1/14. A subtype of sporadic prion disease mimicking fatal familial insomnia.OBJECTIVE: To establish a variant of sporadic prion disease as the sporadic form of fatal familial insomnia (FFI). BACKGROUND: FFI is a recently described prion disease characterized clinically by severe sleep impairment, dysautonomia, and motor signs, and pathologically by atrophy of thalamic nuclei, especially the medial dorsal and anterior ventral, and of the inferior olive. FFI is linked to the D178N mutation coupled with the methionine codon at position 129 in the prion protein gene (PRNP). It is also identified by the properties of the abnormal prion protein (PrP(Sc)), which has the relative molecular mass of 19 kDa, corresponding to the so-called type 2, and a marked underrepresentation of the unglycosylated form relative to the diglycosylated and monoglycosylated forms. methods: Clinical, pathologic, PrP(Sc), and PRNP data from 5 subjects with a sporadic prion disease phenotypically similar to FFI were collected and analyzed. RESULTS: All 5 subjects had a disease clinically similar and histopathologically virtually identical to FFI. PrP(Sc) type 2 was present in all subjects in amount and distribution similar to those of FFI. However, the PrP(Sc) did not show the striking underrepresentation of the unglycosylated isoform of the protein that is characteristic of FFI. Moreover, none of the subjects had the D178N PRNP mutation but all were homozygous for methionine at codon 129. CONCLUSION: This condition is likely to represent the sporadic form of FFI and the term "sporadic fatal insomnia" is proposed.- - - - - - - - - - ranking = 1keywords = insomnia (Clic here for more details about this article) |
2/14. Novel twelve-generation kindred of fatal familial insomnia from germany representing the entire spectrum of disease expression.We present a novel large German kindred of fatal familial insomnia (FFI) consisting of three branches and comprising more than 800 individuals of 12 generations, the largest pedigree of any familial prion disease known today. There is a wide spectrum of clinical presentations leading to misdiagnoses of Olivo-Ponto-Cerebellar atrophy (OPCA), Parkinson's or Alzheimer's disease in addition to Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker (GSS) syndrome. Molecular genetic analysis of the prion protein gene (PRNP) confirmed the mutation D178N segregating with methionine at the polymorphic codon 129 of PRNP in all 7 patients examined. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI; the 129M allele determines FFI and 129V fCJD. Furthermore, heterozygosity at this site appears to induce prolonged disease duration as compared to the homozygous condition. The variability of the clinical and pathological findings documented for our patients indicates the difficulty in establishing the diagnosis of FFI on clinical and on pathological grounds alone. In three cases (IX-97, XI-21, V-2) followed up by us prospectively insomnia was an early and severe symptom; however, in case notes analyzed retrospectively this symptom was frequently missed. In contrast to previous reports and in agreement with recent studies we cannot confirm a clear relationship between the status of the M/V polymorphism at codon 129 and the age-of-onset of this disease.- - - - - - - - - - ranking = 1keywords = insomnia (Clic here for more details about this article) |
3/14. Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family.The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family affected with fatal familial insomnia are reported. The mother and two of her offspring developed a rapidly evolving disease with insomnia and behavioural disorders as the initial symptoms and died between 5 and 10 months after the onset of the illness. Frontal brain biopsy in the mother disclosed only non-significant spongiosis, and full neuropathological examination of her offspring showed thalamic and olivary degeneration with isolated focal cortical spongiosis. Genetic examination could only be performed in the contemporary patients and both harboured the prion protein (PrP) 178Asn mutation and homozygous 129 Met/Met genotype.- - - - - - - - - - ranking = 1keywords = insomnia (Clic here for more details about this article) |
4/14. Inherited prion disease caused by the V210I mutation: transmission to transgenic mice.OBJECTIVE: To describe the clinical and neuropathologic profile and determine the strain characteristics of familial Creutzfeldt-Jakob disease (fCJD) caused by a point mutation of the PRNP gene at codon 210 that results in a valine-to-isoleucine substitution in the prion protein (PrP). methods: The clinicopathologic features of four individuals from the united states who died of fCJD(V210I) were compared. Transgenic (Tg) mice expressing a chimeric human-mouse PrP transgene were inoculated with brain extracts from three fCJD(V210I) cases, sporadic CJD (sCJD), fCJD(E200K), and fatal familial insomnia (FFI), to compare prion strain characteristics. RESULTS: The clinicopathologic profile of fCJD(V210I) was variable among cases but shared similarities with sCJD. The pattern of PrP(Sc) deposition in the brains of Tg mice was similar to that caused by sCJD but different from that associated with fCJD(E200K) or FFI. CONCLUSIONS: Each of these prion diseases is characterized by a rapidly progressive dementia with myoclonus, periodic complexes on EEG, and spongiform change without PrP plaque deposition in the brain. The occurrence of a different PrP(Sc) phenotype with each PRNP mutation argues that each respective amino acid sequence substitution produces a different prion strain.- - - - - - - - - - ranking = 0.16666666666667keywords = insomnia (Clic here for more details about this article) |
5/14. Beta-CIT SPECT demonstrates reduced availability of serotonin transporters in patients with Fatal Familial Insomnia.Fatal familial insomnia (FFI) is a rare hereditary human prion disease with unique clinical features including progressive sleep impairment and autonomic dysfunction. The serotonergic system is considered to be involved in the regulation of the sleep-wake cycle. In this study we demonstrate a reduced availability of serotonin transporters of 57% and 73% respectively in a thalamus-hypothalamus region of two FFI patients examined with beta-CIT SPECT as compared to age-expected control values.- - - - - - - - - - ranking = 0.16666666666667keywords = insomnia (Clic here for more details about this article) |
6/14. Intracerebral distribution of infectious amyloid protein in spongiform encephalopathy.We studied the regional distribution of infectious amyloid protein by western immunoblots of brain tissue extracts from 37 patients with different forms of spongiform encephalopathy, i.e., 16 sporadic cases, 18 familial cases with a variety of mutations, and 3 iatrogenic cases. In sporadic and familial Creutzfeldt-Jakob disease, amyloid protein concentrations were usually highest in the frontotemporal regions of the cerebral cortex, whereas iatrogenic Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker syndrome had as high or higher concentrations in the deep cerebral nuclei and cerebellum. As a group, familial cases had lower amyloid protein concentrations than either sporadic or iatrogenic cases, and fatal familial insomnia patients had the lowest concentrations found in any form of disease. This hierarchy of amyloid protein concentrations corresponds to the experimental transmission rates observed for each form of disease and is consistent with the concept that the protein molecule is an integral component of the infectious agent. Regional amyloid protein pattern analysis of brain and spinal cord may help to distinguish sporadic from environmentally acquired infections, as for example, cases of human disease suspected to have arisen from exposure to sheep or cows infected with scrapie or bovine spongiform encephalopathy.- - - - - - - - - - ranking = 0.16666666666667keywords = insomnia (Clic here for more details about this article) |
7/14. Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200(Lys) mutation.Fatal familial insomnia (FFI) has been exclusively associated with a pathogenic mutation at codon 178 in the PRNP gene coupled with methionine (Met) at codon 129. We now describe a subject with familial Creutzfeldt-Jakob disease, heterozygous for the pathogenic lysine (Lys) mutation at codon 200 and homozygous for Met at codon 129 of the PRNP gene, who was affected by severe insomnia. At autopsy the patient had significant involvement of the thalamus, as previously described in subjects affected by FFI with the codon 178 mutation. This case demonstrates the wide variability of the clinical expressions in patients with the codon 200 mutation, that may include insomnia and thalamic pathology.- - - - - - - - - - ranking = 1.1666666666667keywords = insomnia (Clic here for more details about this article) |
8/14. Fatal familial insomnia with a mutation at codon 178 of the prion protein gene: first report from japan.Fatal familial insomnia (FFI), or familial selective thalamic degeneration with a mutation at codon 178 of the prion protein (PrP) gene, is a rapidly progressive autosomal dominant disease characterized by progressive insomnia, dysautonomia, and myoclonus. We report here the clinical and postmortem findings as well as genomic analysis in a first non-Western case with FFI. This patient also clinically had cognitive impairments such as memory disturbance, delirium, and hallucinations, along with insomnia, dysautonomia, and myoclonus. This case implies a worldwide distribution of FFI and also highlights the need for more aggressive clinical application of genomic analysis of the PrP gene and polysomnographic study in patients with insomnia and cognitive impairments.- - - - - - - - - - ranking = 1.3333333333333keywords = insomnia (Clic here for more details about this article) |
9/14. Fatal familial insomnia: a seventh family.A 60-year-old woman with a typical history of fatal familial insomnia (FFI) had FFI proven by histologic examination and molecular testing. Her son, who died at the age of 20 in 1978, had a rapidly progressive dementing illness without reported insomnia. He carried the characteristic mutation for FFI and is the youngest patient reported with this condition.- - - - - - - - - - ranking = 1keywords = insomnia (Clic here for more details about this article) |
10/14. Familial spongiform encephalopathy associated with a novel prion protein gene mutation.Human prion diseases include Creutzfeldt-Jakob disease, gerstmann-straussler-scheinker disease, fatal familial insomnia, and kuru. Each of these diseases has a specific clinical presentation while spongiform encephalopathy, neuronal loss, and gliosis are their neuropathological hallmarks. We studied a Brazilian family with an autosomal dominant form of dementia. Nine members of the family were affected by a dementia with frontotemporal clinical features, with a mean age at onset of 44.8 /- 3.8 years and a mean duration of symptoms of 4.2 /- 2.4 years. Neuropathological examination of 3 patients showed severe spongiform change and neuronal loss in the deep cortical layers and in the putamen, but minimal gliosis in the most severely affected areas. The putamen and cerebellum, but not other areas of the affected brain, displayed prion protein immunoreactivity. A novel prion protein gene mutation causing a nonconservative substitution at codon 183 was identified in 2 neuropathologically confirmed affected individuals (mother and son). The mutation was transmitted in a mendelian fashion to 12 members of the family. Therefore, we identified a novel prion disease variant characterized by an early onset and long duration of the symptoms, severe spongiform change with minimal gliosis, associated with a prion protein gene mutation at codon 183.- - - - - - - - - - ranking = 0.16666666666667keywords = insomnia (Clic here for more details about this article) |
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