Christopher J Earley1, Keith Hyland, Richard P Allen. 1. Department of Neurology, Johns Hopkins Bayview Medical Center, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA. cearley@jhmi.edu
Abstract
BACKGROUND AND PURPOSE: 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. PATIENTS AND 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.
BACKGROUND AND PURPOSE: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. PATIENTS AND 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.
Authors: Kittisak Sawanyawisuth; Lawrence A Palinkas; Sonia Ancoli-Israel; Joel E Dimsdale; José S Loredo Journal: J Clin Sleep Med Date: 2013-01-15 Impact factor: 4.062
Authors: Shangru Lyu; Mark P DeAndrade; Erica L Unger; Stefan Mueller; Alexander Oksche; Arthur S Walters; Yuqing Li Journal: J Neurosci Res Date: 2020-05-19 Impact factor: 4.164
Authors: Shangru Lyu; Mark P DeAndrade; Stefan Mueller; Alexander Oksche; Arthur S Walters; Yuqing Li Journal: Behav Brain Res Date: 2019-07-31 Impact factor: 3.332
Authors: Shangru Lyu; Atbin Doroodchi; Hong Xing; Yi Sheng; Mark P DeAndrade; Youfeng Yang; Tracy L Johnson; Stefan Clemens; Fumiaki Yokoi; Michael A Miller; Rui Xiao; Yuqing Li Journal: Brain Struct Funct Date: 2020-05-28 Impact factor: 3.270
Authors: Christopher J Earley; Hiroto Kuwabara; Dean F Wong; Charlene Gamaldo; Rachel E Salas; James R Brašić; Hayden T Ravert; Robert F Dannals; Richard P Allen Journal: Sleep Date: 2013-01-01 Impact factor: 5.849