RLS edu slide set

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Published on March 3, 2008

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Restless Legs Syndrome (RLS) 38-page PowerPoint presentation from RLS:UK a newly formed academic group and from The Ekbom Support Group a multidisciplinary academic group run by Eileen Gill in conjunction with RLS:UK:  Restless Legs Syndrome (RLS) 38-page PowerPoint presentation from RLS:UK a newly formed academic group and from The Ekbom Support Group a multidisciplinary academic group run by Eileen Gill in conjunction with RLS:UK “Wherefore to some, when being abed 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 a place of greatest torture" Thomas Willis-1672 (Possibly the First Description by Willis) Slide show presentation of Restless Legs Syndrome (RLS) Teaching Kit To run the presentation, use the scroll wheel Thomas Willis Restless Legs Syndrome Classic Modern Description by Ekbom:  Restless Legs Syndrome Classic Modern Description by Ekbom Also known as Ekbom’s syndrome3 Asthenia crurum paraesthetica: sensory RLS Asthenia crurum dolorosa: painful RLS Movement disorder of sleep and relaxed wakefulness associated with unpleasant sensory symptoms, usually of the lower limbs3 Karl-Axel Ekbom Restless Legs Syndrome Some Basic Facts:  Restless Legs Syndrome Some Basic Facts RLS can be reliably diagnosed by four clinical questions4 Diagnosis can be established in primary care5 Fidgety legs or night time cramps are not RLS6 RLS can be effectively treated6 Slide4:  Restless Legs Syndrome Some Basic Facts Minimum Diagnostic Criteria4 Irresistible urge to move limbs usually associated with paraesthesia/dysaesthesia in legs Symptoms worse or exclusively present at rest – (lying > sitting) Partial or complete relief with activity/movement Symptoms worse in the evening or at night Slide5:  Associated features4 Chronic progressive course with periodic exacerbations Normal neurological examination (except neuropathy) Sleep disturbance (insomnia) Supportive clinical features4 Dopaminergic drug responsiveness PLMS/PLMW Positive family history Restless Legs Syndrome Some Basic Facts Restless Legs Syndrome Key Features:  Restless Legs Syndrome Key Features Relief of symptoms from movement2 Persistence of relief as long as movement occurs2 Circadian pattern2 Usually no physical manifestations in the limbs2 Severe sleep disturbance Restless Legs Syndrome Common Descriptions of RLS Symptoms:  Restless Legs Syndrome Common Descriptions of RLS Symptoms Restless Legs Syndrome Some Basic Facts:  Restless Legs Syndrome Some Basic Facts RLS Secondary RLS Primary (idiopathic) RLS Restless Legs Syndrome Neurological Examination:  Restless Legs Syndrome Neurological Examination Diagnosis requires a basic neurological examination11 Patients should have: Normal power of lower limbs Normal reflexes of lower limb (knee and ankle jerks) A flexor plantar response No obvious sensory deficit to touch and vibration Restless Legs Syndrome How Common is it?:  Restless Legs Syndrome How Common is it? RLS of varying severity affects 5%-10% of the general population8,9,12 Approximately 15% of RLS sufferers (1-2% general population) are estimated to seek treatment13 Age of onset is under 20 years in almost half of all cases14 Prevalence increases with age8,12 Women are more likely to be affected than men8,12 Little prevalence data is available for ethnic groups13 Restless Legs Syndrome Possible Causes:  Restless Legs Syndrome Possible Causes RLS may be due to dysfunction of: Dopamine signalling in brain2 Iron metabolism2 Opioid system10 A combination of above factors2 Both CNS and spinal cord may be involved2 Strong genetic basis2 Restless Legs Syndrome Genetic Basis:  Restless Legs Syndrome Genetic Basis More than 50% of idiopathic RLS cases may have a family history of RLS16 19.9% of first degree relatives may be affected17 1st and 2nd degree relatives have a significantly higher risk of RLS than controls18 Transmission appears to be most likely to be autosomal dominant in young onset RLS (RLS onset < 30 yrs)19 Restless Legs Syndrome UK Perspective (37.6% have family history):  Total One member Two or more members 0 5 10 15 20 25 30 35 40 Yes unspecified RLS patients with family history (%) 4.81 21.4 11.4 37.6 Restless Legs Syndrome UK Perspective (37.6% have family history) Restless Legs Syndrome Search for Genes:  Restless Legs Syndrome Search for Genes No genes found for RLS yet Linkage reported to: RLS – 1: Chromosome 12q21 RLS – 2: Chromosome 14q1 RLS – 3: Chromosome 9p24-p2222 Restless Legs Syndrome The Iron Theory:  Restless Legs Syndrome The Iron Theory Iron deficiency common2 Iron levels have a circadian pattern7 Iron supplementation useful2 Iron is a co-factor in dopamine synthesis2 D2 receptors correlate with iron deficiency2 Ferritin levels correlate with disease severity2 MRI of brain may confirm iron deficiency using a special programme Autopsy shows decreased iron in substantia nigra23 Restless Legs Syndrome The Iron Theory:  Restless Legs Syndrome The Iron Theory RLS may be a functional disorder resulting from impaired iron acquisition by the neuromelanin cells in RLS23 The underlying mechanism may be a defect in regulation of the transferrin receptors23 Secondary RLS Possible Causes:  Secondary RLS Possible Causes Iron deficiency state Renal failure/end-stage renal disease Haemodialysis Pregnancy (usually 3rd trimester) Axonal neuropathy Others (rare): Parkinson’s disease Spinocerebellar ataxia types 2 & 3 Rheumatoid arthritis Diabetes mellitus Restless Legs Syndrome Variations in Clinical Presentation:  Restless Legs Syndrome Variations in Clinical Presentation Early onset <45 yrs Often familial Progressive Late onset >45 yrs Low ferritin Secondary RLS Pain dominant/sensory dominant RLS with dominant periodic leg movements Restless Legs Syndrome Periodic Leg Movements (PLM):  Restless Legs Syndrome Periodic Leg Movements (PLM) Periodic flexion of ankle, knee and thighs with fanning of toes7 Pathological PLMS occur >5 times per hour/sleep4 Polysomnography is required to quantify PLMS4 80% of RLS patients have a PLMS index >54 PLMS also occur in a variety of sleep and neurological disorders4 Restless Legs Syndrome Diagnosis can be ascertained by:  Restless Legs Syndrome Diagnosis can be ascertained by Clinical history (use the IRLSSG criteria)4 Basic neurological examination7 Blood test for: ferritin level, glucose7 In selected cases referral to secondary care for:10 Sleep studies Exclusion of other secondary causes Restless Legs Syndrome Differential Diagnosis:  Restless Legs Syndrome Differential Diagnosis Nocturnal leg cramps Akathisia (restlessness) Insomnia Positional discomfort Restless Legs Syndrome Why Treat RLS?:  Restless Legs Syndrome Why Treat RLS? RLS patients have a significantly impaired QoL27 Untreated, RLS can: Impact on sleep8,9 Impact on mood27 Impact on work30 Impact on relationships30 Restless Legs Syndrome Treatment Issues:  Restless Legs Syndrome Treatment Issues Not all patients with RLS require pharmacological treatment6 Oral iron supplementation should be tried to iron deficient patients as judged by low ferritin levels with monitoring of iron level after treatment6 Approximately 15% of RLS patients may need specific treatment13 Indications for treatment are:7 Severe chronic sleep loss/insomnia Severe daytime fatigue/tiredness Forced lifestyle changes (unable to travel) Severe PLMS Severe sensory symptoms Restless Legs Syndrome Drugs to be Avoided:  Restless Legs Syndrome Drugs to be Avoided Antidepressants (amitryptine/prozac) Antihypertensives (Calcium channel blockers) Antiemetics (metoclopramide) Caffeine at night time Alcohol at night time Treatment of RLS Dopaminergic Drugs are the Mainstay:  Sinemet Madopar Stalevo Pramipexole Ropinirole Rotigotine Cabergoline Treatment of RLS Dopaminergic Drugs are the Mainstay Treatment of RLS Dopaminergic Drugs:  Treatment of RLS Dopaminergic Drugs Levodopa Small evidence base6,32 Augmentation and rebound in over 80% of patients33 Dopamine agonists (DA) Large evidence base of double-blind placebo-controlled studies6,32 Over 300 patients assessed34 Low augmentation/rebound rates6,32 DA vs. levodopa: One trial: Pergolide versus levodopa35 Pergolide significantly more effective on PLMS (79% vs. 45%)35 Treatment of RLS Augmentation and Rebound:  Treatment of RLS Augmentation and Rebound Augmentation Increasing requirement of drug Daytime/evening symptoms Symptoms become refractory to high doses Spread of symptoms to upper limbs and face Up to 80% rate with levodopa treatment Rebound Related to half-life of drug Early morning symptoms Low rates of augmentation and rebound with dopamine agonists Treatment of RLS Non-dopaminergic Therapy:  Treatment of RLS Non-dopaminergic Therapy Other Drugs Dose Range Specific Issues Oxycodon 2.5-25 mg Painful RLS Propoxyphene 100-260 mg Painful RLS Tramadol 50-100 mg Painful RLS Clonazepam 0.5-2 mg evening dose Drowsiness Triazolam 0.125/0.25 mg Insomnia Nitrazepam 2.5 – 10 mg Insomnia Carbamazepine 100 – 600 mg Resistant RLS Gabapentin 300-2400 mg Resistant and painful RLS For Iron deficiency Iron sulphate 200 mg tid Oral Treatment of RLS Treatment Algorithm:  Diagnosis of RLS Moderate- severe RLS needing treatment Non-ergot dopamine agonist Evening dosing If augmentation or rebound use dopamine agonist bid/tid regime Painful RLS Add or substitute opiates, gabapentin Associated insomnia Add clonazepam Titrate up according to response Exclude iron deficiency Iron deficiency (Serum ferritin <45mcg/ml) Add oral iron Exclude other secondary causes Treat underlying disease Non-severe RLS Sleep hygiene Non-pharmacological measures Little impact on Qol/lifestyle QoL review Avoid drugs worsening RLS Neuroleptics Antiemetics Antidepressants Antihistamines Treatment of RLS Treatment Algorithm Severity assessment If low response use an alternative dopamine agonist Treatment of RLS Problems in the UK: In some cases referral may be delayed between 10-40 yrs!!:  Delayed Referral for Treatment Duration of RLS (Years) 36% 20% 24% 11% 2% 4% 3% <5 5-9 10-19 20-29 30-39 40-49 50-59 Treatment of RLS Problems in the UK: In some cases referral may be delayed between 10-40 yrs!! Management of RLS What treatments are currently offered to patients?:  Drug treatment received by patients with RLS38 20% 18% 13% 13% 6% 5% 4% 0 5 10 15 20 25 Anti- depressants Anti- convulsants Quinine Non-narcotic analgesia Hypnotics Dopamine agonists Levodopa RLS sufferers (%) Management of RLS What treatments are currently offered to patients? Support for RLS Patients Ekbom Support Group run by Eileen Gill and RLS:UK:  Support for RLS Patients Ekbom Support Group run by Eileen Gill and RLS:UK Patients can find support for their condition through contact with other sufferers and healthcare professionals with a specialist interest in RLS The Ekbom Support Group is a multidisciplinary academic group run by Eileen Gill in conjunction with RLS:UK RLS:UK is an academic group dedicated to improvinng awareness and research in RLS in the UK. RLS:UK has booklets in relation to RLS for distribution to medical practitioners. (www.restlesslegs.org.uk) References:  References Bonati MT, Ferini-Strambi L, Aridon P et al. Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain 2003;126:1485-1492. Allen RP, Earley CJ. Restless legs syndrome: a review of clinical and pathophysiologic features. J Clin Neurophysiol 2001;18:128-147. Ekbom KA. Restless legs: a clinical study. Acta Med Scand 1945;158(Suppl):1-122. Allen RP, Picchietti D, Hening WA; International Restless Legs Syndrome Study Group. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101-119. Wellbery CE. Getting the facts on Restless legs. Am Fam Physician 2000;62:51-52. Byrne R, Sinha S, Chaudhuri KR. Restless legs syndrome: diagnosis and review of management options. Neuropsychiatric Disease and Treatment 2006;2:1-10. Schapira AHV. Restless legs syndrome: An update on treatment options. Drugs 2004;64:149-158. References:  References Hening W, Walters AS, Allen RP et al. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med 2004;5:237-246. Allen RP, Walters AS, Montplaisir J et al. Restless legs syndrome prevalence and impact: REST General Population Study. Arch Intern Med 2005;165:1286-1292. Chaudhuri KR, Forbes A, Grosset D et al. Diagnosing restless legs syndrome (RLS) in primary care. Curr Med Res Opin 2004;20:1785-1795. Tse W, Koller W, Olanow CW. Restless legs syndrome: differential diagnosis and treatment. In: Chaudhuri KR, Odin R, Olanow CW, eds. Restless Legs Syndrome. Taylor & Francis, London; New York 2004:85-107. Tison F, Crochard A, Léger D et al. Epidemiology of restless legs syndrome in French adults. A nationwide survey: The INSTANT study. Neurology 2005;65:239-246 . Zucconi M, Ferini-Strambi L. Epidemiology and clinical findings of restless legs syndrome. Sleep Medicine 2004;5:293-299. References:  References Walters AS, Hickey K, Maltzman J. A questionnaire study of 138 patients with restless legs syndrome: the ‘night walkers’ survey. Neurology 1996;46:92-95. Appiah-Kubi LS, Pal S, Chaudhuri KR. Restless legs syndrome (RLS), Parkinson’s disease, and sustained dopaminergic therapy for RLS. Sleep Med 2002;3:S51-S55. Winkelmann J, Wetter TC, Collado-Seidel V. Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients. Sleep 2000;23:597-602. TO BE CONFIRMED Allen RP, La Buda MC, Becker P et al. Family history study of the restless legs syndrome. Sleep Med 2002;3:S3-S7. Winkelmann J. The genetics of restless legs syndrome. Sleep Med 2002;3:S9-S12. UK Ekbom Support Group Survey, 2004. Desautels A, Turecki G, Montplaisir J. Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. Am J. Hum. Genet. 2001;69:1266-1270. References:  References Chen S, Ondo WG, Rao S et al. Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p. Am J Hum Genet. 2004;74:876-885. Connor JR, Wang XS, Patton SM et al. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology 2004;62:1563-1567. Ondo W. Secondary restless legs syndrome. In: Chaudhuri KR, Odin R, Olanow CW, eds. Restless Legs Syndrome. Taylor and Francis London; New York 2004:75. Silber MH, Ehrenberg BL, Allen RP et al; for the Medical Advisory Board of the Restless Legs Syndrome Foundation. An algorithm for the management of restless legs syndrome. Mayo Clin Proc 2004;79:916-922. Avecillas JF, Golish JA, Giannini C et al. Restless legs syndrome: Keys to recognition and treatment. Clev Clin J Med 2005;72:769-787. Abetz L, Allen R, Follet A et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther 2004;26:925-935. References:  References Chaudhuri KR, Meilak C. What is restless legs syndrome? In: Chaudhuri KR, Odin R, Olanow CW, eds. Restless Legs Syndrome. Taylor and Francis. London; New York 2004:1-2. Allen 2003 National Institutes of Health. Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome. Am Fam Physician 2000;62:108-114. REF from Ray/ Koller WC, Rueda MG. Mechanism of action of dopaminergic agents in Parkinson’s disease. Neurology 1998;50 (Suppl 6):S11-14. De Koker A, Whitehead H, Chaudhuri KR. Therapeutic strategies for restless legs syndrome. Future Prescriber 2005:5-10. Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996;19:205-213. References:  References Oertel W, Stiasny-Kolster K. Pramipexole is effective in the treatment of restless legs syndrome (RLS): Results of a 6-week, multi-centre, double-blind, and placebo-controlled study [abstract P191]. Mov Disord 2005;20(Suppl 10): S1-S192. Staedt J, Wassmuth F, Ziemann U. Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS). A double-blind randomized crossover trial of pergolide versus L-Dopa. J Neural Transm.1997;104(4-5):461-8. Ferini-Strambi L. Restless legs syndrome augmentation and pramipexole treatment. Sleep Med 2002;3:S23-S25. RLS:UK database Das Gupta RJ & Chaudhuri KR. A retrospective study of drug treatment patterns among UK primary care patients with restless legs syndrome (RLS) between 1st April 2004 and 31st March 2005. Presented at the European Congress of the International Society for Pharmacoeconomic Research. Florence, Italy. November 2005. www.ekbom.org.uk

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