Availability of brain serotonin transporters in patients with restless legs syndrome

Abstract

BACKGROUND: Selective serotonin reuptake inhibitors have been associated with the risk of restless legs syndrome (RLS), suggesting that dysregulation of serotonergic neurotransmission may provoke or exacerbate RLS. METHODS: We compared the availability of serotonin transporter (SERT) between 16 drug-naïve patients with RLS and 16 healthy controls. SERT was measured in the pons and medulla via [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane (beta-CIT) SPECT. A ratio of specific to nonspecific brain uptake (V(3)'') was used for all comparisons. RLS was diagnosed according to the criteria proposed by the National Institute of Health, and its severity was measured using the International RLS Study Group (IRLSSG) Severity Scale. RESULTS: The availability of SERT was similar in the RLS group and the control group with regards to the pons (1.24 +/- 0.31 vs 1.24 +/- 0.25, p > 0.1) and the medulla (0.99 +/- 0.25 vs 1.00 +/- 0.23, p > 0.1). However, IRLSSG Severity Scale scores increased with decrease of SERT availability in both the pons (beta = -0.50, t = -3.19, p = 0.009) and the medulla (beta = -0.42, t = -2.44, p = 0.03). CONCLUSIONS: Although serotonin transporter (SERT) availability in pons and medulla was similar in the restless legs syndrome (RLS) group and the control group, the severity of RLS symptoms increased as the availability of SERT decreased. These data partially support the hypothesis that an increase of serotonergic neurotransmission in the brainstem may exacerbate RLS, possibly via dual modulations on striatal dopaminergic neurotransmission and on the activities of spinal motor and sensory neurons.