***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: ABSTRACT Objectives : Evaluate the safety and efficacy of a sequential dose escalation of rimabotulinumtoxinB ( BoNT-B ) in cervical dystonia ( CD ) subjects . Methods : This multicenter , open-label , within-subject , sequential dose-escalation study ( BoNT-B dosed at 10,000 , 12,500 , and 15,000 Units ) evaluated subjects over each phase of treatment at preinjection and at periodic intervals postinjection . Adverse events , vital signs , and laboratory results were recorded . Efficacy measures included the Toronto Western Spasmodic Torticollis Rating Scale ( TWSTRS ) and three visual analog scales ( VASs ) . Results : 119 out of 145 CD subjects received all three doses in sequence . Dry mouth and dysphagia were the most common adverse events , and both decreased in frequency by the final injection , despite the increasing doses of the escalation . TWSTRS-Total and subscale scores demonstrated significant improvements following all doses at the week 2 , 4 , 8 , and 12 assessment s , with the exception of disability and pain at week 12 with the lowest dose . All VAS scores demonstrated similar improvements following all doses . The mean number of weeks in each phase of the study was 12.1 weeks ( 10,000 Units ) , 12.9 weeks ( 12,500 Units ) , and 13.9 weeks ( 15,000 Units ) . Conclusion : BoNT-B was well tolerated and efficacious at 10,000 , 12,500 , and 15,000 Units in this within-subject , sequential dose-escalation study in CD subjects Cervical dystonia ( CD ) is characterized by abnormal , involuntary contractions of the cervical and /or shoulder muscles . Direct injection of Botulinum toxin type A ( BTX-A ) into the affected muscles has been used successfully to treat this condition . However , clinical resistance to BTX-A therapy develops in a limited number of patients . Moreover , an unknown proportion of treated patients have a suboptimal response to their present therapy . BTX-B is antigenically distinct from BTX-A and possesses a different mechanism of action . Three r and omized , double-blind , placebo-controlled clinical trials evaluated the safety and efficacy of BTX-B ( Elan 's BTX-B evaluated as NeuroBloc ) as a treatment for patients with CD . Patients received a single dose of BTX-B ranging from 2,500 to 10,000 U. The primary efficacy evaluation for each of these studies used the Toronto Western Spasmodic Torticollis Rating Scale ( TWSTRS ) total score . Additional efficacy measures included the TWSTRS severity , disability , and pain subscale scores , as well as the Patient Analog Pain Assessment and Patient 's and Physician 's Global Assessment s of Change . In all three studies , groups receiving BTX-B displayed statistically significant improvements in TWSTRS total score and other efficacy end points compared with those who received placebo treatment . The clinical benefits after BTX-B treatment lasted 12 to 16 weeks and were observed in both BTX-A-responsive and BTX-A-resistant patients . In general , treatment with BTX-B was well tolerated and most of the reported adverse events were of short duration , mild to moderate in severity , and anticipated . The results from the three controlled clinical trials demonstrate the safety and efficacy of BTX-B in the treatment of patients with CD , including those who are resistant to BTX-A treatment 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 , r and omized , 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 clinical ly in CD . The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure . Clinical assessment s 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 r and omly 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 prospect ively 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 We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind , placebo-controlled safety and efficacy study of botulinum toxin type B ( BotB ) .  Both A-responsive and A-resistant patients were enrolled . Patients received intramuscular injections of either BotB ( 2,500 U , 5,000 U , or 10,000 U ) or placebo . The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration . Secondary measures of efficacy were TWSTRS-Severity , -Disability , and -Pain subscale scores , and Analog Pain Assessment , Investigator Global Assessment , Patient Global Assessment , and Sickness Impact Profile scores . Duration of effect was estimated with an intent-to-treat analysis of responders . Safety measures included clinical parameters , laboratory tests , and adverse events . The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response . BotB is safe , well tolerated , and efficacious in the treatment of cervical dystonia at the doses tested In this multicenter study of 100 patients with cervical dystonia , we examined the immunogenicity of botulinum toxin type B ( BTX-B ) and correlated the clinical response with the presence of blocking antibodies ( Abs ) using a novel mouse protection assay . One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit . Thus , the high antigenicity of BTX-B limits its long-term efficacy To evaluate the immunogenicity of botulinum toxin type A ( BoNTA ; BOTOX ) in  cervical dystonia ( CD ) . Subjects diagnosed with CD for > or = 1 year and previously naïve to BoNTs  were treated with BoNTA in a prospect i ve , open-label , multicenter study . Serum sample s were analyzed for BoNTA neutralizing antibodies using the Mouse Protection Assay ( MPA ) . Clinical resistance was assessed with a test injection of 20 U BoNTA placed unilaterally into the frontalis ( Frontalis Antibody Test ; FTAT ) or corrugator muscle ( Unilateral Brow Injection ; UBI ) . Efficacy was assessed and adverse events were recorded . Of 326 subjects enrolled , 251 ( 77 % ) completed the study . Subjects received a median of 9 BoNTA treatments ( mean dose per session ranged from 148.4 to 213.0 U over a mean of 2.5 years [ range : 3.2 months-4.2 years ] ) . Only 4 of 326 subjects ( 1.2 % ) tested positive for antibodies in the MPA ; three of these subjects stopped responding clinical ly to BoNTA ( of whom one also showed clinical resistance in the FTAT ) and one continued to respond . Consistent improvements in the signs/symptoms of CD were noted . The most frequent treatment-related adverse events were mild to moderate weakness , dysphagia , neck pain , and injection-site pain . The current formulation of BoNTA rarely causes neutralizing antibody formation in CD subjects treated < or = 4 years Neck pain is reported in 75 % is strongly associated with greater disability and decreased quality of life .  Botulinum toxin type B ( BoNT-B ; Myobloc ) is a new botulinum toxin that has been proven safe and effective in reducing the pain , severity , and disability of patients with cervical dystonia . We analyzed a subset of efficacy data from two r and omized , double blind , placebo-controlled clinical trials . The first study consisted of three treatment groups in patients who were responders to the type A toxin , including placebo  ( n=36 ) , 5000 units ( U ) ( n=36 ) , 10,000 U ( n=37 ) . The second study consisted of placebo ( n=38 ) and 10,000-U treatment groups ( n=39 ) in patients not responding to the type A toxin . For this analysis , the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-subscale scores for pain and three visual analog scales ( Patient Analog Pain , Patient Global , and Principal Investigator Global Assessment s ) were evaluated . A dose-response effect was observed in the reduction of pain based on the TWSTRS-subscale scores . In both studies , mean improvements from baseline to week 4 for all patients were significant compared with placebo ( P<0.005 ) . BoNT-B also significantly improved mean values for all VAS assessment s. Our analysis confirms that BoNT-B significantly reduces the pain associated with  cervical dystonia  and improves patients ' overall condition . This clinical benefit suggests that BoNT-B may be useful in other pain syndromes involving involuntary muscle spasms or contractions Botulinum toxin ( BT ) has been used with great success to treat various muscle hyperactivity disorders . Occasionally , antibodies against BT ( BT-AB ) can be formed . When they are directed against the neurotoxin component of the BT drug , they are called neutralising antibodies . They can reduce the therapeutic effect partially or completely . We have measured neutralising BT-AB by use of the mouse diaphragm assay ( MDA ) in 42 adult patients with spasticity in the order of their appearance in the clinic . The patients had been treated for at least 2 years with BT type A ( BT-A ) and received on an average 14.2 ± 6.1 BT-A injection series . BT-A was applied as Botox only , Dysport only or by sequential application of both preparations . The mean cumulative doses were 4,610 ± 1,936 units Botox and 14,033 ± 7,566 units Dysport , respectively . The mean treatment time was 4.5 ± 1.8 ( 2–8 ) years . All patients were initially responsive  to BT-A therapy . MDA detected BT-AB in 12 % ( 5/42 ) of patients . However , in three patients the BT-AB titre was very low ( < 0.3 mIU/ml ) , in one it was intermediate ( 0.6 mIU/ml ) and in one patient it was high ( > 1.0 mIU/ml ) . All BT-AB negative patients and also two of the patients with low BT-AB titre remained clinical ly responsive  to BT therapy throughout the study . In conclusion , prevalence of BT-AB formation with clinical relevance ( 6 % , 3/42 ) in adult patients with spasticity is not higher than that of BT-treated patients with cervical dystonia and much lower than that of BT-treated  patients with infantile cerebral palsy Botulinum neurotoxin ( BoNT ) serotype A is commonly used in the treatment of focal dystonia . Nevertheless , some patients are or become resistant to this serotype . Consequently , other different serotypes have to be used . A comparison of the neuromuscular blockade induced by BoNT type A and C in the extensor digitorum brevis muscles of voluntary subjects was studied , by evaluating the amplitude variation over the time ( until 90 days ) of the compound muscular action potential elicited by supramaximal electrical stimulation of the peroneal nerve at the ankle . A very similar effect and temporal profile , was observed for each serotype . On this basis , two patients with idiopathic facial hemispasm and one with blepharospasm were treated with BoNT serotype C with very beneficial long lasting effects In a double-blind trial in 21 patients with spasmodic torticollis botulinum-A toxin  produced both subjective and objective improvement , including significant pain relief in 14 of the 16 patients presenting with pain .  Side-effects were more frequently reported during placebo administration and no significant systemic adverse reactions were noted 
    Output:
    
All tested dosages were efficacious against placebo without clear-cut evidence of a dose-response gradient .
However , duration of effect ( time until return to baseline TWSTRS-total score ) and risk of dry mouth and dysphagia were greater in the subgroup of participants treated with higher BtB doses .
Subgroup analysis showed a higher improvement with BtB among BtA-non-responsive participants , although there were no differences in the effect size between the BtA-responsive and non-responsive subgroups .
A single BtB-treatment session is associated with a significant and clinical ly relevant reduction of cervical dystonia impairment including severity , disability and pain , and is well tolerated , when compared with placebo .
However , BtB-treated patients are at an increased risk of dry mouth and dysphagia .
There are no RCT data to allow us to draw definitive conclusions on the optimal treatment intervals and doses , usefulness of guidance techniques for injection , and impact on quality of life