Absence of sleep EEG markers in fatal familial insomnia healthy carriers: a spectral analysis study

Objectives: Fatal familial insomnia (FFI) is linked to a mutation at codon 178 (C178) of the prion protein gene (PRNP). FFI is pathologically characte rized by selective atrophy of the anteroventral and mediodorsal thalamic nu clei and clinically by loss of sleep, dysautonomia and motor signs. A key e arly polysomnographic sign of the disease onset is the loss of sleep spindl ing (sigma activity, SA). In FFI tho loss of SA leads to the spectral repre sentation of a sudden slow wave activity (SWA) increase from an awake state , the reaching of a stable plateau without oscillations, followed by abrupt fall down to REM sleep. We evaluated the presence of differences in the sp ectral sleep EEG pattern in FFI relatives carriers (C178(pos)) or non-carri ers (C178(neg)) of the C178 mutation. Methods: Seventeen healthy relatives of FFI patients, 8 carriers of the C17 8 FFI mutation in a preclinical condition and 9 non carriers, underwent two -night polysomnography. The absolute and relative EEG power of the 4 main b ands (delta: SWA, 0.5-4.0 Hz; theta: TB, 4.5-8 Hz; alpha: AB, 8.5-12 Hz; si gma: SA, 12.5-16 Hz) has been studied for the total sleep time, the period of delta increase after sleep onset, and the period of delta plateau. Multi ple regression has been applied to investigate relations between the power of the bands studied and 3 parameters: age, the gender of the subjects and the C178 genotype. Results: Our study could not show evidence of differences in the sleep EEG composition between carriers and non-carriers of the C178 FFI mutation. Conclusions: The spectral analysis techniques we used were not able to disc lose sleep EEG markers linked to the FFI C178(pos) in the preclinical condi tion. Key sleep EEG alteration become evident only at the clinical onset of the disease. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.