From the Guidelines
Periodic limb movement disorder (PLMD) is primarily caused by dysfunction in the central nervous system's dopaminergic pathways, and its etiology is multifactorial, involving medical conditions, medications, and lifestyle factors. The primary mechanism involves dysfunction in the central nervous system's dopaminergic pathways, particularly in the basal ganglia and spinal cord 1. Several medical conditions are associated with PLMD, including iron deficiency (especially low ferritin levels below 50 ng/mL), renal failure, diabetes, peripheral neuropathy, spinal cord injuries, and neurodegenerative disorders like Parkinson's disease. Certain medications can trigger or worsen PLMD, including antidepressants (particularly SSRIs and SNRIs), antipsychotics, lithium, and some antihistamines 1.
Key Factors Contributing to PLMD
- Iron deficiency, particularly low ferritin levels below 50 ng/mL, is a significant contributor to PLMD, as evidenced by the American Academy of Sleep Medicine's suggestion to use ferrous sulfate in patients with appropriate iron status 1
- Renal failure, diabetes, peripheral neuropathy, spinal cord injuries, and neurodegenerative disorders like Parkinson's disease are also associated with PLMD
- Medications such as antidepressants, antipsychotics, lithium, and some antihistamines can trigger or worsen PLMD
- Genetic factors likely play a role, as PLMD sometimes runs in families
- Age is another factor, with prevalence increasing significantly in older adults
Relationship with Restless Legs Syndrome (RLS)
The condition frequently co-occurs with restless legs syndrome (RLS), suggesting shared pathophysiological mechanisms, though they are distinct disorders 1. Understanding these various contributing factors is essential for proper diagnosis and targeted treatment approaches. The diagnosis of PLMD is based on the frequency of periodic limb movements during sleep (PLMS) and the presence of clinically significant sleep disturbance and/or daytime dysfunction.
From the Research
Etiology of Periodic Limb Movement Disorder
The etiology of periodic limb movement disorder (PLMD) is complex and multifactorial. Several studies have investigated the underlying mechanisms and potential causes of PLMD.
- Dopaminergic dysfunction is considered a key factor in the development of PLMD, particularly in patients with restless legs syndrome (RLS) 2, 3, 4.
- Iron deficiency has also been proposed as a potential contributor to PLMD, with some studies suggesting that iron supplementation may be beneficial in reducing symptoms 5, 6.
- Other potential underlying mechanisms include thalamic glutamatergic hyperactivity, cortical-subcortical interplay, and a pure motor mechanism originating in the spinal cord 5.
- PLMD has also been associated with various medical and neurological disorders, including sleep apnea syndrome, narcolepsy, and REM sleep behavior disorder 2, 5.
Genetic and Pathophysiological Correlates
Research has identified several genetic and pathophysiological correlates of PLMD, including:
- Separable PLM phenotypes, which may be associated with distinct underlying patho-mechanisms 5.
- Nocturnal features, such as the ratio of limb movements and distribution throughout the night, which may vary across age and co-morbid clinical conditions 5.
- Associations between PLM phenotypes and major neurologic and psychiatric disorders, although these remain controversial 5.
Clinical Significance and Treatment
PLMD can lead to significant sleep fragmentation and functional impairment, including hyperactivity and delayed language development in children, and poor concentration and work performance in adults 2, 5.