Report of eight cases of familial fatal insomnia

Abstract

Objective \nTo investigate the clinical features, polysomnography, imaging examination, genetic analysis and laboratory examination of eight patients with familial fatal insomnia (FFI). \n \n \nMethods \nThe clinical data, neuropsychological examination, results of cerebrospinal fluid analysis, imaging examination and polysomnography of eight patients with FFI in Xuanwu Hospital, Capital Medical University from 2009 to 2018 were retrospectively analyzed and summarized. \n \n \nResults \nAmong the eight FFI patients, there were 3 males and 5 females, the onset age being (49.8±14.3) years (19 to 64 years) and the course of disease being eight to 18 months. D178N mutation in the PRNP gene of chromosome 20 and 129 amino acid polymorphisms of M/M were found in genetic examination in all the eight patients, of which five patients had family history. All the patients had sleep disorders, sleep-related involuntary movement, sleep-related dyspnea, laryngeal stridor. All the patients showed rapid progressive dementia with or without symptoms or signs of psychosis, ataxia, pyramidal and extrapyramidal. All the eight patients had progressive sympathetic symptoms, including hypertension, sweating, tachycardia, irregular breathing, and dysarthria. Cerebrospinal fluid 14-3-3 protein was found positive in one patient, and negative in seven patients. Electroencephalograph showed diffuse slow wave and non periodic synchronous discharge. Single-photon emission computed tomography or 18F fluorodeoxyglucose positron emission tomography showed decreased thalamic glucose metabolism in three patients. Seven patients showed decreased total sleep time, sleep awakening cycle disorder, especially the reduction or loss of rapid eye movement, laryngeal stridor and involuntary movement in polysomnography. \n \n \nConclusions \nFFI is characterized by sleep disorder, sleep-related involuntary movement, dyspnea, laryngosis, rapid progressive dementia and sympathetic symptoms. The family history, polysomnography and positron emission tomography are helpful for the diagnosis of FFI. PRNP gene detection can confirm the diagnosis of FFI. \n \n \nKey words: \nInsomnia, fatal familial;\xa0Dementia;\xa0Polysomnography;\xa0PRNP gene