Fatal Familial Insomnia and Agrypnia Excitata: Insights into Human Prion Disease Genetics and the Anatomo-Physiology of Wake and Sleep Behaviours

Abstract

The circuit controlling and regulating homeostasis in the brain and the entire organism appears to be interrupted at the thalamic level in fatal familial insomnia (FFI), or functionally imbalanced due to a GABA-A neural system block in Morvan syndrome (MS) or concomitant downregulation of the gamma-aminobutyric acid (GABA) system and upregulation of N-methyl-D-aspartate (NMDA) glutamatergic system in DT. This impaired circuit gives rise to the syndrome we named agrypnia excitata (AE). The resulting homeostatic imbalance leads to an inability to generate synchronized (calm) sleep and hence the inability to stay awake. What remains of sleep and wake is a state of subvigilance in which stage 1 is mixed with fragments of rapid eye movement (REM) sleep. This peculiar electrophysiological condition is accompanied by a permanent state of autonomic and motor activation whose hallmarks are stereotypic repetition of gestures mimicking daily-life activities. (PsycINFO Database Record (c) 2019 APA, all rights reserved)