2. 11 YEARS OF CLINICAL PROGRESS RICHARD P ALLEN, PHD, DABSM, FAASM JOHNS HOPKINS UNIV, NEUROLOGY

3. THE START 1945Ekbom –Identified the condition –Gave it a name: Restless Legs Syndrome –Emphasized listening to the patient and interest in sensory phenomena particularly pain.  In his monograph Preface starts out with a quote in French roughly translated here by Dr. Arnulf:  "Doctors... call 'neurotics' or 'predisposed’ those people who have the bad taste to suffer above their forces or to drag on pain against their will. Every case exists. But I acquired the conviction that this is here a major mistake from the contemporary medicine... I am convinced that, almost always, those who suffer suffer exactly as they describe it, and, paying to their pain an extreme attention, they suffer more than one could imagine. There is only one pain easy to bear, that's the pain of other than you.” René Leriche

4. The Restart: Diagnosis 1945EKBOM: “disease in the legs characterized by Peculiar Paresthesia.., Pain and Weakness…” 1997 IRLSSG Art Walters – “Toward a better definition of the ….” – First effort at a consensus clinical criteria for RLS – Restored emphasis on urge to move 2 May 2002 IRLSSG/RLSF at NIH – 2003 “Restless Legs Syndrome: Diagnostic Criteria,. – Updated diagnosis, – 1st diagnostic criteria: children and augmentation 26 Oct 2008 IRLSSG and EU-RLSSG at JHU – Occurrence rate, differential dx, clinical significance, and emphasis on appropriate use of objective tests

5. The Restart: Treatment/pathology 1982Akpinar and Montplaisir –Levo-dopa, dopamine hypothesis 1987Walters and Hening –Efficacy of opioids, and DA agonists 1994O’Keeffe –Iron treatment for iron deficiency 1992Earley and Allen –L-dopa compared to propoxyphene –Iron, brain iron

6. RLS phenotypes Familial vs sporadic –Walters 1990, Ondo 1996 Early vs late age of onset –Allen 2000, Winkelmann 2000 Painful RLS –Hening 2004

7. Progress: RLS Prevalence DiagnosisPaperRLS prevalence Limited questionsLavignel 199415% Full Dx criteria EU: questions/interview Berger 2004 Högl 2005 10.6% Full dx EU:USA all weekly 2/wk + distress Allen et al 20057.2% 4.5% 2.7% MD Dx EU All Clinically significant Allen et al 20083.5% 2.1% Pediatric US/UK 12 - 17 8 - 11 Picchietti et al 2007 (all/2/wk + distress) 2.0% / 1.0% 1.9%/ 0.5%

8. Prevalence RLS 2/wk + distress : age and gender general population US and Western Europe (Allen et al, 2005) Women>men over age 30 Increase with age to age 60 Decrease over age 70?

9. Prevalence of any RLS - significant population factors WESTERN COUNTRIES -- 7 - 11% TURKEY -- 3% Korea ------- 4- 7% Japan/Singapore -- < 3 % (African Americans < ??)

10. Progress epidemiology of RLS: special populations- Any condition that compromises iron status –Pregnancy, End Stage Renal Disease, iron deficiency, gastric surgery,etc. Some Neurological disorders –Multiple Sclerosis, Neuropathies, etc. Medication use? –SSRI, SNRI, Anti-histamines Possible decreased risk for women who have not been pregnant –One Study only

11. Progress: Treatment US - Two FDA approved medications –Ropinirole, pramipexole Newer treatment options –Longer acting DA treatments –Gabapentin /alpha 2 delta –Opioids - longer acting forms –Iron

12. Progress: Clinical Tools/Methods Validated diagnostic instruments –2 - 3 of these now available –Recommended use in clinical trials and studies Validated severity and Quality of Life scales –IRLS –Two QoL scales –MOS for sleep in RLS patients PSG studies: PLMS and PLMW, SIT - severity - maybe diagnosis Activity meters PLM recording methods –Periodicity, nocturnal pattern Blood tests: serum ferritin

13. Clinical problems Augmentation Careless diagnosis Inadequate treatment - –Most severe still poorly treated –Symptomatic treatment may not address all of RLS effects. Uncertain medical consequences –Chronic RLS untreated (Why fewer very old RLS?) –Long term (10-40 years of RLS treatments)