Post-stroke Lower Limb Spasticity Research Articles

Assessment of pain relief after four botulinum toxin A injection cycles in patients with post-stroke lower limb spasticity: A prospective, observational study

IntroductionSpasticity is common after a stroke and is an independent risk factor for developing pain. BotulinumtoxinA injection is the treatment of choice for focal spasticity. We examined the effect of intramuscular botulinumtoxinA on pain relief in patients in routine clinical practice who were experiencing pain as a primary complaint associated with post-stroke lower limb spasticity. MethodsProspective, multicentre, post-marketing observational study. The study period was 16 months. The primary effectiveness variable was the mean change from baseline on the pain 0–10 Numerical Rating Scale after four botulinumtoxinA injection cycles. Secondary endpoints included changes from baseline on the pain 0–100 Visual Analogue Scale, Goal Attainment Scale, modified Ashworth Scale, 10-Meter Walk Test, Penn Spasm Frequency Scale, and 36-item Short-Form Health Survey. ResultsOf 186 enrolled patients, 180 (96.8%) received botulinumtoxinA at least once. The mean (standard deviation) pain 0–10 Numerical Rating Scale score decreased significantly (p<0.0001) from 4.9 (2.2) at baseline to 2.5 (2.1) at study end, representing a 50% decrease in pain severity. Relief of pain due to spasticity was supported by improvement from baseline in all secondary variables except the 10-Meter Walk Test. Two adverse events (erysipelas and phlebitis) in one patient were considered likely to be related to botulinumtoxinA injection. ConclusionBotulinumtoxinA appears to provide pain relief as an additional benefit of local treatment in patients with post-stroke lower limb spasticity for whom pain relief is a primary therapeutic goal (a Lay Abstract has been provided as Appendix A).

Shear Wave Velocity to Evaluate the Effect of Botulinum Toxin on Post-Stroke Spasticity of the Lower Limb.

(1) Background: The evaluation of muscles with spasticity using ultrasound elastography has attracted attention recently, and the shear wave velocity (SWV) technique can measure the mechanical properties of tissues objectively and quantitatively. The purpose of this study was to evaluate the effect of using SWV to assess the effect of Botulinum toxin type A (BoNT-A) treatment in adult patients with post-stroke lower limb spasticity. (2) Methods: We assessed the modified Ashworth Scale, the modified Tardieu Scale, and SWV at rest and after stretching before and at 1 month after BoNT-A treatment in 10 adult participants with post-stroke lower limb spasticity. (3) Results: Significant changes in SWV of the ankle joint in maximum dorsiflexion to the extent possible (SWV stretched) were observed after BoNT-A treatment. SWV stretched was positively correlated with joint range of motion. Participants whose joint range of motion did not improve (i.e., gastrocnemius medialis muscle (GCM) extension distance did not change) had significantly more reductions in SWV stretched after BoNT-A treatment. (4) Conclusions: Our results suggest that the SWV measurements may serve as a quantitative assessment to determine the effect of the BoNT-A treatment in adult stroke patients. SWV measurements to assess GCM spasticity should consider the effects of tension, material properties and activation level of muscles. The challenge is to measure SWV with matching limb positions in patients without contractures.

Effectiveness of Radial Extracorporeal Shock Wave Therapy and Visual Feedback Balance Training on Lower Limb Post-Stroke Spasticity, Trunk Performance, and Balance: A Randomized Controlled Trial.

Stroke remains one of the leading causes of disability in adults, and lower limb spasticity, affected stance, and balance impact everyday life and activities of such patients. Robotic therapy and assessment are becoming important tools to clinical evaluation for post-stroke rehabilitation. The aim of this study was to determine in a more objective manner the effects of visual feedback balance training through a balance trainer system and radial extracorporeal shock wave therapy (rESWT), along with conventional physiotherapy, on lower limb post-stroke spasticity, trunk control, and static and dynamic balance through clinical and stabilometric assessment. The study was designed as a randomized controlled trial. The experimental group underwent conventional physiotherapy, visual feedback balance training, and rESWT. The control group underwent conventional physiotherapy, visual feedback training and sham rESWT. The statistical analysis was performed using GraphPad Software and MATLAB. Primary clinical outcome measures were The Modified Ashworth Scale (MAS), passive range of motion (PROM), Visual Analogue Scale (VAS), and Clonus score. Secondary outcome measures were trunk performance, sensorimotor, and lower limb function. Stabilometric outcome measures were trunk control, static balance, and dynamic balance. Visual feedback training using the Prokin system and rESWT intervention, along with conventional physiotherapy, yielded statistically significant improvement both on clinical and stabilometric outcome measures, enhancing static and dynamic balance, trunk performance, sensorimotor outcome, and limb function and considerably diminishing lower limb spasticity, pain intensity, and clonus score in the experimental group.

Long-Term Efficacy of Extracorporeal Shock Wave Therapy on Lower Limb Post-Stroke Spasticity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this systematic review and meta-analysis is to evaluate the long-term efficacy of Extracorporeal Shock Wave Therapy (ESWT) on reducing lower limb post-stroke spasticity in adults. A systematic electronic search of PubMed/ MEDLINE, Physiotherapy Evidence Database (PEDro), Scopus, Ovid MEDLINE(R), and search engine of Google Scholar was performed. Publications that ranged from January 2010 to August 2020, published in English, French, Spanish, Portuguese, and Italian language and available as full texts were eligible for inclusion and they were searched without any restrictions of country. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. Two authors screened the references, extracted data, and assessed the risk of bias. The primary outcome was spasticity grade mainly assessed by the Modified Ashworth Scale (MAS). Secondary outcomes were passive range of motion (PROM), pain intensity, electrophysiological parameters, gait assessment, and adverse events. A total of seven recent randomized controlled trials (RCTs) were included in the systematic review and meta-analysis, and a beneficial effect on spasticity was found. The high level of evidence presented in this paper showed that ESWT ameliorates spasticity considering the parameters: MAS: standardized mean difference (SMD) = 0.53; 95% confidence interval (95% CI): (0.07–0.99); Modified Tardieu Scale (MTS): SMD = 0.56; 95% CI: (0.01–1.12); Visual Analogue Scale (VAS): SMD = 0.35; 95% CI: (−0.21–0.91); PROM: SMD = 0.69; 95% CI: (0.20–1.19). ESWT presented long-term efficacy on lower limb post-stroke spasticity, reduced pain intensity, and increased range of motion. The effect of this novel and non-invasive therapy was significant and the intervention did not present adverse events, proving a satisfactory safety profile.

Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity: results from the double-blind, placebo-controlled, phase 3 REFLEX study

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.

Impact of abdominal moxibustion in a period of day from 7 am to 9 am on improvement in post-stroke lower limb spasticity and muscle architecture parameter

To compare the therapeutic effect on post-stroke lower limb spasticity between the combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training and the simple rehabilitation training. A total of 100 patients with post-stroke lower limb spasticity were randomized into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 4 cases dropped off ). In the control group, the basic treatment of internal medicine and rehabilitation training of the limbs were adopted. In the observation group, on the basis of the treatment in the control group, at the time zone from 7 am to 9 am, moxibustion on the abdomen with "eight-trigram" moxa box [the central moxa box accurately facing Shenque (CV 8)] was given, lasting for 2 h, once every two days. Both groups were treated for 6 weeks. Separately, before and after treatment, the score of Fugl-Meyer assessment of the lower extremity (FMA-LE) and the grade of modified Ashworth scale (MAS) of ankle joint were evaluated on the affected side in patients of the two groups. Muscle skeleton ultrasound (MSUS) was adopted to determine the first layer muscle thickness (MT) anterior to the tibia, the number of pennation angle (PA) and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side. Besides, after treatment, the therapeutic effect was evaluated in the two groups. After treatment, the score of FMA-LE and the grade of MAS of ankle joint on the affected side were both improved as compared with those before treatment in patients of the two groups (P<0.01, P<0.05). The improvements in the observation group were better than those in the control group (P<0.01, P<0.05). After treatment, MT anterior to the tibia, the number of PA and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side were all increased as compared with before treatment in patients of the two groups (P<0.01). The increase degree in the observation group was larger than that in the control group (P<0.01). The total effective rate was 93.6% (44/47) in the observation group, better than 80.4% (37/46) in the control group (P<0.05). The combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training effectively relieves post-stroke lower limb spasticity and improves the limb functions and muscle structure. The total effective rate of this combined treatment is better than that of simple rehabilitation training.

IncobotulinumtoxinA for upper- and lower-limb spasticity in Japanese patients

Introduction: The safety and tolerability of incobotulinumtoxinA 400 U for upper- and lower-limb post-stroke spasticity was assessed in a small cohort of Japanese patients during the open-label lead-in tolerability periods (LITP) of two phase 3 studies (CTI-153029 and CTI-153030; Japan Pharmaceutical Information Centre).Methods: Adult patients received a single incobotulinumtoxinA injection session (total dose of 400 U) in the upper (J-PURE) or lower limb (J-PLUS). Adverse events (AEs) were assessed at 1, 4, 8 and 12 weeks post-injection during the 12 week follow-up.Results: The LITP of J-PURE and J-PLUS included 11 patients each. Mild/moderate AEs were reported by 5/11 (45.5%) and 8/11 (72.7%) patients in J-PURE and J-PLUS, respectively. No serious AEs were reported. Non-serious, transient AEs of special interest reported by two patients in J-PURE comprised muscular weakness and eyelid ptosis. No patient discontinued due to AEs.Conclusion: Preliminary results in this small population suggest that incobotulinumtoxinA 400 U is well tolerated for treating upper- or lower-limb post-stroke spasticity in Japanese patients.

Poststroke Postural Sway Improved by Botulinum Toxin: A Multicenter Randomized Double-blind Controlled Trial

ObjectiveTo assess the effects of injecting botulinum toxin into the lower limb muscles of people with hemiparesis post stroke in terms of their sway areas. DesignA multicenter randomized double-blind trial on the effects of active botulinum toxin treatment vs placebo. SettingClinical examinations and postural sway assessments were performed before botulinum toxin injection and again 4-6 weeks after the injection. ParticipantsPeople with hemiparesis with chronic post stroke lower limb spasticity (N=40). InterventionsIntramuscular injection of a placebo (physiological serum) was performed on the control group, and botulinum toxin injections were performed on the treatment group. Participants and physical and rehabilitation medicine specialists were given no information as to which of the 2 treatments was applied. Main Outcome MeasuresThe sway area of the center of pressure was recorded for 30 seconds in 3 conditions: eyes open, eyes open in a dual task (a postural control task combined with an arithmetic task), and eyes closed. Spasticity was measured using the Modified Ashworth Scale. ResultsForty people post stroke were enrolled and randomized into 2 groups, one of which was treated with botulinum toxin (n=19) and the other with placebo (n=21). Spasticity decreased significantly in the treatment group (−0.7, P=.049 in the soleus muscles; −0.8, P=.035 in the gastrocnemii muscles). The sway area did not differ significantly between the 2 groups before treatment. The most conspicuous effect was observed in the case of the dual task, where a significant decrease (P=.005) in the sway area occurred in the treatment group (−3.11±6.92) in comparison with the placebo group (+0.27±3.57). ConclusionTreating spasticity by injecting botulinum toxin into people’s lower limb muscles post stroke seems to improve their postural sway. The dual task used here to assess sway seems to be a useful, sensitive test for this purpose.

Efficacy of botulinum toxin in modifying spasticity to improve walking and quality of life in post-stroke lower limb spasticity - a randomized double-blind placebo controlled study

BackgroundPost-stroke lower limb spasticity (PSLLS) has a prevalence of 28–37%. PSLLS can cause difficulty in walking and reduce quality of life (QOL). Post stroke spasticity impairs the ability to intervene to improve walking ability. Botulinum Toxin A (BT) is an effective intervention for focal spasticity, but its use is currently restricted in many countries by their reimbursement system stating that the evidence for improvement in walking and quality of life (QOL) is not robust for treatment in the lower limb. This randomized control trial (RCT) will investigate the effectiveness of BT in modifying spasticity, and improving functioning (mobility, walking, activities of daily living (ADL’s) and QOL.Methods/designA double-blind placebo-controlled trial injection will assess the effect of BT compared with a placebo (normal saline) in a sample of n = 94 patients. Following treatment of spasticity measured by Modified Ashworth Scale (MAS), the primary outcome of gait velocity will be measured by i) Gait Rite (Electronic Walkway); ii) walking by 2 Min Walk Test; iii) balance by Berg Balance Scale; mobility by iv) Timed Up and Go (TUG); v) lower limb function by ABILICO; vi) patient related goal by Goal Attainment Scale (GAS); vii) QOL by SF 12 (Rand version); viii) activities of daily living by the Functional Autonomy Measurement System (SMAF). There will be an associated health economic analysis.DiscussionThe study methodology is based on our systematic review 2026 studies, which concluded the evidence for improving mobility following use of BT to reduce spasticity was not robust. The results of this study could establish the use of BT in improving gait and lower limb function in PSLLS. This study could provide the evidence needed for reimbursement schemes to consider and changes to its funding policy for BT in PSLLS.Trial registrationThe trial is registered with the Australia New Zealand Clinical Trails Registry (ANZCTR)-ANZCTRN12617001603303. Registered 07/12/2017.

A systematic review: Efficacy of botulinum toxin in walking and quality of life in post-stroke lower limb spasticity

We performed a systematic review of the randomized control trials (RCT) to evaluate effectiveness of Botulinum toxin A (BoNTA) injection on walking and Quality of Life (QOL) in post-stroke lower limb spasticity (PSLLS). We searched PubMed, Web of Science, Embase, CINAHL, ProQuest Thesis and Dissertation checks and Google Scholar, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane, ANZ and EU Clinical Trials Register for RCTs looking at improvement in walking and QOL following injection of BoNTA in PSLLS. The original search was carried out prior to 16 September 2015. We conducted an additional verifying search on CINHAL, EMBASE, and MEDLINE (via PubMed) from 16 September 2015 to 6 June 2017 using the same clauses. Of 2026 records, we found 107 full text records and 5 RCTs qualifying our criteria. Two independent reviewers assessed methodological validity prior to inclusion in the review. Two studies reported significant improvement in gait velocity ( P = 0.020 and < 0.05, respectively). One study showed significant improvement in 2-min-walking distance ( P < 0.05). QOL was recorded in one study without any significant improvement. Meta-analysis of reviewed studies could not be performed because of different methods of assessing walking ability, and small sample size with large confidence interval. This review identifies the need for a well-designed RCT to adequately investigate the issues highlighted. This review could not conclude there was sufficient evidence to support or refute improvement on walking or QOL following BoNTA injection. Reasons for this are discussed and methods for future RCTs are developed.

OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity: A Randomized Trial

BackgroundPoststroke distal lower limb spasticity impairs mobility, limiting activities of daily living and requiring additional caregiver time. ObjectiveTo evaluate the efficacy, safety, and sustained benefit of onabotulinumtoxinA in adults with poststroke lower limb spasticity (PSLLS). DesignA multicenter, randomized, double-blind, phase 3, placebo-controlled trial (NCT01575054). SettingSixty study centers across North America, Europe, Russia, the United Kingdom, and South Korea. PatientsAdult patients (18-65 years of age) with PSLLS (Modified Ashworth Scale [MAS] ≥3) of the ankle plantar flexors and the most recent stroke ≥3 months before study enrollment. InterventionsDuring the open-label phase, patients received ≤3 onabotulinumtoxinA treatments (≤400 U) or placebo at approximately 12-week intervals. Treatments were into the ankle plantar flexors (onabotulinumtoxinA 300 U into ankle plantar flexors; ≤100 U, optional lower limb muscles). Main Outcome MeasurementsThe double-blind primary endpoint was MAS change from baseline (average score at weeks 4 and 6). Secondary measures included physician-assessed Clinical Global Impression of Change (CGI), MAS change from baseline in optional muscles, Goal Attainment Scale (GAS), and pain scale. ResultsOf 468 patients enrolled, 450 (96%) completed the double-blind phase and 413 (88%) completed the study. Small improvements in MAS observed with onabotulinumtoxinA during the double-blind phase (onabotulinumtoxinA, –0.8; placebo, –0.6, P = .01) were further enhanced with additional treatments through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, –1.2; placebo/onabotulinumtoxinA, –1.4). Small improvements in CGI observed during the double-blind phase (onabotulinumtoxinA, 0.9; placebo, 0.7, P = .01) were also further enhanced through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, 1.6; placebo/onabotulinumtoxinA, 1.6). Physician- and patient-assessed GAS scores improved with each subsequent treatment. No new safety signals emerged. ConclusionsOnabotulinumtoxinA significantly improved ankle MAS, CGI, and GAS scores compared with placebo; improvements were consistent and increased with repeated treatments of onabotulinumtoxinA over 1 year in patients with PSLLS. Level of EvidenceI

A systematic review: efficacy of botulinum toxin in walking and quality of life in post-stroke lower limb spasticity

BackgroundImproved walking is one of the highest priorities in people living with stroke. Post-stroke lower limb spasticity (PSLLS) impedes walking and quality of life (QOL). The understanding of the evidence of improved walking and QOL following botulinum toxin (BoNTA) injection is not clear. We performed a systematic review of the randomized control trials (RCT) to evaluate the effectiveness of BoNTA injection on walking and QOL in PSLLS.MethodsWe searched PubMed, Web of Science, Embase, CINAHL, ProQuest Thesis and Dissertation checks, Google Scholar, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane, and ANZ and EU Clinical Trials Register for RCTs looking at improvement in walking and QOL following injection of BoNTA in PSLLS. The original search was carried out prior to 16 September 2015. We conducted an additional verifying search on CINHAL, EMBASE, and MEDLINE (via PubMed) from 16 September 2015 to 6 June 2017 using the same clauses as the previous search. Methodological quality of the individual studies was critically appraised using Joanna Briggs Institute’s instrument. Only placebo-controlled RCTs looking at improvement in walking and QOL were included in the review.ResultsOf 2026 records, we found 107 full-text records. Amongst them, we found five RCTs qualifying our criteria. No new trials were found from the verifying search. Two independent reviewers assessed methodological validity prior to inclusion in the review using Joanna Briggs Institute’s appraisal instrument. Two studies reported significant improvement in gait velocity (p = 0.020) and < 0.05, respectively. One study showed significant improvement in 2-min-walking distance (p < 0.05). QOL was recorded in one study without any significant improvement. Meta-analysis of reviewed studies could not be performed because of different methods of assessing walking ability, small sample size with large confidence interval and issues such as lack of power calculations in some studies. Findings from our systematic and detailed study identify the need for a well-designed RCT to adequately investigate the issues highlighted.ConclusionsThis review could not conclude there was sufficient evidence to support or refute improvement on walking or QOL following BoNTA injection. Reasons for this are discussed, and methods for future RCTs are developed.

Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity

Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity

OnabotulinumtoxinA for Lower Limb Spasticity: Guidance From a Delphi Panel Approach

BackgroundOnabotulinumtoxinA 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. ObjectiveTo 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. DesignClinical experts provided insight regarding onabotulinumtoxinA treatment for PSLLS using an adaptation of the Delphi consensus process. SettingDelphi panel. ParticipantsTen expert clinicians in neurology and physical medicine and rehabilitation who treat PSLLS. MethodsA 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 MeasurementsReached 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. ResultsConsensus 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. ConclusionThe 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 EvidenceV

Poster 354 OnabotulinumtoxinA to Treat Common Postures in Post-Stroke Lower Limb Spasticity: Identification of a Treatment Paradigm

Poster 354 OnabotulinumtoxinA to Treat Common Postures in Post-Stroke Lower Limb Spasticity: Identification of a Treatment Paradigm

Poster 361 Impact of Early Intervention with OnabotulinumtoxinA Treatment in Adult Patients with Post-Stroke Lower Limb Spasticity.

Poster 361 Impact of Early Intervention with OnabotulinumtoxinA Treatment in Adult Patients with Post-Stroke Lower Limb Spasticity.

Impact of Early Intervention with OnabotulinumtoxinA Treatment in Adult Patients with Post-Stroke Lower Limb Spasticity (S31.006)

Impact of Early Intervention with OnabotulinumtoxinA Treatment in Adult Patients with Post-Stroke Lower Limb Spasticity (S31.006)

Sustained Benefit with Repeated Treatments of OnabotulinumtoxinA in Post-Stroke Lower Limb Spasticity: 1-Year Open-Label Final Results from a Double-Blind, Placebo-Controlled, Phase 3 Trial (S7.002)

Sustained Benefit with Repeated Treatments of OnabotulinumtoxinA in Post-Stroke Lower Limb Spasticity: 1-Year Open-Label Final Results from a Double-Blind, Placebo-Controlled, Phase 3 Trial (S7.002)

Abstract TMP34: OnabotulinumtoxinA Treatment in Post-stroke Lower Limb Spasticity: Long-term Results From a Phase 3 Study

Introduction: Long-term efficacy of onabotulinumtoxinA (onabotA) in post-stroke lower limb spasticity (PSLLS) is not clearly established. Hypothesis: OnabotA provides sustained efficacy in PSLLS. Methods: A multicenter, phase 3, 12-week, double-blind (DB), placebo-controlled study of patients with ankle PSLLS (Modified Ashworth Scale [MAS] ≥3) was followed by an open-label (OL) extension, during which all patients received 1-3 treatment cycles (∼12-week intervals) of onabotA (≤400U). Endpoints: change from baseline in MAS and Clinical Global Impression of Change (CGI) physician rating, and percent of patients achieving passive and active goals (Goal Attainment Scale [GAS]) by physician and patient. Results: 468 patients enrolled (onabotA, n=233; placebo, n=235); 447 (95.5%) completed the DB and 249 (53.2%) completed the OL phase at DB database lock. Significant improvement in MAS achieved with onabotA in DB was sustained in OL phase (Table). Significant improvements in CGI in DB continued to improve in OL phase. During OL phase, MAS ankle change from baseline and CGI by physician raw scores and proportions of responders were largest at week 6 and generally increased over 3 OL treatment cycles. With onabotA, GAS by patient improved ( P =0.036), as did the proportion that progressed toward active ( P =0.009) and passive ( P =0.044) goal attainment by physician. The percentage of patients who met passive and active goals (GAS by physician≥0) after 1 onabotA treatment increased from 40% to 64% and 27% to 65%, respectively, after 4 treatments. Common DB treatment-related AEs (onabotA vs placebo): injection-site pain (1.7% vs 0.9%) and pain in extremity (0.4% vs 2.1%). Conclusions: OnabotA was well-tolerated and produced improvements in MAS, CGI, and GAS during the DB phase that continued into the OL phase, demonstrating long-term benefits in patients with PSLLS.

Does Poststroke Lower-Limb Spasticity Influence the Recovery of Standing Balance Control? A 2-Year Multilevel Growth Model

Background. Poststroke lower-limb spasticity (LLS) has been shown to degrade standing balance control by disrupting the temporal synchronization between individual limb centers of pressure (COPs). Time-varying changes in standing balance control associated with alterations in the extent of LLS have yet to be documented and are important to informing treatment strategies to improve such functional outcomes. Objective. The present work aimed to understand the natural recovery of standing balance control among stroke survivors with LLS using limb-specific indices of standing balance control. Furthermore, we sought to understand if time-varying changes in LLS were associated with alterations in standing balance control. Methods. A retrospective analysis of 92 participants was performed; 47 participants never exhibited LLS during the study (No_LLS), and 45 participants exhibited LLS during at least 1 testing session (LLS). Quiet standing for a duration of 30 s on 2 force platforms was recorded. Temporal synchrony and spatial symmetry of COP displacements were assessed, along with interlimb weight-bearing symmetry. Results. All variables, except spatial symmetry, indicated initial improvement followed by deceleration in the rate of balance control recovery. Limb-specific measures indicated that individuals with LLS exhibited deficits in balance control. The recovery trajectories were not different between groups, suggesting a similar rate, but reduced extent, of balance control recovery among the LLS relative to the No_LLS group. Only temporal synchrony was altered by time-varying changes in spasticity. Conclusions. The present results suggest that the reduction in spasticity may be beneficial to balance control recovery.