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Treatment Guidelines

TREATMENT STRATEGIES FOR DYSTONIA: MEDICAL and SURGICAL was presented at the Spring 2013 American Academy of Neurology

H. A. Jinnah, MD, PhD
Emory University School of Medicine
Atlanta, GA 30307

The clinical manifestations of the dystonias are extremely varied. The dystonias may involve one body region or many. They may occur in children or adults. They may be progressive, static, task-specific, or paroxysmal. The causes of these varied clinical manifestations are equally varied. Dystonias may be inherited or acquired, with a broad array of underlying biological mechanisms. With all the clinical and etiological heterogeneity, it is not surprising that responses to treatments also vary widely. The heterogeneity makes the design of a universal treatment algorithm for all dystonias challenging.

Although systematic and evidence-based reviews for treatments of dystonia have been published1-3, many commonly used treatments have not been subject to rigorous clinical trials. Much evidence comes from small controlled trials, non-blinded trials or uncontrolled observations, retrospective reviews, anecdotal reports, and personal experience. In the absence of definitive evidence, recommendations regarding treatments reflect a synthesis of the limited available evidence with the experience of providers who treat large numbers of dystonia patients. Thus treatment recommendations from different sources may vary.

Multiple lengthy reviews describing treatment recommendations for dystonia have been published4-8. This syllabus was developed as a practical synopsis and is organized into three parts. The first part provides a catalog of the most common treatment options available, both medical and surgical. The second part provides a summary of how the diagnosis of different types of dystonia influences the selection of these different treatment options. The third part includes a synthesis and conclusions, along with future goals for the development and testing of novel therapies.


  1. Albanese, A., et al., A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: repor of an EFNS/MDS-ES task force. Eur. J. Neurol., 2006. 13: p. 433-444.
  2. Balash, Y. and N. Giladi, Efficacy of pharmacological treatment of dystonia: evidence-based review including meta-anaylsis of the effect of botulinum toxin and other cure options. Eur. J. Neurol., 2004. 11: p. 361-370.
  3. Simpson, D.M., et al., Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 2008. 70: p. 1699-1706.
  4. Adam, O.R. and J. Jankovic, Treatment of dystonia. Parkinsonism Relat Disord, 2007. 13 Suppl 3: p. S362-8.
  5. Jankovic, J., Treatment of dystonia. Lancet Neurol., 2006. 5: p. 864-872.
  6. Goldman, J.G. and C.L. Comella, Treatment of dystonia. Clin Neuropharmacol, 2003. 26: p. 102-8.
  7. Cloud, L.J. and H.A. Jinnah, Treatment strategies for dystonia. Expert Opin Pharmacother, 2010. 11: p. 5-15.
  8. Bhidayasiri, R. and D. Tarsy, Treatment of dystonia. Expert Rev Neurother, 2006. 6: p. 863-86.

Available Treatment Options

Oral Medications


Trihexyphenidyl and related anti-cholinergics (benztropine, biperidin, procyclidine, scopolamine) block muscarinic acetylcholine receptors. Their mechanism of action is thought to involve an influence on the activity of cholinergic neurons of the basal ganglia. The anticholinergics are among the most widely prescribed oral agents for all types of dystonia. However, efficacy is limited and side effects are common because high doses are required. They seem to be most effective and best tolerated in childhood-onset dystonias where their use is supported by two small double-blind clinical trials. Although anticholinergics often are prescribed for adults with dystonia, their value is less clear and not substantiated by rigorous clinical trials. Some adults seem to find them to be useful, while many do not. Effective doses of trihexyphenidyl range from 6-120 mg daily in 3-4 divided doses. Common side effects include sedation, impaired mentation, constipation, urinary retention, restlessness, insomnia, burry vision, and dry mouth.


Levodopa is a precursor in dopamine synthesis, and serves to augment dopamine levels. Its mechanism is thought to involve augmentation of dopaminergic neurotransmission in the basal ganglia.Inchildren with dopa-responsive dystonia, the combination of levodopa with carbidopa is remarkably effective with almost complete elimination of symptoms at low doses. In this population, benefits may last for decades, with minimal side effects. Because of this dramatic response, a trial of levodopa is essential in all childhood-onset dystonias. Levodopa also can be effective in some adults with focal dystonias, particularly those involving the limbs. In some of these adults, limb dystonia may be a manifestation of late-onset dopa-responsive dystonia or early onset Parkinson’s disease. Unlike limb dystonias, the more common craniofacial and cervical dystonias of adults do not typically respond to levodopa. Children with dopa-responsive dystonia may respond to doses as low as ½ of a 25/100 mg levodopa/carbidopa tablet twice daily. However, some children and most adults require higher doses. An adequate trial for both children and adults requires reaching a levodopa dose of 20 mg/kg in 3-4 divided doses for at least one month. Common side effects include nausea and vomiting, immediate or delayed dyskinesias, sedation, orthostasis, and impaired mentation.


Tetrabenazine depletes neuronal dopamine stores by displacing it from storage vesicles. It is thought to work by attenuating dopaminergic transmission in the basal ganglia. It is FDA-approved for the treatment of chorea in Huntington’s disease, but it appears capable of suppressing a variety of hyperkinetic movements. Its use in dystonia is supported by one small double-blind crossover trial, and several open or retrospective studies. Patients with idiopathic primary dystonia may respond, though best responses appear to occur in those with tardive dystonia. The effective dose range is 12.5-300 mg daily in 3-4 divided doses. Common side effects include sedation, Parkinsonism, impaired mentation, depression, orthostasis, and insomnia.

Dopamine receptor antagonists.

Dopamine receptor antagonists (fluphenazine, haloperidol, olanzepine, pimozide, risperdal, and others) block dopamine receptors. They are thought to work by attenuating dopaminergic transmission in the basal ganglia. They sometimes are advocated for the treatment of dystonia. However, these drugs carry a risk of causing tardive syndromes that may confound the dystonic disorder being treated, so the use of these drugs for the treatment of dystonia is generally discouraged. One exception may be clozapine, where the risk of tardive syndromes seems to be vanishingly small. However, this drug is associated with several problematic side effects including sedation, sialorrhea, and life-threatening agranulocytosis. Therefore it is used only rarely.


Baclofen is a GABA receptor agonist. There are no controlled studies to guide recommendations for its use, but retrospective studies and anecdotal experience suggest it is most often useful in childhood-onset dystonias, especially those with concomitant spasticity. Some adults also enjoy benefits, although most do not. Effective doses range from 30-120 mg daily in 3-4 divided doses. Common side effects include sedation, nausea, impaired mentation, dizziness, and loss of muscle tone. Abrupt discontinuation or rapid lowering of the dose can be associated with severe withdrawal reactions that include delirium and seizures.


Clonazepam and related benzodiazepines (chlordiazepoxide, diazepam, lorazepam, and others) are often used in dystonia. There are no controlled trials to guide recommendations for their use, but experience suggests they may be most useful for blepharospasm and dystonias with a jerky or tremulous quality. Effective doses of clonazepam range from 0.5-6 mg daily in 3-4 divided doses. Common side effects include sedation, impaired mentation or coordination, and depression. There also is a risk for dependency and tachyphylaxis. Abrupt discontinuation or rapid lowering of the dose can be associated with severe withdrawal reactions that include delirium and seizures.

Muscle relaxants

Many patients request “muscle relaxants”, a broad category of medications with diverse actions that includes baclofen and benzodiazepines, as well as carisoprodol, cyclobenzeprine, metaxolone, methocarbamol, tizanidine, and others. There are no formal studies to guide recommendations for their use and responses vary widely, but children and adults with many different forms of dystonia often derive at least partial benefits. They may be particularly useful in patients who develop pain from uncontrolled muscle pulling.

Other drugs

Many other drugs sometimes are advocated for specific forms of dystonia, based on evidence from small and non-blinded studies, anecdotal reports, and personal experience. For example, carbamazepine and other anticonvulsants seem effective in paroxysmal kinesigenic dyskinesia, mexilitine and intravenous lidocaine may be useful in some focal dystonias, and alcohol seems to be of benefit in myoclonus dystonia. Among many other drugs sometimes advocated are amphetamines, cannabidiol, cyproheptidine, gabapentin, nabilone, and riluzole. Further studies are needed to delineate the potential usefulness of these drugs in different populations.

Drug: Indications: Titration: Typical doses: Main side effects:
Levodopa childhood-onset dystonias, adult-onset limb dystonias

start with ½ - 1 tablet of 25/100 mg levodopa/carbidopa daily and increase by ½ - 1 tablet every 3-7 days to a maximum dose of 20 mg/kg

100-1200 mg total levodopa per day, divided into 3-4 daily doses

nausea/vomiting, immediate or delayed dyskinesias, sedation, orthostasis, impaired mentation
Trihexyphenidyl generalized, segmental, or focal dystonia

start with 1-2 mg QHS, and increase by 1-2 mg every 3-7 days to a maximum dose of 120 mg daily.

4-120 mg total per day, divided into 3-4 daily doses

sedation, impaired mentation, constipation, urinary retention, restlessness, insomnia, burry vision, dry mouth

tardive dystonia, generalized or segmental dystonia

start with 12.5 – 25 mg QHS, and increase by 1-2 mg every 3-7 days to a maximum dose of 300 mg daily. 12.5-300 mg total per day, divided into 3-4 daily doses

sedation, Parkinsonism, impaired mentation, depression, orthostatis, insomnia

Clonazepam any dystonia, especially blepharospasm or when co-occurring with prominent tremor start with 0.5-1.0 mg QHS, and increase by 0.5-1 mg every 3-7 days to a maximum dose of 8 mg daily.

0.5-8 mg total per day, divided into 3-4 daily doses

sedation, impaired mentation or coordination, depression, drug dependency, severe withdrawal reactions

any dystonia, especially childhood-onset

start with 5-10 mg TID, and increase by 5-10 mg at each dose every 3-7 days to a maximum dose of 120 mg daily.

30-120 mg total per day, divided into 3-4 daily doses sedation, nausea, impaired mentation, dizziness, impaired muscle tone, severe withdrawal reactions

Botulinum Toxins (BTX)

BTX therapy has been the focus of several lengthy reviews and prior educational programs and workshops at the AAN, so this summary addresses only the key aspects1-4. The bacterium Clostridium botulinum makes seven different forms of BTX designated A through G. They block neurotransmission at the neuromuscular junction by acting as proteases that cleave critical proteins required for the docking and exocytosis of synaptic vesicles containing acetylcholine. Weakness occurs until the release apparatus is restored by replacing the cleaved proteins or until axons sprout new terminals. Only two types have been developed for clinical application. BTX-A is available as BotoxTM, DysportTM or XeominTM. BTX-B is available as MyoblocTM or NeuroblocTM.

For many dystonias, therapy with BTX is highly effective and the treatment of choice. Typical success rates are 80-90% for focal craniofacial and cervical dystonias, but lower for oromandibular and limb dystonias. Their use is supported by several double-blind and placebo-controlled trials, and extensive and long-term non-blinded experience. In most cases, benefits become evident 2-10 days after injections, they peak at 2-4 weeks, and they last for 10-14 weeks. Most patients return for re-injection at 3-4 months intervals. Intervals less than 3 months are discouraged because of a theoretical increased risk for developing immunological resistance, while intervals of 5-6 months or longer are discouraged because patients experience complete return of symptoms.

The most important factor determining success with BTX is proper selection of muscles for treatment and proper selection of doses for each muscle. The selection of muscles is based primarily on the clinical examination in concert with knowledge of the types of movements governed by each muscle. The use of ancillary EMG and/or stimulation to confirm targeting to appropriate muscles depends on the condition being treated and the preferences of the provider. EMG is valuable in some cases, such as focal hand dystonia where precise discrimination of multiple small muscles in close proximity in the forearm is challenging by clinical examination alone. On the other hand, EMG is rarely needed for blepharospasm and other facial dystonias, because these injections usually are made subcutaneously where the medication diffuses subcutaneously to the muscles. Many patients with cervical dystonia may not need EMG guidance, unless they have thick necks that make palpation of individual muscles difficult, complex patterns of movement where the involved muscles are unclear, or unreliable responses without EMG.

There are significant variations among providers in the number of injections per muscle, dilution factors, and doses applied. Targeting fewer injection sites minimizes pain from needle penetrations through the skin. At the same time, fewer sites requires delivery of larger volumes per site, thereby increasing local muscle discomfort and the risk of leakage from each site. Detailed guidelines are available for different forms of dystonia, anatomical charts for specific muscles involved, and doses for different formulations of BTX.

Doses and side effects vary according to the disorder treated. For cervical dystonia, the most common side effects include transient injection site pain, muscle weakness, dysphagia and dry mouth. For blepharospasm the most common side effects include transient pain, ecchymoses, ptosis, and dry or watery eyes. For spasmodic dysphonia, hoarseness or breathy voice is common shortly after injections but most often transient. For limb dystonia, the most common side effects are weakness and spread to nearby muscles.

Physical and Occupational Therapy

Many patients request various forms of physical (or occupational) therapy in lieu of other medical or surgical treatments. Although physical therapy rarely provides an adequate substitute for other therapies, it plays an important adjunctive role. Physical therapy can be very useful at the outset to mobilize joints and mitigate against contractures, and to provide safe exercise programs to maintain function. The physical therapist must have experience with dystonia and avoid interventions that cause pain or fatigue. An experienced therapist also may be able to design devices that take advantage of sensory tricks to suppress symptoms.

Voice Therapy for Laryngeal Dystonia

Voice therapy alone is not generally successful in patients with typical abductor or adductor spasmodic dysphonia, but it can be very effective in patients with muscular tension dysphonia. The exact relationship between muscular tension dysphonia and spasmodic dysphonia remains unclear, and the two conditions may co-exist. A trained speech pathologist or otolaryngologist usually can discriminate isolated muscle tension dysphonia from spasmodic dysphonia and determine whether voice therapy is likely to be successful.


Immobilization of a dystonic limb in solid casts or splinting devices, sometimes for periods of a month or more, has been advocated as treatment for dystonia. Unfortunately, the extent and duration of immobilization recommended for success are impractical for many patients. Additionally, therapeutic responses are inconsistent, and some patients may get worse. Immobilization therapy should not be recommended until further studies of its efficacy and safety are available.


  1. Simpson, D.M., et al., Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 2008. 70: p. 1699-1706.
  2. Dressler, D. and F. Adib Saberi, Botulinum toxin: mechanisms of action. Eur Neurol, 2005. 53: p. 3-9.
  3. Jankovic, J., Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry, 2004. 75: p. 951-7.
  4. Hallett, M., et al., Treatment of focal dystonias with botulinum neurotoxin. Toxicon, 2009. 54: p. 628-33.

Deep Brain Stimulation (DBS)

DBS of the internal segment of the globus pallidus is increasingly used in the treatment of medically refractory dystonias, including primary generalized dystonias, and focal or segmental dystonias that do not respond to less invasive methods1-3. The use of DBS is supported by two placebo-controlled clinical trials4-5, and multiple open, non-blinded series from different centers. Improvements vary widely from nil to nearly complete. Two independent and double-blinded trials encompassing a total of 62 patients with primary generalized or segmental dystonia showed average improvements on both the dystonia and disability subscales of the Fahn-Marsden rating scale to be approximately 50% at 3 months. The most significant complications include approximately 1% chance of stroke, immediate or delayed infection of hardware requiring its removal, mood or cognitive change, weakness, and dysphagia. These benefits can be life altering, but candidates must be advised regarding risks and potential for varying outcomes.

Based on early experience, some providers have concluded that primary generalized dystonias respond better than secondary dystonias to DBS. However, more recent studies have revealed this conclusion to be an overgeneralization. Excellent responses are regularly seen in some secondary dystonias, such as tardive dystonia, while consistently poor responses are seen in some others. Consultation with providers with broad experience is needed before recommending DBS for secondary dystonias.

Ablative Procedures

Pallidotomy and thalamotomy have been used for decades in the treatment of different forms of dystonia, including focal task-specific, segmental, and generalized dystonias3. Ablative procedures have been supplanted by DBS, since the latter is reversible and adjustable. Nevertheless, the ablative procedures may still be considered when implantation or maintenance of DBS hardware is not feasible or desired. The most significant complications of ablative procedures include stroke, infection, weakness, and dysphagia.

Selective Denervation

Various procedures have been used for denervating overactive muscles in cervical dystonia6. Patient selection is critical, since certain subpopulations have a better outcome than others. Experienced centers have reported good outcomes for 68-89% of patients. These procedures were used more commonly before the availability of BTX therapy, so they now are reserved primarily for patients who do not respond to chemodenervation. The most significant complications include permanent muscle weakness, cosmetic effects of muscle atrophy, dysesthesia, and dysphagia.


The surgical removal of muscle tissue once was commonly offered to patients with dystonia prior to the introduction of BTX therapy. Myectomy is rarely performed nowadays, although it is sometimes still used for blepharospasm and other medically refractory dystonias as a palliative measure.

Intrathecal Baclofen

Some patients experience significant improvements after chronic intrathecal delivery of baclofen7-8. Patients with leg dystonia seem to have the best responses, particularly if there is concomitant spasticity. Implanted pumps must be refilled regularly and sometimes replaced. Complications may include equipment infection or malfunction, CSF leaks, overdose, and severe withdrawal reactions. This procedure has not gained widespread popularity because of inconsistent responses among different patients, maintenance requirements, risk of severe side effects from sudden medication discontinuation from pump failure, and increasing application of DBS.


  1. Perlmutter, J.S. and J.W. Mink, Deep brain stimulation. Annu. Rev. Neurosci., 2006. 29: p. 229-257.
  2. Ostrem, J.L. and P. Starr, Treatment of dystonia with deep brain stimulation. NeuroRx, 2008. 5: p. 320-330.
  3. Marks, W.J.J., Brain surgery for dystonia, in Handbook of dystonia, M.A. Stacey, Editor. 2007, Informa Healtcare USA, Inc.: New York. p. 393-406.
  4. Vidailhet, M., et al., Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N. Engl. J. Med, 2005. 352: p. 459-467.
  5. Kupsch, A., et al., Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N. Engl. J. Med, 2006. 355: p. 1978-1990.
  6. Arce, C.A., Selective denervation in cervical dystonia, in Handbook of dystonia, M.A. Stacey, Editor. 2007, Informa Healthcare USA, Inc.: New York. p. 381-392.
  7. Albright, A.L., et al., Intrathecal baclofen for generalized dystonia. Dev. Med. Child Neurol., 2001. 43: p. 652-657.
  8. Walker, R.H., et al., Intrathecal baclofen for dystonia: benefits and complications during six years of experience. Mov. Disord., 2000. 15: p. 1242-1247.

Treatment Strategies for Different Populations

Before Starting Treatment

The importance of diagnostic subtype

The dystonias may be categorized by body region affected, age at onset, and etiology.  Each of these categories has important implications for treatment, and accurate diagnosis is important because different forms of dystonia may respond best to different treatments. Most importantly, there are some special populations with highly effective treatments that target underling mechanisms rather than symptoms, as described below1, 2.

Age at onset is important because childhood-onset dystonias are more likely to begin in a limb and progress to generalized involvement. In contrast, adult-onset dystonias are more likely to begin in the craniofacial region or neck with limited spread. Children are more likely to have a discoverable inherited etiology, while the majority of adult cases are idiopathic. In children, the increased risk for progression to generalized dystonia and higher likelihood of finding a cause mandates more extensive diagnostic testing. For children and young adults where dystonia seems to be an isolated problem, genetic testing for DYT1 or DYT6 dystonia merits consideration, especially if there is a family history.

For children and young adults where dystonia is not an isolated feature, such as in the dystonia-plus syndromes and hereditary or degenerative dystonias, there is an enormous list of potential disorders for diagnostic testing1. It is not feasible to test for all potential disorders where dystonia may occur. Instead, the clinical evaluation is helpful for guiding a more selective approach to testing. Consultation with specialists in early-onset dystonias or neurogenetics can be invaluable. Tests for disorders where specific treatments are available are an essential part of the treatment strategy and are outlined below.

The Role of Counseling

Counseling is a critically important pre-requisite for successful treatment for several reasons:

  • First, patients with dystonia may go for several years without a correct diagnosis, and they frequently are offered many ineffective treatments during this time. Many are told their problem is psychological. As a result, patients often arrive to clinic with a sense of frustration that providers do not understand their problem or how to treat it. Helping them find proper sources of information and support is an invaluable part of the treatment strategy.
  • Second, dystonia is a chronic disorder for which a cure does not yet exist. Many useful treatments are available, but an empiric approach is often necessary to find the best solutions with the fewest side effects. Inherent in the empiric approach is the time required to work through some therapies that ultimately do not prove useful.
  • Third, most available treatments require weeks or months to reach peak benefits. Oral medications must be titrated over several weeks, BTX treatments may yield better outcomes over several treatment sessions as target muscles and doses are customized for optimal effect, and optimal benefits from DBS may take 3-12 months. Education is essential to ensure that expectations for treatment are realistic in terms of the magnitude of benefit and the time required to reach the benefits.

Education and counseling of patients is aided by a number of very useful resources. Several patient advocacy groups provide information through internet sites, short educational brochures, and local support groups. 

The Global Dystonia Patient Registry allows patients to sign up to be kept informed of novel research findings and opportunities for participating in research.

Finally, the Dystonia Coalition is a collaboration between multiple academic center and patient advocacy groups that is funded by the NIH to advance clinical and translational research in dystonia through research studies.


  1. Cloud, L.J. and H.A. Jinnah, Treatment strategies for dystonia. Expert Opin Pharmacother, 2010. 11: p. 5-15.
  2. Bhidayasiri, R. and D. Tarsy, Treatment of dystonia. Expert Rev Neurother, 2006. 6: p. 863-86.

Wilson’s Disease

Very effective treatments are available for a few rare disorders where dystonia may be a presenting or dominating feature on examination1-3. Wilson’s disease is the prototype example. It is a disorder of copper metabolism. Approximately 85% of patients have some form of dystonia, often combined with Parkinsonism, tremor, or other neurological features. Copper chelation therapy can prevent progression and even reverse disability. Because Wilson’s disease has a fatally progressive course without treatment, it should be excluded with appropriate diagnostic testing in every child and young adult with dystonia. A low serum ceruloplasmin and a slit lamp exam by an ophthalmologist specifically looking for the presence of Kaiser-Fleischer rings provide useful screening tests. This may be followed by urinary tests of copper excretion and/or liver biopsy if diagnostic uncertainty remains.

Dopa-Responsive Dystonia

Dopa-responsive dystonia presents in children and young adults as a relatively isolated dystonia but it often is combined with Parkinsonism. Corticospinal features are reported for some cases, such as spasticity and brisk reflexes. Although dopa-responsive dystonia constitutes only a small fraction of all childhood dystonias, a trial of levodopa is warranted in all children and young adults with dystonia because of its dramatic and sustained efficacy4. A dramatic and sustained response can be considered diagnostic. Among those who respond to levodopa, the role for confirming the diagnosis via lumbar puncture to identify low CSF biopterin levels remains unclear. There are simple genetic tests for the most common forms of dopa-responsive dystonia associated with mutations of the GCH1 or TH genes, but sensitivity is not 100% for detecting all mutations.

Other Treatments

As ongoing research reveals additional causes for dystonia, the numbers of disorders with specific mechanism-based treatments has continued to grow. Guidelines for which disorders to consider and what tests to employ vary among different centers. The following disorders should be considered in the appropriate clinical setting. Biotin-responsive basal ganglia disease is a very rare condition that may present with prominent dystonia in children or young adults, often in combination with other neurological signs including Parkinsonism, ocular motility defects, and episodes of encephalopathy5-7. An important clue is peculiar signal changes in the caudate and putamen on MRI. Symptoms can be reversed with biotin supplements; death ensues if the disorder untreated.

Vitamin E deficiency is dominated by ataxia with neuropathy, but dystonia may be a presenting feature and may predominate in later stages8-10. Serum vitamin E levels are useful for diagnosis, and treatment involves dietary supplements. Deficiency of the glucose transporter, GLUT1, due to mutations in the SLC2A gene classically presents with psychomotor delay, seizures, and a mixed motor disorder. A more recently recognized phenotype of GLUT1 deficiency is paroxysmal exercise-induced dystonia. The diagnosis can be made via genetic testing and effective treatment requires a ketogenic diet.

Table 2: Treatable Disorders with Dystonia


Typical age of onset

Typical clinical features

Associated laboratory features


Biotin-responsive basal ganglia disease

children through young adults

acute encephalopathy, generalized dystonia, Parkinsonism, quadriparesis

brain MRI shows abnormal signal in caudate and sometimes putamen

biotin supplements reverse disorder

Dopa-responsive dystonia

children through young adults

generalized dystonia, often Parkinsonism, sometimes spasticity

low CSF biopterins, abnormal gene test

levodopa reverses disability

GLUT1 deficiency

children through young adults

paroxysmal dystonia

low CSF glucose

ketogenic diet reduces attacks

Vitamin E deficiency

children through young adults

generalized dystonia, often with ataxia and neuropathy

low serum vitamin E

Vitamin E supplements may retard progression

Wilson’s disease

children through young adults

generalized dystonia, often Parkinsonism, hepatopathy

low serum ceruloplasmin, high urinary copper

copper chelation can reverse disability and prevent progression


  1. Das, S.K. and K. Ray, Wilson's disease: an update. Nat Clin Pract Neurol, 2006. 2: p. 482-93.
  2. Pfeiffer, R.F., Wilson's Disease. Semin Neurol, 2007. 27: p. 123-32.
  3. Mak, C.M. and C.W. Lam, Diagnosis of Wilson's disease: a comprehensive review. Crit Rev Clin Lab Sci, 2008. 45: p. 263-90.
  4. Segawa, M., Y. Nomura, and N. Nishiyama, Dopa-responsive dystonia, in Handbook of dystonia, M.A. Stacey, Editor. 2008, Informa Healthcare, Inc.: Yew York. p. 219-244.
  5. Debs, R., et al., Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations. Arch Neurol, 2010. 67: p. 126-30.
  6. Ozand, P.T., et al., Biotin-responsive basal ganglia disease: a novel entity. Brain, 1998. 121: p. 1267-79.
  7. El-Hajj, T.I., P.E. Karam, and M.A. Mikati, Biotin-responsive basal ganglia disease: case report and review of the literature. Neuropediatrics, 2008. 39: p. 268-71.
  8. Cavalier, L., et al., Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am J Hum Genet, 1998. 62: p. 301-10.
  9. Angelini, L., et al., Myoclonic dystonia as unique presentation of isolated vitamin E deficiency in a young patient. Mov Disord, 2002. 17: p. 612-4.
  10. Garcia Ruiz, P.J., et al., Movement disorders in hereditary ataxias. J Neurol Sci, 2002. 202: p. 59-64.

Focal and Segmental Dystonias

For most patients with focal and segmental dystonia, the treatment of choice is BTX. Although BTX is the treatment of choice, it typically is not provided at the first clinic visit. Instead, the first visit is used to complete diagnostic testing if needed, to provide counseling regarding expectations, to plan the doses and procedure required, and to obtain insurance approvals for the procedure. In the interval between the initial visit and the BTX procedure, a trial of at least one oral agent often can be initiated. Finding an oral agent with at least partial efficacy can be useful as adjunctive therapy or for times when symptoms flare up between BTX treatments. The selection of oral agents for empirical trials is guided by the type of dystonia, and anticipated side effects in relation to the patient’s age and other potential comorbidities.

  • Cervical Dystonia
    For cervical dystonia, the initial choice for an adjunctive oral agent often is trihexyphenidyl. A benzodiazepine can be added if tremor is prominent, and some patients also benefit from a muscle relaxant. BTX alone, or combined with one adjunctive oral agent, suffices for the vast majority of patients. If combined treatment is inadequate or resistance to BTX develops, selective denervation or DBS can be considered. As for any surgical procedure, patient selection and counseling is critical for success.
  • Blepharospasm and Other Lower Facial Dystonias
    For blepharospasm and other lower facial dystonias, a benzodiazepine provides a good initial choice for an adjunctive agent with BTX. Trihexyphenidyl is a second choice. However, BTX alone provides sufficient relief for the majority of these patients, so adjunctive oral medications often are not needed. Myectomy may be offered to those who do not respond to medical therapy.
  • The Limb Dystonias
    The limb dystonias are among the most challenging of the focal dystonias to treat with BTX. BTX can be useful, but it is more difficult to obtain satisfactory results than in cervical and craniofacial dystonias. For limb dystonias of children and limb dystonias that are not task-specific in adults, a good initial choice is levodopa, followed by trihexyphenidyl. A benzodiazepine is useful if tremor is prominent. The adult-onset focal dystonias do not often respond to levodopa, so trihexyphenidyl and benzodiazepines are often used.

Generalized Dystonias

For patients with generalized dystonia, it is not feasible to target all involved body regions with BTX. Instead, the primary treatment modality involves oral medications. Generally, successive trials of oral agents are conducted with levodopa, trihexyphenidyl, baclofen, and sometimes other drugs. Although BTX may not be useful for comprehensive treatment of many generalized dystonias, it may be quite useful for treating the most discomforting aspects of a generalized dystonia. When medical therapy appears inadequate, more invasive approaches involving intrathecal baclofen or DBS are considered. As for any surgical procedure, patient selection is very important. Some generalized dystonias respond better to surgery than others, and some patients may not be good surgical candidates because of other comorbidities. Although these procedures are offered by many neurosurgeons, the best outcomes are likely to be achieved by those who are more experienced, and particularly those who work at centers with multidisciplinary teams.

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Summary and Future Prospects

The dystonias are quite heterogeneous, both clinically and etiologically. Not surprisingly, the many different subtypes of dystonia respond differently to various treatments. There are some special populations of patients who respond remarkably well to very specific therapies. Although these patients are rare, they should not be overlooked because treatment can be lifesaving. For the more common focal and segmental dystonias, BTX is the treatment of choice. It can be combined effectively with oral medications. BTX may also be used to address the most troublesome features in patients who have a broader distribution of dystonia, such as in the generalized dystonias. For most generalized dystonias, empirical trials with several oral agents can sometimes provide at least partial relief of symptoms. When medical therapy seems inadequate, surgery is an option. The successful experiences with DBS in generalized dystonias have led to their increasing popularity and extension to medically refractory segmental and focal dystonias too. Although we do not yet have a definitive cure, careful selection of the right combinations of treatments can result in a substantially improved quality of life for most patients.

While many treatment options exist, most of them focus on symptom control and are not curative. In order to develop more definitive cures, we must devote future efforts towards developing a better understanding of the neural processes underlying dystonia1. Recent progress in both basic and clinical research has dramatically increased our understanding of the pathogenesis of dystonia at the genetic, biochemical, anatomical and physiological levels. We are just now beginning to see some common biological themes, which may help provide insights into the processes that can serve as targets for the rational design of novel interventions in specific subgroups of dystonia. There also has been substantial progress in the development of preclinical experimental models in which promising new therapies can be explored. Eventually, understanding the biological processes and preclinical studies must be translated into clinical application. Developing appropriate tools and methods for testing new treatments is an essential part of this process.


  1. Jinnah, H.A. and E.J. Hess, Experimental therapeutics for dystonia. Neurotherapeutics, 2008. 5: p. 198-209.