We characterized clinical and polysomnographic features including quantitative rapid eye movement (REM) sleep without atonia (RSWA) in patients with leucine-rich, glioma inactivated protein 1 (LGI1) and contactin-associated protein 2 (CASPR2) autoimmunity in comparison to voltage-gated-potassium-channel-complex  (VGKC) double negative patients (VGKC seropositive but LGI1/CASPR2-IgG negative).

Autoimmune encephalopathies are associated with varied sleep disturbances including REM behavior disorder (RBD), characterized by dream enactment behavior (DEB) and RSWA. Previous quantitative RSWA analysis in VGKC-IgG seropositivity (VGKC+) has been limited.

We retrospectively analyzed clinical features and polysomnography between VGKC+ patients with/without LGI1/CASPR2-IgG seropositivity (LGI1+/CASPR2+) and age-sex matched controls, and quantified RSWA in comparison to previously determined normative RSWA percentiles.

Among 11 (9 LGI1+, 2 CASPR2+) patients, insomnia was the most common presenting sleep disturbance (55%). Among 12 VGKC double negative patients, only 1 (8%) reported insomnia. N3 was reduced in LGI1+/CASPR2+ patients compared to controls and VGKC double negative patients (p<0.05). Eight (73%) LGI1+/CASPR2+ patients met RBD diagnostic thresholds, including 4 (36%) who reported dream enactment. LGI1+/CASPR2+ patients had highest RSWA levels, while VGKC double negative patients had intermediate RSWA levels compared to controls when accounting for antidepressant use (p<0.05). All ten LGI1+/CASPR2+ patients treated with immunotherapy benefited, with 6 of 10 having improved sleep disturbances

The sleep phenotype of LGI1/CASPR2-IgG autoimmunity syndromes is associated with reduced N3 and elevated RSWA levels, while VGKC double negative patients also had intermediate RSWA elevation between that of controls and LGI1+/CASPR2+ patients. Polysomnography provides objective markers for monitoring disease progression and treatment outcomes in patients with LGI1, CASPR2, and VGKC autoimmunity syndromes.