Restless Legs Syndrome The Most Common Condition Youve Never Heard of Ayman Krayem, MBChB, ABIM, FCCP Consultant in Pulmonary & Sleep Medicine Chair, Jeddah

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Restless Legs Syndrome The Most Common Condition Youve Never Heard of Ayman Krayem, MBChB, ABIM, FCCP Consultant in Pulmonary & Sleep Medicine Chair, Jeddah Sleep Medicine Club KAMC-Jeddah Slide 2 Restless Legs Syndrome the most common condition youve never heard of Slide 3 RLS Excludes PLMD RLS Includes PLMS RLSPLMD RLSPLMD Slide 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. Slide 5 Willis T. The London practice of physick London: Bassett and Crooke; 1685. Historical References for RLS Therefore to some, on being a bed, they betake themselves to sleep, presently in the arms and legs, leaping and contractions of the tendons, and so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. Slide 6 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). Historical References Slide 7 Common Characteristics Of Restless Legs Syndrome Unpleasant sensations in the legs (sometimes the arms as well).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. Slide 8 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. Slide 9 Terms Used to Describe RLS Sensations Slide 10 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: 10119. Slide 11 Symptoms of RLS Follow Circadian Rhythm Hening W et al, Sleep 22:901-915 1999 Slide 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. Slide 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 severe31-40 very severe Slide 14 Distribution of RLS Scores Neurology 2005;65:239246 n = 731 Slide 15 Differential Diagnosis of RLS Leg cramps Peripheral neuropathy Varicose veins Intermittent claudication Neuroleptic-induced akathisia Slide 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 Slide 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 Slide 18 RLS Prevalence in France n = 10,263 Neurology 2005;65:239246 Slide 19 RLS Prevalence in France n = 10,263 MenWomen Slide 20 Prevalence in Germany n = 431 Arch Intern Med 2004; 164: 196202. Slide 21 Symptoms in a US population Arch Intern Med 2000; 160: 213741. Slide 22 Slide 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 Slide 24 RLS Pathophysiology Central Nervous system dysfunction Cortical subcortical spinal cord Brain Dopaminergic function. Iron Metabolism Slide 25 Brain Iron Insufficiency Restless Legs Syndrome CNS Dopamine Abnormalities Iron-Dopamine Model of RLS Slide 26 Ferritin Levels: Correlate with RLS but not PLMS Slide 27 Iron-Dopamine Model of RLS Earley CJ et al Neurology 2000; 54:1698-1700 control RLS Slide 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 Slide 29 Neurology 2003;61:304309 Impaired Brain Iron Acquisition in Restless Legs Syndrome: Neuropathologic Examination ControlRLS Marked reduction in ferritin in substantia nigra of RLS brain Slide 30 5 secs Slide 31 15 secs Slide 32 30 secs Slide 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) Slide 34 Disease of Conditions Associated with PLMS Narcolepsy REM Sleep Behavior Disorder Neurodegenerative Disorders Tourettes Syndrome Peripheral Neuropathy End Stage Renal Disease Pregnancy Post Traumatic Stress Disorder Obstructive Sleep Apnea Antidepressants (exceptions: bupropion trazodone) Slide 35 Most people are asymptomatic Most people are asymptomatic Poor association between PLMS and sleepiness Poor association between PLMS and sleepiness One third of patients with PLMS have RLS One third of patients with PLMS have RLS Needs PSG for diagnosis Needs PSG for diagnosis Periodic Limb Movement Syndrome Slide 36 Treatment of RLS and PLMS Varies according to the clinical course. Co-morbid medical conditions. Presence or absence of associated pain. Individualize Therapy!! Slide 37 Pharmacologic Rx for RLS Dopamine receptor agonists and dopamine precusors. Opioids Benzodiazepines Anticonvulsants Other Slide 38 Pharmacologic Rx for RLS Slide 39 Slide 40 Slide 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 Slide 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. Slide 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. Slide 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)