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Sleep disturbances are common in patients with autoimmune encephalitis

  • Margaret S. Blattner
  • Gabriela S. de Bruin
  • Robert C. Bucelli
  • Gregory S. DayEmail author
Original Communication
  • 6 Downloads

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 NMDAR encephalitis LGI1 autoantibodies REM behavior disorder Restless legs Sleep apnea Polysomnography 

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

Notes

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).

Compliance with ethical standards

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.

Supplementary material

415_2019_9230_MOESM1_ESM.docx (30 kb)
Supplementary material 1 (DOCX 30 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Margaret S. Blattner
    • 1
  • Gabriela S. de Bruin
    • 1
  • Robert C. Bucelli
    • 1
  • Gregory S. Day
    • 1
    • 2
    Email author
  1. 1.Department of NeurologyWashington University School of MedicineSaint LouisUSA
  2. 2.The Charles F. and Joanne Knight Alzheimer Disease Research CenterWashington University School of MedicineSaint LouisUSA

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