Hypothalamic subfield volumes and morphometric covariance network organization in restless legs syndrome.

OBJECTIVES

The hypothalamus contributes to sleep-wake and circadian regulation, but whether its subfields show structural differences in restless legs syndrome (RLS) remains unclear. We investigated hypothalamic subfield volumes and morphometric covariance network organization in patients with RLS.

METHODS

This secondary analysis included 71 patients with primary RLS and 55 healthy controls who underwent three-dimensional T1-weighted MRI. Hypothalamic subfield volumes were obtained using the FreeSurfer segmentation of hypothalamic subunits module and normalized to estimated total intracranial volume. Bilateral mean hypothalamic subfield volumes were compared between groups using analysis of covariance adjusted for age and sex, with false discovery rate (FDR) correction across six volumetric comparisons. Exploratory morphometric covariance analysis was performed using 10 left and right hypothalamic subfields as network nodes. Associations between hypothalamic volume measures and clinical variables were also examined within the RLS group.

RESULTS

Patients with RLS had a significantly larger bilateral tubular inferior hypothalamic subfield volume than healthy controls (adjusted means, 0.00766 vs. 0.00684; adjusted mean difference, 0.00082; 95% confidence interval, 0.00023-0.00141; adjusted Cohen's d = 0.53; 95% confidence interval, 0.14-0.91; p = 0.007; FDR-corrected p = 0.042). No significant differences were observed in other hypothalamic subfields or whole hypothalamic volume after FDR correction. Global and node-wise morphometric covariance network measures did not differ significantly between groups. No associations between hypothalamic volume measures and clinical variables remained significant after FDR correction.

CONCLUSIONS

RLS was associated with selective enlargement of the bilateral tubular inferior hypothalamic subfield, indicating a localized structural difference rather than widespread alteration of hypothalamic volume or morphometric covariance organization. Because structural MRI cannot identify the cellular or neurochemical basis of this finding, its biological and clinical significance requires confirmation in independent, medication-controlled, and longitudinal studies.