restless legs syndrome 1 national institutes of

restless legs syndrome 1

national institutes of neurological disorders and stroke – ninds. national institutes of health. May 15, 2009 Newman

Restless Legs Syndrome • RLS, Wittmaack-Ekbom's syndrome, or Nocturnal myoclonus, often misdiagnosed, may be described as uncontrollable urges to move the limbs in order to stop uncomfortable sensations in the body, most commonly in the legs, but can also be in the arms. 3

History • Studies were done by Thomas Willis (1622 -1675) and by Theodor Wittmaack. Another description of the disease and its symptoms were made by George Miller Beard (1839 -1883). • In a 1945 publication titled 'Restless Legs', Karl-Axel Ekbom, described the disease and presented eight cases used for his studies. 4

Symptoms • Start at any age • The sensations uncommon, and there is a difficult to describ them. • Spontaneous improvement over a period of weeks or months can occur. 5

Symptoms • Usually occur deep inside the leg, between the knee and ankle; more rarely, in the arms and hands. • Movement bring immediate relief however, often temporary and partial. • Any type of inactivity involving sitting or lying, can trigger the sensations. 6

Symptoms 7

Periodic Limb moviment Disorder • 80 -90% of people with RLS also have Periodic Limb Moviment Disorder, which causes slow "jerks" or flexions of the affected body part. Typically occur every 10 to 60 seconds, sometimes throughout the night. The symptoms cause repeated awakening. • These movements are involuntary. People have no control over them. 8

Incidence/Prevalence • • About 10% of adults in North America and Europe. Underdiagnosed. • Some physicians wrongly attribute the symptoms to insomnia, stress, arthritis, muscle cramps, or aging. • Symptoms can be difficult for a child to describe. Sometimes is misdiagnosed as "growing pains" or attention deficit disorder. 9

types • The cause is unknown. • A family history in most of 40% of cases. (genetic form). (CR 12 q) • People with familial RLS tend to be younger when symptoms start and have a slower progression • Secondary – Often has a sudden onset and occurs after the age of 40. • Iron deficiency, accounts for just over 20% of all cases. • “Sublacta causa, tollitur effectus” 10

types • Primary – • Secondary – • • Early onset. Familial over 40%. Idiopathic. Diagnostic is hard in pediatrics. • Slower progression. Sudden onset. After 40. Iron deficiency over 20%. Treatment of underlying conditions. • Fast progression 11

Causes Spinal cord tumors, peripheral nerve lesions. Sleep apnea* or narcolepsy. Varicose veins. Thyroid problems. Iron deficiency Gen “MEIS 1” Neurology, july 2009. • Researchers also have found that caffeine, alcohol, and tobacco may aggravate or trigger symptoms in patients who are predisposed • Some pregnant women experience RLS, especially in their last trimester. Symptoms usually disappear within 4 weeks after delivery. 12

Causes • An underlying medical • Particular medications problem : • tricyclic • anti-nausea and antiseizure drugs, • diabetes mellitus, (SSRIs), • kidney disease, • Parkinson’s Disease, • lithium, • some cold • rheumatoid arthritis. • allergy drugs 13

International Restless Legs Syndrome Study Group 1995 • A desire to move the limbs, often associated with paresthesias or dysesthesias. • Symptoms that are worse or present only during rest and are partially or temporarily relieved by activity. • Motor restlessness, • Nocturnal worsening of symptoms. 14

Diagnostic • In 2003, a National Institutes of Health (NIH) consensus panel modified their criteria: • (1) an urge to move the limbs with or without sensations. • (2) worsening at rest. • (3) improvement with activity. • (4) worsening in the evening or night. 15

Diagnostic 16

• Sleep pattern of a Restless Legs Syndrome patient (red) vs. a healthy sleep pattern (blue). 17

Diagnostic • • • medical history, family history, current medications, sleepiness, disturbance of sleep, daytime function. • Blood tests to exclude anemia, • decreased iron stores (ferritin level), • diabetes, • thyroid and • renal dysfunctions 18

Treatment • An algorithm for treating Primary RLS was created by leading RLS researchers at the Mayo Clinic and is endorsed by the Restless Legs Syndrome Foundation. • This document provides guidance to both the treating physician and the patient, and includes both nonpharmacological and pharmacological treatments. 19

Lifestyle changes and other nonmedicinal approaches • For those with mild to moderate symptoms, decreased use of caffeine, alcohol, and tobacco may provide some relief. • Supplements to correct deficiencies in iron, folate, and magnesium. • A program of regular moderate exercise. • Taking a hot bath, massaging the legs. 20

Treatment The Mayo Clinic Algorithim includes, medication from four categories: 1 - Dopaminergics such as ropinirole, pramipexole, carbidopa/levodopa or pergolide: A recent study indicated that the used in restless leg patients can lead to an increase in compulsive gambling. 21

Treatment • 2 - Opioids such as propoxyphene, oxycodone, codein. • 3 - Benzodiazepines (clonazepam and diazepam) - May induce or aggravate sleep apnea*. • 4 - Anticonvulsants - sensations as painful, such as gabapentin. • Medications taken regularly may lose their effect, making it necessary to change medications periodically. 22

Treatment • In treatment with levodopa/carbidopa, most patients eventually will develop augmentation, meaning that symptoms are reduced at night but begin to develop earlier in the day than usual. Dopamine agonists such as pramipexole, and ropinirole may be effective in some patients and are less likely to cause augmentation. 23

Treatment • Ropinirole - Approved In 2005 by the Food and Drug Administration to treat moderate to severe Restless Legs Syndrome. The drug was first approved for Parkinson's disease in 1997. • Pramipexole - (Mirapex, Sifrol, Mirapexen in the EU). In February 2006, the EU Scientific Committee issued a positive recommendation for approving for the treatment of RLS in the EU. US FDA approved in 2006. 24

Treatment • Rotigotine - Currently in process for US FDA and EU approval for RLS. Delivered via a transdermal patch. • Pergolide - In March 2007 was withdrawn from the U. S. Market. Withdrawn due to implication in valvular heart disease, that was shown in two independent studies. 25

Prognosis • Is generally a lifelong condition and there is no cure. Symptoms may gradually worsen with age, more slowly for those with the idiopathic form than for patients who have an associated medical condition. Current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. Some patients have remissions, for days, weeks, or months. A diagnosis of RLS does not indicate the onset of another neurological disease. 26

Key points • • Often misdiagnosed. Pediatrics – Attention deficits disorder Treatment of underlying condition. There is no cure to the idiopathic form. NIH criteria. Iron deficiency, 20% of all cases. Family History, 40% of cases. 27

28

29

Newman 30