James A. Sharpe

Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates.

Opsoclonus is a dyskinesia consisting of involuntary, arrhythmic, chaotic, multidirectional saccades, without intersaccadic intervals. We used a magnetic scleral search coil technique to study opsoclonus in two patients with paraneoplastic complications of lung carcinoma. Eye movement recordings provided evidence that opsoclonus is a three-dimensional oscillation, consisting of torsional, horizontal, and vertical components. Torsional nystagmus was also present in one patient. Antineuronal antibody study revealed the presence of anti-Ta (Ma2 onco-neuronal antigen) antibodies in one patient, which had previously been associated only with paraneoplastic limbic encephalitis and brainstem dysfunction, but not opsoclonus, and only in patients with testicular or breast cancer. Neuropathologic examination revealed mild paraneoplastic encephalitis. Normal neurons identified in the nucleus raphe interpositus (rip) do not support postulated dysfunction of omnipause cells in the pathogenesis of opsoclonus. Computer simulation of a model of the saccadic system indicated that disinhibition of the oculomotor region of the fastigial nucleus (FOR) in the cerebellum can generate opsoclonus. Histopathological examination revealed inflammation and gliosis in the fastigial nucleus. This morphological finding is consistent with, but not necessary to confirm, damage to afferent projections to the FOR, as determined by the model. Malfunction of Purkinje cells in the dorsal vermis, which inhibit the FOR, may cause opsoclonus by disinhibiting it.

Smooth pursuit dysfunction in Alzheimer's disease

Smooth ocular pursuit was measured by magnetic search coil oculography in 13 patients with Alzheimers disease and compared with control subjects. Smooth eye movement gain was uniformly reduced in Alzheimers disease at all target velocities for several frequencies of sinusoidal target motion, signifying impairment of steady-state gain. Normal phase relationships between the target and eyes indicated an intact predictor mechanism for smooth pursuit. When peak target velocity was held constant, pursuit gain decreased markedly in response to small increments of target acceleration, indicating involvement of an acceleration saturating nonlinear element that limits smooth pursuit. Large-amplitude saccadic intrusions, in the direction of target motion, often disrupted pursuit; smooth eye movements continued in response to target velocity despite large position errors of the fovea from its target. These disorders of smooth eye movement control can quantify motor dysfunction in Alzheimers disease.

Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion Pathophysiologic correlations

Upward and downward gaze palsy was measured by a magnetic search coil technique and correlated with neuropathologic findings in a patient with a unilateral midbrain infarct. Oculography demonstrated (1) saccadic palsy above primary position and slow, limited vertical saccades below; (2) low-gain, restricted vertical pursuit; and (3) low-gain, abnormal phase lead, and restricted range of the vertical vestibulo-ocular reflex (VOR). Bidirectional palsy of vertical saccades is attributed to unilateral loss of burst cells in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and interruption of burst cell fibers from the opposite riMLF. Pathways mediating vertical pursuit and integration of the vertical VOR also traversed the infarct, which included the interstitial nucleus of Cajal.

Senescent Saccades: Effects of Aging on Their Accuracy, Latency and Velocity

The effects of aging on horizontal saccades were investigated by infrared oculography in young, middle-aged and elderly normal subjects. Saccades were elicited in response to three target conditions: 1) predictable amplitude direct and timing; 2) unpredictable amplitudes and directions at regular intervals; and 3) unpredictably timed targets of predictable amplitude and direction. Peak velocities were significantly reduced in the elderly when target amplitude and direction were predictable. Latencies were prolonged in the elderly under all conditions. Saccadic accuracy was significantly decreased in elderly subjects; the amplitudes of primary saccades were reduced and hypometric saccades were frequent. The results indicate that the diagnosis of saccadic dysfunction in disease should be qualified by the age of the patient and by the target task.

Cerebral hemispheric localization of smooth pursuit asymmetry

We recorded horizontal smooth pursuit in 23 patients with discrete unilateral cerebral hemispheric lesions and in 12 normal subjects. Most patients had bidirectional reduction of smooth pursuit gain, indicating that each cerebral hemisphere participates in smooth pursuit in both directions. Pursuit gain fell proportionately more with increasing target acceleration in patients than in normals. A normal phase relationship between eye and target motion in patients indicated an intact predictor mechanism for smooth pursuit. Ten patients had pursuit asymmetry with lower gain when tracking toward the side of cerebral damage; none had lower gain when tracking away. Two patients with lower ipsilateral gain had frontal lobe lesions. Areas of anatomic overlap of lesions associated with asymmetric pursuit in 8 patients provide evidence for a pursuit pathway that originates from Brodmann areas 19 and 39 and descends to the brainstem through the posterior limb of the internal capsule.

Cerebral square wave jerks.

Abnormal saccadic intrusions consisting of frequent sporadic horizontal saccades followed, after an interval, by corrective saccades occurred in 70% of 17 patients with acute or chronic focal cerebral lesions. These square wave jerks were significantly lower in amplitude than those in cerebellar system disease. The metrics of these jerks were uniform regardless of the site of cerebral damage. Mean durations approximated the reaction time for saccadic refixations triggered by visual feedback. Very short-latency corrective saccades in some patients are attributed to internal (nonretinal) feedback of eye position errors. Low-amplitude cerebral square wave jerks can be detected clinically by funduscopy.

Paralytic pontine exotropia A sign of acute unilateral pontine gaze palsy and internuclear ophthalmoplegia

Paralytic external deviation of one eye with horizontal immobility of the fellow eye specifies an acute brainstem lesion involving the paramedian pontine reticular formation and the medial longitudinal fasciculus on the side opposite the deviated eye. This paralytic pontine exotropia is distinguished from other exotropias. The deviated (exotropic) eye shows abduction nystagmus during attempts to move it further laterally, and extreme slowness of adduction saccades. Normal midbrain ocular motor functions are evidenced by intact vertical gaze, convergence, and pupillary constrictor reflex activity.

Saccades in children

Saccades are necessary for optimal vision. Little is known about saccades in children. We recorded saccades using an infrared eye tracker in 39 children, aged 8-19 years. Participants made saccades to visual targets that stepped 10 degrees or 15 degrees horizontally and 5 degrees or 10 degrees vertically at unpredictable time intervals. Saccadic latency decreased significantly with increasing age, while saccadic gain and peak velocity did not vary with age. Saccadic gains and peak velocities in children are similar to reported adult values. This implies maturity of the neural circuits responsible for making saccades accurate and fast. Saccade latency decreases as the brain matures.

Smooth pursuit in senescence: effects of target acceleration and velocity

Smooth pursuit responses to sinusoidal and triangular waveform targets were investigated in elderly and middle-aged subjects. The middle-aged pursued triangular targets with significantly lower gain than sinusoidal targets. In the elderly, pursuit gain was significantly lower than in the middle-aged under all target conditions. When all smooth eye movements at a constant frequency were correlated with varying target velocity, pursuit gain was uniformly reduced in the elderly, irrespective of target velocity up to 63 degrees/s or accelerations up to 395 degrees/s2. Within these limits, the steady-state gain of pursuit was depressed. At higher target accelerations having the same velocity range, smooth pursuit velocities were further reduced in the elderly. Senescent tracking is depressed by involvement of the steady-state gain element of the pursuit system at low target accelerations and by acceleration saturation at higher demands.

Visual‐vestibular interaction in multiple sclerosis

Visual modulation of the vestibuloocular reflex (VOR) was analyzed in 20 patients with multiple sclerosis who had no vestibular or ocular motor symptoms. Visual suppression of the VOR was impaired in 75% of patients. VOR gains in darkness were elevated in 35% of patients. Elevated VOR gain in darkness is attributed to vestibular adaptation to defective smooth pursuit. This vestibular plasticity achieved retinal image stability by matching eye velocity to head velocity when stationary targets were viewed. The high incidence of impaired visual suppression of the VOR rivals the sensitivity of other physiologic tests used to identify multiple sclerosis.