Donald F. Farrell

Giant axonal neuropathy caused by industrial chemicals: neurofilamentous axonal masses in man.

Symmetrical polyneuropathy developed in two patients after they had been in contact with acrylamide and methyl n-butyl ketone, respectively. In sural nerve biopsy material from both patients, electron microscopy showed frequent focal axonal swellings containing masses of neurofilaments. Some axons undergoing axonal degeneration also were seen. These morphologic features are identical to those produced in experimental animals after exposure to these chemicals and are similar to those found in n-hexane neuropathy and in the three reported cases of giant axonal neuropathy. Sural nerve biopsy is an important diagnostic test in identifying cases of peripheral neuropathy caused by these chemicals.

Ictal patterns of neocortical seizures monitored with intracranial electrodes : correlation with surgical outcome

Summary: Purpose: Numerous factors have been analyzed in attempts to predict the outcome of surgical resections in patients with neocortical epilepsy. We examined the correlation between surgical outcome and electrocorticographic features of neocortical ictal patterns.

Individual variation in human motor-sensory (rolandic) cortex.

Eloquent cortex is generally identified using a variety of techniques including direct electrical stimulation to identify motor-sensory, language, and memory cortex and somatosensory evoked potentials to identify motor-sensory cortex. It is important that these areas of cortex be identified so as to prevent damage during the course of neurosurgical procedures. Seventy epilepsy patients undergoing evaluation for epilepsy surgery with chronically implanted subdural grids were retrospectively studied using both somatosensory evoked potentials and direct electrical stimulation. Direct electrical stimulation of motor-sensory cortex elicited responses over a larger area than did somatosensory evoked potentials. A great deal of individual variation was identified using both techniques. The results presented here support previous conclusions that the concept of homunculus somatotopy (point to point representation) of the motor-sensory cortex be abandoned and that of functional mosaicism of the motor-sensory cortex replace the earlier model. The individual variation found in the human motor-sensory cortex will require a continuation of “brain mapping” to identify eloquent cortex so that these vital areas will be spared during neocortical neurosurgical procedures.

Herpes simplex neuropathy

Article abstract—Atypical facial pain and permanent sensory loss in the second and third divisions of the trigeminal nerve developed in a patient who had had multiple attacks of herpes simplex neuralgia over a period of 8 years. Intravenous cytosine arabinoside failed to prevent a recurrence of the vesicular eruption, but carbamazepine produced symtomatic pain relief. This case demonstrates that herpes simplex can closely mimic herpes zoster as a cause of postherpetic neuralgia and suggests a possible etiology of atypical facial pain and/or trigeminal sensory neuropathy in some patients.

Symptomatic capillary telangiectasis of the brainstem without hemorrhage Report of an unusual case

THE CLASSIFICATION of vascular hamartomas of the brain is well established.1J The classification used in this report includes: [l] capillary telangiectases, [ 21 cavernous angiomas, and [3] venous and arteriovenous angiomas. Capillary telangiectases are usually small and incidental findings which do not cause symptoms during life.2-4 Only occasional cases of capillary telangiectases resulting in neurologic symptoms have been reported. Hemorrhage into the malformation has invariably been present in these patients (see Discussion). The purpose of this communication is to report an unusual and unique case of a capillary telangiectasis which, by its large size and strategic location, resulted in progressive neurologic symptoms over a period of years.

Characterization of lysosomal hydrolases that are elevated in Gaucher's disease.

Abstract Although Gauchers disease occurs in three distinct forms with greatly varying degrees of severity, there is no correlation between the clinical course of the disease and levels of residual glucocerebrosidase, the fundamental enzymatic deficiency. In an effort to study secondary changes which might contribute to the pathology of Gauchers disease, homogenates of spleen, liver, and brain tissue, as well as serum from patients with Gauchers disease were analyzed for their content of a number of lysosomal enzymes. Extracts of 8 Gaucher spleens contained 3- to 4-fold increases in acid phosphatase activity as well as 5-to 10-fold increases in galactocerebrosidase 5 activity. The marked elevation in galactocerebrosidase activity in Gaucher spleen was documented using various [ 3 H]galactose labeled galactocerebrosides as substrates and with [ 3 H]galactose labeled lactocerebroside under the “lactosylceramidase I” 5 assay conditions established by Suzuki (Tanaka, H., and Suzuki, K., 1975, J. Biol. Chem. , 250 , 2324–2332) that measure galactocerebrosidase activity specifically in the presence of G mi -ganglioside β-galactosidase. Acid phosphatase determinations using extracts of liver from a case of infantile, neuropathic Gauchers disease revealed a 2-fold elevation in this activity, whereas brain acid phosphatase activity in this case was similar to that of control tissue. Separation of hexosaminidase A and B activities on DEAE-Sephadex columns indicated increases in both forms of the enzyme in Gaucher tissue with the major increase occurring in the hexosaminidase B component. Glucuronidase and nonspecific esterase were observed to be elevated approximately 2-fold. However, not all lysosomal enzyme activities were increased. Levels of splenic arylsulfatase A and B, α-arabinosidase, sphingomyelinase, α-mannosidase, and G mi -ganglioside β-galactosidase activities in Gaucher spleen were unremarkable. G mi -ganglioside β-galactosidase was measured using 4-methylumbelliferyl-β- d -galactopyranoside and [ 3 H]galactose labeled lactocerebroside under the specific assay conditions described by Suzuki for the determination of “lactosylceramidase II” activity. Although levels of arylsulfatase A and B in Gaucher spleen were similar to those of control tissue, arylsulfatase A activity was markedly reduced (20% of control) in homogenates of brain from the case of infantile (type 2) Gauchers disease. The metabolic and pathologic consequences of these changes in lysosomal enzymes in Gauchers disease are discussed.

Phenotypic Variability Due to a Novel Glu292Lys Variation in Exon 8 of the BEST1 Gene Causing Best Macular Dystrophy

OBJECTIVE To study the phenotypic characteristics of patients with a novel p.E292K mutation in BEST1. METHODS Affected individuals underwent ophthalmic examination and testing that included photography, autofluorescence, optical coherence tomography, and electrophysiological testing. Their DNA was analyzed for BEST1 mutations. RESULTS Five patients aged 5 to 59 years who expressed the p.E292K mutation in BEST1 were identified in 3 families. Electro-oculographic light-rise was subnormal in all probands and carriers. Carriers had normal findings from fundus examination, multifocal electroretinography, and visual acuity, and were emmetropic or myopic. Only probands had hyperopia and fundus findings typical of Best macular dystrophy. Optical coherence tomography of vitelliform lesions demonstrated retinal pigment epithelium elevation without subretinal fluid; atrophic lesions exhibited disruption of the hyperreflective outer retina-retinal pigment epithelium complex. Intense hyperautofluorescence correlated with the vitelliform lesion. CONCLUSIONS Patients with the Glu292Lys variation in BEST1 exhibit intrafamilial and interfamilial phenotypic variability. A disproportionate fraction (26%) of Best disease-causing mutations occurs in exon 8, suggesting that the portion of protein encoded by this exon (amino acids 290-316) may be especially important to bestrophins function. Relatively good visual acuity with vitelliform lesions can be explained by preservation of the outer retina, demonstrated by optical coherence tomography. Clinical Relevance A novel mutation in this region of BEST1 carries implications for disease pathogenesis.

Adult dystonic lipidosis Clinical, histologic, and biochemical findings of a neurovisceral storage disease

A 43-year-old man presented with splenomegaly and a 20-year history of a neurological disorder that included vertical supranuclear ophthalmologic, mild dementia, and a movement disorder. Adult dystonic lipid sis was diagnosed from the clinical picture and demonstration of foamy and sea-blue histiocytes in bone marrow. Ultrastructural patterns in cytolysosomes suggested accumulation of neutral fat and phospholipids. Liver content of this monoacylglycerol) phosphate was increased, probably because the number of liposome had increased. Sphingomyelinase activity was normal in cultured skin fibroblasts. Juvenile and adult dystonic lipidosis form a clinically, histological, and biochemically distinct neurovisceral storage disease that differs from Niemann-Pick disease.

Retinal toxicity to antimalarial drugs: chloroquine and hydroxychloroquine: a neurophysiologic study.

Over a 30-year period, 29 cases of antimalarial retinal toxicity were studied in a tertiary medical center. Three cases of chloroquine and 26 cases of hydroxychloroquine toxicity were studied. A number of these cases were studied before multifocal electroretinogram (mfERG) became available and show how insensitive the corneal full-field flash ERG is in diagnosing this condition. It became apparent that even mfERG failed to diagnose some early patients who either had an abnormal fundus examination or Humphrey’s automated perimetry (protocol 10-2). The age of the patient and the number of years of exposure to antimalarial drugs appears to be directly related to the development of this retinal disorder. All three of the “quantitative retinal tests” recommended in the “Guidelines” – mfERG, spectral domain optical coherence tomography (SD-OCT), and autofluorescence – fail to identify all of the cases of antimalarial retinal toxicity. mfERG is probably the most sensitive of the three tests, but no direct comparison has yet been accomplished. None of these “quantitative tests” appear to provide the “gold standard” necessary for detecting early hydroxychloroquine retinal toxicity.

Electrophysiologic observations in the classical form of Pelizaeus‐Merzbacher disease

In a 20-year-old patient with the classic form of Pelizaeus-Merzbacher disease, electroencephalograms during wakefulness were moderately diffusely abnormal, and an overnight polygraphic sleep recording showed distorted nonrapid eye movement sleep patterns without vertex sharp waves, K-complexes, spindles, or positive occipital sharp transients. Rapid eye movement sleep could be identified. Cerebral responses evoked by light flashes, clicks, and electric stimulation of the median nerves were abnormal.