eMedicine Specialties > Neurology > Pediatric Neurology

Dopamine-Responsive Dystonia: Treatment & Medication

Author: N K Nikhar, MD, MRCP, Assistant Professor, Department of Neurology, George Washington University School of Medicine
Coauthor(s): Haresh Mani, MD,, Associate Medical Director, Pulmonary and Mediastinal Pathology, American International Pathology Laboratories
Contributor Information and Disclosures

Updated: Jul 10, 2009

Treatment

Medical Care

All patients with dopamine-responsive dystonia (DRD) should be treated with the levodopa/carbidopa combination. Early treatment can prevent morbidity and contracture formation. In patients with autosomal recessive TH and SR deficiency, early treatment with levodopa may also reduce the motor and intellectual developmental delay.

Surgical Care

A fixed equinovarus foot deformity has been corrected surgically after treating the dystonia with levodopa.36

Consultations

Physical therapy is particularly important if the patient has a contracture or chronic gait disturbance.

Diet

A recent in vitro study has suggested that oral BH(4) supplementation could have potential benefit in disorders associated with TH misfolding, such as dopamine-responsive dystonia (DRD);37 however, this awaits further confirmation.

Medication

Patients with DRD typically experience marked long-term benefit with low-dose levodopa. The optimal dose differs among patients; while some respond magnificently to small doses, others require higher doses. de la Fuente-Fernández et al reported achieving adequate control with a mean daily dose of 250 mg of levodopa (range, 25-500 mg).38 Others have reported benefit with 20 mg/kg,39 100 mg/d,40 or 750 mg/d.35 Wang et al suggested an optimal dose of 10 mg/kg.41

Other effective medications include the anticholinergic agents, such as trihexyphenidyl, carbamazepine, tetrahydrobiopterin, and 5-hydroxytryptophan.42 The use of botulinum toxin injection for focal dystonia should be considered in resistant cases as it would be for all causes of focal dystonia; this recourse rarely is needed in true DRD.

Motor fluctuations (as may happen in Parkinson disease treated with levodopa) do not occur in patients with DRD.43 Choreic dyskinesias have been reported that disappeared on reducing the dose of levodopa.38

Dopaminergic agents

In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine receptor subtypes is currently unclear.


Levodopa/Carbidopa (Sinemet)

Active component is L-isomer of dopamine (ie, L-dopa). Carbidopa is peripheral DOPA hydroxylase inhibitor and by preventing peripheral metabolism increases concentration of dopamine in CNS. Total L-dopa dose required varies from person to person.

Adult

75 mg-1.5 g PO qd

Pediatric

50 mg-1.5 g PO qd

Hydantoins, pyridoxine, phenothiazine, and hypotensive agents may decrease effects; antacids and MAOIs increase toxicity—discontinue MAOIs at least 2 wk prior to starting levodopa; tricyclic antidepressants may cause hypotension and dyskinesias

Documented hypersensitivity; narrow-angle glaucoma; malignant melanoma; undiagnosed skin lesions; previous occurrence of neuroleptic malignant syndrome

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Obtain regular blood tests looking for hematological, liver, and renal impairment; certain adverse CNS effects (eg, dyskinesias) may occur at lower dosages and earlier in therapy with SR form; caution in patients with history of myocardial infarction, arrhythmias, asthma, or peptic ulcer disease; sudden discontinuation may cause worsening of Parkinson disease; high-protein diets should be distributed throughout day to avoid fluctuations in levodopa absorption

Anticholinergic agents

These agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.


Trihexyphenidyl (Artane)

Synthetic anticholinergic noted to have marked benefit in muscle spasm conditions such as dystonia.

Adult

1-2 mg PO on day 1; increase by 2 mg at intervals of 3-5 d; not to exceed 6-10 mg qd

Pediatric

Not established; 0.25 mg/d suggested, increase slowly according to response; dose usually lower if concomitant therapy with levodopa ongoing

Amantadine may increase anticholinergic side effects that disappear when dose reduced; may decrease serum haloperidol concentrations, worsening schizophrenic symptoms; may reduce pharmacologic/therapeutic actions of phenothiazines

Documented hypersensitivity; glaucoma; peptic ulcers; pyloric or duodenal obstruction; stenosing prostatic hypertrophy or bladder neck obstruction; achalasia; toxic megacolon

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Dose adjustment may be required in elderly patients; caution in patients with tachycardia, cardiac hypotension, prostatic hypertrophy, arrhythmias, hypertension, any tendency toward urinary retention, liver or kidney disorders, or obstructive disease of GI or GU tract; if dry mouth severe and impairs swallowing or speaking, or if loss of appetite and weight, reduce dosage or discontinue medication temporarily; caution in narrow-angle glaucoma

Anticonvulsants

These agents are used to treat severe muscle spasms.


Carbamazepine (Tegretol)

May reduce polysynaptic responses and block posttetanic potentiation.

Adult

200 mg PO tid

Pediatric

10-20 mg/kg/d PO divided bid/tid; may increase weekly to achieve optimal clinical response

Danazol may increase serum levels significantly within 30 days (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (either may increase carbamazepine levels)

Documented hypersensitivity; history of bone marrow depression; MAOIs within last 14 d

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid in conditions of known bone marrow suppression or to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBCs and serum iron baseline prior to treatment, during first 2 mo, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness

Toxins

This agent causes presynaptic paralysis of myoneural junction and reduces abnormal contractions. Therapeutic effects may last 3-6 months.


Botulinum toxin type A (BOTOX)

Useful in reducing excessive, abnormal contractions associated with DRD. Binds to receptor sites on motor nerve terminals and after uptake inhibits release of acetylcholine, blocking transmission of impulses in neuromuscular tissue. Re-examine patients 7-14 d after administering initial dose to assess for satisfactory response. Double previously administered dose for patients who experience incomplete paralysis of target muscle. Do not exceed 50 units when giving as single injection or 400 units as cumulative dose in 30-d period.

Adult

1.25-2.5 U (0.05-0.1 mL volume) injection into abnormally contracting muscles via hollow electromyographic needle

Pediatric

<12 years: Not established
>12 years: Administer as in adults
Suggestions for dosing based on consensus may be found via WeMove organization for movement disorders; in general, dosing for small muscles is up to 1-2 units/kg patient weight and dosing for large muscles is up to 3-6 units/kg patient weight

Aminoglycosides or drugs that interfere with neuromuscular transmission may potentiate effects

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not exceed recommended dosages and frequencies of administration; presence of antibodies to botulinum toxin type A may reduce effects of therapy

More on Dopamine-Responsive Dystonia

Overview: Dopamine-Responsive Dystonia
Differential Diagnoses & Workup: Dopamine-Responsive Dystonia
Treatment & Medication: Dopamine-Responsive Dystonia
Follow-up: Dopamine-Responsive Dystonia
References
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Further Reading

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Keywords

dopamine-responsive dystonia, hereditary progressive dystonia with diurnal fluctuation, HPD, Segawa's disease, Segawa disease, DRD, dopa-responsive dystonia, inherited dystonia, mild parkinsonian features

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Contributor Information and Disclosures

Author

N K Nikhar, MD, MRCP, Assistant Professor, Department of Neurology, George Washington University School of Medicine
N K Nikhar, MD, MRCP is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Coauthor(s)

Haresh Mani, MD,, Associate Medical Director, Pulmonary and Mediastinal Pathology, American International Pathology Laboratories
Disclosure: Nothing to disclose.

Medical Editor

Ann M Neumeyer, MD, Clinic Director, Instructor, Departments of Neurology and Pediatrics, Massachusetts General Hospital, Harvard Medical School
Ann M Neumeyer, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Nestor Galvez-Jimenez, MD, MSc, MHA, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida
Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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