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

soidal pattern, pursuit gain (eye velocity/

target velocity) is decreased, leading to catchup saccades.1125'1480 It appears that at

least part of the defect during tracking of a smoothly moving target is that the catchup saccades are hypometric; thus,

the cumulative tracking eye movement is less than that of the target.1459 Despite the

impairment of smooth-pursuit gain, the phase relationship between eye and target movement during tracking of a periodic target is normal;192 this implies a normal predictive smooth tracking strategy.

Visuovestibular interactions in PD

Both caloric and low-frequency rotational

vestibular responses, in darkness, may be hypoactive in patients with PD.1132'1479 How-

ever, at higher frequencies of head rotation, and particularly during visual fixation, the gain of the VOR is close to 1.0, which accounts for the lack of complaint of oscillopsia in patients with PD.1479 Combined eye-head tracking (VOR cancellation or suppression) is abnormal to a similar degree as smooth pursuit with the head stationary in most patients with PD

(see Disorders of Smooth Eye-Head Tracking in Chap. 7).545'1459'1479 PD patients

show a variety of disorders of eyelid movements, including lid retraction on looking straight ahead and lid lag on down gaze.52

Effects of Treatment on Eye Movements in PD

In general, levodopa treatment of PD does not seem to improve the ocular motor deficits except for improvement of saccadic accuracy (i.e., saccades become larger).513'1125 Some newly diagnosed patients with idiopathic PD may show improved smooth pursuit after the institution of dopaminergic therapy.513 In one patient with advanced PD, electrical stimulation of the pallidum was reported to improve performance on memory-guided and antisaccade tasks.1333 Conversely, pallidotomy is reported to induce squarewave jerks in parkinsonian patients.603

In patients with parkinsonism due to methyl-4-phenyl-1,2,3,6-tetrahydropy- ridine (MPTP) toxicity, saccadic latency was shortened and saccadic accuracy was

improved by dopaminergic agents; in addition, reflex blepharospasm in these patients was improved.653 In monkeys who received MPTP, saccadic abnormalities— including increased latency, increased duration, decreased rate of spontaneous saccades, and inappropriate saccades—were

all reversed by dopaminergic therapy.197'1245 In those patients with idio-

pathic PD who show pronounced drugrelated fluctuations, there is disagreement as to whether smooth pursuit shows an

increase in gain during "on" periods.512'1125'1265 The dopaminergic pars

compacta of the substantia nigra does not appear to contain neurons related to eye movement, whereas the pars reticulata does.627 (The influence of the substantia nigra pars reticulata [SNpr] and the nigrocollicular pathway in the control of saccades is discussed in Chaps. 3 and 6.) In monkeys with MPTP-induced parkinsonism, cerebral metabolic rate was reduced in the frontal eye fields and paralamellar mediodorsal thalamus;633 it is possible that these metabolic changes are secondary to loss of projections from the dopamine-de- pleted substantia nigra.

OTHER CONDITIONS CAUSING PARKINSONISM

Patients with the syndrome of amyotrophic lateral sclerosis, parkinsonism, and dementia (Lytico-Bodig), which is encountered in the inhabitants of the islands of the South Pacific Ocean, including Guam, may show more severe deficits than those with idiopathic PD, including limitation of vertical gaze.854 A common diagnostic challenge is to differentiate patients with other parkinsonian states from those with PD; although general neurologic findings and response to levodopa are important factors, a careful observation or measurement of eye movements can often help. Thus, as discussed above, slow vertical saccades usually indicate progressive supranuclear palsy. Slow saccades are also characteristic of Creutzfeldt-Jakob disease, but in both horizontal and vertical planes.544 Cortical-basal ganglionic degeneration does not cause slow saccades, but

the latency of visually guided saccades is increased beyond that typical of PD.1186'1429

Eye movements in multiple system atro-

phy are similar to those in PD; vertical saccades are not slow but are hypometric.1186

At present there are no published quantitative data on vertical saccades in diffuse Lewy-body disease, which is reported to cause a vertical gaze palsy.332'863

OCULOGYRIC CRISIS

This unusual state was once commonly encountered as a feature of postencephalitic parkinsonism but is now usually a side effect of drugs, especially neuroleptic agents.830 A typical attack is ushered in by feelings of fear or depression, which give rise to an obsessive fixation on a thought. The eyes typically deviate upward, and sometimes laterally; they rarely deviate downward. During the period of upward deviation, the movements of the eyes in the upper field of gaze appear nearly normal. Affected patients have great difficulty in looking down, except when they combine a blink and downward saccade. Thus, the ocular disorder may reflect an imbalance of the vertical gaze-holding mechanism (neural integrator). Anticholinergic drugs promptly terminate the thought disorder and ocular deviation, a finding that has led to the suggestion that the disorders of thought and eye movements are linked

by a pharmacological imbalance common to both.830 Delayed oculogyric crises have been described after striatocapsular infarction,873 and with bilateral putaminal hemorrhage.1282 Oculogyric crises are distinct from the brief upward ocular deviations that occur in Tourette's syndrome,474 Rett's syndrome,460 Lesch-Nyhan disease,7033 in children with benign paroxysmal tonic upgaze,663 in many patients with tardive dyskinesia,459 and rarely as a dopa-induced dyskinesia in Parkinson's disease.8673 In some patients with tardive dyskinesias, however, the upward eye deviations are more sustained and also have the characteristic neuropsychologic syndrome of oculogyric crises.1200 Episodic brief spells of tonic up gaze have also been reported after bilateral lentiform lesions.765

Huntington's Disease (HD)

CLINICAL FINDINGS IN HD

Huntington's disease produces distur-

bances of voluntary gaze, especially saccades (Display 10-32).286-815'816'833'1375 The

disease is due to a defect of the IT15 gene on chromosome 4, causing increased GAG triplet repeat length and the protein "huntingtin". Initiation of saccades may be difficult with prolonged latencies, espe-

532 The Diagnosis of Disorders of Eye Movements

cially when the saccade is made to command or in anticipation of a target that is moving in a predictable fashion. An obliga-

tory blink or head turn may be used to start the eye moving.1522 Saccades may be

slow in the horizontal or vertical plane; this deficit can often be detected early in the disease if eye movements are measured,286 but it may not be evident clinically until late in the course.833 Saccades may be slower in patients who become symptomatic at an earlier age, and it has been suggested that such individuals are more likely to have inherited the disease from their father.817 Slowing of vertical saccades probably does not occur in patients with chorea due to nondegenerative conditions or tardive dyskinesia.654 Smooth pursuit may also be impaired with decreased gain, but it often is relatively spared compared with saccades. By contrast, gaze holding and the VOR are well preserved. Late in the disease, rotational stimulation causes

the eyes to tonically deviate with few or no quick phases. Longitudinal studies of saccades have documented progressive slowing and prolongation of reaction time.1191 Fixation is abnormal in some patients with Huntington's disease because of saccadic intrusions.833 This defect of steady fixation is particularly evident when patients view a textured background.286

PATHOGENESIS OFOCULAR MOTOR FINDINGSIN HD

The paradoxical findings of difficulty in initiating voluntary saccades, but with an excess of extraneous saccades during attempted fixation, has been further elucidated using novel test stimuli. These have revealed an excessive distractibility in, for example, tasks in which patients are required to look in the direction opposite that in which a target suddenly appears (antisaccade task, Fig. 10-31).816 A second

finding is that saccades to visual stimuli are made at normal latency, while those made to command are delayed. These findings can be related to the parallel pathways that control the various types of saccadic responses. On the one hand, disease affecting either the frontal lobes or the caudate nucleus, which inhibits the substantia nigra pars reticulata (SNpr), may lead to difficulties in initiating voluntary saccades in tasks that require learned or predictive behavior.627 On the other hand, Huntington's disease also affects the SNpr.1054 Since this structure inhibits the superior colliculus (nigrocollicular projection), and so suppresses reflexive saccades to visual stimuli, one might expect excessive distractibility during attempted fixation. The slowing of saccades might reflect involvement of saccadic burst neurons,778 but at least some pathologic evidence suggests that disturbance of prenuclear inputs, such as the superior colliculus or frontal eye fields, is responsible.834 The ability of blinks to initiate or speed-up saccades is reviewed in Saccades and Movements of the Eyelids, in Chap. 3).

EYE MOVEMENTS AND THE DIAGNOSIS OF HD

Despite the near-ubiquitous finding of abnormal eye movements in Huntington's disease, some individuals who have been studied at a presymptomatic point in their disease have shown normal eye movements.286'1184 Thus, routine testing of eye movements cannot be regarded as a reliable method for determining which offspring of affected patients will go on to develop the disease. Some improvement of

the eye movement abnormalities in HD has been reported with sulpiride.1139

Disorders to be considered in the differential diagnosis of HD include neuroacanthocytosis, although abnormal eye movements have not been described as an important feature of this disorder.1146 Dentatorubropallidoluysian atrophy,1010 also called the Haw River syndrome,209 is another GAG triplet repeat disease (B37, chromosome 12) and is characterized by slow saccades but also by more myoclonus and ataxia than in HD.

Other Diseases of Basal Ganglia

A number of other conditions that involve the basal ganglia may cause abnormal eye movements. Wilson's disease and Nie- mann-Pick variants are discussed under Ocular Motor Manifestations of Metabolic and Deficiency Diseases. Caudate hemorrhage has been associated with ipsilateral gaze preference,1322 consistent with experimental dopamine depletion of this structure.727 Patients with bilateral lentiform nucleus lesions show abnormalities of predictive and memory-guided saccades (both internally generated), but visually guided saccades and antisaccades (both

triggered by a visual target) are normal.1425 It has been suggested that defects

in the control of predictive smooth-pur- suit eye movements are a feature of striatal damage.844

Patients with Gilles de la Tourette's syndrome may show abnormalities such as blepharospasm and eye tics that include involuntary gaze deviations.420'474 Routine testing of saccades, fixation, and pursuit is normal,153 but patients show increased latency and decreased peak velocity of anti-

saccades, as well as impaired sequencing of memory-guided saccades.999'1335 The lid

abnormalities of Tourette's syndrome must be distinguished from benign eye

movement tics, which children often out-

grow.134'1273

Patients with essential blepharospasm generally show normal eye movements,376 although saccadic latencies may be increased in certain visually guided and memory-guided saccade tasks.43'152 Patients with spasmodic torticollis may show abnormalities of vestibular function including the torsional VOR.60'1326 Whether vestibular abnormalities are the cause or a secondary effect of spasmodic torticollis has not been settled, but affected patients do show changes in their percep-

tions of the visual vertical and straight ahead.31'32

Patients with tardive dyskinesia may display increased saccade distractibility.1364 Patients with active Sydenham's chorea are reported to show saccadic hypometria.233 In Lesch-Nyhan disease, a hereditary disorder characterized by hyperuricemia, recurrent self-injurious be-

havior and extrapyramidal features, patients show impaired ability to make voluntary saccades, errors on the antisaccade task, blepharospasm, and intermittent

gaze deviations similar to Tourette's syndrome.703a

OCULAR MOTOR SYNDROMES CAUSED BY LESIONS IN THE CEREBRALHEMISPHERES

In reviewing the effects of cerebral hemisphere lesions on eye movements, first we describe the effects of acute lesions; second, we identify the enduring effects of large, unilateral lesions; and then we discuss the effects of lesions limited to specific lobes, referring to the scheme laid out in Chap. 6. Ocular motor apraxia, the manifestations of epileptic seizures, and the effects of diffuse processes, such as those causing dementia, are dealt with subsequently.

Disturbances of Gaze With Acute

Hemispheric Lesions

Following an acute lesion of one cerebral hemisphere, the eyes often deviate conjugately toward the side of the lesion—

Prevost's or Vulpian's sign (Display 10-33).531-1382 The head is also often

turned in the same direction (see Chap. 7). Sustained horizontal gaze deviation is more common after large, right-sided strokes that predominantly involve postRolandic cortex or the subcortical fron-

toparietal region and the internal capsule.339'1377'1382 Left hemispheric le-

sions that produce gaze deviations are usually large, covering the entire fronto- temporo-parietal area. With right-sided lesions, visual hemineglect is also often present and may contribute to the "gaze preference."794 In general, the larger the lesion, the more persistent the conjugate deviation. However, most horizontal gaze deviations that occur following a hemispheric stroke resolve within a week. When the gaze deviations are more persistent, there is often a prior lesion in the contralateral hemisphere.1323

Most patients show a conjugate gaze deviation that is ipsilateral to the side of the hemispheric lesion; they appear to "look away from their hemiparesis." Rarely, hemispheric lesions (usually hemorrhages) may cause a contralateral gaze deviation so that the patient appears to "look toward the hemiparesis";1075'1264 such wrong-way deviations are more common with thalamic lesions450 or with pontine lesions that lie below the level of the presumed ocular motor decussation. Another cause of a wrong-way deviation is epilepsy; when the patient is first examined, it should be confirmed that the gaze deviation is sustained and not a transient phenomenon that would suggest seizures.

Although the gaze deviation due to a hemispheric lesion may be quite marked during the acute phase, it is usually possible to drive the eyes across the middle of the orbits with a head rotation or caloric stimulation. This preservation of the range of reflexive eye movements is helpful in distinguishing the gaze deviation from a pontine lesion, in which vestibular stimuli often fail to drive the eyes across the midline.319 When quick phases of caloric nystagmus are absent, consciousness is usually, but not always, impaired

owing to shift of intracranial contents.265'1098

The defect of eye movements after a large hemispheric lesion often corresponds to craniotopic coordinates: There is difficulty moving the eyes in the contralateral orbital hemifield. Even within the remaining field of movement, however, other abnormalities are evident. For example, some patients show a smallamplitude nystagmus with ipsilateral quick phases; a similar finding is reported

acutely after hemidecortication in the monkey.1403 The slow phases of this nys-

tagmus may reflect unopposed pursuit drives directed away from the side of the lesion; recall that unilateral hemispheric lesions produce predominant deficits for contralateral saccades but ipsilateral smooth-pursuit and optokinetic responses (see Fig. 4-11). Support for this interpretation comes from measurement of optokinetic visual tracking in patients with ipsiversive gaze deviation; responses to

stimulus motion toward the intact hemisphere are much greater.959 Within the preserved field of movement, contralateral saccades are hypometric.959'1381 Vertical saccades may also show abnormalities; they are dysmetric with an inappropriate horizontal component toward the side of the lesion.464 Because normally both hemispheres must be activated to elicit a purely vertical saccade, the loss of one hemisphere may cause the abnormal trajectory. In general, for comparably sized lesions, ocular motor defects—both pursuit and saccades—are more profound when the lesion is in the nondominant hemisphere.843

Some further insights into the effects of acute inactivation of one hemisphere

come from observations of gaze control following intracarotid injection of barbiturate (the Wada test to determine cerebral dominance).856'927 At the onset of hemiparesis, a transient horizontal gaze deviation may occur, which is more common with right-sided injections, providing further evidence for the dominance of the right hemisphere in directing attention. During the period of hemiparesis of the Wada test, contralateral and ipsilateral saccades are still possible, with relatively minor slowing of the contralateral ones. This persistence of voluntary saccades is probably due to the influence of posterior cerebral areas, which receive blood supply from the vertebrobasilar system and which

project, independently of the frontal eye fields, to the superior colliculus.856

Enduring Disturbances of Gaze Caused by Unilateral Hemispheric Lesions

Persisting ocular motor deficits caused by large lesions (such as hemidecortication for intractable seizures) are summarized in Table 10-18. Though there may be no resting deviation of the eyes, Cogan pointed out that forced eyelid closure may cause a contralateral "spastic" conjugate eye move-

ment, the mechanism of which is not understood.261'1343 This sign occurs most fre-

quently with parietotemporal lesions.Conjugate deviation during attempted lid closure in patients with hemispheric lesions differs from the deviation (lateropulsion) that occurs in Wallenberg's syndrome (lateral medullary infarction (seeVIDEO: "Wallenberg's syndrome"). With hemispheric lesions, the eyes deviate only with active lid closure or attempted lid closure, but in Wallenberg's syndrome, the deviation occurs even with the eyes open in darkness.

In central position, a small-amplitude nystagmus may be present (best seen during ophthalmoscopy, with slow phases di-

rected toward the side of the intact hemisphere; it may represent an imbalance in smooth-pursuit tone.1270 Horizontal pursuit gain (eye velocity/target velocity) is low for tracking of targets moving toward the side of the lesion for all stimulus velocities. For targets moving slowly toward the intact hemisphere, the eye movements may be too fast (pursuit gain greater than 1.0), requiring back-up saccades (see Fig 4-1IB); for higher target velocities, pur-

suit gain toward the intact side is normal.1270'1395 This disturbance of smooth

pursuit probably reflects loss of both posterior (occipital-parietal-temporal) and frontal influences; possible pathogenetic mechanisms are discussed in the following sections, where the effects of lobar lesions are separately considered.

A convenient way to demonstrate this asymmetry of smooth pursuit is with a hand-held optokinetic drum or tape.272 The response is decreased when the stripes are moved toward the side of the lesion. At the bedside, this "optokinetic" response is usually judged according to the frequency and amplitude of quick phases. Since these quick-phase variables also depend on slow-phase velocity, a decreased response (reduced gain) may reflect impaired slow-phase generation, impaired quick-phase generation, or a combination of the two.

Hemidecortication causes abnormalities

of both contralateral and ipsilateral horizontal saccades.1270'1397 Saccades are usu-

ally slower than normal for refixations into the hemianopic field, and sometimes

cadic reaction time may reflect (1) defects in visual detection due to the hemianopia, (2} defects in directing visual attention, and (3) abnormal motor programing. Saccadic accuracy is impaired asymmetrically:

Most contralaterally directed saccades do not put the eye on target.1397

The horizontal VOR may be mildly asymmetric in hemidecorticate patients at lower test frequencies; the gain (eye velocity/head velocity) is greater for compensa-

tory eye movements directed away from the side of the lesion.424 More asymmetry appears when visual fixation and vestibular stimulation are combined (during rotation while fixating a stationary object), probably reflecting the ipsilateral smooth pursuit deficit. The asymmetry is still present during head rotation if the patient imagines a stationary object.1269 However, if the head is suddenly and rapidly rotated during fixation of a stationary target, gaze is perturbed no more than in normal subjects,665 consistent with the absence of oscillopsia in patients with hemispheric lesions as they make head movements during natural activities.

Effects of Focal Hemispheric

Lesions on Gaze

EFFECTS OF LESIONS OF POSTERIOROCCIPITOTEMPORAL CORTICAL AREAS ON GAZE

Unilateral lesions of the occipital lobes cause a contralateral visual field defect and an ocular motor deficit (saccadic dysmetria) that reflects the patient's homonymous hemianopia (Display 10-34). Saccades into the hemianopic visual field are dysmetric (usually hypometric), and similar patterns of saccades are reported with acoustic targets, implying some degree of common motor programing, perhaps influenced by associated defects in directing spatial attention.1389 Characteristic patterns are also shown in patients who have hemianopic dyslexia.1544

Patients with hemianopia may show compensatory strategies to increase saccadic accuracy,938 unless hemineglect is also present.1003 These strategies include a staircase of search saccades with backward, glissadic drifts; a deliberate overshooting saccade to bring the target into the intact hemifield of vision; and, with predictable targets, saccades using memory of previous attempts. Such findings have been used to develop simple clinical tests for distinguishing hemianopia with and without neglect.931 Rapid gaze shifts achieved by combined movements of eye and head also show increased latency of

head movements and development of compensatory strategies when looking to the hemianopic side.1521 Smooth pursuit remains intact with unilateral lesions of the striate cortex, provided the moving stimulus is presented to the intact hemifield,1252 and optokinetic nystagmus elicited at the bedside is usually symmetric. Within the affected visual field, motion detection is usually abolished.105 However, functional imaging suggests that secondary visual areas at the occipitoparietal region, lying anterior to an occipital lesion, may still respond to moving stimuli either due to extrastriate or interhemispheric callosal inputs.1663

Bilateral occipital lesions cause cortical blindness. A patient with bilateral, con-

genital occipital lesions and little residual vision was reported to be able to make voluntary saccades but not smooth pursuit.1156 Optokinetic responses are present

ther contralateral or ipsilateral deviation of the eyes and nystagmus.

Patients with more anterior lesions that involve cortex at the junction of areas 19,

37, and 39 (see Display 6-14), close to the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus (see Fig.6-8, Chap. 6), are reported to show defects of motion perception (akinetopsia),1283 and impairment

of smooth pursuit,826'1373 similar to those described in monkeys with middle temporal visual area (MT) lesions (see Fig. 4-8). Similarly, lesions may also involve the homologue of the medial superior temporal visual area (MST) and produce a tracking deficit similar to that in monkeys, with impairment of ipsilateral pursuit and a defect of motion processing affect-

ing the contralateral visual hemifield (Fig. 4_H).103,106,605,826,961,1373 Tnese tracking

defects with lesions affecting posterior cortical lesions are most evident when the responses to step-ramp stimuli are measured (see Abnormalities of Pursuit Initiation in Chap. 4). Patients with bilateral MST lesions may experience illusory motion of the stationary world during smooth pursuit.566

Lesions affecting vestibular cortex, a component of which lies in the posterior aspect of the superior temporal gyrus [parieto-insular-vestibular cortex (PIVC)] (see Display 6-15 and Fig. 6-8) cause contralateral tilts of the subjective visual vertical.172 In addition, such lesions may abolish the sense of self-rotation (circularvection) that normally occurs with optokinetic stimulation,1330 and may impair memoryguided saccades if patients are rotated to a new position during the memory period.682 Patients with lesions involving the medial temporal lobe and hippocampus show impairment in the ability to generate sequences of saccades, even though spatial memory is intact.990 Seizures emanating in the temporal lobes may cause a variety of vestibular sensations. Though a mild feeling of dizziness is common with a variety of seizure types, a true sensation of rotation, vestibular or tornado epilepsy, is a rare but well-described epileptic phenom-

enon_92,496,779,1011,1233,1296

EFFECTS OF PARIETAL LOBE LESIONS ON GAZE

Acute unilateral lesions involving the parietal lobe (see Display 6-16, Display 6-17, and Fig. 6-8)often cause an ipsilateral horizontal gaze deviation or preference. Especially when the lesion is right-sided, there is also contralateral inattention. Bi-

lateral ptosis may also occur with acute right parietal lesions,61 although it more commonly occurs with disease located in midbrain (especially involving the oculomotor nucleus), with Miller Fisher syndrome, or with disorders of the neuromuscular junction or the extraocular muscles (see Chap. 9). The defect of ocular motility often corresponds to craniotopic coordinates, reflecting the normal role of parietal areas in directing visual attention in head-centered or spatial coordinates; this is discussed further under Disturbances of Gaze With Acute Hemispheric Lesions. Although ocular motor defects associated with parietal lesions may be partly due to difficulties in shifting

10-35). 1°78,1453

The latency of visually guided saccades to targets presented in either visual hemifield is increased with right-sided lesions; with left-sided lesions, only saccades to contralateral targets are delayed.1089 These increases in saccadic latency are more marked when the fixation light remains on during testing (overlap paradigm) than when it is turned off just before the target light appears (gap paradigm);1090 this may reflect difficulties in disengaging attention prior to initiating the saccade. The accuracy of saccades to contralateral targets may also be impaired, but the most impressive dysmetria occurs when patients are required to respond to a double-step stimulus, in which the target jumps twice before a response can be initiated.409'603 If the targetjumps first into the contralateral hemifield and then into the ipsilateral field, patients cannot make accurate saccades to the final target position, even though it lies in the "intact" hemifield. This finding has been taken as evidence that the parietal lobe plays a pivotal role in computing target position from both visual stimuli and an efference copy of eye

movements (in this case, the change in eye position due to the first saccade).409-603

Asymmetry of smooth pursuit and optokinetic tracking has traditionally been