Pre-symptomatic diagnosis in fatal familial insomnia: serial neurophysiological and 18FDG-PET studies.
Knowing how and when the degenerative process starts is important in neurodegenerative diseases. We have addressed this issue in fatal familial insomnia (FFI) measuring the cerebral metabolic rate of glucose (CMRglc) with 2-[18F]fluoro-2-deoxy-D-glucose PET in parallel with detailed clinical, neuropsychological examinations and polysomnography with EEG spectral analyses. Nine asymptomatic carriers of the D178N mutation, 10 non-carriers belonging to the same family, and 19 age-matched controls were studied over several years. The CMRglc as well as clinical and electrophysiological examinations were normal in all cases at the beginning of the study. Four of the mutation carriers developed typical FFI during the study but CMRglc and the clinical and electrophysiological examinations remained normal 63, 56, 32 and 21 months, respectively before disease onset. The carrier whose tests were normal 32 months before disease onset was re-examined 13 months before the onset. At that time, selective hypometabolism was detected in the thalamus while spectral-EEG analysis disclosed an impaired thalamic sleep spindle formation. Following clinical disease onset, CRMglc was reduced in the thalamus in all 3 patients examined. Our data indicate that the neurodegenerative process associated with FFI begins in the thalamus between 13 and 21 months before the clinical presentation of the disease.
Cortelli
Pietro
P
Department of Neuroscience, C.N.R.-I.B.F.M., Vita-Salute San Raffaele University, Milan, Italy. pietro.cortelli@unibo.it
Perani
Daniela
D
Montagna
Pasquale
P
Gallassi
Roberto
R
Tinuper
Paolo
P
Provini
Federica
F
Federica
Provini
P
Avoni
Patrizia
P
Ferrillo
Franco
F
Anchisi
Davide
D
Moresco
Rosa Maria
RM
Fazio
Ferruccio
F
Parchi
Piero
P
Baruzzi
Agostino
A
Lugaresi
Elio
E
Gambetti
Pierluigi
P
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D042241:Early Diagnosis; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017286:Polysomnography; D049268:Positron-Emission Tomography; D011328:Prions / Q000235:genetics; D019275:Radiopharmaceuticals; D013788:Thalamus / Q000378:metabolism
D001786:Blood Glucose; D011328:Prions; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18