Botulinum Toxin Type A Therapy Research Articles

Effect of botulinum toxin type a combined with physical therapy on functional capacity in children with spastic cerebral palsy: a randomized controlled clinical trial

ABSTRACT Objective Investigate the effects of botulinum toxin type A (BoNT-A) combined with physical therapy on functional capacity in children with spastic cerebral palsy (CP). Methods Twenty-four children with spastic CP were treated with either BoNT-A and physical therapy or physical therapy alone. Results Significant differences (p < 0.05) were found after 30 days of treatment for the Berg Scale, Timed Up and Go (TUG) test, Ashworth Scale and Pediatric Evaluation of Disability Inventory (PEDI) and after three months for the Berg Scale, TUG test and PEDI. No significant differences (p > 0.05) were found in the control group. Discussion BoNT-A combined with physical therapy leads to significant improvements in spasticity and functionality in children with CP within a period of three months from the onset of treatment.

Botulinum Toxin Injections for Psychiatric Disorders: A Systematic Review of the Clinical Trial Landscape.

Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.

Outcome of endo-anal ultrasound-guided injection of botulinum toxin type-A therapy in puborectalis muscle in patients with anismus

Background Anismus is a functional disorder characterized by dyssynergia and incoordination of pelvic floor muscular contractions at defecation. Despite normal propulsive power used when attempting to defecate, a hypertonic pelvic floor dysfunction results in nonrelaxation or even paradoxical contraction of puborectalis muscle, resulting in failure to straighten the anorectal angle, hence impaired stool evacuation. This study aims at evaluating the outcome of injection of botulinum toxin type-A (BTX-A) in puborectalis muscle in patients with anismus. Patients and methods The study included 50 patients who were presented with symptoms of obstructed defecation (OD) and were diagnosed as anismus and failed conservative treatment and biofeedback training. Ultrasound-guided BTX-A injections into puborectalis muscle were done. All patients were followed up for 6 months for OD symptoms and manometric findings. Results The current study included 50 patients with a mean age of 36.6±11.9 years presented with anismus for a mean duration of 6.8±2.64 months. There was a statistically significant improvement in the Longo score of OD at 1, 3, and 6 months when compared with the initial values (P&lt;0.001), while there was no statistically significant difference noticed in the defecation frequency at 3 and 6 months when compared with the initial records. There was a statistically significant decrease in both resting and squeeze pressures after 3 and 6 months when compared with the initial records (P&lt;0.001). The overall satisfaction significantly increased to 68 and 64% after 3 and 6 months, respectively, when compared with 0% satisfaction reported at the initial assessment. Conclusion According to the current results, injection of BTX-A therapy in puborectalis muscle in patients with anismus is assumed to be effective for short term with good overall satisfaction.

Botulinum toxin type A in treatment of chronic migraine, spasticity and bruxism

Introduction: Nowadays, botulinum toxin has found use in many disease entities such as chronic migraine, spasticity, bruxism and many others. Among serotypes A-E, type A is mainly used in treatment. For the therapeutic effect to be maintained, injections need to be repeated most often after 12 weeks. More frequent injections of the toxin may result in the production of neutralizing antibodies. Aim of the study: The aim was to collect and analyze publications of application of botulinum toxin type A (BT-A) in the treatment of chronic migraine, spasticity and bruxism. Methods and materials: We reviewed the literature available in the PubMed database using the key words: “botulinum toxin”; “migraine”; “spasticity”; “bruxism”. Results: The use of botulinum toxin type A in patients with chronic migraine reduces the frequency of pain episodes and alleviates the symptoms. BT-A therapy reduces increased muscle tension, resulting in improved function of the upper or lower limb, facilitating the rehabilitation process, reducing pain associated with spasticity and protecting against the development of muscle contractures and secondary joint deformities. BT-A treatment of patients with bruxism reduces the level of pain and the maximum generated bite force, resulting in an improved quality of life for patients. Conclusion: Intramuscular administration of botulinum toxin is a safe, effective and minimally invasive method of treating chronic migraine, spasticity and bruxism. The botulinum toxin type A is the most studied serotype used for therapeutic purposes. Future research on botulinum toxin will certainly allow wider use.

Early versus late injections of Botulinumtoxin type A in post-stroke spastic movement disorder: A literature review

Post-stroke spastic movement disorder (PS-SMD) is one of the main causes of severe disability in the chronic phase after stroke. The prevalence of SMD goes up with time after stroke to more than 28% in the chronic phase., Its secondary complications such as contracture, abnormal postures and/or movement patterns, spasticity-associated pain also increase with time after stroke when physical and medical management of PS-SMD have been delayed in the early stroke phase. It has been published by several controlled studies that the earlier physical and medical measures, such as botulinum toxin type A (BoNT-A) therapy are included in rehabilitative strategies for the SMD, the fewer secondary complications, especially soft tissue contractures and pain occurred. Several studies showed that goal-orientated management of PS-SMD including BoNT-A therapy, applied within a few weeks and three months - in the early subacute phase after stroke onset - prevented or reduced the development of severe or disabling SMD and its secondary complications, more effective than late application of BoNT-A therapy - in the chronic phase after stroke.In multiple prospective cohort studies, various predictors and predictive approaches for detection of patients on risk to development PS-SMD were found. Based on that information and the controlled studies that showed reduction in PS-SMD complications following early treatment with BoNT-A nowadays, early treatment of PS-SMD in the early subacute phase following stroke is recommended to avoid or reduce the development of post-stroke disability and to improve the outcome of rehabilitation. In this review, we discuss the optimal timing to apply BoNT-A therapy in patients with already present as well as those at high risk of severe PS-SMD.

Botulinum Toxin as an Effective Treatment for Trigeminal Neuralgia in Surgical Practices

Background: Trigeminal neuralgia (TN) is a common cause of craniofacial pain with many medical and surgical therapies, all of which are imperfect. We examine the use of botulinum toxin type-A (BTX-A) as an intermediary approach in surgical practices. Methods: We retrospectively identified TN patients seen by both pain neurology and neurosurgery at our center. Demographics were collected. Pain intensity was assessed using the numerical rating scale (NRS) and compared from baseline to after BTX-A treatment via paired t test. Responder status was assessed, and success of BTX-A was determined for each cohort. Doses of common medications were compared between baseline visit and the most recent BTX-A administration visit. Results: Thirty-one patients underwent BTX-A therapy for TN, 24 (77%) female and 7 (23%) male. Mean age was 62.5 ± 3.1 years and 29 (94%) identified as white. When divided into cohorts according to indication, 11 (35%) failed prior TN surgery, 9 (29%) either declined surgery or were poor surgical candidates, 4 (13%) had multiple sclerosis, 4 (13%) had trigeminal neuropathic pain, and 3 (10%) had atypical TN with pain in additional dermatomes outside the trigeminal distribution. Significant reductions in NRS from baseline to following initial BTX-A treatment were seen in the declined/high risk for surgery (p = 0.004) and those who failed prior TN surgery (p = 0.035) groups. No significant variation in demographics was found between any two groups (p > 0.05 for all). Finally, there was no significant reduction in total daily dose of gabapentin, carbamazepine, oxcarbazepine, baclofen, or lamotrigine in BTX-A responders (p > 0.05 for all). Discussion: Indication is an important predictor for BTX-A, with classical TN patients exhibiting the highest response rates. This research highlights the viability of BTX-A as an important tool in the arsenal of providers seeking to treat TN in a minimally invasive manner.

Is Botox Right for Me: When to Assess the Efficacy of the Botox Injection for Chronic Migraine in Pediatric Population.

Botulinum toxin type A (BoNT-A) has shown to be a safe and effective treatment for children with chronic migraines. Our study was to assess the efficacy of the Onabotulinum toxin type A at different intervals after initiation of therapy. We conducted a retrospective and prospective analysis of 34 patients at a children's hospital where children received four rounds of the BoNT-A therapy for the treatment of chronic migraine. Among the 34 patients, 25 patients (age range: 13-21 years), who responded to the BoNT-A therapy, were included in the analysis. Patients received standard 31 injection, 155 unit's protocol. Patients were assessed every 3 months after their initial injection. Reasons for discontinuation of therapy were analyzed. After the first two BoNT-A sessions, significant improvement was observed with a decrease in headache frequency and intensity (p < 0.001). There was further reduction in headache frequency and intensity with the fourth round of BoNT-A therapy, with comparative analysis between the second and fourth round showing a p-value of <0.001. In terms of reduction of emergency room visits and hospitalization, a significant improvement was seen after the third round of BoNT-A therapy (p < 0.01). A significant decrease in the number of abortive and preventive medications was seen after the second round of BoNT-A therapy (p < 0.001). The efficacy of BoNT-A treatment in decreasing headache frequency, intensity, and the number of abortive and preventive medications can be assessed effectively after two treatment sessions. This trend continued to be observed with additional third and fourth sessions.

Subjective Outcome after Discontinuation of Botulinum Toxin-A Detrusor Injection for Lower Urinary Tract Disorders: The Majority Suffers!

Introduction: According to the EAU guidelines, botulinum toxin type A (BoNT-A) detrusor injections are one of the last options in the management of overactive bladder before opting for invasive surgery. So far, there have been no studies dedicated exclusively to such patients who have undergone this treatment and in whom this treatment has presumably failed. From the patient’s point of view, there are questions regarding what reasons led to discontinuation, how patients perceive their BoNT-A treatment in hindsight, what further treatment do these patients receive, and how satisfied such patients are with their current situation. Methods: A database of clinical and inpatient records was searched, and 695 records from 406 patients were identified in a 6-year period, who had received BoNT-A detrusor injections. There were 255 cases that were treated with BoNT-A injections into the detrusor muscle where the therapy was not repeated for at least 12 months (= suspected treatment failures). Interviews with these patients were conducted by mail and phone, and 115 questionnaires could be included in the analysis. Results: From the subjective and prospective points of view of the patients, the most common reason for stopping the therapy was a lack of efficacy of BoNT-A injections (39.1%). For 26.1% of all patients, side effects were a reason for dissatisfaction but never a reason for discontinuation. For 10.4%, the reason for stopping the therapy was spontaneous improvement. 35.6% of the respondents had no follow-up therapy. Those with a follow-up therapy mostly returned to anticholinergic treatment (33%). Operations were carried out on 13%, of which about half were highly invasive. For 71.3% of those patients, who were under any current therapy, this therapy led to no improvement or only some improvement of the symptoms. Surprisingly, 50.4% of the respondents would choose to undergo BoNT-A injection therapy again. Discussion/Conclusion: The majority of patients who did not continue BoNT-A therapy are still suffering from lower urinary tract symptoms. The lack of efficacy was the reason for stopping the BoNT-A injection therapy for less than half of the patients. From the patient’s point of view, reasons other than the effectiveness also seem to be relevant in the choice of the treatment. When changing therapy, most returned to drug treatment. However, for the majority of patients with any follow-up therapy, this therapy could not improve the symptoms.

Clinical utility of botulinum toxin type A local injection therapy for head and forehead hyperhidrosis.

Head and forehead hyperhidrosis (HFH) is a disease that causes a large amount of sweating from the head region, and it significantly reduces patients' quality of life. Only a few reports have shown the effectiveness of botulinum toxin type A (BTX-A) local injection therapy (BTX-A therapy) for HFH. To clarify the benefits of BTX-A for HFH, BTX-A therapy was performed in 15 patients, and its efficacy was evaluated. The amount of sweating was measured by the ventilation capsule method and Minor's iodine-starch test. Evaluation was also performed using the Hyperhidrosis Disease Severity Scale (HDSS) and the Dermatology Life Quality Index (DLQI). In most cases, a remarkable antiperspirant effect was observed from 2 weeks after the injection, and the effect lasted for approximately 30 weeks. HDSS and DLQI improved along with the decrease in sweating. Two patients (13.3%) complained of transient mild ptosis. There were no serious side-effects. This study showed that BTX-A therapy is a safe and effective treatment for HFH.

Generalized Anxiety Disorder: A Predictor for Poor Responsiveness to Botulinum Toxin Type A Therapy for Pediatric Migraine

BackgroundTo assess the efficacy, safety, and predictors for poor responsiveness of botulinum toxin type A (BoNT-A) for chronic migraine in the adolescent and young adult population. MethodsA retrospective analysis of 56 patients who received BoNT-A for chronic migraine with an age range from 13 to 21 years was performed. Of 56 patients, 34 were enrolled in the study based on the inclusion criterion. Patients who received three dosages of BoNT-A were assessed at nine months from the first injection. Variables including age, body mass index, headache intensity, frequency, character, and side effects were assessed. The patients were divided into two groups based on response to BoNT-A therapy, responders and nonresponders. ResultsOverall among the 34 patients enrolled in the study, the average headache frequency decreased from 18.6 of 28 to 9.9 of 28 days, P value, <0.001 from baseline. There was significant decrease in the average headache intensity, 8.1 to 4.3. Of 34 patients, 25 (73%) patients responded to treatment with decrease in headache frequency by ≥ 50% from the baseline. Among the nonresponder patients, a significant number of patients (six of nine, 67%) had generalized anxiety disorder with Generalized Anxiety Disorder-7 score greater than 15 versus the responder group (six of 25, 24%, P value 0.040). ConclusionsBoNT-A remains a safe and effective therapy for adolescent and young adult patients with chronic migraines at nine months of follow-up. Generalized anxiety disorder with Generalized Anxiety Disorder-7 score greater than 15 can be a major predictor of poor response to this therapy.

Botulinum Toxin Type A Satisfaction in Different Neurological Disorders

Background: The botulinum toxin type A (BoNT-A) is used in a wide range of neurological diseases. We aimed to study the overall patients/caregivers’ satisfaction with BoNT-A treatment in different neurological conditions. Methods: Prospective study included patients who had received at least two BoNT-A treatment sessions. They were asked to rate overall treatment satisfaction at the peak of treatment effect on a 1 to 10 scale (1 = not at all satisfied; 10 = fully satisfied). Subjects with a rating of 1to3 were classified as not at all satisfied, those with a rating of 4 to7 as somewhat satisfied, and those with a rating of 8 to10 as very satisfied. Treatment satisfaction questionnaire for medicine (TSQM) was assessed at the end of observational period. Quality of life QOL was assessed before BoNT-A treatment and at the last visit. Results: The study was conducted from first April 2014 to August 2021. 548 patients were identified with mean age 43.66 ± 14.50. Most of participants 389 (71%) were female. At the end of observational period, the mean satisfaction was 7.28 ± 1.78. There was a highly significant difference (P P P = 0.001). Conclusion: Satisfaction with BoNT-A therapy for different neurological disorders is overall good. The highest patient satisfaction was observed with primary focal HH, and the least satisfaction was observed in writer’s cramp. BoNT-A therapy improved QOL.

Use of botulinum toxin type a in psychiatry - new perspectives and future potential

IntroductionFor almost three decades, botulinum toxin type A (BT-A) has been used for medical purposes. Evidence of the potential use of BT-A is emerging for psychiatric disorders, like unipolar and bipolar depression, borderline personality disorder (BPD), late dyskinesia, amongst others. This may represent a new role of BT-A treatment and could expand the therapeutic arsenal in psychiatry.ObjectivesThe goal is to review current evidence regarding BT-A and psychiatry disorders.MethodsLiterature review of BT-A use in psychiatric conditions using Medline database.ResultsThere’s evidence supporting the use of BT-A in resistant unipolar depression, with studies showing an 8 and 4 times higher response and remission rates comparing with placebo. Beneficial effects were also found in bipolar depression. Preliminary data suggest that BT-A therapy may also be effective in the treatment of mental disorders characterized by an excess of negative emotions, such as BPD. The underlying mechanism might be the “facial feedback hypothesis”. Hyperhidrosis is a common comorbidity in social anxiety disorder and may itself give rise to depressive or anxiety symptoms. BT-A has proved to be a safe and effective treatment for hyperhidrosis. BT-A can also be safely used for dystonia secondary to the use of psychiatric medication, when there’s an inadequate response to anticholinergic medication. Also, BT-A injections in the salivary glands have been investigated for treating clozapine-induced sialorrhea and studies reported successful reduction in hypersalivation.ConclusionsAlthough more studies are needed to evaluate the potential of BT-A in psychiatry, there is growing evidence of its potential use for some psychiatric conditions.

Scientific review of the aesthetic uses of botulinum toxin type A.

Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002, and has also been used widely for aesthetic purposes such as hyperhidrosis, body shape contouring, and other noninvasive facial procedures. BoNT-A inhibits presynaptic exocytosis of acetylcholine (ACh)-containing vesicles into the neuromuscular junction at cholinergic nerve endings of the peripheral nervous system, thereby paralyzing skeletal muscles. ACh is the most broadly used neurotransmitter in the somatic nervous system, preganglionic and postganglionic fibers of parasympathetic nerves, and preganglionic fibers or postganglionic sudomotor nerves of sympathetic nerves. The scientific basis for using BoNT-A in various cosmetic procedures is that its function goes beyond the dual role of muscle paralysis and neuromodulation by inhibiting the secretion of ACh. Although the major target organs for aesthetic procedures are facial expression muscles, skeletal body muscles, salivary glands, and sweat glands, which are innervated by the somatic or autonomic nerves of the peripheral cholinergic nerve system, few studies have attempted to directly explain the anatomy of the areas targeted for injection by addressing the neural physiology and rationale for specific aesthetic applications of BoNT-A therapy. In this article, we classify the various cosmetic uses of BoNT-A according to the relevant component of the peripheral nervous system, and describe scientific theories regarding the anatomy and physiology of the cholinergic nervous system. We also review critical physiological factors and conditions influencing the efficacy of BoNT-A for the rational aesthetic use of BoNT-A. We hope that this comprehensive review helps promote management policies to support long-term, safe, successful practice. Furthermore, based on this, we look forward to developing and expanding new advanced indications for the aesthetic use of BoNT-A in the future.

Brain connectivity abnormalities and treatment-induced restorations in patients with cervical dystonia.

The relationship between brain abnormalities and phenotypic characteristics in cervical dystonia (CD) patients has not been fully established, and little is known about the neuroplastic changes induced by botulinum toxin type A (BoNT-A) treatment. Ninety-two CD patients presenting with rotational torticollis and 45 healthy controls from our database were retrospectively screened. After clinical assessment, the 92 patients underwent baseline magnetic resonance imaging (MRI) followed by a single-dose injection of BoNT-A. Four weeks later, 76 out of the 92 patients were re-evaluated with the Tsui scale for dystonia severity, and 33 out of 76 patients completed post-treatment MRI scanning. Data-driven global brain connectivity and regional homogeneity in tandem with seed-based connectivity analyses were used to examine the functional abnormalities in CD and longitudinal circuit alterations that scaled with clinical response to BoNT-A. Multiple regression models were employed for the prediction analysis of treatment efficacy. Cervical dystonia patients exhibited elevated baseline connectivity of the right postcentral gyrus with the left dorsomedial prefrontal cortex and right caudate nucleus, which was associated with their symptom severity. BoNT-A reduced excessive functional connectivity between the sensorimotor cortex and right superior frontal gyrus, which was significantly correlated with changes in Tsui score. Moreover, pre-treatment regional homogeneity of the left middle frontal gyrus was linearly related to varied response to treatment. Our findings unravel dissociable connectivity of the sensorimotor cortex underlying the pathology of CD and central effects of BoNT-A therapy. Furthermore, baseline regional homogeneity with the left middle frontal gyrus may represent a potential evidence-based marker of patient stratification for BoNT-A therapy in CD.

Association of Long-Term Treatment by Botulinum Neurotoxins and Occupational Therapy with Subjective Physical Status in Patients with Post-Stroke Hemiplegia.

The short-term effects of botulinum toxin type A (BoNT-A) treatment in stroke patients with upper extremity are well established. This study examined the association between the recovery of motor function of the upper extremity with subjective physical symptoms in outpatients receiving long-term BoNT-A and occupational therapy following stroke. We also investigated the expectations of patients who elected to continue treatment. Forty-seven patients (23 men and 24 women) aged 61 years received BoNT-A treatment more than 20 times. The subjective physical status was analyzed by using the visual analogue scale score through an eight-item questionnaire. Recovery of motor function in the upper extremity was detected by calculating the change (delta) in Fugl–Mayer Assessment (FMA), and ordinal logistic modeling analysis was used to determine the association between the delta-FMA score and the subjective level of agreement for each item. When the ordinal logistic modeling fit was statistically significant, results were interpreted as having logistic probability. The logistic curves discriminating one point (strongly disagree) from five points (strongly agree) were fit in a stepwise fashion. This study suggests that patients receiving long-term BoNT-A treatment and occupational therapy experienced an increased upper extremity mitigation and decreased insomnia after injection, regardless of the recovery of motor function.

Treatment of Post-Facelift Facial Paralysis With Botulinum Toxin Type A

BACKGROUND: Nerve injuries post-facelifts are rare but cause serious functional and psychological impairment of self-esteem and quality of life.1,2 Despite being temporary in most cases, facial asymmetry typically lasts for 3 months. We present a treatment protocol for post-facelift facial nerve injuries using botulinum toxin type A (BTXA). MATERIALS AND METHODS: The study was conducted from January 2002 to June 2018. Nine patients (all female; mean age, 58 ± 8.4 years) with asymmetries due to post-rhytidectomy facial palsies were treated in the nonparalyzed side with abobotulinum toxin type A, with 6-month to 5-year follow-up. The 500-U vial was diluted in 4 ml of 0.9% saline. We considered 0.02 ml of the solution (2.5 abobotulinum toxin units) as 1 volume unit. Patients were examined after 15 days for outcomes evaluation. The dose applied to each muscle group1 varied from 1 to 2 volume unit per point. Patients were retreated after 5–6 months in case of asymmetry recurrence. RESULTS: Four patients sought early care (mean, 14.2 ± 6.4 days postoperative, ranging from 5 to 21 days). The others arrived later (mean, 225 ± 80.7 days postoperative, ranging from 150 to 360 days). Two patients had lesions affecting the upper third of the face, and symmetry was achieved after unilateral treatment of the frontalis muscle. Three patients had injury in the middle third; their treatment depended of analysis of the deviation vectors when smiling and frowning, as to decide which muscle groups should be treated (vertical: upper lip lifter muscles; upper oblique: lifters of the angle of the mouth muscles; and horizontal: risorius muscle). Four patients were affected in the lower third (inferior deviation vectors) and were treated with 2 points to paralyze the lower lip depressor muscles. Correction of asymmetry was achieved in all cases. Recovery from the nerve injury and BTXA application occurred symmetrically in both sides of the face in the following months. All patients with early onset of BTXA therapy (<30 days) had complete recovery of facial symmetry with a single application, evidence of neuropraxis. Patients with lesions of the upper third, those with late onset of BTXA treatment (>30 days), and those with >1 affected nervous branch presented definitive lesion, with partial recovery or improvement, and needed BTXA treatment every 6 months. CONCLUSION: Most facial nerve injuries post-facelifts presented favorable evolution for spontaneous resolution, except in the upper third of the face and in case of late lesions. Symmetry was achieved in all cases with low doses of BTXA in the suggested protocol points, avoiding an unhappy asymmetric patient in the following months. REFERENCES: 1. Salles AG, Toledo PN, Ferreira MC. Botulinum toxin injection in long-standing facial paralysis patients: improvement of facial symmetry observed up to 6 months. Aesthetic Plast Surg. 2009;33:582–590. 2. do Nascimento Remigio AF, Salles AG, de Faria JCM, et al. Comparison of the efficacy of onabotulinumtoxinA and abobotulinumtoxinA at the 1: 3 conversion ratio for the treatment of asymmetry after long-term facial paralysis. Plast Reconstr Surg. 2015;135:239–249.

Efficacy and Safety of Botulinum Toxin Type A for Limb Spasticity after Stroke: A Meta-Analysis of Randomized Controlled Trials.

Background Inconsistent data have been reported for the effectiveness of intramuscular botulinum toxin type A (BTXA) in patients with limb spasticity after stroke. This meta-analysis of available randomized controlled trials (RCTs) aimed to determine the efficacy and safety of BTXA in adult patients with upper and lower limb spasticity after stroke. Methods An electronic search was performed to select eligible RCTs in PubMed, Embase, and the Cochrane library through December 2018. Summary standard mean differences (SMDs) and relative risk (RR) values with corresponding 95% confidence intervals (CIs) were employed to assess effectiveness and safety outcomes, respectively. Results Twenty-seven RCTs involving a total of 2,793 patients met the inclusion criteria, including 16 and 9 trials assessing upper and lower limb spasticity cases, respectively. For upper limb spasticity, BTXA therapy significantly improved the levels of muscle tone (SMD=-0.76; 95% CI -0.97 to -0.55; P<0.001), physician global assessment (SMD=0.51; 95% CI 0.35-0.67; P<0.001), and disability assessment scale (SMD=-0.30; 95% CI -0.40 to -0.20; P<0.001), with no significant effects on active upper limb function (SMD=0.49; 95% CI -0.08 to 1.07; P=0.093) and adverse events (RR=1.18; 95% CI 0.72-1.93; P=0.509). For lower limb spasticity, BTXA therapy was associated with higher Fugl-Meyer score (SMD=5.09; 95%CI 2.16-8.01; P=0.001), but had no significant effects on muscle tone (SMD=-0.12; 95% CI -0.83 to 0.59; P=0.736), gait speed (SMD=0.06; 95% CI -0.02 to 0.15; P=0.116), and adverse events (RR=1.01; 95% CI 0.71-1.45; P=0.949). Conclusions BTXA improves muscle tone, physician global assessment, and disability assessment scale in upper limb spasticity and increases the Fugl-Meyer score in lower limb spasticity.

A Comparative In Vivo Study on Three Treatment Approaches to Applying Topical Botulinum Toxin A for Crow's Feet.

Objective To evaluate the efficacy and safety of three treatment approaches to applying Botulinum Toxin Type A (BoNTA) for crow's Feet. Methods Thirty female subjects with moderate-to-severe crow's feet were included in this comparative in vivo study. They were randomly divided into three groups, including the local intramuscular, intradermal microdroplet injection, and nanomicroneedle delivered with BoNTA therapy group. After one session, evaluations were done at the time points of weeks one, four, and twelve after the treatment. The assessments included subjective satisfaction, blinded clinical assessment, and the biophysical parameters (skin collagen content, elasticity, hydration, and sebum contents). Results For dynamic wrinkles, intramuscular injection and intradermal microdroplets injection were more effective than nanomicroneedles. For static wrinkles, nanomicroneedles and intradermal microdroplets injection were more effective. However, the intramuscular injection had no significant effect on static wrinkles. At one week and four weeks after the treatment, the skin elasticity, collagen content, and hydration of nanomicroneedle group and intradermal microdroplet group increased more significantly than those of the intramuscular injection group; at twelve weeks after the treatment, the skin elasticity, collagen content, and hydration of intradermal microdroplet group were higher than those of other two groups. However we observed no statistically significant difference in sebum content between the three groups before and after the treatment. Conclusion BoNTA delivered through nanomicroneedles and intradermal microdroplets injection can effectively treat crow's feet. This trial is registered with [2016]KY018-01, registered 16 Feb 2016.

BOTULINUM TOXIN FOR PAIN SYNDROMES

The purpose of this scientific review was to analyze and summarize the most relevant and new published scientific data on the effectiveness of antinociceptive action of botulinum toxin type A (BTA). The publications were searched for in the Medline, Pub med, Cochrane Library databases. As a result, high-level evidence was selected (RCT, national clinical guidelines, international clinical guidelines, meta-analyzes, systematic reviews). The article is devoted to the problem of pain syndromes in various neurological disorders, features and efficacy of antinociceptive action of botulinum toxin type A (BTA). Data on the efficacy of onаbotulotoxin (Botox®) in the treatment of pain syndromes are presented in accordance with the recorded indications. Also, based on the analysis, it was shown that BTA therapy is a valuable alternative to traditional therapy for many conditions accompanied by pain syndromes.

Effect of early use of AbobotulinumtoxinA after stroke on spasticity progression: Protocol for a randomised controlled pilot study in adult subjects with moderate to severe upper limb spasticity (ONTIME pilot).

IntroductionApproximately 15 million people suffer a stroke annually, up to 40% of which may develop spasticity, which can result in impaired limb function, pain and associated involuntary movements affecting motor control.Robust clinical data on spasticity progression, associated symptoms development and functional impairment is scarce. Additionally, maximal duration of muscle tone reduction following botulinum toxin type A (BoNT-A) injections remains undetermined. The ONTIME pilot study aims to explore these issues and evaluate whether abobotulinumtoxinA 500 U (Dysport®; Ipsen) administered intramuscularly within 12 weeks following stroke delays the appearance or progression of symptomatic (disabling) upper limb spasticity (ULS).MethodsONTIME is a 28-week, phase 4, randomised, double-blind, placebo-controlled, exploratory pilot study initiated at four centres across Malaysia, the Philippines, Singapore and Thailand. Subjects (n = 42) with moderate to severe ULS (modified Ashworth scale [MAS] score ≥2) in elbow flexors or pronators, wrist flexors, or finger flexors will be recruited. Subjects will be randomised 2:1 to abobotulinumtoxinA 500 U or placebo (single dose 2–12 weeks after first-ever stroke).Primary efficacy will be measured by time between initial injection and visit at which reinjection criteria (MAS score ≥2 in the primary targeted muscle group and appearance or reappearance of symptomatic ULS) are met. Follow-up visits will be 4-weekly to a maximum of 28 weeks.DiscussionThis pilot study will facilitate the design and sample size calculation of further confirmatory studies, and is expected to provide insights into the optimal management of post-stroke patients, including timing of BoNT-A therapy and follow-up duration.