Dystonia

Clinical Features?

Dystonia is a disorder characterized by sustained or repetitive involuntary muscle contractions frequently associated with twisting or repetitive movements and abnormal postures. Dystonia can range from minor contractions in an individual muscle group to severe and disabling involvement of multiple muscle groups.. It can be aggravated by stress and fatigue, and attenuated by relaxation and sensory tricks such as touching the affected body part . Dystonia can be classified according to age of onset (childhood vs adult), distribution (focal, multifocal, segmental, or generalized), or etiology (primary or secondary).

Primary Dystonias

Several gene mutations are associated with dystonia. Idiopathic torsion dystonia (ITD) is predominantly a childhood-onset form of dystonia with an autosomal dominant pattern of inheritance The majority of patients have an age of onset younger than 26 years (mean 14 years). In young-onset patients, dystonia typically begins in the foot or the arm and in 60–70% progresses to involve other limbs as well as the head and neck. In severe cases, patients can suffer disabling postural deformities that compromise mobility. Most childhood-onset cases are linked to a mutation in the DYT1 gene located on chromosome 9q34 resulting in a trinucleotide GAG deletion The precise pathology responsible for dystonia is not known.
Dopa responsive dystonia (DRD) or the Segawa variant (DYT5) is a dominantly inherited form of childhood-onset dystonia DRD typically presents in early childhood (1–12 years), and is characterized by foot dystonia that interferes with walking. Patients often experience diurnal fluctuations, with worsening of gait as the day progresses and improvement with sleep. DRD is typified by an excellent and sustained response to small doses of levodopa. Some patients may present with parkinsonian features, but can be differentiated from juvenile PD by normal striatal fluorodopa uptake on positron emission tomography and the absence of levodopa-induced dyskinesias Any patient suspected of having a childhood-onset dystonia should receive a trial of levodopa to exclude this condition.
Myoclonic dystonia (DYT11) results from a mutation in the epsilon-sarcoglycan gene on chromosome 7q21. It typically manifests as a combination of dystonia and myoclonic jerks, frequently accompanied by psychiatric disturbances.

Focal Dystonias

Dystonia1

  • (1) Blepharospasm—dystonic contractions of the eyelids with increased blinking that can interfere with reading, watching TV, and driving. This can sometimes be so severe as to cause functional blindness.
  • Oromandibular dystonia (OMD)—contractions of muscles of the lower face, lips, tongue, and jaw (opening or closing). Meige syndrome is a combination of OMD and blepharospasm that predominantly affects women older than age 60 years.
  • Spasmodic dysphonia—dystonic contractions of the vocal cords during phonation, causing impaired speech. Most cases affect the adductor muscles and cause speech to have a choking or strained quality. Less commonly, the abductors are affected, leading to speech with a breathy or whispering quality.
  • Cervical dystonia—dystonic contractions of neck muscles causing the head to deviate to one side (torticollis), in a forward direction (anterocollis), or in a backward direction (retrocollis). Muscle contractions can be painful, and associated with a secondary cervical radiculopathy.
  • Limb dystonias—These can be present in either arms or legs and are often brought out by task-specific activities such as handwriting (writer’s cramp), playing a musical instrument (musician’s cramp), or putting (the yips).

Focal dystonias can extend to involve other body regions (about 30% of cases), and are frequently misdiagnosed as psychiatric or orthopedic in origin. Their cause is not known.Focal dystonias are often associated with a high-frequency tremor that resembles ET. Dystonic tremor can usually be distinguished from ET because it tends to occur in conjunction with the dystonic contraction and disappears when the dystonia is relieved.

Secondary Dystonias

Drug-induced dystonia is most commonly seen with neuroleptic drugs or after chronic levodopa treatment in PD patients.
Secondary dystonia can also be observed following discrete lesions in the striatum, pallidum, thalamus, cortex, and brainstem due to infarction, anoxia, trauma, tumor, infection, or toxins such as manganese or carbon monoxide. In these cases, dystonia often assumes a segmental distribution.
Dystonia Plus Syndromes
Dystonia may occur as a part of neurodegenerative conditions such as HD, PD, Wilson’s disease, CBGD, PSP, the Lubag form of dystonia-parkinsonism (DYT3), and mitochondrial encephalopathies. In contrast to the primary dystonias, dystonia is usually not the dominant neurologic feature in these conditions.

Pathophysiology of Dystonia

The pathophysiologic basis of dystonia is not known. The phenomenon is characterized by co-contracting synchronous bursts of agonist and antagonist muscle groups. Attention has focused on the basal ganglia as the site of origin of at least some types of dystonia as there are alterations in blood flow and metabolism in basal ganglia structures. Further, ablation or stimulation of the globus pallidus can both induce and ameliorate dystonia. The dopamine system has also been implicated, as dopaminergic therapies can both induce and treat some forms of dystonia.

Treatment:

Dystonia
Treatment of dystonia is for the most part symptomatic except in rare cases where treatment of a primary underlying condition is available. Wilson’s disease should be ruled out in young patients with dystonia. Levodopa should be tried in all cases of childhood-onset dystonia to rule out DRD. High-dose anticholinergics (e.g., trihexyphenidyl 20–120 mg/d) may be beneficial in children, but adults can rarely tolerate high doses because of cognitive impairment with hallucinations. Oral baclofen (20–120 mg) may be helpful, but benefits if present are usually modest and side effects of sedation, weakness, and memory loss can be problematic. Tetrabenazine (the usual starting dose is 12.5 mg/d and the average treating dose is 25–75 mg/d) may be helpful in some patients, but use may be limited by sedation and the development of parkinsonism. Clonazepam and diazepam are rarely effective.
Botulinum toxin has become the preferred treatment for patients with focal dystonia, particularly where involvement is limited to small muscle groups such as in blepharospasm, torticollis, and spasmodic dysphonia. Benefits are transient and repeat injections are required at 2- to 5-month intervals.
Surgical therapy is an alternative for patients with severe dystonia who are not responsive to other treatments. DBS of the pallidum can provide dramatic benefits for patients with primary DYT1 dystonia. Supportive treatments such as physical therapy and education are important and should be a part of the treatment regimen.

Useful links

Botulinum toxin for Neurological Disorders