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Periodic Limb Movement Disorder

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Periodic Limb Movement Disorder

Treatment paradigm similar to that for RLS, except that all medications are off-label for PLMD

Correction of orthopedic, neuropathic, or peripheral vascular problems

11 Garcia-Borreguero D, Stillman P, Benes H, et al. Algorithms for the diagnosis and treatment of restless legs syndrome in primary care. BMC Neurol. 2011;11:28.22 Aurora RN, Kristo DA, Bista SR, et al. 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: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012;35(8):1039 " 1062.

  • PLMD may precede overt RLS by years.
  • Association with RLS is more common than in adults.
  • Symptoms may be more consequential than in adults.
  • Associated with ADHD

PLMD may precede overt RLS by years.

Association with RLS is more common than in adults.

Symptoms may be more consequential than in adults.

Associated with ADHD

  • May be secondary to iron or folate deficiency
  • Most severe in 3rd trimester
  • Usually subsides after delivery

May be secondary to iron or folate deficiency

Most severe in 3rd trimester

Usually subsides after delivery

  • May become a significant source of sleep disturbance
  • May cause or exacerbate circadian disruption and "sundowning " 
  • Many medications given to the elderly cause or exacerbate PLMs, which can lead to PLMD or RLS.

May become a significant source of sleep disturbance

May cause or exacerbate circadian disruption and "sundowning " 

Many medications given to the elderly cause or exacerbate PLMs, which can lead to PLMD or RLS.

DIAGNOSIS

HISTORY

  • Episodes of PLMs during sleep (often reported by bed partner) (1)[A]
  • Insomnia: difficulty maintaining sleep
  • Unrestorative sleep
  • Daytime fatigue, tiredness, and/or somnolence
  • Oppositional behaviors
  • Memory impairment
  • Depression
  • ADHD, particularly in children

PHYSICAL EXAM

DIFFERENTIAL DIAGNOSIS

  • When PLMs occur along with RLS, REM sleep behavior disorder, or narcolepsy, those disorders are diagnosed as "with PLMs, "  and PLMD is not diagnosed separately.
  • Obstructive sleep apnea: Limb movements (LMs) occur during microarousals from apneas; treatment of sleep apnea eliminates these LMs.
  • Sleep starts: nonperiodic, generalized, occur only at wake " “sleep transition, <0.2 seconds duration
  • Sleep-related leg cramps: isolated and painful
  • Fragmentary myoclonus: 75 to 150 ms of EMG activity, minimal movement, no periodicity
  • Nocturnal seizures: epileptiform EEG, motor pattern incongruent with PLMs
  • Fasciculations, tremor: no sleep association
  • Sleep-related rhythmic movement disorder: voluntary movement during wake " “sleep transition; higher frequency than PLMs

DIAGNOSTIC TESTS & INTERPRETATION

  • Polysomnography with finding of repetitive, stereotyped LMs (1)[A]:Tibialis anterior electromyographic (EMG) activity lasting 0.5 to 10 secondsEMG amplitude increases >8 Ž ΌV from baseline.Movements occur in a sequence of ≥4 at intervals of 5 to 90 seconds.Children: ≥5 movements per hour; adults, 15Movement may also involve arms.Associated with heart rate variability from autonomic-level arousalsMost PLM episodes occur in the first hours of non-REM sleep.Significant night-to-night PLM variability
  • Serum ferritin to assess for iron deficiency
  • Tibialis anterior electromyographic (EMG) activity lasting 0.5 to 10 seconds
  • EMG amplitude increases >8 Ž ΌV from baseline.
  • Movements occur in a sequence of ≥4 at intervals of 5 to 90 seconds.
  • Children: ≥5 movements per hour; adults, 15
  • Movement may also involve arms.
  • Associated with heart rate variability from autonomic-level arousals
  • Most PLM episodes occur in the first hours of non-REM sleep.
  • Significant night-to-night PLM variability
  • Ankle actigraphy for in-home use
  • EMG or nerve conduction studies for peripheral neuropathy/radiculopathy

TREATMENT

GENERAL MEASURES

  • Daily exercise
  • Adequate nightly sleep
  • Warm the legs (long socks, leg warmers, electric blanket, etc.).
  • Hot bath before bedtime
  • Avoid nicotine and evening caffeine and alcohol.

MEDICATION

  • Use minimum effective dose.
  • Consider risks, side effects, and interactions individually (e.g., benzodiazepines in elderly).
  • Daytime sleepiness is unusual with the doses and timing employed for PLMD.
  • Dopamine agonists: Take 1 hour before bed; titrate weekly to optimal dose (1,2)[B]:Pramipexole (Mirapex): 0.125 to 0.5 mg; titrate by 0.125 mgRopinirole (Requip): 0.25 to 4 mg; titrate by 0.25 mgTransdermal rotigotine (Neupro): 1 to 3 mg/24 hr patch; initiate with 1 mg/24 hr; titrate by 1 mg weekly to effectiveness.
  • Avoid dopamine agonists in psychotic patients, especially if taking dopamine antagonists.
  • Pramipexole (Mirapex): 0.125 to 0.5 mg; titrate by 0.125 mg
  • Ropinirole (Requip): 0.25 to 4 mg; titrate by 0.25 mg
  • Transdermal rotigotine (Neupro): 1 to 3 mg/24 hr patch; initiate with 1 mg/24 hr; titrate by 1 mg weekly to effectiveness.
  • Anticonvulsants: useful for associated neuropathy (1,2)[B]:Gabapentin enacarbil (Horizant): 600 mg/dayPregabalin (Lyrica): 50 to 300 mg/day
  • Opioids: low risk for tolerance with bedtime doseHydrocodone: 5 to 20 mg/dayOxycodone: 2.5 to 20 mg/day
  • Benzodiazepines and agonists (1,2)[B]:Clonazepam (Klonopin): 0.5 to 3 mg/dayZaleplon, zolpidem, temazepam, triazolam, alprazolam, diazepam
  • Gabapentin enacarbil (Horizant): 600 mg/day
  • Pregabalin (Lyrica): 50 to 300 mg/day
  • Hydrocodone: 5 to 20 mg/day
  • Oxycodone: 2.5 to 20 mg/day
  • Clonazepam (Klonopin): 0.5 to 3 mg/day
  • Zaleplon, zolpidem, temazepam, triazolam, alprazolam, diazepam
  • First-line treatment is nonpharmacologic.
  • Assess/correct iron deficiency.
  • Consider low-dose clonidine or clonazepam.

First-line treatment is nonpharmacologic.

Assess/correct iron deficiency.

Consider low-dose clonidine or clonazepam.

  • Initial approach: iron supplementation, nonpharmacologic therapies
  • Avoid medications class C or D.
  • In 3rd trimester, low-dose clonazepam or opioids may be considered.

Initial approach: iron supplementation, nonpharmacologic therapies

Avoid medications class C or D.

In 3rd trimester, low-dose clonazepam or opioids may be considered.

In weak or frail patients, avoid medications that may cause dizziness or unsteadiness.

ADDITIONAL THERAPIES

  • If iron-deficient, iron supplementation:325 mg ferrous sulfate with 200 mg vitamin C between meals TIDRepletion may require months.Symptoms continue without other treatment.
  • Vitamin/mineral supplements, including calcium, magnesium, B12, folate
  • Clonidine: 0.05 to 0.1 mg/day
  • Relaxis leg vibration device
  • 325 mg ferrous sulfate with 200 mg vitamin C between meals TID
  • Repletion may require months.
  • Symptoms continue without other treatment.

SURGERY/OTHER PROCEDURES

INPATIENT CONSIDERATIONS

  • Control during recovery from orthopedic procedures
  • Addition or withdrawal of medications that affect PLMD
  • Changes in medical status may require medication changes (e.g., Mirapex contraindicated in renal failure and Requip contraindicated in liver disease).
  • Consider iron infusion when oral supplementation is ineffective, not tolerated, or contraindicated.
  • When NPO, consider IV opiates.
  • Evening walks, hot baths, leg warming
  • Sleep interruption risks prolonged wakefulness.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • At monthly intervals until stable
  • Annual and PRN follow-up thereafter
  • If iron-deficient, remeasure ferritin to assess repletion.

DIET

PATIENT EDUCATION

  • National Sleep Foundation: http://sleepfoundation.org/
  • American Academy of Sleep Medicine: http://www.sleepeducation.org/

PROGNOSIS

  • Primary PLMD: lifelong condition with no current cure
  • Secondary PLMD: may subside with resolution of cause(s)
  • Current therapies usually control symptoms.
  • PLMD often precedes emergence of RLS.

COMPLICATIONS

  • Tolerance to medications requiring increased dose or alternatives
  • Augmentation (increased PLMs and sleep disturbance, emergence of RLS) from prolonged use of dopamine agonists:Higher doses increase risk.Iron deficiency increases risk.Add alternative medication, then detitrate dopaminergic agent.
  • Iatrogenic PLMD (from antidepressants, etc.)
  • Higher doses increase risk.
  • Iron deficiency increases risk.
  • Add alternative medication, then detitrate dopaminergic agent.

REFERENCES

ADDITIONAL READING

  • Picchietti ‚ DL, Rajendran ‚ RR, Wilson ‚ MP, et al. Pediatric restless legs syndrome and periodic limb movement disorder: parent-child pairs. Sleep Med. 2009;10(8):925 " “931.

SEE ALSO

CODES

ICD10

ICD9

SNOMED

CLINICAL PEARLS

  • Many patients with PLMs may not require treatment; however, when sleep disturbance from PLMs causes insomnia and/or daytime consequences, PLMD exists and should be treated.
  • Many antidepressants and some antihistamines cause or exacerbate PLMs.
  • Sleep disturbance, including that from PLMs, may cause or exacerbate ADHD.