Dystonia

Ailsa Snaith; Derick Wade

. 2008 Sep 5;2008:1211.

Dystonia

Ailsa Snaith ^1,^#, Derick Wade ^2,^#

PMCID: PMC2907934 PMID: 19445800

Abstract

Introduction

Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal, and for generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: acetylcholine receptor inhibitors, acupuncture, anticholinergic drugs, anticonvulsants, atypical antipsychotic drugs, benzodiazepines, biofeedback, botulinum toxin, chiropractic manipulation, deep brain stimulation of thalamus and globus pallidus, dopaminergic agonists and antagonists, gamma-aminobutyric acid (GABA) inhibitors, microvascular decompression, myectomy, occupational therapy, osteopathy, pallidotomy, physiotherapy, selective peripheral denervation, serotonergic agonists and antagonists, speech therapy, and thalamotomy.

Key Points

Dystonia is characterised by involuntary muscle contractions, resulting in abnormal postures and twisting of body parts.

It is usually a lifelong condition, with persistent pain and disability.
Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body.
It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent.

Botulinum toxin is effective in relieving cervical dystonia symptoms in adults.

Botulinum toxin A and botulinum toxin B are both effective.
We found most evidence for botulinum toxin, and it is the mainstay of modern treatment for focal dystonia.

We don't know whether any other drug treatments (benzodiazepines, GABA inhibitors, atypical antipsychotics, anticonvulsants, dopaminergic agonists and antagonists, and serotonergic agonists and antagonists) are effective for either focal or generalised dystonia.

We don't know whether any surgical interventions (thalamotomy, pallidotomy, deep brain stimulation of thalamus and globus pallidus, selective peripheral denervation, or myectomy) are effective for either focal or generalised dystonia.

Most people will see a physiotherapist after diagnosis, but there is no consistent approach to treatment.

About this condition

Definition

Dystonia is a neurological disorder characterised by involuntary, abnormal muscle contractions that result in sustained abnormal postures, twisting, or both, and repetitive movements of body parts. It arises from dysfunction of the motor control system within the central nervous system. Dystonia is most simply classified by location: focal dystonia involves a single body part; multifocal dystonia involves two or more unrelated body parts; segmental dystonia affects two or more adjacent parts of the body; hemidystonia involves the arm and leg on the same side of the body; and generalised dystonia affects most or all of the body. For the purpose of this review we have classified dystonia into focal dystonia and generalised/other dystonia. However, studies in which dystonia has been classified according to other classification systems are also covered. In addition to focal and generalised dystonia, classification may also be based on age at onset (early onset or late onset), or according to the cause of the dystonia: primary dystonia where dystonia is the only sign and no cause can be identified; dystonia-plus syndrome where dystonia is associated with other pathology (e.g. dopa-responsive dystonia, and myoclonus dystonia); heredodegenerative dystonia where dystonia is a sign associated with neurological conditions, such as Parkinson's Disease and Huntington’s Disease; and secondary dystonia where a cause (usually environmental) can be identified, such as head injury or use of drugs (e.g. neuroleptic drugs and metoclopramide). Certain dystonias may also be classified as task specific; examples of task-specific focal hand dystonia include writer’s cramp, typist’s cramp, and musician’s cramp (affects pianists and flautists). Diagnosis: The clinical diagnosis of dystonia is based on the hallmark features of the abnormal, involuntary, and prolonged muscle contractions with consistent directionality that lead to an abnormal posture of the area affected. There is no definitive diagnostic test for dystonia. Investigation typically involves history and clinical examination, laboratory tests, and imaging, to establish severity and potential cause. Laboratory tests and neuro-imaging may help to rule out metabolic or structural causes. Genetic testing, electro-physiological tests, and tissue biopsy may also be considered. The goal of accurate diagnosis is to facilitate treatment choice.

Incidence/ Prevalence

Dystonia occurs worldwide, with prevalence estimates varying widely depending on study methodology. In the USA, the prevalence of focal dystonia has been reported as 30/100,000 people. Cervical dystonia (torticollis or "wry neck") is the most common adult form of focal dystonia, with a prevalence in Europe of 5.7/100,000. Other frequently occurring focal dystonias are blepharospasm (forceful eyelid closures), which affects 3.6/100,000 people, and limb dystonias (e.g. writer's cramp), which affect 1.4/100,000.In the USA, the prevalence of generalised dystonia has been reported as 0.2-6.7/100,000 population; generalised dystonia affects more people of European Ashkenazi Jewish descent. In Europe, the prevalence of primary dystonia has been estimated at 15.2/100,000.Studies identified to have rigorous methodology estimated the prevalence of early-onset (at less than 20 years of age) dystonia to be 11.1/100,000 for dystonia in Ashkenazi Jews from the New York area, 60/100,000 for late-onset (at more than 20 years of age) dystonia in the overall population of Northern England, and 300/100,000 for late-onset dystonia in the Italian population (aged 50 years or older). Dystonia occurs more frequently in women.

Aetiology/ Risk factors

The pathophysiology of dystonia remains unclear. Dystonia may occur because of abnormal neurochemical transmission in the basal ganglia, brainstem, or both, resulting in abnormal execution of motor control.Focal dystonias have been associated with loss of inhibition, abnormal plasticity in the motor cortex, and impairments in partial and temporal discrimination. There is debate on the extent to which psychological factors cause dystonia, although they can undoubtedly exacerbate it. Dystonia can be classified as primary (where underlying cause is unknown) or secondary (related to known disorders). The primary disorders may be further classified as hereditary or sporadic. Currently, 15 types of dystonia can be distinguished on a genetic basis, six of which are primary dystonias (DYT1, 2, 4, 6, 7, and 13). The remainder are secondary dystonia, dystonia-plus syndromes, and paroxysmal dystonias.

Prognosis

Dystonia is usually a lifelong disorder, although a small minority experience complete remission. Most people with dystonia have a normal life expectancy, but with continued symptoms. The presence and severity of symptoms are unpredictable, as symptoms may fluctuate over time (e.g. stressful situations may make symptoms worse), or may disappear or stabilise for a time. Regardless of the cause, dystonic contractions may have a chronic course, and may lead to severe persistent pain and disability. Also, embarrassment caused by the symptoms may lead to social withdrawal. Prognosis seems to depend on a number of factors, including age at onset, distribution, and cause. Focal dystonia may become generalised over time. Dystonia with a later age of onset has a lower likelihood of spreading compared with dystonia beginning in childhood. Similarly, dystonia starting in the neck is less likely to spread than dystonia starting in the limbs.

Aims of intervention

To improve quality of life by minimising: immediate symptoms (movement, posture, pain); limitation of activities; pain; and social consequences, with minimal adverse effects of treatment.

Outcomes

Neurological disability: In dystonia clinical trials, outcome is usually measured using disease-specific rating scales: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Tsui scale, Cervical Dystonia Severity Scale (CDSS), Jankovic Rating Scale (JRS), and Blepharospasm Disability Index (BSDI; see table 1 ). Quality of life; adverse effects of treatments.

Table 1.

Commonly used rating scales for dystonia.

Scale	Feature	Interpretation	Range*
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)	Three subscales, assessed by clinician: (1) movement disorder severity (range 0–35) (2) disability (range 0–30) (3) pain (range 0–20)	A decrease in TWSTRS-Total or subscale score indicates an improvement in the person's dystonia. Dystonia trials frequently use TWSTRS-Total or the individual TWSTR-Severity, TWSTRS-Pain, or TWSTRS-Disability scales as the primary outcome	0–85
The Tsui scale	Clinician-assessed scale of impairment that grades severity of postural deviance (rotatocollis, antecollis, retrocollis, head tilt, and elevation of shoulder), acknowledges the presence or absence of head tremor, and includes whether the movements are continuous or intermittent		0–25
Cervical Dystonia Severity Scale (CDSS)	Uses a protractor and wall chart to rate the severity of the head's deviation from neutral in each of the three planes of motion (rotation, laterocollis, anterocollis/retrocollis)
Jankovic Rating Scale (JRS)	Includes two categories: severity and frequency, each with 5 rating classes of 0–4 points		0–8
Blepharospasm Disability Index (BSDI)	Disease-specific self-assessment scale consisting of 6 × 5-point items assessing vehicle driving, reading, watching TV, shopping, getting about on foot, and doing everyday activities	0 = no interference in these activities and 30 = severe interference	0–30
Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS)	Assessment of severity and frequency of dystonia in nine body areas (including eyes, mouth, speech or swallowing, neck, right and left arms, trunk, and right and left legs)	0 = no dystonia and 120 = maximum severity	0–120
Writer’s Cramp Rating Scale (WCRS)	Assessment of writing posture (elbow, wrist, and fingers), movements (latency and tremor), and speed of writing	0 = no impairment and 30 = marked impairment	0–30

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*Higher score indicates greater severity in all scales

Methods

BMJ Clinical Evidence search and appraisal July 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to July 2007, Embase 1980 to July 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 2. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs for all interventions in any language, and also case series for physical therapies; single-blind and open studies acceptable for all, containing more than 20 people, of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table.

GRADE evaluation of interventions for dystonia

Important outcomes	Symptom severity, function improvement, quality of life, adverse effects
Number of studies (participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of drug treatments for focal dystonia?
13 (680)	Symptom severity	Botulinum A v placebo	4	−2	0	0	+1	Moderate	Quality points deducted for no long-term results and for reporting effects of one cycle of treatment. Effect-size point added for odds ratio 2–5
3 (308)	Symptom severity	Botulinum B v placebo	4	0	0	0	+1	High	Effect-size point added for odds ratio 2–5
2 (159)	Symptom severity	Botulinum A v Botulinum B	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for not reporting doses in one study
1 (75)	Symptom severity	High-dose botulinum A v low-dose botulinum A	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for no direct comparison between groups
1 (92)	Symptom severity	High-dose botulinum B v low-dose botulinum B	4	−1	0	0	0	Moderate	Quality point deducted for sparse data.
1 (66)	Symptom severity	Botulinum A v anticholinergic drugs	4	−2	−1	−2	0	Very low	Quality points deducted for sparse data and for short follow-up. Consistency point deducted for conflicting results. Directness points deducted for differences in disease severity between groups and for short cycle intervals between injections affecting generalisability of results
1 (92)	Symptom severity	Botulinum B in Botulinum A resistants v Botulinum B in Botulinum A responders	4	−2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
1 (40)	Symptom severity	Botulinum A v placebo (writer’s cramp)	4	−1	0	0	0	Moderate	Quality point deducted for sparse data
1 (40)	Functional improvement	Botulinum A v placebo (writer’s cramp)	4	−1	0	0	0	Moderate	Quality point deducted for sparse data
What are the effects of drug treatments for generalised dystonia?
No studies found
What are the effects of surgical treatments for focal dystonia?
1 (40)	Functional improvement	Deep brain stimulation v sham stimulation	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and for no long-term results. Directness point deducted for inclusion of people with generalised dystonia affecting generalisability of results
1 (33)	Quality of life	Deep brain stimulation v sham stimulation	4	−2	−1	−1	0	Very low	Quality points deducted for sparse data and for no long-term results. Consistency point deducted for lack of consistent benefit. Directness point deducted for inclusion of people with generalised dystonia affecting generalisability of results
What are the effects of surgical treatments for generalised dystonia?
1 (40)	Functional improvement	Deep brain stimulation v sham stimulation	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and for no long-term results. Directness point deducted for inclusion of people with focal dystonia affecting generalisability of results
1 (33)	Quality of life	Deep brain stimulation v sham stimulation	4	−2	−1	−1	0	Very low	Quality points deducted for sparse data and for no long-term results. Consistency point deducted for lack of consistent benefit. Directness point deducted for inclusion of people with focal dystonia affecting generalisability of results
What are the effects of physical treatments for focal dystonia?
No studies found
What are the effects of physical treatments for generalised dystonia?
No studies found

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Type of evidence: 4 = RCT; 2 = Observational Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio

Glossary

Chiropractic manipulation: These involve manipulation of the spine by a chiropractor. It is based on the theory that manipulating the vertebrae helps normal nervous system functioning and the body's ability to heal itself.
High-quality evidence: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate-quality evidence: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Very low-quality evidence: Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Ailsa Snaith, University of Aberdeen, Aberdeen, UK.

Derick Wade, Oxford Centre for Enablement, Oxford, UK.

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BMJ Clin Evid. 2008 Sep 5;2008:1211.

Acetylcholine receptor inhibitors for focal dystonia

Summary

SYMPTOM SEVERITY Botulinum A compared with placebo: Botulinum A toxin is more effective at 3–16 weeks at improving cervical dystonia as assessed by an improvement in Tsui scale, Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), physician- and patient-rated scores, and the number of people reporting pain relief ( moderate-quality evidence ). Botulinum B compared with placebo: Botulinum B toxin is more effective at 4–8 weeks at improving TWSTRS-Total score ( high-quality evidence ). Botulinum A compared with botulinum B: We don't know whether botulinum A toxin is more effective at 2–4 weeks at improving TWSTRS disease-activity rating scale ( very low-quality evidence ). High-dose compared with low-dose botulinum A: We don't know whether high-dose botulinum A toxin is more effective at increasing patient- and physician-rated improvements (very low-quality evidence). Low-dose compared with high-dose botulinum B: Low-dose botulinum B toxin may be less effective at 4 weeks at improving disease-activity TWSTRS pain subscale (moderate-quality evidence). Botulinum A compared with anticholinergic drugs: Botulinum A may be more effective at 12 weeks than trihexyphenidyl at improving TWSTRS disability scores, Tsui scale, and General Health Perception Subscale (very low-quality evidence). Botulinum B in Botulinum A-resistant adults compared with Botulinum B in Botulinum A responders: We don't know whether botulinum B toxin in botulinum A-resistant adults is more effective at 4 weeks at improving TWSTRS-Total scores (low-quality evidence). Botulinum A compared with placebo (writer's cramp): Botulinum A toxin is more effective at 8 weeks at improving symptom severity scores, writer's cramp rating scales, handwriting, and writing speed (moderate-quality evidence). FUNCTIONAL IMPROVEMENT Botulinum A compared with placebo (writer's cramp): Botulinum A toxin is no more effective at 8 weeks at improving functional status scale (moderate-quality evidence). NOTE We found no clinically important results about botulinum A toxin in the treatment of people with focal dystonia of other body sites (eyelid, larynx, and hand). We found no clinically important results about other acetylcholine receptor inhibitors in the treatment of focal dystonia.

Benefits

Botulinum A toxin versus placebo in cervical dystonia in adults:

We found one systematic review (search date 2003; see table 2 ). It found that botulinum A toxin significantly improved Tsui, and physician- and patient-rated scales at 3–16 weeks compared with placebo. The quality of the 13 trials was assessed by Jadad's scale as good. However, all trials were of short duration, and examined the effects of only one injection cycle.

Table 2.

Botulinum toxin for focal dystonia.

Ref	Population	Comparison	Results
BtA versus placebo in cervical dystonia in adults
Systematic review (search date 2003, 13 RCTs, 680 people)	3 RCTs, 113 adults	BtA v placebo	Improvement of at least 3 points on Tsui scale at 3–6 weeks: 32/56 (57%) with BtA v 13/57 (23%) with placebo; OR 4.25, 95% CI 2.00 to 9.05, P = 0.0002; NNT 4, 95% CI 3 to 6
6 RCTs, 353 adults	BtA v placebo	Any improvement in Tsui or TWSTRS at up to 12 weeks: 97/174 (56%) with BtA v 31/179 (17%) with placebo; OR 5.47, 95% CI 3.52 to 8.48, P less than 0.00001; NNT 3, 95% CI 3 to 4
	11 RCTs, 510 adults	BtA v placebo	Any improvement in subjective patient-rated scales at up to 16 weeks: 161/273 (59%) with BtA v 46/237 (19%) with placebo; OR 6.58, 95% CI 4.55 to 9.54, P less than 0.00001; NNT 3, 95% CI 3 to 3
	4 RCTs, 350 adults	BtA v placebo	Physicians reporting improvement at up to 16 weeks: 123/197 (62%) with BtA v 46/153 (30%) with placebo; OR 4.17, 95% CI 2.70 to 6.44, P less than 0.00001; NNT 3, 95% CI 3 to 5
	5 RCTs, 162 adults	BtA v placebo	Number of people reporting pain relief: 60/84 (71%) with BtA v 9/78 (12%) with placebo; OR 11.92, 95% CI 6.32 to 22.5, P less than 0.00001; NNT 2, 95% CI 2 to 3
	6 RCTs, 421 adults	BtA v placebo	Number of people with any adverse effect: 131/226 (58%) with BtA v 89/195 (46%) with placebo; OR 2.10, 95% CI 1.32 to 3.35, P = 0.002, NNH 6, 95% CI 4 to 15
	10 RCTs, 605 adults	BtA v placebo	Number of people with neck weakness: 62/339 (18%) with BtA v 9/266 (3%) with placebo; OR 4.86, 95% CI 2.55 to 9.25, P less than 0.00001, NNH 8, 95% CI 7 to 10
	10 RCTs, 714 adults	BtA v placebo	Number of people with dysphagia: 60/397 (15%) with BtA v 12/317 (4%) with placebo; OR 3.94, 95% CI 2.15 to 7.19, P less than 0.00001, NNH 10, 95% CI 8 to 14
	6 RCTs, 401 adults	BtA v placebo	Number of people with dry mouth/sore throat: 42/216 (19%) with BtA v 15/185 (8%) with placebo; OR 2.54, 95% CI 1.42 to 4.55, P = 0.002, NNH 10, 95% CI 7 to 21.
	2 RCTs, 210 adults	BtA v placebo	Number of people with voice changes/hoarseness: 15/210 (7%) with BtA v 4/90 (4%) with placebo; OR 2.62, 95% CI 0.98 to 7.01, P = 0.05
BtB versus placebo in cervical dystonia in adults
Systematic review (search date 2003, 3 RCTs, 308 adults with cervical dystonia for at least 1 year and previously treated with BtA, TWSTRS-Total score greater than 20 and TWSTRS-Severity greater than 10)	1 RCT, 122 adults	Single injection of BtB (2500–10,000 U) v placebo	Improvement of at least 20% of TWSTRS-Total score at 4 weeks: 60/92 (65%) with BtB v 8/30 (27%) with placebo; OR 4.69, 95% CI 2.06 to 10.69, P = 0.0002; NNT 3, 95% CI 2 to 6
		At 8 weeks: 40/92 (43%) with BtB v 5/30 (17%) with placebo; OR 3.13, 95% CI 1.34 to 7.34, P = 0.008
		At 12 weeks: 23/92 (25%) with BtB v 3/30 (10%) with placebo; OR 2.43, 95% CI 0.89 to 6.61, P = 0.08
		At 16 weeks: 12/92 (13%) with BtB v 2/30 (7%) with placebo; OR 1.86, 95% CI 0.51 to 6.75, P = 0.3
	2 RCTs, 150 adults	BtB (10,000 U) v placebo	Patient Global Assessment of Change (0–100) at 4 weeks: WMD 20.84, 95% CI 14.22 to 27.45, P less than 0.00001
	1 RCT, 72 adults	BtB (5000 U) v placebo	Patient Global Assessment of Change (0–100) at 4 weeks: WMD 17.00, 95% CI 6.93 to 27.07, P = 0.0009
	2 RCTs, 150 adults	BtB (10,000 U) v placebo	Principal Investigator Global Assessment of Change (0–100) at 4 weeks: WMD 12.52, 95% CI 7.97 to 17.08, P less than 0.00001
	1 RCT, 72 adults	BtB (5000 U) v placebo	Principal Investigator Global Assessment of Change (0–100) at 4 weeks: WMD 13.30, 95% CI 5.50 to 21.50, P = 0.001
	2 RCTs, 150 adults	BtB (10 000 U) v placebo	Patient Analog Pain Assessment (0–100) at 4 weeks: WMD 19.63, 95% CI 11.69 to 27.56, P = 0.001
	1 RCT, 72 adults	BtB (5000 U) v placebo	Patient Analog Pain Assessment (0–100) at 4 weeks: WMD 18.00, 95% CI 5.69 to 30.31, P = 0.004
	3 RCTs, 307 adults	BtB (2500–10,000 U) v placebo	Dry mouth: 45/203 (22%) with BtB v 3/104 (3%) with placebo; OR 5.19, 95% CI 2.69 to 10.03; NNH 6, 95% CI 6 to 8; P less than 0.00001
	3 RCTs, 308 adults	BtB (2500–10,000 U) v placebo	Dysphagia: 39/204 (19%) with BtB v 3/104 (3%) with placebo; OR 4.37, 95% CI 2.18 to 8.79; NNH 8, 95% CI 7 to 11, P less than 0.00003
BtA versus BtB in cervical dystonia in adults
Subsequent RCT	139 adults who previously responded to BtA	BtA (up to 250 U Botox) v BtB (up to 10,000 U MyoBloc)	TWSTRS-Total score at 4 weeks: 9.3 with BtA v 10.2 with BtB; P = 0.75
	TWSTRS severity score at 4 weeks: 3.7 with BtA v 3.7 with BtB; P = 0.90
			TWSTRS disability score at 4 weeks: 2.4 with BtA v 2.5 with BtB; P = 0.71
			TWSTRS pain score at 4 weeks: 3.2 with BtA v 4.0 with BtB; P = 0.24
			Median duration of effect of treatment: 13.0 weeks with BtA v 11.7 weeks with BtB; P = 0.095
			Dysphagia at 4 weeks: 19% with BtA v 48% with BtB; P = 0.0005
			Dry mouth at 4 weeks: 41% with BtA v 80% with BtB; P less than 0.0001
Subsequent RCT	20 adults who responded to BtA within the previous year	BtA v BtB (doses not reported)	TWSTRS severity score at 2 weeks: 14 with BtA v 15 with BtB; significance assessment not reported
	TWSTRS pain score at 2 weeks: 6 with BtA v 4 with BtB; significance assessment not reported
			TWSTRS disability score at 2 weeks: 10 with BtA v 12 with BtB; significance assessment not reported
			Dysphagia: 18% with BtA v 55% with BtB; P = 0.081
			Constipation: 0/11 (0%) with BtA v 3/9 (3.3%) with BtB; P = 0.037
High-dose (greater than 200 U Botox/960 U Dysport) versus low-dose (100 U Botox/250 U Dysport) BtA in cervical dystonia in adults
Systematic review (search date 2003, 13 RCTs, 680 people)	1 RCT, 75 adults	High-dose BtA (greater than 200 U of Botox or 960 U of Dysport) v medium-dose BtA (dose not reported) v low-dose BtA (100 U of Botox or 250 U of Dysport)	Number of people with improvement in patient subjective assessment: Between-group comparison not reported
	3 RCTs, 114 adults	Low-dose BtA (100 U of Botox or 250 U of Dysport) v placebo	Number of people with improvement in patient subjective assessment: 24/56 (43%) with low-dose BtA v 9/58 (16%) with placebo; OR 3.99, 95% CI 1.74 to 9.13; P = 0.001
	7 RCTs, 322 adults	Medium-dose BtA (equivalence not reported) v placebo	Number of people with improvement in patient subjective assessment: 99/161 (61%) with medium-dose BtA v 35/161 (22%) with placebo; OR 6.04, 95% CI 3.77 to 9.66; P less than 0.00001
	3 RCTs, 114 adults	High-dose BtA (greater than 200 U of Botox or 960 U of Dysport) v placebo	Number of people with improvement in patient subjective assessment: 38/56 (68%) with high-dose BtA v 6/58 (10%) with placebo; OR 11.51, 95% CI 5.38 to 24.60; P less than 0.0001
	1 RCT, 75 adults	High-dose BtA (greater than 200 U of Botox or 960 U of Dysport) v medium-dose BtA (not reported) v low-dose BtA (100 U of Botox or 250 U of Dysport)	Number of people with improvement in physician subjective assessment: Between-group comparison not reported
	1 RCT, 39 adults	Low-dose BtA (100 U of Botox or 250 U of Dysport) v placebo	Number of people with improvement in physician subjective assessment: 7/19 (37%) with low-dose BtA v 2/20 (10%) with placebo; OR 4.36, 95% CI 1.00 to 19.00; P = 0.05
	3 RCTs, 162 adults	Medium-dose BtA (equivalence not reported) v placebo	Number of people with improvement in physician-subjective assessment: 52/80 (65%) with medium-dose BtA v 20/82 (24%) with placebo; OR 5.77, 95% CI 3.01 to 11.06; P less than 0.00001
	2 RCTs, 189 adults	High-dose BtA (greater than 200 U of Botox or 960 U of Dysport) v placebo	Number of people with improvement in physician subjective assessment: 64/98 (65%) with high-dose BtA v 28/91 (31%) with placebo; OR 3.92, 95% CI 2.21 to 6.94; P less than 0.00001
	2 RCTs, 78 adults	Low-dose BtA v placebo	Number of people with any adverse effect: OR 0.96, 95% CI 0.37 to 2.46
	5 RCTs, 345 adults	Medium-dose BtA v placebo	Number of people with any adverse effect: OR 2.49, 95% CI 1.47 to 4.22
	1 RCT, 38 adults	High-dose BtA v placebo	Number of people with any adverse effect: OR 15.00, 95% CI 3.03 to 74.32
	1 RCT, 75 adults	Low-dose BtA v placebo	Number of people with dysphagia: OR 2.40, 95% CI 0.38 to 14.97
	6 RCTs, 395 adults	Medium-dose BtA v placebo	Number of people with dysphagia: OR 3.69, 95% CI 1.76 to 7.75
	4 RCTs, 284 adults	High-dose BtA v placebo	Number of people with dysphagia: OR 4.80, 95% CI 1.89 to 12.16
	2 RCTs, 78 adults	Low-dose BtA v placebo	Number of people with neck weakness: OR 3.43, 95% CI 0.51 to 22.96
	7 RCTs, 453 adults	Medium-dose BtA v placebo	Number of people with neck weakness: OR 4.14, 95% CI 2.02 to 8.48
	3 RCTs, 114 adults	High-dose BtA v placebo	Number of people with neck weakness: OR 18.33, 95% CI 3.41 to 98.62
	2 RCTs, 78 adults	Low-dose BtA v placebo	Number of people with sore throat/dry mouth: OR 2.69, 95% CI 0.57 to 12.66
	4 RCTs, 287 adults	Medium-dose BtA v placebo	Number of people with sore throat/dry mouth: OR 2.23, 95% CI 1.12 to 4.45
	2 RCTs, 76 adults	High-dose BtA v placebo	Number of people with sore throat/dry mouth: OR 5.87, 95% CI 1.87 to 18.46
	1 RCT, 39 adults	Low-dose BtA v placebo	Number of people with sore throat/dry mouth: 0/19 (0%) with low-dose BtA v 0/20 (0%) with placebo; OR not estimatable
	2 RCTs, 173 adults	Medium-dose BtA v placebo	Number of people with sore throat/dry mouth: OR 2.75, 95% CI 0.93 to 8.15
	1 RCT, 38 adults	High-dose BtA v placebo	Number of people with sore throat/dry mouth: OR 10.67, 95% CI 1.66 to 68.43
	2 RCTs, 78 adults	Low-dose BtA v placebo	Number of people with local pain at injection site: OR 1.05, 95% CI 0.17 to 6.41
	7 RCTs, 480 adults	Medium-dose BtA v placebo	Number of people with local pain at injection site: OR 1.60, 95% CI 1.00 to 2.54
	4 RCTs, 284 adults	High-dose BtA v placebo	Number of people with local pain at injection site: OR 1.26, 95% CI 0.64 to 2.48
	2 RCTs, 78 adults	Low-dose BtA v placebo	Number of people with malaise/upper respiratory infection: OR 1.05, 95% CI 0.17 to 6.41
	3 RCTs, 185 adults	Medium-dose BtA v placebo	Number of people with malaise/upper respiratory infection: OR 2.05, 95% CI 0.51 to 8.17
	3 RCTs, 246 adults	High-dose BtA v placebo	Number of people with malaise/upper respiratory infection: OR 1.45, 95% CI 0.69 to 3.06
	2 RCTs, 78 adults	Low-dose BtA v placebo	Number of people with headache: OR 1.62, 95% CI 0.26 to 9.91
	5 RCTs, 354 adults	Medium-dose BtA v placebo	Number of people with headache: OR 1.24, 95% CI 0.69 to 2.22
	3 RCTs, 246 adults	High-dose BtA v placebo	Number of people with headache: OR 3.04, 95% CI 0.73 to 12.73
Additional RCT	31 adults	BtA (125 U/mL Dysport) v BtA (500 U/mL Dysport)	Improvement in TWSTRS severity score at 4 weeks: 0.27 with BtA 125 U/mL v 1.07 with BtA 500 U/mL; P = 0.19
			Improvement in TWSTRS disability score at 4 weeks: 2.6 with BtA 125 U/mL v 1.2 with BtA 500 U/mL; P = 0.26
			Improvement in TWSTRS pain score at 4 weeks: 2.7 with BtA 125 U/mL v 2.13 with BtA 500 U/mL; P = 0.92
			Improvement in TWSTRS-Total score at 4 weeks: 5.6 with BtA 125 U/mL v 4.4 with BtA 500 U/mL; P = 0.63
Low-dose (2500–5000 U) versus high-dose (10,000 U) BtB in cervical dystonia in adults
Systematic review (search date 2003)	1 RCT, 92 adults	BtB (2500–5000 U) v BtB (10,000 U)	Improvement in TWSTRS-pain subscale at 4 weeks: 39/62 (63%) with low-dose BtB v 25/30 (83%) with high-dose BtB; OR 0.39, 95% CI 0.15 to 0.99, P = 0.05
			Improvement of at least 20% in TWSTRS-Total score at 4 weeks: 37/62 (60%) with low-dose BtB v 23/30 (77%) with high-dose BtB; OR 0.50, 95% CI 0.20 to 1.25, P = NS
			Improvement of at least 20% in TWSTRS-Total score at 8 weeks: 24/62 (39%) with low-dose BtB v 16/30 (53%) with high-dose BtB; OR 0.56, 95% CI 0.23 to 1.33, P = NS
			Improvement of at least 20% in TWSTRS-Total score at 12: 14/62 (23%) with low-dose BtB v 9/30 (30%) with high-dose BtB; OR 0.68, 95% CI 0.25 to 1.84, P = NS
			Improvement of at least 20% in TWSTRS-Total score at 16 weeks: 7/62 (11%) with low-dose BtB v 5/30 (17%) with high-dose BtB; OR 0.63, 95% CI 0.17 to 2.27, P = NS
Systematic review (search date 2003, 3 RCTs, 308 adults with cervical dystonia for at least 1 year and previously treated with BtA, TWSTRS-Total score greater than 20 and TWSTRS-Severity greater than 10)	2 RCTs, 167 adults	BtB (2500–5000 U) v BtB (10,000 U)	Dry mouth: 9/98 (9%) with low-dose BtB v 27/69 (39%) with high-dose BtB; OR 0.19, 95% CI 0.09 to 0.40; P = 0.00002
2 RCTs, 165 adults	BtB (2500–10,000 U) v BtB (10,000 U)	Dysphagia: 12/98 (12%) with low-dose BtB v 16/67 (24%) with high-dose BtB; OR 0.42, 95% CI 0.18 to 0.98; P = 0.04
BtA versus anticholinergic drugs (trihexyphenidyl) in cervical dystonia in adults
Systematic review (search date 2003)	1 RCT, 66 adults	BtA (Dysport, 292 U in first session, 262 U in second session, under EMG guidance) plus placebo tablets v trihexyphenidyl (mean dose 16.25 mg) plus placebo injection	TWSTRS disability score at 12 weeks: WMD 2.50, 95% CI 0.68 to 4.32, P = 0.0097
	Tsui score at 12 weeks: WMD 4.60, 95% CI 2.14 to 7.06, P = 0.0009
		General Health Perception Subscale difference in mean improvement: 6, 95% CI 4 to 12, P = 0.0023
			Number of people with at least 3-point improvement on Tsui scale: OR 3.92, 95% CI 1.48 to 10.40
			Number of people with at least 3-point improvement on TWSTRS scale: OR 3.14, 95% CI 1.10 to 8.97, NNT 4, CI not reported, P = 0.059 (calculated by the RCT)
			Median improvement in TWSTRS pain scores: 3 with BtA plus placebo v 1 with trihexyphenidyl plus placebo; difference +2, 95% CI –1 to +3
		Trihexyphenidyl (mean dose 16.25 mg) plus placebo injection v BtA (Dysport, 292 U in first session, 262 U in second session, under EMG guidance) plus placebo tablets	Number of adverse effect events in each group: 31 in 32 people with BtA plus placebo v 76 in 32 people with trihexyphenidyl plus placebo; P less than 0.0001
		Dry mouth: OR 7.22, 95% CI 2.72 to 19.12 (absolute numbers not reported); NNH 2, CI not reported
			Forgetfulness: OR 3.51, 95% CI 1.25 to 9.89 (absolute numbers not reported); NNH 3, CI not reported
			Fatigue: OR 9.12, 95% CI 1.92 to 43.40 (absolute numbers not reported); NNH 4, CI not reported
BtB in BtA resistant versus respondent adults
Systematic review (search date 2003)	1 RCT, 92 adults	BtB in people resistant to BtA v BtB in people responsive to BtA	Improvement of at least 20% in TWSTRS-Total score at 4 weeks: No significant difference; data not reported
BtA versus placebo in writer's cramp
RCT	40 treatment-naive people with symptoms of idiopathic writer's cramp for at least 1 year	BtA versus placebo	Mean improvement in symptom severity (assessed using symptom severity scale, reduction in score indicates improvement): –3.60 with botulinum A v –1.16 with placebo; P = 0.02
	Mean improvement in writer's cramp rating scale: –2.30 with botulinum A v –0.79 with placebo; P less than 0.01
			Mean improvement in handwriting (assessed using a visual analogue scale from 0–10 cm): 1.85 with botulinum A v 0.53 with placebo; P = 0.01
			Mean change in writing speed (number of lines written in 2 minutes): 1.41 with botulinum A v 0.27 with placebo; P = 0.04
			Mean improvement in functional status scale (assessed using a 12-item disability scale): +0.65 with botulinum A v –1.42 with placebo; P = 0.10
			Adverse effects: Weakness in the hand: 18/20 (90%) with botulinum A v 2/19 (11%) with placebo; significance not assessed; P value not reported Pain at injection site: 1/20 (5%) with botulinum A v 3/19 (16%) with placebo; significance not assessed; P value not reported

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BtA, botulinum A toxin; BtB, botulinum B toxin; EMG, electromyogram; NS, not significant; Ref, reference; TWSTRS, Toronto Western Spasmodic Torticollis Rating Scale.

Botulinum B toxin versus placebo in cervical dystonia in adults:

We found one systematic review (search date 2003; see table 2 ). It found that a single injection cycle of botulinum B toxin (dose 2500–10,000 U) significantly improved the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total score at 4 and 8 weeks by at least 20% compared with placebo, but found no significant difference at 12 or 16 weeks. The review also found that botulinum B toxin (5000–10,000 U) significantly improved Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, and Patient Analog Pain Assessment at 4 weeks compared with placebo. Of the three RCTs included in the systematic review, one RCT included both people responsive and resistant to botulinum A toxin, one RCT included only people resistant to botulinum A toxin, and one RCT included only people responsive to botulinum A toxin. The quality of the three RCTs was assessed as good by Jadad's scale.

Botulinum A toxin versus botulinum B toxin in cervical dystonia in adults:

We found one systematic review (search date 2003), which identified no RCTs. We found two subsequent RCTs (see table 2 ). The first RCT found no significant difference between botulinum A toxin (up to 250 U) and botulinum B toxin (up to 10,000 U) in TWSTRS scores at 4 weeks. It also found no significant difference between botulinum A and botulinum B toxin in the median duration of effect of treatment. The second RCT found similar TWSTRS scores at 2 weeks between botulinum A (dose not reported) and botulinum B toxin (dose not reported).

High-dose (greater than 200 U Botox/960 U Dysport) versus low-dose (100 U Botox/250 U Dysport) botulinum A toxin in cervical dystonia in adults:

We found one systematic review (search date 2003; see table 2 ). It found no RCTs directly comparing high- and low-dose botulinum A toxin. However, it reported indirect meta-analyses by dose of botulinum A toxin compared with placebo. It found limited evidence that higher doses increased effect sizes for improvement of patient and physician subjective assessment (time of follow-up unclear). Indirect comparisons should be treated with caution as they lose the benefit of the randomisation in the trials they analyse. We found one additional RCT (see table 2 ). It found no significant difference in improvement in TWSTRS scores at week 4 between high- (500 U/mL) and low-dose (125 U/mL) botulinum A toxin.

Low-dose (2500–5000 U) versus high-dose (10,000 U) botulinum B toxin in cervical dystonia in adults:

We found one systematic review (search date 2003; see table 2 ). It found that significantly fewer people had improved TWSTRS pain subscale at 4 weeks with low-dose botulinum B toxin compared with high-dose botulinum B toxin. However, it found no significant difference for the same comparison in TWSTRS-Total score at 4–16 weeks.

Botulinum A toxin versus anticholinergic drugs (trihexyphenidyl) in cervical dystonia in adults:

We found one systematic review (search date 2003; see table 2 ). It found that botulinum A toxin significantly improved a number of outcomes at 12 weeks compared with trihexyphenidyl (TWSTRS disability score, Tsui scale, and number of people with at least 3-point improvement on Tsui scale, General Health Perception Subscale difference in mean improvement). The systematic review found that significantly more people had at least a three point improvement on the TWSTRS scale, but the RCT itself found no significant difference between treatments. The review also found no significant difference between treatments in the median improvement in TWSTRS pain score. The systematic review commented on some limitations of the RCT it found: there were significantly fewer people with history of progressive disease in the botulinum A toxin group than in the trihexyphenidyl group (9/33 [27%] with botulinum A toxin v 21/33 [64%] with trihexyphenidyl; P = 0.003); the short duration of the RCT may not favour trihexyphenidyl; and people were injected with botulinum A toxin at baseline and 8 weeks later, which is a shorter interval than the 12–16 week interval between injections which would generally be used in clinical practice.

Botulinum B toxin in botulinum A toxin-resistant versus respondent adults:

We found one systematic review (search date 2003; see table 2 ). It found no significant difference after botulinum B toxin in TWSTRS-Total score at 4 weeks between people resistant to botulinum A toxin and people responsive to botulinum A toxin.

Botulinum A toxin versus placebo in blepharospasm (eyelid closure):

We found one systematic review (search date 2003). It identified no RCTs of sufficient quality.

Botulinum A toxin versus placebo in spasmodic dysphonia (laryngeal dystonia):

We found one systematic review (search date 2005). The review identified one RCT that did not meet BMJ Clinical Evidence inclusion criteria (RCT included only 13 people), and so the results are not discussed further.

Botulinum A toxin versus placebo in writer's cramp:

We found one RCT (40 treatment-naive people with symptoms of idiopathic writer's cramp for at least 1 year), which compared botulinum A versus placebo. At 8 weeks, the RCT found significant improvements in symptom severity, writer's cramp rating scale, handwriting, and speed of writing with botulinum A compared with placebo (see table 2 ). However, there was no significant difference between treatments in functional status (see table 2 ). To optimise treatment effect, people were treated in two sessions: initially after baseline assessment, and then 1 month later. People expressing satisfaction with their improvement after one treatment did not receive a second injection. However, if people showed no response to treatment after one session, the dose was doubled for the second session. The primary outcome assessed was the person's response to a question on whether they wished to continue with treatment (assessed at 12 weeks). This is not one of our outcomes of interest, and so the results are not discussed further. Clinical rating scales were measured as secondary outcomes.

Harms

Botulinum A toxin versus placebo in cervical dystonia in adults:

The review found generally transient, mild to moderate or intermittent adverse effects in people taking botulinum A toxin (neck weakness, dysphagia, dry mouth/sore throat, voice changes, hoarseness, pain at injection site, drowsiness, vertigo, dizziness, diffuse weakness, asthenia, tiredness, malaise, upper respiratory infection, headache, and paraesthesias; see table 2 ). It found that significantly more people had any adverse effect (neck weakness, dysphagia, or dry mouth/sore throat) with botulinum A toxin compared with placebo (see table 2 ).

Botulinum B toxin versus placebo in cervical dystonia in adults:

The review found significantly more dry mouth and dysphagia with botulinum B toxin than with placebo (see table 2 ).

Botulinum A toxin versus botulinum B toxin in cervical dystonia in adults:

The first subsequent RCT found significantly less dysphagia and dry mouth with botulinum A toxin than with botulinum B (see table 2 ). The second subsequent RCT found no significant difference in dysphagia. It found significantly less constipation with botulinum A toxin than with botulinum B.

High-dose (greater than 200 U Botox/960 U Dysport) versus low-dose (100 U Botox/250 U Dysport) botulinum A toxin in cervical dystonia in adults:

The review found no RCTs directly comparing high- and low-dose botulinum A toxin. However, it reported meta-analyses by dose of botulinum A toxin compared with placebo (see table 2 ). It found increasing incidence of the following adverse effects with increasing dose of botulinum A toxin compared with placebo: neck weakness, dysphagia, dry mouth/sore throat, and voice changes/hoarseness. It did not find the same association for pain at injection site, malaise/upper respiratory infection, and headache. The additional RCT gave no information on adverse effects (see table 2 ).

Low dose (2500–5000 U) versus high-dose (10,000 U) botulinum B toxin in cervical dystonia:

The review found significantly less dry mouth and dysphagia with low-dose compared with high-dose botulinum B toxin.

Botulinum A toxin versus anticholinergic drugs (trihexyphenidyl) in cervical dystonia in adults:

The review found significantly fewer adverse effects (dry mouth, forgetfulness, and fatigue) with botulinum A toxin than with trihexyphenidyl (see table 2 ). It also found no significant difference between botulinum A toxin and trihexyphenidyl for other adverse events reported (blurred vision, dizziness, depression, disturbances of micturition, weight loss, dyspepsia, pain at injection site, dysphagia, and neck weakness).

Botulinum B toxin in botulinum A toxin-resistant versus respondent adults:

The review gave no information on adverse effects for this comparison.

Botulinum A toxin versus placebo in blepharospasm (eyelid closure):

The review identified no RCTs.

Botulinum A toxin versus placebo in spasmodic dysphonia (laryngeal dystonia):

We found one systematic review, which identified no RCTs meeting BMJ Clinical Evidence inclusion criteria.

Botulinum A toxin versus placebo in writer's cramp:

The RCT found that only two types of adverse effect (hand weakness and injection-site pain) were treatment related. A larger proportion of people in the botulinum A toxin group than in the placebo group reported hand weakness (see table 2 ). However, a smaller proportion of people in the botulinum A toxin group than in the placebo group reported injection-site pain (see table 2 ).

Comment

Clinical guide:

Botulinum toxin injections are the mainstay of management of cervical dystonia, and have replaced most treatments used in previous decades. It is sometimes used for other focal dystonias, but with caution, because many focal dystonias may have a primarily psychological origin. The evidence supporting botulinum toxin in focal dystonias is strong, partly because there is a strong commercial imperative to show effectiveness, but also because treatment can be localised, and because botulinum toxin is effective at reducing neuromuscular transmission. Its main limitation is that the effect wears off after 12–16 weeks, but repeated injections are usually equally effective. Invasive surgical procedures have largely been displaced by local botulinum toxin injections.

Dosage:

The two commercially available formulations of botulinum A toxin, Dysport and Botox, differ in potency, and so are not interchangeable. One crossover RCT suggested a conversion of 3 U of Dysport to 1 U of Botox, although there were differences in both beneficial outcomes and in adverse effects. The adverse effects unequivocally associated with botulinum toxin injection are those expected from its local action, and they are more common with higher doses — as one would expect from local spread from the injected muscle. The differences in beneficial and adverse effects reflect relative differences in dosage, not intrinsic differences between preparations.

Substantive changes

Botulinum toxin (focal) One RCT on the effects of botulinum A in treatment of writer's cramp added;benefits and harms data enhanced; categorisation unchanged (Beneficial). At 8 weeks, the RCT found significant improvements in symptom severity, writer's cramp rating scale, handwriting, and speed of writing with botulinum A compared with placebo. However, there was no significant difference between groups at 8 weeks in functional status.

BMJ Clin Evid. 2008 Sep 5;2008:1211.

Anticholinergic drugs for focal dystonia

Summary

SYMPTOM SEVERITY Compared with Botulinum A: Trihexyphenidyl may be less effective at 12 weeks at improving Toronto Western Spasmodic Torticollis Rating Scale disability scores, Tsui scale, and General Health Perception Subscale ( very low-quality evidence ).

Benefits

Anticholinergic drugs versus botulinum toxin A in cervical dystonia:

See benefits of botulinum toxin A versus anticholinergic drugs (trihexyphenidyl) in cervical dystonia.

Harms

Anticholinergic drugs versus botulinum toxin A in cervical dystonia:

See harms of botulinum toxin A versus anticholinergic drugs (trihexyphenidyl) in cervical dystonia.

We found no RCTs.

We found no RCTs.

We found no RCTs.

Comment

See comment on myectomy under surgical treatments for focal dystonia.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Sep 5;2008:1211.

Deep brain stimulation of thalamus and globus pallidus for generalised dystonia

Summary

Benefits

We found no systematic review or RCTs of deep brain stimulation of the thalamus in people with only generalised dystonia. We found one RCT (40 people aged 14–75 years with primary segmental [16 people] or generalised dystonia [24 people] for a minimum of 5 years) which compared deep brain stimulation of the internal globus pallidus versus sham stimulation.The RCT found that, at 3 months, deep brain stimulation significantly improved total movement (with imputation) and disability scores on the Burke–Fahn–Marsden Dystonia (BFMD) Rating Scale, and physical component of the quality-of-life score (assessed using SF-36 questionnaire) compared with sham stimulation (change in BFMD score from baseline for movement [possible range of scores of 0–120]: –15.8 with neurostimulation v –1.4 with sham stimulation; P less than 0.001: change in BFMD score from baseline for disability [possible range of scores of 0–30]; –3.9 with neurostimulation v –0.8 with sham stimulation; P less than 0.001: change in SF-36 physical component score [possible range of scores of 0–100]: 10.1 with neurostimulation v 3.8 with sham stimulation; P = 0.02). However, there was no significant difference between groups in the mental component of the quality-of-life score (change in SF-36 mental component score [33 people assessed; possible range of scores of 0–100]: 5.2 with neurostimulation v 0.2 with sham stimulation; P = 0.39). The RCT analysed data for all people who underwent randomisation (last observation carried forward). The RCT did not carry out a subgroup analysis of people with generalised dystonia, which may affect the generalisability of the results.

Harms

Comment

Studies with longer follow-up are required (see comment in deep brain stimulation of thalamus and globus pallidus in people with focal dystonia). See comment on acetylcholine receptor inhibitors for generalised dystonia.

No new evidence

BMJ Clin Evid. 2008 Sep 5;2008:1211.

Physiotherapy for focal dystonia

Summary

We found no clinically important results about the effects of physiotherapy in the treatment of children with developmental cervical dystonia or early congenital cervical dystonia. We found no clinically important results about physiotherapy compared with myomectomy in people with focal dystonia.

Benefits

Physiotherapy in children with developmental cervical dystonia:

We found no systematic review or RCTs. We found one case series (23 children, mean age 3.8 months [range 3 weeks–10.5 months] diagnosed with developmental cervical dystonia), which examined the effect of passive cervical stretching by positioning and active strengthening of identified weak muscles (see comment below). The average number of treatments was 3.8 [range 1.0–10.0] provided over mean treatment duration of 2.9 months. At follow-up (mean age at follow-up: 18 months, range 5–49 months), the case series found that a similar number of parents reported “good” or “excellent” outcomes in their children (excellent = symmetrical head features, symmetrical facial features, passive cervical rotation of at least 75 bilaterally, passive cervical lateral flexion of at least 40 bilaterally, complete head righting, and lack of resting head tilt; good = 4–5 of these outcomes; fair = 3 of these outcomes; poor = 1–2 of the outcomes: 11/23 [48%] excellent v 11/23 [48%] good v 1/23 [4%] fair v 0/23 [0%] poor).

Physiotherapy in children with early congenital cervical dystonia:

We found no systematic review or RCTs. We found one case series (126 children with mild to severe congenital cervical dystonia seen over 30 years), which examined the effect of passive stretching exercises (PSE). Subjective physician measurement of PSE showed that PSE for early congenital cervical dystonia (less than 3 months) produced excellent results in 52/81 (65%) of cases at an average follow-up of 9 months (excellent = full rotation and no asymmetry; good = full rotation and mild asymmetry or mild limitation of rotation and no asymmetry; fair = mild limitation of rotation and mild asymmetry; poor = no improvement: 65% excellent v 27% good v 8% fair v 0% poor).

Physiotherapy versus myectomy:

We found no systematic review, RCTs, or case series.

Harms

Physiotherapy in children with developmental cervical dystonia:

The case series gave no information on adverse effects.

We found no RCTs or case series.

Comment

See comment on acetylcholine receptor inhibitors for generalised dystonia.

Substantive changes

No new evidence

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PERMALINK

Dystonia

Ailsa Snaith

Derick Wade

Roles

Abstract

Introduction

Methods and outcomes

Results

Conclusions

Key Points

About this condition

Definition

Incidence/ Prevalence

Aetiology/ Risk factors

Prognosis

Aims of intervention

Outcomes

Table 1.

Methods

Table.

Glossary

Disclaimer

Contributor Information

References

Acetylcholine receptor inhibitors for focal dystonia

Summary

Benefits

Botulinum A toxin versus placebo in cervical dystonia in adults:

Table 2.

Botulinum B toxin versus placebo in cervical dystonia in adults:

Botulinum A toxin versus botulinum B toxin in cervical dystonia in adults:

High-dose (greater than 200 U Botox/960 U Dysport) versus low-dose (100 U Botox/250 U Dysport) botulinum A toxin in cervical dystonia in adults:

Low-dose (2500–5000 U) versus high-dose (10,000 U) botulinum B toxin in cervical dystonia in adults:

Botulinum A toxin versus anticholinergic drugs (trihexyphenidyl) in cervical dystonia in adults:

Botulinum B toxin in botulinum A toxin-resistant versus respondent adults:

Botulinum A toxin versus placebo in blepharospasm (eyelid closure):

Botulinum A toxin versus placebo in spasmodic dysphonia (laryngeal dystonia):

Botulinum A toxin versus placebo in writer's cramp:

Harms

Botulinum A toxin versus placebo in cervical dystonia in adults:

Botulinum B toxin versus placebo in cervical dystonia in adults:

Botulinum A toxin versus botulinum B toxin in cervical dystonia in adults:

High-dose (greater than 200 U Botox/960 U Dysport) versus low-dose (100 U Botox/250 U Dysport) botulinum A toxin in cervical dystonia in adults:

Low dose (2500–5000 U) versus high-dose (10,000 U) botulinum B toxin in cervical dystonia:

Botulinum A toxin versus anticholinergic drugs (trihexyphenidyl) in cervical dystonia in adults:

Botulinum B toxin in botulinum A toxin-resistant versus respondent adults:

Botulinum A toxin versus placebo in blepharospasm (eyelid closure):

Botulinum A toxin versus placebo in spasmodic dysphonia (laryngeal dystonia):

Botulinum A toxin versus placebo in writer's cramp:

Comment

Clinical guide:

Dosage:

Substantive changes

Anticholinergic drugs for focal dystonia

Summary

Benefits

Anticholinergic drugs versus botulinum toxin A in cervical dystonia:

Harms

Anticholinergic drugs versus botulinum toxin A in cervical dystonia:

Comment

Clinical guide:

Substantive changes

Anticonvulsants for focal dystonia

Summary

Benefits

Harms

Comment

Substantive changes

Atypical antipsychotic drugs for focal dystonia

Summary

Benefits

Harms

Comment

Substantive changes

Benzodiazepines for focal dystonia

Summary

Benefits

Harms

Comment