Phenotypical predictors of Restless Legs Syndrome in pregnancy and their association with basal ganglia and the limbic circuits

ABSTRACT The pregnancy-related restless legs syndrome (RLS) is thought to have a multifactorial etiology. However, the reason behind the manifestation of RLS during pregnancy remains largely elusive. A neurological and obstetrical cohort of 308 postpartum women was screened for RLS symptoms twice: 1 to 6 days (T0) and 12 weeks postpartum (T1). 57 participants were identified as affected by pregnancy-associated RLS. The clinical and anamnestic indicators of the condition were assessed by a pattern-learning classifier trained to predict the RLS status. Structural MRI was obtained from 25 of the 57 participants with RLS history in pregnancy. In this sample, a multivariate two-window algorithm was employed to systematically chart the relationship between brain structures and phenotypical predictors. The RLS prevalence rate in our sample was 19% (n=57), with the women suffering from RLS being older, more often unmarried, affected by gestational diabetes and having been more exposed to stressful life events. A history of RLS and the severity and frequency of repetitive compulsive movements were found to be the strongest predictors of RLS manifestation. In the RLS group, high cortisol levels, being married and receiving iron supplements were found to be associated with increased volumes in the bilateral striatum. Investigating pregnancy-related RLS in a frame of brain phenotype modes may help shed light on the heterogeneity of the condition.