Treatment of Cervical Dystonia

175. Sweat reduction depending on botulinum neurotoxin concentration: a randomized, double-blind study

Cervical dystonia is a disease of the nervous system characterized by forcible discoordinated abnormal postures of the head and neck. There are several approaches to the treatment of dystonia: conservative drug treatment, botulinum therapy and neurosurgery. The latter includes deep brain stimulation, radiofrequency ablation, focused ultrasound, gamma knife. Literature data on this problem from open statistical and information databases such as Web of Science, PUBMED, Movement Disorders Society; International Association of Parkinsonism and Related Disorders were analyzed. Through a comparative approach, the advantages and disadvantages of modern approaches and interventions used in the treatment of cervical dystonia are noted. Among the modern methods of treating cervical dystonia, there are a large number of approaches that improve the methods of managing such patients. This review allowed us to summarize the experience of their application. A significant growth of abilities of stereotactic techniques used in the treatment of cervical dystonia was also noted.

Botulinum neurotoxin type A (BTX-A) weakens voluntary muscle strength and is an effective therapy for focal dystonia, including cervical dystonia (CD) and benign essential blepharospasm (BEB). It is also known to relieve hemifacial spasm and focal spasticity in children and adults. In addition, BTX-A has been shown to be effective in a wide range of other indications, such as gastrointestinal disorders, hyperhidrosis and cosmetic wrinkle correction (e.g. glabellar frown lines). A new formulation of BTX-A, NT 201 (XEOMIN((R))) has been developed. NT 201 is a formulation of pure BTX-A free of complexing proteins and, therefore, may have a reduced immunogenic potential compared with other BTX-A preparations. The pre-clinical and clinical development of NT 201 is reviewed in this article.A total of five clinical trials were completed in Europe and Israel. Two studies were conducted in 46 healthy volunteers. A further three studies in 816 patients were conducted to provide data on the safety and efficacy of NT 201 in the treatment of CD and BEB. NT 201 was found to provide non-inferior efficacy and safety profiles in the treatment of CD and BEB compared with a BTX-A preparation containing complexing proteins (BOT [BOTOX((R))]). The clinical development programme of NT 201 showed a 1 : 1 NT 201 to BOT dose ratio. The pre-clinical studies conducted with NT 201 showed an acceptable safety profile and support the use of NT 201 in an intramuscular administration regimen for patients with CD and BEB. NT 201 was effective, well tolerated and non-inferior to BOT in the treatment of both CD and BEB. In addition, there were no differences between the two therapies in terms of onset of action, duration and waning of effect. Further research is required to determine the long-term efficacy and safety profile of NT 201.

Introduction: Treatment of cervical dystonia (CD) with the highly purified Botulinum neurotoxin type A (BTX-A) free of complexing proteins (Xeomin) is mainly based on the largest controlled study of BTX-A ever performed (Benecke et al. 2005) demonstrating that Xeomin is non-inferior to Botox and that in average the efficacy of one Xeomin unit is equivalent to one Botox unit.

Cervical dystonia is the most common form of focal dystonia characterized by involuntary muscle contractions causing abnormal movements and posturing of the head and neck and is associated with significant pain. Botulinum toxin is considered first-line therapy in the treatment of pain and abnormal head posturing associated with cervical dystonia. There are currently three botulinum toxin type A neurotoxins and one botulinum type B neurotoxin commercially available and US Food and Drug Administration (FDA) labeled for the treatment of cervical dystonia. This review will focus on the efficacy, safety, and therapeutic use of botulinum type A neurotoxins in the treatment of cervical dystonia. We conclude with a discussion of factors influencing toxin selection including therapeutic effect, duration of effect, side effect profile, cost, and physician preference.

Treatment of cervical dystonia and focal hand dystonia by high cervical continuously infused intrathecal baclofen: A report of 2 cases

Botulinum toxin A (BTA) is considered an effective treatment of cervical dystonia. The aim of this prospective, randomized, double-blind study was to compare Botox and Prosigne, a BTA of Chinese origin, with a view to establish the safety, the efficacy, and the equivalence of doses of the 2 formulations in the treatment of cervical dystonia. Twenty-four patients were randomized to receive 300 U of Botox or Prosigne (12 patients in each group). The patients were assessed before the injection and after 4 and 16 weeks by the Toronto Western Spasmodic Torticollis Rating Scale and the Short-Form 36 for quality of life before and 16 weeks after the injection. All patients were comparable in age, time since onset, number of previous injections, and time since last BTA application. According to the Toronto Western Spasmodic Torticollis Rating Scale scores, the patients improved after injection and the scores increased after 16 weeks, without returning to baseline values. Both pain and burning during the injection and the treatment outcomes were similar in both groups. No systemic adverse events occurred, and the severity and frequency of local events were comparable in both groups. Average duration of effect was similar in both groups (11 weeks). The quality-of-life evaluations before and after the injections were comparable in both groups. Social aspects, pain, and vitality improved after 16 weeks in both groups. In conclusion, Botox and Prosigne were determined to have equivalent efficacy, safety, and tolerability profiles and dose equivalence for cervical dystonia treatment is 1:1.

We report the results of electromyographic (EMG) guidance in the treatment of cervical dystonia with botulinum toxin. Eight-four patients received a total of 225 injection sessions. Overall there was moderate objective improvement in 78.7%. The mean dose of toxin was 269 +/- 39 mouse lethal units and the mean duration of maximum effect was 107 +/- 49 days. Complications included excessive neck weakness in 16.0% and dysphagia in 11.1% of the injection sessions. We conclude that EMG guidance is a safe and effective method of administering botulinum toxin in the treatment of cervical dystonia.

Botulinum toxin type A (BoNT/A) is a highly effective and well-tolerated treatment for focal dystonias. The BoNT/A in Botox and Dysport is part of a high-molecular-weight complex that contains hemagglutinins and other non-toxic proteins, whilst Xeomin is a highly purified BoNT/A free of such complexing proteins. In the largest controlled study of BoNT/A published to date (Neurology 2005; 64: 1949), it was demonstrated that Xeomin is non-inferior to Botox and has 1:1 efficacy in the treatment of cervical dystonia. A possible limitation of continued BoNT/A treatment is antibody development. Based on its physiochemical properties and toxicological evidence, Xeomin is expected to have a reduced incidence of non-responders after long-term treatment compared with other marketed BoNT/A products. In our ongoing open-label study, 100 patients suffering from cervical dystonia are continuously treated with Xeomin; 50 patients were treated de novo, the remaining patients had been previously treated with Botox, Dysport or NeuroBloc/Myobloc. All patients showed negative results in antibody testing at the beginning of Xeomin treatment. During continuous treatment with Xeomin up to 2 years, patients continued to respond well to Xeomin treatment. The treatment was well tolerated and no patient has developed neutralizing antibodies as measured using the sensitive mouse hemidiaphragma assay within these first 2 years.

Cervical dystonia is the most frequent type of primary focal dystonia and treatment with botulinum toxin (BTX) is currently the criterion standard. In this study, we compared the safety and efficacy of the following 2 formulations of BTXs available in Brazil: abobotulinumtoxin A (Dysport) and Lanzhou BTX type A (Prosigne), during a follow-up of 13 months. We conducted a prospective, randomized, double blind trial with 1 group being treated with Dysport and the other with Prosigne. Fourteen patients were randomized to receive Dysport and 20 patients to receive Prosigne, each patient was followed during 13 months and received 5 injections of BTX in this period. The dose equivalency used was 3 U of Dysport for 1 U of Prosigne. After each treatment session, we assessed improvement with the Clinician Interview-Based Impression of Change scale and asked about adverse effects and duration of improvement. We also used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) before and after the first and fifth treatment sessions. After the first injection, mean TWSTRS values reduced 12.78 points in the Dysport group and 9.98 in the Prosigne group (P = 0.38). After the last injection, the reduction in TWSTRS values was 11.87 points for Dysport and 11.35 points for Prosigne (P = 0.86). Our data showed similar efficacy and safety profiles when comparing both toxins in the treatment of cervical dystonia.

BackgroundBotulinum toxins are considered first-line therapy for treatment of cervical dystonia (CD) and must be injected on a repeat basis. Understanding the duration of clinical benefit of botulinum toxins and its impact on health care utilization are thus important in the contemporary environment. However, there is currently no overall consensus on the duration of effect of onabotulinumtoxinA in the treatment of CD. We performed a systematic review and meta-analysis to identify the duration of effect of onabotulinumtoxinA in CD and investigate factors that may influence it.MethodsA systematic literature search identified prospective or retrospective studies reporting duration of effect of onabotulinumtoxinA for the treatment of CD. Inclusion criteria included peer-reviewed, non-review, English-language articles published between January 1980 and January 2013. A formal meta-analysis using Comprehensive Meta-Analysis Version 2 was conducted to identify the duration of effect of onabotulinumtoxinA in the treatment of CD; both fixed and random effects models were performed. Subgroup analyses were performed to identify factors that influenced the duration of effect of onabotulinumtoxinA.ResultsA total of 18 studies (including >1,900 patients) met the inclusion criteria and were used for the meta-analysis. The mean duration of effect of onabotulinumtoxinA in CD was found to be 93.2 days (95% CI 91.8-94.6 days) for the fixed effects model and 95.2 days (95% CI 88.9-101.4 days) for the random effects model. A meta-regression found that dose of onabotulinumtoxinA and country of origin influenced the duration of effect of onabotulinumtoxinA, whereas quality score of the article and study type did not. In particular, doses ≥180 Units were associated with longer durations of effect than doses <180 Units (107-109 days vs. 86-88 days, respectively; p < 0.01). Limitations included pooling studies that used discrete definitions of duration and had different designs and study quality.ConclusionsBased on the published literature, the mean duration of effect of onabotulinumtoxinA in CD was 93-95 days (13.2-13.5 weeks). This suggests that, in general, patients with CD treated with onabotulinumtoxinA should require ~4 treatments per year.

Cervical dystonia (CD), the most common focal dystonia encountered in neurologic practice, is a chronic disorder in which the muscles of the neck involuntarily contract and cause abnormal postures and movements of the head, neck, and shoulders. Treatment of CD prior to botulinum toxin was unsatisfactory, as existing therapies often did not improve symptoms. The use of botulinum toxin for CD grew out of its success in treating blepharospasm, another type of focal dystonia. On the basis of results from a double-blind, placebo-controlled trial, onabotulinumtoxinA was approved in 2000 in the US for the treatment of CD in adults in order to alleviate abnormal head position and neck pain. A subsequent large observational trial further demonstrated the effectiveness of onabotulinumtoxinA for CD, showing improvements in various rating scales, physician-reported measures, and profound positive effects on patient quality of life, including in amelioration of pain and improvements in work productivity. In addition, onabotulinumtoxinA treatment also reduced the complications of CD, as patients no longer develop contractures (permanent muscle and tendon shortening from prolonged untreated dystonia), which markedly limited the range of neck motion. The onset of onabotulinumtoxinA treatment also accompanied advances in understanding the functional anatomy of neck muscles, basal ganglia physiology, and video and other recording technology. Following the success of onabotulinumtoxinA in the treatment of CD, its use has been expanded into numerous other therapeutic indications, and these advances stimulated educational and training programs by various neurologic and other medical societies.

Sensory trick imagery as a potential adjunctive treatment in cervical dystonia – A preliminary study

Treatment with botulinum toxin A is the evidence-based first-line therapy of cervical dystonia. The aim of this study was to analyze long-term data of the most commonly used products concerning safety and efficacy in a big cohort over decades. We retrospectively analyzed the treatment data of all cervical dystonia patients in our outpatient clinic having at least three treatment sessions with current onabotulinumtoxinA or abobotulinumtoxinA. The observation period was up to 17years for onabotulinumtoxinA and 27years for abobotulinumtoxinA. We report on safety and efficacy, comparing parameters such as dose, treatment intervals, side effects, occurrence and reasons of primary or secondary non-response. We analyzed a total of 2592 and 6660 treatment sessions in 135 patients with onabotulinumtoxinA, 209 with abobotulinumtoxinA and 10 having received both preparations. We found a moderate increase of dosage in the first years which was succeeded by a stable mean dose (138 and 663 mouse units, respectively) and stable injection intervals from the beginning. The most frequent side effects were mild dysphagia (2/6%), muscle weakness (2/6%) and pain (2/2%). Reasons for therapy discontinuation were change to a nearby doctor, age, other diseases, spontaneous improvement, side effects or possible treatment failure. Of all patients, only two tested positive for neutralizing antibodies against botulinum toxin A. We show that treatment of cervical dystonia with the two most frequently used botulinum toxin A preparations is a safe and effective therapy even over a long treatment duration of up to 27years.

Introduction: Botulinum toxin (BoNT) injections represent the gold standard treatment for cervical dystonia (CD). Different types of BoNT have been used for the treatment of CD, but only two serotypes, BoNT type A (BoNT-A) and type B (BoNT-B), have been approved by regulatory agencies. Efficacy and safety of BoNT have been well documented by many short-term studies, but the longterm effects have been investigated only relatively recently. Areas covered: In the present review, we aimed to critically reappraise the existing evidence on the long-term efficacy and safety of BoNT treatment in CD. The examined studies mainly explored BoNT-A serotypes. Only a few studies examined the long-term effects of BoNT-B serotypes, and only one head-to-head comparison between BoNT-A and BoNT-B was found. BoNT was consistently reported to be an effective and safe treatment for CD patients, with good outcomes and a few adverse events in the long-term. However about a third of patients still drop out from the treatment during a long-term follow-up. Expert opinion: We conclude that BoNT is safe and effective in the long-term treatment of patients with CD. Additional studies are needed to further explore patients real-life experiences and perspectives to better understand the long-term outcomes and reasons for discontinuation of treatment.