Description

Sleep-related movement disorder characterized by periodic limb movements of sleep (PLMS) with significant sleep disturbance and/or daytime functional impairment:

• PLMS demonstrated during polysomnography (PSG)
• PLMS are repetitive contractions of 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).
• A clinical history of significant sleep disturbance and/or functional impairment is necessary for diagnosis.
• Complaints include insomnia, nonrestorative sleep, daytime fatigue, somnolence.
• Bed partner may complain of patient’s movements.
• Other sleep disorders such as obstructive sleep apnea (OSA), narcolepsy, and restless legs syndrome do not explain the PLMS.
• No associated restlessness or dysesthesia while awake
  • If there is an associated sensory perception or restlessness, the diagnosis is not PLMD but possibly restless leg syndrome (RLS).
• System(s) affected: musculoskeletal, nervous
• Synonym(s) referring to the PLMS: nocturnal myoclonus; sleep myoclonus

Epidemiology

• PLMD is rare, affecting children and adults (1).
• PLMS occurs in >15% of insomnia patients.
• PLMS are frequent in rapid eye movement (REM) sleep behavior disorder (RBD) occurring during REM sleep.
• PLMS are frequent in narcolepsy, in OSA, and during initiation of CPAP.

• No 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 PLMD.
• PLMD is much less common: <5% of adults, but also underdiagnosed (1)
• 85% of RLS patients have PLMS (2).

Etiology and Pathophysiology

• Understudied; most data reports on PLMS as it pertains to RLS:
  • Brain iron deficiency causing CNS dopamine dysregulation
  • Suprasegmental 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) and decreased incidence of PLMS in schizophrenia
• 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 antidementia medications
    • Antiemetics (dopaminergic)
    • Sedating 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
• History of prematurity

General Prevention

• Promoting adequate sleep
• Avoid PLMS triggers such as iron deficiency, frequently observed in children (3).
• Awareness, including family history

Commonly Associated Conditions

• Narcolepsy
• 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 disorder, anxiety, oppositional behaviors

Pediatric Considerations

• PLMD may precede overt RLS by years (3).
• Association with RLS is more common.
• Symptoms may be more resultant than in adults (4).
• Association and differential diagnosis with ADHD, oppositional behaviors, mood disorders, growing pains (3)

Pregnancy Considerations
PLMD is not well studied in pregnant women; implying from literature on RLS with PLMS in pregnant women:

• May be secondary to iron, folate deficiency
• Most severe in the 3rd trimester
• Usually resolves after delivery

Geriatric Considerations

• Potential source of sleep disturbance
• May cause or exacerbate circadian disruption and “sundowning”
• Medications that may trigger or exacerbate PLMs, which can lead to PLMD
• PLMS may increase risk of atrial fibrillation in elderly.