Dystonia

Dystonia is a neurologic syndrome characterized by involuntary, sustained, patterned and often repetitive muscle contractions of opposing muscles, causing twisting movements or abnormal postures. Dystonia is a fairly common neurological disorder with a prevalence of approximately 1 in 3,400 for focal dystonia and 1 in 29,400 for generalized dystonia.(1) If patients with drug-induced tardive dystonia related to neuroleptic medications and secondary dystonia related to brain injury are added to this group, the prevalence figure can probably be doubled and approaches that of multiple sclerosis.(2) All gender, ethnic, and socioeconomic groups are equally affected.

Clinical presentation
If one dichotomizes movement disorders to those with reduced movement (akinetic-rigid syndromes) versus those with excessive movement (hyperkinetic syndromes), dystonia falls into the hyperkinetic disorder category. However, distinguishing dystonia from other hyperkinetic movement disorders may be challenging. The clinical characteristic of dystonia that helps differentiate it from other hyperkinetic movement disorders is that dystonic movements are repetitive and stereotyped, with involvement of the same group of muscles. For instance, a patient with idiopathic cervical dystonia or spasmodic torticollis with involuntary right-head rotation will continue to have right-head rotation throughout the duration of his disorder. By comparison, choreic movements are brief, continuous, non-stereotyped and random. Tics involve brief and intermittent movements or sounds. Compared to dystonia, tics may be suppressed or more abrupt, and are often proceeded by a subjective compulsive urge or sensation, which is temporarily relieved after the tic occurs. Dystonia is often associated with tremor, which may make the diagnosis somewhat more difficult. Essential tremor and dystonia have been observed to coexist frequently, although tremors associated with dystonia may represent a forme-fruste of dystonia.(3)

In anatomical classification of dystonia, a focal dystonia is restricted to a single, specific part of the body-- most often the cranial and cervical-innervated muscles. Segmental dystonia involves two or more contiguous body parts. Multifocal dystonia involves two or more noncontiguous body parts. Hemidystonia involves the ipsilateral arm and leg, and often represents a structural lesion involving the contralateral basal ganglia. Generalized dystonia involves either both lower extremities and another body part or a single lower extremity, the trunk and another body part.

Blepharospasm is dystonia involving the upper face, with contraction of the orbicularis oculi muscles. In its early stages, blepharospasm may present with eye irritability. With more advanced disease, there may be more forceful and sustained eye closure, which may result in legal blindness. Dystonia in the lower face is often associated with blepharospasm and may manifest as repetitive lip puckering or retraction. In oromandibular dystonia, lower facial dystonia is often seen with involuntary jaw opening or closure. This may significantly interfere with speech and eating. The combination of oromandibular dystonia and blepharospasm is also known as Meige Syndrome. Pharyngeal muscles may develop dystonia and result in dysphagia, dysarthria or dysphonia. Lingual dystonia is frequently associated with oromandibular dystonia and often manifests as involuntary tongue protrusion while speaking or eating. Dystonia involving the laryngeal muscles may produce spasmodic dysphonia.

When vocal cord adductors are affected, speech may sound tight and restricted, while involvement of vocal cord adductors produces a more breathy dysphonia.

The most common form of dystonia is idiopathic cervical dystonia. When head rotation represents the most prominent posture, this is known as torticollis (Figure 1). Retrocollis refers to abnormal neck extension, while antecollis refers to abnormal flexion of the head on the trunk. Laterocollis involves tilting of the head toward the shoulder. Cervical dystonia often involves combinations of head turning, tilting and flexion/extension. Brachial dystonia refers to dystonia involving the arm and is often task-specific. For example, writers cramp represents a brachial dystonia elicited by handwriting (Figure 2), while musician's cramp may occur in pianists or violinists. Truncal dystonia may present with lordosis, scoliosis, kyphosis or opisthotonic posturing. Limb dystonia involving the legs may present with equinovarus posturing of the foot (Figure 3), particularly in children with primary dystonia.


Figure 1: Idopathic cervical dystonia in a 52-year old man manifest as right torticollis	Figure 2: Task-specific right brachial dystonia (writer's cramp) with flexion of digits 2-5 and thumb extension

Figure 3: Limb dystonia involving plantar flexion and extension of the right foot.

Classification

Traditionally, dystonia has been divided into primary and secondary forms. Primary dystonias included both inherited diseases, in which dystonia was the only manifestation, and idiopathic dystonias. Secondary dystonias referred to diseases in which dystonia represented one manifestation of an underlying neurological disorder (e.g. Huntington's disease) or resulted from a metabolic abnormality (e.g., Wilson's disease).

The most contemporary etiologic classification system, however, proposes four classifications of dystonic disorders.(4) Primary dystonia refers to disorders in which the only manifestation is dystonia. This term includes inherited dystonias (e.g., dystonia musculorum deformans associated with the DYT-1 gene on chromosome 9) along with idiopathic dystonias (the most common forms of dystonia). Dystonia plus syndromes refer to a group of dystonias related to disorders of catecholamine synthesis and biopterin metabolism, such as dopa-responsive dystonia. Secondary dystonias relate to underlying brain esions and their sequelae, such as athetoid cerebral palsy following neonatal kernicterus, encephalitis, head trauma, brain neoplasms and toxins such as manganese. Finally, heredodegenerative diseases represent a separate category of neurological degeneration that produce dystonia as a prominent feature-such as Huntington's disease, Wilson's disease and dystonia associated with Parkinsonian Syndromes.

In general, the younger the patient at presentation, the more likely dystonia will be on a secondary basis. Adult onset of dystonia is more frequently focal and idiopathic. A secondary dystonia should be suspected in patients presenting with dystonia in childhood or adolescence, when there are other neurological findings (e.g., memory/cognitive decline, optic atrophy, abnormal eye movements, pigmentary retinopathy, organomegaly, cataracts, corticospinal findings, cerebellar findings).

Two types of dystonia merit special mention since their underlying causes are quite treatable. Wilson's disease should be considered in all patients presenting with dystonia before age 50 years, particularly in the setting of liver failure. Screening should include liver transaminases, serum cerruloplasmin and a slit-lamp examination for Kayser-Fleischer rings. Dopa-responsive dystonias result from inherited abnormalities in catecholamine and biopterin metabolism. These disorders may present in childhood or adolescence, with dystonia involving the lower extremities and a secondary gait disorder. Parkinsonian features and a diurnal variation are typical. A trial of levodopa advanced to 500 mg per day circumvents the metabolic abnormality in dopamine synthesis and elicits dramatic improvement in abnormal movements.

Treatment Considerations
Medical treatment of dystonia includes anticholinergic medications such as trihexyphenidyl and benztropine. These medications are often significantly effective, although they exhibit dose-dependent side effects of sedation, dry mouth and reduced short-term memory. Benzodiazepines may reduce the intensity of the dystonic muscle spasms, but their use may also be encumbered by sedation and cognitive side-effects. Clonazepam is often used due to its long duration of action. Baclofen may also be helpful in reducing the intensity of dystonic muscle spasms. Selective chemodenervation with botulinum toxin type A and type B injections has proven effective for symptomatic treatment of dystonia, particularly for focal or segmental dystonias. The toxin is injected intramuscularly into the most dystonically active muscles to relieve discomfort related to sustained muscle contractions and to improve abnormal postures. Chemodenervation selectively delivers botulinum toxin to dystonically active muscles. This is technically straightforward in blepharospasm, where the superficially located orbicularis oculi muscles are injected. It is more problematic in cervical dystonia, where deep cervical muscles responsible for dystonic postures must be identified using electromyographic guidance.

Some patients receiving botulinum toxin type A injections may develop clinical resistance to the paralytic effects of the toxin. This resistance is immunologically mediated, and relates directly to the toxin dosage and frequency. Botulinum toxin type B injections represent an alternative treatment option for patients who have developed this resistance. In addition to improved efficacy, electromyographic guidance may help to minimize the amount of botulinum toxin required and thus reduce the risk of developing clinical resistance to the injections.

The University of Virginia Chemodenervation/Dystonia Clinic provides a full range of diagnostic and treatment services for patients with dystonia and other indications for chemodenervation. Patients may be referred by calling the Clinic at (434) 924-8023.

Vern C. Juel, M.D., vj2n@virginia.edu

(1)Nutt JG, Muenter MD, Aronson A, Kurland LT, Melton LJ. Epidemiology of focal and generalized dystonia in Rochester, Minnesota. Mov Disord 1983; 3:188-194.

(2)Marsden CD, Fahn S. Dystonia 3: Advances in Neurology, Vol. 78. Philadelphia: Lippincott-Raven, 1998:359-364.

(3)Rivest J, Marsden CD. Trunk and head tremor as isolated manifestations of dystonia. Mov Disord 1990; 5:60-65.

(4)Fahn S, Bressman SB, Marsden CD. Classification of dystonia. In: Dystonia 3: Advances in Neurology, Vol. 78. Philadelphia: Lippincott-Raven, 1998:1-10.

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