You are in: eMedicine Specialties > Neurology > Sleep-Related Diseases Periodic Limb Movement DisorderArticle Last Updated: Mar 30, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 9
  Author: Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center Wayne E Anderson is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Medical Association, American Society of Law Medicine and Ethics, California Medical Association, and San Francisco Medical Society Editors: Sydney Louis, MD, Emeritus Professor, Department of Neurology, Brown University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: PLM, restless leg syndrome, RLS, nocturnal myoclonus, sleep disorders, PLMS, periodic limb movements during sleep, ADHD, attention deficit hyperactivity disorder, PLM disorder, diabetes mellitus, spinal cord tumor, sleep apnea syndrome, narcolepsy, uremia, anemia, sleep disturbances, sleep apnea INTRODUCTIONSection 2 of 9
  BackgroundPeriodic 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. PathophysiologyThe 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. FrequencyUnited StatesThe exact frequency is not known. InternationalThe exact frequency is not known. Mortality/MorbidityComorbid conditions may include other sleep disturbances or coexisting disorders (see Causes). The morbidity of PLM disorder itself is related to sleep disturbance. AgePrevalence increases with increasing age. The idiopathic form is rare before age 40 years. CLINICALSection 3 of 9
History
PhysicalPhysical and neurological examinations are normal. In some cases, excessive somnolence may be noted. Causes
DIFFERENTIALSSection 4 of 9
Chorea in Adults Chorea in Children Complex Partial Seizures Early Myoclonic Encephalopathy Epilepsia Partialis Continua Frontal Lobe Epilepsy Narcolepsy Parkinson Disease Parkinson-Plus Syndromes Psychogenic Nonepileptic Seizures Restless Legs Syndrome Seizures and Epilepsy: Overview and Classification Sleep Stage Scoring Temporal Lobe Epilepsy Tourette Syndrome and Other Tic Disorders Uremic Encephalopathy Uremic Neuropathy
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| Drug Name | Clonazepam (Klonopin) |
|---|---|
| Description | Useful in suppressing muscle contractions by facilitating action of GABA and other inhibitory neurotransmitters. |
| Adult Dose | 0.5-3 mg PO qhs; in some cases, tid schedule used |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma |
| Interactions | Clearance may be increased and effects reduced by phenytoin and barbiturates; toxicity of benzodiazepines in CNS significantly increased when used concurrently with other CNS depressants |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Causes sedation; should not be used with alcohol; habit forming; use caution in patients with chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation |
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 | Carbidopa/levodopa (Sinemet) |
|---|---|
| Description | Large neutral amino acid absorbed in proximal small intestine by saturable carrier-mediated transport system. Absorption decreased by meals, which include other large neutral amino acids. However, only patients with meaningful motor fluctuations need consider low-protein or protein-redistributed diet. Greater consistency of absorption achieved when levodopa taken > 1 h after meals. Nausea often reduced if taken immediately following meals. Some patients with nausea benefit from additional carbidopa up to 200 mg/d. Half-life approximately 2 h. Most common acute adverse effects are nausea, hypotension, and hallucinations. Long-term adverse effects include motor fluctuations and dyskinesia (chorea). |
| Adult Dose | Effective dose varies; can be as low as 10/100 mg PO qhs |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; narrow-angle glaucoma; malignant melanoma; undiagnosed skin lesions |
| Interactions | Effects decreased by hydantoins, pyridoxine, phenothiazine, and hypotensive agents; toxicity increased by antacids or MAOIs. |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Certain adverse CNS effects (eg, dyskinesias) occur at lower dosages and earlier in therapy with sustained release form; use caution in patients with history of myocardial infarction, arrhythmias, asthma, peptic ulcer disease; may worsen Parkinson disease if discontinued suddenly; patients on high-protein diets should distribute protein intake throughout day to avoid fluctuations in levodopa absorption |
| 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 |
These agents are useful in managing severe muscle spasms.
| Drug Name | Gabapentin (Neurontin) |
|---|---|
| Description | Mechanism of action uncertain; although has GABA-like structure, action at GABA receptors not shown clearly. Fortunately, considered relatively safe and thus may be considered for PLM disorder. |
| Adult Dose | 300 mg/d PO initial dose; increase by 300 mg/d each week until 900 mg tid or 1200 mg tid; more rapid titration appears to increase somnolence and dizziness |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Bioavailability may be reduced significantly by antacids–wait > 2 h following antacid administration; may increase norethindrone levels significantly |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Use caution in severe renal disease and elderly patients |
These agents exert their effects by inhibiting release of excitatory neurotransmitters.
| Drug Name | Baclofen (Lioresal) |
|---|---|
| Description | GABA agonist at slower potassium channels in cerebellum and spinal cord. May have efficacy in PLM disorder. Because works in spinal cord and less in brain cortex, calls into question neurologic origin of PLM. |
| Adult Dose | 5 mg (1/2 tab) PO qhs; increase slowly to avoid sedation and other adverse effects, by 10 mg/d q5d; not to exceed 40 mg tid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Effects may be increased by opiate analgesics, benzodiazepines, alcohol, tricyclic antidepressants, guanabenz, MAOIs, clindamycin, and hypertensive agents |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Use caution when spasticity utilized to obtain increased function and in patients with history of autonomic dysreflexia; withdrawal can cause autonomic dysreflexia; use caution in renal impairment |
| 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 |
Periodic Limb Movement Disorder excerpt
Article Last Updated: Mar 30, 2007
