What is Restless Legs Syndrome? A Clinical View Christopher J Earley MB, BCh, PhD, FRCP(I) Professor Department of Neurology Johns Hopkins School of Medicine Christopher J Earley MB, BCh, PhD, FRCP(I) Professor Department of Neurology Johns Hopkins School of Medicine

Thomas Willis 1695 “Wherefore to some, on being a bed, they betake themselves to sleep, presently in the arms and legs, leaping and contractions of the tendons, and so great a restlessness and tossings of their members ensue that the diseased are no more able to sleep than if they were in the place of the greatest torture.”

George Beard 1880 Neuroasthenia “Fidgetiness and nervousness, inability to keep still – a sensation that amounts to pain – is sometime unspeakably distressing. When the legs feel this way, the sufferer must get up and walk or run, even though he be debilitated and is made worse by severe exercise.”

Karl Ekbom 1944 Ekbom’s Syndrome  First detail description of RLS; initially referred to as “irritable legs”  Syndrome later referred to as “restless legs” - “creeping or crawling sensation…legs” - sensation “deep inside, in the muscle or bone…” - symptoms only appeared when “the limbs were at rest” - relieved with movement  High prevalence in pregnancy and with iron deficiency  1960 – Worsened with promethazine  First detail description of RLS; initially referred to as “irritable legs”  Syndrome later referred to as “restless legs” - “creeping or crawling sensation…legs” - sensation “deep inside, in the muscle or bone…” - symptoms only appeared when “the limbs were at rest” - relieved with movement  High prevalence in pregnancy and with iron deficiency  1960 – Worsened with promethazine

Restless Legs Syndrome is an ABNORMAL SENSATION THE SENSATION IS Uncomfortable, distressing, hard to describe Overwhelming urge to move –Induced by rest –Stops with movement –Worse at night THE SENSATION IS Uncomfortable, distressing, hard to describe Overwhelming urge to move –Induced by rest –Stops with movement –Worse at night

Uncomfortable Sensations  Creepy, crawly - crawling or creeping  Worms crawling in veins  Pespi-Cola in the veins  Nervous feet  Itching under the skin  Crazy Legs  Tooth ache feeling -Can’t leave it alone  Excited nerves, Electric-like shocks  JUST NEED TO MOVE  Pain about 35% of cases  Creepy, crawly - crawling or creeping  Worms crawling in veins  Pespi-Cola in the veins  Nervous feet  Itching under the skin  Crazy Legs  Tooth ache feeling -Can’t leave it alone  Excited nerves, Electric-like shocks  JUST NEED TO MOVE  Pain about 35% of cases

Urge to Move (Akathisia)  Increasing (crescendo) compulsion or urge to move the limb results in a voluntary or involuntary movement  Movement is followed by a brief period of relief  Then the sensation returns with increasing urgency and the cycle begins again.  The objective component of this cycle (movement) has been the research focus (SIT or PSG)  So the recording show semi-rhythmic movements (PLMW or PLMS) and by implication RLS considered a movement disorder  Clinically it is clear that the sensation is driving the subject towards relief (movement) – the movement therefore is normal, it is the sensation which is abnormal  Increasing (crescendo) compulsion or urge to move the limb results in a voluntary or involuntary movement  Movement is followed by a brief period of relief  Then the sensation returns with increasing urgency and the cycle begins again.  The objective component of this cycle (movement) has been the research focus (SIT or PSG)  So the recording show semi-rhythmic movements (PLMW or PLMS) and by implication RLS considered a movement disorder  Clinically it is clear that the sensation is driving the subject towards relief (movement) – the movement therefore is normal, it is the sensation which is abnormal

Periodic Leg Movements of Wake (PLMW) and Sleep (PLMS) Rhythmic or semi-rhythmic movements of the legs that can be measured by surface EMG Suggested Immobilization Test (SIT) Polysomnogram (PSG)

RLS Patient: PLMS on a Compressed, 4-minute Segment of PSG

PLS Patient: PLMW on a Compressed, 2-minute Segment of a SIT

Causes of PLMS PLMS are a non-specific electrophysiological finding of unclear clinical significance. Apnea, Antidepressant, Aging, RLS Neurodegenerative disorders, Spinal disease, Narcolepsy, PLMD PLMS are a non-specific electrophysiological finding of unclear clinical significance. Apnea, Antidepressant, Aging, RLS Neurodegenerative disorders, Spinal disease, Narcolepsy, PLMD

Cosine Fit: Core Body Temperature (TEMP), Subject Symptoms (SBJ) and Leg Activity (ACT) for mSIT over 3, 24-hours Periods Hening et al. Sleep 1999

PLM Decrease with Increased Activity

PLM Decrease with Increase Arousal

Secondary Causes of RLS Iron Deficiency Pregnancy Dialysis Neuropathy Iron Deficiency Pregnancy Dialysis Neuropathy

1. Allen RP, Walters AS, Montplaisir J, et al. Arch Intern Med. 2005;165: Women Men All RLS sufferers (n=116) Prevalence (%) Age group (years) Prevalence by Age and Gender From the REST Population-based Survey

RLS Prevalence by Severity REST population based study: UK, France, Germany, Spain, Italy, and USA  RLS at any frequency/severity 7.2%  RLS at least weekly 5.0%  RLS  2/week and distressing 2.7% 1.7% men 3.7% women REST population based study: UK, France, Germany, Spain, Italy, and USA  RLS at any frequency/severity 7.2%  RLS at least weekly 5.0%  RLS  2/week and distressing 2.7% 1.7% men 3.7% women

Times woken/night None (not woken) OnceTwice3 times4 times>4 times No answer given Number of patients 4.9% 6.9% 22.9% 24.5% 17.1% 18.5% 5.3% 60% reported waking 3 times or more per night Sleep Disruption 1. Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Sleep Med. 2004;5:

Number of Hours Awake on a Poor Night 11.7% 75% reported spending 2 or more hours awake per night No answer given None<11–22–3 >6 Time spent awake (h) 3–44–55–6 1.0% 2.4% 9.9% 21.9% 17.7% 14.1% 8.8% 12.4% Number of patients 1. Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Sleep Med. 2004;5:

SF-36 as Measure of Disability in Those with “Severe” RLS Physical functioning Role physical Bodily pain General health Energy/ vitality Social functioning Role emotional Mental health SF-36 domain Mean SF-36 score Severe RLS (N=63) Age- and gender-adjusted population norm (N=2,474) * ** * * ***

Video How to sleep with RLS: Patient’s home remedy

The Core Features of Restless Legs Syndrome are:  An Abnormal Sensation that is driving the system towards activity ( = relief)  The sensation is triggered by inactivity and is biological tied to the circadian system  An Abnormal Sensation that is driving the system towards activity ( = relief)  The sensation is triggered by inactivity and is biological tied to the circadian system