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Dystonia
Clinical Vignette
A 22-year-old previously healthy woman developed slurred speech, difficulty walking, and hand tremors over the course of 1 month after a severe psychologic trauma. She had mild neck pain and took cyclobenzaprine without benefit. She denied any history of fever, head trauma, or exposure to dopamine receptor blocking agents. There was no family history of neurologic disease. Exam revealed lower facial dystonia, including risus sardonicus and tongue dystonia, dysarthria, bradykinesia, mild cogwheel rigidity, mild rest and kinetic tremor, dystonic gait, and loss of postural reflexes. After several weeks her symptoms plateaued. A trial of carbidopa/levodopa was ineffective. She reported slight benefit on high doses of trihexyphenidyl.
Workup included blood glucose, creatinine, electrolytes, complete blood count, liver function tests, thyroid-stimulating hormone, erythrocyte sedimentation rate, antinuclear antibodies test, vitamin B 12 , ceruloplasmin, and 24-hour urine copper, all of which were within normal limits. Slit-lamp exam was negative for Kayser-Fleischer rings. Genetic testing for spinocerebellar ataxia was negative. Magnetic resonance imaging of the brain was unremarkable, as were electroencephalography and electromyography. ATP1A3 genetic sequencing revealed a mutation, confirming the diagnosis of rapid-onset dystonia-parkinsonism (RPD).
Dystonia is a hyperkinetic movement disorder characterized by involuntary sustained muscle contractions that frequently cause twisting and repetitive movements or abnormal postures. Dystonic movements are patterned, meaning that they repeatedly involve the same group of muscles. There is simultaneous contraction of agonist and antagonist muscles. In general the duration of dystonic muscle contractions is longer than other hyperkinesias (i.e., chorea), though sometimes the movements can be rapid enough to resemble repetitive myoclonic jerking. One of the characteristic features of dystonia is that it is often temporarily diminished by tactile sensory tricks (gestes antagonistes). For example, a patient with cervical dystonia may be able to reduce dystonic movements by placing a hand on his or her chin or side of the face. Patients with orobuccolingual dystonia often experience improvement by touching their lips or placing an object, such as a toothpick, into their mouths. In some patients, simply thinking about performing the sensory trick diminishes the dystonia. The efficacy of sensory tricks can be exploited in the development of therapies. For example, some patients with lower cranial dystonia may benefit from wearing a mouth guard.
The initial presentation of dystonia is usually focal (affecting one body part) and task-specific—the dystonia occurs with a particular action. For example, a subject with foot dystonia may initially note dystonia when walking forward but not walking backward or running. In the majority of patients, the dystonia remains focal without spreading to other parts of the body. If dystonia spreads, it tends to involve contiguous body parts and becomes a segmental dystonia. In more severe cases, the dystonia can become generalized. As a rule, the younger the age at onset, the more likely it is that the dystonia will spread. Recent data have also suggested that in the primary dystonias there is a caudal-to-rostral anatomic gradient in the site of onset as a function of age.
As dystonia progresses, it emerges with other actions of the affected body part, therefore becoming less task-specific. For example, the patient with foot dystonia may experience it when walking forward and backward, running, or tapping the foot. Further progression can lead to “overflow dystonia,” in which movement of a distant body part elicits the dystonia. As dystonia worsens, it can occur at rest. In the most severe cases of dystonia, contractures may develop.
Dystonia is frequently worsened by fatigue and stress and diminished with relaxation and sleep. Pain is generally uncommon in dystonia except for cervical dystonia, in which approximately 75% of patients report pain.
Classification of Dystonia
There are several recognized classification schemes for dystonia: (1) age at onset, (2) anatomic distribution, and (3) etiology.
Age at Onset
Early-onset dystonia is defined as dystonia developing at or before the age of 26 years; late onset is defined as dystonia developing after the age of 26 years. Age at onset is an important factor determining prognosis in patients with dystonia, with earlier age at onset correlating with an increased likelihood that the dystonia will spread to other body parts. In general, young-onset dystonia tends to begin in a limb and become generalized, whereas adult-onset dystonia tends to be craniocervical and to remain focal or become segmental.
Anatomic Distribution
The topographic characteristics of dystonia are useful in defining its severity and guiding treatment. Focal dystonia affects a single body part. Virtually any part of the body can be involved in dystonia, and many types of focal dystonia have specific names: blepharospasm (dystonic eye closure), spasmodic torticollis (rotational cervical dystonia), and writer's cramp (focal hand dystonia). When dystonia involves two or more contiguous body parts/regions, it is referred to as segmental dystonia. Multifocal dystonia refers to the involvement of two or more noncontiguous body parts. Generalized dystonia represents a combination of crural dystonia (one or both legs plus trunk) and any other area of the body. Hemidystonia, as its name implies, affects one-half of the body. Hemidystonia suggests a symptomatic (secondary) rather than primary dystonia.
Etiology
The growth in our understanding of the genetics of dystonia has contributed significantly to the etiologic classification of this disorder. There are essentially two broad categories of dystonia: primary and secondary.
Primary Dystonia
Primary dystonias are characterized by isolated dystonia (with the exception that tremor can be present) and may be sporadic or familial. Most primary dystonias are sporadic, with onset in adulthood and a focal or segmental presentation. The most common focal dystonia presenting to movement disorder clinics is cervical dystonia ( Fig. 31.1 ). After cervical dystonia, the most common focal dystonias are blepharospasm, spasmodic dysphonia, oromandibular dystonia, and hand dystonia.
A minority of primary dystonias have an identified genetic etiology ( Box 31.1 ). Perhaps the best studied of the primary dystonias is DYT1 dystonia, or Oppenheim dystonia, a generalized torsion dystonia that usually begins in childhood and affects the limbs first. DYT1 dystonia is caused by a deletion in the DYT1 gene, which encodes for the torsin A protein. The disease is inherited in an autosomal dominant fashion and has 30% to 40% penetrance. Phenotype can vary widely within an affected family. The DYT1 mutation is estimated to account for 90% of the cases of limb-onset dystonia in the Ashkenazi Jewish population and 50% to 70% of cases in the non-Jewish population. A number of other primary dystonias have had their genetic loci mapped ( Table 31.1 ).
Box 31.1
Classification Schemes for Dystonia
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