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Autonomic Neuroscience : Basic &... Dec 2005The clinical significance of evaluating autonomic nervous system functions in the early stages of olivopontocerebellar atrophy (OPCA) has been investigated in 13 OPCA... (Clinical Trial)
Clinical Trial
The clinical significance of evaluating autonomic nervous system functions in the early stages of olivopontocerebellar atrophy (OPCA) has been investigated in 13 OPCA out-patients (7 males and 6 females, mean age: 51.0 years). We have employed measurements of blood pressure, plasma norepinephrine (NE), CVR-R, low-frequency power/high-frequency power ratio (L/H), high-frequency power (HF) score and heart rate (HR) monitoring using Holter ECG recording for evaluation of CVR-R. We have also carried out urodynamic examinations, focusing on the possible existence of bladder dysfunction. Although no significant changes were noted between control and OPCA groups concerning HR, CVR-R, L/H, plasma levels of norepinephrine and systolic blood pressure, HF (high-frequency power) (ms(2)), especially at night time, invariably showed a significant decline in OPCA groups. All OPCA patients who showed a decreased circadian HF also exhibited a tendency towards urinary bladder dysfunction. The present results appear to relate to disorder of the parasympathetic autonomic nervous system and neuromuscular dysfunction in the lower urinary tract. In conclusion, HRV (heart rate variability) analysis is a useful and safe tool and a keen predictor for evaluating functional states of autonomic nervous activity, especially in the early stages of OPCA. This study has also suggested the possible efficacy of urodynamic measurements in OPCA patients as an indicator of neuromuscular dysfunction in the lower urinary tract and of parasympathetic malfunction.
Topics: Adult; Autonomic Nervous System; Blood Pressure; Brain; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Norepinephrine; Olivopontocerebellar Atrophies; Urodynamics
PubMed: 16289940
DOI: 10.1016/j.autneu.2005.09.004 -
Olivopontocerebellar atrophy studied by positron emission tomography and magnetic resonance imaging.Journal of the Neurological Sciences Aug 1994We examined 9 patients with olivopontocerebellar atrophy (OPCA) using positron emission tomography and magnetic resonance imaging (MRI). Regional cerebral blood flow and...
We examined 9 patients with olivopontocerebellar atrophy (OPCA) using positron emission tomography and magnetic resonance imaging (MRI). Regional cerebral blood flow and oxygen metabolism were compared with the findings in 10 normal age-matched volunteers. The volumes of the basis pontis and the cerebellar hemispheres were quantitated by MRI to assess the relationship between morphological changes of the pons or cerebellum and the cerebellar circulation and metabolism. In the patients with OPCA, cerebellar hemispheric blood flow and oxygen metabolism were significantly lower than in the normal volunteers. Pontine volume showed a significant correlation with the cerebellar blood flow and the metabolic rate of oxygen. In contrast, the cerebellar hemispheric volume showed no correlation with either of these parameters. Our results suggest that the disruption of pontocerebellar pathway may contribute to the reduction of both blood flow and oxygen metabolism in the cerebellum of OPCA and that detection of cerebellar circulatory impairment without marked cerebellar atrophy by neuroimaging may be suggestive of OPCA.
Topics: Adult; Brain Stem; Cerebellum; Cerebrovascular Circulation; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olivopontocerebellar Atrophies; Oxygen; Pons; Reference Values; Tomography, Emission-Computed
PubMed: 7964889
DOI: 10.1016/0022-510x(94)90242-9 -
The Tohoku Journal of Experimental... Feb 2012Generation of induced pluripotent stem (iPS) cells from somatic cells of patients represents a powerful tool for disease modeling, and they may have a wide range of...
Generation of induced pluripotent stem (iPS) cells from somatic cells of patients represents a powerful tool for disease modeling, and they may have a wide range of applications in cell therapies. Olivopontocerebellar atrophy (OPCA) is a rare and debilitating neurologic disease of insidious onset, characterized by atrophy of the cerebellum pons and inferior olivary nuclei with concomitant ambulation deficits and dyscoordination. Here, we report the generation of iPS cells from skin fibroblasts of a 56-year-old female patient with familial OPCA. OPCA is classified in the autosomal dominant ataxia that is also named spinocerebellar ataxia (SCA) 7. The disease allele of SCA7 gene of the patient contains 45 CAG trinucleotide repeats, the number of which is larger than the normal repeat number (4 to 36 CAG repeats). The OPCA-iPS cells were generated via ectopic expression of four transcription factors: OCT4, SOX2, KLF4 and c-MYC. The OPCA-iPS cells expressed the pluripotency markers, and they can be differentiated into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells. Therefore, the OPCA-iPS cells offer an unprecedented cell model to investigate disease mechanisms, discover novel drugs, and develop new therapies for OPCA.
Topics: Alkaline Phosphatase; Ataxin-7; Base Sequence; Cell Differentiation; Cell- and Tissue-Based Therapy; Cells, Cultured; DNA Fingerprinting; DNA Primers; Female; Fibroblasts; Genes, myc; Histocompatibility Testing; Humans; Immunohistochemistry; Induced Pluripotent Stem Cells; Karyotyping; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Middle Aged; Molecular Sequence Data; Nerve Tissue Proteins; Neurons; Octamer Transcription Factor-3; Olivopontocerebellar Atrophies; Real-Time Polymerase Chain Reaction; SOXB1 Transcription Factors; Sequence Analysis, DNA; Skin; Transcription Factors; Trinucleotide Repeat Expansion
PubMed: 22301348
DOI: 10.1620/tjem.226.151 -
Journal of Neurology, Neurosurgery, and... Dec 1993
Topics: Autonomic Nervous System Diseases; Cerebellum; Humans; Movement Disorders; Olivopontocerebellar Atrophies; Parkinson Disease; Pyramidal Tracts; Shy-Drager Syndrome
PubMed: 8270919
DOI: 10.1136/jnnp.56.12.1239 -
Lancet (London, England) Sep 1993
Topics: Central Nervous System Diseases; Humans; Olivopontocerebellar Atrophies; Parkinson Disease
PubMed: 8103165
DOI: 10.1016/0140-6736(93)91789-o -
Acta Neuropathologica 1995Neuropathological investigations performed on autopsied brain and spinal cords from 11 patients showed that spinocerebellar ataxia type 1 (SCA-1) can be distinguished...
Neuropathological investigations performed on autopsied brain and spinal cords from 11 patients showed that spinocerebellar ataxia type 1 (SCA-1) can be distinguished from autosomal dominant spinocerebellar ataxia linked to SCA-2 and -3 loci on chromosomes 12 and 14, spinopontine, and the multisystem atrophies. The major diagnostic criteria were: absence of significant pars compacta nigral and locus coeruleus lesions, severe degeneration of olivocerebellar and dentatorubral pathways, extensive loss of Purkinje cells with partial sparing of flocculonodular lobes, severe atrophy of specific cranial nerve nuclei, mostly the third and 12th, extensive loss of motor neurons in anterior horns and Clarke's columns, and lack of oligodendroglial or neuronal cytoplasmic cytoskeletal inclusions. None of the brains displayed any significant immunoreactivity for the amyloid precursor protein or beta-amyloid peptide throughout the cortex. In conclusion, the type and neuroanatomical distribution of structural lesions were similarly reproduced in all probands at the end stage of SCA-1, to the point that they appeared to constitute a unique phenotype.
Topics: Adolescent; Adult; Atrophy; Brain; Child; Chromosome Mapping; Chromosomes, Human, Pair 6; Dentate Gyrus; Humans; Immunohistochemistry; Middle Aged; Mutation; Neural Pathways; Olivopontocerebellar Atrophies; Phenotype; Red Nucleus; Spinal Cord; Spinocerebellar Degenerations
PubMed: 8615077
DOI: 10.1007/BF00318569 -
Neuropathology and Applied Neurobiology Jun 1992A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with...
A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities.
Topics: Aged; Cytoskeletal Proteins; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Male; Middle Aged; Nerve Fibers; Nerve Tissue Proteins; Nervous System Diseases; Oligodendroglia; Olivopontocerebellar Atrophies; Silver Staining
PubMed: 1630577
DOI: 10.1111/j.1365-2990.1992.tb00786.x -
Neuropathology and Applied Neurobiology Feb 1994Purkinje cells were examined in three familial cases of olivopontocerebellar atrophy (OPCA) by means of the Golgi method, and neurofilament and calcium-binding protein...
Purkinje cells were examined in three familial cases of olivopontocerebellar atrophy (OPCA) by means of the Golgi method, and neurofilament and calcium-binding protein immunocytochemistry. Reduced dendritic arborizations, as seen with different techniques, early formation of axonal spheroids, and abnormal accumulation of phosphorylated neurofilament epitopes in dendrites, somata and axonal spheroids, together with limited formation of proximal spine-like protrusions were the main changes in Purkinje cells. These lesions are unlikely to be the consequence of anterograde degeneration secondary to olivary atrophy, as postulated by some investigators, but probably represent primary damage to Purkinje cells in patients with OPCA. Reduced dendritic arborizations result in a decrease of receptor sites for parallel fibres and deprive granule cells of their main targets. Abnormal accumulation of neurofilaments in somata, dendrites and axonal spheroids may contribute to an abnormal transport and may impair protein turnover in the distal regions of Purkinje cells.
Topics: Adult; Brain; Calbindins; Cerebellum; Dendrites; Female; Humans; Immunohistochemistry; Male; Middle Aged; Olivopontocerebellar Atrophies; Parvalbumins; Purkinje Cells; S100 Calcium Binding Protein G; Spinal Cord; Staining and Labeling
PubMed: 7516051
DOI: 10.1111/j.1365-2990.1994.tb00955.x -
Annals of Neurology Jun 1988We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (lCMRGlc) in 30 patients with olivopontocerebellar atrophy... (Comparative Study)
Comparative Study
We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (lCMRGlc) in 30 patients with olivopontocerebellar atrophy (OPCA). Perceptual analysis was used to examine the speech disorders, and rating scales were devised to quantitate the degree of ataxia and spasticity in the speech of each patient. lCMRGlc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). PET studies revealed marked hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem of OPCA patients compared with 30 control subjects. With data normalized to the cerebral cortex, a significant inverse correlation was found between the severity of ataxia in speech and the lCMRGlc within the cerebellar vermis, cerebellar hemispheres, and brainstem, but not within the thalamus. No significant correlation was found between the severity of spasticity in speech and lCMRGlc in any of these structures. The findings support the view that the severity of ataxia in speech in OPCA is related to the functional activity of the cerebellum and its connections in the brainstem.
Topics: Adult; Brain; Deoxyglucose; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Male; Olivopontocerebellar Atrophies; Organ Specificity; Reference Values; Speech Disorders; Spinocerebellar Degenerations; Tomography, Emission-Computed
PubMed: 3261572
DOI: 10.1002/ana.410230604 -
Neuromuscular Disorders : NMD Jan 1995Two sisters with infantile OPCA plus spinal muscular atrophy (SMA) are reported. Both showed severe hypotonia and psychomotor delay from birth, and in addition,...
Exclusion of the gene locus for spinal muscular atrophy on chromosome 5q in a family with infantile olivopontocerebellar atrophy (OPCA) and anterior horn cell degeneration.
Two sisters with infantile OPCA plus spinal muscular atrophy (SMA) are reported. Both showed severe hypotonia and psychomotor delay from birth, and in addition, nystagmoid eye movements and vision impairment were evident. Cerebellar hypoplasia with cystic dilatation was seen by neuro-imaging methods. Pathoanatomically, a marked cerebellar hypoplasia and neuronal loss in the basal ganglia, brainstem and anterior horns were found in the deceased girl. Linkage studies with polymorphic markers of the region 5q11.2-q13.3 flanking the gene locus for infantile SMA showed identical parental haplotypes in the patients and their older healthy sister. It can be concluded that the gene locus for infantile SMA on chromosome 5q is not responsible for infantile OPCA plus anterior horn cell degeneration in the described family which might apply to this disorder in general.
Topics: Chromosome Mapping; Chromosomes, Human, Pair 5; Family; Female; Genetic Linkage; Haplotypes; Humans; Infant; Olivopontocerebellar Atrophies; Pedigree; Spinal Muscular Atrophies of Childhood
PubMed: 7719136
DOI: 10.1016/0960-8966(94)e0025-4