RESUMO
Fatal insomnia is a rare human prion disease characterised by sleep-wake disturbances, thalamic degeneration and deposition of type 2 disease-specific prion protein (PrP(Sc)). This report details a patient with sporadic fatal insomnia who exhibited cerebral deposition of type 1 PrP(Sc) and neuropathological changes largely in the basal ganglia. Previous damage of this brain region by a surgically removed colloid cyst and the insertion of two intracerebral shunts may have influenced the distribution of PrP(Sc) through a chronic inflammatory process. These findings add to our knowledge of the phenotypic variability of human prion diseases with prominent sleep disturbances.
Assuntos
Insônia Familiar Fatal/patologia , Proteínas PrPSc/metabolismo , Western Blotting , Encéfalo/patologia , Síndrome de Creutzfeldt-Jakob/patologia , Eletroencefalografia , Humanos , Imuno-Histoquímica , Insônia Familiar Fatal/genética , Insônia Familiar Fatal/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Proteínas PrPSc/genética , Tomografia Computadorizada por Raios XRESUMO
Cerebral accumulation of hyperphosphorylated tau (phospho-tau) occurs in several neurodegenerative conditions including Alzheimer disease. In prion diseases, phospho-tau deposition has been described in a rare genetic form, Gerstmann-Sträussler-Scheinker disease, but is not considered part of the neuropathological picture of Creutzfeldt-Jakob disease. Aim of this study was to investigate whether changes related to phospho-tau accumulation are present in the brain of patients with variant Creutzfeldt-Jakob disease (vCJD) that shares with Gerstmann-Sträussler-Scheinker disease abundant prion protein (PrP) deposition in amyloid form. The analysis was extended to experimental mouse models of vCJD. We detected a large number of phospho-tau-immunoreactive neuritic profiles, often clustered around PrP amyloid deposits, not only in the cerebral cortex, but also in the cerebellum of all vCJD patients examined, in the absence of Abeta. Although less constantly, phospho-tau was localized in some perikaria and dendrites. The biochemical counterpart was the presence of phospho-tau in the detergent-insoluble fraction of cerebral cortex. Phospho-tau-immunoreactive neuronal profiles were also found in association with PrP deposits in mouse models of vCJD. These findings suggest that the abnormal forms of PrP associated with vCJD trigger a tauopathy, and provide a paradigm for the early stages of tau pathology associated with cerebral amyloidoses, including Alzheimer disease.
Assuntos
Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Síndrome de Creutzfeldt-Jakob/metabolismo , Modelos Animais de Doenças , Proteínas tau/metabolismo , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Distribuição TecidualRESUMO
An atypical case of sporadic Creutzfeldt-Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrP(Sc)) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype.
Assuntos
Síndrome de Creutzfeldt-Jakob/genética , Proteínas PrPSc/genética , Idoso , Anticorpos/imunologia , Anticorpos Monoclonais/imunologia , Antiparkinsonianos/uso terapêutico , Western Blotting , Encéfalo/imunologia , Encéfalo/patologia , Códon/genética , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/imunologia , Feminino , Humanos , Imuno-Histoquímica , Levodopa/uso terapêutico , Imageamento por Ressonância Magnética , Metionina/genética , Transtornos Parkinsonianos/tratamento farmacológico , Fenótipo , Polimorfismo Genético/genética , Proteínas PrPSc/imunologia , Valina/genéticaRESUMO
Three members of an Italian family with autosomal dominant dementia and multiple strokes had the A713T mutation of the APP gene. The neuropathologic examination of the proband disclosed Alzheimer disease (AD) with severe cerebral amyloid angiopathy and multiple infarcts. This indicates that the A713T mutation of the APP gene, lying at the gamma-secretase cleavage site, can be responsible for AD with symptomatic cerebral amyloid angiopathy.
Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Angiopatia Amiloide Cerebral/genética , Infarto Cerebral/genética , Mutação de Sentido Incorreto , Mutação Puntual , Doença de Alzheimer/patologia , Substituição de Aminoácidos , Secretases da Proteína Precursora do Amiloide , Precursor de Proteína beta-Amiloide/química , Ácido Aspártico Endopeptidases , Encéfalo/patologia , Angiopatia Amiloide Cerebral/patologia , Infarto Cerebral/patologia , Códon/genética , Análise Mutacional de DNA , Progressão da Doença , Endopeptidases/metabolismo , Feminino , Genes Dominantes , Humanos , Itália , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
The authors investigated two unrelated patients with Creutzfeldt-Jakob disease (CJD) with clinical features of sporadic CJD (sCJD) carrying one extra octapeptide repeat in the prion protein (PrP) gene (PRNP). A synaptic type PrP distribution throughout the cerebral gray matter and plaque-like PrP deposits in the subcortical gray structures were detected immunocytochemically. The different patterns of PrP deposition were associated with distinct types of protease-resistant PrP, similar to type 1 and type 2 of sCJD. The features suggest that this insertion is a pathogenic mutation.
Assuntos
Amiloide/genética , Síndrome de Creutzfeldt-Jakob/genética , Príons/genética , Precursores de Proteínas/genética , Proteínas 14-3-3 , Encéfalo/patologia , Química Encefálica , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Eletroencefalografia , Endopeptidases/química , Heterozigoto , Homozigoto , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Proteínas Priônicas , Príons/química , Tirosina 3-Mono-Oxigenase/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
Workers' compensation costs for management of soft tissue disorders continue to increase. The complexity of medical management of these cases has increased due to social factors. The purpose of this study is to improve the physician's ability to recognize nonmedical issues that prevent a rapid return to employment. A classification system is presented that will allow the clinician to identify administrative and pyschosocial issues that prolong disability. Additionally, the patients' job demands were classified by known ergonomic risk factors. The system was applied retrospectively to 50 random cases referred to two occupational hand clinics over a 1-year period. The results indicated that the psychosocial classification of the patient and the current employment status are the most important factors in prolonging disability workers.
