Periodic Limb Movement Disorder (PLMD)

Description

• Sleep-related movement disorder with episodes of periodic limb movements (PLMs) occurring during sleep (1)[A]
  • Periodic limb movements of sleep (PLMS) demonstrated during polysomnography combined with clinical symptoms
  • Clinical history of significant sleep disturbance or functional impairment is necessary for diagnosis.
  • PLMS are repetitive contractions of the tibialis anterior muscles occurring mainly in non-rapid eye movement (NREM) sleep.
  • Movements consist of unilateral or bilateral, simultaneous or not, rhythmical extension of the big toe and ankle dorsiflexion.
  • Sometimes, knee and hip flexion is noted.
  • Arm movements or more generalized movements occur less commonly.
  • Movements might be associated with cortical arousals from sleep unbeknownst to the patient (PLMs with Arousals—PLMA).
  • Complaints include insomnia, nonrestorative sleep, daytime fatigue, and/or somnolence.
  • Bed partner may complain of patient’s movements.
  • Another sleep disorders: Obstructive sleep apnea, narcolepsy, restless legs syndrome do not explain the PLMS (2)[A].
• No wakeful perception of the PLMS or associated restlessness
  • If there is wakeful perception, the diagnosis is not periodic limb movement disorder (PLMD) but possibly RLS.
• System(s) affected: musculoskeletal, nervous
• Synonym(s): nocturnal myoclonus; sleep myoclonus; periodic leg movements of sleep

Epidemiology

• PLMD is rare, reported in both children and adults (1).
• PLMS occurs in at least 15% of insomnia patients.
• PLMS is frequent in rapid eye movement (REM) sleep behavior disorder (RBD) occurring during REM sleep.
• PLMS is frequent in narcolepsy, in OSA, and during initiation of continuous positive airway pressure (CPAP).

• No predominant sex preference; male = female
• PLMS >5/hr is uncommon before age 40 years.
• PLMS increases with age: 45% of patients >65 years exhibit PLMS >5/hr but not necessarily PLMD.
• PLMD is much less common: <5% of adults but is underdiagnosed (1)
• 85% of RLS patients have PLMS (3).

Etiology and Pathophysiology

• Understudied; most data pertain to PLMS in RLS.
• Brain iron deficiency
• Supra-segmental disinhibition at the brainstem and spinal cord levels
• Spinal cord excitability
• CNS dopamine dysregulation supported by increased incidence of PLMS in untreated Parkinson disease (PD) patients
• Decreased incidence of PLMS in schizophrenia patients
• Triggering and exacerbating factors:
  • Peripheral neuropathy
  • Arthritis
  • Renal failure
  • Synucleinopathies (multiple-system atrophy)
  • Spinal cord injury
  • Pregnancy
  • Medications:
    • Most antidepressants (except bupropion or desipramine) and lithium
    • Some antipsychotic and anti-dementia medications
    • Antiemetics (metoclopramide)
    • Antihistamines

Genetics
BTBD9 on chromosome 6p associated with PLMS in patients with or without RLS, but not in RLS patients without PLMS

Risk Factors

• Family history of RLS
• Iron deficiency and associated conditions
• Peripheral neuropathy
• Arthritis, orthopedic problems
• Chronic limb pain or discomfort

General Prevention

• Adequate nightly sleep
• Avoid PLMS triggers such as iron deficiency, frequently observed in children.
• Awareness, including family history

Commonly Associated Conditions

• Narcolepsy
• Iron deficiency
• End-stage renal disease (ESRD)
• Cardiovascular disease; stroke
• Gastric surgery
• Pregnancy
• Arthritis
• Synucleinopathies (multiple-system atrophy)
• Lumbar spine disease; spinal cord injury
• Peripheral neuropathy
• Insomnia, insufficient sleep, parasomnias
• ADHD
• Mood disorders, anxiety, oppositional behaviors