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Sleep disturbances associated with DPPX autoantibodies: a case series

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Abstract

Study objectives

To describe a case series of patients with prominent sleep disturbances and their polysomnography findings in six patients with dipeptidyl-peptidase-like protein-6 (DPPX) autoimmunity syndrome.

Methods

Of 13 patients with DPPX autoimmunity evaluated at Mayo Clinic, 6 were seen by Sleep Medicine with polysomnography and were assessed with blood and cerebrospinal fluid, neuroimaging, neuropsychological testing, and evaluation tailored to clinical presentation.

Results

Median age of our six DPPX autoimmunity patients was 57 (range 27–70) years, with one woman. All patients had prominent gastrointestinal disturbances, most with prominent and early weight loss, and a spectrum of neuropsychiatric disturbances including cognitive impairment, myoclonus, exaggerated startle, and dysautonomia. Sleep disturbances included insomnia and obstructive sleep apnea in six patients, periodic leg movements of sleep in four, and REM sleep behavior disorder in two. Polysomnography demonstrated REM sleep-atonia loss in four patients, and ambiguous sleep with status dissociatus (mixed features of wakefulness, non-rapid eye movement [NREM], and REM sleep) appeared in one patient. Five of six patients showed neurological improvement with immunotherapy, including three with at least partial improvement in sleep disturbances.

Conclusion

Our patients with DPPX autoimmunity syndrome had prominent sleep disturbances including sleep-disordered breathing, REM sleep behavior disorder, and abnormal NREM sleep architecture with highly variable clinical presentations. DPPX autoimmunity should be considered in cases with a triad of sleep disturbance, neurological features of hyperexcitability, and systemic symptoms of gastrointestinal disturbance and weight loss. Future prospective studies of DPPX autoimmunity syndrome including detailed sleep evaluation and follow-up are necessary.

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Data availability

Data will be provided for qualified investigators by request to the corresponding author (EKStL).

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Acknowledgements

The authors also thank Ms. Lea Dacy, Department of Neurology, for secretarial support during the submission process.

Funding

This work was supported in part by the National Center for Advancing Translational Sciences grant Number UL1 TR002377, and by the National Institute on Aging grant R34 AG056639. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Author information

Author notes

  1. Avi Gadoth and Michelle F. Devine have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Avi Gadoth, Michelle F. Devine, Sean J. Pittock, Andrew McKeon, W. Oliver Tobin, Stuart J. McCarter & Erik K. St. Louis

  2. Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Avi Gadoth, Sean J. Pittock & Andrew McKeon

  3. Encephalitis Center, Tel-Aviv Medical Center, Tel-Aviv, Israel

    Avi Gadoth

  4. Center for Sleep Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA

    Michelle F. Devine, Thomas R. Gossard, Elena F. D. Cattaneo, Stuart J. McCarter & Erik K. St. Louis

  5. Olmsted Medical Center, Rochester, MN, USA

    Michelle F. Devine

  6. St. Olaf College, Northfield, MN, USA

    Thomas R. Gossard

  7. The University of Minnesota-Twin Cities, Minneapolis, MN, USA

    Elena F. D. Cattaneo

Authors
  1. Avi Gadoth
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Corresponding author

Correspondence to Erik K. St. Louis.

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Conflicts of interest

The following authors have nothing to disclose: Gadoth, McCarter, Gossard, Cattaneo, Devine. Non-financial Interests: S.J. Pittock has provided consultation to Alexion Pharmaceuticals and MedImmune but has received no personal fees or personal compensation for these consulting activities. A. McKeon has consulted for MedImmune, LLC, Grifols and Euroimmun but has not received personal compensation for these activities. E. St. Louis has consulted for Axovant, Inc., but has not received personal compensation for these activities. Financial Interests: S. J. Pittock has received research support from Alexion Pharmaceuticals, MedImmune and Grifols. W. O. Tobin receives research support from the National Institute of Neurological Disorders and Stroke, the National Institute of Allergy and Infectious Diseases, Alexion Pharmaceuticals, Sanofi US Services Inc., and UCB Biosciences. A. McKeon receives research support from MedImmune, LLC. E. St. Louis receives research support from the National Center for Advancing Translational Sciences, the National Institute of Neurological Disorders and Stroke, the National Heart, Lung and Blood Institute, Axovant, Inc., and Sunovion, Inc.

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Gadoth, A., Devine, M.F., Pittock, S.J. et al. Sleep disturbances associated with DPPX autoantibodies: a case series. J Neurol 270, 3543–3552 (2023). https://doi.org/10.1007/s00415-023-11698-y

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  • DOI: https://doi.org/10.1007/s00415-023-11698-y

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