Headache and CNS white matter abnormalities associated with gluten sensitivity.

The authors describe 10 patients with gluten sensitivity and abnormal MRI. All experienced episodic headache, six had unsteadiness, and four had gait ataxia. MRI abnormalities varied from confluent areas of high signal throughout the white matter to foci of high signal scattered in both hemispheres. Symptomatic response to gluten-free diet was seen in nine patients.

Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction.

PURPOSE: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin-attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin. METHODS: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro-oculography, and flash and pattern visual evoked potentials, was undertaken. RESULTS: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro-oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30-Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level. CONCLUSION: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.

Visual field defects associated with vigabatrin therapy.

OBJECTIVE: To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug vigabatrin and to characterise the features of visual dysfunction found. METHODS: Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16 patients with epilepsy unexposed to vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. RESULTS: Of 31 assessable patients treated with vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12 patients (39%) in whom a definite bilateral field defect was found, possibly caused by vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking vigabatrin, although this returned towards normal when vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. CONCLUSIONS: Treatment with vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of vigabatrin on the retina and seemed to persist if the drug was withdrawn.

Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.

A large English family with autosomal dominant segregation of presenile dementia, ataxia and other neuropsychiatric features is described. Diagnoses of demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome have been attributed to particular individuals at different times. An Irish family, likely to be part of the same kindred, is also described, in which diagnoses of multiple sclerosis, dementia, corticobasal degeneration and new variant CJD have been considered in affected individuals. Molecular genetic studies have enabled the classification of this disease at the molecular level as one of the group of inherited prion diseases, with the substitution of valine for alanine at codon 117 of the prion protein gene (PRNP). Only three other kindreds have been described world-wide with this mutation and only limited phenotypic information has been reported. Here we describe the phenotypic spectrum of inherited prion disease (PrPA117V). The diversity of phenotypic expression seen in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopathological syndrome. Indeed, inherited prion disease should be excluded by PRNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new variant CJD.

Remembered saccades with variable delay in Parkinson's disease.

The effect of increasing delay on the metrics of remembered saccades was studied in 10 subjects with mild Parkinson's disease, none of whom was receiving treatment with L-dopa, and nine age-matched control subjects. Delays of 1 msec, 250 msec, 1000 msec, 2500 msec, and 5000 msec were used, and reflexive saccades used as a control condition. Results were analyzed for the gain of the primary saccade and the accuracy of the final eye position (FEP gain). Reflexive saccades were normal in subjects with Parkinson's disease, but remembered saccades showed marked hypometria of primary saccade gain at all delays. FEP gain was unimpaired in Parkinson's disease, and primary saccade gain and FEP gain did not vary as a function of delay. Hypometria of primary saccades is compatible with dysfunction in striato-collicular inhibitory pathways in Parkinson's disease, arising as a functional consequence of dopamine deficiency in the basal ganglia. Maintenance of an accurate FEP gain suggests no deficit in oculomotor spatial working memory in Parkinson's disease, at least at delays of up to 5 sec.

Colour identification and colour constancy are impaired in a patient with incomplete achromatopsia associated with prestriate cortical lesions.

We have examined visual functions, including colour vision, in a patient with bilateral cortical lesions involving mainly the fusiform and lingual gyri, areas known to be involved in the central processing of chromatic stimuli. The patient has near normal (6/9) acuity, and his responses to tests of binocular function and spatial vision are normal, as are his discrimination of changes in target speed and surface lightness. He does, however, exhibit minor losses in the upper visual field, mild prosopagnosia and topographical agnosia, all conditions commonly associated with cerebral achromatopsia. Colour matches and spectral response data establish that his cone photoreceptors have normal spectral characteristics and his spectral sensitivity measured against a white background reveals normal postreceptoral chromatic function. The patient's colour discrimination for differences in wavelength, hue or saturation is, however, impaired and his colour naming is significantly disturbed, particularly for blues and greens. We have determined the areas of the chromaticity chart that correspond to his naming categories for surface colours, and show that changes in illuminant cause him to alter the names of surface colours in a manner consistent with the changes in their chromaticities. Other subjects with normal or congenital red-green deficient colour vision make many fewer name changes under changes in illuminant. We conclude that the patient's colour constancy is impaired as a consequence of abnormal central processing of colour vision.

An effect of structured backgrounds on smooth pursuit eye movements in patients with cerebral lesions.

The oculomotor smooth pursuit system is driven by the slip of the target image upon the retina arising from errors in matching eye and target velocities. However, pursuit of an object moving against a structured background causes most retinal flow to be in the direction opposite to target movement. Central mechanisms allow these distracting signals to be overridden effortlessly. To isolate the anatomical substrate of this capacity we studied the effect of the presence of a structured background upon smooth pursuit in 26 patients with focal cerebral lesions. In normal control subjects, studies confirmed that a background has little effect upon pursuit. Eye movements were recorded by the scleral search coil method or by infra-red oculography. The target was a bright spot moving horizontally in a triangular waveform of amplitude +/- 11.25 degrees visual angle, at either 10, 20, 30 or 36.5 degrees/s. Data were collected in darkness and with a structured background: 14 patients showed a significant reduction of gain with a structured background, while the remaining 12 showed little or no effect. Comparison of the location of the cerebral lesions in these two groups suggested that lesions in the inferior parietal cortex (area 40) or in white matter containing parieto-frontal connections result in disruption of pursuit in the presence of a background.

Repetitive paroxysmal nystagmus and vertigo.

A 55-year-old woman had paroxysms of vertigo and visual blurring associated with complex combined torsional, horizontal, and vertical nystagmus. These episodes occurred regularly at 2-minute intervals, each attack lasting for 15 seconds. Between attacks, there was a much finer asymptomatic nystagmus whose components were in the opposite direction to those associated with the paroxysmal attacks. A brain MRI revealed an arteriovenous malformation in close proximity to the left vestibular nucleus, with evidence of previous bleeding. Caloric testing demonstrated a left-sided vestibular paresis. We suggest that neurons in this patient's damaged left vestibular nucleus are usually underactive but regularly produce pathologic brief bursts of hyperactivity causing episodic reversal and gross exacerbation of her resting nystagmus. Treatment with low-dose carbamazepine was successful in abolishing both the paroxysms of nystagmus and the symptoms of vertigo and visual disturbance.

Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high dose.

A randomised double-blind placebo-controlled trial of intravenous methylprednisolone versus oral methylprednisolone at equivalent high dose was carried out on 35 patients with an acute relapse of multiple sclerosis (MS). After baseline evaluation each was randomly allocated to oral treatment and intravenous placebo or intravenous treatment and oral placebo, receiving 500 mg of methylprednisolone for five consecutive days and with reassessment at days five and twenty-eight. There was no significant difference in response when disability or functional scores were compared in the two groups. Adverse effects were minor and equally distributed. In this study oral treatment with methylprednisolone was as effective as intravenous treatment in acute relapse of MS.

Achromatopsia in the aura of migraine.

A 49 year old woman reported an attack of transient neurological dysfunction associated with unilateral headache. A prominent feature of the aura was a period of complete achromatopsia, so that the visual scene was experienced in monochrome. The episode developed to include features of prosopagnosia and spatial agnosia before resolving completely. Other episodes of transient neurological dysfunction followed at regular intervals until prophylactic antimigrainous therapy was initiated. Four vessel cerebral angiography and MRI of the brain were normal. Possible causes of this unusual migrainous aura are discussed with reference to current concepts of cerebral localisation.

An investigation of the ability of the human visual system to encode spatial phase relationships.

Evidence is presented that the human visual system contains broad-band mechanisms capable of encoding the spatial phase relationship between a fundamental spatial frequency and higher frequencies up to its third harmonic. Compounds of a fundamental and its harmonics above the third become progressively more difficult to discriminate by means of phase information alone. Measurements were also made of the amount of spatial summation found in various detection and phase discrimination tasks using simple or compound gratings composed of a fundamental frequency (F) and its third harmonic (3F). A task requiring the discrimination of the phase relationship between a low contrast (F) and a high contrast (3F) shows less spatial summation than does a task requiring the detection of the (F) component by itself. A simple model is advanced to account for these results qualitatively. The model is based upon the hypothesis that the human visual system analyses the retinal image in patches of a range of sizes and that phase relationships may be discerned only between components that are detected by different elements of the same patch mechanism.

The analysis of spatial phase in amblyopia.

Anomalies in the contrast sensitivity functions of amblyopes are usually insufficient to account for the degree of visual deficit found in more complex tasks. Evidence is presented that many of the defects of amblyopic vision arise from a failure to encode the spatial phase relationships between detectable components of different spatial frequencies. It appears that visual processing in amblyopia occurs over a more truncated frequency range than is implied by detection experiments.