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Journal of Neurology, Neurosurgery, and... Mar 1994The presence of reflex myoclonus in response to touching and pin-pricking the wrist or stretching the fingers and to photic stimulation was assessed in 24 patients with...
The presence of reflex myoclonus in response to touching and pin-pricking the wrist or stretching the fingers and to photic stimulation was assessed in 24 patients with a presumed diagnosis of olivopontocerebellar atrophy (OPCA) and in 30 age matched control subjects. Reflex myoclonus to soma-esthetic stimulation was found in 23 patients and in none of the controls. Photic myoclonus was present in 12 patients and in none of the controls. Electrophysiological study of the reflex myoclonus showed enhanced (> 10 microV) somatosensory evoked potentials and an associated reflex electromyographic discharge (C-wave) in 15 patients. These findings indicate that reflex myoclonus is common in OPCA and probably of cortical origin.
Topics: Atrophy; Brain; Electromyography; Evoked Potentials, Somatosensory; Female; Humans; Kinesthesis; Male; Middle Aged; Myoclonus; Olivopontocerebellar Atrophies; Photic Stimulation; Physical Stimulation; Reflex; Sensation; Tomography, X-Ray Computed
PubMed: 8158179
DOI: 10.1136/jnnp.57.3.316 -
Archives of Neurology Sep 1990We used standardized neuropsychological measures of intellectual, cognitive, psychomotor, and emotional functioning to compare 39 patients with olivopontocerebellar...
We used standardized neuropsychological measures of intellectual, cognitive, psychomotor, and emotional functioning to compare 39 patients with olivopontocerebellar atrophy and 25 normal controls of similar age. The patients reflected greater depression, anxiety, and subjective emotional discomfort than did the control subjects. While 4 of the patients had below-normal IQ scores (Wechsler Adult Intelligence Scale [WAIS-R] Full-Scale IQ [FSIQ] less than 80), their clinical histories suggested lifelong functioning at such levels. As a group, the patients were not abnormal in general intellectual functioning and related cognitive abilities (WAIS-R FSIQ, mean [+/- SD], 93.46 +/- 13.19; Wechsler Memory Scale mental quotient, 108.95 +/- 17.43). These scores were lower than those of the normal controls (WAIS-R FSIQ, 113.72 +/- 12.68; mental quotient, 127.80 +/- 12.40); however, the controls were a highly educated group with intelligence levels that were higher than those of the average population. Moreover, when education and motor dysfunction were statistically covaried, no significant differences between the patients and the normal controls were apparent on the cognitive and intellectual tasks. Further analysis of specific memory performance in a subgroup of patients and controls matched for age, sex, and education yielded findings that were comparable with the overall group analysis. We conclude that motor dysfunction and depressed mood could leave patients with olivopontocerebellar atrophy appearing to be impaired in memory, even demented, when they are not.
Topics: Adult; Aged; Educational Status; Female; Humans; Intelligence; Male; Memory; Middle Aged; Neuropsychological Tests; Olivopontocerebellar Atrophies; Spinocerebellar Degenerations; Wechsler Scales
PubMed: 2396941
DOI: 10.1001/archneur.1990.00530090071015 -
Neurology Nov 1986Brain tissue was obtained promptly after death from a patient with autosomal dominant olivopontocerebellar atrophy and studied by immunocytochemistry and a Golgi...
Brain tissue was obtained promptly after death from a patient with autosomal dominant olivopontocerebellar atrophy and studied by immunocytochemistry and a Golgi technique. Antiglutamic acid decarboxylase showed severe loss of Purkinje cells and their terminals in the dentate nucleus. Stains for neuron-specific enolase (NSE) and microtubule-associated proteins (MAP) confirmed the integrity of the dentate nucleus. Basket and stellate cells revealed secondary changes, but Golgi neurons were intact. Methods for NSE and MAP disclosed dendritic alterations and loss of neurons in the basis pontis and inferior olivary nuclei. Golgi impregnation of Purkinje cells showed loss of major dendrites, paucity of spiny branchlets, and axonal expansions.
Topics: Aged; Cerebellum; Cerebral Cortex; Glutamate Decarboxylase; Humans; Immunochemistry; Male; Microtubule-Associated Proteins; Middle Aged; Olivopontocerebellar Atrophies; Phosphopyruvate Hydratase; Purkinje Cells; Spinocerebellar Degenerations
PubMed: 3463885
DOI: 10.1212/wnl.36.11.1478 -
Ophthalmology Jan 1993Olivopontocerebellar atrophy is an uncommon disorder with variable clinical manifestations that affects the cerebellum, the spinocerebellar tracts, and other structures...
BACKGROUND
Olivopontocerebellar atrophy is an uncommon disorder with variable clinical manifestations that affects the cerebellum, the spinocerebellar tracts, and other structures of the brainstem. A deficiency of glutamate dehydrogenase, which results in an excess of glutamate, has been suggested to play a role in the pathogenesis of olivopontocerebellar atrophy. In experimental animals, toxic levels of glutamate are known to cause a selective loss of the b-wave on electroretinographic (ERG) testing and a degeneration of the inner retinal layers. One of the subtypes of olivopontocerebellar atrophy, type II, according to Harding's classification, is associated with retinal degeneration.
METHODS
The authors describe the ophthalmologic and ERG findings in a family with olivopontocerebellar atrophy type II. Histopathologic study of an eye from a 6-year-old family member who died of severe neurologic deterioration secondary to olivopontocerebellar atrophy type II was performed.
RESULTS
Electroretinographic changes may be present in affected family members who are entirely asymptomatic and have a normal ophthalmologic evaluation. The changes on the ERG in one patient suggest that cone dysfunction is one of the subtle changes that may be seen in olivopontocerebellar atrophy type II. Our ERG results did not show a selective loss of the b-wave but instead showed a loss of both the a-wave and b-wave in affected family members. Results of light and electron microscopic examination showed diffuse and extensive degeneration of the photoreceptors involving both rods and cones, the most prominent changes being present in the macula. An amorphous debris, presumably degenerated photoreceptors, was noted between the outer nuclear layer and retinal pigment epithelium.
CONCLUSION
Patients with olivopontocerebellar atrophy type II have photoreceptor abnormalities as revealed in abnormal ERGs seen in many patients and histopathologic study of an autopsy eye from an affected 6-year-old boy. Our results do not support the hypothesis that glutamate toxicity may be responsible for the development of retinal degeneration in this condition.
Topics: Adult; Bruch Membrane; Child; Child, Preschool; Electroretinography; Female; Humans; Male; Middle Aged; Olivopontocerebellar Atrophies; Pedigree; Photoreceptor Cells; Pigment Epithelium of Eye; Retinal Degeneration
PubMed: 8433819
DOI: 10.1016/s0161-6420(93)31702-1 -
Journal of Neuropathology and... Jun 1998Efforts to classify the hereditary ataxias by their clinical and neuropathological phenotypes are troubled by excessive heterogeneity. Linkage analysis opened the door... (Review)
Review
Efforts to classify the hereditary ataxias by their clinical and neuropathological phenotypes are troubled by excessive heterogeneity. Linkage analysis opened the door to a new approach with the methods of molecular biology. The classic form of autosomal recessive ataxia, Friedreich's ataxia (FA), is now known to be due to an intronic expansion of a guanine-adenine-adenine (GAA)-trinucleotide repeat. The autosomal dominant ataxias such as olivopontocerebellar atrophy (OPCA), familial cortical cerebellar atrophy (FCCA), and Machado-Joseph disease (MJD) have been renamed the spinocerebellar ataxias (SCA). Specific gene loci are indicated as SCA-1, SCA-2, SCA-3, SCA-4, SCA-5, SCA-6, and SCA-7. In 5 of them (SCA-1, SCA-2, SCA-3, SCA-6, and SCA-7), expanded cytosine-adenine-guanine (CAG)-trinucleotide repeats and their abnormal gene products cause the ataxic condition. The most common underlying loci for olivopontocerebellar atrophy (OPCA) are SCA-1 and SCA-2, although other genotypes may be added in the future. A major recent advance was the identification of the gene for SCA-3 and MJD, and the high prevalence of this form of autosomal dominant ataxia. In FA and the SCA with expanded CAG-trinucleotide repeats, clinical and neuropathological severity are inversely correlated with the lengths of the repeats. Anticipation in the dominant ataxias can now be explained by lengthening of the repeats in successive generations. Progress is being made in the understanding of the pathogenesis of FA and SCA as the absent or mutated gene products are studied by immunocytochemistry in human and transgenic murine brain tissue. In FA, frataxin is diminished or absent, and an excess of mitochondrial iron may cause the illness of the nervous system and the heart. In SCA-3, abnormal ataxin-3 is aggregated in neuronal nuclei, and in SCA-6, a mutated alpha1A-calcium channel protein is the likely cause of abnormal calcium channel function in Purkinje cells and in the death of these neurons.
Topics: Friedreich Ataxia; Genotype; Humans; Olivopontocerebellar Atrophies; Phenotype
PubMed: 9630233
DOI: 10.1097/00005072-199806000-00001 -
Annals of Neurology Sep 1991The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine...
The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine receptors in this entity. We describe a patient with olivopontocerebellar atrophy whose clinical presentation was levodopa-responsive parkinsonism in whom pathological examination disclosed pronounced nigral cell loss with no striatal damage. Autoradiographic labeling with 3H-spiperone showed normal densities of D2 dopamine striatal receptors. These data show that indistinguishable nigral, presynaptic parkinsonism occurs in patients with idiopathic Parkinson's disease and in patients with olivopontocerebellar atrophy, and also how a favorable response to levodopa is neither synonymous with idiopathic Parkinson's disease, nor does it exclude multiple-system, atrophy-related parkinsonism.
Topics: Aged; Autoradiography; Humans; Male; Olivopontocerebellar Atrophies; Parkinson Disease; Receptors, Dopamine
PubMed: 1952831
DOI: 10.1002/ana.410300318 -
Brain & Development 1995A family with olivopontocerebellar atrophy is presented. Out of 7 siblings two male and one female were involved at a similar age of 5 years. Early onset of the disease...
A family with olivopontocerebellar atrophy is presented. Out of 7 siblings two male and one female were involved at a similar age of 5 years. Early onset of the disease is striking. The index case presented with progressively increasing choreiform movements and cerebellar signs. Magnetic resonance imaging morphology revealed the diagnosis.
Topics: Adolescent; Brain; Child; Consanguinity; Female; Humans; Magnetic Resonance Imaging; Male; Nuclear Family; Olivopontocerebellar Atrophies
PubMed: 7625548
DOI: 10.1016/0387-7604(95)00005-v -
Journal of Neuropathology and... Sep 1990Oligodendroglial microtubular tangles (OMT), a distinctive oligodendroglial change, was observed in seven of eight cases of olivopontocerebellar atrophy (OPCA). This...
Oligodendroglial microtubular tangles (OMT), a distinctive oligodendroglial change, was observed in seven of eight cases of olivopontocerebellar atrophy (OPCA). This change was a well-defined glassy cytoplasmic structure showing intense argyrophilia. OMT were distributed in the brain stem, cerebellum, and basal ganglia where severe neurodegenerative changes were consistently observed. In 45 control cases, no OMT were found regardless of the presence or absence of neurological disorders. The OMT were immunostained by anti-tubulin antibodies, but no other antibodies reacted with them. Each OMT consisted of a meshwork of randomly oriented fibrils studded with granular and fuzzy material. The fibrillary elements were between 20 and 30 nm in diameter. It is suggested that OMT are primarily composed of altered microtubules, and are related to the neurodegenerative process of OPCA.
Topics: Humans; Immunohistochemistry; Microscopy, Electron; Microtubules; Oligodendroglia; Olivopontocerebellar Atrophies; Silver; Staining and Labeling
PubMed: 1703225
DOI: 10.1097/00005072-199009000-00007 -
Movement Disorders : Official Journal... Mar 1996Olivopontocerebellar atrophy (OPCA) is widely accepted as part of the neuropathological spectrum of multiple system atrophy (MSA). The distribution of affected sites in...
Olivopontocerebellar atrophy (OPCA) is widely accepted as part of the neuropathological spectrum of multiple system atrophy (MSA). The distribution of affected sites in the olivopontocerebellar (OPC) system and their interrelationship remain poorly understood due to lack of quantitative studies. To further investigate the OPC pathology in MSA, we performed a morphometric analysis of 20 MSA cases and eight healthy controls. In the MSA cases, mean neuronal cell densities were significantly reduced in (medial and dorsal) accessory and principal inferior olives, pontine nuclei, cerebellar vermis (except nodulus), and hemispheres. Inferior olives and pontine nuclei were more severely affected than cerebellar Purkinje cells in most cases. Cerebellar Purkinje cells were more severely depleted in vermis rather than in hemisphere. There was a poor topographic correlation between neuronal cell loss in inferior olives and cerebellar cortex. These results suggest a primary degeneration of olivopontine nuclei and cerebellar Purkinje cells in OPCA. Inferior olives, pontine nuclei and cerebellar cortex were all significantly more severely affected in cases with a pure or predominating cerebellar syndrome (OPCA type, n = 4) compared to those with pure or predominating parkinsonism (SND type, n = 14). However, although cerebellar signs had been noted in life in only six cases, morphometry revealed OPCA in 17 of the 20 MSA brains.
Topics: Adult; Aged; Brain; Cell Count; Cerebellum; Cerebral Cortex; Female; Humans; Male; Middle Aged; Nerve Degeneration; Neurons; Olivary Nucleus; Olivopontocerebellar Atrophies; Parkinson Disease; Pons; Purkinje Cells
PubMed: 8684385
DOI: 10.1002/mds.870110207 -
Annals of Neurology Dec 1996We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic...
We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic presynaptic terminals in 4 patients with multiple system atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control subjects. Specific binding in the striatum was significantly reduced in the multiple system atrophy patients as compared with the normal control group, with average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the putamen (p = 0.009). Smaller reductions were found in the sporadic olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p = 0.05) and 24% in the putamen (p = 0.11). Mean blood-to-brain [11C]dihydrotetrabenazine transport (K1) was significantly different between groups only in the cerebellum, with values for the sporadic olivopontocerebellar atrophy group diminished compared with the normal control group. Cerebellar K1 was not significantly decreased in the multiple system atrophy group. The finding of reduced striatal VMAT2 in sporadic olivopontocerebellar atrophy patients suggests nigrostriatal pathology, indicating that some may later develop symptomatic extrapyramidal disease.
Topics: Adult; Aged; Autonomic Nervous System Diseases; Basal Ganglia Diseases; Biological Transport; Cerebellar Diseases; Corpus Striatum; Female; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Neuropeptides; Olivopontocerebellar Atrophies; Presynaptic Terminals; Tetrabenazine; Tomography, Emission-Computed; Vesicular Biogenic Amine Transport Proteins; Vesicular Monoamine Transport Proteins
PubMed: 9007093
DOI: 10.1002/ana.410400610