Treatment Of Cervical Dystonia Research Articles

PND4 - A Mixed Treatment Comparison (Mtc) To Compare The Efficacy Of Botulinum Toxin Type A Treatments For Cervical Dystonia

PND4 - A Mixed Treatment Comparison (Mtc) To Compare The Efficacy Of Botulinum Toxin Type A Treatments For Cervical Dystonia

Cost analysis of the use of botulinum toxin type A in Spain

To estimate treatment costs of blepharospasm, cervical dystonia(CD), upper limb spasticity (ULS) and spasticity in children with cerebral palsy (SCCP) with botulinum neurotoxin type A (BoNT-A) in Spain. Annual BoNT-A treatment costs were calculated (2013 ex-factory price () applying RDL 8/2010 and RDL 9/2011 deductions), based on initial dose (id), average dose (ad) and maximum dose (md) according to Summary of Product Characteristics of Botox® (100U/50U), Dysport®(500U) and Xeomin® (100U) and considering the use of complete vials.In addition, annual treatment costs were calculated considering the useof vials in more than one patient and also patient population annual treatment costs based on diseases' prevalence. Annual BoNT-A treatment costs per patient were estimated at between 265 and 2,120 with savings from 10% to 55% accordingto the selected BoNT-A. CD and ULS treatment provided the greatest cost per patient. Botox® provided greater savings in ULS (id/ad), CD(id), and in blepharospasm and SCCP (id/ad/md). Dysport® treatment was less costly in CD (md) and ULS (md), while Xeomin® was in CD(ad). Based on the estimated treated population in Spain, the annual treatment costs ranged from 368,392 to 13,958,836 depending on indication, dose and BoNT-A considered. The appropriate BoNT-A choice would lead to considerable savings for the National Health System. Botox® would generate lower costs per patient than other BoNT-A products in 9 out of 12 scenarios considered.

Systematic review and meta-analysis of the duration of clinical effect of onabotulinumtoxinA in 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 and pain: characteristics and treatment patterns from CD PROBE (Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy)

To compare profiles of subjects with and without cervical dystonia (CD)-associated pain, to evaluate the contribution of pain and the motor component of CD on quality of life, and to compare the initial botulinum toxin treatment paradigm between pain groups, baseline data were used from the CD Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE), a multicenter, prospective, observational registry designed to capture real-world practices and outcomes for onabotulinumtoxinA CD treatment. Subjects were divided into no/mild pain [Pain Numeric Rating Scale (PNRS) score 0–3] and moderate/severe pain groups (PNRS score 4–10). Descriptive and differential statistics were utilized to compare groups. 1,037 subjects completed the first treatment session, reported baseline botulinum toxin status, and completed baseline PNRS. Those with no/mild pain were significantly older at baseline. Those subjects with moderate/severe pain had higher Toronto Western Spasmodic Torticollis Rating Scale Severity (17.7 ± 5.1 vs. 16.2 ± 5.6, p < 0.0001) and Disability (12.7 ± 6.1 vs. 7.5 ± 5.6, p < 0.0001). CD subjects with moderate/severe pain received a higher mean dose (177.3 ± 82.9 vs. 158.0 ± 67.1 U, p = 0.0001) of onabotulinumtoxinA and were injected in more muscles (4.1 ± 1.4 vs. 3.7 ± 1.2, p < 0.0001) at initial treatment. CD PROBE clearly demonstrates the frequency of pain in CD and substantiates its importance when determining an optimal treatment paradigm. Future analyses of CD PROBE will further our understanding of the treatment patterns and outcomes related to onabotulinumtoxinA therapy for this disabling condition.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-014-7343-6) contains supplementary material, which is available to authorized users.

28. Modulation of cerebral sensorimotor circuits during botulinum toxin treatment of cervical dystonia

Objective Neurophysiological and lately also functional brain imaging studies in cervical dystonia (CD) patients indicate a disorder of sensorimotor integration within extensive cortico-subcortical brain networks. Intramuscular botulinum toxin type A (BoNT-A) application has a proven clinical effect on pathological muscle activation in CD but recently has also been shown to modulate sensorimotor networks. To clarify cervical dystonia pathophysiology through functional magnetic resonance imaging of sensorimotor network changes associated with first-time botulinum toxin treatment. Methods We have studied 12 BoNT-A naive CD patients using functional MRI during specific hand motor task performance. Clinical and imaging examinations were performed before the first BoNT-A application and subsequently 4 weeks after application, at the time of maximal clinical effect of BoNT-A. Clinical treatment response was evaluated with the Tsui score, functional MRI data were analyzed with a general linear model implemented in FSL software, treatment effects were tested in pair-wise linear contrasts. Results First BoNT-A injection, although it had a good clinical effect, did not lead to any significant changes in activation of cortex or basal ganglia in our group of CD patients. Discussions Within the context of previously described sensorimotor network hypoactivation during motor task performance in CD, our observed effect of no significant change in sensorimotor cortex activation would suggest the hypothesis that robust central changes develop after long-term regular BoNT-A treatment, although even the first BoNT-A application is clinically effective. Acknowledgment Research supported by Grant IGA MH CR NT13575.

Complementary/alternative medicine and physiotherapy usage in German cervical dystonia patients

BackgroundPatients with cervical dystonia (CD) frequently express interest in complementary and alternative medicine (CAM) methods. We assessed the frequency of CAM utilization (including physiotherapy), evaluated perceived effectiveness and identified predictors for the treatment choice. MethodsStandardized questionnaires of 266 patients, recruited from two diverse sources, were analyzed. Group 1 (n=101) comprised patients recruited from two centers specialized in treatment of CD while group 2 (n=165) consisted of volunteers of the German national patient advocacy group. ResultsAt least one CAM-classified therapy was used by 81%. Those CAM therapies which were used most frequently (massages, acupuncture, chiropraxy) were not judged as effective or even had negative effects on dystonic symptoms. Special physiotherapy and psychotherapy were evaluated as most beneficial. Most patients made use of CAM in addition to botulinum toxin (BTX) injections, in particular when they were less satisfied with BTX treatment or had adverse effects. Other predictors of CAM-treatment choice were a long duration of CD, male sex, psychological stress and group 2 membership. ConclusionsSome treatment combinations (conventional treatment and special physiotherapy or psychotherapy) may hold promise for further evaluation, especially when long-term monotherapy with BTX is no longer satisfactory.

The effectiveness of physiotherapy for cervical dystonia: a systematic literature review

Cervical dystonia is a form of adult-onset, focal dystonia characterized by involuntary contractions of the neck muscles, leading to a disabling, abnormal head posture. CD has a great impact on the activities of daily living (ADL) and quality of life. Currently, the most widely used and recommended first line treatment is botulinum toxin type A (BoNT/A) injections. Physiotherapy is a potentially useful adjuvant, but little is known about its effectiveness. Consequently, our objective was to investigate the effectiveness of physiotherapy alone or as an adjuvant treatment to BoNT/A injections in cervical dystonia (CD) by means of a systematic literature review. Two online databases, PubMed and Web of Science, were searched for articles describing the effectiveness of physiotherapy treatment for CD. After screening, based on predefined in- and exclusion criteria, 16 studies were retained. Their methodological quality was assessed according to Cochrane guidelines. The methodological quality of most studies was low. Examples of shortcomings are small sample sizes, lack of randomization or blinding, and diversity in therapeutic techniques and outcome measures. Only seven studies were clinical trials; the remaining were either case reports or case series. The reported physiotherapy treatments included EMG biofeedback training, muscular elongation, postural exercises and electrotherapy. Improvements in head position, pain, cervical range of motion, quality of life and ADL have been reported, which is promising. Cautious interpretation on the effectiveness of physiotherapy as an adjuvant therapy is required. Before firm conclusions can be drawn, additional high quality trials are needed.

Incobotulinumtoxin A (Xeomin®) injected with flexible intervals is a well-tolerated long-term treatment of cervical dystonia

Incobotulinumtoxin A (Xeomin®) injected with flexible intervals is a well-tolerated long-term treatment of cervical dystonia

Botulinum toxin type A: implications in wound healing, facial cutaneous scarring, and cleft lip repair

Botulinum toxin is a neurotoxin that has been utilized to induce chemo-denervation of muscles. Cutaneous wounds represent a special situation in which the tensile forces applied by these muscles on wound edges might have deleterious effects on the healing process. The aim of this review was to investigate such an effect and to review other mechanisms this toxin might have on the healing process. We also reviewed the role of botulinum toxin in the management of hypertrophic scars and cleft lip repair.

S1-4. The effect of repetitive Transcranial Magnetic Stimulation (rTMS) in patients with intractable cervical dystonia and/or post-stroke central pain

Non-invasive rTMS has been recently used in the evaluation of various neurological disorders. The aim of this study is to clarify the therapeutic effects of rTMS in patients with intractable cervical dystonia (CD) and/or central post-stroke pain (CPSP). In 6 patients with CD, low-frequency rTMS (0.2 Hz) was applied to the frontal area (including pre-motor cortex), 100 times per session once a week for 6 months. Only single session reduced the muscle pain for 4–7 days. Reduction of Pain Scale and Severity Scale of Toronto Western Spasmodic Torticollis Rating Scale was observed among 2 months’ session. Not only abnormal postures but also repetitive movements were reduced among 6 months’ session. In 8 patients with CPSP, high-frequency rTMS (10 Hz) was applied to the primary motor cortex, 500 times per session among every 3 days. The pain was dramatically reduced by single session alone. But, the effect on spontaneous pain is limited in all sessions. The improvement on affective component of the McGill Pain Questionnaire (MPQ) was better than the other component of MPQ in all sessions. In conclusion, rTMS is useful as one of the option in the treatment of intractable CD and CPSP.

Long-term efficacy and safety of incobotulinumtoxinA injections in patients with cervical dystonia

IntroductionPreviously, controlled trials have demonstrated the efficacy and tolerability of fixed doses of incobotulinumtoxinA (Xeomin, NT 201, botulinum toxin type A free from complexing proteins) to treat cervical dystonia (CD)....

Expanding Treatment Options for Neuromodulators

In the early 21st century, members of the medical community have been both witnesses to and participants in significant changes in the field of aesthetic surgery and medicine, including nonsurgical facial rejuvenation. Although some of dermal fillers were available prior to 2000, their indications were primarily therapeutic. Now, various categories of dermal fillers exist, including hyaluronic acid, poly-L-lactic acid, polymethylmethacrylate, calcium hydroxylapatite, and patients' own fibroblasts. Neuromodulators (ie, botulinum toxin type A [BoNTA] formulations) were first approved for therapeutic purposes but quickly gained popularity for aesthetic applications. According to the American Society for Aesthetic Plastic Surgery, in 2010, more than 2.4 million patients received treatment with a BoNTA product. Clearly, BoNTA injections have been widely adopted in aesthetic practice, beginning with the approval of onabotulinumtoxinA (Botox; Allergan, Irvine, California) in 2002 by the US Food and Drug Administration (FDA) for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adults 65 years or younger. Off-label applications in areas such as horizontal forehead lines, “crow's feet,” and the perioral area followed. A new neuromodulator, abobotulinumtoxinA, was introduced in 2009, expanding the treatment options for physicians. AbobotulinumtoxinA (Dysport; Medicis Aesthetics, Scottsdale, Arizona) was approved by the FDA for the treatment of cervical dystonia in adults and for the aesthetic treatment of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adults 65 years or younger. As was the case …

Cervical Dystonia: From Pathophysiology to Pharmacotherapy

Background: Dystonia is a chronic disorder characterised by an aberration in the control of movement. Sustained co-contraction of opposing agonist and antagonist muscles can cause repetitive and twisting movements, or abnormal postures. Cervical dystonia (CD), often referred to as spasmodic torticollis, is a type of focal dystonia involving the muscles of the neck and sometimes the shoulders.Methods: This systematic review collates the available evidence regarding the safety and efficacy of a range of treatments for CD, focusing on their effectiveness as shown by double-blinded, randomised controlled trials.Results: Our review suggests that botulinum toxin type A (BTA), botulinum toxin type B (BTB) and trihexyphenidyl are safe and efficacious treatments for CD. Evidence shows that botulinum toxin therapies are more reliable for symptomatic relief and have fewer adverse effects than trihexyphenidyl. When comparing BTA to BTB, both are found to have similar clinical benefits, with BTA possibly having a longer duration of action and a marginally better side effect profile. BTB is also safe and probably just as efficacious a treatment in those patients who are unresponsive or have become resistant to BTA.Discussion: The current evidence shows that the pharmacological management of CD relies on BTA and BTB, two agents with established efficacy and tolerability profiles.

Cervical dystonia: from pathophysiology to pharmacotherapy.

Background: Dystonia is a chronic disorder characterised by an aberration in the control of movement. Sustained co-contraction of opposing agonist and antagonist muscles can cause repetitive and twisting movements, or abnormal postures. Cervical dystonia (CD), often referred to as spasmodic torticollis, is a type of focal dystonia involving the muscles of the neck and sometimes the shoulders. Methods: This systematic review collates the available evidence regarding the safety and efficacy of a range of treatments for CD, focusing on their effectiveness as shown by double-blinded, randomised controlled trials. Results: Our review suggests that botulinum toxin type A (BTA), botulinum toxin type B (BTB) and trihexyphenidyl are safe and efficacious treatments for CD. Evidence shows that botulinum toxin therapies are more reliable for symptomatic relief and have fewer adverse effects than trihexyphenidyl. When comparing BTA to BTB, both are found to have similar clinical benefits, with BTA possibly having a longer duration of action and a marginally better side effect profile. BTB is also safe and probably just as efficacious a treatment in those patients who are unresponsive or have become resistant to BTA. Discussion: The current evidence shows that the pharmacological management of CD relies on BTA and BTB, two agents with established efficacy and tolerability profiles.

Abstracts from the TOXINS 2012

Abstracts from the TOXINS 2012

Effects of EMG Biofeedback on Pain and Quality of Life in Cervical Dystonia

Abstract Cervical dystonia (CD) is a focal dystonia affecting cervical muscles leading to abnormal postures and movements of the head, neck and shoulders. Cervical dystonia is a chronic disease with unwanted side effects. Although muscle contractions represent the most visible disease feature, associated symptoms such as pain are frequent and relevant contributors to disability. At the same time, pain constitutesone of the most important factors in term of poor quality of life (QOL) and is one of the most affected QOL domains in CD patients. However, the mechanism underlying the pain associated with CD remains unclear. There are no therapeutic controlled trials that have evaluated pain or QOL as a primary outcome, but the available data suggest that therapeutic interventions that improve dystonia also alleviate pain and have a beneficial effect on QOL. Recent studies have demonstrated that Electromyography (EMG) biofeedback is a good option for treatment of CD. The main aim of present research was to investigate the effect of EMG biofeedback on pain and health related quality of life of cervical dystonia patients. To do so, a sample of 30 subjects with cervical dystonia was selected for experimental and control groups by an accessible sampling procedure. Subjects were assessed with the pain subscale of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Short-form Health Survey with 36 questions (SF-36) in two stages (pre-test, post-test). The obtained data were analyzed through covariance analysis method. After 30 sessions of EMG biofeedback training, the mean scores of pain in the experimental group were significantly diminished. Also, the mean of SF-36 scores in the experimental group showed a significantly higher increase in comparison to that of the control group. The results suggested that EMG biofeedback was effective on pain and health related QOL of CD patients.

Immunogenicity and Long-Term Efficacy of Botulinum Toxin Type B in the Treatment of Cervical Dystonia

Therapeutic botulinum toxins are antigenic proteins with the potential to produce antibodies (Abs). It is, however, unclear whether Abs to Myobloc® (rimabotulinumtoxinB, botulinum toxin type B, BoNT-B) impact the efficacy and safety of BoNT-B treatment of cervical dystonia (CD). The objective was to determine if Abs to BoNT-B impact the efficacy or safety of long-term BoNT-B treatment of CD. Four separate prospective clinical trials, with a combined total of 1134 subjects evaluable for immunogenicity over total treatment durations of up to 6+ years, were conducted studying the efficacy, safety, and immunogenicity of BoNT-B treatment of CD. Botulinum toxin type B injections were administered approximately every 3 months. Efficacy was assessed using the Toronto Western Spasmodic Torticollis Rating Scale-Total Score, the Subject Global Assessment, or the Treatment Assessment Scale. The presence of Abs to BoNT-B was assessed using the mouse neutralizing antibody (MNA) assay. Cross-sectional and longitudinal statistical analyses were performed to compare efficacy by MNA status at each time point and over time in Ab-positive individuals before and after seroconversion. Safety was assessed by summarizing adverse events by Ab status. Long-term efficacy was observed with multiple treatments of BoNT-B. Across all 4 studies, there was no correlation between MNA status and rates of clinical response, study withdrawal, or safety profile. Botulinum toxin type B is effective and safe in the repeat, long-term treatment of CD. The presence of Abs to BoNT-B as detected by the MNA assay does not have any meaningful clinical impact or correlation.

Multichannel Electromyographic Mapping to Optimize OnabotulinumtoxinA Efficacy in Cervical Dystonia.

Cervical dystonia (CD) is characterized by sustained, involuntary contraction of head and neck muscles. Botulinum toxin injections are established as safe and effective, but unfortunately 15-25% of patients fail to respond. The aim of this study was to examine whether multichannel electromyogaphic mapping improved outcomes in a cohort of antibody-negative onabotulinumtoxinA non-responders by more precisely identifying which muscles were involved in the dystonia. Patients with cervical dystonia who had "failed chemodenervation therapy" administered by an outside provider were enrolled in a single-blind, randomized, crossover design study. Patients received either a multichannel electromyographic mapping study prior to the first botulinum toxin injection, which was followed by use of only a single-lead injection 16 weeks later (injected by an alternate and blinded movement disorders specialist) or vice versa. The primary outcome measure was change in total Toronto Western Spasmodic Torticollis Rating Scale score 4 weeks after each injection compared with each pre-injection baseline score. Nine subjects completed this study. Mean percentage improvement in Total Toronto Western Spasmodic Torticollis Rating Scale was 23.5% using multichannel electromyography compared with 9% using the single-channel technique (p = 0.11). This pilot study suggests that multichannel electromyographic mapping may result in improved efficacy in the treatment of antibody-negative onabotulinumtoxinA refractory CD.

AbobotulinumtoxinA (Dysport) dosing in cervical dystonia: an exploratory analysis of two large open-label extension studies

Treatment with botulinum toxin-A is recommended as first-line treatment for cervical dystonia (CD). In clinical practice many factors appear to influence dose adjustment and the retreatment regimen; however, there is little information available in the literature regarding the evolution of dosing over treatment cycles. We report on two similarly designed, long-term, multicenter, open-label extension studies of Dysport for the treatment of CD, which followed 500U fixed-dose placebo-controlled trials. Both studies specified a fixed 500U dose for the first open-label treatment cycle, with dose adjustment in subsequent treatment cycles according to the clinical response. These analyses include 218 patients who entered the two studies; doses in the subsequent treatment cycles ranged between 250 and 1,000U. During open-label treatment, all treatment cycles resulted in improvements in mean Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores. However, increasing the dose of Dysport above the initial 500U dose was not observed to result in an incremental improvement in response as measured by the TWSTRS. No individual patient characteristic was found to reliably predict the use of higher doses at each treatment cycle. Dysport was generally well tolerated with no major differences in the incidence of adverse events (AEs) observed with different doses. Dysphagia was considered an AE of special interest and dysphagia data from the open-label studies were combined with two Phase II studies. Analysis of this enhanced database indicates that unilateral injections of >150U into the sternocleidomastoid muscle is associated with a higher dysphagia risk. Thus, limiting the dose in the sternocleidomastoid may help reduce the incidence of dysphagia.

Botulinum Toxin Type A Application for the Treatment of Cervical Dystonia

Botulinum Toxin Type A Application for the Treatment of Cervical Dystonia