Fatal familial insomnia: a model disease in sleep physiopathology.
Fatal Familial Insomnia (FFI) is characterized by loss of sleep, oneiric stupor with autonomic/motor hyperactivity and somato-motor abnormalities (pyramidal signs, myoclonus, dysarthria/dysphagia, ataxia). Positon emission tomography (PET) disclosed thalamic hypometabolism and milder involvement of the cortex; neuropathology severe neuronal loss in the thalamic nuclei variably affecting the caudate, gyrus cinguli and fronto-temporal cortices. Genetic analysis disclosed a mutation in the PRNP gene and FFI was transmitted to experimental animals, thus classifying FFI within the prion diseases. Rare Sporadic Fatal Insomnia (SFI) cases occur without PRNP mutation but with features similar to FFI. FFI represents a model disease for the study of sleep-wake regulation: (I) the profound thalamic hypometabolism/atrophy associated with lack of sleep spindles and delta sleep implicate the thalamus in the origin of slow wave sleep (SWS); (II) loss of SWS is associated with marked autonomic and motor hyperactivity; termed 'agrypnia excitata', this association has been proposed as a useful clinical concept representative of thalamo-limbic dysfunction; (III) lack of SWS occurs with substantial preservation of stage 1 NREM sleep, implying that the latter has mechanisms different from SWS and unaffected by thalamic atrophy; accordingly, conflating stage 1 NREM with SWS into NREM sleep is inappropriate.
Montagna
Pasquale
P
Center for Sleep Disorders, Department of Neurological Sciences, University of Bologna Medical School, Via Ugo Foscolo 7-40123 Bologna, Italy. pmontagn@neuro.unibo.it
D000328:Adult; D000682:Amyloid / Q000235:genetics; D002421:Caudate Nucleus / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis; D005625:Frontal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000473:pathology; D009483:Neuropsychological Tests; D017354:Point Mutation / Q000235:genetics; D049268:Positron-Emission Tomography; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages / Q000502:physiology; D013702:Temporal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D013787:Thalamic Nuclei / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology
D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors