Agrypnia Excitata: a generalized overactivity syndrome and a useful concept in the neurophysiopathology of sleep

Objectives: To analyse the clinicophysiological features of delirium tremens (DT), Morvanʹs fibrillary chorea (MC) and fatal familial insomnia (FFI) as representative of the new concept of Agrypnia Excitata (AE). Methods: DT, MC and FFI were compared for their clinical and polysomnographic features and, for MC and FFI, post-mortem verification. Results: DT, MC and FFI all display profound loss of slow-wave sleep (SWS) and abnormal rapid eye movement (REM) sleep with lack of muscular atonia and enacted dreams. Sleep spindles and K complexes are severely reduced. Motor overactivity is associated with increased sympathergic functions. Neuropathology discloses severe loss of neurons in the thalami and cingular areas in FFI, and leakage of antibodies in the thalamus in MC. Conclusions: Based on the similarities in DT, MC and FFI, we propose the new concept of AE as a clinical condition characterized by loss of SWS and abnormal REM sleep, associated with motor and autonomic sympathergic activation. AE is due to dysfunction of the thalamo-limbic system. Moreover, the preservation of light sleep in the face of severe loss of deep sleep in AE argues that 3 rather than the usually considered two (non REM and REM) independent states of sleep exist.