Cervical dystonia: clinical and therapeutic features in 85 patients

We studied patients with cervical dystonia (CD) to determine clinical features and response to botulinum toxin A (BoNT/A). Patients were submitted to clinical, laboratory and neuroimaging evaluation. BoNT/A was injected locally in 81 patients using electromyographic guidance. Four patients who had had previous treatment were considered to be in remission. The average ages at onset of focal dystonia and segmental dystonia were greater than for generalized dystonia (p<0.0003). The severity of the abnormal head-neck movements were more severe among the patients with generalized dystonia (p<0.001). Pain in the cervical area was noted in 59 patients. It was not possible to determine the etiology of the disease in 62.3% of patients. Tardive dystonia was the most common secondary etiology. A major improvement in the motor symptoms of CD and pain was observed in patients following treatment with BoNT/A. The tardive dystonia subgroup did not respond to the treatment. Dysphagia was observed in 2.35% of the patients.     

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD). Background: Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients. METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16. RESULTS: A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group. CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.     

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.     

Health related quality of life is improved by botulinum neurotoxin type A in long term treated patients with focal dystonia

OBJECTIVES: The advent of botulinum neurotoxin type A (BoNT/A) gave rise to substantial progress in the treatment of focal dystonias. In the light of the high costs of the toxin and the necessity to establish valid outcome indices for this treatment apart from sheer reduction of dystonic muscle tone and posture, the impact of focal dystonia and its treatment with BoNT/A on patients' health related quality of life (HRQL) was determined. METHODS: Fifty patients with cranial and cervical dystonia treated long term with BoNT/A were enrolled in a prospective, open labelled cohort study. The HRQL was assessed using the EuroQol (EQ-5D) and the short form 36 health survey questionnaire (SF-36) at baseline before BoNT/A injections and at two follow up visits after 6 and 12 weeks covering one BoNT/A treatment period with maximum effect size at the first follow up. RESULTS: Compared with a general population sample, a considerable negative impact of focal dystonia on HRQL was found in patients under investigation. In both disease types, BoNT/A treatment led to a significant improvement in several HRQL dimensions, in particular providing moderate to marked effect sizes in the fields of mental health and pain. The impairment of HRQL due to pain as well as the BoNT/A induced improvement within this SF-36 subscore were significantly higher in patients with cervical dystonia. Under BoNT/A therapy, no correlation was found between changes of clinical outcome scores and HRQL measures. CONCLUSIONS: The data confirm that BoNT/A is able to induce a significant, but temporary amelioration of several aspects of HRQL in both types of focal dystonia. This may substantially contribute to the patients' subjective benefit from the therapy. Moreover, the data provide further arguments to accept high costs of the BoNT/A treatment in these severely handicapped patients, as a consequence of its considerable benefit on quality of life.     

EFNS guidelines on diagnosis and treatment of primary dystonias

Objectives: To provide a revised version of earlier guidelines published in 2006. Background: Primary dystonias are chronic and often disabling conditions with a widespread spectrum mainly in young people. Diagnosis: Primary dystonias are classified as pure dystonia, dystonia plus or paroxysmal dystonia syndromes. Assessment should be performed using a validated rating scale for dystonia. Genetic testing may be performed after establishing the clinical diagnosis. DYT1 testing is recommended for patients with primary dystonia with limb onset before age 30, and in those with an affected relative with early‐onset dystonia. DYT6 testing is recommended in early‐onset or familial cases with cranio‐cervical dystonia or after exclusion of DYT1. Individuals with early‐onset myoclonus should be tested for mutations in the DYT11 gene. If direct sequencing of the DYT11 gene is negative, additional gene dosage is required to improve the proportion of mutations detected. A levodopa trial is warranted in every patient with early‐onset primary dystonia without an alternative diagnosis. In patients with idiopathic dystonia, neurophysiological tests can help with describing the pathophysiological mechanisms underlying the disorder. Treatment: Botulinum toxin (BoNT) type A is the first‐line treatment for primary cranial (excluding oromandibular) or cervical dystonia; it is also effective on writing dystonia. BoNT/B is not inferior to BoNT/A in cervical dystonia. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for primary generalized or cervical dystonia, after medication or BoNT have failed. DBS is less effective in secondary dystonia. This treatment requires a specialized expertise and a multidisciplinary team.     

Neutralizing botulinum toxin type a antibodies: clinical observations in patients with cervical dystonia

Neutralization of antibodies poses a problem for a substantial number of cervical dystonia (CD) patients treated with botulinum toxin type A (BoNT/A). Presence of these antibodies may lead to a secondary nonresponse to BoNT/A treatment. In this study, we compared 6 antibody-positive (Ab+) with 12 antibody- negative (Ab-) CD patients treated with BoNT/A (Dysport) and matched for du- ration of treatment, number of BoNT/A injections, and severity of clinical symptoms. The two groups differed in cumulative BoNT/A dose (Ab+, 5984 mouse units [MU ], SD = 3151 MU; Ab-, 3143 MU, SD =1294 MU; P <.05), in addition, ab+ patients were significantly younger (ab+ mean age = 41.3 y, sd =5.9 y; ab - mean age = 56.8 y, sd = 15.3 y; p <.05), in or- der to avoid formation of neutralizing antibodies, doses of bont/a should be kept as low as possible, the risk of antibody formation seems to be higher in younger patients.     

Depletion of neutralising antibodies resensitises a secondary non-responder to botulinum A neurotoxin

The objective was to evaluate whether removal of neutralisingantibodies potentially resensitises a secondary non-responder tobotulinum neurotoxin A (BoNT/A). Neutralising antibodies directed against BoNT/A are produced during long term treatment withBoNT/A-hemagglutinin complex in up to 10% of patients with cervicaldystonia. These patients become secondary non-responders. Otherserotypes of BoNT are not yet generally available and may also bear therisk of inducing antibody formation. Plasma exchange (PE) (onetreatment cycle) and immunoadsorption on a protein A column (IA-PA;three treatment cycles) was employed over 15 months to removeneutralising antibodies from a severely disabled secondarynon-responder with cervical dystonia. After plasmaexchange or IA-PA, BoNT/A was reinjected. Antibodies were measured witha sensitive functional toxin neutralising test.
Repeated use of plasma exchange and IA-PA depletedneutralising antibodies to below the detection limit and subsequently allowed successful BoNT/A injection into dystonic muscles. No seriousside effects were found related to the depletion of IgG.
In conclusion PE or IA-PA performed before BoNT/Areadministration may provide an alternative strategy in treatingselected secondary non-responders who are severely disabled.

     

Botulinum toxin therapy for cervical dystonia

Cervical dystonia (CD) is the most common form of focal dystonia treated with botulinum toxin (BoNT) injections. BoNT has been shown in numerous clinical trials to correct the abnormal posture and movement and to markedly reduce pain associated with CD. In addition, BoNT has favorably modified the natural history of the disease by preventing contractures and other complications of CD, such as secondary degenerative changes of the cervical spine and associated radiculopathy. In a long-term follow-up of patients treated for up to 20 years, the duration of response appears to be sustained and the risk of immunoresistance due to blocking antibodies is relatively small. This review provides and update on the treatment of CD with BoNT type A (BOTOX, Dysport, Xeomin and BoNT type B (Myobloc, NeuroBloc.     

The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part I): muscle afferent block versus botulinum toxin-A in cervical and limb dystonias

Botulinum toxin (BoNT) is an established mainstay treatment for dystonia. However, its use, especially in developing countries, is significantly limited by its cost. Chemodenervation with muscle afferent block (MAB) using lidocaine-ethanol may provide a more cost-effective alternative to traditional BoNT injections. A study comparing MAB with BoNT type-A in cases of X-linked dystonia-Parkinsonism (XDP) having cervical dystonia indicated a modest and short-lived efficacy with MAB, while a more robust efficacy in dystonia and pain parameters, lasting up to 11 weeks, was observed in the two BoNT type-A preparations (Dysport? and Botox?). In another study comparing BoNT type-A formulations for limb dystonia of XDP, a prior MAB was used to select target muscles for toxin injection. During toxin injections in the limb muscles, Dysport? and Botox? did not show significant differences with regard to global severity and disability scales, duration of effect, and adverse event (AE) profile. Dysphagia was the most common AE following BoNT type-A injections in cervical dystonia, while weakness was the most frequent AE noted with injections for limb dystonia. MAB injections carried a high incidence of dizziness and pain during injections. However, because MAB is a more cost-effective alternative that can be given repeatedly, it has been used in the XDP population while awaiting funds for BoNT type-A and/or for selecting muscles for injection as a test drug.     

Human T-cell responses to botulinum neurotoxin: proliferative responses in vitro of lymphocytes from botulinum neurotoxin A-treated movement disorder patients

We determined the T-cell responses against botulinum neurotoxin type A (BoNT/A) and tetanus toxin (TeNT) of peripheral blood lymphocytes from 95 BoNT-treated patients and 63 non-treated control subjects. The patient group included 80 cervical dystonia and 15 other movement disorder cases. Positive T-cell responses to BoNT/A were detected in 70% of the treated patients, and in only 3% of controls. T-cell responses of BoNT-treated patients against BoNT/A did not differ between patients who were clinically responsive and those who had become non-responsive to the treatment. BoNT-treated patients gave significantly higher in vitro T-cell responses to TeNT than did the controls.     

Botulinum toxin type B vs. type A in toxin‐naïve patients with cervical dystonia: Randomized,double‐blind,noninferiority trial

The objective of this study was to compare efficacy, safety, and duration of botulinum toxin type A (BoNT‐A) and type B (BoNT‐B) in toxin‐naïve cervical dystonia (CD) subjects. BoNT‐naïve CD subjects were randomized to BoNT‐A or BoNT‐B and evaluated in a double‐blind trial at baseline and every 4‐weeks following one treatment. The primary measure was the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) from baseline to week 4 post‐injection. Secondary measures included change in TWSTRS‐subscale scores, pain, global impressions, and duration of response and safety assessments. The study was designed as a noninferiority trial of BoNT‐B to BoNT‐A. 111 subjects were randomized (55 BoNT‐A; 56 BoNT‐B). Improvement in TWSTRS‐total scores 4 weeks after BoNT‐B was noninferior to BoNT‐A (adjusted means 11.0 (SE 1.2) and 8.8 (SE 1.2), respectively; per‐protocol‐population (PPP)). The median duration of effect of BoNT‐A and BoNT‐B was not different (13.1 vs. 13.7 weeks, respectively; P‐value = 0.833; PPP). There were no significant differences in the occurrence of injection site pain and dysphagia. Mild dry mouth was more frequent with BoNT‐B but there were no differences for moderate/severe dry mouth. In this study, both BoNT‐A and B were shown to be effective and safe for the treatment of toxin‐naive CD subjects. © 2007 Movement Disorder Society     

Ninhydrin sweat test: a simple method for detecting antibodies neutralizing botulinum toxin type A.

Approximately 5% of patients with cervical dystonia receiving repeated botulinum neurotoxin A (BoNT/A) injections develop secondary loss of treatment benefit. Currently available tests to directly detect neutralizing BoNT/A antibodies (BoNT/A-AB) are either expensive or time consuming. To establish a simple, clinically useful test for antibody detection, we adapted the ninhydrin sweat test (NST). Eighteen dystonic patients with secondary nonresponse and clinically suspected BoNT/A-AB formation were tested for BoNT/A-AB in the mouse diaphragm test (MDT). In addition, the size of the anhidrotic area was determined by the NST 21 days after an intradermal dose of 10 U Dysport into the hypothenar region of the left palm. In nine patients, positive BoNT-AB titers were found in the MDT. There was a significant correlation between the BoNT/A-AB titers and the anhidrotic area (Spearman's rho = -0.9, P < 0.0001). Both tests provided comparably good results with respect to qualitative antibody detection. In the clinical situation of secondary nonresponse to BoNT/A therapy, the economical NST may be a helpful tool to detect neutralizing BoNT/A-AB.     

Clinical application of botulinum toxin

The clinical application of botulinum toxin (BoNT) was first proposed by Justinus Kerner in 1822. BoNT was formally accepted as a therapeutic agent in the 1970s, and currently, it is used worldwide for treating diseases as well as for cosmetic conditions. In Japan, Botox? is the only type A formulation that has been officially approved for the treatment of blepharospasm, hemifacial spasm, cervical dystonia, pes equinus of cerebral palsy, adult spasticity of upper and lower limbs, and Botox Vista? is applied for glabellar frown lines. Its effect is symptomatic, but long-lasting remission is noted after treatment in more than 30% of cases with cervical dystonia. Ultrasound guidance is useful and may be even superior to electromyographic monitoring, especially when the obliquus capitis inferior muscle is targeted in rotatocollis, because the vertebral artery or upper cervical nerve root(s) may be injured when the needle penetrates the muscle. BoNT alleviates pain or glandular secretion besides causing a neuromuscular block. After being transported to the axons, BoNT is carried centrally and even to the adjacent neurons via synapses (toxin jump). A direct central action has also been postulated. BoNT is generally safe, but serious adverse reactions may occur very rarely. Individual differences in toxin sensitivity may be considerably greater than assumed, and even the routine clinical dose may be too high in some patients. The future strategy includes clinical application of other types of toxin or chimera toxins, or the use of the toxin as a cargo ("Trojan Horse") carrying some bioactive molecules into the cell. A non-injection procedure for mucosal application or cosmetic use is currently under clinical trials.     

Botulinum toxin type A and cervical dystonia: a seven-year follow-up

Most cases of cervical dystonia (CD) are idiopathic, and focal injections of botulinum toxin A (BoNT/A) are the treatment of choice. The objective of our study was to document the effects of long-term BoNT/A treatment in idiopathic CD patients. Fifty-eight patients with idiopathic CD were recruited from March 2001 to May 2002. Twenty-eight of the subjects were available for reassessment after seven years. During this period, all had received regular treatment with BoNT/A injections. Clinical information about patients and the severity of CD (TWSTRS and VAPS) at baseline assessment (2001-2002) and follow-up (2008-2009) was compared. Significant motor improvement was detected based on TWSTRS scale scores, which were used to analyze clinical severity (19.6 ± 6.6 and 17.7 ± 4.8; p<0.05). There was no improvement in the severity of cervical pain (p=0.43). In conclusion, BoNT/A was a safe and effective long-term therapy for CD.     

Use of botulinum neurotoxin therapy

Botulinum neurotoxins (BoNTs), produced by the gram-positive anaerobic bacterium Clostridium botulinum, act on motor nerve endings and induce muscle relaxation. BoNT type A and B are used as therapeutic agents. Several preparations of BoNT type A are commercially available; Botox?, Dysport?, and Xeomin? are popular. They differ in the manufacturing method used, for example, BoNT consists of neurotoxin and a complex protein, Botox? and Dysport? contain a complex protein, whereas Xeomin? is free from the protein. However, when applied clinically, there is no significant difference in the efficacy and adverse effects between these BoNT products. Intramuscular BoNT injection is widely recognized as a safe and effective treatment for blepharospasm, hemifacial spasm, cervical dystonia, spasticity, squint, migraine, hyperhidrosis, wrinkles (cosmetic purpose), achalasia, hyperactive bladder, etc. BoNT preparations are used in more than 70 countries. In Japan, BoNT is used to treat blepharospasm, hemifacial spasm, cervical dystonia, and spasticity in addition to being used to treat wrinkles. However, its use is not yet widespread in Japan. This article reviews the structure and characteristics of BoNT, and throws light upon the technique of injecting BoNT.     

A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task Force

To review the literature on primary dystonia and dystonia plus and to provide evidence-based recommendations. Primary dystonia and dystonia plus are chronic and often disabling conditions with a widespread spectrum mainly in young people. Computerized MEDLINE and EMBASE literature reviews (1966-1967 February 2005) were conducted. The Cochrane Library was searched for relevant citations. Diagnosis and classification of dystonia are highly relevant for providing appropriate management and prognostic information, and genetic counselling. Expert observation is suggested. DYT-1 gene testing in conjunction with genetic counselling is recommended for patients with primary dystonia with onset before age 30 years and in those with an affected relative with early onset. Positive genetic testing for dystonia (e.g. DYT-1) is not sufficient to make diagnosis of dystonia. Individuals with myoclonus should be tested for the epsilon-sarcoglycan gene (DYT-11). A levodopa trial is warranted in every patient with early onset dystonia without an alternative diagnosis. Brain imaging is not routinely required when there is a confident diagnosis of primary dystonia in adult patients, whereas it is necessary in the paediatric population. Botulinum toxin (BoNT) type 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 and can be effective in writing dystonia. Actual evidence is lacking on direct comparison of the clinical efficacy and safety of BoNT-A vs. BoNT-B. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for generalized or cervical dystonia, after medication or BoNT have failed to provide adequate improvement. Selective peripheral denervation is a safe procedure that is indicated exclusively in cervical dystonia. Intrathecal baclofen can be indicated in patients where secondary dystonia is combined with spasticity. The absolute and comparative efficacy and tolerability of drugs in dystonia, including anticholinergic and antidopaminergic drugs, is poorly documented and no evidence-based recommendations can be made to guide prescribing.     

Treatment with botulinum toxin: An update

Botulinum neurotoxin (BoNT) is a potent toxin produced by the anaerobic bacterium clostridium botulinum. It causes flaccid, long-lasting, local and reversible paralysis. In addition, BoNT inhibits the secretion of the exocrine glands and could have properties in the control of pain. Thus, BoNT is useful in the treatment of many neuromuscular conditions where an increase of muscle tone is associated with the pathogenic mechanism. Furthermore, BoNT is recommended in the treatment of some hypersecretion disorders of the exocrine gland and could play a role in the treatment of migraine and other chronic pain conditions. In the BoNT therapy adverse effects are usually mild and reversible. However, repeated injections of BoNT can lead to the development of neutralizing antibodies that can subsequently inhibit the biological activity of the toxin. In this sense, many factors can influence the immunogenicity of the BoNT, such as product-related factors, the dose of BoNT used, the frequency of injection and the previous exposure to the toxin. In this review, we are going to discuss the current clinical applications of BoNT with a special focus on evidence, doses, injection technique and adverse effects for those applications more frequently used in neurology, namely spasticity, blepharospasm, hemifacial spasm, cervical dystonia and other focal dystonias, as well as chronic migraine, tremor, sialorrhea, facial palsy, neurogenic bladder and many other neurological condition.     

Very early reduction in efficacy of botulinum toxin therapy for cervical dystonia in patients with subsequent secondary treatment failure: a retrospective analysis

The objective of this study was to estimate the probability of development of partial secondary treatment failure (PSTF) in patients with cervical dystonia (CD) who had been treated over up to 9 years with repetitive intramuscular injections of botulinum neurotoxin type A (BoNT/A). The temporal course of treatment response in patients in whom PSTF was detected retrospectively was compared to patients with a normal clinical response. For this purpose, charts of all CD patients treated in our outpatient clinic between 1988 and 2001 were retrospectively analyzed. Extracted data included time of all injections, dose per visit, disease severity measured by TSUI scores, and time of determination of neutralizing antibodies. Final data analysis using a special formal definition of PSTF was based on charts of 568 patients having exclusively been treated with abobotulinumtoxinA. PSTF onset was observed in our CD cohort during the entire treatment period analyzed, with no clustering at any time point. Probability to develop PSTF was 14.5 % in 9 years. Thus, mean PSTF incidence was 1.6 % per year. The mean TSUI score of patients with retrospectively defined PSTF (n = 33) became already significantly worse after the second injection when compared with the group without PSTF (n = 535). Our data indicate that clinical response in patients developing PSTF later on differs from that of patients without PSTF already very early in the course of botulinum neurotoxin type A treatment, and that PSTF remains undetected at this early stage. Reduced response may therefore be present in a number of CD patients who think they still respond normally to continuous BoNT/A treatment.     

Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective,multicentre, randomised,double-blind,placebo-controlled,parallel group study

Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score ≥ 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49 %) than placebo (33 %) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42 %) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia. Received: 3 October 2000, Received in revised form: 20 March 2001, Accepted: 2 May 2001     

Paramedical treatment in primary dystonia: A systematic review

Dystonia is a disabling movement disorder with a significant impact on quality of life. The current therapeutic armamentarium includes various drugs, botulinum toxin injections, and occasionally (neuro)surgery. In addition, many patients are referred for paramedical (including allied health care) interventions. An enormous variation in the paramedical treatment is provided, largely because evidence‐based, accepted treatment regimes are not available. We have conducted a systematic review of studies that explored the effect of various paramedical interventions in primary dystonia. Only studies that have used clinical outcome measures were included. There were no class A1 or A2 studies and therefore, level 1 or 2 practice recommendations for a specific intervention could not be deducted. Many papers were case reports, mostly with a very limited number of patients and a clear publication bias for beneficial effects of a particular paramedical intervention. Some potentially interesting interventions come from class B studies, which include physical therapy in addition to botulinum toxin injections (BoNT‐A) in cervical dystonia; sensorimotor training and transcutaneous electrical nerve stimulation (TENS) in writer's cramp; and speech therapy added to BoNT‐A injections in laryngeal dystonia. Good quality clinical studies are therefore warranted, which should have the aim to be generally applicable. A design in which the paramedical intervention is added to a current gold standard, for example, BoNT‐A injections in cervical dystonia, is recommended. © 2009 Movement Disorder Society