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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
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Restless Legs Syndrome
“the most common condition you’ve never heard of”
www.rls.org
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RLS Excludes PLMD
RLS Includes PLMS
RLS PLMD
RLS PLMD
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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.
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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Historical References for RLS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.”
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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Historical References
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Common Characteristics OfRestless 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.
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Common Characteristics OfRestless 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.
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Terms Used to Describe RLS Sensations
Creeping Aching Restless
Crawling Pulling Painful
Itching Drawing Indescribable
Burning Electric current-like
Searing Like water flowing
Tugging Like worms or bugs crawling under the skin
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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.
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Symptoms of RLS Follow Circadian Rhythm Hening W et al, Sleep 22:901-915 1999
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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.
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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 severe 31-40 very severe
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Distribution of RLS Scores
Neurology 2005;65:239–246
n = 731
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Differential Diagnosis of RLS
Leg cramps
Peripheral neuropathy
Varicose veins
Intermittent claudication
Neuroleptic-induced akathisia
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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
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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
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RLS Prevalence in Francen = 10,263
Neurology 2005;65:239–246
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RLS Prevalence in Francen = 10,263
Men Women
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Prevalence in Germanyn = 431
Arch Intern Med 2004; 164: 196–202.
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Symptoms in a US population
Arch Intern Med 2000; 160: 2137–41.
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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
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RLS Pathophysiology
Central Nervous system dysfunction– Cortical
– subcortical
– spinal cord
Brain Dopaminergic function.
Iron Metabolism
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Brain Iron Insufficiency
Brain Iron InsufficiencyRestless Legs Syndrome
CNS Dopamine Abnormalities
Iron-Dopamine Model of RLS
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Ferritin Levels: Correlate with RLS but not PLMS
0 25 50 75 100 125 150 175 200 225
Ferritin mcg/l
0
1
2
3
RLS
sev
erity
r=0.43
0 25 50 75 100 125 150 175 200 225 250
Ferritin mcg/l
-200
20406080
100120140160180200
PLM
/hr
r=0.13
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Iron-Dopamine Model of RLS
Earley CJ et al Neurology 2000; 54:1698-1700
contro
l
RLS
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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
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Neurology 2003;61:304–309
Impaired Brain Iron Acquisition inRestless Legs Syndrome:
Neuropathologic Examination
Control RLS
Marked reduction in ferritin in substantia nigra of RLS brain
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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)
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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)
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Most people are asymptomatic
Poor association between PLMS and sleepiness
One third of patients with PLMS have RLS
Needs PSG for diagnosis
Periodic Limb Movement Syndrome
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Treatment of RLS and PLMS
Varies according to the clinical course.
Co-morbid medical conditions.
Presence or absence of associated pain.
Individualize Therapy!!
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Pharmacologic Rx for RLS
Dopamine receptor agonists and dopamine precusors.
Opioids
Benzodiazepines
Anticonvulsants
Other
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Pharmacologic Rx for RLS
Agent Advantages Disadvantages
Dopaminergic Carbidopa- Levadopa
Use as required; Good for intermittent RLS
Symptom augmentation; GI upset; Insomnia Take without food
Dopamine agonists Pramipexole Ropinirole
Good for moderate to severe RLS; highly effective
GI upset, dizziness, extreme sleepiness
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Agent Advantages Disadvantages
OpioidsCodeinePropoxypheneoxycodone
Use as required;Good forintermittent RLS
Constipation, urinaryretention, nausea;tolerance andaddiction
BenzodiazepinesClonazepamTemazepam
May improve sleep;useful when othermedications nottolerated
Daytime sleepiness;cognitive impairment(esp elderly)
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Agent Advantages Disadvantages
Anticonvulsants Gabapentin Carbamazepine Prigabalin (Lyrica)
Use when dopamine agonists not working; Good in augmentation and if pain is present
Constipation, urinary retention, nausea; sleepiness, tolerance and addiction
Opiates / Benzodiazepines
Alternate meds Pain control
Constipation, Sedation Tolerance
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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
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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.
26
10
0
5
10
15
20
25
30
RLS Score
Pre Treatment
Post Treatment
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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.
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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)