UMLS:C0004134 - FACTA Search

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Query: UMLS:C0004134 (ataxia)
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There have been identified 1051 cases of prion dsease in Japan since 1999 by the surveillance committee, of which idiopathic prion disease held 77.8%, hereditary 15.9% and infectious 6.6%. Idiopathic prion disease is sporadic Creutzfeldt-Jakob disease (sCJD) and most sCJD cases were classified into MM1 presenting with classical clinical features. MM2, MV2, VV1 and VV2 sCJD cases were rare and showed atypical features including prolonged course, lack of myoclonus and absence of PSD. In such occasions, high signal intensities on DW-MRI as well as increased 14-3-3 and tau proteins in CSF were very helpful. MM2 tharamic sCJD may lack all these laboratory findings but reduction of tharamic CBF in SPECT or PET would support the diagnosis. Hereditary prion disease are classified into 3 major phenotypes such as familial CJD, Gerstmann-Straeussler-Scheinker disease (GSS) mainly showing spinocerebellar ataxia, and fatal familial insomunia. While there have been known many mutations of prion protein gene, only V180I (fCJD), E200K (fCJD), M232R (fCJD) and P102L (GSS) mutations were common. Because most cases did not have family history, genetic test is mandatory in all the cases of prion disease including seemingly "sporadic" CJD. All the cases but 1 case of variant CJD were dura-grafted CJD in infectious prion disease.
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PMID:[Prion disease--the present status and recent progress in Japan]. 1919 1

Multiple system atrophy (MSA) is a sporadic alpha-synucleinopathy clinically characterized by variable degrees of parkinsonism, cerebellar ataxia and autonomic dysfunction. The histopathological hallmark of MSA is glial cytoplasmic inclusion (GCI). It is considered to represent the earliest stage of the degenerative process in MSA and to precede neuronal degeneration. Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal, rapidly progressive dementia generally associated with ataxia, pyramidal and extrapyramidal symptoms and myoclonus. Definite diagnosis needs neuropathological demonstration of variable degrees of spongiform degeneration of neuropil, neuronal loss, astro- and microgliosis, and the presence of abnormal deposits of the misfolded prion protein PrP(res) . Both diseases, CJD and MSA are infrequent among neurodegenerative diseases. In the present report we describe clinical and neuropathological findings of a previously healthy 64-year-old woman who developed symptoms of classical CJD. At post mortem examination, the brain showed in addition to classical methionine/methionine PrP(res) type 1 (MM1) sCJD changes and moderate Alzheimer-type pathology, features of "preclinical" MSA with minimal histopathological changes. These were characterized by discrete amounts of alpha-synuclein immunoreacive glial cytoplasmic inclusions in the striato-nigral system, isolated intraneuronal inclusions in pigmented neurons of the substantia nigra, as well as some vermiform intranuclear inclusions. To our knowledge, this is the first report on the coexistence of definite sCJD and "minimal changes" MSA in the same patient.
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PMID:"Preclinical" MSA in definite Creutzfeldt-Jakob disease. 2169 62

Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrP^Sc). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85-90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10-15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases.We report a novel PRNP mutation (V189I) in four CJD patients from three unrelated pedigrees. In three patients, the clinical features were typical for CJD and the diagnosis was pathologically confirmed, while the fourth patient presented with a complex phenotype including rapidly progressive dementia, behavioral abnormalities, ataxia and extrapyramidal features, and the diagnosis was probable CJD by current criteria, on the basis of PrP^Sc detection in CSF by Real Time Quaking-Induced Conversion assay. In all the three patients with autopsy findings, the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrP^res), and type 1 PrP^res was identified in the brain by western blot analysis. So, the histopathological and biochemical profile associated with the V189I mutation was indistinguishable from the MM1/MV1 subtype of sporadic CJD.Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrP^Sc detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes.
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PMID:Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene. 3060 47