Fatal familial insomnia and Agrypnia Excitata: Autonomic dysfunctions and pathophysiological implications

Sleep Disorders in Leucine-Rich Glioma-Inactivated Protein 1 and Contactin Protein-Like 2 Antibody-Associated Diseases

“…The most severe type of SD, associated with nearly continuous motor overactivation and peculiar dream-like behavior, was known as agrypnia excitata. Agrypnia excitata had been reported in Morvan's syndrome, familial insomnia, and alcohol withdrawal syndrome (18,19). Patients who had difficulty in initiating sleep, difficulty maintaining sleep, waking up too early, or TST of <360 min resulting in daytime sleep impairment were considered to have insomnia.…”

Fatal Familial Insomnia: A Rare Disease with Unique Clinico‐Neurophysiological Features

“…129MV patients present fragmented and less prominent autonomic hyperactivation, ataxia can be the earliest symptom, while sleep and autonomic derangement, dysarthria, and bulbar dysfunctions can manifest at a later stage. 2,5 In conclusion, this patient and his relatives showed typical features of 129MV FFI. Patients reporting sleep disturbances and positive familiar history with rapidly fatal progression should always be suspected for FFI and undergo 24-hours (if available) polygraphic sleep and autonomic assessment (blood pressure and heart rate) to exclude this rare but unique disorder.…”

“…Blood pressure and heart rate circadian rhythms are the ones initially impaired, while acute responses of autonomic nervous system still work. 2 It should be also pointed out that progressive ataxia, highlighted here as an atypical feature, is indeed a typical motor manifestation of FFI 129MV patients, 3 that eventually evolves towards complete inability to stand and walk ("thalamic astasia"), as shown in the last video fragment. Moreover, erratically saccadic ocular movements were already described 4 in FFI (where they are not so infrequent -P.C.…”

“…Indeed, SRBD are not so infrequent at FFI onset, sometimes associated with vocal cord dysfunction. 2 In addition, at the beginning of FFI, autonomic tests are usually normal, especially in 129MV patients. Blood pressure and heart rate circadian rhythms are the ones initially impaired, while acute responses of autonomic nervous system still work.…”

Thirty years of fatal familial insomnia and autonomic research: celebrating the past, embracing the future

“…Our breakthroughs helped Stanley Prusiner in his work on prions [8], awarded with a muchdeserved Nobel Prize in 1997, as well as the definition of the role of the medial thalamus in the central autonomic network [9,10]. From a pathophysiology perspective, our initial hunch that an excessive sympathetic tone was both cause and effect of the severe slow-wave sleep deprivation has been confirmed, and is the rationale to swap the ambiguous and misleading "insomnia" with "agrypnia excitata" (agrypnia-wakefulness in Greek; and excitataexcited in Latin, in reference to the permanent motor and autonomic hyperactivation in these patients) [11].…”