Experimental allergic encephalomyelitis. Passive transfer by the intraocular injection of sensitized cells.

Experimental allergic encephalomyelitis is a disease of cell-mediated immunity and can be transferred passively to virgin recipients by lymphoid cells from sensitized donors. The rabbit eye contains myelinated medullary rays that can be visualized ophthalmoscopically. Intraocular injection of autologous lymph node cells from myelin basic protein (BP)-immunized rabbits into the vitreous leads to readily visualized optic neuritis while injection of cells from adjuvant immunized control rabbits does not. Microscopical study confirmed the presence of myelin destruction in recipients of cells from BP-sensitized donors. This eye chamber technique provides a simple model for the study of demyelination in vivo under direct observation.

Spatial vision in Alzheimer's disease. General findings and a case report.

Visual contrast sensitivity to sinusoidal gratings of five spatial frequencies was measured in 15 patients with Alzheimer's disease and in eight control subjects. Contrast sensitivity thresholds were elevated at all frequencies in 14 patients compared with control subjects. The 15th patient was unique: she had an impairment in object and face recognition so severe that she could not recognize her husband visually. Her sensitivity to low and intermediate frequencies was markedly reduced in relation to that of other patients, whereas her sensitivity to the highest frequency tested equaled theirs. These observations emphasize the importance of low spatial frequency information for visual object and face recognition.

Pupil dilation to tropicamide is not specific for Alzheimer disease.

BACKGROUND: The extent of pupil dilation after instillation of a dilute tropicamide solution was proposed as a noninvasive neurobiological diagnostic test for Alzheimer disease (AD). Pupils in patients with AD dilated 23% vs only 5% in control subjects. OBJECTIVE: To determine whether pupil dilation in response to tropicamide distinguishes patients with AD from control subjects without dementia. METHODS: There were 50 patients with AD and 51 control subjects; no participant had primarily ocular pathological conditions or took drugs that affected cholinergic tone. All participants received 1 drop of 0.01% tropicamide in 1 eye and 1 drop of 0.9% saline solution in the other eye in random order. Pupil measurements were obtained using a pupil and corneal reflection tracking system (RK-426 PC system, ISCAN Inc, Burlington, Mass) that illuminated the eye with a low-level infrared source and measured pupil diameters, fixation, and light level every 16.7 milliseconds during each 30-second-measurement. Pupil measurements were obtained from each eye at baseline and 5, 10, 15, and 30 minutes after drop instillation. RESULTS: The increase in pupil size after tropicamide instillation was equal between patients with AD and control subjects. The mean (+/- SD) pupil diameter increased from 4.5 +/- 1.1 to 5.5 +/- 1.1 mm after 30 minutes in patients with AD and from 4.7 +/- 0.9 to 5.8 +/- 0.9 mm in control subjects. Anisocoria and the mean rate of dilation did not differ between patients with AD and control subjects. Eye color and corneal moisture did not affect these results. The extent of pupil dilation in patients with AD was not related to clinical estimates of dementia severity. CONCLUSION: Pupil dilation in response to instillation of 0.01% tropicamide is not useful as an antemortem diagnostic test for AD.

Neuropathic findings in oculopharyngeal muscular dystrophy. A report of seven cases and a review of the literature.

We describe seven patients with clinical evidence of oculopharyngeal muscular dystrophy. Four of these patients were members of the same Italian-American family. The age at onset was after the fourth decade in all patients. All seven patients had extraocular muscle involvement, and six of the seven patients had clinical, electrophysiological, and/or pathological evidence of neuropathy in addition to features that were suggestive of myopathy. An autopsy was performed on one patient. We discuss the significance of the concurrence of neuropathic features with oculopharyngeal muscular dystrophy in relation to these patients and previously reported cases.

The one-and-a-half syndrome--a unilateral disorder of the pontine tegmentum: a study of 20 cases and review of the literature.

The one-and-a-half syndrome is a clinical disorder of extraocular movements characterized by a conjugate horizontal gaze palsy in one direction plus an internuclear ophthalmoplegia in the other. The syndrome is usually due to a single unilateral lesion of the paramedian pontine reticular formation or the abducens nucleus on one side (causing the conjugate gaze palsy), with interruption of internuclear fibers of the ipsilateral medial longitudinal fasciculus after it has crossed the midline from its site of origin in the contralateral abducens nucleus (causing failure of adduction of the ipsilateral eye). Twenty cases are reported; 14 had multiple sclerosis.

Vertical gaze ophthalmoplegia: selective paralysis of downgaze.

A 58-year-old man developed a selective supranuclear paralysis of downgaze, which was repeatedly documented until it completely resolved after 6 weeks. At autopsy, there was a bilaterally symmetric old infarct in the mesodiencephalic region. In common with four previous similar reports, the lesion involved structures bordering the dorsomedial aspect of the red nucleus. This same region has been implicated in the control of vertical eye movements in recent neuroanatomic and physiologic experiments in nonhuman primates.

Contrast visual testing in neurovisual diagnosis.

Contrast visual testing (CVT) is a psychophysical visual test of undetermined diagnostic capability in many neurovisual disorders. CVT of 32 controls and 39 patients was compared with the pattern visual evoked response (PVER) from each group. CVT was more sensitive than PVER in detecting visual dysfunction in pseudotumor cerebri and subclinical optic neuritis and showed potential in distinguishing papilledema from pseudopapilledema. PVER was more sensitive than CVT in detecting subclinical visual dysfunction in MS and optic nerve compression. Neither was abnormal in asymptomatic Leber's optic neuropathy. In nonorganic visual loss, CVT data were variable and inconsistent, supporting this diagnosis; PVER was consistently normal. Although in certain disease conditions, each detected subclinical visual dysfunction, neither CVT nor PVER provided specific information leading to an etiologic diagnosis.

Misdiagnosis of spasm of the near reflex.

A bilateral sixth nerve palsy portends serious disease of the central nervous system and precipitates extensive patient studies. Spasm of the near reflex, characterized by intermittent convergence, accommodation, and miosis, is a functional disturbance. Five patients with hysterical spasm of the near reflex erroneously diagnosed as a bilateral sixth nerve palsy are reported. The pupillary sign, intense miosis on attempted lateral gaze, is emphasized as an important clue to the correct diagnosis. Despite extensive investigation, no disease of the central nervous system was found. Neurotic or hysterical features were evident in every patient.

The pattern electroretinogram: a long-term study in acute optic neuropathy.

We report a 2-year prospective study of the electroretinographic response to reversal of checkerboard patterns (P-ERG) obtained in 63 eyes with acute optic nerve lesions. The aim of the study was to document the value of P-ERG regarding diagnosis and prognosis of four types of optic neuropathy: optic neuritis, compressive or hereditary optic atrophy, and traumatic optic neuropathy. We documented visual loss by neuro-ophthalmologic examination and recorded pattern-reversal visual evoked potentials (P-VEP). The initial P-ERG was normal to large- and medium-sized checks in 89% and the P-VEP abnormal in 94% of eyes with acute optic nerve lesions. Forty-six eyes were followed for up to 2 years. Two groups emerged. Group A (n = 17) gradually and permanently had significant reduction of the P-ERG to three separate check sizes. All 17 had no improvement in acuity better than 20/100, retained centrocecal scotomas, and developed optic atrophy. In group B (n = 29) the P-ERG remained within normal limits to one or more check sizes. Twenty-two of these eyes recovered acuity to 20/25 or better and had resolution of the field defect. The data showed that P-VEP was superior to P-ERG in diagnosis of acute and chronic optic nerve lesions. However, significant reduction of the b-wave of the P-ERG to three separate check sizes correlated closely with failure of visual recovery and the eventual development of severe optic atrophy, suggesting a prognostic value for P-ERG in optic neuropathy.

A study of B and T cells in multiple sclerosis.

Peripheral blood T and B lymphocytes were enumerated using E and EAC red blood cell rosetting techniques. The percentage of EAC-binding cells in peripheral blood of multiple sclerosis patients is elevated (31.7 plus or minus 2.4S.E.M.) when compared with the percentage in healthy controls (18.5 plus or minus 1.1 S.E.M.). The total T cell percentage is not significantly lower in multiple sclerosis than in controls, but fewer T cells in patients with multiple sclerosis are able to bind 10 or more red blood cells.

Chronic progressive external ophthalmoplegia (CPEO): clinical, morphologic, and biochemical studies.

We studied skeletal muscles from eight chronic progressive external ophthalmoplegia patients with ragged-red fibers (group A), five CPEO patients without ragged-red fibers (group B), and five controls. The EM morphometric fraction of structurally abnormal mitochondria was increased in group A, and there was a similarly increased fraction of normal-appearing mitochondria in group B. State 3 respiration and uncoupled respiration were severely decreased in both groups. The morphometric mitochondrial fraction and respiratory functions were inversely related in all three groups. The cytochrome content in group A was normal; cytochromes b and cc1 were decreased in group B. These studies point to a central role of mitochondrial dysfunction in all types of CPEO, but the basic abnormalities remain to be elucidated.

The judgement of absence in neglect.

The usual way of looking at neglect is by investigating how neglect patients fail to detect that something is there. In this study, we look at how neglect patients correctly detect that something is not there. Patients with parietal lesions (11 with and 16 without neglect) and 23 control subjects indicated whether a dot target was or was not present in a geometrical display. While control subjects were consistently (and unexpectedly) faster in the no-dot than in the dot condition, the distinguishing response time pattern of right parietal patients with neglect was not--as one might expect--a relatively longer response time to left vs right targets, but a longer response time to target absence vs presence. This may be due to a serial search or, alternatively, it might result from double-checking for target absence, produced by lowered perceptual confidence. Since this "wariness" about stimulus absence seems to operate in parallel with neglect patients' denial of the deficit, we conclude that the response time pattern observed in this study could be used as a measure of subjective (un)awareness of neglect.

The pattern visual evoked potential and pattern electroretinogram in drusen-associated optic neuropathy.

Sixteen patients (29 eyes) with optic disc drusen were studied prospectively for clinical and electrophysiologic evidence of impaired optic nerve conduction. Abnormalities were detected in the following areas: visual acuity, eight (28%) of 29 eyes; kinetic visual field, 22 (76%) of 29 eyes; results of Farnsworth-Munsell 100-Hue test, 12 (41%) of 29 eyes; and flash visual evoked potential, 13 (54%) of 24 eyes. Simultaneous pattern visual evoked potentials and results of pattern electroretinograms were recorded. The P100 latency of the pattern visual evoked potential was prolonged in 41% of eyes. The P50 and N95 components of the pattern electroretinogram were also analyzed. The P50 amplitude was reduced in only four (17%) of 24 eyes. The most common abnormality was a reduction in amplitude or the absence of the N95 component in 19 (79%) of 24 eyes, reflecting ganglion cell dysfunction. The data support mounting evidence that the P50 and N95 components of the pattern electroretinogram have different retinal origins.

In vivo test for myelinotoxicity of cerebrospinal fluid.

A quantitative double blind procedure is described to test the myelinotoxicity of cerebrospinal fluid (SSF) by using optic nerves of Xenopus tadpoles as an in vivo model of a myelinated CNS tract. Only 0.5 ml of unconcentrated CSF is needed for a test and the result is known in 5 days. Groups of 8-10 Xenopus tadpoles received a subcutaneous injection of 12-13 muL of a coded CSF sample or of a saline control solution around the right optic nerve. After 48 h, whole mounts of the right optic nerves were prepared and the slides were randomized before using a differential-interference contrast microscope to count the myelin lesions. The myelinotoxicity of a CSF sample was considered positive (+) when it produced significantly higher (P less than 0.01) counts than the saline control. When P was less than 0.05, the counts were recorded as borderline (+/-) and it was negative (-) when P was greater than 0.05.

Vascular occlusions in the eye from cardiac myxomas.

Vascular occlusion in the eyes from cardiac myxomas was diagnosed in two cases, belatedly in one and not until after death in the other. Suspicion of a myxomatous origin should be aroused by the combination of unexplained retinal (or choroidal) vascular disease occurring with multifocal neurological symptoms and with systemic symptoms suggesting atypical subacute bacterial endocarditis. The first patient had unilateral retinal artery occlusion by embolic material believed to have been myxomatous. Removal of the cardiac myxoma resulted in disappearance of this material (although the eye remained blind). The second patient who had had evidence of retinal artery occlusion in the clinical course of her multisystemic disease was found at autopsy to have extensive myxomatous involvement of the posterior ciliary arteries and of the choroidal arteries of both eyes and of the retinal artery in one eye.

Acquired color vision defects in retrobulbar neuritis.

We used the Farnsworth-Munsell 100 Hue Test to study the incidence of acquired color vision defects in 16 patients with unilateral and and seven patients with bilateral retrobulbar optic neuritis whose visual acuity had recovered to 6/12 (20/40) or better. We recorded the visual-evoked response to a pattern stimulus on the same day. All 30 affected eyes showed an excessive number of errors on Farnsworth-Munsell 100 Hue testing. The number of errors increased with greater residual optic nerve damage. One false-positive and two false-negative visual-evoked responses were found.

Optic canal fractures after rhinologic surgery.

In two women, 26 and 24 years old, respectively, polytomography revealed optic canal fractures. The investigation of visual loss after orbital or otolaryngologic surgery included tomography of the optic canals to rule out compression of the intracanalicular optic nerve.

Central retinal artery occlusion.

Data regarding the etiology and subsequent course of 54 patients with an occlusion of the central retinal artery included the following: of 44 patients over 40 years of age at the time of the central retinal artery occlusion, eight (18%) had cerebrovascular accidents, but only two patients (5%) had a stroke clearly related to the vessels involving the affected central retinal artery. Five patients (11%) had occlusive disease of the ipsilateral internal carotid artery; two of these had cerebral involvement later or simultaneously. Ten of the older patients had cardiac valvular disease and presumed embolic occlusion of the central retinal artery. Associated medical disorders were common. Of the ten patients under 40 years of age, six occlusions were secondary to atrial myxoma, mitral insufficiency with Marfan's syndrome, polycythemia, hypercoagluopathy, hypertension, and orbital compression. Four had no apparent etiology at onset and were in good health many years later.

Adrenoleukodystrophy with disease of the eye and optic nerve.

Adrenoleukodystrophy is an X-chromosome-linked recessive disease characterized by primary atrophy of the adrenal glands with or without Addison's disease and low plasma cortisol levels, and a degeneration of white matter of the central nervous system with blindness. In suspected cases of adrenoleukodystrophy an impaired rise in plasma cortisol levels after adrenocorticotrophin stimulation may be diagnostic. With the electron microscope, pathognomonic intracytoplasmic lamellar inclusions have been seen in adrenal cortical cells, peripheral nerve Schwann's cells, testicular interstitial cells, and in macrophages of the brain. Adrenoleukodystrophy appears to be a genetically determined lipid storage disease with an error in membrane sterol metabolism. A 10-year-old boy with adrenoleukodystrophy had visual loss, a prominent early symptom. The ocular abnormality consisted of a disproportionate loss of nerve fibers from the macular region. No intracytoplasmic lamellar inclusions were identified in cells representing macrophages within the optic nerve. They contained myelin debris suggestive of end-stage disease.

Optic atrophy and visual loss in craniometaphyseal dysplasia.

Four members of one family had craniometaphyseal dysplasia. Two of the four had severe optic atrophy with profound loss of vision as a complication of this disorder. Optic nerve decompression attempted in one patient may have caused a reduction in the vision of that eye. Eight years later this patient underwent craniofacial surgery uneventfully for contouring of her facial and cranial bones, but osteotomies and intracranial surgery were specifically avoided because of bony over-growth in the foramen magnum region.