Absence of sleep EEG markers in fatal familial insomnia healthy carriers: a spectral analysis study.
OBJECTIVE
Fatal familial insomnia (FFI) is linked to a mutation at codon 178 (C178) of the prion protein gene (PRNP). FFI is pathologically characterized by selective atrophy of the anteroventral and mediodorsal thalamic nuclei and clinically by loss of sleep, dysautonomia and motor signs. A key early polysomnographic sign of the disease onset is the loss of sleep spindling (sigma activity, SA). In FFI the loss of SA leads to the spectral representation 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 spectral sleep EEG pattern in FFI relatives carriers (C178(pos)) or non-carriers (C178(neg)) of the C178 mutation.


METHODS
Seventeen healthy relatives of FFI patients, 8 carriers of the C178 FFI mutation in a preclinical condition and 9 non carriers, underwent two-night polysomnography. The absolute and relative EEG power of the 4 main bands (delta: SWA, 0.5-4.0 Hz; theta: TB, 4.5-8 Hz; alpha: AB, 8.5-12 Hz; sigma: 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. Multiple 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 disclose sleep EEG markers linked to the FFI C178(pos) in the preclinical condition. Key sleep EEG alteration become evident only at the clinical onset of the disease.
Ferrillo
F
F
Sleep Disorder Center, DISMR, University of Genoa, Genoa, Italy. fifi@dism.unige.it
Plazzi
G
G
Nobili
L
L
Beelke
M
M
De Carli
F
F
Cortelli
P
P
Tinuper
P
P
Avoni
P
P
Vandi
S
S
Gambetti
P
P
Lugaresi
E
E
Montagna
P
P
D000328:Adult; D000368:Aged; D000513:Alpha Rhythm; D015415:Biomarkers; D002353:Carrier State; D003062:Codon / Q000235:genetics; D003700:Delta Rhythm; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017286:Polysomnography; D017096:Prion Diseases / Q000235:genetics / Q000503:physiopathology*; D011328:Prions / Q000235:genetics; D012890:Sleep / Q000502:physiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000503:physiopathology*; D012894:Sleep Stages / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology*; D013826:Theta Rhythm; D013997:Time Factors
D015415:Biomarkers; D003062:Codon; D011328:Prions