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Circadian rhythm of CSF monoamines and hypocretin-1 in restless legs syndrome and Parkinson's disease

Academic Article
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Overview

authors

  • Poceta, J. Steven
  • Parsons, Loren (Larry)
  • Engelland, S.
  • Kripke, D. F.

publication date

  • January 2009

journal

  • Sleep Medicine  Journal

abstract

  • The symptoms of restless legs syndrome (RLS) have a circadian pattern and central nervous system dopamine has been implicated in the pathogenesis of the condition. We sought to characterize circadian variation in dopamine and related compounds in human cerebro-spinal fluid (CSF). CSF was continuously withdrawn for 22 h from an implanted lumbar intradural catheter and sampled from three patients with RLS, three patients with Parkinson's disease (PD) and three healthy volunteers. Patients had moderate disease severity and took no medications. We assayed CSF dopamine (DA), homovanillic acid (HVA), dihydroxy-phenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) from samples every 30 min by reversed-phase HPLC coupled with electrochemical detection. We also measured CSF levels of hypocretin-1 every hour by RIA. The procedure was well-tolerated. One patient ended the study early due to lumbar radicular pain and was not included in the analysis. There were no changes in CSF cell counts or protein levels from the first to the last samples. There was no difference in any of the compounds between groups, so we fit 24-h cosines to examine if the entire group had significant phase consistency. There was a peak for dopamine at 10 a.m. (p<0.025) and for HVA at 2 p.m. (p<0.01), but no evidence of a significant 24-h rhythm for DOPAC, 5-HIAA, the HVA/5-HIAA ratio, or hypocretin-1. These results demonstrate a circadian rhythm for CSF dopamine and HVA concentrations in humans, with higher levels in the daytime than at nighttime. This circadian variation could underlie the symptoms of RLS and sleep-related variation in motor function in PD.

subject areas

  • 3,4-Dihydroxyphenylacetic Acid
  • Aged
  • Biogenic Monoamines
  • Chromatography, High Pressure Liquid
  • Circadian Rhythm
  • Dopamine
  • Feasibility Studies
  • Female
  • Homovanillic Acid
  • Humans
  • Hydroxyindoleacetic Acid
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Neuropeptides
  • Orexins
  • Parkinson Disease
  • Pilot Projects
  • Restless Legs Syndrome
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Research

keywords

  • CSF
  • Circadian rhythm
  • Dopamine
  • Hypocretin
  • Parkinson's disease
  • RLS
  • Restless legs syndrome
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Identity

International Standard Serial Number (ISSN)

  • 1389-9457

Digital Object Identifier (DOI)

  • 10.1016/j.sleep.2007.11.002

PubMed ID

  • 18207455
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Additional Document Info

start page

  • 129

end page

  • 133

volume

  • 10

issue

  • 1

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