Effectiveness of different doses of botulinum neurotoxin in lateral epicondylalgia: A network meta-analysis.

BACKGROUND: Previous studies have investigated the role of botulinum neurotoxin (BoNT) in lateral epicondylalgia, with controversial results. We hypothesized that BoNT would be effective and safe for the treatment of lateral epicondylalgia. OBJECTIVE: To investigate the effectiveness and safety of different doses of BoNT in participants with lateral epicondylalgia. METHODS: PubMed, Embase, and Cochrane Library were searched up to August 27, 2022, for randomized controlled trials (RCTs) of BoNT treatment for epicondylalgia. The Cochrane risk of bias tool was used for quality assessment. A network meta-analysis and a trial sequential analysis (TSA) were conducted on pain, grip strength and adverse events. Meta-regression was applied for high heterogeneity comparisons. RESULTS: We included 8 RCTs consisting of 448 participants. Four studies scored low risk of bias in all categories, whereas the other 4 studies had unclear risk only in the selection bias category. The network meta-analysis and TSA revealed that corticosteroid (standardized mean difference [SMD]: -1.32, 95% CI: -2.13; -0.50), high-dose BoNT (SMD -1.32, -2.04; -0.61), and low-dose BoNT (SMD -0.52, -0.93; -0.10), relieved pain significantly better than placebo for up to 7 to 10 weeks. High-dose BoNT demonstrated a significantly greater reduction in pain than low-dose BoNT for up to 7 to 10 weeks (SMD -0.81, -1.39; -0.22). Finally, after low-dose BoNT, younger participants (p = 0.023) and women (p = 0.012) showed more pain decrease than older individuals and men at 2 to 6 weeks. As for grip strength and adverse events, only grip strength after low-dose BoNT versus placebo (SMD -0.49, -0.88; -0.10) and corticosteroid (SMD -1.36, -2.15; -0.57) at 2 to 6 weeks reached significance after threshold adjustment in TSA. CONCLUSIONS: Our meta-analysis confirmed the effectiveness of low-dose BoNT in the reduction of pain for lateral epicondylalgia. Further conclusions cannot be drawn due to insufficient available data.

Meta-Analysis of Effectiveness and Safety of Botulinum Toxin in the Treatment of Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is characterized by pain, limited range of motion, swelling, skin changes, vasomotor instability, and patchy bone demineralization. Conservative management strategies for CRPS include physical and occupational therapy, psychosocial and behavioral therapy, and pharmacotherapy. However, some patients still experience CRPS symptoms after receiving conventional treatments. Therefore, botulinum toxin (BoNT) has been applied to patients with CRPS in several trials considering its analgesic effect in musculoskeletal and neuropathic pain; however, the results were controversial. We conducted the study to explore the effectiveness and safety of BoNT in patients with complex regional pain syndrome (CRPS). A search was performed using the following electronic databases up to 19 October 2022: PubMed, Embase, and Cochrane Library. We included both randomized controlled trials and nonrandomized controlled studies involving patients with complex regional pain syndrome managed with botulinum toxin. Cochrane risk-of-bias tool and Joanna Briggs Institute Critical Appraisal Checklist were used for quality assessment for randomized controlled trials and quasi-experimental studies. Only randomized controlled trials entered the meta-analysis. The primary outcome was the visual analogue scale of pain presented as a weighted mean difference (WMD) and 95% confidence interval (CI). The secondary outcome was the risk of adverse events presented as an odds ratio (OR) with 95% CI. We analyzed eight articles with 176 patients, including three randomized controlled trials with 62 participants. The age of the patients ranged from 23.8 to 51 years old. The duration of the disease ranged from 2.2 to 11.8 years. The proportion of females ranged from 16.6% to 100%. The route of administration of BoNT included: (1) lumbar sympathetic block (LSB), (2) intramuscular injection, (3) subcutaneous or intradermal injection (SC/ID). Improvement in pain was revealed in six studies, and adverse events were all self-limited and temporary. Meta-analysis revealed a significant reduction in pain at the first follow-up between 3 weeks to 1 month after intervention (WMD, -1.036, 95% CI, -1.673 to -0.400) but not at the second follow-up between 2 to 3 months after treatment (WMD, -0.895, 95% CI, -2.249 to 0.458). Subgroup analyses between LSB and SC/ID were nonsignificant at both follow-up periods (p = 0.422, 0.139). The risk of adverse events was similar between the BoNT and control group (OR, 0.698, 95% CI, 0.136 to 3.581). In conclusion, BoNT may be effective and safe for alleviating pain in patients with CRPS. However, we could not draw definite conclusions due to small sample size and high between-study heterogeneity. The limited number of participants may conceal the possibility of serious adverse events. Further large-scale randomized controlled trials are warranted to delineate the role of BoNT in CRPS.

The Effectiveness and Safety of Botulinum Neurotoxin in Obstetric Brachial Plexus Injury: A Systematic Review and Meta-Analysis.

Obstetric brachial plexus injury, also known as neonatal brachial plexus injury, is not unusual in newborns. Given the lack of a comprehensive synthesis of the available data on the effectiveness of botulinum neurotoxin (BoNT) in treating children with obstetric brachial plexus injury, we conducted a systematic review and meta-analysis. We searched PubMed, Embase, Web of Science, and Cochrane databases from inception to 25 November 2022. Outcomes were function of the shoulder and elbow joints, muscle power of the deltoid, biceps brachii and triceps brachii, and the recurrence rate of subluxation or dislocation after reduction of the shoulder joint after BoNT application. Meta-regression was conducted to assess the moderator effect of age. We included 11 case series and 2 cohort studies. Passive range of motion of shoulder external rotation (standardized mean difference [SMD], 0.678; 95% confidence interval [95%CI], 0.423 to 0.934), Active Movement Scale for shoulder external rotation (SMD, 0.47; 95%CI, 0.131 to 0.808), and active range of motion of elbow extension (SMD, 2.445; 95%CI, 1.556 to 3.334) increased significantly after BoNT. However, the modified Gilbert scale for shoulder abduction (SMD, 1.239; 95% CI, -0.2 to 2.678), the Toronto score for active elbow flexion (SMD, 1.099; 95% CI, -0.053 to 2.252), muscle power of deltoid (SMD, 0.675; 95% CI, -0.599 to 1.949), biceps brachii (SMD, 0.225; 95% CI, -0.633 to 1.083), and triceps brachii (SMD, 1.354; 95% CI, -1.493 to 4.202) did not reach statistical significance. The moderator effect of age was not significant (p = 0.88). Meta-analysis was not done for recurrence rate of subluxation or dislocation due to insufficient data. In conclusion, our data support BoNT use in patients with obstetric brachial plexus injury. However, definite conclusions cannot be drawn due to small sample size and the lack of randomized controlled trials. More research is warranted to clarify the effectiveness of BoNT in patients with obstetric brachial plexus injury by using standardized injection protocols and outcome measurements.

Effectiveness of Botulinum Neurotoxin in Treatment of Scoliosis among Children and Adolescents: A Systematic Review and Meta-Analysis.

Scoliosis refers to a three-dimensional deviation in the axis of the spine. Muscle imbalance is believed to play a role in scoliosis. Botulinum neurotoxin (BoNT) can reduce muscle overactivity and may have the potential to ameliorate spinal scoliosis. This study investigated the effectiveness of intramuscular BoNT injection in vertebral curve correction and reviewed the possible influencing factors. PubMed, Medline, Cochrane Central Register of Controlled Trials, Web of Science, Airiti Library, and Index of the Taiwan Periodical Literature System databases were searched from inception until 7 September 2022 for eligible studies. The main outcome was the change in Cobb angle after BoNT application. Subgroup analysis was conducted according to differences in study designs, etiology of scoliosis, and methods used for target muscle selection. We enrolled three studies including 31 participants aged between 2 and 18 years. The meta-analysis revealed no significant reduction in the Cobb angle after BoNT injection (standardized mean difference, -0.783, 95% CI, -2.142 to 0.576). Study designs (p = 0.011) and methods used for target muscle selection (p = 0.017) but not etiology of scoliosis (p = 0.997) reached statistical significance between subgroups. In conclusion, the current meta-analysis does not support the application of BoNT in children and adolescents with scoliosis. However, a decisive conclusion could not be made due to high between-study heterogeneity and small sample size. More randomized controlled trials with appropriate target muscle selection and standard outcome measurement should be conducted to examine the efficacy of botulinum neurotoxin in treating scoliosis. INPLASY ID: INPLASY202290031.

Efficacy and safety of botulinum toxin type A in distraction osteogenesis of the lower extremities: a meta-analysis of randomized controlled trials.

BACKGROUND: To explore the efficacy and safety of botulinum toxin in patients who received distraction osteogenesis of the lower extremities. METHODS: We searched the PubMed, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials that administered botulinum toxin to individuals who underwent distraction osteogenesis of the lower limbs. The final search was conducted on July 6, 2021. Quality assessments were conducted using the Cochrane risk of bias tool and the Jadad scale. We performed random-effects meta-analysis to calculate the standardized mean differences (SMDs) and confidence intervals (CIs) of the pooled effect sizes, and subgroup analysis and meta-regression were performed for potential moderators. RESULTS: Our analysis of four randomized controlled trials, which enrolled a total of 257 participants, revealed that the difference in pain during the distraction phase was not statistically significant between groups (SMD, - 0.165; 95% CI, - 0.379 to 0.050, p = 0.133, I2 = 0.0%). The meta-regression analyses did not find any influence on the effect size, considering age (ß = - 0.0092; p = 0.61) and the amount of lengthening (ß = 0.0023; p = 0.99). Subgroup analysis did not reveal difference between different doses of botulinum toxin and single or multi-site study design. An analysis of two randomized controlled trials enrolling a total of 177 individuals demonstrated a limited effect of botulinum toxin in reducing postoperative pain (SMD, - 0.239; 95% CI, - 0.641 to 0.162, p = 0.24, I2 = 37.6%), total adverse events (SMD, - 0.207; 95% CI, - 0.505 to 0.090, p = 0.17, I2 = 0.0%), and infection of pin site (SMD, - 0.131; 95% CI, - 0.428 to 0.165, p = 0.39, I2 = 0.0%). No botulinum toxin-related adverse events were reported. CONCLUSIONS: The current evidence does not support the administration of botulinum toxin in patients who receive distraction osteogenesis of the lower limbs. However, we were unable to draw decisive conclusions because of the limitations of our meta-analysis. Future well-designed, large-scale randomized controlled trials are necessary to confirm our conclusions.

Botulinum Toxin Injections for Treatment of Drooling in Children with Cerebral Palsy: A Systematic Review and Meta-Analysis.

BACKGROUND: We aimed to review and analyse the effectiveness and safety of botulinum toxin type A (BoNT-A) injections for drooling in children with cerebral palsy. DATA SOURCES: We searched the EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) databases from inception to January 2020. METHODS: We included randomized controlled trials and observational studies which (1) involved children with cerebral palsy, (2) used BoNT-A for control of drooling, and (3) provided quantitative evaluations of drooling before and after intervention with BoNT-A. RESULTS: Twenty-one trials met the inclusion criteria. Most studies showed that BoNT-A injections are safe and efficacious as a treatment for drooling in children with cerebral palsy. Four trials had sufficient data to pool the results for the meta-analysis. Both the drooling quotient (p = 0.002) and drooling Ffrequency and severity scale (p = 0.004) supported this conclusion. CONCLUSION: BoNT-A injections are a safe, reversible, effective treatment for drooling control in children with cerebral palsy that can offer effectiveness for more than 3 months with few side effects. The dosage of BoNT-A should not exceed 4 units/kg. Further studies are required to determine the optimal dosage and target glands.

Effectiveness and Safety of Botulinum Toxin Type A in Treatment of Restless Legs Syndrome: A Systematic Review and Meta-Analysis.

Our study aimed to investigate the effectiveness and safety of botulinum toxin type A in patients with restless legs syndrome. We searched electronic databases, including PubMed, Cochrane Library, and Web of Science, up to 12 June 2021, for published articles. We enrolled randomized controlled clinical trials and non-randomized controlled studies involving patients with restless legs syndrome who were treated with botulinum toxin. Quality assessment was performed using the Cochrane risk of bias tool and Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies. As for the results, we included four articles comprising 62 participants, two studies were randomized controlled trials. Improvement in International Restless Legs Syndrome Study Group (IRLSSG) rating scale was observed in three studies. Adverse events were temporary and self-limited. Meta-analyses were performed, including the two randomized controlled trials with 27 participants. Compared with placebo, botulinum toxin injection significantly reduced scores of IRLSSG rating scale (SMD, -0.819, 95% confidence interval [CI], -1.377 to -0.262). A total of 11.8% (95% CI, 0.7-72.4%) of patients reported at least one adverse event. In conclusion, botulinum toxin injection may relieve restless legs syndrome related symptoms. However, decisive conclusions cannot be drawn because of the small number of patients included in our meta-analysis. Large-scale, randomized controlled trials are warranted to discover the optimal dose, safety, and long-term effect of intervention with botulinum toxin type A for patients with restless legs syndrome.

A Meta-Analysis and Meta-Regression of Frequency and Risk Factors for Poststroke Complex Regional Pain Syndrome.

Background and Objectives: This article aimed to investigate the risk factors for poststroke complex regional pain syndrome (CRPS). Materials and Methods: We searched electronic databases including PubMed, Medline, Web of Science, Cochrane Library, and Embase up to 27 October 2021. We enrolled analytical epidemiological studies comprising cohort, case-control, and cross-sectional studies. A quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies and the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Binary outcomes were reported as odds ratios (ORs), and continuous outcomes were described as standardized mean differences (SMDs) with 95% confidence intervals. For the meta-regression, beta coefficient and p value were adopted. Results: We included 21 articles comprising 2225 participants. Individuals with shoulder subluxation and spasticity were found to have higher risks for poststroke CRPS. Spasticity with higher modified Ashworth scale score, lower Brunnstrom hand stage, and inferior Barthel index scores were observed in patients with poststroke CRPS. The pooled incidence proportion in nine articles was 31.7%, and a correlation was found between effect sizes and the ratio of women and the proportion of left hemiparesis. The summarized prevalence in nine cross-sectional studies was 33.1%, and a correlation was observed between prevalence and the subluxation ratio and Brunnstrom stage. Conclusions: Based on our meta-analysis, being female, left hemiparesis, shoulder subluxation, spasticity, a lower Brunnstrom stage of distal upper limb, and an inferior Barthel index are all features for poststroke CRPS. Larger studies with greater statistical power may confirm our findings and clarify some other unknown risk factors for poststroke CRPS.

Efficacy of Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This article aimed to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia. The PubMed, Medline, Cochrane Library, and Web of Science databases were searched for articles published through 14 August 2021. We enrolled only randomized controlled trials. The Cochrane Collaboration risk of bias tool was used for quality assessment. Outcomes were analyzed as standardized mean differences (SMDs) with 95% CIs. The beta coefficient and p value were adopted for meta-regression. We included 18 studies comprising 643 participants. A significant reduction in disease influence, as measured by the Fibromyalgia Impact Questionnaire, was observed (SMD, -0.700, 95% CI, -1.173 to -0.228), and the reduction was larger in older patients (ß = -0.1327, p = 0.008). The effect persisted at least two weeks after the final treatment session (SMD, -0.784, 95% CI, -1.136 to -0.432). Reductions in pain, depression, and anxiety were discovered, which persisted for at least two weeks after the last intervention. The effects on pain and depression remained significant up to one and a half months after the final session. No serious adverse events were reported by the included articles. In conclusion, our systematic review and meta-analysis revealed that rTMS is safe and effective for managing multiple domains of fibromyalgia-related symptoms and older patients may have a stronger treatment effect. Larger randomized controlled trials with sufficient male populations are warranted to confirm our findings, detect rare adverse events, and determine the optimal stimulation parameters.

Botulinum toxin injection for Cockayne syndrome with muscle spasticity over bilateral lower limbs: A case report.

BACKGROUND: Cockayne syndrome (CS) is a rare inherited disease characterized by progressive motor symptoms including muscle weakness, joint contracture, ataxia, and spasticity. Botulinum neurotoxin type A has been used for conditions such as dystonia and spasticity, but it has rarely been used in patients with CS. CASE SUMMARY: We report a 6-year-and-9-mo old girl diagnosed with CS who received an injection of botulinum neurotoxin type A to manage her difficulty with walking. A total dose of 210 units of botulinum neurotoxin type A was administered into the bilateral tibialis posterior and gastrocnemius muscles. To evaluate the treatment effects on spasticity, joint contracture, pain, and ataxia, measurement tools including the Modified Ashworth Scale, the passive range of motion, the Faces Pain Scale-Revised, and the Scale for the Assessment and Rating of Ataxia, were employed. The first week after the injection, the Modified Ashworth Scale score for the plantar flexors and foot invertors improved bilaterally, along with advancements in the passive range of motion of the bilateral ankles and a lower score for the Faces Pain Scale-Revised. These treatment effects persisted to the 8th week post-injection, but returned to baseline values at the 12th week post-injection, except for the pain scale. CONCLUSION: Botulinum toxin injection can thus be considered as a treatment option for lower extremity spasticity, joint contracture, and pain derived from CS.

Comparison Between Steroid and 2 Different Sites of Botulinum Toxin Injection in the Treatment of Lateral Epicondylalgia: A Randomized, Double-Blind, Active Drug-Controlled Pilot Study.

OBJECTIVE: To compare the effects of 2 different injection sites of low doses of botulinum toxin type A with steroid in treating lateral epicondylalgia. DESIGN: Double-blind, randomized, active drug-controlled trial. SETTING: Tertiary medical center. PARTICIPANTS: Patients with lateral epicondylalgia for >6 months were recruited from a hospital-based outpatient population (N=26). A total of 66 patients were approached, and 40 were excluded. No participant withdrew because of adverse effects. INTERVENTIONS: Patients were randomly assigned into 3 groups: (1) botulinum toxin epic group (n=8), who received 20U of botulinum toxin injection into the lateral epicondyle; (2) botulinum toxin tend group (n=7), who received 20U of botulinum toxin injected into tender points of muscles; and (3) steroid group (n=11), who received 40mg of triamcinolone acetonide injected into the lateral epicondyle. MAIN OUTCOME MEASURES: A visual analog scale, a dynamometer, and the Patient-Rated Tennis Elbow Evaluation were used to evaluate the perception of pain, maximal grip strength, and functional status, respectively. Outcome measures were assessed before intervention and at 4, 8, 12, and 16 weeks after treatment. The primary outcome measure was a visual analog scale. RESULTS: At 4 weeks after injection, the steroid group was superior to the botulinum toxin tend group in improvement on the visual analog scale (P=.006), grip strength (P=.03), and Patient-Rated Tennis Elbow Evaluation (P=.02). However, these differences were not observed at the 8-, 12-, and 16-week follow-up assessments. There was no significant difference between the steroid and botulinum toxin epic groups. CONCLUSIONS: Injections with botulinum toxin and steroid effectively reduced pain and improved upper limb function in patients with lateral epicondylalgia for at least 16 weeks. The onset of effect was earlier in the steroid and botulinum toxin epic groups than in the botulinum toxin tend group.

Rehabilitation for a child with recalcitrant anti-N-methyl-d-aspartate receptor encephalitis: case report and literature review.

Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is a newly recognized, potentially fatal, but treatable autoimmune disease. Good outcome predictors include milder severity of symptoms, no need for intensive care unit admission, early aggressive immunotherapy, and prompt tumor removal. We report a case of a young girl aged 3 years 2 months and diagnosed as recalcitrant anti-NMDA receptor encephalitis without any underlying neoplasm. The patient had initial symptoms of behavioral changes that progressed to generalized choreoathetosis and orofacial dyskinesia, which resulted in 6 months of hospitalization in the pediatric intensive care unit. One year after initial onset of the disease, she had only achieved the developmental age of an infant aged 6-8 months in terms of gross and fine motor skills, but she resumed total independence in activities of daily living after receiving extensive immunotherapy and 28 months of rehabilitation. Our brief review will help clinical practitioners become more familiar with this disease and the unique rehabilitation programs.

Effect of acetazolamide for long-lasting paroxysmal dystonia in a patient with multiple sclerosis: a case report and review of literature.

Dystonia is a rare manifestation of multiple sclerosis (MS), but it always interferes with the functional performance and quality of life. We report a rare case of long-lasting paroxysmal dystonia associated with MS. The patient was a 40-year-old woman with relapsing- remitting MS for 6 years. During the latest attack of MS, she suffered from long-lasting paroxysmal dystonia in her left hand. Despite treatment with pulse high-dose intravenous methylprednisolone, interferon, and baclofen, along with occupational therapy, the dystonia persisted and significantly bothered her daily activities. Finally, she was treated with oral acetazolamide (250 mg, three times a day for 4 days), which was very effective for the control of her dystonia. The dystonic movement subsided without recurrence in a follow-up of 17 months. We advocate this effective and safe treatment for patients with paroxysmal dystonia associated with MS.