Multimodal assessment of sleep and regional brain volumes in AQP4-IgG-positive neuromyelitis optica spectrum disorder: An exploratory cross-sectional study

Sleep disturbance is common in aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), but its clinical and neurobiological correlates remain incompletely characterized; prior studies used single-modality assessments. In this exploratory cross-sectional study we characterized sleep-wake patterns in clinically stable AQP4-IgG-positive NMOSD and explored volume-sleep associations. Patients and controls underwent questionnaires, 7-day wrist actigraphy and structural MRI; intracranial volume-normalized regional volumes and within-patient volume-sleep associations were examined, with Benjamini-Hochberg false discovery rate (FDR) correction. Twenty-four patients and 26 controls were enrolled; 20 patients and 20 database-derived controls contributed MRI. Patients were older than controls (49.7 versus 33.0 years; g = 1.40); analyses were adjusted for age and body mass index (BMI). After adjustment, patients showed longer time in bed (+58 min) and total sleep time (+50 min), whereas sleep efficiency and wake after sleep onset did not differ. Higher BMI was associated with lower sleep efficiency (r = -0.44) and longer sleep onset latency. Subjective sleep disturbance and pain-related quality of life were worse in NMOSD. After FDR correction, volume reductions were observed in bilateral hippocampal molecular-layer subfields and all five corpus callosum segments, with suggestive thalamic reductions; no volume-sleep association survived. Sleep disturbance in clinically stable AQP4-IgG-positive NMOSD was characterized by greater subjective sleep burden and altered sleep-wake timing, with associations observed with clinical and metabolic factors. These hypothesis-generating findings are consistent with a multifactorial pattern of associations and highlight the need for longitudinal studies integrating objective sleep measurement, neuroimaging and biomarkers.