Fatal insomnia and agrypnia excitata: sleep and the limbic system.
Fatal familial insomnia, a human prion disease, Morvan's chorea, an autoimmune limbic encephalopathy, and delirium tremens, the well-known alcohol (or benzodiazepine [BDZ]) withdrawal syndrome, share a clinical phenotype largely consisting in an inability to sleep associated with motor and autonomic activation. Agrypnia excitata is the term which aptly defines this clinical condition, whose pathogenetic mechanism consists in an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from corticolimbic inhibitory control. Severance of cortical-subcortical limbic structures is due to visceral thalamus degeneration in fatal familial insomnia, and may depend on autoantibodies blocking voltage-gated potassium channels within the limbic system in Morvan's chorea, and the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in delirium tremens. On the basis of these findings, we suggest that a neuronal network, extending from the medulla to the limbic cortex, controls the sleep-wake cycle, operating in an integrated fashion following a caudorostral organization.
Provini
F
F
Department of Neurological Sciences, University of Bologna, Bologna, Italy. federica.provini@unibo.it
Cortelli
P
P
Montagna
P
P
Gambetti
P
P
Lugaresi
E
E
D006801:Humans; D034062:Insomnia, Fatal Familial / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D008032:Limbic System / Q000503:physiopathology*; D009460:Neurologic Examination; D011328:Prions / Q000032:analysis; D012890:Sleep / Q000502:physiology*
D011328:Prions