insult, even when no pathologic lesions are found in the midbrain.743 In those patients that survive, downbeating nystagmus develops. It has been suggested that upward drift is due to loss of inhibition on the upward vertical VOR.995 Upward deviation also occurs as a component of oculogyric crises, which usually occur as a side effect of certain drugs, especially neuroleptic agents.830 Tonic uninhibited elevation of the lids (eyes-open coma) may also occur in unconscious patients and may be related to pontomesencephalic dysfunction.739

Deviations of the visual axes in coma may be due to palsied oculomotor, trochlear, or abducens nerve (see Clinical Features of Ocular Nerve Palsies, in Chap. 9), skew deviation, or a phoria that is normally compensated for by fusional mechanisms.

Restrictive ophthalmopathy, particularly blow-out fracture of the orbit, may be a mechanism in patients who have suffered head trauma. Diagnosis of the cause of the deviation depends upon determining whether the range of movement of the eyes, induced by head rotation or caloric

stimulation (seeReflex Eye Movements in

Unconscious Patients, below), is reduced in a pattern corresponding to specific muscle weakness. In addition, involvement of the pupils and other brain stem reflexes may help with the diagnosis.

Complete oculomotor nerve palsy causes pupillary dilatation, ptosis, and deviation of the eye "down and out." Pupillary in-

volvement is an early sign of uncal herniation,1098 and disturbance of eye move-

ments usually follows.748 Vertical tropias are usually due to skew deviation or to trochlear nerve palsy, which is common following head trauma. Bilateral abducens palsy occurs when increased intracranial pressure compromises the nerves as they bend over the petroclinoid ligament. Occasionally, skew deviation and internuclear ophthalmoplegia are encountered in

metabolic encephalopathy,232'455 or with drug intoxication.29U98,4i6,655,i 155

Spontaneous Eye Movements in

Unconscious Patients

Always consider epileptic seizures in the unconscious patient who shows spontaneous eye movements (see discussion in preceding section). Slow conjugate or disconjugate roving eye movements are similar to the eye movements of light sleep (but slower than the rapid movements of paradoxical or REM sleep). They imply that brain stem gaze mechanisms are intact.452 A spectrum of abnormal eye movements is encountered almost exclusivelyin unconscious patients and is summarized in Table 10-19.

Unreliable for localization;

may occur with metabolic disorders323'1384

Unreliable for localization;

pontine infarction and with

AIDS522-929

Bilateral cerebral hemispheric dysfunction676

Hepatic encephalopathy;58 disorders causing periodic alternating nystagmus and unconsciousness or vegetative state544

Pontine strokes747

Pontine or midbrain destructive lesions, perhaps with coexistent seizures1289

Ocular bobbing consists of intermittent, usually conjugate, rapid downward movement of the eyes followed by a slower return to the central position (see VIDEO: "Ocular bobbing").114-449'929 Reflex horizontal eye movements are usually absent. Ocular bobbing is a classic sign of intrinsic pontine lesions, usually hemorrhage, but it has also been reported with cerebellar lesions that secondarily compress the pons (Fig. 10-34), as well as in metabolic or toxic encephalopathy. A variant, inverse bobbing, has an initial downward movement that is slow and the return to midposition is rapid; this has also been called ocular dipping. Reverse ocular bobbing consists of rapid deviation of the eyes upward and a slow re-

turn to the horizontal. Finally, the termreverse ocular dipping or converse bobbing has been used to describe a slow upward drift of the eyes followed by a rapid return to central position. Rarely, the bobbing is variably disconjugate.503a These variants of ocular bobbing are less reliable for localization. Nevertheless, the report that some patients have shown several types of bobbing suggests a common underlying pathophysiology.201'522'1173'1384 Since the pathways that mediate upward and downward eye movements differ anatomically, and probably pharmacologically, it seems likely that these movements represent a varying imbalance of mechanisms for vertical gaze. Rarely, large-amplitude vertical

554 The Diagnosis of Disorders of Eye Movements

pendular oscillations (myoclonus), in association with horizontal gaze palsy, occur in the acute phase of a brain stem stroke;747 some patients survive to develop oculopalatal tremor. Repetitive vertical eye movements, including variants of ocular bobbing, that contain convergent-diver- gent components usually indicate disease affecting the dorsal midbrain.745'1015'1175 Monocular bobbing movements may occur as a synkinesis withjaw movement and are a variant of the Marcus Gunn jaw winking phenomenon, involving the inferior rectus in otherwise normal individuals.1031 Pingpong gaze consists of slow, horizontal, conjugate deviations of the eyes alternating every few seconds.676 Ping-pong gaze usually occurs with bilateral infarction of the cerebral hemispheres or of the cerebral peduncles.812 Sometimes a rapid horizontal head rotation will induce transient oscillations with a similar periodicity to pingpong gaze in patients with bilateral hemispheric disease.831 A saccadic form of ping-pong gaze has been reported as a transient finding in patients who survive in a persistent vegetative state.704 Periodic alternating gaze deviation, in which conjugate gaze deviations change direction every 2 minutes, has been reported in hepatic encephalopathy.58 This phenomenon is related to periodic alternating nystagmus (see Display 10-5).

Rapid, small-amplitude, vertical eye movements may be the only manifestation of epileptic seizures in patients with coexistent brain stem injury.1289 Rapid, monocular eye movements with horizontal, vertical, or torsional components, which occur in coma, may also indicate brain stem dysfunction.

Identification of patients who are conscious but quadriplegic, the locked-in or de-efferented state, depends upon identi-

fying preserved voluntary vertical eye movements.813'1098 The syndrome is typi-

cally caused by pontine infarction with a variable loss of voluntary and reflex horizontal movements, so that eyelid or vertical eye movements may be the only means of communication in the acute illness. The locked-in syndrome also occurs with midbrain lesions, in which case ptosis and ophthalmoplegia may be associated.935

Reflex Eye Movements in Unconscious Patients

The examination of the unconscious patient is incomplete without attempting to elicit reflex eye movements, either by head rotation (the doll's-head or oculo-

cephalic maneuver) or by caloric stimulation.206'1001'1098 Always check that there has

been no neck injury or abnormality before rotating the head, and inspect the tympanic membranes before carrying out caloric testing.

What do these time-honored clinical methods test? Head rotation, with the patient supine, potentially stimulates the labyrinthine semicircular canals, the otoliths, and neck muscle proprioceptors. Unless there has been prior loss of vestibular function (e.g., from aminoglycoside antibiotic toxicity), the contribution made by neck muscle proprioceptors in generating reflex eye movements (the COR) is insignificant.831 Furthermore, the otolithic contribution is probably small compared with that of the labyrinthine semicircular canals. Finally, although visually mediated eye movements, such as fixation and smooth pursuit, can influence the eye movements produced by head rotation in normal, awake subjects, this is unlikely to be the case in unconscious patients. Therefore, eye rotations induced by head rotation in unconscious individuals are principally due to the effects of the semicircular canals and their central connec- tions—the VOR. Conventionally, highfrequency (1 to 2 Hz) quasi-sinusoidal rotations are applied, or position-step stimuli, which consist of a sudden head turn to a new steady position. Both horizontal and vertical rotations should be performed. If small-amplitude head rota- tions—are performed, the adequacy of the VOR can be estimated by observing the

optic disc of one eye with an ophthalmoscope.1526 If reflex eye movements are in-

tact in an unconscious patient, then when the head is rapidly rotated horizontally to a new position (position-step stimulus), the eyes are carried into a corner of the orbit (Fig. 10-35). If the head is held stationary in its new position, the eyes may drift back to the midline. This implies that

the gaze-holding mechanism (neural integrator) is not functioning normally. Patients with more rapid centripetal drift may have more severe brain injury.831

Caloric irrigation of the external auditory meatus causes convection currents of the vestibular endolymph that displace the cupula of a semicircular canal; thus, this procedure also tests the VOR. The canal

stimulated depends upon the orientation of the head; with the head elevated 30° from supine position, the horizontal canals are principally stimulated. Large quantities (100 ml or more) of ice water may be necessary.Caloric stimulation with ice water may be a more effective stimulus than head rotation, perhaps owing to the sustained nature of the stimulusas well as

556 The Diagnosis of Disorders of Eye Movements

the arousing effect of the cold water. Combined cold caloric stimulation and head rotation may be the most effective stimulus in the unconscious patient,452 producing tonic deviation of the eyes toward the irrigated ear.

In testing reflex eye movements in unresponsive patients, it is important to note the magnitude of the response and whether or not the ocular deviation is conjugate; the dynamic response to positionstep head rotations; and the occurrence of any quick phases of nystagmus, particularly during caloric stimulation. When reflex eye movements are present in an unresponsive patient, the brain stem is likely to be structurally intact. When reflex eye movements are abnormal or absent, the cause may be structural disease (especially brain stem strokes), metabolic and deficiency states (including Wernicke's encephalopathy), or drug intoxication (see Table 10-21).583'1171 Complete ophthalmoplegia in an unresponsive patient should also prompt consideration of acute neuropathy (such as Guillain-Barre syndrome) and neuromuscular block due to drugs or botulism.746 Vertical reflex eye movements may be impaired with disease of the midbrain1406 or bilateral lesions of the MLR Pontine lesions may abolish the reflex eye movements in the horizontal plane but spare the vertical responses. Impaired abduction suggests sixth nerve palsy; impaired adduction implies either internuclear ophthalmoplegia or third nerve palsy. Occasionally, impaired adduction to vestibular stimulation may be ob-

served in patients with metabolic coma232 or drug intoxication.291'398'416'655'1155 Pa-

tients in barbiturate coma may show downward deviation of their eyes with caloric stimuli,1288 or no response. When used in combination with other clinical signs, reflex eye movements have been

useful in predicting the outcome of coma.859'976

Quick phases of nystagmus are usually absent in acutely unconscious patients, so their presence, without a tonic deviation of the eyes, should raise the possibility of feigned coma. In patients who are stuporous but uncooperative, caloric nystagmus may be a useful way of inducing eye

movements that cannot be initiated voluntarily. For example, in a patient with a pineal tumor, retraction nystagmus was induced with caloric stimulation.1291 Patients who survive coma but who are left in a persistent vegetative state, with severe damage of the cerebral hemispheres but preservation of the brain stem,1098 regain

nystagmus with caloric or rotational stimulation.831 Recovery of eye tracking of the

examiner or family members is an indication of those patients who may show some recovery from this state.39 Caloric nystagmus has been reported in patients with neocortical death and an isoelectric electroencephalogram.1003

OCULAR MOTOR DYSFUNCTION AND MULTIPLE SCLEROSIS

Multiple sclerosis causes a variety of ocular motor deficits (Display 10-37), of which bilateral internuclear ophthalmoplegia (INO) (see VIDEO: "Bilateral internuclear ophthalmoplegia"), cerebellar eye signs (including gaze-evoked nystagmus), and

acquired pendular nystagmus (Fig. 10-11) are most commonly recognized.480-1324

The pendular nystagmus is frequently visually disabling (see VIDEOS: "Acquired nystagmus impairing vision").48'879 Acute vertigo may occur during an exacerbation, and sometimes is recurrent and troublesome.

Measurement of eye movements may help make the diagnosis during early stages of the disease by demonstrating saccadic abnormalities, especially INO (Fig. 10-27). Detection of a saccadic abnormality may be better when targets are presented randomly, so that neither their time of onset nor their location can be predicted. Large saccades (20° or greater) are more likely to show changes in velocity than are small saccades.936 Comparison of the peak velocity of abducting and adducting saccades to identify subtle degrees of INO requires caution because normal subjects show greater peak velocities in the abducting eye. A solution to this problem is to compare the ratio of movements of the two eyes (i.e., measures of conjugacy

during saccades). Normal subjects show

little variation in the ratio of either peak eye velocity1419 or peak acceleration467-468

of the adducting saccades to abducting saccades. Patients with INO have greater disconjugacy of saccades, manifested as adduction/abduction ratios of peak velocity or peak acceleration that fall outside corresponding ranges for normal subjects. Other saccadic abnormalities in multiple sclerosis include prolonged latency, inaccuracy, and decreased velocity.181'936'1138 Some patients with multiple sclerosis show

saccadic oscillations and intrusions (see Display 10-14).49'618

Smooth-pursuit gain may be de-

creased.1138'1266 Impaired cancellation of the horizontal VOR has been reported.1266

Abnormalities of vertical gaze holding,

smooth pursuit, and eyehead tracking occur in patients with bilateral INO,1122 be-

cause the medial longitudinal fasciculus (MLF) (Display 6-2) carries signals important for nonsaccadic vertical move-

ments. Other abnormalities include horizontal and vertical gaze palsies,907-1455

gaze-evoked blepharoclonus,740 upbeat and downbeat nystagmus,86'446'912 various vestibular and optokinetic abnormalities,670'729 superior oblique myokymia (Chap. 9), and convergence spasm (Chap. 8). Patients may also develop oculomotor, trochlear or abducens palsies (see Chap. 9). An MRI is often successful in identifying brain stem or cerebellar lesions responsible for such abnormalities.145

Diagnosis of early multiple sclerosis depends on demonstration of lesions disseminated throughout the nervous system. Early diagnosis has become more important because beta-interferon may reduce the rate of relapses. Sometimes, subtle deficits of ocular motility provide a sensitive method for identifying subclinical lesions, but there is need for caution: These tests are not specific for multiple sclerosis. The clinician must weigh the results of ocular motor studies with other clinical or

laboratory findings before making a diag-

nosis. Recent studies have demonstrated that gabapentin62 and memantine1316 may

ameliorate the visually disabling acquired pendular nystagmus that often occurs in multiple sclerosis (see Treatment of Acquired Pendular Nystagmus).

OCULAR MOTOR MANIFESTATIONS OF METABOLIC AND DEFICIENCY DISORDERS

The current genetic revolution has illuminated the biochemical basis for many disorders, and so the spectrum of diseases considered "metabolic" now incorporates some disorders previously described as "degenerative." With this caveat in mind,

we review selected metabolic and deficiency disorders. Some of the main ocular motor findings of selected hereditary disorders are listed in Table 10-20.

It is important to note that some normal infants who ultimately develop normally may show transient ocular motor "abnormalities." These include upward or downward deviation of the eyes (butwith a full range of reflex vertical movement), inter-

mittent opsoclonus, and skew deviation.18,598,659,663,1053 However, skew devia-

tion and transient tonic up gaze may be associated with later appearance of horizontal strabismus and intellectual or language disability.598 Premature babies may show reduced excursion of the adducting eye with caloric stimulation, suggesting internuclear ophthalmoparesis, but a full deviation of both eyes usually occurs with rotational stimuli, although quick phases

Vitamin E deficiency: hereditary (e.g., abetalipoproteinemia) or acquired

Progressive restriction of horizontal and vertical gaze;

dissociated nystagmus, in which adduction is faster than abduction301'1510

of nystagmus may be absent.1469 The time constant (as a reflection of duration) of the VOR in newborns is low (typically 6 sec-

onds) and does not reach adult values until the infant is about 2 months old.1469

The lipid storage diseases are often characterized by gaze palsies. Tay-Sachs disease impairs vertical and, subsequently, horizontal eye movements. Adult-onset hexosaminidase A deficiency also preferentially affects vertical gaze.587 Variants of Niemann-Pick disease that begin after the first year of life (previously called the seablue histiocyte syndrome or juvenile dystonic lipidosis) are characterized by deficits of voluntary vertical eye movements.270 Early in the course of NiemannPick type C (2S) disease, which presents during adolescence with intellectual impairment, ataxia, and dysarthria, there may be selective slowing of vertical

ease").270-1187 Diagonal saccades may show a curved trajectory (Fig.3-3B), evident during the clinical examination. Gaucher's disease is associated with a more prominent deficit of horizontal gaze; in adult pa-

tients, slow saccades may be a prominent finding.1071'1435

Wernicke's encephalopathy is characterized by the triad of ophthalmoplegia, mental confusion, and gait ataxia.225 It is caused by thiamine deficiency and is most commonly encountered in alcoholics. The ocular motor findings include weakness of abduction, gaze-evoked nystagmus, internuclear ophthalmoplegia, central positional vertical nystagmus (usually upbeat), impaired vestibular responses to caloric and rotational stimulation, and horizontal and vertical gaze palsies that may progress to total ophthalmoplegia (see VIDEO: "Wernicke's encephalopathy'').273'297'337.495.945* The ophthalmoplegia is bilateral but may be asymmetric. Experimental thiamine deficiency in monkeys causes an orderly progression of ophthalmoplegia associated with well-circumscribed histopathologic changes.274 These changes consist of neuronal loss and gliosis in the oculomotor, trochlear, abducens, and vestibular nuclei. In humans, demyelination, vascu-

lar changes, and hemorrhage may occur; in addition to the sites listed above, the lesions are found in the periventricular regions of the thalamus, the hypothalamus, the periaqueductal gray matter, the superior vermis of the cerebellum, and the

dorsal motor nucleus of the vagus (Fig. 10-36).945a Thus, gaze-evoked nystagmus

and the impaired caloric responses can be attributed to vestibular nucleus involvement (NPH-MVN region). The abduction weakness may reflect involvement of the abducens nerve, and the internuclear ophthalmoplegia (INO) may reflect involvement of the medial longitudinal fasciculus. Paralysis of horizontal gaze may be due to involvement of the abducens nucleus, and total ophthalmoplegia may indicate involvement of all the ocular motor nerve nuclei. Affected areas of the brain most likely contain neurons that use high amounts of glucose and are therefore particularly dependent upon thiamine, an important coenzyme in glucose metabolism.1492 Administration of thiamine usually causes rapid improvement of the ocular motor signs, although complete recovery may take several weeks. Coexistent magnesium deficiency should also be treated. In those patients with Wernicke's disease who go on to develop Korsakoff's syndrome, which is primarily characterized by a severe and enduring memory loss, ocular motor abnormalities may persist.759'760 The ocular motor abnormalities include slow and inaccurate saccades, impaired smooth pursuit, and gaze-evoked nystagmus.

Leigh's syndrome is a subacute necrotizing encephalopathy of infancy or childhood characterized by psychomotor retardation, seizures, and brain stem abnormalities that involve eye movements.1542 It may either be caused by abnormalities of mitochondrial DNA or be an autosomal recessive disorder. Deficiency of respiratory chain complexes I and IV has been identified.956 Early onset cases show disturbances of ocular motility similar to that caused by experimental thiamine deficiency or Wernicke's encephalopathy. In addition, seesaw nystagmus (Display 10-6) and the ocular tilt reaction (OTR) are reported in Leigh's syndrome.578 Later-onset cases share clini-