Analysis of a large case series of fatal familial insomnia to determine tests with the highest diagnostic value.

Journal of neuropathology and experimental neurology 2023 Jan 20

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Fatal familial insomnia (FFI) is a rare prionopathy with unusually high incidence in the Basque Country. We report detailed data on clinical, diagnostic, histopathological, and biochemical characteristics of a recent FFI case series. The Basque Brain Bank database was screened for patients diagnosed from 2010 to 2021 with standard genetic and/or neuropathological criteria. This series includes 16 patients, 25% without family history, with 12 cases from 9 unrelated (but geographically-linked, Basque country) kindreds, onset ranging from 36 to 70 years, and disease course from 7 to 11.5 months. Insomnia was the initial symptom in most cases, with consistent polysomnography in 92% of the cases. In contrast, 14-3-3 and RT-QuIC from cerebrospinal fluid were negative. Most patients were homozygous for methionine. Gliosis and neuronal loss in basal ganglia and thalamus were the main histopathological findings; Western blotting identified preferentially the protease-resistant prion protein (PrPres) type 2, although detection of the scrapie isoform of the prion protein (PrPSc) identified using brain tissue RT-QuIC was more successful. This is one of the largest current studies on FFI patients performed to provide improvements in diagnostic reliability. Among the analyzed tests, polysomnography and the genetic study show the highest diagnostic value in FFI. © The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Citation

Izaro Kortazar-Zubizarreta, Hasier Eraña, Arrate Pereda, Jorge M Charco, Africa Manero-Azua, Rebeca Ruiz-Onandi, Urko Aguirre, Gonzalo Gonzalez-Chinchon, Basque Prionopathies Study Group, Guiomar Perez de Nanclares, Joaquín Castilla. Analysis of a large case series of fatal familial insomnia to determine tests with the highest diagnostic value. Journal of neuropathology and experimental neurology. 2023 Jan 20;82(2):169-179