0. 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

1. Restless Legs Syndrome “the most common condition you’ve never heard of”

2. RLS Excludes PLMD RLS Includes PLMS

3. 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.

4. Historical References for RLS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.

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 Historical References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

6. Common Characteristics Of Restless 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.

7. Common Characteristics Of Restless 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.

8. Terms Used to Describe RLS Sensations

9. Primary Features of RLS Essential 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 Med 2003; 4: 101–19.

10. Symptoms of RLS Follow Circadian Rhythm Hening W et al, Sleep 22:901-915 1999

11. 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.

12. 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 moderate
21-30 severe very severe

13. Distribution of RLS Scores
Neurology 2005;65:239–246

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

15. 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

16. 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

17. RLS Prevalence in France n = 10,263
Neurology 2005;65:239–246

18. RLS Prevalence in France n = 10,263
Men
Women

19. Prevalence in Germany n = 431
Arch Intern Med 2004; 164: 196–202.

20. Symptoms in a US population
Arch Intern Med 2000; 160: 2137–41.

22. 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

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

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

25. Ferritin Levels: Correlate with RLS but not PLMS

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

27. 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

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

29. 5 secs

30. 15 secs

31. 30 secs

32. 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)

33. 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: bupropion trazodone)

34. 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

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

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

37. Pharmacologic Rx for RLS

40. 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

41. Vitamin D deficiency is associated with Restless Legs Syndrome
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.

42. 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.

43. 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)