Restless Leg Syndrome What does it mean to you in the middle of the night?

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2 Restless Leg Syndrome What does it mean to you in the middle of the night? David A. Weed, DO, FCCP, D, ABSM Sleep Disorders Center ~ The Aroostook Medical Center Presque Isle, Maine S

3 1990 S 22 year old woman presents after participating in a sleep research study S No sleep or daytime functioning complaints S Obtains 7 hours of regular and restored sleep S Told she had a lot of leg activity

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6 Pearls

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8 Michael Silber, MBChB, FAAN S In order to diagnose PLMD then PLMS must be present on PSG >15/hr in adults + a clinical disturbance attributed to the PLMS and not better explained by any other current sleep, medical, neurologic, or substance use disorders. S A diagnosis of PLMD is thus not used for RLS with PLMS and considerable cautions should be exercised in diagnosing PLMD in setting of sleep apnea or narcolepsy.

9 RLS excludes PLMD RLS often includes PLMS, and PLMD requires PLMS

10 PLMS ~ What is it? Can it hurt me? S Single study: 39% controls > 49 y.o. PLMS 30/hr S Community dwelling study: 45-85% subjects > 60 y.o > 5 PLMS/hr S Epiphenomenon

11 Can it hurt me?

12 Treat or Not Treat PLMS? S What about to preserve better sleep quality? S What about with arousal? S What about cardiovascular risk association?

13 Clinical Significance: PLMS and Sleep Quality SNo association between PLMS and PSG measures of sleep quality in asymptomatic patients

14 Clinical Significance: What about with Arousal? S No definite correlation with PLMS and timing of EEG arousal: 50% before, 30% during, and 23% after S Levadopa gets rid of PLMS but not arousals S PLMS represent a physiologic response and not cause of the arousal

15 Clinical significance: What about CV protections? S HRV and blood pressure swings seen with PLMS S Variability seen with and without arousals S Autonomic variations usually occur prior to PLMS S PLMS represent a physiologic response instead of cause of this autonomic instability

16 Back to Our Patient: Final Plan S Reassurance S No treatment required

17 2000 Ten years later S

18 She s back: Pregnant, Tired, with the URGE S 6 months pregnant S Insomnia S Creepy crawly things in her legs has to just keep moving S Sensations regularly begin between 8-9pm S She has had a healthy uneventful pregnancy S An active sleeper, kicking, thrashing, with sleep initiation issues due to leg complaints

19 During the day S Awakens feeling unrestored S Memory and concentration difficulty S Changes in mood

20 Diagnosis S A: PLMD secondary to pregnancy S B: PLMS secondary to pregnancy S C: RLS secondary to pregnancy S D: Pregnancy

21 Diagnosis S A: PLMD secondary to pregnancy S B: PLMS secondary to pregnancy S C: RLS secondary to pregnancy S D: Pregnancy

22 The Wayne Hening URGE S U = urge to move the legs, usually associate with unpleasant leg sensations S R = rest induces symptoms S G = getting active (physically and mentally) brings relief S E = Evening and night make symptoms worse

23 RLS in Pregnancy: Prevalence

24 Prevalence of RLS Based on Adequate RLS Diagnostic Surveys

25 Mechanism S Pregnancy lowers the symptomatic threshold for RLS S Potential factors: Hormones, iron deficiency, dopaminergic alterations, vitamin deficiency

26 Mystery continues S Incidence not affected by pre-emptive iron supplementation S Not affected by severity, anesthesia, delivery route, complications, birth weight, breastfeeding, newborn weight

27 RLS in Pregnancy S 4 fold increase in developing idiopathic RLS within 3 years S Investigate the genes of women who develop RLS in pregnancy since they may represent genetic predisposition

28 RLS Secondary to Pregnancy: Management S Education and counseling S Iron replace if ferritin < 50 mcg/l S Dopamine Agents effect lactation S Severe cases after full disclosure: S Opioids Category C S Clonazepam Category D S Stop Caffeine; healthy sleep habits

29 Back to our Patient: Final Plan S Reassurance S Optimized good sleep behavioral habits S Resolution of symptoms 3 weeks before delivery

30 2005 Five years later S

31 The Creepy-Crawly every night S She is now 42 S Reports insomnia for the last year S Similar leg complaints of pregnancy S Sensations regularly begin between 8-9pm

32 During the day S Daytime fuzziness S Depression S Prior history of alcohol abuse (sober last 5 years) S Hypertension S Physical exam unremarkable

33 Supportive Clinical Features of RLS S Positive family history of RLS S Improvement with dopaminergic therapy S Periodic Limb Movements in Sleep (PLMS) S Involuntary leg movements associated with sensory symptoms

34 RLS: Identify Potential Aggravators S Nicotine S Antidepressants S Central-acting antihistamines S Dopaminergic antiemetics S Antipsychotics S Sleep deprivation S Alcohol

35 Treat or Not to Treat? S

36 Further Treatment Considerations S RLS effects on quality of life and sleep S Frequency and severity of symptoms S Co-morbid medical conditions S Presence of iron deficiency

37 My PCP says I m not iron deficient

38 RLS: Always Look for Iron Deficiency (Preferably fasting) ~Ferritin < 50 ng/ml; ~Percent iron saturation < 16% ~TIBC > 400% ~Iron < 60 ng/ml

39 My PCP says I am not iron deficient

40 Iron Replacement Therapy Oral S Give 2 doses of iron, mg/ day S Recheck ferritin every 6 months Intravenous S Option in oral admin. resistance or intolerance S Use iron gluconate or iron sucrose S Iron dextran may cause anaphylactic reactions

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43 Patient asked, Can RLS hurt me? S

44 Back to Our Patient: Final Plan

45 years later S

46 I m eating and spending S Zolpidem for insomnia S Low dose dopamine agent S Confesses conscious compulsion for nocturnal eating and 9 lb weight gain S Impulsive spending sprees x 1 year

47 Non-motor RLS symptoms i.e. Restless Behaviors S RLS patients often have other nocturnal compulsions S Nocturnal eating make it easier to fall asleep S Smoke later in the evening, and are more likely after waking up in the middle of the night S Restless smoking and restless eating often coincide

48 Zolpidem-induced sleepwalking and amnestic eating S Referrals for amnestic zolpidem-induced sleepwalking and SRED (amnestic binge eating) have increased since the 1990s S S S Many of these patients had undiagnosed and atypical RLS GABA and opioid agents can confound diagnoses by masking motor restlessness Dopaminergic agents relieve both nocturnal eating and SRED

49 Impulse Control Disorder S Failure to resist an impulsive act or behavior that may be harmful to self or others S Eg. Violent behavior, sexual behavior, gambling behavior, fire starting, stealing, shopping, and self-abusive behaviors

50 Impulse Control Disorder

51 Impulse Control Disorder S ICD 6-12 % prevalence: 4 studies S Risk factors: Dose, female sex, young age, experimental drug use, family history of gambling, depression, stress, sleep problems

52 Back to Our Patient: Final Plan re. eating SDiscontinued Zolpidem SNocturnal eating resolved

53 What about the spending? S I heard an ad for Mirapex on TV and the word compulsive was mentioned. Let me tell you about my problem and PLEASE keep this confidential. My husband does not know this. In the past few years I have been shopping compulsively and have now run my credit card debt up to over $40,000. Just recently, I have sat back and tried to examine why this happened. I never used to be this way. Since I stopped Mirapex and started the new regimen with Neurontin I have also noticed that my behavior is not so compulsive and I am not reckless with my spending. In fact, I no longer have an interest in shopping.

54 years later S

55 Do I still have RLS or some new disease? S Back for routine annual follow-up S Done well with her regimen of Gabapentin and maintains good iron status with oral supplementation S Active in the RLS support group and likes to remain abreast of the latest findings regarding the condition S She has heard that RLS definition and criteria has changed. Is that true?

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57 RLS: Essential Criteria Met S U = Urge to move the legs, usually associate with unpleasant leg sensations S R = Rest induces symptoms S G = Getting active (physically and mentally) brings relief S E = Evening and night make symptoms worse S R = Rule out mimics

58 The Challenges of a Clinical Diagnosis

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60 An old condition with a new name RLS Willis-Ekbom Disease S

61 Back to Our Patient: Final Plan

62 A pessimist sees the difficulty in every opportunity; an optimist sees the opportunity in every difficulty. Winston Churchill ( )