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Periodic Limb Movement Disorder
Donald E. Watenpaugh, PhD
John R. Burk, MD
image BASICS
DESCRIPTION
  • Sleep-related movement disorder with these features:
    • Episodes of periodic limb movements (PLMs) during sleep
    • Movements consist of bilateral ankle dorsiflexion, sometimes with knee and hip flexion.
    • Arm or more generalized movements occur less commonly.
    • Movements may cause brief microarousals from sleep unbeknownst to the patient.
    • Complaints include insomnia, unrestorative sleep, daytime fatigue, and/or somnolence.
    • Bed partner may complain of movements.
    • Another sleep disorder (e.g., obstructive sleep apnea) does not cause the PLMs.
  • System(s) affected: musculoskeletal, nervous
  • Synonym(s): nocturnal myoclonus; sleep myoclonus; periodic leg movements of sleep
EPIDEMIOLOGY
Incidence
  • Increases with age: 1/3 of patients >60 years exhibit PLMs but not necessarily periodic limb movement disorder (PLMD).
  • Predominant sex: male = female
  • PLMs in 15% of insomnia patients
Prevalence
  • PLMs in sleep: common and often of no clinical consequence
  • PLMs constituting PLMD (causing sleep complaints and/or daytime consequences) much less common: <5% of adults (but underdiagnosed)
ETIOLOGY AND PATHOPHYSIOLOGY
  • Unstudied
  • Primary: probable CNS dopaminergic impairment
  • Secondary:
    • Iron deficiency
    • Peripheral neuropathy
    • Arthritis
    • Renal failure
    • Synucleinopathies (multiple-system atrophy)
    • Spinal cord injury
    • Pregnancy
    • Medications:
      • Most antidepressants (not bupropion or desipramine)
      • Some antipsychotic and antidementia medications
      • Antiemetics (metoclopramide)
      • Antihistamines
Genetics
Unstudied, but see “Restless Legs Syndrome” (RLS)
RISK FACTORS
  • Family history of RLS
  • Iron deficiency and associated conditions (e.g., pregnancy, gastric surgery, renal disease)
  • Attention deficit hyperactivity disorder (ADHD)
  • Aging
  • Peripheral neuropathy
  • Arthritis, orthopedic problems
  • Chronic limb pain or discomfort
GENERAL PREVENTION
  • Regular physical activity
  • Adequate nightly sleep
  • Avoid causes of secondary PLMD.
  • Avoid causes of RLS.
COMMONLY ASSOCIATED CONDITIONS
  • RLS
  • Rapid eye movement (REM) sleep behavior disorder
  • Narcolepsy
  • Iron deficiency
  • Renal failure
  • Cardiovascular disease; stroke
  • Gastric surgery
  • Pregnancy
  • Arthritis
  • Synucleinopathies (multiple-system atrophy)
  • Lumbar spine disease; spinal cord injury
  • Peripheral neuropathy
  • Insomnia, insufficient sleep
  • ADHD
  • Depression
Pediatric Considerations
  • 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
Pregnancy Considerations
  • May be secondary to iron or folate deficiency
  • Most severe in 3rd trimester
  • Usually subsides after delivery
Geriatric Considerations
  • 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.
image DIAGNOSIS
PHYSICAL EXAM
No specific findings
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 seconds
    • EMG amplitude increases >8 &mgr;V 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
  • Serum ferritin to assess for iron deficiency
P.787

Diagnostic Procedures/Other
  • Ankle actigraphy for in-home use
  • EMG or nerve conduction studies for peripheral neuropathy/radiculopathy
Test Interpretation
Serum ferritin should be >75 ng/mL.
image TREATMENT
Treatment paradigm similar to that for RLS, except that all medications are off-label for PLMD
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.
First Line
  • 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 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.
  • Avoid dopamine agonists in psychotic patients, especially if taking dopamine antagonists.
Second Line
  • Anticonvulsants: useful for associated neuropathy (1,2)[B]:
    • Gabapentin enacarbil (Horizant): 600 mg/day
    • Pregabalin (Lyrica): 50 to 300 mg/day
  • Opioids: low risk for tolerance with bedtime dose
    • Hydrocodone: 5 to 20 mg/day
    • Oxycodone: 2.5 to 20 mg/day
  • Benzodiazepines and agonists (1,2)[B]:
    • Clonazepam (Klonopin): 0.5 to 3 mg/day
    • Zaleplon, zolpidem, temazepam, triazolam, alprazolam, diazepam
Pediatric Considerations
  • First-line treatment is nonpharmacologic.
  • Assess/correct iron deficiency.
  • Consider low-dose clonidine or clonazepam.
Pregnancy Considerations
  • Initial approach: iron supplementation, nonpharmacologic therapies
  • Avoid medications class C or D.
  • In 3rd trimester, low-dose clonazepam or opioids may be considered.
Geriatric Considerations
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 TID
    • Repletion 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
SURGERY/OTHER PROCEDURES
Correction of orthopedic, neuropathic, or peripheral vascular problems
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).
IV Fluids
  • Consider iron infusion when oral supplementation is ineffective, not tolerated, or contraindicated.
  • When NPO, consider IV opiates.
Nursing
  • Evening walks, hot baths, leg warming
  • Sleep interruption risks prolonged wakefulness.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • At monthly intervals until stable
  • Annual and PRN follow-up thereafter
  • If iron-deficient, remeasure ferritin to assess repletion.
DIET
Avoid caffeine and alcohol late in the day.
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.
REFERENCES
1. 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.
2. 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.
Additional Reading
&NA;
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
&NA;
Restless Legs Syndrome
Codes
&NA;
ICD10
G47.61 Periodic limb movement disorder
Clinical Pearls
&NA;
  • 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.