Search Results (124)

Many patients with spasticity report pain which can be debilitating. Numerous studies have shown onabotulinumtoxinA (onabotA) is efficacious in the management of spasticity but comprehensive data on its impact on spasticity-associated pain is limited. This systematic review aimed to assess the published evidence on the efficacy of onabotA in the management of pain in adults with spasticity. Search strategies were conducted from 1990 to 2023 for journal publications and from 2020 to 2023 for congress proceedings to identify relevant studies on onabotA in adults with spasticity where pain was a reported outcome. Of 665 records identified, 31 unique studies from 33 publications were included (2740 patients). Twenty-seven studies demonstrated a reduction in pain compared to baseline following treatment with onabotA in adults with spasticity (n = 2740). Of these, 12 studies reported a statistically significant reduction in pain with onabotA versus baseline. Sixteen studies reported a clinically meaningful reduction in pain (≥30% reduction). The reduction in pain with onabotA was consistent across etiologies and a range of pain measures. There was a high level of heterogeneity in the design and quality of the studies identified, which limited statistical analysis; however, the published evidence overall shows a consistent positive trend for the use of onabotA in reducing spasticity-related pain in adults. Full article

Purpose: Detrusor sphincter dyssynergia (DSD), a common lower urinary tract condition in patients with suprasacral spinal cord injury (SCI), can lead to urological complications and reduced quality of life. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to promote spontaneous voiding, albeit with limited success. This study aimed to identify predictive factors for treatment success. Methods: This retrospective analysis included 207 patients (157 males and 50 females) with chronic SCI and varying DSD grades treated with urethral sphincter BoNT-A injection. Each received 100 U of onabotulinumtoxinA via transurethral sphincter injection. The primary outcome was voiding efficiency (VE) and symptom improvement, assessed via global response evaluation 3 months post-treatment. Baseline videourodynamic parameters were used to predict success. Results: Successful outcomes were observed in 33.8% of patients. These patients were older and had higher voiding pressure, maximum flow rate (Qmax), voided volume, bladder contractility index, and VE, as well as lower post-void residual (PVR) volume and bladder outlet obstruction index. Patients with SCI and DSD grade 1 had the highest success rate (65.7%) compared to those with DSD grade 2 (14.3%) or 3 (7.1%). Patients with DSD grade 3 had the highest failure rate (55.8%). Multivariate analysis showed that higher Qmax and lower PVR significantly predicted success, consistent with lower DSD grades. Conclusion: Grade 1 DSD, higher Qmax, and lower PVR were associated with higher success after urethral BoNT-A injection, whereas grade 3 DSD predicted failure. Thus, careful patient selection is essential for effective DSD treatment with urethral BoNT-A injection. Full article

OnabotulinumtoxinA (OnaBoNT-A) is approved for chronic migraine prevention and follows the PREEMPT protocol with injections in the glabellar and forehead regions. While aesthetic changes are considered a side effect, their effect on patient satisfaction has not been thoroughly assessed. This study evaluated patient satisfaction with facial aesthetic outcomes after repeated OnaBoNT-A treatment for chronic migraine. Conducted at specialist headache centers, it included adult patients with chronic migraine who had received at least three OnaBoNT-A cycles. Participants completed a structured questionnaire on demographics, migraine history, facial wrinkles and age perception, appearance satisfaction, psychological impact, treatment satisfaction, and adverse aesthetic events. A total of 124 patients (92.7% female; median age 42.5 years) participated. OnaBoNT-A reduced wrinkle severity (p < 0.0001). Most patients (74.2%) reported aesthetic improvement post-treatment. The majority of patients (76.7%) declared that treatment met or exceeded expectations. 32% reported looking younger post-treatment, with a median perceived age difference of 5 years. Adverse event frequency was similar to pivotal trial outcomes, mostly mild, with no treatment discontinuations. OnaBoNT-A for chronic migraine, following the PREEMPT protocol, provides significant therapeutic benefits and high patient satisfaction regarding aesthetic outcomes. Although aesthetic side effects were generally mild, they were not uncommon. Full article

Background: Cervical dystonia (CD) is a chronic neurological disorder characterized by involuntary neck muscle contractions, leading to abnormal head postures, pain, and functional impairment. Botulinum toxin type A (BoNT-A) remains the treatment of choice, but its efficacy is highly dependent on injection accuracy. Various techniques, including palpation-guided, ultrasound-guided, and electromyography-guided (EMG), have been developed to optimize delivery, each with distinct advantages and limitations. Methods: A systematic search of PubMed and Scopus was conducted up until 30 December 2024, using defined keywords related to BoNT-A, CD, and injection techniques. Studies were included if they reported clinical outcomes of BoNT-A injection methods in adult CD patients. Data on efficacy, safety, accuracy, and muscle targeting were extracted and synthesized. Results: Seven studies comprising 239 patients were included: two randomized controlled trials, one retrospective study, one cohort study, one systematic review, one literature review, and one cadaveric study. The most common CD subtype was torticollis/torticaput (49.79%). Frequently targeted muscles included the trapezius (56.9%), levator scapulae (51.7%), and splenius capitis (48.3%). Ultrasound guidance consistently demonstrated superior injection accuracy and reduced adverse effects due to real-time anatomical visualization. EMG-guided techniques showed advantages in identifying dystonic muscles, especially when anatomy was unclear. In contrast, palpation-guided injections were less accurate and suitable only for superficial muscles. Dosing varied by product, with mean doses of 117–118 units for onabotulinumtoxinA and incobotulinumtoxinA, and 405 units for abobotulinumtoxinA. Adverse events were generally mild, including local discomfort, dysphagia, and transient muscle weakness. Conclusions: Ultrasound- and EMG-guided injections enhance the precision, safety, and efficacy of BoNT-A therapy for CD compared to anatomy-guided techniques. While ultrasound guidance improves anatomical accuracy, EMG remains valuable for functionally identifying dystonic muscles. Integration of both may offer optimal outcomes. However, further high-quality, standardized trials are needed to definitively establish best practices. Full article

TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24–27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule. Full article

Introduction and Objectives: Onabotulinum toxin A (BTXA) is an effective treatment for refractory idiopathic overactive bladder (iOAB). Given the wide spectrum of patient factors and combination of symptoms, a tailored approach to management is needed. This scoping review assesses injection paradigms for iOAB. Prior studies have established the safety and efficacy of BTXA injections, and this review focuses on exploring variations in injection techniques that may inform more tailored approaches and support future research toward optimizing patient outcomes. Methods: We conducted a systematic literature search. Inclusion criteria included full-text English language and primary research studies assessing outcomes in adults undergoing BTXA for iOAB. Findings are summarized using narrative synthesis. Results: Forty-three articles were identified. Key findings include fewer injections (1–10 vs. 20–40) maintains efficacy while reducing procedure time, discomfort, and retreatment hesitancy. Durability appears to be lower with suburothelial and bladder base injections and higher with detrusor and bladder body injections, though these may carry an increased risk of urinary retention requiring clean intermittent catheterization. Trigone inclusion appears safe and effective without increased vesicoureteral reflux risk. Conclusions: Study heterogeneity and inconsistent reporting limit strong conclusions. Included injection paradigms demonstrated efficacy, high tolerability, symptom relief, and quality-of-life improvements with few adverse events. Further research is needed to refine optimal injection strategies to enhance patient comfort, maximize efficacy, and minimize adverse events. Future studies should ensure comprehensive data collection to clarify these associations. Full article

Background: Chronic migraine (CM) is a debilitating neurological disorder that imposes substantial burdens on individuals and society, including diminished quality of life and increased healthcare utilization. While the efficacy of botulinum neurotoxin type A (BoNT-A) has been demonstrated in controlled trials, this longitudinal, real-world study offers unprecedented evidence of its long-term benefits, with patients followed for a median of 15 months (interquartile range: 6–36 months) and up to 11 years. Methods: This retrospective analysis included 579 patients diagnosed with CM who were newly treated with BoNT-A, according to the PREEMPT protocol, receiving injections every 12 weeks at doses of 155–195 units across 31–39 sites. Outcomes were assessed through changes in monthly headache days, frequency, symptomatic medication use, and migraine-related disability using Migraine Disability Assessment (MIDAS) scores up to 60 months from recruitment. Safety was evaluated by recording treatment-emergent adverse events (TEAEs), with a focus on long-term tolerability and subgroup variability. Results: Patients showed sustained improvements, with the mean number of monthly headache days decreasing from 22.7 to 5.5, and symptomatic medication use dropping from 33.4 to 3.7 mean doses at 60 months. Additionally, over 60% of patients improved from severe (MIDAS Grade IV) to minimal disability (MIDAS Grade I). Subgroup analysis revealed variability in response rates, emphasizing the need for personalized approaches. TEAEs were predominantly mild, with no new adverse events reported after 36 months, supporting the long-term safety of BoNT-A in real-world settings. Conclusions: This real-world study provides significant evidence for the long-term efficacy, safety, and tolerability of BoNT-A in the preventive treatment of CM. The findings highlight the importance of real-world data to account for patient variability and tailoring treatment strategies. Full article

OnabotulinumtoxinA is an FDA-approved treatment for adults with overactive bladder (OAB) who have an inadequate response to, or are intolerant of, oral pharmacotherapies including anticholinergics or beta-3 agonists. However, procedural practices of onabotulinumtoxinA intradetrusor injection vary among practitioners and can affect patient experience. To address this, a panel of six high-volume intravesical onabotulinumtoxinA providers with 100 years of combined experience convened to discuss the best office practices when treating patients with OAB. These key best practices include counseling patients on available OAB therapies, including onabotulinumtoxinA, at the initial consultation in accordance with established AUA and SUFU guidelines in a way that is easily understood. An office setting is preferred over a hospital or surgery center when performing the procedure. Staff involvement, from scheduling to post-procedure, is essential for establishing the relationships necessary to optimize patient experience and encourage compliance and retreatment. Experts generally recommend using a viscous lidocaine bladder instillation for an anesthetic 15 min prior to the reconstitution of onabotulinumtoxinA with 5 to 10 mL of normal saline. A range of one to 20 injection sites is acceptable, with a smaller number preferred. Starting in the lower bladder, experts recommend using a slower speed of injection to improve distribution and decrease patient discomfort. Subsequent treatments should be regularly scheduled at six-month intervals with the option of re-treating earlier if symptoms return, but no sooner than 12 weeks. For office intravesical onabotulinumtoxinA procedures, optimization of the patient experience by the physician and their staff, starting with the initial visit through the post-treatment follow-up, is key to long-term patient compliance. Full article

Onabotulinumtoxin-A (onabotA) is a neurotoxin widely used for several indications, including chronic migraine (CM) preventive treatment, due to its well-demonstrated efficacy, tolerability, and safety. However, onabotA safety during pregnancy and breastfeeding remains unclear, as these populations are typically excluded from clinical trials. The action of onabotA starts locally at the injection sites, modulating the pain pathway with minimal systemic absorption, which theoretically minimizes risks to the fetus or breastfeeding infant. Preclinical studies demonstrate that onabotA does not distribute systemically in significant amounts after administration, although adverse fetal outcomes in rats and rabbits were reported when injected at high doses. Limited human data suggest that onabotA exposure during pregnancy may not be associated with major malformations or significant adverse outcomes for the fetus, especially when used at therapeutic doses for migraine prevention during the first trimester or earlier. Data on breastfeeding are even scarcer but indicate a low likelihood of drug transfer into breast milk. This narrative review highlights the available evidence on the use of onabotA in pregnancy and breastfeeding women, including real-word evidence, with a focus on the use for CM. Full article

The RELY-CD study investigated the long-term clinical response to botulinum neurotoxin type A in cervical dystonia within a multicenter, real-world setting. This retrospective study focused on patients treated with complex-free (incobotulinumtoxinA) and complex-containing (onabotulinumtoxinA and abobotulinumtoxinA) BoNT/A formulations over an up to 10-year period. The novel dose–effect parameter “DEff” was introduced to quantify the relationship between dose adjustments and clinical outcomes, enabling the identification of partial treatment failures. The primary endpoint was a comparison of a clinically meaningful worsening in DEff in treatment year 7 compared to year 2 between complex-free and complex-containing botulinum neurotoxin type A. The RELY-CD study provides unique insights into long-term treatment patterns, clinical resistance phenomena, and the implications of formulation differences on treatment outcomes, addressing a critical gap in the literature on real-world botulinum neurotoxin type A application. The study methodology, including the definition and calculation of the novel DEff, as well as clinical baseline characteristics, are presented. Full article

MBA-P01 is a newly developed botulinum toxin A (BoNT-A) product designed to provide similar clinical effects as OnabotulinumtoxinA (ONA-BoNT-A), thereby providing an alternative treatment option for glabellar lines. It is another holotoxin preparation containing BoNT-A1. This randomized, double-blind, active-controlled, multi-center, Phase III clinical trial aimed to evaluate the efficacy and safety of MBA-P01 compared with OnabotulinumtoxinA (ONA-BoNT-A). In total, 318 participants were enrolled and received 20 units of MBA-P01 or ONA-BoNT-A on the forehead and glabella. At the 4-week assessment, the primary endpoint revealed no significant difference in the improvement rate of glabellar wrinkles between the two groups, confirming the non-inferiority of MBA-P01 to ONA-BoNT-A. Furthermore, some evaluation variables showed higher improvement rates for MBA-P01 than for ONA-BoNT-A. Adverse reactions and other safety analysis results were considered acceptable. Interestingly, a subgroup analysis of patients with the coronavirus disease (COVID-19) showed that the duration of BoNT-A treatment was shorter among those who contracted COVID-19 after BoNT-A treatment compared with those who have not. The limitations of this study include the predominance of female participants and the exclusive enrollment of Korean patients. MBA-P01 is expected to be clinically useful in terms of the efficient and safe reduction of glabellar wrinkles, which will provide patients with additional treatment options. Full article

Oromandibular dystonia (OMD) is a focal dystonia characterized by contractions of the masticatory, lingual, and other muscles of the stomatognathic system. We conducted a systematic review and meta-analysis to elucidate the impact and safety of botulinum toxin in OMD. The eligibility criteria were full-length original articles that provided data evaluating the efficacy and adverse effects of onabotulinumtoxinA injections in patients with OMD. PubMed and Embase were searched for articles published before 31 May 2023. We analyzed cases that showed a favorable response (>0% improvement), moderate or greater response (>50% improvement), and adverse effects. A fixed-model meta-analysis of 26 studies involving 1103 patients revealed that an overall favorable effect of onabotulinumtoxinA injection was observed in 96.2% (95% confidence interval [CI], 95–97.5%, p < 0.00001) of patients, with significant heterogeneity (p < 0.00001, I² = 85%). A moderate response (>50% improvement) was observed in 88.9% of patients (95% CI, 87–90.8%, p < 0.00001) with significant heterogeneity (p < 0.00001, I² = 85%). Adverse effects were detected in 17.8% of patients, and the most common event was dysphagia (10.1%). Our systematic review found that onabotulinumtoxinA injection was effective, with a low rate of side effects. Further randomized controlled trials are required to clarify the evidence-based efficacy and adverse effects. Full article

Background/Objectives: Comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) patients are at a significantly higher risk of adverse outcomes, including opioid use disorder, depression, suicidal behaviors, and death, yet limited treatment options exist for this population. This study aimed to build on previous research by incorporating drug target information into a novel deep learning model, T-DeepBiomarker, to predict adverse outcomes and identify potential therapeutic medications. Methods: We utilized electronic medical record (EMR) data from the University of Pittsburgh Medical Center (UPMC), analyzing 5565 PTSD + AUD patients. T-DeepBiomarker was developed by integrating multimodal data, including lab results, drug target information, comorbidities, neighborhood-level social determinants of health (SDoH), and individual-level SDoH (e.g., psychotherapy and veteran status). The model was trained to predict adverse events, including opioid use disorder, suicidal behaviors, depression, and death, within three months following any clinical encounter. Candidate medications targeting significant proteins were identified through literature reviews. Results: T-DeepBiomarker achieved high predictive performance with an AUROC of 0.94 for adverse outcomes in PTSD + AUD patients. Several medications, including OnabotulinumtoxinA, Dronabinol, Acamprosate, Celecoxib, Exenatide, Melatonin, and Semaglutide, were identified as potentially reducing the risk of adverse events by targeting significant proteins. Conclusions: T-DeepBiomarker demonstrates high accuracy in predicting adverse outcomes in PTSD + AUD patients and highlights candidate drugs with potential therapeutic effects. These findings advance pharmacotherapy for this high-risk population and identify medications that warrant further investigation. Full article

Botulinum toxin type A1 is a first-line treatment for adult and pediatric spasticity. However, when considering the quantity of 150 kDa neurotoxin protein in relation to patient weight and the maximum recommended dose for treating adult and pediatric patients with spasticity, several concerns arise. First, the therapeutic margin (the ratio of the actual maximum quantity of toxin recommended for treating adult spasticity to its median lethal dose) appears to be relevant. Second, there is no consistency between adult and pediatric dosing of botulinum toxin type A1 for spasticity. The third point concerns the suitability of the recommended doses for treating spasticity in pediatric patients. Based on the average body weight of American children and adolescents, the maximum weight-based doses for abobotulinumtoxinA and onabotulinumtoxinA could be administered to children as young as 9 years old. Additionally, the maximum weight-based dose for incobotulinumtoxinA could be administered to children as young as 6 years old. The final point concerns managing the maximum dose of BoNT/A1 in pediatric patients with spasticity who weigh more than 25 kg for incobotulinumtoxinA, or more than 34 kg for abobotulinumtoxinA and onabotulinumtoxinA. No labeled recommendations are given on the weight cut-off for transitioning to adult dosing in pediatric patients. Full article

Trigeminal neuralgia is a neuropathic pain syndrome responsive to botulinum toxin type A therapy. This review had the goal of analyzing the different studies published from 2002 to January 2024 to better define the techniques and the types of botulinum toxin type A used, the doses, the injection routes, and the different populations of trigeminal neuralgia patients treated. We considered only articles in which the therapy was administered to humans to treat trigeminal neuralgia. Case reports, case series, open-label, retrospective, and RCT studies were considered. The research was conducted on MEDLINE and the keywords included (trigeminal neuralgia) and (botulinum). Thirty-five articles were considered suitable for this review. Botulinum toxin type A was shown to be an effective therapy for TN pain in all the articles analyzed, albeit there is a lack of standardization in methods and outcomes. The techniques, the doses, and the injection approaches were very heterogeneous among the studies. Only two botulinum toxin type A formulations have been used in this setting: onabotulinumtoxinA and lanbotulinumtoxinA. There were 300 patients treated with onabotulinumtoxinA and 760 treated with lanbotulinumtoxinA overall (in 42 patients, the formulation was not specified). The distinction between etiological and clinical types of TN has been made by only a small portion of the studies. The main adverse event was transient facial asymmetry. Botulinum toxin type A is indeed a promising therapy that is clearly effective for trigeminal neuralgia. OnabotulinumtoxinA is the most common formulation used in Western countries; however, the meager sample of TN patients treated, and the lack of standardization are not sufficient for this therapy to be approved by the FDA or EMA. Indeed, more studies with standardized methods and larger samples are needed for this purpose. Full article