Medical Care
Available therapies for dystonia include oral medications or subcutaneous botulinum toxin injections, surgical procedures, and physical and/or rehabilitation therapies. [28, 29] Therapy for most people with dystonia is symptomatic, directed at controlling the intensity of the dystonic contractions.
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Although no curative treatment for dystonia is available, treatment of the underlying disorder may help reverse symptoms in patients with secondary forms of dystonia (eg, from Wilson disease or DRD).
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Early diagnosis and start of treatment for dystonia, though not proven to alter its course or increase the likelihood for remission, may improve quality of life and alleviate the disability of patients with dystonia.
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Overall, about 40% of patients improve with oral therapy. Adverse effects of the particular agents used can limit the benefits.
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Overall, the goals of therapy should be directed at increasing movement, alleviating pain, preventing contractures, restoring functional abilities, and minimizing adverse effects from medical therapy. [30]
Surgical Care
Surgical care is reserved for patients with severe symptoms in whom drug therapy fails. In general, it should be considered in patients with generalized dystonia because these patients are severely affected, because their condition is most likely to be refractory to therapy, or because they have unfavorable responses to medical therapy primarily due to adverse effects related to their need for increasing doses or to drug interactions from polypharmacy. Careful patient selection is one of the most important aspects of ensuring a successful surgical outcome.
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Thalamotomy was originally the preferred surgery for dystonia. [31] However, GPI pallidal deep brain stimulation (DBS) has produced remarkable improvement in dystonic symptoms associated with Parkinson disease. In light of this, pallidotomy or thalamotomy is no longer considered appropriate.
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With the development of high-frequency stimulation as an alternative to the creation of surgical lesions, surgical procedures have become safer and adverse effects are easier to control than before. As the disease progresses, stimulation may be varied. [32]
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GPI DBS is becoming popular in patients with primary dystonia because of its effectiveness and safety. It can be proposed at the initial phase of the disease to limit the functional consequences and to improve the prognosis for functional recovery. The consensus is that the secondary forms are less responsive than primary forms, yet responses in secondary forms do occur. [39]
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Selective peripheral denervation with partial rhizotomy performed by an experienced surgeon may have a role in cervical dystonia that does not respond to other therapies. [41]
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Myectomy may be beneficial for blepharospasm and minimally effective for cervical dystonia. Problems include weakness and disfigurement.
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Idiopathic torsion dystonia. Major nuclear complex of the basal ganglia is the striatum, which is composed of the caudate and putamen. The striatum receives glutamatergic input from the cerebral cortex and dopaminergic input from the substantia nigra pars compacta (SNc). Two types of spiny projection neurons receive cortical and nigral inputs: those that project directly and those that project indirectly to the internal segment of the globus pallidus (GPI), which is the major output site of the basal ganglia. Complementary action of both of these pathways regulates the overall function of the GPI. The GPI, which, in turn, provides tonic inhibitory (ie, gamma-aminobutyric acid [GABA]–ergic) discharges downstream into the thalamic nuclei that project to the frontal cortical and other CNS areas. Direct pathway (D1) inhibits the substantia nigra pars reticulata (SNr) and the GPI, which are the major output sites, resulting in a net disinhibition and facilitation of thalamocortical circuits. Indirect pathway (D2), through serial connections with the globus pallidus pars externa (GPe) and the subthalamic nucleus (STN), is excitatory to the GPI, resulting in further inhibitory action on thalamocortical pathways. In this model, the mean discharge rate of the GPI is the key factor that determines a hypokinetic or hyperkinetic movement disorder. Increased inhibitory influences of the GPI on the thalamocortical circuitry result in hypokinetic disorders, such as Parkinson disease, whereas decreased GPI activity results in hyperkinetic disorders, such as hemiballismus. VL = ventrolateral thalamus.
Tables
Focal |
Body Site |
Segmental |
two or more contiguous body regions |
Multifocal |
two or more noncontiguous body regions |
Generalized |
involving atleast one leg, the trunk and another body region |
Hemidystonia |
involving one side of the body |
| Type | Designation | Mode of Inheritance | Gene | Gene Locus | OMIM# |
|---|---|---|---|---|---|
DYT1 |
Early-onset generalized | Autosomal dominant | TOR1A | 9q.34.11 | 128100 |
| DYT2 | Early-onset generalized | Autosomal recessive | Uknown | Uknown | 224500 |
| DYT3 | X-linked dystonia parkinsonism (Lubag syndrome) | X-chromosomal recessive | TAF1 | Xq13.1 | 314250 |
| DYT4 | Torsion dystonia (Whispering dysphonia) | Autosomal dominant | TUBB4A | 19p13.3 | 128101 |
| DYT5a | Dopa-responsive dystonia (Segawa disease) | Autosomal dominant | GCH1 | 14q22.1–22.2 | 128230 |
| DYT5b | Dopa-responsive dystonia | Autosomal recessive | TH | 11p15.5 | 605407 |
| DYT6 | Adolescent-onset mixed phenotype | Autosomal dominant | THAP1 | 8p11.21 | 602629 |
| DYT7 | Paroxysmal dystonic choreoathetosis | Autosomal dominant | Unknown | 18p | 602124 |
| DYT8 | Paroxysmal kinesigenic, nonkinesigenic dyskinesia | Autosomal dominant | MR-1 | 2q33–35 | 118800 |
| DYT9 | Paroxysmal choreoathetosis with spasticity | Autosomal dominant | CSE | 1p | 601042 |
| DYT10 | Paroxysmal kinesigenic dystonia | Autosomal dominant | PRRT2 | 16q11.2–12.1 | 128200 |
| DYT11 | Myoclonus dystonia | Autosomal dominant | SGCE | 7q21.3 | 159900 |
| DYT11 | Myoclonus dystonia | Autosomal dominant | DRD2 | 11q23.2 | 159900 |
| DYT12 | Rapid-onset dystonia parkinsonism (syndrome) | Autosomal dominant | ATP1A3 | 19q12–13.2 | 128235 |
| DYT13 | Early- and late-onset focal or craniocervical dystonia | Autosomal dominant | Unknown | 1p36.32-p36.13 | 607671 |
| DYT14 | Dopa-responsive generalized dystonia | ||||
| DYT15 | Myoclonus-dystonia | Autosomal dominant | Unknown | 18p11 | 607488 |
| DYT16 | Dystonia-parkinsonism syndrome | Autosomal recessive | PRKRA | 2q31.2 | 612067 |
| DYT17 | Adolescent onset | Autosomal recessive | Unknown | 20p11.2-q13.12 | 612406 |
| DYT18 | Paroxysmal exertion-induced dyskinesia | Autosomal dominant | SLC2A1 | 1p34.2 | 612126 |
| DYT19 | Paroxysmal kinesigenic dyskinesia 2 | Autosomal dominant | Unknown | 16q13-q22.1 | 611031 |
| DYT20 | Paroxysmal nonkinesigenic dyskinesia 2 | Autosomal dominant | Unknown | 2q31 | 611147 |
| DYT21 | Late-onset torsion dystonia | Autosomal dominant | Unknown | 2q14.3-q21.3 | 614588 |
| DYT22 | Unknown | Unknown | Not listed | ||
| DYT23 | Adult-onset cervical dystonia | Autosomal dominant | CIZ1 | 9q34 | 614860 |
| DYT24 | Focal dystonia | Autosomal dominant | ANO3 | 11p14.2 | 615034 |
| DYT25 | Adult-onset focal dystonia | Autosomal dominant | GNAL | 18p11.21 | 615073 |
