Restless Legs Syndrome “ The Most Common Condition You’ve Never Heard of”

1. Restless Legs Syndrome“The Most Common Condition You’ve Never Heard of” Ayman Krayem, MBChB, ABIM, FCCP Consultant in Pulmonary & Sleep Medicine Chair, Jeddah Sleep Medicine Club KAMC-Jeddah

2. Restless Legs Syndrome“the most common condition you’ve never heard of” www.rls.org

3. RLS Excludes PLMD RLS Includes PLMS RLS PLMD RLS PLMD

4. Definitions • RLS = Restless Legs Syndrome • PLM = Periodic Limb Movements • PLMS = PLM in sleep: characteristic movement that occur during sleep. • PLMW = PLM in wake (usually seen as part of a nocturnal PSG) • PLMD = PLM disorder: a sleep disorder based on a finding of PLMS (Usually < 5/hr of sleep) with an associated sleep dysfunction that cannot be otherwise explained.

5. Historical References for RLS “Therefore to some, on being a bed, they betake themselves to sleep, presently in the arms and legs, leaping and contractions of the tendons, and so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 tossing of their members ensue that the diseased are no more able to sleep than if they were in the place of the greatest torture.” Willis T. The London practice of physick London: Bassett and Crooke; 1685.

6. Historical References • Wittmaack T. Pathologie und therapie der sensibilitat neurosen Liepzig: Schafer; 1861. “anxietas tibiarum” - Felt to be of hysterical origin. • Ekbom K. Acta Med Scand. 1944;118:197-209. Asthenia crurum paraesthetica (irritable legs).

7. Common Characteristics OfRestless Legs Syndrome • Unpleasant sensations in the legs (sometimes the arms as well). • often described as creeping, crawling, tingling, pulling, or rarely painful. • Leg sensations are relieved by walking, stretching, knee bends, massage, or hot or cold baths. • Leg discomfort occurs when lying down or sitting for prolonged periods of time.

8. Common Characteristics OfRestless Legs Syndrome • The symptoms are worse in the evening and during the night. • Involuntary leg (and occasionally arm) movements while asleep; • Difficulty falling asleep or staying asleep; • Sleepiness or fatigue during the daytime; • Cause of discomfort not detected by medical tests; • Family members with similar symptoms.

9. Terms Used to Describe RLS Sensations

10. Primary Features of RLSEssential for Diagnosis • A sensation of an urge to move the limbs (usually legs) accompanied by uncomfortable or unpleasant sensation . • Motor restlessness to reduce sensation. • Onset or worsening of symptoms when at rest. • Marked circadian variation in occurrence or severity of symptoms (night time) • No other identifiable cause Sleep Med2003; 4: 101–19.

11. Symptoms of RLS Follow Circadian RhythmHening W et al, Sleep 22:901-915 1999

12. Associated Features • Periodic Limb Movements in sleep • Sleep disturbance, especially difficulty in sleep initiation. • Positive family history • Onset at any age • Chronic and progressive course with remissions.

13. RLS Severity Scale • 10 Questions • Specific to leg discomfort, movement • Effects on sleep • Overall quality of life • 0-4 rating of various symptoms for each question; 0= none – 4 = very severe 0-10 mild 11-20 moderate 21-30 severe 31-40 very severe

14. Distribution of RLS Scores n = 731 Neurology 2005;65:239–246

15. Differential Diagnosis of RLS • Leg cramps • Peripheral neuropathy • Varicose veins • Intermittent claudication • Neuroleptic-induced akathisia

16. Symptomatic Restless Legs • Iron deficiency • Hemoglobin Normal but Low Ferritin • Uremia, Caffeine, Nicotine • Diabetes • Peripheral neuropathy or radiculopathy • Fibromyalgia • Rheumatoid arthritis • Pregnancy • Vitamin D Deficiency

17. RLS Epidemiology • Affects 5-10% of population. • ? Increased in French Canadians (Lavigne G & Montplaisir J Sleep 1994; 17:739-43) • Prevalence increase with age • Women more affected than men

18. RLS Prevalence in Francen = 10,263 Neurology 2005;65:239–246

19. Men Women RLS Prevalence in Francen = 10,263

20. Prevalence in Germanyn = 431 Arch Intern Med2004; 164:196–202.

21. Symptoms in a US population Arch Intern Med2000; 160: 2137–41.

23. Genetics of Restless Legs Syndrome • Familial nature first described by Ekbom • Complex inheritance • 3 major loci identified • 12q - French Canadian • 14q - Italian, Canadian • 9p - 2 US Families

24. RLS Pathophysiology • Central Nervous system dysfunction • Cortical • subcortical • spinal cord • Brain Dopaminergic function. • Iron Metabolism

25. Brain Iron Insufficiency CNS Dopamine Abnormalities Brain Iron Insufficiency Restless Legs Syndrome Iron-Dopamine Model of RLS

26. Ferritin Levels:Correlate with RLS but not PLMS

27. control RLS Iron-Dopamine Model of RLS Earley CJ et al Neurology 2000; 54:1698-1700

28. MRI Measurement of Brain Iron in RLS Patients • Iron content is reduced in both red nucleus and substantia nigra for RLS patients compared to controls • Allen RP et al; Neurology 2001;56:263-65

29. Impaired Brain Iron Acquisition inRestless Legs Syndrome: Neuropathologic Examination Marked reduction in ferritin in substantia nigra of RLS brain Control RLS Neurology 2003;61:304–309

30. 5 secs

31. 15 secs

32. 30 secs

33. Periodic Limb Movements • Characteristic limb movements • 0.5 – 10 sec duration movements • Recur periodically (every 4 to 90 sec) • Must occur in a series of 4 or more in any sleep or wake state. • Diagnosis of PLMD with the above and: - > 5 h in children, >15/h in adults - Clinical Sleep Disturbance or Daytime Fatigue - Not better explained by another disorder - Cannot diagnose RLS and PLMD at same time (ICSD)

34. Disease of Conditions Associated with PLMS • Narcolepsy • REM Sleep Behavior Disorder • Neurodegenerative Disorders • Tourette’s Syndrome • Peripheral Neuropathy • End Stage Renal Disease • Pregnancy • Post Traumatic Stress Disorder • Obstructive Sleep Apnea • Antidepressants (exceptions: bupropiontrazodone)

35. Periodic Limb Movement Syndrome • Most people are asymptomatic • Poor association between PLMS and sleepiness • One third of patients with PLMS have RLS • Needs PSG for diagnosis

36. Treatment of RLS and PLMS • Varies according to the clinical course. • Co-morbid medical conditions. • Presence or absence of associated pain. • Individualize Therapy!!

37. Pharmacologic Rx for RLS • Dopamine receptor agonists and dopamine precusors. • Opioids • Benzodiazepines • Anticonvulsants • Other

38. Pharmacologic Rx for RLS

41. Iron supplements as Rx for RLS • Check serum ferritin levels • Add iron in patients with serum ferritin < 50mg/L • Ideal supplement not known • May take several months to be effective • May be poorly tolerated

42. Vitamin D deficiency is associated with Restless Legs Syndrome. Ayman Krayem, FCCP, Siraj Wali, FCCP, Afnan Shukr, MBBS, Ayah Boudal, MBBS, Ahmad Alsaiari, MBBS. (Abstract)Poster # 704. American Academy of Sleep Medicine annual meeting, June 1-5, 2013, Biltmore, USA.

43. Manifestations of Augmentation • Increase in RLS symptom severity during treatment: • Frequency of symptoms or earlier symptoms. • Duration of symptoms • Number of body parts affected • Intensity • Most commonly during treatment with L-DOPA and estimated to occur in 27-82% of cases. • Not reported during treatment with opiates, anticonvulsants or other dopaminergic drugs.

44. Conclusion • RLS is common but under-diagnosed • Consequences: Insomnia, bed partners separation, depression & sexual dysfunction • Diagnosis: History • Workup: Iron, Vitamin D, Folic Acid, Vitamin B12 • Management: Replacement, Specific Drug Therapy (Dopanergic)