What are the diagnosis and treatment options for Periodic Limb Movement during Sleep (PLMS)?

Diagnosis and Treatment of Periodic Limb Movement Disorder (PLMD)

Periodic Limb Movement Disorder (PLMD) requires polysomnography for diagnosis and is best treated with alpha-2-delta ligands (gabapentin, pregabalin) as first-line therapy, with iron supplementation recommended for patients with ferritin ≤75 ng/mL or transferrin saturation <20%. 1, 2

Diagnosis of PLMD

PLMD is diagnosed when the following criteria are met:

1. Frequent periodic limb movements during sleep (PLMS):

   • 15 events/hour in adults

   • 5 events/hour in children 1

2. Clinical presentation:

   • Coexisting clinically significant sleep disturbance and/or daytime dysfunction
   • Symptoms not better explained by another concurrent sleep, medical, neurological, or mental disorder
   • Absence of other sleep disorders commonly associated with high PLMS rates (RLS, untreated obstructive sleep apnea, REM sleep behavior disorder, narcolepsy) 1, 2

3. Polysomnographic characteristics:

   • Brief (0.5-10 seconds) recurrent movements of lower extremities
   • Movements occur roughly every 15-30 seconds
   • Particularly prominent during first 4 hours of sleep
   • High night-to-night variability 1
   • Movements associated with heart rate and blood pressure elevations 1

Diagnostic Tools

• Polysomnography: Gold standard for PLMD diagnosis 1, 3
• Leg actigraphy: Alternative method but with significant limitations including:
  • Heterogeneity in device types and placement
  • Variable sensitivity and specificity
  • Limitations in combining data from both legs 3

Treatment Options for PLMD

First-line Treatments

1. Alpha-2-delta ligands:

   • Gabapentin and pregabalin are recommended first-line treatments 2
   • Particularly beneficial for patients with comorbid PTSD 2

2. Iron supplementation:

   • Recommended when ferritin ≤75 ng/mL or transferrin saturation <20% 2
   • Iron deficiency is a significant risk factor for PLMD 2

Medications to Avoid

1. Triazolam: The American Academy of Sleep Medicine suggests against the use of triazolam for PLMD (conditional recommendation, very low certainty of evidence) 1

2. Valproic acid: The AASM suggests against the use of valproic acid (conditional recommendation, very low certainty of evidence) 1

3. Medications that can worsen symptoms:

   • Antidepressants (particularly mirtazapine and venlafaxine)
   • Dopamine antagonists (neuroleptics and antiemetics)
   • Antihistamines 4

Risk Factors for PLMD

• Advanced age
• Iron deficiency
• Uremia
• Pregnancy
• Polyneuropathy
• Certain medications (antidepressants, antipsychotics) 2

Clinical Implications and Pitfalls

1. Diagnostic challenges:

   • PLMD is a diagnosis of exclusion 4
   • Must rule out other conditions that cause PLMS, including RLS, untreated sleep apnea, and narcolepsy 1
   • PLMS are common findings in polysomnography but most individuals with PLMS do not have PLMD 4

2. Treatment considerations:

   • While dopaminergic agents (levodopa, pergolide, pramipexole, ropinirole) have been used historically, they may lead to rebound and augmentation with long-term use 5
   • Alpha-2-delta ligands are now preferred as first-line treatment 2
   • Address modifiable risk factors, particularly iron deficiency 2

3. Cardiovascular implications:

   • PLMS have been implicated as a contributing factor to cardiovascular disease development 6
   • PLMS are associated with elevations in heart rate and blood pressure 1

By following these diagnostic criteria and treatment recommendations, clinicians can effectively identify and manage patients with PLMD, improving sleep quality, reducing daytime dysfunction, and potentially mitigating cardiovascular risks.