title: Abnormally increased CSF 3-Ortho-methyldopa (3-OMD) in untreated restless legs syndrome (RLS) patients indicates more severe disease and possibly abnormally increased dopamine synthesis.
abstract: BACKGROUND
  Abnormally high CSF 3-OMD occurs frequently for RLS patients indicating either increased l-dopa synthesis, limitations in l-dopa decarboxylation or increased MAT/COMT activity, or some combination of these. Increased tyrosine hydroxylase activity was found on both the RLS autopsy and the rodent iron-deprivation model of RLS, suggesting increased DA synthesis in RLS. We, therefore, hypothesized elevated 3-OMD in RLS results from increased DA synthesis and that this should occur accordingly with increased HVA. It would then also reflect both the more severe iron insufficiency pathology of RLS and greater clinical severity, shown by the objective measure of PLMS/hr.
  
  
  METHODS
  Patients off RLS medications and matched controls had lumbar punctures at either 10 a.m. or 10 p.m.; RLS patients were grouped by normal or abnormally high 3-OMD (>10 nmol/l).
  
  
  RESULTS
  Forty-nine RLS patients (30 high, 19 normal 3-OMD) and 36 age- and gender-matched controls, analyzed separately by time of CSF collection, did not significantly differ in age or gender. RLS patients with high 3-OMD had significantly higher CSF HVA, while those with normal 3-OMD had consistently lower CSF HVA than controls. CSF ferritin was consistently lower compared to controls for the high 3-OMD but not the normal 3-OMD RLS patients. The PLMS/hr was significantly higher for RLS patients with high compared to normal 3-OMD, indicating high 3-OMD patients had more severe RLS.
  
  
  CONCLUSIONS
  Abnormal elevation in 3-OMD for RLS patients may reflect increased dopamine synthesis for more severe but perhaps not mild RLS. These differences in the putative dopamine pathology of RLS may indicate different phases or expression of RLS biology or different underlying disease processes.
authors.affiliation: Johns Hopkins University, School of Medicine, Department of Neurology, Asthma & Allergy Building, 1B76B 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. richardjhu@mac.com
authors.forename: Richard P
authors.initials: RP
authors.lastname: Allen
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
authors.forename: Keith
authors.initials: K
authors.lastname: Hyland
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Earley
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002940:Circadian Rhythm; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D004298:Dopamine / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012148:Restless Legs Syndrome / Q000134:cerebrospinal fluid* / Q000503:physiopathology*; D012720:Severity of Illness Index; D013129:Spinal Puncture; D014443:Tyrosine / Q000031:analogs & derivatives; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; C008404:3-methoxytyrosine; D004298:Dopamine