Glutamate, Hyperarousal and Restless Legs Syndrome

Inclusion Criteria:

• All subjects

  1. 18 years or older
  2. Normal mental status and able to give informed consent.
  3. Regular sleep times start between 21:00 and 01:00 5 out of 7 days a week
  4. General good health and ambulatory

• RLS patients

  1. Diagnosis of primary RLS confirmed by the PI or Dr. Earley

  2. History indicating if RLS symptoms were not treated, thy would for the last 6 months

     1. Occur at least 5 out of 7 days a week
     2. Almost always disrupt sleep
  3. For phase 2 admission to the Clinical Research Unit: Home screening on a clinical log shows RLS symptoms for at least 5 of 7 days, IRLS score at the end of home monitoring ≥ 15 and PAM-RL measures show average PLMS/hr ≥15.

• Control subjects

  1. No history of any of the 4 essential criteria for diagnosis of RLS (1).
  2. For phase 2 admission to the Clinical Research Unit: Home screening on the PAM-RL indicates average PLMS/hr ≤ 10 and the sleep-wake log shows regular times in bed between 21:00 and 01:00 bed times with 6.0 to 10.0 hours in bed for 5 out of for 7 nights.

Exclusion Criteria:

• All subjects

  1. Major mental history as determined by history
  2. Clinically significant sleep apnea on prior PSG or on screening first night PSG (apnea/hypopnea rate >15/hr).
  3. Any medical or neurological disorder other than RLS likely to compromise normal sleep, interfere with interpretation of results, or would place the subject at risk when participating in the study (e.g. Chronic pain, dementia, ALS, stroke, MS, untreated thyroid).
  4. Any use of DA antagonists for more than one week in the past 6 months, other than for nausea.
  5. Women who are pregnant or lactating or at risk for getting pregnant (not using appropriate birth control nor post-menopausal).
  6. Failure to have clear hand dominance, ambidextrous as assessed by the Edinburgh Handedness Inventory (Could influence outcomes on TMS).
  7. Musicians and professional typists (Might influence performance on TMS measure)
  8. A significant neurological disorder (such as stroke, Parkinson's Disorder, Multiple Sclerosis) that could impair fine motor performance.
  9. Metal in the body (e.g., pacemakers, implantable pumps, stimulators, orthodontics, etc) that would cause problems for the MRI or TMS.
  10. Medication use that would alter sleep including any GABA active medications and any anti- depressants or other significant psychiatric medications or medications that would affect Glu.
  11. History of claustrophobia or problems with closed MRI scans not resolved.
  12. History of vertigo, seizure disorder, middle-ear disorder, or double vision.
  13. Body size not compatible with using T7 MRI.

• RLS patients

  1. History of clinically significant sleep disorder other than that with RLS.
  2. Medical disorder or current medication use that exacerbates or might have started the RLS

• Control subjects

  1. History of clinically significant sleep disorder including insomnia (primary or psycho-physiological)
  2. Score on the Pittsburgh Sleep Quality Inventory (PSQI) >5
  3. Family history indicating possible RLS in a first-degree relative