Analysis of ciclic alternating patterns in Agrypnia Excitata (AE): Insights from a case of limbic autoinmune encephalopathy (AE-LAE)

Abstract

Agrypnia Excitata” (AE) is a term coined originally by Lugaresi and Provini to describe a syndrome caused by a dysfunction in thalamo-limbic circuits producing severe insomnia, mental confusion, dream enactment, motor and autonomic activation. This syndrome is observed in fatal familial insomnia (FFI), limbic autoinmune encephalopathy, delirium tremens and the Mulvihill-Smith syndrome. Oscillatory EEG rhythms could be observed in these patients, resembling the named cyclic alternating pattern (CAP) in NoREM sleep, but, during REM sleep (”pseudosleep”) in patients with FFI (Garay A., Neurology 1994). Now, we attempt to characterize a peculiar CAP rhythm observed in our case of proven LAE. We analyzed polysomnograms of our case of LAE-VGKC (PSGs, n = 3). During PSGs the following variables were monitored: electroencephalogram (EEG), electrooculogram (EOG), electromyogram (EMG), nasal and oral airflow, thoracic and abdominal effort and pulse oximetry. Sleep-wake patterns were scored in 30 s. epochs according standard criteria (AAMS2007) and 3–5 s epochs for spectral analysis of the frequency components from Fast Fourier Transform (FFT) of the raw data of EEG and ECG activities and thorough continuous wavelet transform (CWT) using a multirresolution wavelet filter (Daubechies-level 7) we analyzed synchronized EEG–ECG activity removing muscular artifacts related to CAP rhythm. (a) LAE was characterized by a drastic decrease of TST, sparse atypical REM/NoREM sleep and for a CAP rhythm during states named as quiet and active wakefulness (qW–aW), (b) LAE intra-wakefulness structure showed a CAP rhythm with an increase of 30–60 s centered bursts ( p < 0.05. K.W. NP test), (c) wakefulness EEG activity showed oscillations bellow 1 Hz, (d) CWT ECG R-R interval analysis showed reduced variability when analyzing qW–aW transitions. The AE-LAE case of this study presented sparse episodes of atypical sleep and showed presleep behavior during quiet and active wakefulness with a CAP behavior expressed as brief episodes of motor quiescence and overactivity. The observed reduction of variability of CWT R-R interval analysis and background FFT EEG activity bellow 1 Hz could be related to thalamo-cortico-limbic alterated modulation/disconnection and to the appearance of cortical top-down oscillations liberated of caudal- rostral influences (Kuhn B. et al. PNAS, 2008). Thus, subtyping AEs could be a way to the understanding of the role of thalamus regulation in wakefulness and sleep during health and illness. CEMIC-CONICET, Buenos Aires, Argentina.