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Sleep disturbances are common in patients with autoimmune encephalitis

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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.

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Notes

  1. Details available via the Mayo Clinic website: https://www.mayocliniclabs.com/test-catalog/Overview.

  2. Details available via the Athena Diagnostics website: https://www.athenadiagnostics.com/view-full-catalog/r/recombx-trade;-mata-autoantibody-test-(1).

Abbreviations

AASM:

American Academy of Sleep Medicine

AE:

Autoimmune encephalitis

AHI:

Apnea-hypopnea index

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CRMP5:

Collapsin response-mediator protein-5

CSF:

Cerebrospinal fluid

EEG:

Electroencephalography

GABA:

Gamma-aminobutyric acid

Hu:

Type 1 anti-neuronal nuclear antibody

LGI1:

Leucine-rich glioma-inactivated protein 1

MRI:

Magnetic resonance imaging

N1:

Stage I sleep

N2:

Stage II sleep

N3:

Stage III sleep

NMDAR:

N-Methyl-d-aspartate receptor

PSG:

Polysomnography

REM:

Rapid eye movement

RLS:

Restless legs syndrome

VGCC:

Voltage-gated calcium channel

Yo:

Purkinje cell cytoplasmic antibody type 1

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Acknowledgements

Funding was provided by the American Academy of Neurology/American Brain Foundation (Clinical Research Training Fellowship to GSD), and via philanthropic contributions from patients and family members to promote research and education into Autoimmune Encephalitis (GSD).

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Authors and Affiliations

  1. Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA

    Margaret S. Blattner, Gabriela S. de Bruin, Robert C. Bucelli & Gregory S. Day

  2. The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, 4488 Forest Park Avenue, Suite 160, Saint Louis, MO, 63108, USA

    Gregory S. Day

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  1. Margaret S. Blattner
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  2. Gabriela S. de Bruin
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  3. Robert C. Bucelli
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Correspondence to Gregory S. Day.

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Ethical standards

All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all the individual participants included in the study.

Conflicts of interest

On behalf of all the authors, the corresponding author states that there are no conflicts of interest. Dr. Blattner has no disclosures to report. Dr. de Bruin has equity in Neuroquestions, LLC. Dr. Bucelli receives an annual gift from a patient’s family for Parsonage-Turner research; served on an advisory board for MT Pharma; and has equity in Neuroquestions, LLC. Dr. Day has served as a topic editor on dementia for DynaMed Plus (EBSCO Industries, Inc) and as clinical director for the Anti-NMDA Receptor Encephalitis Foundation (uncompensated). He receives research/grant support from The American Academy of Neurology/American Brain Foundation, Avid Radiopharmaceuticals, the Foundation for Barnes Jewish Hospital, and the National Institutes of Health (P01AG03991, R56AG057195, U01AG057195) and holds stock in ANI Pharmaceuticals, Inc. Dr. Day has provided record review and expert medical testimony on legal cases pertaining to the management of Wernicke encephalopathy.

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Blattner, M.S., de Bruin, G.S., Bucelli, R.C. et al. Sleep disturbances are common in patients with autoimmune encephalitis. J Neurol 266, 1007–1015 (2019). https://doi.org/10.1007/s00415-019-09230-2

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  • DOI: https://doi.org/10.1007/s00415-019-09230-2

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