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

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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4 Historical References for RLS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5 Historical References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)

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