Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 60 year-old man was admitted to our hospital because of gait disturbance and dizziness. At 57 years of age, he noticed his walking unstable. After then, he had dizziness due to orthostatic hypotension, urinary difficulty, loss of livid, and forgetfulness. Neurological examination revealed he had severe orthostatic hypotension, cerebellar ataxia, dysarthria, hyperreflexia of four limbs, myoclonus of right leg, and atonic bladder. His brain CT showed cerebellar atrophy. Thereafter he had recurrent syncopic attacks. His gait disturbance progressed steadily, so he became bedridden. In his terminal stage, his limbs showed rigidity. About 3 years later he died of pneumonia and sepsis. At autopsy brain weighted 1,230 g. Glossly the putamens was bilaterally shrunken, the color of the substantia nigra and locus ceruleus became pale. Base of the pons and the cerebellum were atrophic. Microscopical examination confirmed the degeneration of striato-nigral and olivo-ponto-cerebellar systems without Lewy body. In the spinal cord there was depletion of neuronal cells in the intermediolateral nuclei and Onufrowitz nuclei. In addition to the conventional neuropathological staining methods, we performed the immunohistochemical studies using monoclonal antibody against synthetic peptide of beta protein which detected senile plaque of every stages with formic acid pretreatment, and compared to the modified Bielschowsky method and Congo red method. Our case showed many very primitive and primitive senile plaque in neocortices and hippocampal region. A few neurofibrally tangle were seen in hippocampus. We supposed our case might combine multiple system atrophy and Alzheimer' pathology.
 ...
PMID:[An autopsy case of multiple system atrophy with many senile plaques]. 262 28

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized clinically by varying degrees of Parkinsonism, cerebellar ataxia and autonomic dysfunction and pathologically by degeneration in the substantia nigra, putamen, olivary nucleus, pontine nuclei and cerebellum. In addition to selective neuronal loss, iron pigment accumulation and gliosis, myelin pathology is increasingly recognized. In affected white matter, myelin displays signs of degeneration and oligodendroglia contain argyrophilic inclusion bodies, so-called glial cytoplasmic inclusions (GCI). GCI are composed of 10-15-nm diameter coated filaments that are immunoreactive for ubiquitin and alpha-synuclein. Similar inclusions are occasionally found in neuronal cell bodies and cell processes in MSA. Given the presence of inclusion bodies composed of synuclein, it is reasonable to assume that biochemical alterations would be detected in synuclein in MSA and indeed this is the case. In MSA synuclein has biophysical properties that suggest increasing insolubility such as sedimentation in dense fractions in sucrose gradients and ready extraction into detergents and formic acid. Surprisingly, these biochemical modifications in synuclein are more widespread in the brain that the obvious pathology and suggest a fundamental molecular characteristic of the disorder. Similar neuronal, and less frequently glial, inclusions are detected in Lewy body disease, where there is also evidence for biophysical alterations in synuclein. Thus, MSA and LBD are both synucleinopathies, and they may comprise different poles of a disease spectrum that includes sporadic disorders as well as genetically determined disorders such as familial Lewy body Parkinsonism.
 ...
PMID:Multiple system atrophy: a sporadic synucleinopathy. 1051 10

Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome, is a rare neurodegenerative disorder characterized clinically by Parkinsonism, cognitive impairment, pseudobulbar features, as well as cerebellar ataxia, and neuropathologically by neuronal loss, gliosis, and iron deposition in the globus pallidus, red nucleus, and substantia nigra. The hallmark pathological lesions of NBIA 1 are axonal spheroids, but Lewy body (LB)-like intraneuronal inclusions, glial inclusions, and rare neurofibrillary tangles also occur. Here we show that there is an accumulation of alpha-synuclein (alphaS) in LB-like inclusions, glial inclusions, and spheroids in the brains of three NBIA 1 patients. Further, beta-synuclein (betaS) and gamma-synuclein (gammaS) immunoreactivity was detected in spheroids but not in LB-like or glial inclusions. Western blot analysis demonstrated high-molecular weight alphaS aggregates in the high-salt-soluble and Triton X-100-insoluble/sodium dodecyl sulfate-soluble fraction of the NBIA 1 brain. Significantly, the levels of alphaS were markedly reduced in the Triton X-100-soluble fractions compared to control brain, and unlike other synucleinopathies, insoluble alphaS did not accumulate in the formic acid-soluble fraction. These findings expand the concept of neurodegenerative synucleinopathies by implicating alphaS, betaS, and gammaS in the pathogenesis of NBIA 1.
 ...
PMID:Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology. 1093 40