Dystonia

What is dystonia?

Dystonia is a neurologic movement disorder dominated by involuntary, sustained or repetitive, patterned muscle contractions or spasms, frequently causing squeezing, twisting, and other movements or abnormal postures. Typically, dystonia begins in a single body part (focal dystonia), such as the hand, neck or eyelids, and then it spreads to adjacent body parts (segmental dystonia). Blepharospasm, a focal dystonia manifested by an involuntary eye closure produced by spasmodic contractions of the eyelids and eyebrows, is often associated with dystonic movements of facial, jaw, laryngeal, and neck muscles. Oromandibular dystonia may be manifested by involuntary jaw opening or closing associated with clenching (trismus) and teeth grinding (bruxism), which may lead to secondary dental wear and temporal-mandibular joint (TMJ) syndrome. In our Movement Disorders Clinic at Baylor College of Medicine, neck or cervical dystonia is clearly the most frequent form of dystonia. This form of focal dystonia is characterized by patterned (same group of muscles), repetitive, head movements or more sustained abnormal postures of the head. The term “spasmodic torticollis” is still occasionally used to describe this form of dystonia. However, since it is not always spasmodic and it does not always consist of head turning (torticollis), the term “cervical dystonia” is preferred as a generic descriptor of dystonic movements or postures involving the neck. In addition to torticollis (turning of the head), cervical dystonia may be manifested by neck flexion (anterocollis), extension (retrocollis), or head tilt (laterocollis). In approximately a third of all patients, cervical dystonia progresses to involve contiguous body parts such as the oromandibular region, shoulder, trunk, and arm. Cervical dystonia is associated with pain in about 75% of patients and most patients have discovered certain maneuvers or “tricks”, such as touching the chin or neck, to correct the abnormal postures. Segmental dystonia involving eyelids (blepharospasm) and other facial, jaw (oromandibular) and neck (cervical) muscles is still sometimes referred to as “Meige's syndrome”, but the term “cranial-cervical dystonia” is preferred because it more accurately describes the anatomical distribution of the dystonic movements. Spasmodic dysphonia, a focal dystonia of the vocal cords and larynx, is characterized by strained, effortful voice interrupted by uncontrollable pitch breaks or voiceless pauses (adductor spasmodic dysphonia) or whispering, breathy voice (abductor spasmodic dysphonia).

While cervical dystonia is the most common form of dystonia encountered in a specialized clinic, writer's cramp is probably more common in general population. In addition to this “task-specific” dystonia, there are many other examples of occupational dystonias affecting the performance of musicians, sportsmen, and others whose skills depend on finely coordinated movements. Dystonia, particularly of childhood onset, may spread to involve the legs, trunk and other body parts (generalized dystonia). Unilateral dystonia, confined to only one half of the body, is referred to as hemidystonia. In contrast to focal and segmental dystonia, which is usually “idiopathic” or “primary” (no other neurological abnormality and no specific cause except possibly genetic), majority of patients with hemidystonia have an identifiable etiology such as head trauma, stroke, arteriovenous malformation, tumor, encephalitis or other pathology affecting the opposite basal ganglia.

One of the most common forms of primary, childhood-onset, dystonia is the so-called DYT1 dystonia. This dystonia, which occurs with particularly high frequency in Ashkenazi Jewish population, is manifested by onset of writer’s cramp, foot inversion, or other dystonia of the limbs, typically before the age of 10, and progressing to a more generalized dystonia involving legs, arms and trunk. Although the progression may vary between individuals of the same or different families, many children with DYT1 dystonia require assistance with ambulation by the time they reach early teens. The diagnosis of DYT1 dystonia can be confirmed by a genetic DNA test (see below).

What causes dystonia?

The cause of primary dystonias is not always apparent, but most are probably due to some genetic abnormalities. Although in most patients with dystonia no specific abnormality or lesion can be identified by neuroimaging or even autopsy studies, there is convincing evidence that this movement disorder is due to abnormal function of the deep portion of the brain, called basal ganglia. The most important advance in our quest to understand the cause of dystonia has been the identification of a gene, called DYT1 on chromosome 9, the mutation of which causes primary dystonia. The DYT1 gene codes for the protein TorsinA which accumulates abnormally in selected neurons of the brainstem. It is not yet known, however, how this abnormality leads to dystonia. Besides DYT1, there are many other genetic forms of dystonia, and new gene abnormalities are being added to the growing list of genetic forms of dystonia.

Not all dystonias, however, are of genetic origin; some are sporadic (no family history) and others are secondary to some specific causes such as certain metabolic and neurodegenerative disorders (e.g. Wilson's disease), brain injury or other lesions (e.g. cerebral palsy), certain drugs that block dopamine receptors, and many other causes. The dopamine receptor blocking drugs, also called neuroleptics, such as the major tranquilizers (e.g. haloperidol) and gastrointestinal drugs (e.g. metoclopramide) can cause not only an acute transient dystonic reaction, but more importantly a persistent dystonic disorder (tardive dystonia). Besides central etiologies, which presumably account for the vast majority of dystonias, peripherally-induced dystonia caused by an injury to the affected body part is being increasingly recognized as an important cause of focal and segmental dystonia. Finally, physical or emotional stress and a variety of other psychological factors may be associated with abnormal movements resembling dystonia, the so-called “psychogenic dystonia”.

How is dystonia treated?

Despite the paucity of knowledge about causes of dystonia, the treatment of this condition has markedly improved, largely as a result of application of botulinum toxin (BTX). Before contemplating BTX therapy, however, potentially curable causes of dystonia, such as certain drug-induced dystonias or Wilson's disease, should be considered. Physical therapy, including well fitted braces may be helpful to some dystonic patients, but are usually unsatisfactory when used alone. Some patients, particularly those with generalized dystonia, may benefit from pharmacologic therapy using medications such as trihexyphenidyl, baclofen, tetrabenazine, and levodopa. Surgical techniques, such as local nerve or muscle excision and ablation or high frequency deep brain stimulation (DBS) have been used successfully in patients who continue to have disabling dystonia despite optimal medical or BTX therapies. DBS of the globus pallidus internum (GPi) has emerged as the surgical treatment of choice in patients with severe generalized or segmental dystonia as well as hemidystonia.

Selected References

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Diamond A, Shahed J, Azher S, Dat-Vuong K, Simpson R, Jankovic J. Globus pallidus deep brain stimulation in dystonia. 2006;21:692-5.
Fahn S, Jankovic J. Principles and Practice of Movement Disorders, Churchill Livingstone, Elsevier, Philadelphia, PA, 2007:1-652. (Accompanied by a DVD of movement disorders).
Jankovic J, Vuong KD, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology 2003;60:1186-1188.
Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry 2004;75:951-7.
Jankovic J. Treatment of cervical dystonia with botulinum toxin. Mov Disord 2004;19 (Suppl 8):S109-S115.
Jankovic J, Esquenazi A, Fehling D, Freitag F, Lang AM, Naumann M. Evidence-based review of patient reported outcomes with botulinum toxin type A. Clin Neuropharmacol 2004;27:234-244.
Jankovic J. Botulinum toxin therapy for cervical dystonia. Neurotoxicity Research 2006;9:145-148.
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Jankovic J, Tsui J, Bergeron C. Prevalence of cervical dystonia and spasmodic torticollis in the United States. Parkinsonism Related Disorders 2007;13:411-416.
Jankovic J. Dystonic disorders. In: Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders, 5th edition, Lippincott Williams and Wilkins, Philadelphia, PA, 2007:321-47.
Jankovic J, Shannon KM. Movement disorders. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in Clinical Practice, 5th Edition, Butterworth-Heinemann (Elsevier), Philadelphia, PA, 2008.
Kabakci K, Hedrich K, Leung JC, et al. Mutations in DYT1: extension of the phenotypic and mutational spectrum. Neurology 2004;62:395-400.
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McNaught KS, Kapustin A, Jackson T, et al. Brainstem pathology in DYT1 primary torsion dystonia. Ann Neurol 2004;56:540-7.
Németh AH. The genetics of primary dystonias and related disorders. Brain 2002;125:695-721.
Opal P, Tintner R, Jankovic J, Leung J, Breakfield XO, Friedman J, Ozelius L. Intrafamilial phenotypic variability of the DYT1 dystonia: From asymptomatic TOR1A gene carrier status to dystonic storm. Mov Disord 2002;17:339-345.
Rosset-Llobet J, Candia V, Fabregas S, Ray W, Pascual-Leone A. Secondary motor disturbances in 101 patients with musician's dystonia. J Neurol Neurosurg Psychiatry 2007;78:949-53.
Schrag A, Trimble M, Quinn N, Bhatia K. The syndrome of fixed dystonia: an evaluation of 103 patients. Brain 2004;127:2360-72.
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Sitburana O, Jankovic J. Focal hand dystonia, mirror dystonia and motor overflow. J Neurol Sci 2007 (in press).
Vidailhet M, Vercueil L, Houeto JL, et al. Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: a prospective 3 year follow-up study. Lancet Neurol 2007;6:223-9.

Appendix

Dystonia Medical Research Foundation
One East Wacker Drive Suite 2430
Chicago, IL 60601-1905
Tel: 312-755-0198
Fax: 312-803-0138
www.dystonia-foundation.org

WE MOVE (Worldwide Education and Awareness for Movement Disorders)
204 West 84 th Street
New York, NY 10024
Tel: 800-437-6682 (MOV2)
Fax: 212-875-8389
www.wemove.org