Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family

Abstract

The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family aVected with fatal familial insomnia are reported. The mother and two of her oVspring 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 oVspring 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. (J Neurol Neurosurg Psychiatry 2000;68:774-777)

The diversities of PrPSc distributions and pathologic changes in various brain regions from a Chinese patient with G114V genetic CJD

“…In other types of human genetic prion disease, for example FFI, massive gliosis in the thalamus is regular but PrP Sc deposition is usually mild. 17 The inconsistency of PrP Sc deposits and gliosis in some brain regions of CJD may reflect that gliosis in prion diseases is a common mechanism for reacting to neuron degeneration. Actually, various degrees of gliosis have been observed in other neurodegenerative disorders.…”

Serial Positron Emission Tomographic Findings in an Atypical Presentation of Fatal Familial Insomnia

“…Genetic investigations revealed a D178N mutation of the prion protein with a Val/Met polymorphism on position 129 and Met on the mutated allele, thus making the diagnosis of FFI, and more specifically indicating the slowly progressive subtype of FFI. 5 Postmortem macroscopic examination of the brain solely showed ventricular enlargement and minor cerebellar atrophy. Histologic study revealed severe neuronal loss and astrogliosis in the thalamus (particularly mediodorsal, centromedian, and reticular nuclei), with spongiform change mainly in ventrolateral nuclei, as well as marked gliosis in the inferior olivary nucleus (without spongiform change) and the dentate nucleus of the cerebellum (Figure 2B-C).…”

Manganese and Prion Disease

“…61 is associated with ataxia and dysarthria at onset, and after prolonged disease, with widespread neuropathological damage and cortical spongiosis. 62,63 Biochemically, FFI is quite distinct from other prion diseases: the prions involved in fCJD and sCJD give a B21 kDa protein fragment after digestion with protease, while FFI produces i a shorter, B19 kDa, protein fragment. 64 These results further confirm the ''prion strain'' hypothesis, allowing researchers to identify two different strains from their origin to their experimental transmission to laboratory animals.…”