Restless leg syndrome

Restless leg syndrome

• 1.
  Dr Parag Moon Seniorresident, Dept. Of Neurology GMC, Kota.
• 2.
   Ekbom syndromeaka Anxietas tibiarum  Leg jitters- colloquial term  Periodic limb movements in sleep (PLMS)  Motor counterpart of RLS  Formerly nocturnal myoclonus and periodic leg movements in sleep.
• 3.
   Affects about10% of adults  Approximately one third-symptoms prior to age of 18  Prevalence-increases with age  More common in females  Family history-frequently in those who experience early symptoms.
• 4.
   Early-onset RLS-startsbefore age of 45 years, progress gradually.  Late-onset RLS-advances more quickly and occurs more often.  Primary RLS- occurs independently of other disorders.  Secondary RLS- precipitated by other disorders and resolves when other disorders treated.
• 5.
   May besecondary to- ◦ Iron deficiency, vit. B12 deficiency ◦ Pregnancy ◦ End stage renal disease (ESRD) ◦ Diabetes ◦ Hypothyroidism ◦ Rheumatoid arthritis ◦ Sjogren syndrome ◦ Peripheral neuropathy ◦ Parkinson disease ◦ Drugs (antidepressants, antipsychotics, lithium etc.)
• 6.
   Diphenhydramine  Metoclopramide Prochlorperazine  Chlordiazepoxide  Traditional antipsychotics (phenothiazines)  Atypical neuroleptics (olanzapine and risperidone)  Antidepressants (especially norepinehrine or selective serotonin reuptake inhibitors)  Anticonvulsants (zonisamide, phenytoin, methsuximide)  Antihistamines  Opiods
• 7.
   Characterised-irresistible urgeto move legs especially at rest.  Symptoms worsen in evening and night and improve with activity such as walking.  Sensations described as crawling, pins and needles, tingling, prickly, painful, or worming or other indescribable feelings in their legs.  May simply have a need to move.  Sensation decreased by movement, massaging.
• 8.
   Rarely occuron arms  Can cause sleep disturbances  Most have mild or intermittent symptoms  30 percent-moderate to severe symptoms.  Severe-15 days or more per month.  Often associated with depression and anxiety  Can have negative effect on quality of life.
• 9.
   Periodic limbmovements of sleep (PLM or PLMS)  Brief repetitive movements  Mostly of legs  Occur every 20-40 seconds.  Often present in RLS patients  Initial jerk followed by tonic spasm.  Dorsiflexion of big toe, foot and even leg  Occurs during stage I and II of sleep
• 10.
   Underlying causesof RLS or PLMS remain unclear  Central dopaminergic system, particularly striatonigral system, implicated  Hypothesis supported by beneficial effects of dopaminergic agents  SPECT and PET-reduced striatal D2 receptor binding using123I-IBZM and 11C-raclopride.  18F-DOPA PET-decrease in striatal18F-DOPA uptake  Decrease in cerebral blood flow in caudate nuclei and increase in anterior cingulate gyrus-familial RLS.
• 11.
   Reduced CSFferritin and increased transferrin concentrations in idiopathic RLS  Serum iron concentrations exhibit circadian variation with up to 50% drop in iron concentration at night  Iron-cofactor for hydroxylation of tyrosine hydroxylase-rate limiting enzyme for dopamine production.
• 12.
   PLMS andspinal flexor reflexes share common spinal origin  Disinhibition of reticulospinal excitatory responses may lead to pathological recruitment of spinal motor neurons.  Spinal flexor reflexes seem to be under partial dopaminergic control and levodopa depresses both facilitatory and inhibitory flexor reflex afferents.
• 13.
   Coexistence ofRLS and Parkinson's disease is controversial  Increased PLM index-reported in untreated patients with Parkinson's disease.  Misdiagnosis of RLS-nocturnal dyskinesias and akathisia in PD  Genetic basis for RLS-positive family history in 63%-92% & autosomal dominant pattern of inheritance  Associated with spinocerebellar ataxia (type 3).
• 14.
   Panic attacks Akathisia  Painful legs and moving toes syndrome-similar distribution but not relieved by movement.  “Vesper’s curse”-associated with congestive heart failure, in which engorgement of lumbar veins at night brings transient stenosis of lumbar cord causing nocturnal pain in lower limbs extending to lumbosacral region.  Polyneuropathies  Meralgia paraesthetica  Sleep onset myoclonus and nocturnal myoclonus
• 15.
   Essential criteria Urge to move or Urge to move legs, usually accompanied/caused by uncomfortable/ unpleasant sensations in legs.  Unpleasant sensations begin or worsen during periods of rest or inactivity.  Urge to move or unpleasant sensations are partially/totally relieved by movement, at least as long as activity continues.  Urge to move or unpleasant sensations worse in evening/night than during day, or only occur in evening/night.
• 16.
   Positive familyhistory of RLS.  Positive response to dopaminergic Drugs.  PLMS as assessed with polysomnography or leg activity devices.
• 17.
   Natural clinicalcourse of disorder.  Sleep disorders-frequent but unspecific symptom of the RLS.  Medical evaluation/physical examination: neurological examination usually normal.  Probable causes for secondary RLS should be excluded.
• 18.
   POLYSOMNOGRAPHY  RecordsPLMS  Correlates strongly but indirectly with RLS  Useful measure for diagnosing RLS and monitoring of treatment.  Tibialis anterior muscle-recorded  PLM scoring-pathological value >five PLM/hour of sleep.  Evidence of arousal.
• 19.
   ACTIGRAPHY  Muscleactivity monitored by small portable meter  Usually worn at ankle.  Allows monitoring in patient’s own home  Actigraphical devices do not differentiate between PLM and other involuntary movements associated with apnoea.
• 20.
   IMMOBILISATION TESTS Suggested immobilisation test (SIT)-Patients attempt to maintain seated posture without moving their legs  Forced immobilisation test (FIT)-legs are physically restrained while anterior tibial EMGs record PLM  Discomfort of patients.
• 21.
   Primary RLS-requiretreatment throughout their lives  Secondary RLS -remit underlying condition resolved  RLS treatment symptomatic, not preventive.  Non-pharmacological measures-advice on improvement of sleep hygiene and avoidance of stimulants or aggravating drugs (caffeine, alcohol, hot baths).
• 22.
   Levodopa  Inprimary RLS and at short-term follow-up- effective in reducing symptoms of RLS and improving sleep quality and quality of life and reducing PLMS (level A rating).  Adverse events minor (level A).  In long-term follow-up its still effective  30–70% dropped out due to adverse events or lack of efficacy (level C).
• 23.
   Augmentation-20-82%  InRLS secondary to uraemia, at short-term follow-up, levodopa probably effective in reducing symptoms, improving quality of life and reducing PLMS (level B).
• 24.
   Ergot derivatives In primary RLS pergolide effective at mean dosages of 0.4–0.55 mg/day (level A)  Possibly effective in long term (level C).  Cabergoline effective at 0.5–2 mg/day (level A) and possibly effective in long term (level C).  Bromocriptine 7.5 mg probably effective (level B).
• 25.
   In secondaryRLS associated with chronic haemodialysis, pergolide probably ineffective at 0.25 mg/day (level B).  Adverse events- nausea, headache, nasal congestion, dizziness and orthostatic hypotension  Augmentation not assessed with pergolide in class I studies
• 26.
   Non ergotderivatives  Primary RLS ropinirole effective 1.5–4.6 mg/day (level A)  Rotigotine transdermal patch delivery effective in short term (level A)  Pramipexole probably effective (level B).  In RLS secondary to uraemia ropinirole probable effective (level B).  Augmentation-7% with ropinirole (class I evidence).  Insufficient evidence about use of non-ergot in PLMD.
• 27.
   Gabapentin 800–1800mg/day effective in primary RLS (level A) and probably effective in secondary RLS after haemodialysis (level B).  Carbamazepine 100–300 mg and valproate slow release 600 mg/day-probably effective in primary RLS (level B).  Pregabalin also effective.
• 28.
   Clonidine-probably effectivein reducing symptoms and sleep latency in primary RLS at short term (level B).  Mean dosage 0.5 mg 2 h before onset of symptoms) for 2–3 weeks  Adverse events (dry mouth, decreased cognition and libido, lightheadedness, sleepiness, headache  Other drugs-talipexole, propranolol and phenoxybenzamine
• 29.
   Clonazepam -probablyeffective for improving symptoms in primary RLS when given at 1 mg before bedtime  Probably ineffective when given at four doses (level B).  For PLMD, clonazepam at 0.5–2 mg/daily probably effective (level B)  Triazolam (0.125–0.50 mg/day)-probably effective in ameliorating sleep efficiency and probably ineffective in reducing PLMS (level B).
• 30.
   Adverse events-morningsedation, memory dysfunction, daytime somnolence and muscle weakness  No recommendation for other benzodiazepines/hypnotics and in secondary RLS.
• 31.
   Primary RLSoxycodone at 11.4 mg probably effective in improving RLS symptoms, PLMS and sleep efficiency on short-term basis (level B).  Adverse events-mild sedation and rare nocturnal respiratory disturbances on long-term use  Insufficient evidence about morphine, tramadol,  codeine and dihydrocodeine, tilidine, and methadone and intrathecal route  Insufficient evidence in secondary RLS.
• 32.
   Primary RLSiron sulphate at daily dose 325mg probably ineffective (level B).  Insufficient evidence to about use of intravenous iron dextran, magnesium oxide and amantadine.  In RLS secondary to uraemia, iron dextran 1000 mg in single intravenous dose is probably effective in short term (<1 month) (level B).  Iron sucrose ineffective.
• 33.
   PLMS- transdermaloestradiol ineffective (level A)  Modafinil and 1-day nocturnal haemodialysis probably ineffective(level B)  Cognitive-behavioural therapy as effective as clonazepam (level B).  5-OH-tryptophan, trazodone possibly ineffective  Apomorphine and physical exercise (in myelopathy) possibly effective (level C).
• 35.
  Thank you
• 36.
   Algorithms forthe diagnosis and treatment of restless legs syndrome in primary care; Garcia-Borreguero et al. BMC Neurology 2015, 11:28  Hornyak M et al; What treatment works best for restless legs syndrome? Meta-analyses of dopaminergic and non- dopaminergic medications. Sleep Med Rev. 2014 Apr;18(2):153-64.  Rios R. Et al; Treatment of restless legs syndrome. Curr Treat Options Neurol. 2013 Aug;15(4):396-409.  The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder in Adults—An Update for 2012: Practice Parameters with an Evidence-Based Systematic Review and Meta-Analyses; SLEEP, Vol. 35, No. 8, 2012  EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep; European Journal of Neurology 2010, 13: 1049–1065