Joel M. Weinstein

Paraneoplastic Retinopathy Associated with Andretinal Bipolar Cell Antibodies in Cutaneous Malignant Melanoma

Purpose: It has been shown previously that the sera, from patients with visual paraneoplastic syndrome associated with lung cancer, contain immunoglobulins that are reactive with the tumor and with photoreceptor and large retinal ganglion cells. The purpose of this study is to determine the retinal cell population that reacts with immunoglobulins in the sera of patients with melanoma-associated retinopathy. Methods: Clinical and electrophysiologic studies were used to determine the locus responsible for the visual defect in each patient. Sera from two patients with melanomaassociated retinopathy, from a patient with herpes zoster, and from a patient who had a colon tumor were obtained. The sera were incubated with sections of retina obtained from a healthy 3-year-old child who had died of asphyxiation. The tissue sections subsequently were incubated with biotin-labeled anti-human immunoglobulin G, and then with streptavidin-labeled peroxidase. Finally, the tissue sections were developed to show peroxidase activity in the targeted retinal cells. Results: Clinical and electrophysiologic studies were consistent with a defect in intraretinal transmission distal to the photoreceptors. The immunoglobulins from the patients with the melanoma-associated retinopathy reacted selectively with the bipolar cells of the retina; approximately 30% of the bipolar cells were immunoreactive. The sera from the other two patients were not reactive with any of the retinal cells examined. Conclusions: The sera of patients with the paraneoplastic syndrome, melanomaassociated retinopathy, contain high titer immunoglobulins that are reactive only with a subset of the bipolar retinal cells. The clinical, electrophysiologic, and immunologic studies are all consistent with an intra-retinal transmission defect at the level of the bipolar cells.

Congenital Horner's Syndrome

Patients with congenital Horners syndrome (who seemed, on the basis of their clinical history and the distribution fo anhidrosis, to have a preganglionic lesion) had partial mydriatic failure with hydroxyamphetamine hydrobromide and a supersensitivity to phenylephrine hydrochloride. This apparent paradox can be readily explained by postulating an aorthograde transsynaptic dysgenesis of the postganglionic neuron, such as has been demonstrated in the sympathetic nervous system of newborn animals. The failure of hydroxyamphetamine to cause mydriasis indicates damage to the postganglionic sympathetic neuron, but in the neonate this damage may be secondary to a preganglionic lesion.

The human pre-saccadic spike potential: Influences of a visual target, saccade direction, electrode laterality and instructions to perform saccades

Three components of pre-saccadic evoked potentials have been identified in humans: a slow negative shift (SNS), a positive antecedent potential (AP) and a spike potential (SP). This study examined the influences of: instructions to the subject to make saccades; the presence of a visual target; and the direction of the saccades on the amplitude of the averaged SP, which was recorded from P3 and P4 (International 10/20 System) in 20 normal, right-handed subjects. Recordings were made for spontaneous saccades prior to receiving instructions in six subjects. Twenty subjects performed self-paced saccades in the presence of a 10 degrees visual target (two red LEDs) and while blindfolded in a dark room. The SP was either absent or grossly altered (broadened) for spontaneous saccades in an illuminated room; it was robust for self-paced saccades in light or darkness. Three-way analysis of variance revealed a highly significant cortical laterality (P3 vs P4) X saccade direction interaction (P less than 0.001), reflecting that for a given saccade direction, the SP was larger over the contralateral recording site for the self-paced light (SPL) paradigm (Newman-Keuls test). In the self-paced dark (SPD) paradigm, though, this was only true for saccades to the right. By contrast, scatter plots of the directional indices (D.I. = [(SP for contralateral) - (SP for ipsilateral)]/[(SP for contralateral) + (SP for ipsilateral saccades)] for left (P3) and right (P4) recording sites from individual subjects revealed a significant negative correlation for both SPL (r = 0.78) and SPD (r = 0.74) paradigms.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachnoid cyst causing third cranial nerve palsy manifesting as isolated internal ophthalmoplegia and iris cholinergic supersensitivity.

An 8-month-old boy presented with anisocoria, a sluggishly reactive right pupil, and cholinergic supersensitivity as the only signs of what proved months later to be compressive third cranial nerve palsy due to an arachnoid cyst. Tonic constriction and dilation, segmental iris sphincter palsy, aberrant regeneration phenomena, ductional deficits, and ptosis were absent. The initial diagnosis was postganglionic internal ophthalmoplegia attributed to a viral ciliary ganglionopathy. Nineteen months later, he had developed an incomitant exodeviation and a supraduction deficit. Brain MRI revealed a mass consistent with an arachnoid cyst compressing the third cranial nerve in the right interpeduncular cistern. Resection of the cyst led to a persistent complete third cranial nerve palsy. This is the second reported case of prolonged internal ophthalmoplegia in a young child as a manifestation of a compressive third cranial nerve palsy. Our patient serves as a reminder that isolated internal ophthalmoplegia with cholinergic supersensitivity is compatible with a preganglionic compressive third nerve lesion, particularly in a young child.

Directional tuning of the human presaccadic spike potential

This study examined the behavior of the presaccadic spike potential (SP) in 20 normal, right-handed subjects for self-paced 10 degree saccades along vertical, horizontal and oblique meridians. The SP was recorded differentially between posterior parietal sites and a linked ear reference. The SP amplitude showed clear directional tuning properties with the maximum response prior to saccades directed in an oblique, downward and contralateral direction. The minimum response was obtained for upward saccades. The data were fitted to a model consisting of 3 components: (1) a constant component reflecting saccadic amplitude; (2) a component with narrow directional tuning that is modeled from properties of frontal eye field neurons in monkeys; and (3) a component with broad directional tuning that is designed to reflect directional tuning properties of potentials originating from horizontal and vertical saccade generators, motoneurons and extraocular muscles. The narrowly tuned mechanism is sufficient to encode the direction of saccades. One surprising finding, though, was that the broadly tuned mechanism was necessary and sufficient to account for differences in SP amplitude as a function of electrode laterality. Application of this model approach to published data for periorbital SP, recorded between periorbital and parietal sites (G. W. Thickbroom and F. L. Mastaglia, Electroencephalogr. Clin. Neurophysiol., 64 (1986) 211-214), suggested that this potential represents a broadly tuned mechanism with directional tuning opposite the parietal SP. These data indicate that the periorbital and parietal SPs represent activation of different networks of central generators.

Defective motion processing in children with cerebral visual impairment due to periventricular white matter damage

Aim  We sought to characterize visual motion processing in children with cerebral visual impairment (CVI) due to periventricular white matter damage caused by either hydrocephalus (eight individuals) or periventricular leukomalacia (PVL) associated with prematurity (11 individuals).

A Comparison of the Pupillary and Cardiovascular Effects of Various Mydriatic Agents in Preterm Infants

We conducted a randomized, masked study of pupillary dilating capabilities and associated cardiovascular effects of three solutions. Thirty-four babies less than 1500 grams at birth were studied at six to eight weeks. Group A (n = 10) received phenylephrine (PE) 2.5% and tropicamide 1.0%; Group B (n = 10) PE 2.5%, tropicamide 0.5%, and cyclopentolate 0.5%, Group C (n = 10) PE 1.0% and tropicamide 1.0%; Group D (n = 4) saline 0.9%. One drop was placed in each eye and repeated five minutes later. Pupillary dilation was measured with a metric ruler by direct observation at one hour. Blood pressure (BP) and heart rate (HR) were monitored, using an oscillometer, immediately prior to the instillation of the drops and at five-minute intervals, for 60 minutes. BP and HR increased transiently in all groups receiving mydriatics but returned to baseline values in 25 minutes. This increase was significant in Groups A and B (2.5% PE: p less than 0.02). Group D (saline) showed no change in BP or HR. Postdrop pupillary size was largest in Group A but the differences were not significant. On exposure to bright light, the pupillary size in Group C was significantly smaller than Groups A or B (7.35 +/- 0.59 mm, 7.23 +/- 0.38 mm and 6.75 +/- 0.57 mm in Groups A, B and C, p less than .01). Nevertheless, dilation was sufficient to allow appropriate examination in all infants (pupillary diameter greater than 6.0 mm). Solutions containing 2.5% PE are most effective for use in LBW infants, but produce cardiovascular effects. Solutions containing 1% PE provide adequate dilation with minimum cardiovascular effects.

Optic glioma associated with Beckwith-Wiedemann syndrome

A 6-year-old boy with decreased vision was found to have Beckwith-Wiedemann syndrome with an associated glioma involving the intracranial optic nerves, chiasm, and optic tracts. The association of this syndrome with visceral and central nervous system neoplasms is discussed.

Cortical Evoked Potentials Preceding Voluntary Saccadic Eye Movements

An antecedent potential (AP) and a positive spike (SP) potential that precede saccades have been described in normal human subjects using evoked potential techniques. These responses can be recorded over parietal cortex (P3, P4) with linked ear reference. The AP-SP was examined in two patients with progressive supranuclear palsy (PSP) and in two patients with congenital ocular motor apraxia. The response was grossly abnormal in both PSP patients and in one of the congenital ocular motor apraxia patients. This indicates that pre-saccadic cortical activity may be altered in these patients. Thus, these potentials may be of diagnostic value in the evaluation of supra-nuclear disorders of ocular motility.

Observations on Transsynaptic Changes in Acquired Horner's Syndrome

Hydroxyamphetamine eyedrops may fail to dilate the affected pupil of an infant who has acquired a preganglionic Horners syndrome; that is, the pupil will behave pharmacologically as if there were a postganglionic lesion, even though the damage is known to be in the preganglionic neuron. 1