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Periodic Limb Movement Disorder

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Last Update: November 25, 2021.

Continuing Education Activity

Sleep-related movement disorders are an important group of sleep diseases encountered commonly in clinical practice that requires thorough evaluation and treatment. This article explains the pertinent facts regarding a common finding PLMS (periodic limb movements of sleep) in polysomnogram and PLMD (periodic limb movement disorders) and highlights the role of the interprofessional team in evaluation and management of this condition.

Objectives:

  • Identify the etiology periodic limb movement disorder.
  • Summarize the appropriate evaluation of periodic limb movement disorder.
  • Outline the management options available for periodic limb movement disorder.
Access free multiple choice questions on this topic.

Introduction

Sleep-related movement disorders are an important group of sleep diseases encountered commonly in clinical practice that requires thorough evaluation and treatment. Some of the conditions included are restless leg syndrome (RLS), periodic limb movement disorder (PLMD), Sleep-related leg cramps, and bruxism. PLMD is also referred to as sleep-related myoclonus syndrome or nocturnal myoclonus syndrome. Periodic limb movements (PLM) is a common finding in a sleep study, and its mere presence alone does not satisfy the diagnosis of PLMD if there are no appropriate clinical symptoms.

Etiology

It is unclear what causes primary periodic limb movement disorder. PLMS can be associated with conditions like RLS (80% to 90% of patients with RLS will have PLMS during the sleep study), Obstructive sleep apnea, Narcolepsy, REM behavioral disorder, uremia, spinal cord tumor, and ADHD.[1][2][3][4][5][6][7][8][9][10] To diagnose PLMD, patients should have subjective sleep complaints with evidence of PLMS in the absence of other sleep disorders.

Even though it is not clear what causes periodic limb movements, several risk factors have correlations with this condition. The family history of RLS may be a risk factor for PLMS and, as a result, PLMD.[11] Certain genes like MEIS1, BTBD9 that have links with RLS may be causing an increased incidence of PLMS.[12][13] Similarly, iron deficiency and decreased ferritin may aggravate PLMS.[14] Medications like dopamine blockers, SSRIs, TCAs could also increase the risk of PLMS.[15][16]

Epidemiology

The prevalence of PLMS could be 4% to 11 %.[17] A European study estimated the prevalence to be 3.9% in the general population.[18] In this study, patients were diagnosed with PLMD based on a telephone-based screening questionnaire without any PSG evidence. So, this might not accurately reflect the prevalence. Older age, female gender, shift work, stress, and caffeine intake were thought to be some risk factors in this study. Some studies have found a reduced prevalence of PLMS in individuals of the Black race than the White race.[19]

Pathophysiology

The pathogenesis of PLMD is not clearly defined. Previous studies suspected cortical or subcortical involvement in patients with PLMS.[20] However, recent studies favor the spinal cord location as a movement generator due to the similarity clinically to the spinal flexor withdrawal reflex.[21][22] The hyperexcitability of spinal flexor pathways, especially during NREM sleep, could link to increased limb movements in sleep. Dopamine deficiency could be an underlying factor in triggering these pathways.[10]

History and Physical

Repeated stereotyped lower extremity movements occur that resemble Babinski sign (extension of big toe and flexion of the ankle, knees, and hip).[23] These movements could cause autonomic arousal, which causes a change in heart rate and blood pressure or cortical arousal either before or after the PLMS. As a result, patients may complain of disturbed or non-restorative sleep with daytime fatiguability. History should focus on asking for sleep-related symptoms like jerking, leg movements, frequent nocturnal awakenings, non-restorative sleep, and also daytime symptoms like excessive daytime sleepiness and fatigue.

The clinician should query about symptoms of RLS and other sleep disorders like sleep apnea, narcolepsy, insomnia, parasomnia as the presence of these would rule out the possibility of PLMD. The examination should not only focus on evaluating upper airway obstruction but also to look for other abnormalities like peripheral neuropathy, peripheral vascular disease, and varicose veins.[24] As these can also present as increased limb movements and leg discomfort in sleep.

Evaluation

The polysomnogram serves as an important diagnostic tool for PLMD.

As per the American Academy of Sleep Medicine (AASM) scoring criteria, each LM (limb movement) is scored if there is an increase in anterior tibialis EMG activity of >8 microvolts above the EMG activity at rest, lasting for a duration of 0.5 to 10 seconds. If there are > 4 LMs, then they can be included as PLM series (PLMS) as long as they are 5 to 90 seconds apart.  

According to ICSD-3, the diagnostic criteria includes the presence of PLMS of more than 15 periodic limb movements per hour in adults and more than five periodic limb movements per hour in children causing sleep problems, which impacts daytime functioning in the absence of any other sleep, psychiatry or medical illnesses.

Once again, PLMD is a diagnosis of exclusion.

Treatment / Management

Dopaminergic medications such as pramipexole, ropinirole, rotigotine, and other drugs like gabapentin, pregabalin that are the mainstay of treatment for RLS may also cause a reduction in periodic limb movements in patients with PLMD.[25] Although there are no studies to support this treatment in patients with PLMD. Based on a few small trials, some medications that researchers have tried in patients with PLMD are clonazepam, melatonin, valproate, and selegiline. Their effect on PLMS and other sleep indices appear below.

  • Clonazepam 1 mg at bedtime: Improves sleep efficiency, sleep quality, and PLMS during wakefulness and REM sleep but no reduction in PLM index.
  • Melatonin 3 mg 30 minutes before bedtime: Improves PLM and PLM arousal indices.
  • Valproate 125 to 600 mg at bedtime: Causes a non-significant reduction in PLM and PLM arousal indices. It improves sleep efficiency and the first and third sleep stages.

Due to a lack of evidence on the pharmacological treatment of PLMD, clinical judgment is crucial before choosing the appropriate therapy.

Physicians should also be cautious in avoiding certain antidepressants like mirtazapine, venlafaxine, sertraline, fluoxetine, amitriptyline as they may aggravate periodic limb movements. Bupropion is the preferred medication in treating patients with concomitant depression. Other antidepressants like trazodone, nefazodone, and doxepin do not worsen PLMS.[26]

In children, iron deficiency is a frequent finding in patients with RLS/PLMD. The primary focus should be initially on treating underlying iron deficiency anemia. There is not much data available on using dopamine agonists in children with RLS/PLMD.

Differential Diagnosis

The clinical focus while evaluating any patient with sleep-related limb movements is to ask for symptoms of restless leg syndrome. Then consider other common sleep disorders that can be associated with PLMS like narcolepsy, OSA, REM behavioral disorder, and uremia. If any of these are present, then the diagnosis of PLMD cannot be made. Clinicians should also keep in mind about the less common sleep-related movement disorders like excessive fragmentary myoclonus (EFM), sleep-related leg cramps, bruxism, rhythmic feet movements (RFM), hypnagogic foot tremors (HFT) and alternating leg muscle activation (ALMA).[27]

Prognosis

Symptomatically patients who receive treatment with dopamine agonists and other medications notice an improvement in the nocturnal sleep quality, sleep efficiency, and sleep stages even though there is no significant reduction in the PLM index in the sleep study.[25]

Complications

Studies have shown abnormal blood pressure response and hypertension in patients with movement disorders in sleep due to an imbalance between the sympathetic and parasympathetic nervous systems.[28] As a result of increased sympathetic activity, RLS and PLMD patients are at a higher risk of hypertension, stroke, and heart disease.[29]

Enhancing Healthcare Team Outcomes

Periodic limb movements in sleep is a common finding in a polysomnogram. Unfortunately, it is an underdiagnosed condition. Having understood the potential cardiovascular adverse effects and the benefits in quality of sleep with treatment, all health care providers should be vigilant in diagnosing and treating patients with PLMD.

Review Questions

References

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