What are the risk factors for Periodic Limb Movement Disorder (PLMD)?

Risk Factors for Periodic Limb Movement Disorder (PLMD)

The primary risk factors for Periodic Limb Movement Disorder (PLMD) include aging, iron deficiency, uremia, pregnancy, polyneuropathy, and certain medications, particularly antidepressants and antipsychotics. 1, 2, 3

Established Risk Factors

Medical Conditions

• Iron deficiency: Low ferritin levels (≤75 ng/mL) or transferrin saturation <20% 1, 4
• Uremia/End-stage renal disease: Significantly increases risk of PLMD 2, 3
• Polyneuropathy: Peripheral nerve damage is associated with higher PLMD prevalence 2, 3
• Diabetes mellitus: Can contribute to development of PLMD 5
• Parkinson's disease: Associated with higher rates of PLMD 3

Demographic Factors

• Aging: Prevalence of PLMD increases significantly with age 5
• Pregnancy: Represents a temporary risk factor for developing PLMD 2, 3

Medications

• Antidepressants: Particularly selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and some tetracyclic antidepressants 6
• Antipsychotics: Can induce or exacerbate PLMD 6
• Lithium: Associated with increased risk of PLMD 6
• Opioid withdrawal: Can trigger or worsen PLMD symptoms 6

Associated Conditions

• Restless Legs Syndrome (RLS): Frequently co-occurs with PLMD 3
• Sleep apnea syndrome: PLMD is commonly found in patients with this condition 5
• Attention-deficit/hyperactivity disorder (ADHD): Particularly relevant in pediatric PLMD 7
• Neurodevelopmental disorders: Associated with higher rates of PLMD in children 7
• Delayed sleep phase syndrome: Has been reported to co-occur with PLMD 5
• Narcolepsy: Associated with higher prevalence of PLMD 5

Clinical Implications

Diagnostic Considerations

• PLMD diagnosis requires polysomnography to document periodic limb movements during sleep (>15 events/hour in adults) 4
• Symptoms may include excessive daytime sleepiness or insomnia 5
• Many patients with PLMD may be undiagnosed due to lack of awareness or limited access to sleep studies 2

Management Approach

• Address underlying risk factors when possible (e.g., iron supplementation for iron deficiency) 4
• Consider medication review for patients taking drugs known to exacerbate PLMD 6
• Alpha-2-delta ligands (gabapentin, pregabalin) are first-line pharmacological treatments 4
• Avoid medications that can worsen symptoms, particularly certain antidepressants and antipsychotics 6

Pediatric Considerations

• In children, PLMD may present differently and is often associated with ADHD and neurodevelopmental disorders 7
• Iron deficiency is a particularly important modifiable risk factor in pediatric PLMD 7
• Recent evidence suggests considering a broader diagnostic category ("Sleep Leg Movement Disorder of Childhood") to better capture the spectrum of pediatric limb movement disorders 7

Understanding these risk factors is essential for early identification and appropriate management of PLMD, which can significantly impact sleep quality and daytime functioning if left untreated.