Botulinum toxin type B in upper-limb poststroke spasticity: a double-blind, placebo-controlled trial

OBJECTIVE: To determine whether botulinum toxin type B (BTX-B) is effective in controlling upper-limb spasticity. DESIGN: A single-site, double-blind, placebo-controlled, randomized trial and open-label study. SETTING: Outpatient. PARTICIPANTS: Subjects with an Ashworth Scale score of 2 or more at the elbow, wrist, and fingers. INTERVENTIONS: Subjects were injected with 10000 U of BTX-B or placebo at the elbow, wrist, and finger flexors.Main outcome measures Measures recorded at weeks 0, 2, 4, 8, 12, and 16, with a 12-week open-label study. Ashworth Scale score, a global assessment of change (GAC), adverse events and mouse neutralization antibody testing. RESULTS: BTX-B did not decrease muscle tone in the elbow, wrist, or finger flexors at 10000 U over the 16-week period. A decrease in Ashworth Scale score for the BTX-B patient group was present at the wrist at week 2 of the double-blind study (P=.003) but was not statistically significant at other visits. In the open-label study, improvement was noted at week 4 for the elbow (P=.039), wrist (P=.002), finger (P=.001), and thumb flexors (P=.002). In the double-blind study, the Physician GAC did not reach significance. Dry mouth was reported by 8 of 9 BTX-B subjects in the double-blind study. Mouse neutralization antibodies were negative. CONCLUSIONS: Our study does not show a significant decrease in tone from 10000 U of BTX-B. Dry mouth was common.     

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

Elovic EP, Brashear A, Kaelin D, Liu J, Millis SR, Barron R, Turkel C. 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.     

Dose-dependent response to intramuscular botulinum toxin type A for upper-limb spasticity in patients after a stroke

OBJECTIVE: To test the hypothesis that intramuscular (IM) botulinum toxin type A (BTX) reduces excessive muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke. DESIGN: Randomized, double-blind, placebo-controlled, multicenter, 24-week trial. SETTING: Six academic and 13 private US outpatient medical centers. PARTICIPANTS: Ninety-one patients with a mean age of 60 years (range, 30-79 y). Mean time elapsed from ischemic or hemorrhagic stroke to study enrollment was 25.8 months (range, 0.9-226.9 mo). INTERVENTIONS: Up to 2 treatments of placebo, or 90, 180, or 360U of BTX. Concurrent splinting and physical therapy protocols were permitted, but no changes were allowed during the study. MAIN OUTCOME MEASURES: Wrist, elbow, and finger flexor tone assessed by the Modified Ashworth Scale, physician and patient global assessments, pain, FIM instrument, and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Muscle tone decreased more with injections of BTX than with placebo in the wrist flexors at weeks 1, 2, 3, 6, and 9 (P< or =.026); in the elbow flexors at weeks 1, 2, 3, 4, 5, and 9 (P< or =.033); and in the finger flexors at weeks 1 and 3 (P< or =.031). A dose-dependent response was generally observed in tone reduction but not in pain, FIM, or SF-36 measures. CONCLUSIONS: IM BTX reduced muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke but did not appear to affect global quality of life or disability.     

Time course analysis of the effects of botulinum toxin type a on elbow spasticity based on biomechanic and electromyographic parameters

Lee H-M, Chen J-JJ, Wu Y-N, Wang Y-L, Huang S-C, Piotrkiewicz M. Time course analysis of the effects of botulinum toxin type A on elbow spasticity based on biomechanic and electromyographic parameters.

Objective

To quantify changes of elbow spasticity over time after botulinum toxin type A (BTX-A) injection in the upper extremity of stroke patients.

Design

Before-after trial in which the therapeutic effects were followed up at 2, 6, and 9 weeks after the BTX-A injection (Botox).

Setting

Hospital.

Participants

Chronic stroke patients (N=8) with upper-limb spasticity.

Intervention

BTX-A was injected in upper-limb muscles, including the biceps brachii.

Main Outcome Measures

Treatment effects were quantified as the changes in the velocity and the length dependence of hyperexcitable stretch reflexes. Manual sinusoid stretches of the elbow joint at 4 frequencies (1/3, 1/2, 1, 3/2Hz) over a movement range of 60° were performed on patients by using a portable device. The Modified Ashworth Scale (MAS), biomechanic viscosity, and the reflexive electromyography threshold (RET) of the biceps brachii were used to evaluate the degree of hypertonia.

Results

The statistical analyses of the MAS score, biomechanic viscosity, and RET revealed a significant decrease in spasticity after the injection (all P<.05). Moreover, our quantitative parameters (biomechanic viscosity, RET) revealed small changes in spasticity after the BTX-A injection that could not be observed from clinical MAS evaluations. Five of 8 subjects showed a maximal reduction in spasticity (in terms of biomechanic viscosity value) within 6 weeks after the injection, whereas it was notable that all subjects exhibited peak RET values at either 2 or 6 weeks after the injection with variable degrees of relapse of spasticity.

Conclusions

Early relapse of spasticity (within 9 weeks of the injection) can be detected from biomechanic and neurophysiologic assessments in a clinical setup. These quantitative indices provide valuable information for clinicians when making decisions to perform additional rehabilitation interventions or another BTX-A injection in the early stages of treatment.     

Pooled analysis of the safety of botulinum toxin type A in the treatment of poststroke spasticity

OBJECTIVE: To examine the safety of botulinum toxin type A (BTX-A). DESIGN: Analysis of pooled data of 9 double-blind, placebo-controlled studies of patients with spasticity after stroke. SETTING: University hospitals and specialty rehabilitation centers in the United States. PARTICIPANTS: A total of 482 patients with upper-limb spasticity and 310 with lower-limb spasticity (overall mean age, 58y; 60% men). INTERVENTION: Treatment with BTX-A (n=534; 1-3 treatments; mean dose, 231U) or placebo (n=258). MAIN OUTCOME MEASURE: Adverse events. RESULTS: Most patients (69%) received only 1 treatment with BTX-A. Patients were followed for a mean of 17.8 weeks (range, 0.1-44.7wk) after each treatment. A total of 352 (65.9%) patients in the BTX-A group and 163 (63.2%) in the placebo group reported at least 1 adverse event (P=.475). The most frequent adverse events reported by patients (>5% but <10% in either group) were respiratory infection, seizures, incoordination, and injection site pain, none of which occurred at a significantly higher rate in the BTX-A group (all P>.05). The majority of adverse events were rated as mild or moderate in severity. Only nausea was reported at a significantly higher rate in the BTX-A group (12/534 [2.2%]) than the placebo group (0/258) (P=.011); in contrast, injection site pain, chest pain, and allergic reaction were reported significantly more frequently in the placebo group. CONCLUSIONS: BTX-A has an acceptable safety profile for treatment of patients with focal spasticity following stroke, a population in which adverse events and comorbidities are common.     

Comparative impact of 2 botulinum toxin injection techniques for elbow flexor hypertonia

Mayer NH, Whyte J, Wannstedt G, Ellis CA. Comparative impact of 2 botulinum toxin injection techniques for elbow flexor hypertonia.

Objective

To compare 2 techniques of botulinum toxin injection for elbow flexor hypertonia.

Design

Parallel-group, randomized, controlled trial with blinded outcome assessment.

Setting

Laboratory, tertiary rehabilitation hospital.

Participants

Adults (N=31) with acquired brain injury (21 with traumatic brain injury, 8 with stroke, 2 with hypoxic encephalopathy) provided 36 sets of elbow flexors with Ashworth Scale scores equal to 3.

Intervention

Botulinum toxin type A (BTX-A) was injected with a motor point or a multisite injection technique after obtaining 2 baseline evaluations of the main outcome measures. Motor point technique involved decremental electric stimulation with delivery of 60U of BTX-A (Botox) in 2.4mL or 30U BTX-A in 1.2mL of preservative-free saline at single biceps and brachioradialis motor points, respectively. Distributed injection was performed using electromyographic feedback. Fifteen units in 0.6mL were delivered to each of 4 biceps sites and 2 brachioradialis sites. Total dose (90U) and total injection volume (3.6mL) were identical across groups. Only sites and injection techniques varied. The brachialis was not injected in either group.

Main Outcome Measures

Ashworth Scale, Tardieu catch angle, and root mean square surface electromyographic activity of the biceps, brachialis, and brachioradialis.

Results

Postintervention testing at 3 weeks showed no significant differences between groups (P range, .31-.82 across 3 outcome measures). However, within each group, significant treatment effects were observed on all outcome measures (all P<.01). For the uninjected brachialis muscle, electromyographic reduction was greater for the distributed group.

Conclusions

In 31 adults with acquired brain injury, single motor point and multisite distributed injections of low-dose, high-volume BTX-A had similar impact. Findings suggest that low-dose, high-volume strategies may have a potential role in reducing drug cost and helping clinicians stay within accepted limits for total body dose in patients with upper motoneuron syndrome requiring many injections.     

Parent evaluation of spasticity treatment in cerebral palsy using botulinum toxin type A

OBJECTIVE: To assess parent ratings of treatment acceptability associated with botulinum toxin type A (BTX-A) injection for spasticity in children with cerebral palsy (CP). DESIGN: A single-point survey design across a sequentially recruited cohort, using a standardized evaluation measure. SETTING: Regional specialty health care center medical clinic and pain research program. PARTICIPANTS: Fifty-nine parents of children with CP receiving BTX-A injection for spasticity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Treatment Evaluation Inventory. RESULTS: Overall, parent ratings of treatment acceptability ranged from moderate to high. There were no significant differences for caregiver ratings in relation to characteristics of the raters (age, sex, marital status) or of the children (age, sex, mental retardation, severity of disability) characteristics. CONCLUSIONS: These findings indicate that on average, parents of children with CP consider BTX-A treatment for the management of spasticity to be an acceptable form of treatment.     

Combining botulinum toxin and phenol to manage spasticity in children

OBJECTIVE: To describe the specific techniques and adverse reactions of using concurrent, multiple injections of both botulinum toxin and phenol to manage spasticity in children with cerebral palsy (CP) and other neurologic conditions. DESIGN: A retrospective case series. SETTING: A tertiary care children's hospital. PARTICIPANTS: Consecutive patients (N=68) with spasticity related to CP or other neurologic conditions. INTERVENTION: Ninety injection sessions combining botulinum toxin and phenol to manage spasticity. MAIN OUTCOME MEASURE: Documentation of adverse reactions. RESULTS: The mean phenol dosage was 9.5mL at a mean of 0.6mL/kg per injection dose. The mean botulinum toxin type A (Botox) dose injected was 193U (12U/kg), and the mean of botulinum toxin type B (Myobloc) dose injected was 7750U (530U/kg). The mean number of muscles injected was 14. Adverse reactions are described but were infrequent. Dysesthetic hand pain occurred in 2 patients. One patient developed a systemic reaction to Myobloc. CONCLUSIONS: Using botulinum toxin and phenol injections allowed many muscles to be injected to manage spasticity in children with CP and other neurologic conditions. Using this combination allowed an increased number of injections at the maximal recommended dose.     

The use of a portable muscle tone measurement device to measure the effects of botulinum toxin type a on elbow flexor spasticity

OBJECTIVE: To use a portable muscle tone assessment device to measure spasticity after a botulinum toxin type A (BTX-A) injection. DESIGN: Before-after trial. SETTING: Hospital. PARTICIPANTS: Ten chronic stroke patients with upper-limb spasticity. INTERVENTION: BTX-A was injected in the biceps brachii. MAIN OUTCOME MEASURES: The biomechanic parameters, viscous component, and averaged viscosity derived from the acquired reactive resistance and angular displacements, as well as the reflex electromyographic threshold of biceps brachii, were used for spasticity evaluation. RESULTS: A statistically significant decrease in averaged viscosity and a significant increase in reflex electromyographic threshold (P<.05) both indicated reduction in spasticity owing to BTX-A intervention. There was no clear reflex electromyographic activity detected at lower stretch frequencies. CONCLUSIONS: Our portable design allows for the convenient use of the device for quantifying spasticity in clinics. All quantitative measurements suggest that BTX-A decreases spasticity within 2 weeks of injection. Our portable muscle tone measurement device may be useful for the clinical assessment of elbow flexor spasticity.     

The effect of hippotherapy on spasticity and on mental well-being of persons with spinal cord injury

OBJECTIVES: To determine the effect of hippotherapy on spasticity and on mental well-being of persons with spinal cord injury (SCI), and to compare it with the effects of other interventions. DESIGN: Crossover trial with 4 conditions. SETTING: Swiss paraplegic center. PARTICIPANTS: A volunteer sample of 12 people with spastic SCI (American Spinal Injury Association grade A or B). INTERVENTIONS: Hippotherapy, sitting astride a Bobath roll, and sitting on a stool with rocking seat. Each session lasted 25 minutes and was conducted twice weekly for 4 weeks; the control condition was spasticity measurement without intervention. MAIN OUTCOME MEASURES: Clinical rating by a blinded examiner of movement-provoked muscle resistance, using the Ashworth Scale; self-rating of spasticity by subjects on a visual analog scale (VAS); and mental well-being evaluated with the self-rated well-being scale Befindlichkeits-Skala of von Zerssen. Assessments were performed immediately after intervention sessions (short-term effect); data from the assessments were analyzed 3 to 4 days after the sessions to calculate the long-term effect. RESULTS: By analyzing the clinically rated spasticity, only the effect of hippotherapy reached significance compared with the control condition (without intervention); median differences in the Ashworth scores' sum before and after hippotherapy sessions ranged between -8.0 and +0.5. There was a significant difference between the spasticity-reducing effect of hippotherapy and the other 2 interventions in self-rated spasticity by VAS; median differences of the VAS before and after hippotherapy sessions ranged between -4.6 and +0.05cm. There were no long-term effects on spasticity. Immediate improvements in the subjects' mental well-being were detected only after hippotherapy (P=.048). CONCLUSIONS: Hippotherapy is more efficient than sitting astride a Bobath roll or on a rocking seat in reducing spasticity temporarily. Hippotherapy had a positive short-term effect on subjects' mental well-being.     

Effectiveness of static stretching positioning on post-stroke upper-limb spasticity and mobility: Systematic review with meta-analysis

ObjectiveTo systematically review the effects of static stretching with positioning orthoses or simple positioning combined or not with other therapies on upper-limb spasticity and mobility in adults after stroke.MethodsThis meta-analysis was conducted according to PRISMA guidelines and registered at PROSPERO. MEDLINE (Pubmed), Embase, Cochrane CENTRAL, Scopus and PEDro databases were searched from inception to January 2018 for articles. Two independent researchers extracted data, assessed the methodological quality and rated the quality of evidence of studies.ResultsThree studies (57 participants) were included in the spasticity meta-analysis and 7 (210 participants) in the mobility meta-analysis. Static stretching with positioning orthoses reduced wrist-flexor spasticity as compared with no therapy (mean difference [MD] = −1.89, 95% confidence interval [CI] −2.44 to −1.34; I² 79%, P < 0.001). No data were available concerning the spasticity of other muscles. Static stretching with simple positioning, combined or not with other therapies, was not better than conventional physiotherapy in preventing loss of mobility of shoulder external rotation (MD = 3.50, 95% CI −3.45 to 10.45; I² 54.7%, P = 0.32), shoulder flexion (MD = −1.20, 95% CI −8.95 to 6.55; I² 0%, P = 0.76) or wrist extension (MD = −0.32, 95% CI −6.98 to 5.75; I² 38.5%, P = 0.92). No data were available concerning the mobility of other joints.ConclusionThis meta-analysis revealed very low-quality evidence that static stretching with positioning orthoses reduces wrist flexion spasticity after stroke as compared with no therapy. Furthermore, we found low-quality evidence that static stretching by simple positioning is not better than conventional physiotherapy for preventing loss of mobility in the shoulder and wrist. Considering the limited number of studies devoted to this issue in post-stroke survivors, further randomized clinical trials are still needed.Clinical Trial RegistrationPROSPERO (CRD42017078784).     

Serial injection of botulinum toxin for muscle imbalance due to regional spasticity in the upper limb

Background and purpose. Three-dimensional movement in the upper limb presents a challenge for functional management of regional spasticity. Potential toxicity of botulinum toxin limits the number of muscles which may be injected in any one session. Serial injection may offer a solution, but carries theoretical risk of development of resistance due to antibody formation. This article reviews a small case series, gathered in a post-acute neuro-rehabilitation setting, to evaluate the use of serial botulinum toxin injection in terms of goal achievement and clinical evidence for toxicity or resistance.

Methods. Nine patients with regional spasticity following acute stroke or brain injury had serial injection of botulinum toxin to muscle groups around the shoulder, elbow and/or wrist. Injection was followed by splinting/physiotherapy as appropriate. Goal attainment scaling was used to assess outcome.

Results. Functional goals achieved were reduction of pain (n = 6/7) associated reaction (n = 4/5) or care needs (n = 5/6), improved gait (n = 2/3) or independence in self-care (n = 2/5). Two ‘golden responder’ cases are presented in detail to demonstrate resolution of symptoms with up to four serial injections of botulinum toxin over a period of up to 6 months. No clinical evidence of toxicity or resistance was seen in any case.

Conclusion. These preliminary findings suggest that serial botulinum toxin injection followed by appropriate physiotherapy/splinting may provide effective treatment for regional spasticity. Resistance has not presented a problem in this post-acute situation, where treatment has not been required beyond a few months. Ongoing evaluation is underway.     

Motor points for the neuromuscular blockade of the subscapularis muscle

OBJECTIVE: To locate the motor points of the subscapularis muscle in relation to palpable anatomic landmarks and hence suggest a technique for botulinum toxin injection into subscapularis applicable to patients of all ages. DESIGN: Anatomic dissection of the innervation of 20 subscapular muscles. SETTING: University dissecting room. CADAVERS: Ten formalin-preserved cadavers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The location of motor points in relation to anatomic landmarks. RESULTS: The median number of motor points for the subscapularis was 5 (range, 3-6). All motor point measurements were related to surface points and converted into proportional values along reference lines. Motor points from the 20 dissections showed clustering in a band. A line of best fit was calculated (y=1.48x-0.743). CONCLUSIONS: We describe an injection technique that would deliver botulinum toxin close to the motor points of the subscapularis, a surrogate marker of the motor endplate zones. By using proportional distances, this technique is applicable to an adult and pediatric population. This should lead to an increased efficacy and decreased side-effect profile in clinical practice, although clinical trials will need to confirm this.     

Effect of botulinum toxin injection in the rectus femoris on stiff-knee gait in people with stroke: a prospective observational study

Stoquart GG, Detrembleur C, Palumbo S, Deltombe T, Lejeune TM. Effect of botulinum toxin injection in the rectus femoris on stiff-knee gait in people with stroke: a prospective observational study.

Objective

To study the effect of botulinum toxin type A (BTX-A) injection in the rectus femoris on the decreased knee flexion during the swing phase of gait (stiff-knee gait) in people with stroke.

Design

Intervention study (before-after trial) with an observational design.

Setting

Outpatient rehabilitation clinic and gait laboratory.

Participants

Nineteen chronic hemiparetic adults presenting with stiff-knee gait.

Intervention

Injection of 200U of BTX-A (Botox) into the rectus femoris.

Main Outcome Measures

Before and 2 months after BTX-A rectus femoris injection: Stroke Impairment Assessment Set (SIAS), Duncan-Ely test, and an instrumented gait analysis.

Results

Median SIAS score improved from 53 (range, 36−65) to 57 (range, 42−70) (signed-rank test, P=.005) and the Duncan-Ely score from 3 (range, 1−3) to 1 (range, 0−3) (P<.001). In gait analysis, mean (± standard deviation) maximum knee flexion improved from 26°±13° to 31°±14° during the swing phase (paired t test, P<.001), knee flexion speed at toe-off improved from 82°±63° to 112°±75°/s (P=.009), and knee negative joint power (eccentric muscular contraction) improved from −.27±.23 to −.37±.26W/kg (P<.001). The 4 patients who almost did not flex the knee (<10°) before the BTX-A rectus femoris injection did not improve after the injection. The other 14 patients who flexed the knee more than 10° before the BTX-A rectus femoris injection decreased the walking energy cost from 5.4±1.6 to 4.6±1.3J·kg⁻¹·m⁻¹ (P=.006).

Conclusions

BTX-A rectus femoris injection may be beneficial in patients with a stiff-knee gait after stroke, particularly in patients with some knee flexion (>10°).     

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity.

Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000 U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS).

Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500 U and the peak improvement was at week 8 after injection. A dose of 1000 U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication.

Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500 U.     

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity.

Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000?U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS).

Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500?U and the peak improvement was at week 8 after injection. A dose of 1000?U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication.

Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500?U.     

Immunogenicity induced by botulinum toxin injections for limb spasticity: A systematic review

BackgroundThe imputability of neutralizing antibodies (NABs) in secondary non-response (SnR) to botulinum toxin (BoNT) injections for limb spasticity is still debated.ObjectiveThis systematic literature review aimed to determine the prevalence of NABs after BoNT injections for limb spasticity and analyze their determinants and their causal role in SnR.MethodsWe searched MEDLINE via PubMed, Cochrane and Embase databases for articles published during 1990–2018. Two independent reviewers extracted the data and assessed the quality of studies with a specific scale (according to PRISMA and STROBE guidelines). Because the techniques used to detect NABs did not influence the results, we calculated the global (all studies) sensitivity and specificity of NAB positivity to reveal SnR.ResultsWe included 14 articles published from 2002 to 2018 (including an epublication) describing 5 randomized controlled trials and 5 interventional and 4 observational studies. The quality was satisfactory (mean score 18/28 arbitrary units). NAB detection was the primary criterion in 5 studies and a secondary criterion in 9. In total, 1234 serum samples for 1234 participants (91% with stroke) were tested after injection. NAB prevalence was about 1%, with no significant difference among formulations. NAB positivity seemed favoured by long-duration therapy with high doses and a short interval between injections. The identification of non-response by NAB positivity had poor global sensitivity (56%) but very high specificity (99.6%). No consensual criteria were used to diagnose non-response to BoNT injection.ConclusionsNAB prevalence is much lower after BoNT treatment for limb spasticity than cervical dystonia. Consensual criteria must be defined to diagnose non-response to BoNT injection. Because immunogenicity is not the most common cause of non-response to BoNT injection, NABs should be sought in individuals with SnR with no other cause explaining the treatment inefficacy. A test with 100% specificity is recommended. In cases for which immunogenicity is the most likely cause of non-response to BoNT injections, some biological arguments suggest trying another BoNT, but no clinical evidence supports this strategy.     

Neuromuscular Partitioning of Subscapularis Based on Intramuscular Nerve Distribution Patterns: Implications for Botulinum Toxin Injections

Subscapularis muscle spasticity is commonly treated with botulinum toxin injections; however, there are challenges in determining optimal injection sites within the muscle. The purpose of this study was to document the intramuscular innervation patterns of the subscapularis (1) to determine how the muscle is neuromuscularly partitioned and (2) to identify a strategy for botulinum toxin injection based on neuromuscular partitioning. In 50 formalin-embalmed cadaveric specimens, the extramuscular and intramuscular innervation was (1) serially dissected, digitized, and reconstructed in 3 dimensions (n=7); or (2) serially dissected and photographed (n=43). Intramuscular innervation patterns were compared among specimens to identify neuromuscular partitions. Variation was observed in the number (2–5) and origin of extramuscular nerve branches to the subscapularis. Despite variation in extramuscular innervation, the intramuscular innervation was consistent. Based on intramuscular innervation patterns, the subscapularis had 3 neuromuscular partitions (superior, middle, inferior) in 78% of specimens, and 2 partitions (superior, inferior) in 22% of specimens. The superior and middle partitions were most commonly innervated by branch(es) from the posterior cord, and the inferior partition by branch(es) from the axillary nerve. Injection of botulinum toxin into each partition may help to optimize results in the treatment of shoulder spasticity, and may be achieved by a combination of medial and inferior approaches. Clinical studies are required to determine whether the combination approach is more effective than any single approach and whether the number of partitions injected correlates with clinical outcomes.     

The effect of combined use of botulinum toxin type A and functional electric stimulation in the treatment of spastic drop foot after stroke: a preliminary investigation

OBJECTIVE: To investigate the effect of combined botulinum toxin type A (BTX) and functional electric stimulation (FES) treatment on spastic drop foot in stroke. DESIGN: Nonblinded randomized controlled trial. SETTING: Hospitals. PARTICIPANTS: Consecutive sample of 21 ambulant adults within 1 year after stroke with a spastic drop foot, of whom 18 completed the study. INTERVENTIONS: The treatment group received BTX injections (Dysport) on 1 occasion into the medial and lateral heads of the gastrocnemius (200U each) and tibialis posterior (400U each) muscles and FES, used on a daily basis for 16 weeks to assist walking. Both groups continued with physiotherapy at the same rate. MAIN OUTCOME MEASURES: Walking speed, Physiological Cost Index, Modified Ashworth Scale, Rivermead Motor Assessment, and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Walking speed increased over 12 weeks in both control (P=.020) and treatment groups (nonstimulated, P=.004; stimulated, P=.042). The baseline corrected (analysis of covariance) increase in mean walking speed at 12 weeks, relative to controls, was.04m/s (95% confidence interval [CI],.003-.090) without stimulation, and.09m/s (95% CI,.031-.150) with stimulation. CONCLUSIONS: Combined treatment effectively improved walking and function. A larger study is needed to quantify the treatment effect and to investigate its impact on quality of life.     

Adjunct therapies after botulinum toxin injections in spastic adults: Systematic review and SOFMER recommendations

BackgroundAdjunct therapies (ATs) may further improve outcomes after botulinum toxin injections in spastic patients, but evidence was unclear in previous systematic reviews.ObjectiveTo assess the efficacy of non-pharmacological ATs in spastic adults according to the International Classification of Functioning, Disability and Health and build an expert consensus-based on a Delphi process.MethodsFour electronic databases were searched up to May 2020 for reports of comparative trials of non-pharmacologic ATs after botulinum toxin injections in spastic adults. Then, 25 French experts participated in a two-round Delphi process to build recommendations on the use of ATs.ResultsWe included 32 studies (1202 participants, median 32/study) evaluating the effects of physical agents (n = 9), joint posture procedures (JPPs, n = 11), and active ATs (n = 14), mainly after stroke. The average quality of articles was good for randomised controlled trials (median [interquartile range] PEDro score = 7 [6–8]) but moderate (n = 2) or poor (n = 2) for non-randomised controlled trials (Downs & Black checklist). Meta-analysis was precluded owing to the heterogeneity of ATs, control groups and outcome measures. There is evidence for the use of JPPs except low-dose manual stretching and soft posture techniques. Continuous postures (by taping or casting) are recommended; discontinuous postures (by orthosis) may be preferred in patients with active function. Device-free or device-assisted active ATs may be beneficial in the mid-term (> 3 months after botulinum toxin injections), particularly when performed at a high-intensity (> 3 h/week) as in constraint-induced movement therapy. Self-rehabilitation remains understudied after a focal treatment, but its interest is highlighted by the experts. The use of physical agents is not recommended.ConclusionsJPPs and active ATs (device-assisted or device-free) may further improve impairments and activities after botulinum toxin injections. Further studies are needed to better define the best strategies for ATs as a function of the individual treatment goals, participation and quality of life.Review RegistrationPROSPERO (CRD42018105856).