Low-dose botulinum toxin-a treatment of cervical dystonia - a double-blind,randomized pilot study

The purpose of the study was to evaluate the clinical efficacy of low-dose botulinum toxin (BTX) treatment of cervical dystonia in a double-blind, randomized pilot study. Thirty-one patients with cervical dystonia and a minimum of 2 previous Dysport treatments received either a mean total target dose of 547 +/- 113 mouse units (MU) (group A, 500 MU Dysport/ml) or a 4-times-diluted preparation 130 +/- 32 MU (group B, 125 MU Dysport/ml). Assessment was made before and 4 weeks after the injection using Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS). Additionally, a self-response scale evaluated the patients' subjective condition for 12 weeks after injection. TWST rating before and after injection revealed comparable clinical improvement in both groups. The severity of cervical dystonia at study entry had no effects on therapeutic effects of either preparation. Self-rating revealed comparable subjective improvement in both groups; however, 3 patients of group B received reinjections due to insufficient effects of the injection. Our findings suggest that low-dose treatment of cervical dystonia with Dysport may be clinically effective during maintenance therapy, at least for a limited period of time. Long-lasting effects of previous Dysport treatments at conventional doses and possibly improved diffusion of a highly diluted toxin preparation may have contributed to the effects of the low-dose regimen. Our data emphasize the need for further studies in order to clearly identify optimal toxin preparations for therapeutic uses of BTX-A in neurologic disorders.     

Factors affecting the health-related quality of life of patients with cervical dystonia and the impact of botulinum toxin type A injections

The purpose of this study was to analyze the health-related quality of life (HRQL) of patients with cervical dystonia (CD) and the impact of botulinum toxin A (BTX-A) therapy in these patients. The authors recruited 101 patients with CD, all previously treated with BTX-A. Both before and 4 weeks after injection of BTX-A the patients were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), a Visual Analogue Scale for pain (VAS: 0-100%), the Short Form 36 health survey questionnaire (SF-36), and the Montgomery-Asberg Depression Rating Scale (MADRS). A control group of 84 healthy volunteers was also evaluated. The patients? baseline SF-36 scores were worse in all the domains when compared with those of the controls. Depression was found in 47.5% of the patients. Improvements were noticed 4 weeks after the single BTX-A injections in all the SF-36 domains, and in the VAS, TWSTRS and MADRS scores. The TWSTRS results did not correlate with any of the SF-36 subscores. Stepwise backward regression analysis revealed depression as the main predictor of poor HRQL, as well as female sex, poor financial situation, and living alone. On contrary, longer treatment with BTX-A was associated with better scores. Cervical dystonia has a marked impact on HRQL and treatment with BTX-A injections has a beneficial effect, seen both in objective and in subjective measures. Depression in CD patients is a main predictor of worse HRQL.     

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.     

The botulinum toxins in the treatment of cervical dystonia

The use of botulinum toxin to treat cervical dystonia (CD) has dramatically improved the quality of life of patients with this disabling, often painful disease. Two forms of toxins, botulinum toxin type A (BTX-A) and botulinum toxin type B (BTX-B), have each been studied in large multicenter trials in subjects with CD. A study of BTX-A demonstrated improvement of 5.15 to 10.65 degrees in head position using the Cervical Dystonia Severity Scale (CDSS) in those treated with BTX-A (trade name BOTOX) compared with placebo. A study in patients who continued to respond to BTX-A and a similarly designed study in patients who were resistant to BTX-A demonstrated statistical improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in those treated with BTX-B (evaluated as NeuroBloc) compared with placebo. The potential availability of both forms of toxin will allow physicians to offer further treatment options to patients with CD.     

CDIP-58 can measure the impact of botulinum toxin treatment in cervical dystonia

We compared the responsiveness of the Cervical Dystonia Impact Profile (CDIP-58), Medical Outcome Study Short Form-Health Survey (SF-36), Functional Disability Questionnaire (FDQ), and Pain and Activities of Daily Living subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in participants with cervical dystonia treated with botulinum toxin A. Subscales of CDIP-58 were more sensitive in detecting statistical and clinical change than comparable subscales of the SF-36, FDQ, and TWSTRS.     

Ptosis as a remote effect of therapeutic botulinum toxin B injection

The authors report a patient with cervical dystonia, previously treated with botulinum toxin A (BTX-A), who developed bilateral ptosis and difficulty with accommodation only after botulinum toxin B (BTX-B). High-frequency repetitive nerve stimulation of the abductor digiti minimi demonstrated a 34% increment in compound muscle action potential. No increment in 20 people injected with BTX-A and no cases of ptosis in a chart review of 1,606 BTX-A injections for cervical dystonia were found. The authors conclude that systemic spread of BTX-B can cause symptomatic involvement of autonomic neurons.     

Autonomic function after botulinum toxin type A or B: a double-blind, randomized trial

To compare autonomic effects of botulinum toxin (BTX), we randomized patients with cervical dystonia to receive either BTX-A or BTX-B in a double-blind manner. Efficacy and physiologic questionnaire measures of autonomic function were assessed at baseline and 2 weeks after injection. Patients treated with BTX-B had less saliva production (p < 0.01) and greater severity of constipation (p = 0.037) than those treated with BTX-A, but did not differ in other tests of autonomic functions.     

Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia

OBJECTIVES: Botulinum toxin type A is a potent neuromuscular paralyzing agent used in various disorders including cervical dystonia. Two preparations of botulinum toxin are now commercially available ( Dysport and Botox), but much controversy remains about their respective potencies. The aim of the study was to compare the efficacy of Botox with two different ratios of Dysport. METHODS: A double blind, randomised, three period cross over study involving 54 patients with cervical dystonia was performed. The patients received the following treatments in a randomised order: Botox at the usually effective dose, Dysport at a dose of 1:3 (conversion factor of 3 between Botox and Dysport units-that is, one Botox unit=three Dysport units) and at a dose of 1:4 (conversion factor of four). The improvement of the Tsui (primary outcome criteria) and of the TWSTRS pain scales between baseline and a control visit 1 month after each of the three injections, as well as the incidence of adverse events, were assessed. RESULTS: Comparison of the Tsui scores and of the TWSTRS pain scores showed a better effect on impairment and pain with Dysport 1:3 (p=0.02 and 0.04, respectively) and 1:4 (p=0.01 and 0.02, respectively) than with Botox. The number of adverse events was higher with both Dysport treatments. The most frequent adverse event was dysphagia, found in 3%, 15.6%, and 17.3% (Botox, Dysport 1:3 and 1:4, respectively) of the patients. No adverse event required withdrawal of therapy or specific management. CONCLUSIONS: Dysport 1:3 (and Dysport 1:4 to a greater extent) is more efficient than Botox for both impairment and pain in cervical dystonia although with a somewhat higher incidence of minor adverse effects. This strongly suggests that the most appropriate conversion factor between Botox and Dysport units is less than 3 in cervical dystonia.     

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.     

Long-term remission of idiopathic cervical dystonia after treatment with botulinum toxin

Botulinum toxin type A (BTX-A) treatment for cervical dystonia is traditionally considered a purely symptomatic treatment. BTX-A blocks acetyl choline exocytosis for 3-6 months and most patients require reinjection after this period. We report on 6 patients (mean age 41.6 years, range 18-69) with idiopathic cervical dystonia who were treated with BTX-A injections and became asymptomatic for 2-4 years. Four patients showed remission after the first BTX-A treatment, 1 patient after the second set of injections and 1 after the third session. Amelioration of neck dystonia was observed within 1-4 weeks after the last BTX-A treatment and all 6 patients are symptom-free, off antidystonic medications for over 2 years. The possibility that BTX-A treatment may increase the chances of development of clinical remission in patients with idiopathic cervical dystonia is discussed.     

Botulinum toxin type A: new therapeutic directions

Intramuscular injections of botulinum toxin type A (BTX-A) have been used successfully to treat disorders such as cerebral palsy and cervical dystonia for many years. New and exciting directions for the toxin are currently under clinical investigation for a number of unlicensed indications including tension-type headache, myofascial pain and hyperhidrosis. Although research on BTX-A is prolific, there is still much to be learnt regarding the toxin's mode of action, clinical application and perhaps more importantly, its place in the overall treatment strategy implemented by physicians to ensure treatment is a success for both the patient and the physician. This review will focus on these issues, by outlining some of the future directions for BTX-A research.     

Molding the sensory cortex: spatial acuity improves after botulinum toxin treatment for cervical dystonia.

Disorganization of sensory cortical somatotopy has been described in adult onset primary torsion dystonia (AOPTD). Although botulinum toxin type A (BTX-A) acts peripherally, some studies have suggested a central effect. Our primary hypothesis was that sensory cortical reorganization occurs after BTX-A treatment of AOPTD. Twenty patients with cervical dystonia and 18 healthy age-matched control patients had spatial discrimination thresholds (SDTs) measured at baseline and monthly for 3 months. Mean baseline SDT (+/-SD) was 1.75 +/-0.76 mm in the dystonia group, greater than the control group mean of 1.323 +/- 0.45 mm (P = 0.05). Mean control group SDT did not vary significantly over time. A transient improvement of 23% from baseline (P = 0.005) occurred in the dystonia group 1 month after injection, which did not positively correlate with changes in physician and patient ratings of torticollis severity. The presumed mechanism of SDT improvement is a modulation of afferent cortical inputs from muscle spindles. Society.     

Efficacy and safety of a new bulk toxin of botulinum toxin in cervical dystonia: a blinded evaluation

We investigated the efficacy and safety of botulinum toxin A (BTX) manufactured from a new bulk strain for the treatment of cervical dystonia. This was a single-blinded retrospective comparison of length of benefit, subjective improvement, and complications of treatment in 50 patients treated with the old form of toxin designated 79-11 and the new toxin strain BCB2024. The mean duration of benefit of the 79-11 strain and the BCB2024 strain were the same. Subjective efficacy, measured on a -4 to +4 scale, demonstrated no difference between the two strains. Dysphagia occurred in 12% of patients injected with the 79-11 strain and 14% of subjects injected with the BCB2024 strain. We also used a clinician's global assessment that incorporated the duration of benefit, subjective efficacy, and complications as a secondary analysis. There was no significant difference between the two forms of botulinum toxin A according to this scale. We conclude that the 79-11 strain and the BCB2024 strain offer similar peak efficacy duration of benefit, and adverse events.     

Botulinum toxin A relieved neuropathic pain in a case of post-herpetic neuralgia

Botulinum toxin type A (BTX-A) has been widely used in many clinical disorders including migraine, cervical dystonia, etc. The use of BTX-A in neuropathic pain, however, is uncommon, and the application of the anti-nociceptive effect of botulinum toxin is emerging. Here we report a case of an 80-year-old man who suffered from severe pain of post-herpetic neuralgia which was refractory to the usual therapies. However, this neuropathic pain was dramatically relieved by multiple BTX-A injection and the pain relief lasted 52 days.     

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.     

Predictable variables for short- and long-term botulinum toxin treatment response in patients with cervical dystonia

We retrospectively evaluated 118 patients with cervical dystonia (CD) treated with botulinum toxin type A (BTX-A) for the following variables: gender, age at evaluation, age at symptom onset, disease duration, presence of head/neck pain and/or tremor, pattern of head deviation, disease progression (spreading of symptoms), etiology (primary vs. secondary), pretreatment with oral medication, and Tsui score. We investigated whether these parameters could predict the clinical outcome in a short- (<30 days) and long-term basis. On short-term treatment, there were no clinically significant differences between BTX-A responsive and non-responsive patients. On long-term treatment, however, intake of oral medication previously to BTX-A injection and higher Tsui scores were predictors of favorable response. These results suggest that the greater CD severity the more likely patients will respond to BTX-A.     

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     

肌电图引导局部肌肉注射A型肉毒毒素治疗痉挛性斜颈的疗效观察

目的 观察肌电图(EMG)引导局部肌肉注射A型肉毒毒素(BTX-A)治疗痉挛性斜颈(CD)的疗效.方法 应用EMG检查19例CD患者头颈部152块肌肉,针对放松状态下出现的多频群放电位的114块靶肌肉进行BTX-A局部肌肉注射;治疗前后分别采用Tsui量表对病情和疗效进行评估;随访观察疗效持续时间以及不良反应.结果 治疗后EMG发现靶肌肉5块;根据Tsui量表评分,治疗后总有效率第1周为47.3%,第2周为78.9%,第3、4周均为94.7%;随访显示疗效平均保持10个月;不良反应轻微,均在4周内自行缓解.结论 EMG引导局部肌肉注射BTX-A治疗CD安全有效.     

An update on the treatment of detrusor-sphincter dyssynergia with botulinum toxin type A

The aim of this study was to evaluate the relaxant effect of two preparations (BOTOX® versus Dysport®) of botulinum toxin type A (BTX-A) on the external urethral sphincter in patients with neurogenic voiding disorders. Ten male spinal cord injury patients with detrusor- external urethral sphincter dyssynergia (DSD) were clinically assessed before, and 4–6 weeks after, transurethral or transperineal BTX-A injections (BOTOX® 100 U or Dysport® 250 U) into the external urethral sphincter. Patients with persistent difficulties in voiding or high post-void residual volumes were re-injected with the same product up to three times. All patients were urodynamically examined within 120 days of injection. In total, 30 BTX-A injection cycles (one to three injections) were administered. Significant ( P < 0.05) reductions in the DSD duration post-injection, the time interval between the start of bladder contractions and voiding, and DSD seventy post-treatment were observed. All patients who presented with a residual volume pre-treatment showed a marked decrease post-treatment. These effects lasted 6 months. Improvements in urodynamic parameters were significantly better following BOTOX® than DysporP treatment ( P < 0.05), although the Dysport® dose used is now considered less potent than that of BOTOX®. Thus, injections of BTX-A into the external urethral sphincter are a valuable treatment option for DSD in spinal cord injury patients. Treatment success appears to depend on the seventy of DSD before treatment.     

Epidural premotor cortical stimulation in primary focal dystonia: clinical and 18F-fluoro deoxyglucose positron emission tomography open study

The aim of this study was to evaluate the efficacy and safety of epidural premotor stimulation in patients with primary focal dystonia. Seven patients were selected: 6 had cervical dystonia and 1 had right upper limb dystonia. In 2 patients, sustained muscle contractions led to a prevalently fixed head posture. Patients with cervical dystonia received a bilateral implant, whereas the patient with hand dystonia received a unilateral implant. Neurological and neuropsychological evaluations were performed before surgery (baseline), and 1, 3, 6, and 12 months afterward. The Burke-Fahn-Marsden scale (BFMS) and the Toronto Western spasmodic torticollis rating scale (TWSTRS) were administered at the same time points. Patients underwent resting (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans, before and 12 months after surgery. No adverse events occurred. An overall improvement was observed on the BFMS and TWSTRS after surgery. Patients with prevalently fixed cervical dystonia had a reduced benefit. Presurgical neuroimaging revealed a significant bilateral metabolic increase in the sensorimotor areas, which was reduced after surgery.