Sustained efficacy of incobotulinumtoxina repeated injections for upper-limb post-stroke spasticity: A post hoc analysis.

OBJECTIVE: This post hoc analysis assessed the impact of repeated incobotulinumtoxinA injections on muscle tone, disability, and caregiver burden in adults with upper-limb post-stroke spasticity. DESIGN: Data from the double-blind, placebo-controlled main period and three open-label extension cycles of two Phase 3, randomized, multicentre trials were pooled. METHODS: Subjects received incobotulinumtoxinA 400 Units at 12-week intervals (±3 days) (study 3001, NCT01392300) or ≤ 400 Units at ≥12-week intervals based on clinical need (study 0410, NCT00432666). Ashworth Scale (AS) arm sumscore (sum of elbow, wrist, finger and thumb flexor, and forearm pronator AS scores), Disability Assessment Scale (DAS), and Carer Burden Scale (CBS) scores were assessed. RESULTS: Among 465 subjects, from study baseline to 4 weeks post-injection, mean (standard deviation) AS arm sumscore improved continuously: main period, -3.23 (2.55) (placebo, -1.49 (2.09)); extension cycles 1, 2, and 3, -4.38 (2.85), -4.87 (3.05), and -5.03 (3.02), respectively. DAS principal target domain responder rate increased from 47.4% in the main period (placebo 27.2%) to 66.6% in extension cycle 3. Significant improvements in CBS scores 4 weeks post-injection accompanied improved functional disability in all cycles. CONCLUSION: IncobotulinumtoxinA conferred sustained improvements in muscle tone, disability, and caregiver burden in subjects with upper-limb post-stroke spasticity.

Duration of Treatment Effect Using IncobotulinumtoxinA for Upper-limb Spasticity: A Post-hoc Analysis.

The efficacy and safety of incobotulinumtoxinA ≤400 U was demonstrated in subjects with post-stroke upper-limb spasticity in a randomized, double-blind Phase 3 study with an open-label extension (OLEX; EudraCT number 2005-003951-11, NCT00432666). We report a post-hoc analysis of the duration of the treatment effect. Subjects completing the placebo-controlled main period (single injection cycle with 12-20-week observation) entered the OLEX and received a maximum of five further treatments (maximum duration 69 weeks) with incobotulinumtoxinA ≤400 U at flexible intervals with a minimum duration of 12 weeks, based on clinical need. Intervals between two consecutive incobotulinumtoxinA injections, excluding treatment intervals prior to the end-of-study visit, were evaluated. Of 437 incobotulinumtoxinA treatment intervals, 415 received by 136 subjects were included in the post-hoc analysis. More than half (52.3%; 217/415) of all incobotulinumtoxinA reinjections were administered at Week ≥14, 31.1% (129/415) at Week ≥16, 19.0% (79/415) at Week ≥18, and 11.6% (48/415) at Week ≥20. The duration of effect may vary and can exceed 20 weeks or more, which was observed in at least one injection cycle in 29.4% (40/136) subjects over the course of their treatment. Data show that incobotulinumtoxinA retreatment for upper-limb spasticity may not be required at 12-week intervals and provides evidence for flexible treatment intervals beyond this time frame.

IncobotulinumtoxinA Treatment in Upper-Limb Poststroke Spasticity in the Open-Label Extension Period of PURE: Efficacy in Passive Function, Caregiver Burden, and Quality of Life.

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 naïve, 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 < .0001). Carer Burden Scale scores also significantly improved from the main period baseline to the end-of-study visit (P < .05 for all caregiving activities except "applying a splint"). At the end-of-study visit, versus the main period baseline, 19.7%-33.3% of patients experienced improvements for each parameter on the EQ-5D-3L, except "mobility," with significant improvement in EQ-5D visual analog scale scores (P < .001). CONCLUSIONS: Repeated incobotulinumtoxinA treatments at 12-week intervals in participants with chronic poststroke upper-limb spasticity resulted in significant improvements in QoL, as well as significant reductions in upper-limb functional disability and caregiver burden.

IncobotulinumtoxinA Efficacy and Safety in Adults with Upper-Limb Spasticity Following Stroke: Results from the Open-Label Extension Period of a Phase 3 Study.

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 < 0.0001 for all). Over 90% of subjects were assessed by the investigator to be at least minimally improved (4 weeks post-injection) on the GICS during each injection cycle; 61.0% in the 1st cycle, 58.2% in the 2nd cycle, and 57.4% in the 3rd cycle were considered much improved or very much improved on the GICS. Three percent of subjects (9/296) reported treatment-related AEs; the most frequently reported were pain in the extremity (n = 2, 0.7%) and constipation (n = 2, 0.7%). Serious AEs were reported by 22 subjects (7.4%); however, none were considered treatment-related. CONCLUSIONS: Repeated injections of incobotulinumtoxinA for the treatment of post-stroke upper-limb spasticity led to significant improvements in muscle tone and investigator's global impression of change. Treatment was well tolerated, with no serious treatment-related AEs. FUNDING: Merz Pharmaceuticals GmbH.

Relationship between disability and health-related quality of life and caregiver burden in patients with upper limb poststroke spasticity.

OBJECTIVE: To evaluate the relationship between disability and both health-related quality of life (HRQoL) and caregiver burden in patients with upper limb poststroke spasticity. DESIGN: Multicenter open-label study. SETTING: Thirty-five sites in North America. PARTICIPANTS: Patients (N = 279) with upper limb poststroke spasticity. METHODS: Post hoc analyses of data from an open-label study were performed to estimate HRQoL and caregiver burden at study baseline across levels of disability in 4 problem domains: hygiene, dressing, limb posture, and pain. Disability severity in these areas was determined by using the 4-point Disability Assessment Scale rated by the physicians. MAIN OUTCOME MEASUREMENTS: HRQoL measured by the patient-reported EuroQol 5 Dimensions questionnaire and the Stroke-Adapted Sickness Impact Profile and caregiver burden. RESULTS: At study baseline, increasing disability in the hygiene, dressing, and pain domains of the Disability Assessment Scale was associated with diminishing HRQoL scores (P < .002) measured by the EuroQol 5 Dimensions. By using the Stroke-Adapted Sickness Impact Profile, greater disability scores in all problem domains were significantly associated with higher overall dysfunction scores (P ≤ .05). Within the physical dimension of the Stroke-Adapted Sickness Impact Profile, significant associations also were observed in all domains. At baseline, caregiver burden was significantly related to increasing levels of hygiene and dressing domain severity (P ≤ .05). Caregiver assistance requirement increased from approximately 9.0-28.2 hours per week in the hygiene domain and 3.3-32.1 hours per week in the dressing domain as disability increased from "none" to "severe." CONCLUSIONS: In patients with upper limb poststroke spasticity, increasing disability in the hygiene, dressing, and pain domains of the Disability Assessment Scale were associated with diminishing HRQoL. Furthermore, these patients required caregiver assistance proportionally related to the severity of their disability in the hygiene and dressing domains.

Evaluation of a dynamic ankle foot orthosis in hemiplegic gait: A case report.

This investigation utilized a single case design to evaluate the effects of a dynamic AFO on ambulation in post stroke hemiplegia. A single patient with stroke related hemiplegia using a dynamic AFO underwent gait analysis while walking on level ground. Outcome measures included temporal-spatial gait parameters and bilateral kinematic joint angles at the ankle, knee, and hip with and without AFO. Walking speed, stride length, step length and cadence increased with the dynamic AFO. Step width and double support decreased, while single support remained unchanged on the affected limb with the dynamic AFO. With the dynamic AFO there was increased hip flexion at foot strike and toe-off, increased hip sagittal plane angular velocity during swing, and decreased abduction. The dynamic AFO had a positive effect on the participant's overall gait which included improved temporal-spatial parameters and gait velocity which is likely due to a decrease in the overall energy cost of walking. Kinematic angles at the hip were most notably affected by brace utilization and this effect should be more fully explored. Further research with a larger sample utilizing dynamic AFOs is indicated to explore the generalizability of these findings and to determine the potential utility of these braces as an alternative to the traditionally prescribed solid AFO.

Chemodenervation and nerve blocks in the diagnosis and management of spasticity and muscle overactivity.

This article will discuss many of the key concepts regarding chemodenervation and neurolysis in the management of spasticity. Topics that will be discussed include techniques for localization, strengths and limitations of various agents (botulinum toxin, phenol, and alcohol), the value of combination therapies, and the role of nerve blocks (diagnostic and therapeutic). With advancing technology have come newer methods to improve accuracy of localization for the performance of chemodenervation and neurolysis such as electromyographic guidance, electrical stimulation, and ultrasound guidance. During the last 2 decades, the addition of botulinum toxin chemodenervation as an adjunct to traditional neurolysis, medication, and therapy modalities has expanded the field of treatment of intramuscular hyperactivity in upper motor neuron syndrome. The technique of diagnostic blocks as predictors of response and the therapeutic value of nerve blocks will be discussed.

Objective assessment of functional ambulation in adults with hemiplegia using ankle foot orthotics after stroke.

OBJECTIVE: To objectively evaluate the effect of ankle foot orthotics (AFOs) on functional ambulation in individuals with hemiplegia secondary to stroke using quantifiable outcome measures. DESIGN: With-without repeated measures design. SETTING: Rehabilitation research center. PARTICIPANTS: Eighteen adults with stroke-related hemiplegia 6 months using a prescribed AFO. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENTS: The distance (m) and velocity (m/s) during the 6-Minute Walk Test (6MWT) and total time (s) and velocity (m/s) during the 25-ft walk (25ftW). Secondary analysis evaluated the 6MWT and 25ftW grouped by the time component of the Ambulatory Index (AI). RESULTS: Distance walked during the 6MWT was significantly greater with AFO (228.54 +/- 103.93) than without AFO (197.49 +/- 104.13), P = .002. Time to complete the 25ftW was significantly greater without AFO (21.22 +/- 20.57) than with AFO (15.49 +/- 14.65), P = .010. There was a significant difference in average velocity between the 25ftW and 6MWT during the with AFO condition, P = .010. Secondary analysis grouped by the AI time showed that as level of function decreases, brace effect on functional ambulation increases (Group 3: 25ftW with AFO, P = .040). CONCLUSIONS: AFO usage in hemiplegic stroke patients improves functional ambulation, particularly in individuals with a slower gait velocity. The 25ftW, with and without AFO, may be useful to the patient and clinician when determining the importance of brace utilization. Speed modulation was improved when the AFO was added to the paretic limb, and AI grouping indicated that the AFO was more beneficial in people with a slower gait velocity (>20 seconds for the 25ftW). A more definitive study is needed to more completely address this issue. As an exploratory study, the feasibility of different walking assessments was determined so that future studies can validate which objective measures can be used and easily implemented in clinical settings.

Contralateral weakness and fatigue after high-dose botulinum toxin injection for management of poststroke spasticity.

A 53-yr-old woman developed contralateral weakness and fatigue, without autonomic symptoms, 2 wks after receiving an injection with 800 units of botulinum toxin A for management of her poststroke spasticity. Although the patient reported resolution 4 wks later, clinical evaluations suggested an even longer time course. The patient then experienced the same contralateral symptoms again more than a year later, after a 500-unit injection, which took a similar length of time to resolve. We report the first known case of repeated contralateral weakness and fatigue after high-dose botulinum toxin A injection. Currently, dosage is largely titrated by the practitioner based on individual patient response. Before performing botulinum toxin A injections for therapeutic purposes, the expected risks and benefits for each patient must be carefully considered.

Repeated treatments with botulinum toxin type a produce sustained decreases in the limitations associated with focal upper-limb poststroke spasticity for caregivers and patients.

OBJECTIVE: To assess the safety and evaluate the effects of repeated treatments with botulinum toxin type A (BTX-A) on functional disability, quality of life (QOL), and muscle tone of patients with upper-limb poststroke spasticity, as well as its effect on caregivers. DESIGN: Multicenter, open-label, repeated-dose study. SETTING: Thirty-five clinical sites in North America. PARTICIPANTS: Patients (N=279) with upper-limb poststroke spasticity at 6 months or more poststroke. INTERVENTION: Up to 5 intramuscular injections of BTX-A (200-400U) divided among the wrist, finger, thumb, and elbow flexors, with at least 200U in the wrist and finger flexors. Retreatment was permitted at 12 weeks or more after the last treatment. MAIN OUTCOME MEASURES: Investigators rated disability using the Disability Assessment Scale and muscle tone using the Ashworth Scale. Each patient's health-related QOL was assessed by using the Stroke Adapted Sickness Impact Profile and the visual analog scale of the European Quality of Life-5 Dimensions questionnaires. RESULTS: Patients treated with BTX-A reported improvements in muscle tone, disability, and ability to function that were statistically significant and clinically meaningful. Significant improvements were observed at week 30 and at subsequent time points in QOL in the overall group and the high-dose group. CONCLUSIONS: Up to 5 treatments with BTX-A every 12 weeks for up to 56 weeks in patients with poststroke spasticity was well tolerated and significantly improved muscle tone, lessened disability, and improved patients' QOL. Further research is required to examine the effectiveness of repeated injections of BTX-A in patients with poststroke spasticity.

MRI findings in the painful poststroke shoulder.

BACKGROUND AND PURPOSE: We describe the structural abnormalities in the painful shoulder of stroke survivors and their relationships to clinical characteristics. Method- Eighty-nine chronic stroke survivors with poststroke shoulder pain underwent T1- and T2-weighted multiplanar, multisequence MRI of the painful paretic shoulder. All scans were reviewed by one radiologist for the following abnormalities: rotator cuff, biceps and deltoid tears, tendinopathies and atrophy, subacromial bursa fluid, labral ligamentous complex abnormalities, and acromioclavicular capsular hypertrophy. Clinical variables included subject demographics, stroke characteristics, and the Brief Pain Inventory Questions 12. The relationship between MRI findings and clinical characteristics was assessed through logistic regression. RESULTS: Thirty-five percent of subjects exhibited a tear of at least one rotator cuff, biceps or deltoid muscle. Fifty-three percent of subjects exhibited tendinopathy of at least one rotator cuff, bicep or deltoid muscle. The prevalence of rotator cuff tears increased with age. However, rotator cuff tears and rotator cuff and deltoid tendinopathies were not related to severity of poststroke shoulder pain. In approximately 20% of cases, rotator cuff and deltoid muscles exhibited evidence of atrophy. Atrophy was associated with reduced motor strength and reduced severity of shoulder pain. CONCLUSIONS: Rotator cuff tears and rotator cuff and deltoid tendinopathies are highly prevalent in poststroke shoulder pain. However, their relationship to shoulder pain is uncertain. Atrophy is less common but is associated with less severe shoulder pain.

Congenital and acquired brain injury. 3. Spectrum of the acquired brain injury population.

UNLABELLED: This self-directed learning module highlights the subpopulations of traumatic brain injury (TBI) that are treated by the rehabilitation practitioner. It is part of the chapter on TBI in the self-directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Specifically, this article focuses on the management of patients with mild TBI, children, and individuals with acquired brain injury from other etiologies, such as anoxic events or neoplastic lesions. The clinical spectrum of TBI, from the most severe presentation to the mildest, requires similar clinical skills to evaluate and manage. OVERALL ARTICLE OBJECTIVE: To describe the spectrum of brain injury populations based on age, severity, and etiology.

Congenital and acquired brain injury. 5. Emerging concepts in prognostication, evaluation, and treatment.

UNLABELLED: This self-directed learning module describes recent developments in the field of traumatic brain injury (TBI) rehabilitation. In particular, it focuses on the implications of recent technological advances for evaluation, prognostication, and treatment. It is part of the chapter on TBI medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on neuroplasticity and its implications for rehabilitation interventions, the role of innovative neuroimaging modalities, improvements in our ability to prognosticate made possible by newer technologies, technologically based enhancement of motor rehabilitation, and the role of alternative and complementary medicine in TBI rehabilitation. OVERALL ARTICLE OBJECTIVE: To describe recent advances in our ability to evaluate, prognosticate, and treat traumatic brain injury.

Congenital and acquired brain injury. 4. Outpatient and community reintegration.

UNLABELLED: This self-directed learning module highlights the rehabilitation aspects of care for people with traumatic brain injury (TBI) after the acute phase. It focuses on issues important to community reentry, outpatient care, and return to work. It is part of the chapter on TBI medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on the formulation of rehabilitation plans to address the issues of cognitive dysfunction, behavioral disturbances, and community reintegration. Topics covered include pharmacologic and nonpharmacologic approaches to cognitive and affective disorders, intimacy, social isolation, mobility, and return to work. Finally, the critical issues of legal competency and obtaining informed consent in the population with cognitive impairment are discussed. OVERALL ARTICLE OBJECTIVE: To summarize the issues that affect outpatient care, independence, and community reentry after traumatic brain injury.

Congenital and acquired brain injury. 1. Epidemiology, pathophysiology, prognostication, innovative treatments, and prevention.

UNLABELLED: This self-directed learning module reviews the current epidemiology of traumatic brain injury (TBI), its pathophysiology, prognostication after injury, currently available innovative early approaches to diagnosis and treatment, and effective methods of prevention. It is intended to provide the rehabilitation clinician with current knowledge to accurately inform patients, families, significant others, referring physicians, and payers and to aid in clinical decision making while caring for patients after TBI. OVERALL ARTICLE OBJECTIVE: To describe current knowledge in traumatic brain injury epidemiology, pathophysiology, prognostication, acute treatment, and prevention.

Congenital and acquired brain injury. 2. Medical rehabilitation in acute and subacute settings.

UNLABELLED: This self-directed learning module reviews common clinical problems and issues pertaining to early management of persons with traumatic brain injury (TBI). It is part of the study guide on brain injury medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Acute TBI is frequently complicated by agitation, dystonia, and numerous orthopedic and neurologic comorbidities, often causing a decrement in function, which requires careful assessment and treatment. Individuals with acute brain injury typically receive rehabilitation in a setting determined by numerous factors, including medical stability and tolerance to rehabilitation interventions. OVERALL ARTICLE OBJECTIVES: To describe (a) common traumatic brain injury-related comorbidities and treatment strategies, (b) potential causes of declining patient performance, and (c) appropriate settings for rehabilitation interventions.

Complications of interlaminar cervical epidural steroid injections: a review of the literature.

STUDY DESIGN: A comprehensive literature review. OBJECTIVES: To review and critically evaluate the past literature focusing on incidence and clinical presentation of complications associated with interlaminar cervical epidural steroid injection (ICESI). The overall goal is to guide the direction of future research and improve clinical care by increasing awareness of complications, their presentations, and management. SUMMARY OF BACKGROUND DATA: Although ICESI is considered a relatively safe procedure, a number of minor and major complications have been reported across the literature. Thus far, reports of complications are limited to retrospective studies, case reports, and data extrapolated from lumbar and thoracic procedures. As a result, the past literature has been of limited value with regard to facilitating both clinical care and future research efforts. METHODS: Medical databases were searched for studies of ICESI. The bibliographies of these papers were then searched as well. Papers focusing on cervical techniques that did not involve injection into the epidural space were discarded, as were studies of thoracic and lumbar spine injections. Reports of complications associated with ICESI were further subdivided into major and minor categories. RESULTS: The reported rate of complications associated with ICESI varied between 0 and 16.8%. CONCLUSION: There are significant limitations in the available literature discussing the complications associated with ICESI, but they strongly suggest that ICESI is a relatively safe procedure. Numerous potential adverse reactions have been associated with ICESI, with the vast majority being minor and transient in nature. However, serious complications may also result and may be technique related. Injectionists should be aware of the clinical presentations, rates, potential consequences, and appropriate techniques to avoid these complications. More studies are needed with specific focus on cervical complication rates, standardization of injection techniques, and differentiation between complications and poor efficacy. In addition, the use of a prospective randomized blinded controlled design would be beneficial.

Formation of neutralizing antibodies in patients receiving botulinum toxin type A for treatment of poststroke spasticity: a pooled-data analysis of three clinical trials.

OBJECTIVE: The purpose of this study was to investigate the incidence of neutralizing antibody (NAb) formation in patients with poststroke spasticity treated with a specific formulation of botulinum toxin type A (BoNTA). METHODS: Data from 3 previous clinical trials of BoNTA in patients with upper and/or lower limb spasticity were pooled and evaluated. Study 1 was a randomized, double-blind, placebo-controlled, multicenter trial of BoNTA in patients aged >/=21 years who had experienced a stroke >6 months before the initiation of the study. Study 2 was an open-label extension of study 1. Study 3 was a randomized, double-blind, multicenter trial of a specific BoNTA formulation in patients aged >/= 21 years who had experienced a stroke >/=6 weeks before study entry. Patients with a fixed contracture of the studied limb were excluded from participation in studies 1 and 2. Serum samples were obtained from each patient before each BoNTA treatment and at the end of each study. The mouse protection assay (MPA) was used for detection of NAbs to BoNTA in serum. RESULTS: A total of 235 individual patients with post-stroke spasticity were enrolled in the 3 trials, including 126, 111 (all of whom participated in study 1), and 109 in studies 1, 2, and 3, respectively. Study 1 had an equal (50.0%) distribution of male and female patients (63/63). The distribution of male and female patients was 56 (50.5%) and 55 (49.5%), respectively, in study 2, and 55 (50.5%) and 54 (49.5), respectively, in study 3. The mean (SD) ages of patients in studies 1, 2, and 3 were 61.4 (13.8), 61.5 (14.1), and 58.5 (13.9) years, respectively. The MPA was used for detection of NAbs to BoNTA in the serum samples of 191 patients, including 64 from study 1, 111 from study 2 (55 of these patients were placebo recipients and 56 received their first BoNTA injection in study 1), and 72 (a sample was not obtained for 1 patient who had not received an injection) from study 3. The median number of BoNTA treatments received by these patients was 2 (range, 1-4 treatments) over a period lasting from 12 to 42 weeks. The mean dose of BoNTA was 241 U (range, 100-400 U), with a maximum dose of 960 U in any 1 patient. NAbs to BoNTA were detected in the serum sample of 1/191 (0.5%) patient who had participated in studies 1 and 2. Based on muscle-tone scores (3 and 4 for wrist and fingers, respectively) on a 5-point Ashworth Scale (0 = none to 4 = severe), the patient did not appear to exhibit a clinical response to BoNTA at any time during the studies. CONCLUSION: Formation of NAbs was rare (1/191) in this group of adults with poststroke spasticity from three 12- to 42-week clinical trials who received >/=1 treatment with a specific BoNTA formulation at doses ranging from 100 to 400 U.

Intramuscular electrical stimulation for shoulder pain in hemiplegia: does time from stroke onset predict treatment success?

BACKGROUND: A randomized clinical has shown the effectiveness of intramuscular electrical stimulation for the treatment of poststroke shoulder pain. OBJECTIVE: Identify predictors of treatment success and assess the impact of the strongest predictor on outcomes. METHOD: This is a secondary analysis of a multisite randomized clinical trial of intramuscular electrical stimulation for poststroke shoulder pain. The study included 61 chronic stroke survivors with shoulder pain randomized to a 6-week course of intramuscular electrical stimulation (n = 32) versus a hemisling (n = 29). The primary outcome measure was Brief Pain Inventory Question 12. Treatment success was defined as > or = 2-point reduction in this measure at end of treatment and at 3, 6, and 12 months posttreatment. Forward stepwise regression was used to identify factors predictive of treatment success among participants assigned to the electrical stimulation group. The factor most predictive of treatment success was used as an explanatory variable, and the clinical trials data were reanalyzed. RESULTS: Time from stroke onset was most predictive of treatment success. Subjects were divided according to the median value of stroke onset: early (<77 weeks) versus late (> 77 weeks). Electrical stimulation was effective in reducing poststroke shoulder pain for the early group (94% vs 7%, P < .001) but not for the late group (31% vs 33%). Repeated-measure analysis of variance revealed significant treatment (P < .001), time from stroke onset (P = .032), and treatment by time from stroke onset interaction (P < .001) effects. CONCLUSIONS: Stroke survivors who are treated early after stroke onset may experience greater benefit from intramuscular electrical stimulation for poststroke shoulder pain. However, the relative importance of time from stroke onset versus duration of pain is not known.