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Torsion Dystonias Workup

  • Author: Priyantha Herath, MD, PhD; Chief Editor: Selim R Benbadis, MD  more...
 
Updated: Feb 15, 2016
 

Approach Considerations

Routine laboratory and neurophysiological investigations are not recommended as part of workup to diagnosis and classify dystonia. Most often, the diagnosis is clinical. However, a useful investigative algorithm for dystonia workup is given here. 

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Laboratory Studies

The following is recommended when age of onset is younger than 26 years (or the patient has a relative with early-onset dystonia):

  • DYT1 testing (with genetic counseling)
  • If negative for DYT1 testing, consider trial of levodopa
  • If no response to levodopa trial, perform MRI, ceruloplasmin test, and slitlamp examination

The following is recommended when age of onset is older than 26 years:

  • MRI
  • 24-hour copper urinary excretion

To differentiate patients with dopa-responsive dystonia from junvenile Parkinson disease presenting with dystonia, one can consider presynaptic dopaminergic scan (DAT) or fluorodopa (F-DOPA) scanning.[27]

The following is the proposed algorithm for dystonia workup when the history and physical findings show dystonia and other deficits:

  • Possibly tardive condition: Assess for a history of exposure to a dopamine- blocking agent
  • Possibly structural condition: Perform MRI and CT angiography
  • Possibly metabolic and/or neurodegenerative: Perform the following:
    • Trial of levodopa
    • Measurement of 24-hour serum copper excretion
    • Slitlamp examination
  • MRI of brain
  • Blood smear for acanthocytes
  • Antiphospholipid antibody testing
  • Genetic testing for Huntington disease, SCA, mitochondrial diseases
  • Lysosomal screening (GM1, GM2 gangliosidoses)
  • Test for serum and urine organic acids and amino acids
  • Chromosomal analysis
  • Alpha-fetoprotein test
  • Determination of lactate and pyruvate in serum and CSF with the lactate-pyruvate ratio
  • Skin, muscle, and nerve biopsy
  • CSF analysis
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Contributor Information and Disclosures
Author

Priyantha Herath, MD, PhD Director of Movement Disorders Clinic, Attenting Neurologist, Department of Neurology, University of South Carolina School of Medicine at Columbia

Priyantha Herath, MD, PhD is a member of the following medical societies: American Academy of Neurology, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Coauthor(s)

Souvik Sen, MD, MPH, MS, FAHA Professor and Chair, Department of Neurology, University of South Carolina School of Medicine

Souvik Sen, MD, MPH, MS, FAHA is a member of the following medical societies: American Academy of Neurology, Association for Patient-Oriented Research, American Heart Association

Disclosure: Nothing to disclose.

Sonal Mehta, MD Clinical Assistant Professor, Department of Neurology, University of South Carolina School of Medicine

Sonal Mehta, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Stroke Association, Neurocritical Care Society, Society of Vascular and Interventional Neurology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nestor Galvez-Jimenez, MD, MSc, MHA The Pauline M Braathen Endowed Chair in Neurology, 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, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Chief Editor

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

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.

Additional Contributors

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, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, 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, American Medical Association

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

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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
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
Table.
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
Table.
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