RESUMEN
We report here an autopsy case of sporadic Creutzfeldt-Jakob disease (CJD) without hereditary burden and with a clinical course typical of sporadic CJD. A 77-year old man developed memory disturbance, followed by gait disturbance and myoclonus. He died of bronchopneumonia 5 months after the disease onset. Post-mortem examination revealed neuronal loss, astrocytosis, and patchy spongiosis in the cerebral cortex and lenticular nuclei. Synaptic-type deposits of prion protein were present in the cerebral cortex. Additionally, Lewy bodies were observed in the cerebral cortex and substantia nigra. Furthermore, senile plaques compatible with definite Alzheimer's disease according to Consortium to Establish a Registry for Alzheimer's disease criteria and neurofibrillary changes of the limbic system consistent with Braak stage IV were found. Based on a review of the published literature, this autopsy case is very rare, and we suppose that the incidence of CJD accompanied by Lewy body disease and Alzheimer's disease is very low.
Asunto(s)
Enfermedad de Alzheimer/complicaciones , Síndrome de Creutzfeldt-Jakob/complicaciones , Enfermedad por Cuerpos de Lewy/complicaciones , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/patología , Diagnóstico Diferencial , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/patología , MasculinoRESUMEN
Microtubule-associated protein tau is the major component of the filamentous neurofibrillary lesions of Alzheimer's disease (AD) and other tauopathies. Recently, it has been reported that tau isoforms lacking both N-terminal exon 2 and exon 3 do not form straight filament- or paired helical filament-like filaments in vitro, and that the N-terminal exons facilitate assembly of full-length tau. However, neuropathological and biological studies on the N-terminal region of tau protein in human tissue have been limited. We performed a biochemical study on the abnormally phosphorylated tau in brains affected by AD and corticobasal degeneration (CBD), and an immunohistochemical study on tau-positive structures in neurodegenerative diseases, to clarify whether tau with the exon 3 insert was present in abnormal tau-positive structures. On immunoblots of sarkosyl-insoluble tau, anti-exon 3 antibody (anti-E3 Ab) recognized two bands of 68 and 72 kDa in AD and only one band of 72 kDa in CBD. Immunohistochemically, anti-E3 Ab recognized most parts of the neurofibrillary tangles (NFT) in AD and Pick bodies in Pick's disease. In progressive supranuclear palsy (PSP) and CBD, most NFT and pretangles were positive for anti-E3 Ab, as were a small number of glial inclusions. These results indicate that abnormally phosphorylated tau containing the exon 3 insert is present in both PSP and CBD brain, and that CBD cannot be distinguished from PSP by immunoreactivity for anti-E3 Ab. Although most intraglial inclusions were negative for anti-E3 Ab, a few were positive. Therefore, tau isoforms containing the exon 3 insert are expressed at low levels in glial cells.
Asunto(s)
Encéfalo/patología , Exones , Enfermedades Neurodegenerativas/patología , Proteínas tau/genética , Anciano , Anciano de 80 o más Años , Encéfalo/metabolismo , Femenino , Humanos , Immunoblotting , Inmunohistoquímica , Cuerpos de Inclusión/metabolismo , Masculino , Microscopía Confocal , Persona de Mediana Edad , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Neuroglía/metabolismo , Neuroglía/patología , Proteínas tau/metabolismoRESUMEN
Ataxia severity, cerebellar hemispheric blood flow (CHBF), ascorbate free radical (AFR), superoxide dismutase protein, superoxide scavenging activity, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in cerebrospinal fluid (CSF) were compared before and after an 8-week course of repetitive transcranial magnetic stimulation (rTMS) in 20 patients with spinocerebellar degenerations (SCD). SCD patients showed higher AFR, 8-OHdG, and superoxide scavenging activity than 19 controls. In SCD patients, AFR and ataxia severity declined, and CHBF increased after rTMS. As the SCD patients showed negative correlations between ataxia severity and CHBF or superoxide scavenging activity, the therapeutic mechanism of rTMS may involve decreased oxidative stress and increased CHBF.
Asunto(s)
Terapia por Estimulación Eléctrica , Depuradores de Radicales Libres/líquido cefalorraquídeo , Estrés Oxidativo , Degeneraciones Espinocerebelosas , Estimulación Magnética Transcraneal , Adulto , Ácido Ascórbico/líquido cefalorraquídeo , Circulación Cerebrovascular/fisiología , Desoxiadenosinas/líquido cefalorraquídeo , Terapia por Estimulación Eléctrica/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Persona de Mediana Edad , Flujo Sanguíneo Regional/fisiología , Índice de Severidad de la Enfermedad , Degeneraciones Espinocerebelosas/líquido cefalorraquídeo , Degeneraciones Espinocerebelosas/clasificación , Degeneraciones Espinocerebelosas/fisiopatología , Degeneraciones Espinocerebelosas/cirugía , Superóxido Dismutasa/líquido cefalorraquídeo , Factores de TiempoAsunto(s)
Encéfalo/patología , Calcinosis/patología , Demencia/patología , Ovillos Neurofibrilares/patología , Encéfalo/metabolismo , Calcinosis/diagnóstico , Calcinosis/psicología , Demencia/diagnóstico , Demencia/psicología , Humanos , Plomo/metabolismo , Repeticiones de Microsatélite , Proteínas del Tejido Nervioso/metabolismo , Estándares de Referencia , Sinucleínas , Proteínas tau/genética , Proteínas tau/metabolismoRESUMEN
A 66-year-old man had suffered from a slow and steady decline in both physical and cognitive function for four years. He showed bradykinesia and small step gait with supranuclear vertical gaze palsy, especially upward gaze palsy. He was started on levodopa therapy but without response. A diagnosis of progressive supranuclear palsy was clinically suspected. He died at age 69. Pathologically, many alpha-synuclein positive inclusions were detected both in the brain stem and cerebral cortices, and the diagnosis of dementia with Lewy bodies was made. Scattered alpha-synuclein-positive inclusions and threads, which may be a pathological substrate for supranuclear gaze palsy, were identified in the rostal midbrain. From a review of five cases of dementia with Lewy bodies with supranuclear gaze palsy including this case, the absence of falls in the early stage of the disease, fluctuation of cognition, hallucination and vertical gaze palsy with a more severe defect in the upward direction distinguished dementia with Lewy bodies with vertical gaze palsy from progressive supranuclear palsy. In the differential diagnosis of parkinsonism with gaze palsy, clinicians should consider dementia with Lewy bodies with gaze palsy as well as progressive supranuclear palsy.