CSF dopamine, serotonin, and biopterin metabolites in patients with restless legs syndrome

To evaluate the role of CNS dopaminergic systems in Restless Legs Syndrome (RLS), homovanillic acid (HVA), tetrahydrobiopterin (BH4), and neopterin (NEOP), were assayed in CSF from RLS patients. The serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was also measured.

CSF was taken from 16 RLS patients after 2 weeks off medication and from 14 control subjects. The CSF metabolites were determined using HPLC techniques.

There was no significant difference in HVA or 5-HIAA, but NEOP and BH4 were higher in RLS patients. The RLS group was significantly older than the control group (64.2 +/- 9.2 years vs. 51.4 +/- 6.3 years; P < 0.001). A multiple regression analysis showed a strong correlation between age and 5-HIAA (r = 0.46, P = 0.04) and between age and NEOP (r = 0.61, P < 0.01). To eliminate the potential error created by the age difference between groups, an age-adjusted subgroup of RLS and control subjects were compared. There was still no difference found for HVA; however, 5-HIAA was now significantly lower (P < 0.01) in the RLS subgroup. Age-adjustment eliminated the differences previously found for NEOP, (P = 0.12), but BH4 continued to remain higher in the RLS group (P < 0.01).

Differences in CSF HVA concentrations were not found. The changes in 5-HIAA and BH4 are of unclear clinical significance and require further assessment with appropriate age-matched controls.