Circadian changes in CSF dopaminergic measures in restless legs syndrome.
OBJECTIVE
Restless legs syndrome (RLS) has a circadian component with symptoms being prominent at night. The dopaminergic (DAergic) system, which plays a role in RLS, entails circadian changes that parallel RLS symptom changes. The aim of this study was to look for relative and diurnal differences in DAergic activity.


METHODS
All RLS subjects were treated prior to their enrollment in the study but were all drug-free for at least 2 weeks prior to evaluation. Cerebrospinal fluid (CSF) collected at 10 p.m. was used to determine DA-related co-factors and metabolites. These were compared to CSF values collected in a previous study at 10 a.m.


RESULTS
The only significant finding from the 10 p.m. samples (30 RLS; 22 control) was increased 3-ortho-methyldopa (3OMD) for RLS compared to controls. A comparison of the 10 p.m. to 10 a.m. values (16 RLS; 9 controls) showed small, non-significant diurnal changes for controls but large diurnal changes in tetrahydrobiopterin (BH4), HVA:5HIAA ratio and 3OMD for RLS, with the 10 a.m. sample showing increases in all three CSF factors compared to the 10 p.m. sample.


CONCLUSIONS
The greater diurnal changes in RLS suggest greater fluctuations than normal in DAergic circadian dynamics. The increased 3OMD concentration in the absence of concurrent exogenous levodopa (l-dopa) suggests changes in synthesis or metabolism of l-dopa in RLS.
Earley
Christopher J
CJ
Department of Neurology, Johns Hopkins Bayview Medical Center, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA. cearley@jhmi.edu
Hyland
Keith
K
Allen
Richard P
RP
D001708:Biopterins / Q000134:cerebrospinal fluid; D021081:Chronobiology Disorders / Q000453:epidemiology*; D004298:Dopamine / Q000134:cerebrospinal fluid*; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008750:Methyldopa / Q000134:cerebrospinal fluid; D008875:Middle Aged; D017286:Polysomnography; D012148:Restless Legs Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000453:epidemiology*
D001708:Biopterins; D006897:Hydroxyindoleacetic Acid; D008750:Methyldopa; D004298:Dopamine; D006719:Homovanillic Acid