Fatal familial insomnia (FFI) is a hereditary prion disease linked to a missense mutation at codon 178 of the prion-protein gene (PRNP) located on chromosome 20, determining severe and selective atrophy of mediodorsal and anteroventral thalamic nuclei. FFI is characterized by physiological sleep loss, polygraphically appearing as a slow wave sleep loss, autonomic and motor hyperactivation with peculiar episodes of oneiric stupor. Dysfunction of the autonomic system is a great burden for FFI patients consisting of sympathetic overactivation, dysregulation of its physiological responses, and disruption of circadian rhythms. Cardiovascular and thermoregulatory systems are the most frequently affected, confirming the increased sympathetic drive with preserved parasympathetic responses. Sleep loss, autonomic, and motor hyperactivation define agrypnia excitata (AE), which is not exclusive to FFI, but described also in Morvan syndrome (MS) and delirium tremens (DT). These three conditions (FFI, MS and DT) present different pathophysiological mechanisms but share the same thalamolimbic impairment of which AE is one of the possible clinical presentations. FFI, and consequently AE, is a model for the investigation of the essential role of the thalamus in the organization of body homeostasis, integrating both sleep and autonomic function control.
Baldelli L., Calandra Buonaura G., Provini F., Cortelli P. (2021). Fatal familial insomnia. Cham : Springer [10.1007/978-3-030-62263-3_18].
Fatal familial insomnia
Baldelli L.Primo
Writing – Original Draft Preparation
;Calandra Buonaura G.Secondo
Supervision
;Provini F.Writing – Review & Editing
;Cortelli P.Ultimo
Conceptualization
2021
Abstract
Fatal familial insomnia (FFI) is a hereditary prion disease linked to a missense mutation at codon 178 of the prion-protein gene (PRNP) located on chromosome 20, determining severe and selective atrophy of mediodorsal and anteroventral thalamic nuclei. FFI is characterized by physiological sleep loss, polygraphically appearing as a slow wave sleep loss, autonomic and motor hyperactivation with peculiar episodes of oneiric stupor. Dysfunction of the autonomic system is a great burden for FFI patients consisting of sympathetic overactivation, dysregulation of its physiological responses, and disruption of circadian rhythms. Cardiovascular and thermoregulatory systems are the most frequently affected, confirming the increased sympathetic drive with preserved parasympathetic responses. Sleep loss, autonomic, and motor hyperactivation define agrypnia excitata (AE), which is not exclusive to FFI, but described also in Morvan syndrome (MS) and delirium tremens (DT). These three conditions (FFI, MS and DT) present different pathophysiological mechanisms but share the same thalamolimbic impairment of which AE is one of the possible clinical presentations. FFI, and consequently AE, is a model for the investigation of the essential role of the thalamus in the organization of body homeostasis, integrating both sleep and autonomic function control.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
