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Neurological Sciences : Official... Dec 2002Sporadic olivopontocerebellar atrophy (OPCA) is a neurodegenerative disorder that presents a wide clinical spectrum. Motor neuron disease (MND) is characterized by a...
Sporadic olivopontocerebellar atrophy (OPCA) is a neurodegenerative disorder that presents a wide clinical spectrum. Motor neuron disease (MND) is characterized by a selective degeneration of motor neurons. A 60-year-old man developed slurred speech and unsteadiness of gait. He had also noticed difficulty in holding his head upright and shoulder weakness. The disease had a rapid progression. At the age of 63 years, magnetic resonance imaging supported a diagnosis of OPCA, and a diagnosis of MND was suggested by clinical and electrophysiological findings. He also had upward gaze palsy. A muscular biopsy showed sporadic ragged red and Cox deficient fibers. The present case could define a unique disorder, as the occasional occurrence of two degenerative disorders appears unlikely.
Topics: DNA-Binding Proteins; Deglutition Disorders; Electromyography; Gait Ataxia; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Motor Neuron Disease; Muscle Fibers, Skeletal; Olivopontocerebellar Atrophies; Viral Proteins
PubMed: 12522682
DOI: 10.1007/s100720200049 -
Annals of Neurology Aug 1988A cerebral cortical cholinergic reduction in dominantly inherited olivopontocerebellar atrophy (OPCA) was recently described. Although the magnitude of the cholinergic...
A cerebral cortical cholinergic reduction in dominantly inherited olivopontocerebellar atrophy (OPCA) was recently described. Although the magnitude of the cholinergic reduction was similar to that observed in Alzheimer's disease (AD), none of the OPCA patients was reported to have been demented. We now describe a comprehensive neuropsychological assessment of 11 patients from one of the OPCA pedigrees which we examined biochemically. Detailed neuropsychological testing disclosed previously unrecognized deficits in verbal and nonverbal intelligence, memory, and frontal system function which were positively correlated with the severity of cerebellar ataxia. However, our OPCA patients appeared to be at most only mildly disabled by their cognitive impairment and scored within or close to the normal range on a simple mental status screening examination. This, as well as an absence of any aphasia, apraxia, or agnosia, contrasts with the profile and severity observed in advanced AD dementia, characterized by a similar cortical cholinergic deficit. This finding also suggests that cholinergic reduction may explain only part of the pathophysiology underlying the dementia of AD.
Topics: Adult; Alzheimer Disease; Cognition Disorders; Depressive Disorder; Female; Humans; Intelligence Tests; Male; Neuropsychological Tests; Olivopontocerebellar Atrophies; Parasympathetic Nervous System; Psychomotor Performance; Spinocerebellar Degenerations
PubMed: 3178175
DOI: 10.1002/ana.410240205 -
Neurology Nov 1989One-hundred cases of olivopontocerebellar atrophy, type 1, were found and studied in the Iakut population of Eastern Siberia. The disease followed a slowly progressive...
One-hundred cases of olivopontocerebellar atrophy, type 1, were found and studied in the Iakut population of Eastern Siberia. The disease followed a slowly progressive course of cerebellar insufficiency caused by degeneration in the cerebellar cortex, nuclei pontis, and inferior oliva. The disorder shows an autosomal dominant pattern of inheritance with a lower penetrance in females. The disease spread from a small region in the Aldan valley 200 to 300 years ago.
Topics: Adolescent; Adult; Aged; Ethnicity; Female; Genes, Dominant; Humans; Male; Middle Aged; Nervous System; Olivopontocerebellar Atrophies; Pedigree; Siberia; Spinocerebellar Degenerations
PubMed: 2812335
DOI: 10.1212/wnl.39.11.1527 -
Orphanet Journal of Rare Diseases Jul 2011Pontocerebellar Hypoplasia (PCH) is group of very rare, inherited progressive neurodegenerative disorders with prenatal onset. Up to now seven different subtypes have... (Review)
Review
Pontocerebellar Hypoplasia (PCH) is group of very rare, inherited progressive neurodegenerative disorders with prenatal onset. Up to now seven different subtypes have been reported (PCH1-7). The incidence of each subtype is unknown. All subtypes share common characteristics, including hypoplasia/atrophy of cerebellum and pons, progressive microcephaly, and variable cerebral involvement. Patients have severe cognitive and motor handicaps and seizures are often reported. Treatment is only symptomatic and prognosis is poor, as most patients die during infancy or childhood. The genetic basis of different subtypes has been elucidated, which makes prenatal testing possible in families with mutations. Mutations in three tRNA splicing endonuclease subunit genes were found to be responsible for PCH2, PCH4 and PCH5. Mutations in the nuclear encoded mitochondrial arginyl- tRNA synthetase gene underlie PCH6. The tRNA splicing endonuclease, the mitochondrial arginyl- tRNA synthetase and the vaccinia related kinase1 are mutated in the minority of PCH1 cases. These genes are involved in essential processes in protein synthesis in general and tRNA processing in particular. In this review we describe the neuroradiological, neuropathological, clinical and genetic features of the different PCH subtypes and we report on in vitro and in vivo studies on the tRNA splicing endonuclease and mitochondrial arginyl-tRNA synthetase and discuss their relation to pontocerebellar hypoplasia.
Topics: Animals; Arginine-tRNA Ligase; Brain; Child; Child, Preschool; Disease Models, Animal; Endoribonucleases; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Mutation; Olivopontocerebellar Atrophies; Radiography
PubMed: 21749694
DOI: 10.1186/1750-1172-6-50 -
The Journal of the Association of... Feb 1999
Topics: Humans; Molecular Biology; Olivopontocerebellar Atrophies; Peripheral Nervous System Diseases; Saccades
PubMed: 10999111
DOI: No ID Found -
Neuroscience Letters Oct 1993We measured metabolic precursors and breakdown products of phosphatidylcholine (choline, glycerophosphocholine (GPC) and phosphatidylethanolamine (ethanolamine,...
We measured metabolic precursors and breakdown products of phosphatidylcholine (choline, glycerophosphocholine (GPC) and phosphatidylethanolamine (ethanolamine, glycerophosphoethanolamine (GPE)) as well as the amino acid serine, a precursor of phosphatidylserine, in four morphologically unaffected cerebral cortical areas obtained at autopsy from 14 patients with dominantly inherited olivopontocerebellar atrophy (OPCA) and 13 controls matched for age and postmortem interval. As compared with the controls, mean GPE levels were elevated by 49-57% in frontal and parietal cortices of OPCA brains whereas concentrations of ethanolamine were significantly reduced in temporal, occipital and parietal cortex (-40 to -54%). This resulted in increased GPE/ethanolamine ratios (+80 to +146%). GPC levels were significantly increased (by 53%) in the frontal cortex of OPCA patients relative to controls. Free serine levels were reduced by 20 to 28% in frontal, parietal, temporal, and occipital cortices. These abnormalities in phospholipid metabolite levels in OPCA resemble those seen in Alzheimer's disease, although the changes in GPC are less pronounced. These changes in phospholipid metabolism in OPCA cerebral cortex, a brain area spared from neurodegenerative changes, points to generalized disturbances in cellular membrane function in this disease.
Topics: Adult; Cerebral Cortex; Choline; Ethanolamines; Female; Humans; Male; Membranes; Olivopontocerebellar Atrophies; Phospholipids; Serine
PubMed: 8272265
DOI: 10.1016/0304-3940(93)90291-r -
Revue Neurologique 1992Nine cases of multiple system atrophy and 1 case of autosomal dominant olivopontocerebellar atrophy (neuropathological diagnosis) were retrospectively examined for the... (Review)
Review
Nine cases of multiple system atrophy and 1 case of autosomal dominant olivopontocerebellar atrophy (neuropathological diagnosis) were retrospectively examined for the presence of oligodendroglial inclusions. Clinical diagnosis in the first 9 cases had been: olivopontocerebellar atrophy (3 cases), atypical Parkinson's disease (2 cases), Shy-Drager syndrome (2 cases) and multiple system atrophy (1 case); one of the patients could not be included in any of the above mentioned groups. The oligodendroglial inclusions were argyrophilic and located in the cytoplasm around the nucleus. They were revealed by Bodian's method in all cases of multiple system atrophy. They were not found in the case of autosomal dominant olivopontocerebellar atrophy. They were labelled by anti-ubiquitin antibodies, and were negative with anti-tau antibodies. At electron microscopy, they consisted of rectilinear profiles coated with a fuzzy material (diameter: 20-33 nm); this aspect was compatible with microtubules. Oligodendroglial inclusions were prominent in regions selectively vulnerable in multiple system atrophy (tegmentum pontis, putamen, inferior olives, substantia nigra and cerebellar white matter), even in those areas where neuronal loss or fascicular atrophy were minimal or absent. They were also observed in regions considered to be spared in multiple system atrophy, such as the motor cortex and the corpus callosum. Argyrophilic oligodendroglial inclusions are an early and specific marker of multiple system atrophy. It is suggested that autosomal dominant olivopontocerebellar atrophy lacking oligodendroglial inclusions does not belong to multiple system atrophy.
Topics: Adult; Aged; Atrophy; Brain; Female; Humans; Inclusion Bodies; Male; Middle Aged; Oligodendroglia; Olivopontocerebellar Atrophies; Shy-Drager Syndrome
PubMed: 1332174
DOI: No ID Found -
Neurology Jul 1995In sporadic cases of olivopontocerebellar atrophy (OPCA), to determine whether local cerebral blood flow (lCBF) is reduced, whether lCBF is coupled to local cerebral...
OBJECTIVE
In sporadic cases of olivopontocerebellar atrophy (OPCA), to determine whether local cerebral blood flow (lCBF) is reduced, whether lCBF is coupled to local cerebral metabolic rate for glucose (lCMRglc), and whether lCBF measurements are potentially useful in diagnosing OPCA.
DESIGN
Positron emission tomography was used with [15O]H2O to measure lCBF and with [18F]fluorodeoxyglucose to measure lCMRglc in 17 patients with OPCA and 21 normal control subjects.
RESULTS
In OPCA patients, lCBF was significantly decreased in the cerebellum, but not in the cerebral cortex, basal ganglia, thalamus, or brainstem. In the same patients, lCMRglc was significantly decreased in the cerebellum and brainstem, where the largest changes were observed, and also in the cerebral cortex, basal ganglia, and thalamus. The ratio of lCBF to lCMRglc, an indicator of the coupling of blood flow to metabolism, was similar in OPCA patients and normal subjects for all regions except the brainstem, where the ratio was marginally decreased in OPCA patients. Using logistic discriminant analysis to assess the ability of lCBF and lCMRglc to differentiate OPCA patients from normal subjects, we found the cross-validated sensitivity of absolute lCMRglc as a predictor of OPCA was 82% with a corresponding specificity of 71%; the sensitivity of absolute lCBF was 71% and the specificity 76%.
CONCLUSIONS
In sporadic cases of OPCA, lCBF is reduced in the cerebellum, CBF remains coupled to lCMRglc, and the lCBF pattern is a useful predictor of the diagnosis.
Topics: Aged; Brain; Cerebrovascular Circulation; Female; Glucose; Humans; Male; Middle Aged; Olivopontocerebellar Atrophies; Tomography, Emission-Computed
PubMed: 7617196
DOI: 10.1212/wnl.45.7.1345 -
Pediatric Pathology & Laboratory... 1995
Topics: Cerebellum; Congenital Disorders of Glycosylation; Humans; Infant; Kidney Glomerulus; Liver; Male; Olivopontocerebellar Atrophies; Purkinje Cells
PubMed: 8736608
DOI: 10.3109/15513819509026951 -
Internal Medicine (Tokyo, Japan) Jun 1994We investigated the survival of patients with multiple system atrophy (MSA) in a follow-up study of 59 patients admitted to Nagoya University Hospital between 1976 and... (Comparative Study)
Comparative Study
We investigated the survival of patients with multiple system atrophy (MSA) in a follow-up study of 59 patients admitted to Nagoya University Hospital between 1976 and 1991. They consisted of 24 patients with olivopontocerebellar atrophy (OPCA), 25 with Shy-Drager syndrome (SDS) and 10 with striatonigral degeneration (SND). The mean age at onset was 54 years, the 3-year survival rate from onset was 90%, and the 6-year survival rate was 54%. Comparison of survival curve by clinical type revealed poorer survival in SDS and SND than in OPCA cases. Although in OPCA, SND and SDS the pathological alterations of the central nervous system are known to be very similar, characterized as MSA, the present study suggests that the earlier and the more severe the involvement of the autonomic nervous system, and to a lesser extent the striatonigral system, the poorer the prognosis may be.
Topics: Adult; Age Factors; Age of Onset; Aged; Brain Diseases; Corpus Striatum; Female; Humans; Male; Middle Aged; Olivopontocerebellar Atrophies; Prognosis; Retrospective Studies; Shy-Drager Syndrome; Substantia Nigra; Survival Rate
PubMed: 7919616
DOI: 10.2169/internalmedicine.33.321