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Introduction The safety and efficacy of both abobotulinumtoxinA and onabotulinumtoxinA for upper limb spasticity are well established, but head-to-head comparisons are lacking. Methods DIRECTION is an international, randomized, double-blind, crossover study comparing the safety and efficacy of abobotulinumtoxinA with onabotulinumtoxinA in the management of upper limb spasticity at doses at or near maximum recommended in product labelling. Participants (18–75 years) will be randomized (1:1) to either one cycle of abobotulinumtoxinA (900U) followed by onabotulinumtoxinA (360U) or vice versa. To maintain blinding, a fixed volume (3.6 ml) will be injected into the target upper limb muscles (four wrist and finger flexors and biceps brachii). The second treatment cycle will begin at Week 12 if retreatment criteria are fulfilled, and if not, they will be reassessed every 4 weeks until they meet retreatment parameters. Planned Outcomes The primary hypothesis is that there is comparable safety between products; non-inferiority will be tested based on treatment-emergent adverse event (TEAE) rates from injection to Week 12. A secondary hypothesis is that abobotulinumtoxinA has longer duration of effect than onabotulinumtoxinA. This hypothesis will be tested with secondary efficacy endpoints, including injection cycle duration, Modified Ashworth Scale, Disability Assessment Scale and Physician Global Assessment. Trial Registration EudraCT (http://eudract.ema.europa.eu): 2021-000161-32 and Clinicaltrials.gov (http://clinicaltrials.gov): NCT04936542. Overview of the study protocol by the principal investigator (MP4 185265 KB) Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01896-3. more...

The aim of this study in patients with post-stroke lower limb spasticity (PSLLS) was to evaluate the relationship between time of onabotulinumtoxinA treatment relative to stroke and efficacy outcomes. This was a phase 3, international, multicenter, randomized, 12-week, double-blind study, followed by a repeated treatment, open-label extension. Patients were aged 18–85 years with PSLLS (Modified Ashworth Scale [MAS] ≥ 3) of the ankle with the most recent stroke occurring ≥ 3 months before screening. Patients (double-blind phase) were randomized (n = 468) to onabotulinumtoxinA 300–400 U (300 U, mandatory ankle muscles (gastrocnemius, soleus, tibialis posterior); and ≤ 100 U, optional lower limb muscles (flexor digitorum longus, flexor hallucis longus, flexor digitorum brevis, extensor hallucis, and rectus femoris]) or placebo. Primary endpoint: MAS change from baseline (average score of weeks 4 and 6). Secondary endpoints: physician-assessed Clinical Global Impression of Change (CGI) average score of weeks 4 and 6 and physician-assessed Goal Attainment Scale (GAS; active and passive, weeks 8 and 12). When stratified by time since stroke (≤ 24 months, n = 153; > 24 months, n = 315, post hoc), patients treated ≤ 24 months post-stroke experienced greater improvements from baseline versus placebo in MAS (− 0.31 vs − 0.17), CGI (0.49 vs 0.12), and passive GAS scores (week 12, 0.37 vs 0.26). A ≥ − 1-point improvement in active (week 12; p = 0.04) and passive (week 8; p = 0.02) GAS scores versus placebo was achieved by more patients treated ≤ 24 months post-stroke; in patients treated > 24 months post-stroke, improvements were only observed in active scores (week 8; p = 0.04). OnabotulinumtoxinA 300–400 U was well tolerated, with no new safety findings. more...

BACKGROUND Poststroke spasticity affects motor function and the ability to perform activities of daily living, with the potential to affect quality of life (QoL) and increase caregiver burden. OBJECTIVE To investigate the effect of repeated incobotulinumtoxinA treatment on spasticity-associated functional disability, caregiver burden, and QoL in the 36-week open-label extension of the phase 3 PURE study (NCT01392300). DESIGN Open-label extension period of a prospective, double-blind, placebo-controlled, randomized, multicenter study. SETTING Forty-six investigation sites in seven countries (Czech Republic, Germany, Hungary, India, Poland, Russia, United States). PARTICIPANTS Adults, aged 18-80 years, ≥12 months since last botulinum neurotoxin injection or entirely toxin naive, with median poststroke upper-limb spasticity of >2 years' duration. METHODS Participants who completed the 12-week, double-blind main period could enter the open-label extension and receive up to three additional incobotulinumtoxinA treatments (fixed total dose 400 U at 12-week intervals) into the affected muscles of one upper limb. MAIN OUTCOME MEASURES Functional disability (Disability Assessment Scale; DAS), caregiver burden (Carer Burden Scale), and quality of life (QoL; EuroQol [EQ] 5-dimensions three-level [EQ-5D-3L]). RESULTS The open-label extension included 296 treated patients. Mean DAS score for the principal target domain improved significantly from the main period baseline to the end-of-study visit (P more...

Cervical dystonia (CD) is primarily treated with botulinum toxin, at intervals of ≥ 12 weeks. We present efficacy, patient-reported outcomes (PROs), and safety in adults with CD at the last available visit after a single set of abobotulinumtoxinA (aboBoNT-A) injections versus placebo using 500 U in a 2-mL injection volume. In this 12-week, randomized, double-blind trial, patients were ≥ 18 years of age with primary idiopathic CD, had a Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥ 20, and TWSTRS-Severity subscale score > 10 at baseline. Patients (N = 134) were randomized (2:1) to aboBoNT-A (n = 89) or placebo (n = 45), with aboBoNT-A patients treated with 500 units (U) if toxin-naïve, and 250 to 500 U based on previous onabotulinumtoxinA dose if non-naïve. Endpoints included total TWSTRS, Pain Numeric Rating Scale (NRS-Pain; 24-hour), Treatment Satisfaction Questionnaire for Medication, and other PROs for pain, depression, and global health. Results are for the intent-to-treat population, with “Week 12” (Wk12) comprising the last available post-baseline assessment (end-of-study or early withdrawal). Mean TWSTRS total scores improved from 42.5 at baseline to 35.4 at Wk12 with aboBoNT-A and 42.4 to 40.4 with placebo (treatment difference: –4.8; 95% confidence interval [CI]: –8.5, –1.1; p = 0.011). At Wk12, mean (95% CI) change from baseline in NRS-Pain was –1.0 (–1.59, –0.45) for aboBoNT-A and –0.2 (–0.96, 0.65) for placebo. AboBoNT-A demonstrated numeric improvements in other PROs. More aboBoNT-A–treated patients than patients receiving placebo reported being at least “somewhat satisfied” with treatment (60.4% vs 42.2%, respectively), symptom relief (57.0% vs 40.0%), and time for treatment to work (55.8% vs 33.3%). No new adverse events were reported. Results indicate that in patients with CD, treatment with aboBoNT-A using a 2-mL injection provided sustained improvement in the TWSTRS total score and patient-perceived benefits up to 12 weeks. Trial registration: Clinicaltrials.gov Identified: NCT01753310. more...

This chapter provides a guide for prescribing and outlines the basic principles for using upper limb orthotic devices, commonly known as splints or braces. The goal is to cover the principles of upper extremity orthoses and make the indications for when to use them very clear and easy to learn. A multitude of different diagnoses are covered in detail, with a rationale for how the orthosis will correct the pathophysiology of the disease process. more...

Introduction The objective of the study was to investigate the efficacy and safety of repeated incobotulinumtoxinA injections for the treatment of upper-limb post-stroke spasticity in adults. Methods Adults 18–80 years of age with post-stroke upper-limb spasticity who completed the 12-week randomized, double-blind, placebo-controlled main period (MP) of a phase 3 trial (NCT01392300) were eligible to enrol in the 36-week open-label extension period (OLEX). The OLEX included three treatment cycles at fixed 12-week injection intervals; subjects were injected with 400 U incobotulinumtoxinA into the affected upper limb. Efficacy assessments included evaluation of muscle tone using the Ashworth Scale (AS) and the Global Impression of Change Scale (GICS) assessed by the investigator, subject, and caregiver. The incidence of adverse events (AEs) was monitored throughout the OLEX. Results A total of 296 of 299 subjects (99.0%) who completed the MP received incobotulinumtoxinA in the OLEX, and 248 subjects completed the 36-week OLEX. The proportion of subjects with at least a 1-point improvement in AS score from each incobotulinumtoxinA treatment to the respective 4-week post-injection visit ranged by cycle from 52.3% to 59.2% for wrist flexors, 49.1% to 52.3% for elbow flexors, 59.8% to 64.5% for finger flexors, 35.5% to 41.2% for thumb flexors, and 37.4% to 39.9% for forearm pronators (P more...

Background: Injectable daxibotulinumtoxinA (an investigational botulinum toxin, RT002) may offer a more prolonged duration of response – and therefore less frequent dosing – than onabotulinumtoxinA. Objectives: To perform a phase 2, open-label, dose-escalation study to assess the efficacy and safety of daxibotulinumtoxinA in cervical dystonia. Methods: Subjects with moderate to severe isolated cervical dystonia were enrolled in sequential cohorts to receive a single open-label, intramuscular dose of injectable daxibotulinumtoxinA of up to 200U (n=12), 200–300U (n=12), or 300–450U (n=13) (clinicaltrials.gov identifier NCT02706795). Results: Overall, 33/37 enrollees completed the trial. DaxibotulinumtoxinA was associated with reductions in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total score of 16.8 (38%) at week 4, 21.3 (50%) at week 6, and 12.8 (30%) at week 24. The proportion of subjects who were responders (achieved ≥ 20% reduction in TWSTRS-Total score) was 94% at week 6 and 68% at week 24. The median duration of response (time until > 20% of the improvement in TWSTRS-Total score achieved at week 4 was no longer retained or re-treatment was needed) was 25.3 weeks (95% CI, 20.14–26.14 weeks). There were no serious adverse events and there was no apparent dose-related increase in the incidence of adverse events. The most common treatment-related adverse events were dysphagia (14%) and injection site erythema (8%). Conclusions: Preliminary assessments suggest that injectable daxibotulinumtoxinA at doses up to 450U is well tolerated and may offer prolonged efficacy in the treatment of cervical dystonia. Further studies involving larger numbers of patients are now warranted. This article is protected by copyright. All rights reserved. more...

BACKGROUND Patient- and caregiver-reported data are lacking on the burden of spasticity, and the impact of botulinum neurotoxin type A (BoNT-A) treatment for this condition, on patients' daily lives. As recommended in recent guidance from the US Food and Drug Administration, online patient communities can represent a platform from which to gather specific information outside of a clinical trial setting on the burden of conditions experienced by patients and caregivers and their views on treatment options in order to inform evidence-based medicine and drug development. OBJECTIVE The objective of our study is to characterize spasticity symptoms and their associated burdens on Western European and US patients and caregivers in the realms of work, daily activities, quality of life (QoL), as well as the positive and negative impacts of treatment with BoNT-A (cost, time, QoL) using Carenity, an international online community for people with chronic health conditions. METHODS We performed a noninterventional, multinational survey. Eligible participants were 18 years old or older and had, or had cared for, someone with spasticity who had been treated with BoNT-A for at least 1 year. Patients and caregivers were asked to complete an internet-based survey via Carenity; caregivers reported their own answers and answered on behalf of their patients. Questions included the burden of spasticity on the ability to work, functioning, daily-living activities, and QoL, the impact of BoNT A therapy on patients' lives, and the potential benefits of fewer injections. RESULTS There were 615 respondents (427 patients and 188 caregivers). The mean age of patients and caregivers was 41.7 years and 38.6 years, respectively, and the most commonly reported cause of spasticity was multiple sclerosis. Caregivers were most often the parents (76/188, 40%) or another family member (51/188, 27%) of their patients. Spasticity had a clear impact on patients' and caregivers' lives, including the ability to work and injection costs. For patients, spasticity caused difficulties with activities of daily living and reduced QoL indices. The median number of BoNT-A injections was 4 times per year, and 92% (393/427) of patients reported that treatment improved their overall satisfaction with life. Regarding the BoNT-A injection burden, the greatest patient-reported challenges were the cost and availability of timely appointments. Overall, 86% (368/427) of patients believed that a reduced injection frequency would be beneficial. Caregivers answering for their patients gave largely similar responses to those reported by patients. CONCLUSIONS Spasticity has a negative impact on both patients' and caregivers' lives. All respondents reported that BoNT A treatment improved their lives, despite the associated challenges. Patients believed that reducing the frequency of BoNT-A injections could alleviate practical issues associated with treatment, implying that a longer-acting BoNT-A injection would be well received. more...

Background Patient- and caregiver-reported data are lacking on the burden of spasticity, and the impact of botulinum neurotoxin type A (BoNT-A) treatment for this condition, on patients' daily lives. As recommended in recent guidance from the US Food and Drug Administration, online patient communities can represent a platform from which to gather specific information outside of a clinical trial setting on the burden of conditions experienced by patients and caregivers and their views on treatment options in order to inform evidence-based medicine and drug development. Objective The objective of our study is to characterize spasticity symptoms and their associated burdens on Western European and US patients and caregivers in the realms of work, daily activities, quality of life (QoL), as well as the positive and negative impacts of treatment with BoNT-A (cost, time, QoL) using Carenity, an international online community for people with chronic health conditions. Methods We performed a noninterventional, multinational survey. Eligible participants were 18 years old or older and had, or had cared for, someone with spasticity who had been treated with BoNT-A for at least 1 year. Patients and caregivers were asked to complete an internet-based survey via Carenity; caregivers reported their own answers and answered on behalf of their patients. Questions included the burden of spasticity on the ability to work, functioning, daily-living activities, and QoL, the impact of BoNT A therapy on patients' lives, and the potential benefits of fewer injections. Results There were 615 respondents (427 patients and 188 caregivers). The mean age of patients and caregivers was 41.7 years and 38.6 years, respectively, and the most commonly reported cause of spasticity was multiple sclerosis. Caregivers were most often the parents (76/188, 40%) or another family member (51/188, 27%) of their patients. Spasticity had a clear impact on patients' and caregivers' lives, including the ability to work and injection costs. For patients, spasticity caused difficulties with activities of daily living and reduced QoL indices. The median number of BoNT-A injections was 4 times per year, and 92% (393/427) of patients reported that treatment improved their overall satisfaction with life. Regarding the BoNT-A injection burden, the greatest patient-reported challenges were the cost and availability of timely appointments. Overall, 86% (368/427) of patients believed that a reduced injection frequency would be beneficial. Caregivers answering for their patients gave largely similar responses to those reported by patients. Conclusions Spasticity has a negative impact on both patients' and caregivers' lives. All respondents reported that BoNT A treatment improved their lives, despite the associated challenges. Patients believed that reducing the frequency of BoNT-A injections could alleviate practical issues associated with treatment, implying that a longer-acting BoNT-A injection would be well received. more...

Supplemental digital content is available in the text., Objective The aim of the study was to report physician experience–based “real-world” treatment patterns with botulinum toxin type A in patients with stroke and traumatic brain injury. Design A prospective, multicenter, international observational registry design was used. Results Six hundred twenty-seven participants with stroke and 132 participants with traumatic brain injury were assessed and treated by 17 more experienced physicians and 12 less experienced physicians. Due to the limited usage of abobotulinumtoxinA Dysport and incobotulinumtoxinA Xeomin, data were reported on onabotulinumtoxinA BOTOX only. Based on physician experience, onabotulinumtoxinA doses were statistically different with larger mean doses injected by more experienced physicians in the upper limb (59.9 [39.0], P = 0.001) and in the lower limb (101.8 [69.2], P < 0.001). Treated deformities significantly differed for both upper limb and lower limb (P < 0.001). More experienced physicians showed a larger mean change in Ashworth Scale scores from baseline for the equinovarus/equinus foot and stiff knee (P = 0.001 and 0.03). Less experienced physicians showed a larger mean change in Ashworth Scale scores from baseline for the adducted thigh (P = 0.05). Less experienced physicians had statistically significant larger change in hand pain scores for clenched fist deformity treatment at follow-up compared with more experienced physicians (P = 0.01). Physician experience demonstrated a significant difference on patients reported satisfaction toward their secondary goal with higher scores for more experienced physician (P = 0.04). Conclusions This international registry provides clinical nuances of treatment based on physician clinical experience in a robust sample size. more...

Introduction: OnabotulinumtoxinA (onabotA) is approved for treatment of post-stroke upper limb spasticity (PSULS) at a maximum dose of 400U across elbow, wrist, and finger sites. Safety and efficacy of a higher dose for PSULS were evaluated in elbow and shoulder sites not previously assessed. Methods: A multicenter, double-blind, randomized, placebo-controlled study evaluated a single treatment of onabotA 300U (150U: elbow flexors; 150U: shoulder adductors) or 500U (250U; 250U) vs placebo in adults with PSULS (Modified Ashworth Scale [MAS] score ≥3). Safety and efficacy were assessed at weeks 2, 4, 6, 8, and 12. The study was terminated early for administrative reasons. Results: All 53 enrolled patients completed the study. Baseline characteristics were similar between groups, except the onabotA 500U group had more men. Most patients were Caucasian and had a cerebral ischemic stroke of moderate severity (mean=101.7 months before enrollment). Mean change from baseline in elbow MAS for onabotA 500U was significantly greater than placebo at all time points (300U at wks 2 and 4, Figure 1) . Significant tone reductions were also observed in the shoulder adductors with 500U (wks 2 and 4). The proportion of treatment responders (≥1-grade reduction in elbow MAS) was numerically greater for onabotA 500U and 300U than placebo at all time points (300U significant [ P Conclusions: Preliminary results from this randomized trial investigating the safety and efficacy of higher-dose onabotA for elbow and shoulder spasticity indicate a dose-related benefit. At the higher dose of 500U onabotA, no new safety signals were observed; AEs did not appear to be dose-related. Funding: Allergan more...

Background OnabotulinumtoxinA is approved for the treatment of upper and lower limb spasticity in adults. Guidance on common postures and onabotulinumtoxinA injection paradigms for upper limb spasticity has been developed via a Delphi Panel; however, similar guidance for lower limb spasticity has not been established. Objective To define a clinically recommended treatment paradigm for the use of onabotulinumtoxinA for each common posture among patients with poststroke lower limb spasticity (PSLLS) and to identify the most common PSLLS aggregate postures. Design Clinical experts provided insight regarding onabotulinumtoxinA treatment for PSLLS using an adaptation of the Delphi consensus process. Setting Delphi panel. Participants Ten expert clinicians in neurology and physical medicine and rehabilitation who treat PSLLS. Methods A minimum of 2 rounds of anonymous voting occurred for each recommendation until consensus was reached (≥66% agreement). The first round was conducted via a survey; the second round was an in-person meeting. Main Outcome Measurements Reached consensus on muscle selection for injection, overall and per-muscle dose of onabotulinumtoxinA, number of injection sites/muscle, onabotulinumtoxinA dilution, and use of localization techniques. The most common PSLLS postures were reviewed. Recommendations were tailored toward injectors with less experience. Results Consensus was reached on targeted subsets of muscles for each posture. Doses ranged from 20 to 150 U for individual muscles and 50 to 300 U for limb postures. OnabotulinumtoxinA dilution 50 U/mL (2:1 ratio) was considered most appropriate but varied based on muscles selected (range, 2:1-4:1). Experts agreed that localization techniques for muscle identification during injection for all postures would be useful. For suboptimal response to injection, all panel members would increase the dose, and the majority (89%) would increase the number of treated muscles. The panel identified 3 common aggregating lower limb postures: (1) equinovarus foot and flexed toes; (2) extended knee and plantar flexed foot/ankle; and (3) plantar flexed foot/ankle and flexed toes. The recommended starting doses for each aggregate posture were 400 U, 400 U, and 300 U, respectively. Conclusion The modified Delphi panel process provided consensus on common muscles and corresponding onabotulinumtoxinA treatment paradigms for postures associated with PSLLS that can be used for guidance in optimizing care delivery. Level of Evidence V more...

The AAOS Evidence-Based Guideline on Management of Carpal Tunnel Syndrome (CTS) includes both diagnosis and treatment. This clinical practice guideline has been endorsed by the American Society for Surgery of the Hand (ASSH), the American College of Radiology (ACR), the American College of Surgeons (ACS), and the American Society of Plastic Surgeons (ASPS). This brief summary of the AAOS Clinical Practice Guideline contains a list of the recommendations and the rating of strength based on the quality of the supporting evidence. Discussion of how each recommendation was developed and the complete evidence report are contained in the full guideline at www.aaos.org/guidelines. ### OBSERVATION Strong evidence supports that thenar atrophy is strongly associated with ruling in CTS but poorly associated with ruling out CTS. Strength of Recommendation: Strong ★★★★ ### PHYSICAL SIGNS Strong evidence supports not using the Phalen test, Tinel sign, or upper limb neurodynamic/nerve test (ULNT) criterion A/B as independent physical examination maneuvers to diagnose CTS, because alone, each has a poor or weak association with ruling in or ruling out CTS. Strength of Recommendation: Strong ★★★★ ### MANEUVERS Moderate evidence supports not using the following as independent physical examination maneuvers to diagnose CTS, because alone, each has a poor or weak association with ruling in or ruling out CTS more...

As seen in this CME online activity (available at http://courses.elseviercme.com/spasticity/662e), treatment of patients with spasticity due to upper motor neuron syndromes, including traumatic brain injury, stroke, and cerebral palsy, is multifaceted, involving chemodenervation, systemic medications, surgical therapy, rehabilitation efforts, and home care. Optimal care begins with the recognition that each patient's impairments are unique and must be assessed carefully to determine the impact of muscle overactivity, loss of dexterity, and weakness on passive and active function in the context of the patients' goals. While botulinum toxin plays a major role in providing symptomatic relief and functional improvement from hypertonia, it should rarely be used as a standalone treatment. more...

Introduction/Background OnabotulinumtoxinA treatment for spasticity is variable as treatment is individualized and dependent on numerous factors. Here, we explore real-world patterns of onabotulinumtoxinA utilization in patients with upper limb spasticity over 2 years. Material and method Multicenter, international, prospective, observational study ( NCT01930786 ), examining adult patients with focal spasticity across multiple etiologies treated with onabotulinumtoxinA at their physician's discretion. Assessments include utilization (each treatment visit) and patient/physician satisfaction (5 ± 1 weeks post-treatment). Results Patients (n = 731) were on average 53.6 years of age (18.5–93.2 years), 52% female, and predominantly Caucasian (77%). Stroke was the most frequently reported etiology (56%). The most commonly treated upper limb spasticity presentation was clenched fist (52%). Across all clenched fist treatment sessions (n = 1505), percentage injected and dose (mode) injected into each muscle are as follows: flexor digitorum superficialis (86%, 50U), flexor digitorum profundus (80%, 50U), flexor pollicis longus (25%, 20U), flexor pollicis brevis (9%, 25U), other (6%, 20U). EMG was frequently used to localize muscles to treat clenched fist (> 44%). Across all treatment sessions, 93% of physicians and 86% of patients reported being satisfied/extremely satisfied that treatment helped manage spasticity, 84% of physicians and 76% of patients reported treatment benefit was sustained, and 99% of physicians and 92% of patients would definitely/probably continue treatment with onabotulinumtoxinA. Two hundred and sixty-one patients (36%) reported 831 adverse events (AEs); 23 AEs in 20 patients (3%) were considered treatment-related. Ninety-four patients (13%) reported 195 serious AEs; 3 serious AEs in 2 patients (0.3%) were considered treatment-related. No new safety signals were identified. Conclusion ASPIRE provides valuable, real-world data on dosing, injection guidance, and muscle targeting over 2 years, that may help guide clinical strategies. This study captured the individualized nature of onabotulinumtoxinA utilization for spasticity, while demonstrating consistently high satisfaction. These results add to the body of evidence on the safety and effectiveness of onabotulinumtoxinA for spasticity. more...

Introduction/Background Etiology-specific differences in onabotulinumtoxin A utilization to treat spasticity are largely unknown. Real-world clinical practice data from the ASPIRE study may help optimize onabotulinumtoxin A treatment for spasticity. Our objective is to evaluate real-world utilization of onabotulinumtoxin A for spasticity caused by various etiologies. Material and method 1-year interim analysis; international, multicenter, prospective, observational study ( NCT01930786 ) examining adult patients with spasticity across etiologies. Patients were treated with onabotulinumtoxin A at the physician's discretion; utilization patterns were recorded at each visit. Results A total of 731 patients received ≥ 1 onabotulinumtoxinA treatment; 37% of patients were naive to botulinum toxins for spasticity. The most common etiology was stroke (n = 411/731, 56%), followed by multiple sclerosis (MS; n = 119/731, 16%), cerebral palsy (CP; n = 77/731, 11%), traumatic brain injury (TBI; n = 45/731, 6%), spinal cord injury (SCI; n = 42/731, 6%), and other (n = 72/731). Across etiologies (n = 731), total onabotulinumtoxin A doses per treatment session ranged from 45–1038 U. The most frequently treated lower limb presentations, with mean doses injected per presentation, varied by etiology. Stroke: equinovarus foot (223 U [SD = 131]), flexed toe (64 U [SD = 51]), and flexed knee (143 U [SD = 86]); MS: equinovarus foot (206 U [SD = 124]), stiff extended knee (155 U [SD = 134]), and adducted thigh (173 U [SD = 112]); CP: equinovarus foot (162 U [SD = 116]), flexed knee (150 U [SD = 89]), and adducted thigh (163 U [SD = 94]); TBI: equinovarus foot (223 U [SD = 109]), flexed toe (89 U [SD = 61]), and flexed knee (154 U [SD = 60]); and SCI: equinovarus foot (277 U [SD = 168]), adducted thigh (140U [SD = 66]), and flexed knee (165 U [SD = 84]). In the overall population (n = 731), adverse events (AEs) were reported by 28.9% of patients, with 2.3% of events considered treatment-related. Serious AEs were reported by 10.3% of patients, with 0.3% of events considered treatment-related. No new safety signals were identified. Conclusion Real-world 1-year interim data from ASPIRE captured etiology-specific utilization of onabotulinumtoxin A for spasticity in clinical practice, while further demonstrating safety across etiologies. more...

Introduction/Background Spasticity can have a considerable impact on patients’ lives, causing pain and loss of mobility with resultant burden to patients and caregivers. Botulinum toxin-A (BoNT-A) injections have proven to be an efficacious and well-tolerated treatment for spasticity. The objectives were: (1) to measure the impact of spasticity on patients’ and caregivers’ employment and quality of life, (2) to better understand patient perceptions of BoNT-A injections. Material and method A survey is currently being conducted by Carenity (an online patient community) in the US and Europe (France, Germany, Italy, Spain, UK). A committee (a patient, 3 neurologists and a physiatrist) approved the questionnaire. This analysis reports data from 333 participants enrolled to date, (target: 600) including 210 patients with spasticity receiving BoNT-A injections, and 123 caregivers. Results The respondents’ spasticity was caused by multiple sclerosis (40%), stroke (22%) and spinal cord injury (9%). Mean age was 47.6 years and 54% of patients were women. Impact on work: – 50% of patients work part-time or do not work due to their condition; – 32% of caregivers limit their work activity to help the patient; – professional life was the most affected area (mean = 6.9/10, 0 = no impact, 10 = a great impact). Spasticity also had an impact on patients’ leisure activities (mean = 6.7/10), self-esteem (mean = 6.6/10) and sexual life (mean = 6.6/10). The overall level of satisfaction regarding BoNT-A injections was acceptable (mean = 5.9/10), despite the inconvenience associated with the injections, including pain during/after injections (mean = 4.1/10), logistic constraints such as travel (mean = 3.8/10) or difficulties related to frequency of injections (mean = 3.5/10). Seventy-one percent of respondents would feel benefits from having 1 or 2 fewer injections per year. Conclusion These results emphasize the multifaceted impact of spasticity on patients’ and caregivers’ quality of life. Patients receiving BoNT-A injections are mostly satisfied with their treatment, but report some inconvenience and would prefer less frequent injections. more...

1. Which factor is an absolute contraindication for usingrecombinant tissue plasminogen activator (TPA) in anacute stroke?(a) A score of 20 or greater on the National Institutesof Health Stroke Scale.(b) A history of stroke or myocardial infarctionwithin the previous 3 months.(c) Systolic blood pressure above 185 mmHg.(d) Platelets greater than 100,000 mm more...

Background OnabotulinumtoxinA reduces muscle hypertonia associated with poststroke spasticity (PSS). PSS manifests as several common postures. Objective To define treatment paradigms for PSS upper-limb common postures. Design Modified Delphi method. Setting Expert panel. Participants Ten injectors experienced in the treatment and clinical research of PSS (physiatrists and neurologists) were invited to participate in the Delphi panel. Methods The Delphi panel reviewed an electronic worksheet with PSS upper-limb postures to define onabotulinumtoxinA treatment paradigms (Round 1). During Round 2, panel members discussed in person Round 1 results and voted until consensus (≥66% agreement). Recommendations were geared toward those with new or early injection experience. Main Outcome Measurements Expert consensus on onabotulinumtoxinA treatment parameters for PSS including muscles to inject, dose per muscle and posture, and treatment adjustments for suboptimal response. Results For each posture, consensus was reached on targeted subsets of muscles. Doses ranged for individual muscles (10-100 U) and total doses per posture (50-200 U). An onabotulinumtoxinA dilution 50 U/mL (2:1 dilution ratio) was considered most appropriate; dilution ratios of 1:1 to 4:1 may be appropriate in some circumstances. The majority (89%) of panel members would increase the dose and/or the number of muscles treated for a suboptimal response to onabotulinumtoxinA. The panel identified 3 common aggregate upper-limb postures: (1) adducted shoulder + flexed elbow + pronated forearm + flexed wrist + clenched fist; (2) flexed elbow + pronated forearm + flexed wrist + clenched fist; and (3) flexed wrist + clenched fist. The recommended starting dose per aggregate was 300 U, 300 U, and 200 U, with a total maximum dose of 400 U, 400 U, and 300 U, respectively. Localization guidance techniques were considered essential for all postures. Conclusions Consensus on common muscles and onabotulinumtoxinA treatment paradigms for postures associated with upper-limb PSS was achieved via a modified Delphi method. The purpose of this analysis is to educate early onabotulinumtoxinA injectors rather than provide an evidence-based review. Level of Evidence V more...

Background Pain is a prevailing feature of cervical dystonia (CD), the most common form of focal dystonia. This analysis examined pain relief after onabotulinumtoxinA treatment in CD subjects with moderate/severe pain from the Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE). Methods CD PROBE was a prospective, multicenter, observational registry of CD subjects who were naive to botulinum toxin (BoNT), new to physician, or had not received BoNT within ≥ 16 weeks if in a clinical trial. Subjects were eligible for 3 treatments, with variable session intervals. Descriptive and inferential statistics were utilized to evaluate the change in pain scores in the population with moderate/severe neck pain at baseline (Pain Numeric Rating Scale [PNRS] score 4 to 10). Results Of 1046 enrolled, 733 (70.7%) had moderate/severe neck pain at baseline. Postinjection pain questionnaire responses 4 to 6 weeks after each of the 3 treatments revealed that a majority of subjects (67.1%, 72.4%, and 76.4%) reported pain relief; mean time to pain relief was 7.1, 7.4, and 7.6 days. All pain scales showed significant improvements from baseline to final visit (all P < 0.0001): PNRS, mean 6.6 to 3.8; CD Impact Profile-58 Pain and Discomfort subscale, mean 78.7 to 56.5; and Toronto Western Spasmodic Torticollis Rating Scale Pain subscale, mean 12.6 to 8.5. Multivariable regression models showed that initial pain score significantly contributed to the final pain score for all scales. Conclusion Results from this real-world clinical registry indicate that a majority of CD subjects with moderate/severe neck pain experience significant relief following onabotulinumtoxinA treatment. more...