Primary Torsion Dystonia Treatment & Management

  • Author: Vijaya K Patil, MD; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Mar 11, 2010
 

Medical Care

Therapy for most people with dystonia is symptomatic, directed at controlling the intensity of the dystonic contractions.

  • 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).
  • 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.
  • Available therapies for dystonia include oral medications, intramuscular or subcutaneous botulinum toxin injections, surgical procedures, and physical and/or rehabilitation therapies.[26, 27]
  • Overall, about 40% of patients improve with oral therapy. Adverse effects of the particular agents used can limit the benefits.
  • 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.[28]
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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.

  • Thalamotomy was originally the preferred surgery for dystonia.[29] However, pallidotomy or pallidal deep brain stimulation (DBS) have produced remarkable improvement in dystonic symptoms associated with Parkinson disease. Bilateral pallidotomy may be associated with uncontrollable adverse effects, and initial improvement of symptoms may not be sustained.
  • 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.[30]
  • Over the past few years, DBS of the globus pallidus interna (GPI) has gained widespread acceptance as an effective treatment for primary generalized dystonia.[31, 32, 33, 34]
    • In a 2-year follow-up study, French researchers found that GPI DBS was efficient in most cases of primary dystonia, whatever the topography of the symptoms (ranging from spasmodic torticollis to generalized dystonia).[35]
    • In a 3-year follow up study by Krause et al, patients with primary generalized dystonia benefited from GPI stimulation, though in 1 patient had secondary worsening of symptoms approximately 3 years after DBS implantation.[30]
    • Further work by the French group has shown that the efficacy of DBS in patients with DYT1 dystonia can be maintained for up to 10 years. New symptoms may appear over time, but in some of these patients, the implantation of an additional GPI lead may bring improvement.[36]
  • 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.[37]
  • At present, the GPI is the most common target for dystonia. Other targets used in the past, including pallidal and nigral outflow or the thalamus, should also be considered.[38]
  • 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.[39]
  • Myectomy may be beneficial for blepharospasm and minimally effective for cervical dystonia. Problems include weakness and disfigurement.
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Contributor Information and Disclosures
Author

Vijaya K Patil, MD  Assistant Professor, Department of Neurology, Loyola University, Chicago Stritch School of Medicine, Edward Hines Jr Veterans Affairs Hospital

Vijaya K Patil, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Medical Council of India

Disclosure: Nothing to disclose.

Coauthor(s)

Jasvinder Chawla, MBBS, MD, MBA  Chief of Neurology, Hines Veterans Affairs Hospital; Associate Professor and Director, Neurology Residency Training Program, Loyola University Medical Center

Jasvinder Chawla, MBBS, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephen T Gancher, MD  Adjunct Associate Professor, Department of Neurology, Oregon Health Sciences University

Stephen T Gancher, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and Movement Disorders Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Nestor Galvez-Jimenez, MD, MSc, MHA  Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Ortho McNeil Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Speaking, consulting

Chief Editor

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Ortho McNeil Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Speaking, consulting

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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.
Table 1. Anatomic Distribution of Primary Torsion Dystonia
FocalSingle Body Site
SegmentalContiguous body regions
MultifocalMultiple, noncontiguous body sites
GeneralizedLeg involvement with other body sites
HemidystoniaUnilateral
Table 2. Clinical Characteristics of Primary Torsion Dystonia Associated With Different Genes
CharacteristicDYT1DYT6DYT7DYT13
Age of onsetEarly (< 26 y); rare cases of late onsetChildhood or adulthoodAdult5-40 y (mean, 15.6 y)
Site of involvementLimb onset (>95% of patients have arm involvement), trunk, neck, cranial (< 15%)Limb, neck, or cranial muscles; cranial involvement with dysarthria and dysphagiaCervicocranialProminent cervicocranial and upper-limb involvement
Mode of transmissionAutosomal dominant with reduced penetrance (30-40%)Autosomal dominant with reduced penetranceAutosomal dominant with reduced penetrance (12-15%)Autosomal dominant
Locus9q328p18p1p36.13-p36.32
PathophysiologyMutation in gene TOR1A coding for an adenosine-triphosphate-binding protein, resulting from a GAG deletionVarious mutations in the THAP1 geneNo dataNo data
Families describedAshkenazi and on-Ashkenazi groupsMennonite or Amish and others[17] GermanItalian
Table 3. Genetic Loci for Dystonia
GeneLocusFeatures
DYT1*9q34Early, limb-onset primary torsion dystonia; autosomal dominant with 30% penetrance; gene encodes torsin A; all mutations except 1 are GAG deletions
DYT2NoneAutosomal recessive in Gypsy populations; early onset
DYT3Xq13.1X-linked (ie, Lubag) dystonia parkinsonism; almost all due to a founder Filipino mutation; young adult-onset, cranial (including larynx and/or stridor) and limb dystonia, parkinsonism develops (or is present at onset) with shuffling, drooling
DYT4NoneWhispering dysphonia in Australian family (autosomal dominant)
DYT514q22.1Childhood-onset dopa-responsive dystonia (DRD) and parkinsonism; autosomal dominant, sex influenced, reduced penetrance (higher in girls than in boys); gene encodes guanosine triphosphate cyclohydrolase I, with many different mutations
DYT6*8pAdolescent and early-adult onset, mixed phenotype with limb, cervical, and cranial onset and limited and generalized spread; originally found in Amish-Mennonite families, but numerous variants have subsequently been found in families of European descent[11] ; autosomal dominant with reduced penetrance
DYT7*18pLate-onset primary cervical dystonia in North German families; autosomal dominant with reduced penetrance
DYT82q33-35Paroxysmal nonkinesiogenic dyskinesia or chorea, autosomal dominant
DYT91p21Episodic choreoathetosis/spasticity (CSE), episodic choreoathetosis with spasticity, autosomal dominant
DYT1016p11.2-q12.1Paroxysmal kinesiogenic dyskinesia or chorea, autosomal dominant
DYT117q21Myoclonus-dystonia, autosomal dominant, childhood-onset dystonia (especially limbs and neck) and myoclonus (especially neck, shoulders, face); often improves with alcohol
DYT1219q13Rapid-onset dystonia parkinsonism
DYT13*1p36.13-35.32Prominent craniocervical and upper-limb involvement and mild severity in a large Italian family
DYT14Redefined as DYT5[20]
DYT1518p11Myoclonus dystonia; autosomal dominant[21]
DYT162q31Progressive, generalized, early-onset dystonia with axial muscle involvement, oromandibular (sardonic smile), laryngeal dystonia, and sometimes parkinsonian features, unresponsive to levodopa therapy; autosomal recessive[22]
DYT1720p11.22-q13.12Primary focal torsion dystonia in a large Lebanese family; autosomal recessive[23]
DYT181p35-p31.3Paroxysmal exertion-induced dystonia with hemolytic anemia; autosomal dominant
Note: Although the etiologies for these dystonic syndromes are attributed mainly to genetic causes and to no other secondary causes, only some of these conditions have dystonia as the sole clinical finding to fulfill the criteria for a diagnosis of primary torsion dystonia.



*Adapted from Bressman et al.[24]



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