AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Periodic limb movement (PLM) disorder is unique in that the movements occur during sleep. Most other movement disorders manifest during wakefulness. The condition is remarkably periodic, and the movements may cause poor sleep and subsequent daytime somnolence. PLM disorder may occur with other sleep disorders and is related to, but not synonymous with, restless leg syndrome (RLS), a less specific condition with sensory features that manifest during wakefulness. The majority of patients with RLS have PLM disorder, but the reverse is not true. Treatment involves either dopaminergic medication in an attempt to modify activity of the subcortical motor system or, more commonly, sedative medications to allow uninterrupted sleep. Many new agents are proving efficacious for treatment as well.

Symonds first described PLM disorder in 1953. The original name, "nocturnal myoclonus," does not describe the condition accurately, since the movements are slower than are those of myoclonus. The original name seldom is used today.

Pathophysiology

The etiology of the primary form of PLM disorder is uncertain. Suprasegmental disinhibition of the descending inhibitory pathways may be a factor. Vetrugno and colleagues report that evidence supports neuronal hyperexcitability with involvement of the central pattern generator for gait as the pathophysiology of PLM. This results in decreased dopamine transmission, potentially supporting the use of dopaminergic therapy to treat the condition.

Because the etiology is not clear, treatment is primarily to treat symptoms and does not modify the disease. Studies differ regarding the frequency of polyneuropathy in cases of PLM disorder. Martinez-Mena and Pastor found that only 1 of 9 patients had signs of neuropathy (Martinez-Mena, 1998).

The secondary forms of PLM disorder may be due to diabetes mellitus, spinal cord tumor, sleep apnea syndrome, narcolepsy, uremia, or anemia. Many authors report an association between attention deficit hyperactivity disorder (ADHD) and PLM disorder. Antidopaminergic, dopaminergic, or tricyclic drug therapy or cessation of treatment with barbiturates or benzodiazepines may initiate the syndrome as well. Voderholzer and colleagues noted an increased incidence of periodic limb movements during sleep in patients with Gilles de la Tourette syndrome. However, the authors emphasized that the different responses to pharmacological treatments are evidence against a pathophysiological relationship between PLM disorder and Gilles de la Tourette syndrome.

Frequency

United States

The exact frequency is not known.

International

The exact frequency is not known.

Mortality/Morbidity

Comorbid conditions may include other sleep disturbances or coexisting disorders (see Causes). The morbidity of PLM disorder itself is related to sleep disturbance.

Age

Prevalence increases with increasing age. The idiopathic form is rare before age 40 years.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

• The presenting symptom may be stereotyped periodic limb movements that cause awakening during the night, but often the presenting complaint is poor sleep and daytime somnolence. Haba-Rubio et al report that sleep changes induced by periodic limb movements during sleep (PLMS) are associated with decreased physical and psychological fitness on awakening.
• • Occasionally, a bed partner may provide the history of limb movements.
  • Nozawa and colleagues studied arousal index and movement index in PLM disorder and noted that the sleep-wake disorders associated with PLM relate to threshold of awakening.
• Leg movements are stereotyped and involve one or both limbs.
• • The movement simulates triple flexion with leg flexion, ankle dorsiflexion, and great toe extension; it lasts approximately 2 seconds and thus is not consistent with the rapid jerk that defines true myoclonus.
  • The periodicity ranges from 20-40 seconds with a variable duration. The movements are said to occur mainly in non–rapid eye movement (REM) sleep.

Physical

Physical and neurological examinations are normal. In some cases, excessive somnolence may be noted.

Causes

• Potential risk factors or etiologic factors for secondary PLM disorder include the following:
• • Sleep apnea
  • Narcolepsy
  • Cataplexy
  • Drug dependency
  • Benzodiazepine withdrawal
  • Barbiturate withdrawal
  • Neuroleptic medication
  • Dopaminergic medication
  • Uremia
  • Anemia
  • Iron deficiency
  • Spinal cord injury
  • Diabetes mellitus

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Anemia
Back pain
Benign epilepsy syndromes
Iron deficiency
Myoclonic epilepsy
Myoclonus
Paroxysmal kinesigenic choreoathetosis
Sleep apnea
Spinal injury

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• Because anemia, uremia, and the use of tricyclic antidepressant, antidopaminergic, or dopaminergic medications can lead to a secondary form of PLM disorder, laboratory screening studies should be obtained to rule out anemia or significant metabolic abnormalities.
• A urine drug screen may be appropriate.

Other Tests

• Sleep laboratory
• • Definitive diagnosis requires polysomnography.
  • Observation in a sleep laboratory allows documentation of the movements and rapid diagnosis.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

Patient reassurance is essential.

Consultations

Because the differential diagnosis of PLM disorder includes seizure and other forms of myoclonus, a neurology consultation is indicated to exclude other conditions.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Therapy does not modify the disease but does relieve symptoms. The arsenal of medication options is expanding and includes dopaminergic medications, antiepileptic agents, and even opioids, although the controlled substances may not be appropriate first-line agents. Because most studies focused on restless legs syndrome (RLS), a similar and related (but separate) disorder, the best treatments for PLM are not known. However, using RLS guidelines, dopaminergic agents are first-line treatment.

Drug Category: Benzodiazepines

Inami and colleagues have demonstrated efficacy of clonazepam in reducing the total number of periodic limb movements per hour.

Drug Category: Dopaminergic agents

The levodopa/carbidopa combination has been considered an effective treatment for this condition in specific patients; on the other hand, some studies suggest that the medication may be the etiology of secondary PLM disorder in other patients. Pieta and colleagues studied pergolide in patients with secondary PLM disorder caused by uremia and found subjective improvement in sleep quality and objective reduction in limb movements during the first hour of sleep; however, no objective improvement in sleep architecture was observed.

Drug Name	Pergolide (Permax)
Description	Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to abruptly stop pergolide. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market. Studies in patients with secondary PLM disorder caused by uremia revealed subjective improvement in sleep quality and objective reduction in limb movements during first hour of sleep; however, no objective improvement in sleep architecture was observed.
Adult Dose	0.05 mg/d PO initial dose; titrate to > 1 mg/d in divided doses
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Use caution with dopamine antagonists such as antipsychotics and gastric motility agents; use with levodopa may cause or exacerbate preexisting states of confusion and hallucinations or dyskinesia; because >90% bound to plasma proteins, use caution if coadministered with other drugs known to affect protein binding
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adverse effects include hypotension; use caution in patients who have been treated for cardiac dysrhythmias

Drug Category: Anticonvulsants

These agents are useful in managing severe muscle spasms.

Drug Category: Skeletal muscle relaxants

These agents exert their effects by inhibiting release of excitatory neurotransmitters.

Drug Name	Tiagabine (Gabitril)
Description	Antiepileptic agent FDA approved for adjunctive treatment of certain seizure types. Recent evidence supports use in PLM disorder possibly because of GABA enhancing activity or because of improved sleep quality. FDA approved for seizures at doses up to 56 mg/d. Evidence suggests that use for PLM disorder requires far lower doses, possibly 4-8 mg at bedtime.
Adult Dose	4-8 mg PO hs; titration may begin at 2 mg hs with an increase of 2-4 mg/wk
Pediatric Dose	Not studied for the off-label use of PLM disorder
Contraindications	Documented hypersensitivity
Interactions	Cleared more rapidly in patients treated with carbamazepine, phenytoin, primidone, and phenobarbital than in patients not treated with these drugs
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	For on-label use, patients receiving valproate monotherapy may require lower doses or a slower dose titration for clinical response; moderately severe to incapacitating generalized weakness has been reported following administration in up to 1% of patients with epilepsy; weakness may resolve after reduction in dose or discontinuation of drug; should be withdrawn slowly to reduce potential for increased seizure frequency; slow titration is recommended, beginning at 2 mg hs

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Inpatient Care

• PLM disorder may be treated on an outpatient basis. Diagnosis may involve an overnight stay in a sleep laboratory.

Further Outpatient Care

• Efficacy of treatment should be determined at the time of follow-up visits. If no information from a bed partner was available at the time of initial evaluation and diagnosis, such information–if available–can help to determine the effectiveness of treatment.

Complications

• Picchietti and colleagues suggested that the sleep disruption in PLM disorder could contribute to the inattention and hyperactivity of some children who have ADHD.

Prognosis

• The idiopathic form of this syndrome may be chronic. Relapses and remissions may occur, but treatment does not appear to modify the disease.
• The secondary form of this syndrome may cease with treatment of the underlying cause.

Patient Education

• Informing the bed partner of the condition is important so that potentially negative physical contact may be explained on a neurological (rather than an intentional) basis.
• For excellent patient education resources, visit eMedicine's Sleep Disorders Center. Also, see eMedicine's patient education articles Periodic Limb Movement Disorder, Restless Legs Syndrome, Sleep Disorders in Women, and Sleep Disorders and Aging.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• Haba-Rubio J, Staner L, Krieger J, Macher JP. What is the clinical significance of periodic limb movements during sleep?. Neurophysiol Clin. Dec 2004;34(6):293-300. [Medline].
• Hening WA, Allen RP, Earley CJ, et al. An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep. May 1 2004;27(3):560-83. [Medline].
• Horiguchi J, Inami Y, Sasaki A, et al. Periodic leg movements in sleep with restless legs syndrome: effect of clonazepam treatment. Jpn J Psychiatry Neurol. Sep 1992;46(3):727-32. [Medline].
• Inami Y, Horiguchi J, Nishimatsu O, et al. A polysomnographic study on periodic limb movements in patients with restless legs syndrome and neuroleptic-induced akathisia. Hiroshima J Med Sci. Dec 1997;46(4):133-41. [Medline].
• Iriarte J, Urrestarazu E, Alegre M, et al. Oscillatory cortical changes during periodic limb movements. Sleep. Dec 15 2004;27(8):1493-8. [Medline].
• Littner MR, Kushida C, Anderson WM, et al. Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep. May 1 2004;27(3):557-9. [Medline].
• Martinez-Mena JM, Pastor J. [Polyneuropathy in patients with periodic leg movements during sleep]. Rev Neurol. Nov 1998;27(159):745-9. [Medline].
• Mello MT, Silva AC, Rueda AD, et al. Correlation between K complex, periodic leg movements (PLM), and myoclonus during sleep in paraplegic adults before and after an acute physical activity. Spinal Cord. Apr 1997;35(4):248-52. [Medline].
• Nozawa T, Ichikawa H, Takeuchi T. Periodic limb movements and sleep-wake disorder. Psychiatry Clin Neurosci. Apr 1998;52(2):192-4. [Medline].
• Picchietti DL, England SJ, Walters AS, et al. Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder. J Child Neurol. Dec 1998;13(12):588-94. [Medline].
• Pieta J, Millar T, Zacharias J, et al. Effect of pergolide on restless legs and leg movements in sleep in uremic patients. Sleep. Sep 15 1998;21(6):617-22. [Medline].
• Ulfberg J, Jonsson R, Lindberg E, et al. [Restless legs. A much neglected syndrome]. Lakartidningen. Mar 10 1999;96(10):1183-4, 1187-8. [Medline].
• Vetrugno R, D'Angelo R, Montagna P. Periodic limb movements in sleep and periodic limb movement disorder. Neurol Sci. Jan 2007;28 Suppl 1:S9-S14. [Medline].
• Vignatelli L, Billiard M, Clarenbach P. EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep. Eur J Neurol. Oct 2006;13(10):1049-65. [Medline].
• Voderholzer U, Muller N, Haag C, et al. Periodic limb movements during sleep are a frequent finding in patients with Gilles de la Tourette''s syndrome. J Neurol. Aug 1997;244(8):521-6. [Medline].
• Wetter TC, Pollmacher T. Restless legs and periodic leg movements in sleep syndromes. J Neurol. Apr 1997;244(4 Suppl 1):S37-45. [Medline].

Article Last Updated: Mar 30, 2007