Sleep disturbances are common in patients with autoimmune encephalitis

Abstract

Objectives: Autoimmune encephalitis (AE) is increasingly recognized as an important cause of subacute cognitive decline, seizures, and encephalopathy, with an ever-broadening clinical phenotype. Sleep disturbances are reported in AE patients, including rapid eye movement sleep behavior disorder, hypersomnia, fragmented sleep, and sleep-disordered breathing; however, the prevalence of sleep disturbances and contributions to outcomes in AE patients remain unknown. There is a need to determine the prevalence of sleep disturbances in AE patients, and to clarify the relationship between specific autoantibodies and disruptions in sleep.

Methods: Clinical history, results of serum and cerebrospinal fluid testing, electroencephalography, and neuroimaging were reviewed from 26 AE patients diagnosed and managed at our tertiary care hospital. Polysomnography was performed in patients with clinical indications, yielding data from 12 patients.

Results: The median age of AE patients was 53 years (range 18-83). Autoantibodies against intracellular antigens (including Ma and Hu autoantibodies) were identified in 6/26 (23%) patients, while autoantibodies against cell-surface neuronal antigens (including NMDAR and LGI1) were identified in 20/26 (77%) patients. New sleep complaints were reported by 19/26 (73%) AE patients, including gasping or snoring (9/19, 47%), dream enactment behavior (6/19, 32%), insomnia (5/19, 29%), hypersomnia (4/19, 21%), other parasomnias (4/19, 21%), and dream-wake confusional states (2/19, 11%). Dream enactment behaviors were particularly common in AE associated with LGI1 autoantibodies, reported in 4/7 (57%) patients. Polysomnography showed reduced total sleep time, stage 3 and rapid eye movement sleep, and prominent sleep fragmentation.

Conclusion: Sleep disturbances are common in AE, warranting active surveillance in affected patients. Improved identification and treatment of sleep disorders may reduce morbidity associated with AE and improve long-term outcomes.

Keywords: Autoimmune encephalitis; LGI1 autoantibodies; NMDAR encephalitis; Polysomnography; REM behavior disorder; Restless legs; Sleep apnea.

Figure 1:

Sleep fragmentation in AE. Tracings of representative sleep stages from three AE patients. A: 52 year-old woman with AE associated with NMDAR antibodies (Case 20), B: 66 year-old man with Hu antibodies (Case 6), C: 83 year-old woman with LGI1 antibodies (Case 8). The x-axis depicts sleep study duration (hours). The y-axis depicts sleep stages: movement time (MT), wake (W), rapid eye movement sleep (R), stage I sleep (N1), stage II sleep (N2), and stage III sleep (N3).