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Abstract(s)
A doença de Creutzfeldt-Jakob é a mais comum das doenças priónicas, resultando da
conversão da proteína priónica PrPc na forma patológica PrPsc, com posterior acumulação nos
tecidos, sobretudo no SNC, onde provoca alterações espongiformes com perda neuronal e
possível formação de placas amilóides.
Existem quatro variantes de CJD: a esporádica, a familiar, a iatrogénica e a variante
sendo que a esporádica corresponde a aproximadamente 85% dos casos.
A incidência da CJD em Portugal foi, segundo dados de 2004, de 0,1 casos por 100.000
habitantes.
Apesar da baixa incidência, a CJD é uma patologia que apresenta taxa de mortalidade
de 100% em todas as variantes. Do início dos sintomas à morte decorrem, em média, 8 meses.
O quadro clínico caracteriza-se pela evolução rapidamente progressiva de alterações de
personalidade e comportamento, comprometimento de funções corticais e de integração
sensoriomotora, com estágio final de mutismo acinético. As mioclonias são típicas dos
estágios mais avançados da doença e raras à apresentação clínica.
Uma grande variedade de patologias podem apresentar-se com um quadro de
demência rapidamente progressiva e, como tal, mimetizar a CJD, pelo que é fundamental um
correto diagnóstico diferencial.
O diagnóstico definitivo da patologia apenas é possível pela observação das alterações
espongiformes e agregados de PrPsc em amostras de tecido cerebral, obtido por biópsia ou
autópsia. No entanto, na atualidade, muitas técnicas permitirem um diagnóstico in vivo
provável, como é o caso da EEG, da RMN e dos biomarcadores do LCR.
A única forma de impedir mortes por CJD é prevenindo a patologia. A prevenção
apenas é possível nas variantes adquiridas, vCJD e iCJD.
Atualmente, não existe tratamento para a patologia. Vários fármacos têm sido
estudados para impedir a conversão de PrPc em PrPsc, impedir a acumulação de PrPsc ou para
promover a depleção dos agregados de PrPsc e, assim, prevenir ou tratar a CJD. Também a
abordagem vacinal com anticorpos anti-PrP foi testada.
Alguns fármacos parecem atrasar a progressão da doença e aumentar a sobrevida,
como o pentosano polissulfato sódico. No entanto, até hoje, nenhum se mostrou eficaz no
tratamento da doença.
Creutzfeldt-Jakob disease is the most common prion disease, resulting from conversion of PrPc in pathological prion protein PrPsc form, with subsequent accumulation in tissues, especially in the CNS, where it causes spongiform changes with neuronal loss and possible formation of amyloid plaques. There are four CJD variants: sporadic, familial, iatrogenic and variant. Sporadic variant corresponds to approximately 85% of cases. The incidence of CJD in Portugal was, according to 2004 data, 0.1 cases per 100,000 inhabitants. Despite the low incidence, CJD is a disease that has a mortality rate of 100% in all variants. On average, patients die 8 months after the onset of symptoms. Clinically, patients present rapid and progressive changes in personality and behavior, involvement of cortical functions and sensorimotor integration, with the final stage of akinetic mutism. Myoclonus are typical in the later stages of the disease and are rare at clinical presentation. A wide range of diseases may present with a rapidly progressive dementia and, thus, mimic CJD. Therefore it is essential a correct differential diagnosis. The definitive diagnosis of the disease is only possible by observation of spongiform changes and aggregates of PrPsc in brain tissue samples, obtained by biopsy or autopsy. However, nowadays, many techniques allow a likely in vivo diagnosis, as is the case of EEG, MRI and CSF biomarkers. The only way to prevent deaths from CJD is preventing pathology. Prevention is possible only in the acquired variants, vCJD and iCJD. Currently, there is no treatment for the disease. Many drugs have been studied to prevent the conversion of PrPc to PrPsc, prevent the accumulation of PrPsc or to promote depletion of PrPsc aggregates and thus prevent or treat CJD. Also, the vaccine approach with anti-PrP antibodies was tested. Some drugs appear to delay disease progression and increase survival, such as pentosan polysulfate sodium (PPS). However, to date, none has proven effective in treating the disease.
Creutzfeldt-Jakob disease is the most common prion disease, resulting from conversion of PrPc in pathological prion protein PrPsc form, with subsequent accumulation in tissues, especially in the CNS, where it causes spongiform changes with neuronal loss and possible formation of amyloid plaques. There are four CJD variants: sporadic, familial, iatrogenic and variant. Sporadic variant corresponds to approximately 85% of cases. The incidence of CJD in Portugal was, according to 2004 data, 0.1 cases per 100,000 inhabitants. Despite the low incidence, CJD is a disease that has a mortality rate of 100% in all variants. On average, patients die 8 months after the onset of symptoms. Clinically, patients present rapid and progressive changes in personality and behavior, involvement of cortical functions and sensorimotor integration, with the final stage of akinetic mutism. Myoclonus are typical in the later stages of the disease and are rare at clinical presentation. A wide range of diseases may present with a rapidly progressive dementia and, thus, mimic CJD. Therefore it is essential a correct differential diagnosis. The definitive diagnosis of the disease is only possible by observation of spongiform changes and aggregates of PrPsc in brain tissue samples, obtained by biopsy or autopsy. However, nowadays, many techniques allow a likely in vivo diagnosis, as is the case of EEG, MRI and CSF biomarkers. The only way to prevent deaths from CJD is preventing pathology. Prevention is possible only in the acquired variants, vCJD and iCJD. Currently, there is no treatment for the disease. Many drugs have been studied to prevent the conversion of PrPc to PrPsc, prevent the accumulation of PrPsc or to promote depletion of PrPsc aggregates and thus prevent or treat CJD. Also, the vaccine approach with anti-PrP antibodies was tested. Some drugs appear to delay disease progression and increase survival, such as pentosan polysulfate sodium (PPS). However, to date, none has proven effective in treating the disease.
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Keywords
Demência Rapidamente Progressiva Doença de Creutzfeldt-Jakob Doença Priónica Prpsc