11/15. kuru with incubation periods exceeding two decades. The clinical characteristics of kuru in 15 patients are described. All the patients had a history of joint pains preceding difficulty walking. The severity of the neurological dysfunction varied from mild truncal and limb ataxia necessitating the use of a stick for walking to terminal illness accompanied by marked ataxia, rigidity, spasticity, and dementia. All the patients with kuru in this study had a apprehensive, frightened facial expression. Most of the patients examined showed diminished or absent optokinetic nystagmus bilaterally. Apprehensive facies and diminished optokinetic nystagmus have not previously been described in kuru. The other clinical features of the current patients with kuru are similar to those recorded twenty years ago. Epidemiological surveillance, anamnesis, and missionary reports strongly suggest that all the patients described in this study were exposed to the kuru agent more than two decades ago through ritualistic cannibalism. Thus the incubation period or time interval from exposure to the onset of clinical illness exceeds two decades, while the duration of illness is two years or less. The cause of these extraordinarily long incubation periods is unknown but may result in part from exposure to small doses of the kuru agent through an inefficient oral route. ( info) |
12/15. A transmissible subacute spongiform encephalopathy in a visitor to the eastern highlands of new guinea. A Caucasian male, clinically ill with a respiratory disease, visited the Eastern Highlands of new guinea (endemic for kuru in the Fore people) and developed subacute spongiform encephalopathy (Jakob-Creutzfeldt disease) ten weeks later, from which he subsequently died. brain material was inoculated intracranially into squirrel monkeys, and several of them developed a spongiform encephalopathy. Monkeys that received control material (normal brain) were normal. Electronmicroscopic features in affected brain tissue are described, and the question of a relationship between Jakob-Creutzfeldt disease and kuru is considered. ( info) |
13/15. pathology and immunocytochemistry of a kuru brain. We report here results of modern staining techniques including anti-prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old male who died from kuru in 1967. brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare "florid" plaques with surrounding vacuolation. We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease variant recently reported in the UK and france; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis. ( info) |
14/15. Creutzfeldt-Jakob disease with long duration and panencephalopathic lesions: molecular analysis of one case. A 49-year-old woman presented with isolated aphasia followed by dementia and ataxia with a duration of 4 years. Histopathologically there was panencephalic involvement, status spongiosus, and kuru-type plaques. Molecular analysis showed heterozygosity at codon 129 in the prion protein (PrP) gene, and type 2 protease-resistant PrP. The comparison between this case and those previously reported suggests that the panencephalopathic variant of Creutzfeldt-Jakob disease (CJD) is an aspecific end-stage condition displayed by most if not all CJD variants in individual patients with an unusually prolonged course. ( info) |
| We report a kindred of French/Alsatian origin with symptoms of gerstmann-straussler-scheinker disease over 3 generations. In the propositus, cerebellar signs and memory disturbance were the presenting features, followed by other neurological manifestations. biopsy of the cerebral cortex showed numerous multicentric and "kuru"-type amyloid plaques that on immuno-light and electron microscopy stained with antibody to prion protein. Molecular genetic analysis revealed an A117V mutation in the open reading frame of the prion protein gene. Questions as to pathology and spread of this mutation are discussed. ( info) |