Agrypnia excitata
 Read with caution! This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk. |
Agrypnia excitata is the name given to the state of constant arousal that prevents sleep. It is associated with FFI (though not other spongiform encephalopathies) as well as other, non-prion-related diseases.
“Insomnia in neurological diseases,” Provini et al., Semin Neurol (2005)
http://www.ncbi.nlm.nih.gov/
CNS lesions and/or dysfunction in three specific neurological conditions (fatal familial insomnia, Morvan’s chorea, and delirium tremens) impair the basic mechanisms of sleep generation inducing a syndrome in which the inability to sleep is consistently associated with motor and sympathergic overactivation. Agrypnia excitata is the term that aptly defines this generalized overactivation syndrome.
“Agrypnia excitata: current concepts and future prospects in management,” Hazin et al., J Neuropsychiatry Clin Neurosci (2009)
http://www.ncbi.nlm.nih.gov/
Agrypnia excitata is an extremely rare, life-threatening syndrome characterized by autonomic activation, persistent insomnia, and generalized overactivity. Agrypnia excitata describes a triad of three separate conditions: delirium tremens, Morvan’s chorea, and familial fatal insomnia (FFI). Each of the aforementioned three conditions have sleep disturbances as a unifying theme and results in distinct neurophysiological findings. The following is an overview of agrypnia excitata with a particular emphasis placed upon each of the three individual conditions that constitute the syndrome with recommendations on appropriate management.
“Fatal familial insomnia and agrypnia excitata,” Lugaresi et al., Rev Neurol Dis (2007)
http://www.ncbi.nlm.nih.gov/
This review summarizes the pioneering steps culminating in the identification of a novel disease, fatal familial insomnia (FFI), a hereditary prion disease. Together with Morvan’s chorea and delirium tremens, FFI is characterized by an inability to sleep associated with motor and autonomic overactivation. We named this pattern agrypnia excitata, a syndrome caused by a dysfunction in thalamolimbic circuits. This review highlights the strategic role of the limbic thalamus in the central autonomic network running from the limbic cortex to the lower brainstem and regulating sleep and wakefulness.
“Fatal familial insomnia: a model disease in sleep physiopathology,” Montagna, Sleep Med Rev (2005)
http://www.ncbi.nlm.nih.gov/
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.