Sleep Disturbances Associated with Neurological Autoimmunity

Abstract

Associations between sleep disorders and neurological autoimmunity have been notably expanding recently. Potential immune-mediated etiopathogenesis has been proposed for various sleep disorders including narcolepsy, Kleine-Levin syndrome, and Morvan syndrome. Sleep manifestations are also common in various autoimmune neurological syndromes, but may be underestimated as overriding presenting (and potentially dangerous) neurological symptoms often require more urgent attention. Even so, sleep dysfunction has been described with various neural-specific antibody biomarkers, including IgLON5; leucine-rich, glioma-inactivated protein 1 (LGI1); contactin-associated protein 2 (CASPR2); N-methyl-D-aspartate (NMDA)-receptor; Ma2; dipeptidyl-peptidase-like protein-6 (DPPX); alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R); anti-neuronal nuclear antibody type-1 (ANNA-1, i.e., Hu); anti-neuronal nuclear antibody type-2 (ANNA-2, i.e., Ri); gamma-aminobutyric acid (GABA)-B-receptor (GABA-B-R); metabotropic glutamate receptor 5 (mGluR5); and aquaporin-4 (AQP-4). Given potentially distinctive findings, it is possible that sleep testing could potentially provide objective biomarkers (polysomnography, quantitative muscle activity during REM sleep, cerebrospinal fluid hypocretin-1) to support an autoimmune diagnosis, monitor therapeutic response, or disease progression/relapse. However, more comprehensive characterization of sleep manifestations is needed to better understand the underlying sleep disruption with neurological autoimmunity.

Keywords: Autoimmunity; Diagnosis; Neurological autoimmunity; Polysomnography; Sleep disorders; Therapy..

Fig. 1

Rapid eye movement (REM) sleep without atonia (RSWA). A 30 second epoch from the polysomnogram of a leucine-rich glioma inactivated-protein-1-IgG positive (LGI1+) patient demonstrating increased phasic muscle activity in the anterior tibialis (linked legs) during REM sleep. LOC, left outer canthus; ROC, right outer canthus; EMG, electromyogram; ECG, electrocardiogram; PAP Flow, positive airway pressure airflow; Sono, sonogram; O2Sat, oxyhemoglobin saturation; Pleth, impedance plethysmography; Abd, abdomen

Fig. 2

Magnetic resonance imaging (MRI) brain with leucine-rich glioma inactivated-protein-1 IgG. Coronal T2 fluid-attenuated inversion recovery (FLAIR) of an leucine-rich glioma inactivated-protein-1-IgG positive (LGI1+) limbic encephalitis patient with bilateral (left more than right) mesial temporal hyperintensities (a, arrow), axial T2 FLAIR of an LGI1+ limbic encephalitis patient with bilateral (mesial temporal hyperintensities consistent with limbic encephalitis (b, arrows), axial T2 of an LGI1+ patient with a non-enhancing caudal pontine lesion (c, arrow)