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Periodic Limb Movement Disorder (PLMD)

BASICS

  • Definition: Sleep-related movement disorder with periodic limb movements of sleep (PLMS) and associated sleep disturbance/daytime impairment.
  • Clinical criteria: PLMS seen on polysomnography (PSG), causing insomnia, nonrestorative sleep, fatigue, or somnolence; diagnosis requires exclusion of other sleep disorders (e.g., RLS, OSA).
  • Movements: Repetitive contractions (usually tibialis anterior), mainly during NREM sleep, often extension of big toe and ankle dorsiflexion; may include knee/hip flexion.

EPIDEMIOLOGY

  • Incidence: PLMD is rare; PLMS frequent in insomnia, narcolepsy, OSA, elderly.
  • Prevalence: Increases with age; PLMD <5% adults, underdiagnosed.
  • PLMS: Seen in >15% of insomnia patients, 45% of patients >65 years old (>5/hr), but not all have PLMD.

ETIOLOGY & PATHOPHYSIOLOGY

  • Pathogenesis: Likely CNS dopamine dysregulation; increased PLMS in untreated Parkinson’s, decreased in schizophrenia.
  • Triggers: Peripheral neuropathy, arthritis, renal failure, spinal cord injury, pregnancy, iron deficiency.
  • Medications: Most antidepressants (except bupropion/desipramine), lithium, antipsychotics, antidementia drugs, antiemetics, sedating antihistamines.
  • Genetics: BTBD9 on 6p associated with PLMS.

RISK FACTORS

  • Family history of RLS, iron deficiency, history of prematurity

PREVENTION

  • Adequate sleep, avoid iron deficiency (especially in children), minimize triggers

ASSOCIATED CONDITIONS

  • RLS, narcolepsy, OSA, renal disease, CVD, stroke, pregnancy, arthritis, lumbar spine disease, neuropathy, insomnia, ADHD, anxiety, oppositional behaviors

DIAGNOSIS

History

  • Insomnia, nonrestorative sleep, daytime fatigue/somnolence, memory problems, ADHD (esp. children)
  • Bed partner may note movements

Physical Exam

  • No specific findings

Differential Diagnosis

  • RLS, OSA, REM behavior disorder, narcolepsy, sleep starts, leg cramps, fragmentary myoclonus, nocturnal seizures, fasciculations, tremor, sleep-related rhythmic movement disorder, restless sleep disorder

Tests

  • Polysomnography (PSG): Required for diagnosis
    • PLMS: β‰₯4 limb movements, 5–90 sec apart, EMG burst 0.5–10 sec, amplitude >8 Β΅V
    • Diagnostic cutoff: >5/hr in children, >15/hr in adults
    • Most episodes in first hours of NREM
  • Labs: Ferritin, iron panel (especially if suspected deficiency)
  • Additional: EMG/NCS if neuropathy suspected

TREATMENT

General Measures

  • Correct iron insufficiency (target ferritin >75)
  • Adequate sleep, exercise (low impact), leg warming, hot baths
  • Avoid caffeine, alcohol (especially late in day)
  • Weighted blanket

Medication (all off-label for PLMD)

First Line

  • Calcium channel Ξ±2Ξ΄ ligands
  • Gabapentin enacarbil (600 mg early evening)
  • Gabapentin (300–600 mg HS)
  • Pregabalin (75–300 mg HS)
  • Dopamine agonists
  • Pramipexole (0.125–0.5 mg, titrate, 2 hr HS)
  • Ropinirole (0.25–4 mg, titrate, 0.5–1 hr HS; preferred if renal impairment)
  • Rotigotine patch (1–3 mg/24 hr, titrate)
    • Caution: Avoid in psychosis, risk of augmentation

Second Line

  • Benzodiazepines & related
  • Clonazepam (0.5–2 mg HS), zaleplon, zolpidem, temazepam, triazolam, alprazolam, diazepam
  • Use caution in elderly

Additional

  • Clonidine (0.05–0.3 mg/day)
  • Iron supplementation if deficient (325 mg ferrous sulfate + 200 mg vit C QD between meals)
  • Consider vitamins/minerals (Ca, Mg, D, B12, folate)

Special Populations

  • Children: Nonpharmacologic first; correct iron; consider clonidine (0.1–0.3 mg HS, monitor BP)
  • Pregnancy: Iron, nonpharmacologic, clonazepam or carbidopa/levodopa (2nd/3rd trimester only, avoid late in pregnancy)
  • Geriatric: Avoid meds causing dizziness/instability

ISSUES FOR REFERRAL

  • Sleep clinic or neurology: intractable symptoms, need for high-dose meds, refractory iron deficiency, special populations

FOLLOW-UP & ONGOING CARE

  • Monthly until stable, then annual/PRN
  • Recheck ferritin if low previously
  • Assess symptoms, med side effects, augmentation

PATIENT EDUCATION

PROGNOSIS

  • Primary PLMD: Lifelong, no cure; symptoms usually controllable
  • Secondary PLMD: May resolve with cause correction (e.g., iron repletion)
  • PLMD often precedes RLS

COMPLICATIONS

  • Medication tolerance
  • Augmentation (esp. with dopamine agonists): increased PLMs, sleep disturbance, emergence of RLS
  • Iatrogenic (from antidepressants, antihistamines)

ICD-10

  • G47.61 Periodic limb movement disorder

CLINICAL PEARLS

  • Only treat PLMD if PLMs cause sleep disturbance or daytime consequences.
  • Ensure ferritin >75.
  • Many antidepressants and antihistamines worsen PLMs.