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

ascribed to parietal lobe lesions. Thus, decreased nystagmus elicited when a hand-

held optokinetic drum or tape moves toward the side of the lesion has been taken

as indicating involvement of the inferior parietal lobule and underlying deep white matter.272'605 Functional imaging studies suggest that secondary visual areas at the temporooccipitoparietal junction are probably responsible for these defects in smooth tracking (see Fig. 6-7). More specific to parietal lobe lesions is loss of the ability to attend to the image of a moving target and to "ignore" the smeared images of the stationary background consequent to the eye movement. Thus, patients with lesions affecting Brodmann area 40 show impaired smooth pursuit when the target moves across a structured background compared with pursuit across a dark background.820 Impairment of the same mechanism may explain why patients with parietal lesions show relative preservation of responses to full-field optokinetic stimuli, which demand less selective visual attention.87 Bilateral posterior parietal lesions

cause Balint's syndrome,1085 which is discussed below, under Ocular Motor Apraxia.

EFFECTS OF FRONTAL LOBE

LESIONS ON GAZE

Experimental and clinical studies, reviewed in Chap. 6, have made it possible to identify three distinct regions in the frontal lobes that contribute to the control of eye movements (see Fig. 6-8): the frontal eye field (FEF) (see Display 6-19), the supplementary eye field (SEF) (see Display 6-20) in the supplementary motor area, and the dorsolateral prefrontal cortex (DLPC) (see Display 6-21). Although there is some overlap of function, lesions affecting each of these three areas produce certain behavioral deficits that are distinctive (Display 10-36).1082

Effects of FEF Lesions on Gaze

Acute lesions of the FEF may produce an ipsilateral horizontal gaze deviation that resolves with time.319'1226 Acute pharma-

542 The Diagnosis of Disorders of Eye Movements

cological inactivation of the FEF also abolishes all contralateral, voluntary saccades.384'1307 Rarely, contralateral deviation has been observed with acute, hemor-

rhagic frontal lesions1264 or frontoparietal lesions.1075

The enduring deficits of saccades and smooth pursuit with FEF lesions are often not obvious at the bedside and require laboratory testing to identify. Thus, an increased reaction time to initiate a saccade is more evident when the fixation light remains on during testing (overlap paradigm), when saccades are made to remembered target locations, and especially during the antisaccade task (Fig. 10-31).1086,1152 These increases in latencies occur whether the target is located ipsilateral or contralateral to the lesion. There is mild hypometria of saccades made to vi-

sual or remembered targets located contralateral to the side of the lesion.177'896'1152

Another deficit concerns the ability to make saccades in anticipation of target jumps that occur predictably, when the

target moves away from the side of the le- Sion.38o,io9o,i263 Mild slowing of contralat-

eral saccades occurs in some patients.1263 Deep, unilateral frontal lobe lesions cause

increased latency for contralateral saccades.1091 This deficit is probably due to

damage of efferent and afferent connections of the frontal eye fields. Paradoxically, patients with FEF lesions may show difficulty in suppressing saccades to novel visual targets—for example, during the antisaccade task.1152

FEF lesions also impair smooth pursuit.176'605'843'844'962-1152 With unilateral

FEF lesions, horizontal pursuit is impaired bilaterally, but more so for tracking of targets moving toward the side of the lesion. Both the initiation and maintenance of pursuit are affected, more so at higher target speeds and frequencies.

Effects of SEF Lesions on Gaze

Visually guided saccades are not noticeably affected by SEF lesions, and memoryguided saccades only become inaccurate if there is a gaze shift during the memory period.1086 The defect that is characteristic of SEF lesions is a loss of the ability to

make a sequence of saccades to an array of visible targets in the order that they were turned on.504'506 This is especially true with left-sided SEF lesions. Thus, the SEF seems essential for programing a series of saccades as part of a learned behavior. Note, however, that impaired ability to remember a sequence of saccades also occurs with lesions affecting the hippocampus.990 SEF lesions may also impair the predictive smooth-pursuit response.605-843

Effects of DLPC Lesions on Gaze

Pharmacological inactivation of the DLPC with Dj dopamine antagonists specifically impairs the ability of monkeys to make accurate memory-guided saccades toward contralateral targets.1222 Similarly, patients with lesions affecting the DLPC show defects of memory-guided saccades, antisaccades, and predictive saccades.564'1086'1087 Pursuit defects with unilateral DLPC lesions may be bilateral.843

Memory-guided saccades are also affected by lesions involving the posterior portion of the right cingulate cortex. Such patients also make increased errors on the antisaccade test and when they attempt to make, from memory, a sequence of saccades.5053

Ocular MotorApraxia

ACQUIRED OCULAR MOTOR APRAXIA

Acute bilateral frontal or frontoparietal lesions may produce a striking disturbance of ocular motility that has been called acquired ocular motor apraxia.M4'1081 It is usually due to bihemispheric infarcts and may be a complication of cardiopulmonary bypass.382 It is characterized by loss of voluntary control of saccades and pursuit, with preservation of certain reflex movements. Patients have difficulties making horizontal and vertical saccades to command and following a pointer moved by the examiner (see VIDEO: "Acquired ocular motor apraxia"). Gaze shifts are achieved more easily with combined eye-head movements, often in association with a blink. Vestibular eye movements (both slow and

quick phases) are preserved. In addition, some patients are able to initiate saccades reflexively to novel visual targets. The defect of voluntary eye movements probably

3-8), so the superior colliculus and brain stem reticular formation are bereft of their cortical inputs. The behavioral deficit is similar to that produced by bilateral, combined, experimental lesions of the frontal eye fields and superior colliculus,1226 or frontal and parietal eye fields.890

When a similar disorder of ocular motility, called psychic paralysis of gaze, is associated with inaccurate arm pointing (optic ataxia) and disturbance of visual attention

(simultagnosia), the eponym Balint's syn-

drome has been used.265'637'639-667'1081'1154'1410

The lesions are more parietal or occipital, and voluntary saccades may be made more easily than in response to visual stimuli.1085 Thus, the main abnormality appears to be a defect in the visual guidance of saccades, manifested by increased latency and decreased accuracy

and impaired ability to conduct visual search.109'888-1545 Smooth pursuit is also im-

paired.840 Spontaneous blinking may be absent.1461 In one patient, the visual scene was reported to fade during fixation and to be restored by intentional blinks.535 (The effects of blinks on eye movements are reviewed in Saccades and Movements of the Eyelids, in Chap. 3).

Some patients with ocular motor apraxia may show spasm of fixation, the inability to generate a voluntary eye movement to shift gaze when a fixation target is continuously present; only when the fixation target is removed can a gaze shift be made.639 Holmes,639 assisted by DennyBrown, noted that if affected patients viewed a homogenous white screen, then voluntary eye movements became possible. The anatomic basis for this disturbance is uncertain, although defects in the inhibitory control of the superior colliculus by the substantia nigra pars reticulata (SNpr) have been proposed.709

The following case history illustrates some features of the syndrome of acquired ocular motor apraxia.

CASE HISTORY:Acquired Ocular Motor Apraxia in Multiple Sclerosis (see video: "Acquired ocular motor apraxia")

A 28-year-old woman was in good health until 8 months prior to admission, when she suffered a "whiplash" neck injury in an automobile accident. Subsequently, she developed transient mild weakness of the left side of the body, which resolved in a few weeks. She suffered several further transient neurologic deficits, including loss of vision in first the right and then the left eye. Just prior to admission, she developed right-sided weakness, difficulty with speech, and emotional behavior that her husband characterized as "child-like."

On examination, she had strikingimmobility of gaze. She was emotionally labile and had difficultieswith calculations and short-term memory, but was cooperative and could follow instructions. Both optic discs were pale. Her visual acuity was 20/200 OS and 20/100 OD. She had no difficulty in recognizing or naming objects. There were bilateral pyramidal tract signs.

With the head still, she had great difficulty initiating saccades to command or to visual targets. When saccades did occur, they were often associated with a blink. With her head free to move, she could change gaze more easily. Her saccades were of small amplitude but appeared to be of normal velocity. On occasion, she would change gaze by moving first the trunk, then her head, and finally making a small saccade. With an optokinetic tape, quick phases of nystagmus were easily elicited, though they seemed to be reduced in frequency. Smooth tracking was also impaired. Rotational testing elicited normal quick and slow phases ofvestibular nystagmus.

Computed tomography (Fig. 10-32) showed bilateral lucencies in the centrum semiovale and deep portions of the posterior frontal and parietal lobes. Spinal fluid findings supported a diagnosis of multiple sclerosis. She improved while in the hospital and 1 year later was reported to have no ocular motor deficit.

Comment: This patient's ocular motor deficit involved voluntary eye movements: saccades and pursuit. Her "reflex" eye move- ments—vestibular nystagmus—and eye-head gaze shifts were relatively spared. Thus, the term ocular motor apraxia might be correctly ap-

plied to this deficit, which reflects disease involving both cerebral hemispheres.

CONGENITAL OCULAR MOTOR APRAXIA

Congenital ocular motor apraxia was first described by Cogan.262'266'271 An abnor-

mality may be recognized at several months of age when the child does not appear to fixate upon objects normally and may be thought to be blind. Some children with congenital ocular motor apraxia have also been reported to have had a transient head and limb tremor in the first few days of life. Between the ages of 4 and

6 months, characteristic, thrusting horizontal head movements develop (see VIDEO: "Congenital ocular motor apraxia"), sometimes with prominent blinking or even rubbing of the eyelids when the child attempts to change fixation. In children with poor head control, development of head thrusting may be delayed or absent. Almost all patients also show a defect in generating quick phases of nystagmus,591 which can usually be appreciated at the bedside by manual spinning of the patient, either when holding the child out at arm's length or by rotating the child on a swivel chair—if necessary, sitting in an adult's lap (see VIDEO: "Congenital ocular motor apraxia"). Despite difficulties in

shifting horizontal gaze, vertical voluntary eye movements are normal.

Measurements of eye and head move-

ments have documented the characteristics of this disorder.439'591'1540 With the

head immobilized, patients show both impaired initiation (increased latency) and decreased amplitude (hypometria) of voluntary saccades in response to either a simple verbal command to look left or right or, less so, to track a step displacement of a target (Fig. 10-33). Saccades are also delayed during attempted refixations between auditory targets in complete darkness, so the saccadic initiation abnormality cannot be ascribed to a defect of the visual responses. Saccadic velocities are normal and saccades or quick phases of nystagmus of large amplitude can occasionally be generated. These findings indicate that, in these patients, the premotor

brain stem burst neurons that generate saccadic eye movements are intact. Especially in younger patients, however, the timing and amplitude (but not velocity)of quick phases of vestibular and optokinetic nystagmus may be impaired; the eyes intermittently deviate tonically in the direction of the slow phase because of a defect in the initiation of the quick phase of nystagmus. Sometimes the saccade defect (and head thrusts) is asymmetric.241 Pursuit eye movements may also be of low gain, but the corrective saccades are usually promptly generated. The defects in congenital ocular motor apraxia are usually restricted to the horizontal plane, an important differential diagnostic point, because most acquired cases also have defects in the vertical plane.

The head thrusts made by affected patients probably reflect one of several adap-

tive strategies to facilitate changes in gaze.425'1540 Younger patients appear to use their intact VOR, which drives their eyes into an extreme contraversive position in the orbit. As the head continues to move past the target, the eyes are dragged along in space until they become aligned with the target. Then the head rotates backward and the eyes maintain fixation as they are brought back to the central position in the orbit by the VOR. In contrast, older patients appear to use the head movement per se to trigger the generation of a saccadic eye movement that cannot normally be made with the head still (Fig 10-33, right panel). This strategy may reflect the use of a phylogenetically old linkage between head and saccadic eye movements that occurs reflexively in afoveate animals, when they desire to redirect their center of visual attention (see Rapid Gaze Shifts Achieved by Combined Eye-Head Movements, in Chap. 7).

The cause of congenital ocular motor apraxia is unknown. Cogan suggested that it may reflect a delay in the normal development of the mechanisms by which we assume voluntary control over eye movements.271 Affected patients usually improve with age: The head movements become less prominent as the patients are better able to direct their eyes voluntarily. The presence of normal-velocity saccades suggests an intact brain stem mechanism for generating eye movements. The propensity of these children to blink in order to initiate a saccade suggests a prob-

lem with gating of brain stem burst neurons.1528 (The effects of blinks on eye

movements are reviewed in Saccades and Movements of the Eyelids, in Chap. 3).

Delayed psychomotor development (especially in learning to read and in speech), infantile hypotonia, strabismus, incoordination, torsional nystagmus, and clumsiness occur in some patients.1197 Associated

anomalies include agenesis of the corpus callosum, collicular abnormalities, and cerebellar vermian dysplasia or hypoplasia

(for example, as part of Joubert's syndrome).1217'1276'1483 It seems more likely

that such anomalies are markers of abnormal development rather than being directly responsible for the eye movement disorder. Congenital ocular motor apraxia is occasionally familial and has been reported in monozygotic twins.565'1107

Apart from the idiopathic type of congenital ocular motor apraxia, a variety of hereditary disorders that directly involve the brain stem mechanisms for generating saccades are characterized by the development of a strategy of head thrusting or blinking to shift gaze, and hence superficially appear as congenital ocular motor apraxia. Some of these conditions are discussed in the section on Ocular Motor Manifestations Of Metabolic And Deficiency Disorders. Other disorders reported in association with horizontal saccadic failure include GM1 gangliosidosis, Krabbe's leukodystrophy, peroxisomal assembly disorders, Lesch-Nyhan disease,7033 proprionic acidemia, Bardet-Biedl syndrome, Cornelia de Lange syndrome, and a variety of developmental abnormalities of the midline cerebellum.591 These disorders can be distinguished from Cogan's form of congenital ocular motor apraxia when vertical saccades are affected and when saccades are slow. In early stages of these diseases, however, distinguishing the ocular motor apraxia from Cogan's type may be difficult.270 Purely vertical ocular motor apraxia is rare and usually reflects direct in-

volvement of saccade-generating pathways in the midbrain or pons (Display 10-24).412

Eye Movements During

Epileptic Seizures

Eye and head movements are common manifestations of epileptic seizures, if carefully looked for. A variety of abnormal eye movements has been reported, including horizontal or vertical conjugate gaze deviation, and skew deviation.499 Horizontal gaze deviations are usually contralat-

eral, but occasionally ipsilateral, to the side of the seizure focus.1329'1378 The dis-

tinction between a paretic and epileptic gaze deviation (Display 10-33) is made by observing the patient's eye for a few minutes; epileptic deviations are seldom sustained. Epileptic seizures also cause a variety of forms of nystagmus: conju-

gate, retraction, convergence, or mono-

cular.590'695'721'1169'1289'1374'1399 Convergence

nystagmus has been reported with either periodic lateralizing epileptiform discharges1516 or burst-suppression pat- terns.180-1005 Epileptic nystagmus has also been reported with typical absence seizures1457 and with infantile spasms.647 Eyelid flutter may be the only clinical manifestation of seizures.945 Some patients may show both intermittent gaze deviations and nystagmus.1374 How can these diverse manifestations be related to the known mechanisms that control gaze, which we summarized in Chap. 6?

Although eye movements may be a manifestation of a seizure focus in any lobe,958 the most commonly reported site in patients with epileptic nystagmus is the temporo-occipital-parietal region.721'722 In most such cases, the eyes initially deviate contralateral to the seizure focus. This initial deviation may be due to activation of the parietal eye fields, which, in the monkey homologue (the lateral intraparietal area, LIP), have a low electrical threshold for eliciting saccades. In one such patient, who had a right temporo-occipital focus, the seizure began with a contraversive (leftward) gaze deviation due to a staircase of small saccades.1374 After a few seconds, left-beating nystagmus commenced, with slow phases that showed a decreasing-ve- locity waveform. The nystagmus was accompanied by high-voltage 11-14 Hz spike activity that did not spread to frontal cortex. At the end of the seizure, the eyes returned to central position. It seems possible that the centripetal slow phases of such nystagmus are similar to those of gaze-evoked nystagmus (Fig. 10-1B). The reason for the unsustained gaze deviation, centripetal drifts, and nystagmus may be either effects of anticonvulsants1374 or impaired consciousness831 or a deficient eye position signal due to seizure activity ema-

nating from cortical areas.958 Rarely, patients show an initial gaze deviation that is ipsiversive and is followed by quick phases which generate nystagmus.721'1399 In such cases, activation of pursuit mechanisms at the occipitotemporoparietal junction (Fig. 6-8) may be responsible. Experimental studies in awake monkeys indicate that the threshold for stimulating pursuit eye movements is lower than that for stimulating saccades.781 Support for this hypothesis comes from documentation that the slow phases of subsequent nystagmus are linear (see Fig 10-1A) and move the eyes across the midline. A further point is that such patients are usually awake, and the quick phases are then generated in response to the pursuit-mediated eye deviation. Finally, a patient with a temporoparietal seizure focus has been described who showed no gaze deviation prior to onset of nystagmus.496 Her attacks were accompanied by vertigo, and slow phases were linear, suggesting involvement of the cortical areas involved in vestibular and optokinetic or pursuit mechanisms (Fig. 6-7).

Thus, contraversive quick phases in epileptic patients may be due to two different mechanisms: (1) primary, contraversive saccades due to epileptic activity in the saccadic regions, followed by centripetal drift due to impaired gaze holding; and (2) secondary, reflexive contraversive saccades, which correct for slow ipsiversive deviation across the midline due to epileptic activation of either the smooth-pursuit or optokinetic regions. In patients with coexistent brain stem lesions, the only manifestation of epileptic activity

may be rapid, small-amplitude, vertical eye movements.1289 The absence of hori-

zontal movements suggests dysfunction of the paramedian pontine reticular formation (PPRF—see Display 10-21).

Frontal lobe foci may cause contraversive deviations but, if bilateral, will lead to vertical deviations of gaze.720 These results are consistent with stimulation studies in monkeys: Unilateral stimulation of the frontal eye field typically causes oblique saccades with a contralateral horizontal component; the direction of the vertical saccade depends upon a cortical map.199 Purely vertical movements require bilat-

eral stimulation of the frontal eye fields. Because there are also neurons in the frontal eye fields that contribute to smooth pursuit, it is theoretically possible that frontal lobe foci could lead to an ipsiversive deviation.

Head turning is a common accompaniment of epileptic gaze deviation (see Head Turning as a Feature of Epilepsy, in Chap. 7). In patients who are conscious during the seizure, a frontal focus is likely and the initial direction of head turning is usually, but not invariably, contralateral to the seizure focus.1497'1498 A contralateral focus is also likely in a patient who shows marked and sustained lateral positioning of head and eyes. In patients who are unconscious during the seizure, the focus may arise from any lobe and head turning

may be toward or away from the side of the lesion.518'1030

As discussed above, seizures emanating from the superior temporal lobes may cause a variety of vestibular sensations, and occipital lobe seizures may produce oscillopsia.113 Rarely, seizures may be precipitated by movements of the eyes such as convergence1430 or sustained lateral deviation.1262 We have observed a patient in whom left horizontal gaze deviation consistently precipitated adversive seizures, with head turning to the left and tonic flexion of the left elbow. He had recently undergone partial resection of a right frontotemporal glioblastoma.

Finally, disturbances of gaze during disturbance of consciousness need not imply epilepsy. Experimentally induced syncope is reported to cause tonic upward gaze deviation and downbeat nystagmus.848 An increase in the gain of the vestibulo-ocular reflex was also noted. Consideration of all the clinical and laboratory findings is required before a diagnosis of epilepsy can be made.

ABNORMALITIES OF EYE MOVEMENTS IN PATIENTS WITH DEMENTIA

A variety of disease processes that cause global impairment of cognitive function may also impair the control of eye move-

ments. Often the changes are subtle at the bedside, and they may require special testing procedures. However, application of experimental paradigms that are known to test specific cortical and subcortical areas has proved useful in better defining the extent of involvement in these diseases. Moreover, although no test is diagnostically specific, serial testing provides one index of progression of the disease and so may be useful in evaluating new therapies.

Alzheimer's Disease

Most disorders of eye movements in Alzheimer's disease reflect an underlying loss of the ability to focus or shift visual attention. Thus, the ability to sustain steady fixation of a visual target may be disrupted by large saccadic intrusions, which are distinct from the small, to-and-fro square-

wave jerks (Fig. 10-16A) that are also common in this age group.617'711'969'1267 These

larger, inappropriate saccades are often due to a distracting stimulus or occur because patients cannot suppress eye movements made in anticipation of the expected appearance of a stimulus.656 They have been studied using the antisaccade test stimulus, in which the subject is required to suppress a reflexive saccade toward a

visual stimulus and, instead, look in the opposite direction (Fig. 10-31).312'465 Pa-

tients affected by Alzheimer's disease are quite unable to suppress such reflexive saccades; this has been called a visual grasp reflex.465

When patients with Alzheimer's disease make visually guided saccades, the reaction time is prolonged if the appearance of the target is unpredictable.465-619'1096 Saccades are hypometric465 and may be slow if the target stimulus is unpredictable,465 more so vertically.656 When patients with Alzheimer's disease are asked to study a complex visual scene, their ability to scan it with saccades is diminished.316'969 This impaired ability to direct visual attention may mimic Balint's syndrome.635

Smooth pursuit in patients with Alzheimer's disease often shows reduced gain, with catch-up saccades, for all frequencies

and velocities of target motion, with a fur-

ther decline for higher target accelerations.466'1518 Similar to what occurs during

fixation, smooth pursuit may be disrupted by large saccadic intrusions as the patient looks toward the anticipated target position. Predictive aspects of smooth pursuit are relatively preserved in this disorder, as is the vestibulo-ocular reflex.805

In summary, in Alzheimer's disease, the impaired ability to suppress saccades to novel visual stimuli on the antisaccade task suggests frontal lobe involvement, whereas patients who show impaired ability to shift visual attention probably have parietal lobe involvement. Impairment of smooth pursuit may reflect involvement of secondary visual areas in parietal cortex, and it is of interest that one patient with Pick's disease, which predominantly affects the frontal and temporal lobes, had relative preservation of smooth pursuit.668

Creutzfeldt-Jakob Disease

Patients with Creutzfeldt-Jakob disease may show limitation of vertical gaze and slow vertical saccades, and two rare forms of nystagmus, periodic alternating nystagmus (see Display 10-5) and centripetal nystagmus (see Display 10-7).544'606 Eventually, patients may lose saccades and quick phases, but continue to show periodic alternating gaze deviation.544 Other

affected patients show sustained gaze or skew deviations with head turns.1515 This

spectrum of disturbance of eye movements attests to prominent involvement of the cerebellum and brain stem in some patients with Creutzfeldt-Jakob disease. Overdoses of lithium or bismuth may lead to syndromes that mimic CreutzfeldtJakob disease.532'1302 Cerebellar eye signs are typically found in another prion disor-

der, Gerstmann-Straussler-Scheinker dis-

ease.429'1511

AIDS andDementia

Human immunodeficiency virus (HIV) encephalopathy may cause several disturbances of ocular motility reflecting frontal