The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good practice point) are defined at the end of the "Major Recommendations" field.
Diagnosis and Classification
- Diagnosis and classification of dystonia are highly relevant for providing appropriate management, prognostic information, genetic counseling and treatment (good practice point). (Refer to Table 1 in the original guideline documentation)
- Based on the lack of specific diagnostic tests, expert observation is recommended. Referral to a movement disorder's expert increases the diagnostic accuracy (good practice point).
- Neurological examination alone allows the clinical identification of primary dystonia and dystonia plus, but not the distinction amongst different aetiological forms of heredo-degenerative and secondary dystonias (good practice point).
Use of Genetic Test in Diagnosis and Counseling
- Diagnostic DYT-1 testing in conjunction with genetic counseling is recommended for patients with primary dystonia with onset before age 30 years (level B; Klein et al., 1999).
- Diagnostic DYT-1 testing in patients with onset after age 30 years may also be warranted in those having an affected relative with early onset (level B; Klein et al., 1999; Bressman et al., 2000).
- Diagnostic DYT-1 testing is not recommended in patients with onset of symptoms after age 30 years who either have focal cranial-cervical dystonia or have no affected relative with early onset dystonia (level B: Klein et al., 1999; Bressman et al., 2000).
- Diagnostic DYT-1 testing is not recommended in asymptomatic individuals, including those under the age of 18, who are relatives of familial dystonia patients. Positive genetic testing for dystonia (e.g. DYT-1) is not sufficient to make a diagnosis of dystonia unless clinical features show dystonia (level B; Klein et al., 1999; "Points to consider: ethical, legal, and psychosocial," 1995).
- A diagnostic levodopa trial is warranted in every patient with early onset dystonia without an alternative diagnosis (good practice point; Robinson et al., 1999).
- Individuals with myoclonus affecting the arms or neck, particularly if positive for autosomal dominant inheritance, should be tested for the DYT-11 gene (good practice point; Valente et al., 2005).
- Diagnostic testing for the paroxysmal non-kinesigenic form of dystonia (PNKD) gene (DYT- 8) is not widely available, but this may become possible in the near future (good practice point).
Use of Neurophysiology in the Diagnosis and Classification of Dystonia
- Neurophysiological tests are not routinely recommended for the diagnosis or classification of dystonia; however, the observation of abnormalities typical of dystonia is an additional diagnostic tool in cases where the clinical features are considered insufficient to the diagnosis (good practice point; Hughes & McLellan, 1985; Deuschl et al., 1992).
Use of Brain Imaging in the Diagnosis of Dystonia
- Structural brain imaging is not routinely required when there is a confident diagnosis of primary dystonia in adult patients, because a normal study is expected in primary dystonia (good practice point; Rutledge et al., 1988).
- Structural brain imaging is necessary for screening of secondary forms of dystonia, particularly in the paediatric population due to the more widespread spectrum of dystonia at this age (good practice point; Meunier et al., 2003).
- Magnetic resonance imaging (MRI) is preferable to computed tomography (CT), except when brain calcifications are suspected (good practice point).
- There is no evidence that more sophisticated imaging techniques (e.g. voxel-based morphometry, diffusion-weighted imaging, functional MRI [fMRI]) are currently of any value in either the diagnosis or the classification of dystonia (good practice point).
Treatment
Botulinum Toxins (BoNT)
- BoNT-A (or type B if there is resistance to type A) can be regarded as first line treatment for primary cranial (excluding oromandibular) or cervical dystonia (level A; Costa et al., 2005; American Academy of Ophthalmology, 1989).
- Due to the large number of patients who require BoNT injections, the burden of performing treatment could be shared with properly trained nurse specialists, except in complex dystonia or where electromyography (EMG) guidance is required (level B; Whitaker et al., 2001).
- BoNT-A may be considered in patients with writing dystonia (level C; Balash & Giladi, 2004).
Anticholinergic Drugs
The absolute and comparative efficacy and tolerability of anticholinergic agents in dystonia is poorly documented in children and there is no proof of efficacy in adults; therefore, no recommendations can be made to guide prescribing (good practice point).
Antiepileptic Drugs
There is lack of evidence to give recommendations for this type of treatment (good practice point).
Anti-dopaminergic Drugs
There is lack of evidence to give recommendations for this type of treatment (good practice point).
Dopaminergic Drugs
Following a positive diagnostic trial with levodopa, chronic treatment with levodopa should be initiated and adjusted according to the clinical response (good practice point; Hwang et al., 2001).
Neurosurgical Procedures
Deep Brain Stimulation (DBS)
Pallidal DBS is considered a good option, particularly for generalized or cervical dystonia, after medication or BoNT have failed to provide adequate improvement. Whilst it can be considered second-line treatment in patients with generalized dystonia, this is not the case in cervical dystonia since there are other surgical options available (see below). This procedure requires a specialized expertise, and is not without side effects (good practice point; Vidailhet et al., 2005; Eltahawy et al., 2004).
Selective Peripheral Denervation and Myectomy
Selective peripheral denervation is a safe procedure with infrequent and minimal side effects that is indicated exclusively in cervical dystonia. This procedure requires a specialized expertise (level C; The National Institute for Clinical Excellence, 2004).
Intrathecal Baclofen
There is insufficient evidence to use this treatment in primary dystonia; the procedure can be indicated in patients where secondary dystonia is combined with spasticity (good practice point; Albright et al., 2001).
Radiofrequency Lesions
Radiofrequency ablations are currently discouraged for bilateral surgery because of the relatively high risk of side effects (good practice point). The focus of treatment has currently shifted to DBS because of its lower risk for bilateral procedures.
Rare, Uncommon or Obsolete Procedures
- Intradural rhizotomy has been replaced by selective ramisectomy and peripheral denervation or myotomy. These procedures are no longer recommended.
- Microvascular decompression is not recommended for treatment of cervical dystonia.
Definitions:
Evidence Classification Scheme for a Diagnostic Measure
Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation
Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations for a Diagnostic Measure
Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.
Rating of Recommendations for a Therapeutic Intervention
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good practice point Where only class IV evidence was available but consensus could be achieved the Task Force has proposed good practice points.
