Search Results (505)

Botulinum neurotoxin type A (BoNT-A) injection for lateral canthal rhytids is among the most frequently performed nonsurgical aesthetic procedures; however, procedure-related hematoma and ecchymosis remain frequent local adverse events associated with the multiple puncture sites required in the conventional three-point technique. This prospective single-center preliminary clinical observation evaluated a single-point intramuscular injection technique designed to reduce percutaneous vascular-layer penetrations while preserving treatment territory, dose, and intramuscular target localization. A total of 152 consecutive patients (104 female and 48 male) underwent bilateral treatment between May 2025 and May 2026 using a single skin entry point per side, positioned 10–15 mm caudal to and 10 mm temporal to the lateral canthus, followed by 18–20 mm intramuscular advancement within the lateral orbicularis oculi and continuous retrograde infusion of 12 U of onabotulinumtoxinA per side. Post-procedural assessment after injection demonstrated small unilateral ecchymosis in 2 of 304 treated sides (0.66%; Clopper–Pearson 95% Confidence Interval (CI), 0.08–2.36%). After the 10-day follow-up, no persistent bruising or other adverse events were reported, and all patients confirmed satisfaction with the treatment. At the structured one-year follow-up, the satisfactory reduction in dynamic lateral canthal rhytids and continued patient satisfaction with the treatment were confirmed, while a subset elected to return for a subsequent treatment session during the observation period. By reducing bilateral percutaneous venous-layer penetrations from six to two while maintaining dose and treatment-territory equivalence, the single-point intramuscular technique may represent a structurally coherent refinement of established BoNT-A treatment concepts for lateral canthal rhytids. Because this was an uncontrolled preliminary clinical observation, the observed rate should be interpreted as descriptive only; any potential reduction in hematoma risk remains hypothetical. Full article

Schwann cells (SC) myelinate peripheral axons and orchestrate nerve regeneration after injury by switching between myelinating, proliferative and repair states. Evidence suggests that Botulinum Neurotoxin Type A (BoNT/A) influences SC biology, potentially supporting nerve repair and pain relief in peripheral neuropathic pain (PNP) models. However, BoNT/A receptor and target expression in human SC (hSC) remains poorly explored. Here, this translational gap was addressed by transcriptionally profiling genes encoding BoNT/A-relevant receptors and targets in primary hSC and testing whether paclitaxel evokes hSC phenotype plasticity in vitro based on changes in gene expression. Primary hSC were isolated, cultured, and treated with paclitaxel or vehicle, followed by RT-qPCR profiling of hSC markers and BoNT/A receptor/targets genes. Untreated hSC expressed moderate NGFR and S100β, with low MBP levels, suggesting a non-myelinating state profile. Transcripts encoding the BoNT/A receptor machinery (SV2A, SYT1) and the target SNAP25 were detectable at moderate levels. Paclitaxel induced changes in gene expression: SV2A and SYT1 decreased (up to two-fold), whereas SNAP25 and MBP increased, accompanied by reduced NGFR, indicating a shift toward a more differentiated transcriptional state. These data indicate hSC transcriptional plasticity in vitro and provide transcriptional evidence for the expression of BoNT/A-related molecular components in non-neuronal human cells. Full article

Background: In recent years, aesthetic medicine has progressively prioritized conservative treatment volumes, subtle enhancements, and skin quality improvement over volumization. This study evaluates patient-reported psychosocial outcomes, satisfaction, and regret rates following minimally invasive aesthetic procedures using validated instruments. Methods: A review was conducted in accordance with PRISMA guidelines. PubMed, Scopus, and Cochrane Library were searched for studies reporting outcomes using validated PROMs (FACE-Q, GAIS, Decision Regret Scale, BDDQ, DCQ and COPS) with a minimum follow-up of 6 months. Studies evaluating facial botulinum neurotoxins, hyaluronic acid fillers, and biostimulation treatments were included. Given the heterogeneity in study design and outcome reporting, findings were synthesized narratively with descriptive comparisons across treatment modalities. Results: Increased treatment intensity was not consistently associated with greater satisfaction, and higher dose or volume often corresponded to more dissatisfaction and regret. The evidence for this pattern was stronger for botulinum toxin and hyaluronic acid fillers; weaker for biostimulators and preliminary for post-GLP-1 facial changes. Conservative approaches were associated with favorable PROMs, and unrealistic expectations, body dysmorphic disorder, and insufficient pre-treatment counseling were the principal predictors of poor outcomes. Conclusions: Patient satisfaction was not proportional to treatment intensity, particularly when results were perceived as unnatural or overcorrected. This relationship appears associative rather than causal, as patients receiving more intense treatment may differ in expectations, history, and psychological profile. A PROM-driven, patient-tailored approach seems more likely to produce durable satisfaction and minimize regret. Full article

Spasticity is a common and disabling consequence of upper motor neuron lesions, and its follow-up relies largely on clinical scales that may not fully reflect daily-life mobility. This prospective single-arm exploratory pilot study examined wearable-derived daily-life mobility metrics around a scheduled botulinum neurotoxin type A (BoNT-A) injection cycle and assessed their associations with established clinical measures. Thirteen patients with focal spasticity secondary to stroke (n = 11) or multiple sclerosis (n = 2) underwent baseline and 6-week follow-up assessment using the Modified Ashworth Scale (MAS), Motricity Index (MI), the Timed Up and Go test (TUG) and a multi-sensor wearable monitoring system. Device-derived outcomes included gait impairment, gait speed, stride length, angular velocity, and lack of movement. Clinical scales generally changed in the expected post-treatment direction, with reduced MAS scores and descriptive or directional improvements in MI scores and TUG performance. Wearable metrics captured descriptive changes in daily mobility, notably a reduction in lack of movement. Furthermore, in exploratory pooled analyses, selected gait-related metrics tended to be associated with TUG performance and lower-extremity MAS. These findings highlight the potential of wearable telemonitoring to complement conventional clinical scales by providing objective, real-world data, supporting its further validation as a tool for longitudinal spasticity management and neurorehabilitation. These device-derived metrics should be interpreted as mobility-related digital biomarkers rather than direct surrogate measures of spasticity. Full article

Botulinum neurotoxin (BoNT) injection into the masseter muscle is used in selected conditions associated with excessive or painful masseter activity, including oromandibular dystonia, masseter-related myalgia, and bruxism-associated masticatory muscle pain. However, clinical outcomes and adverse-event profiles vary widely, partly because injection technique, dose, dilution, injection depth, anatomical targeting, patient selection, and injector experience have not been consistently standardized. This review examines the anatomical and pharmacological rationale for motor endplate zone (MEZ)-targeted BoNT injection into the masseter muscle. MEZ-targeted injection is not presented as an established clinical guideline or as a proven superior technique but as a hypothesis-generating framework for future controlled studies. Anatomical and electrophysiological studies indicate that neuromuscular junctions in the masseter muscle are concentrated within relatively restricted MEZs. From a pharmacological perspective, delivery of BoNT close to these zones may allow more efficient neuromuscular blockade with lower doses, although direct clinical evidence demonstrating superiority over conventional techniques remains insufficient. Reported adverse events may be influenced by excessive dosing, inaccurate injection depth, diffusion into adjacent structures, or repeated high-dose injections. Future studies should evaluate anatomically informed, dose-minimized injection strategies using clearly defined clinical populations, standardized diagnostic criteria, detailed reporting of injection technique, objective functional outcomes, and systematic adverse-event assessment. Full article

Objective: Residency programs in the United States lack the necessary training for physicians to confidently and competently inject botulinum neurotoxin (BoNT) and manage complex spasticity patients. This creates an unmet need for spasticity patients who could benefit from BoNT injections. This study measured the impact of additional BoNT injection and spasticity management training on post-residency medical practice. Design: Graduates from our Physical Medicine and Rehabilitation residency from 2008 to 2024 were surveyed. Responses were collected from physicians who had residency BoNT injection and spasticity management training (RT) and compared to fellowship BoNT injection and comprehensive spasticity management training (FT). Results: 15 RT and 14 FT physicians completed the survey and were evaluated using descriptive statistics. Spasticity and dystonia treatments comprised an average of 10% of the RT and 62% of the FT clinical practice. BoNT injections involved 5% of the RT practice and 52% of the FT practice. Conclusion: Disabling spasticity is undertreated in this country, partly due to a shortage of training programs for physicians to become skilled and confident at injecting BoNT and comprehensive spasticity management. FT programs can help meet this unmet need by increasing the number of physicians who can provide specialized BoNT injections and spasticity management. Full article

The eyebrows are a central element of facial harmony, influenced by individual and external factors such as gender, ethnicity, facial shape, age, culture, and fashion trends. Traditional methods for esthetically enhancing eyebrows include plucking, highlighting, and surgical interventions. Another minimally invasive option for altering, thus enhancing eyebrow positioning, is botulinum toxin type A (BoNT-A) injection. The objective was to demonstrate a systematic, customizable approach for BoNT-A injections to reshape and reposition eyebrows according to individual facial shape enhancing balance. To determine optimal BoNT-A dose and injection points, an individualized assessment of facial and eyebrow shape and position was performed, leading to a customized protocol of neurotoxin injections according to each patient’s needs. The assessment method aims for the best match between the individual facial shape and eyebrow form and position. This technique enables individualized modulation of eyebrow position and shape, improving facial balance while addressing dynamic upper facial rhytides, thereby promoting harmonious outcomes that preserve individual facial characteristics and providing an additional approach to conventional eyebrow enhancement techniques. Full article

We previously demonstrated that botulinum neurotoxin A (BoNT-A) exerts bilateral antinociceptive effects, involving trans-synaptic transport at the level of the lumbar spinal cord. However, the potential distribution of the toxin to supraspinal sites has not yet been investigated. In the present study, we examined the distribution of cleaved SNAP-25 (cl-SNAP-25), a marker of BoNT-A activity, in the rat brain following peripheral unilateral BoNT-A administration. Brain tissues from rats treated with BoNT-A (7 U/kg, into the hind paw) were analyzed using immunofluorescent tyramide signal amplification to detect cl-SNAP-25. To assess the contribution of trans-synaptic transport, a BoNT-A-neutralizing antitoxin (2 IU) was administered intrathecally 24 h after BoNT-A injection. Signal intensity was evaluated using a semi-quantitative immunohistochemical scoring method based on cl-SNAP-25-positive nerve fibers. Bilateral cl-SNAP-25 immunoreactivity was observed in multiple supraspinal regions, most prominently within the trigeminal complex and the facial and gracile nuclei. Signal intensity was significantly reduced by intrathecal antitoxin, indicating that trans-synaptic transport contributes to central BoNT-A distribution. Peripherally administered BoNT-A reaches distant supraspinal regions, possibly via neuronal retrograde and trans-synaptic transport. Further studies are warranted to clarify exact pathways and alternative distribution routes, determine the functional relevance of central BoNT-A presence, and assess its clinical implications. Full article

Facial paralysis leads to static and dynamic asymmetry, hyperkinesis of the non-paralyzed side, and synkinesis, with major functional and psychosocial consequences for patients. Botulinum neurotoxin serotype A (BoNT-A) injections are an effective therapeutic option since they denervate overactive muscles, thereby reducing hyperkinesis or synkinesis and eventually improving asymmetry. This narrative review summarizes relevant literature on the use of BoNT-A for facial paralysis. It provides a summary of dosing strategies and treatment plans, discusses the use of functional scales for assessing facial paralysis and improvement after treatment, and outlines the use of electromyography (EMG) or ultrasound-guided injections to improve treatment outcomes. Finally, it discusses its potential role in the preparation for functional microsurgery. We also present the authors’ anecdotal experience, with three case reports: a woman with facial paralysis caused by Ramsay Hunt Syndrome, treated with a full-face and neck BoNT-A protocol and followed-up for 18 months with photographic documentation, to further assess the aesthetic improvement; a young woman with familiarity of facial paralysis, contralateral hyperkinesis, and synkinesis, managed with EMG-guided and landmark-guided injections; and her mother, with recurrent facial paralysis and chronic synkinesis, treated with stepwise BoNT-A sessions. All three cases demonstrated clinically meaningful improvements, as evidenced by the photographic material and functional grading scores presented. Full article

The neurotoxin botulinum toxin type A (BoNT/A), produced by the bacteria Clostridium botulinum, is commonly injected intramuscularly (IM) for the management of chronic muscle hyperactivity, such as post-stroke spasticity. New indications such as peripheral neuropathic pain require alternative routes of BoNT/A administration, such as subcutaneous (SC) or intradermal (ID). While IM BoNT/A injections may elicit anti-drug-antibodies (ADAs), their occurrence following SC or ID administration is unknown. Therefore, we investigated whether repeated SC or ID injections of 150 kDa BoNT/A can elicit ADAs in a dose-dependent manner, and whether these differ depending upon the route of administration. Mice were injected 5 times ID or SC with 150 kDa BoNT/A or, for higher doses, inactive mutant BoNT/A (DRBoNT/A) or inactivated toxoid (IA-BoNT/A). Total ADAs were analyzed by an immunoassay and the subgroup of neutralizing ADAs by an in vivo digit abduction score (DAS) assay following a challenge of 0.6 U BoNT/A IM. DRBoNT/A and IA-BoNT/A injections elicit ADAs (22.7 U/mL vs. 460.5 U/mL for ID; 4.7 U/mL vs. 339.4 U/mL for SC), while therapeutic doses of 150 kDa BoNT/A do not. Whereas mice with repeated 150 kDa BoNT/A injections at therapeutic dose show an unrestricted DAS of 3.7 (ID) or 3.4 (SC), mice injected repeatedly with 1.8 µg/kg DRBoNT/A or 500 µg/kg IA-BoNT/A show only a minimal DAS of ≤0.7, indicating a high titer of neutralizing ADAs. No differences were observed between administration routes. Accordingly, repeated ID or SC injections of pure 150 kDa BoNT/A at therapeutic doses fail to induce ADA formation in mice. On the other hand, DRBoNT/A ID injections induce higher ADA concentrations than SC, but generate similar amounts of neutralizing ADAs. IA-BoNT/A injections induce ADAs and neutralizing ADAs similarly after ID and SC injections. ADA development at intermediate BoNT/A doses can be higher after ID injection, but does not lead to differences in neutralizing ADAs. Our data demonstrate that the antibody response to botulinum toxin depends predominantly on the protein load, and less on the administration route. Full article

The efficacy of botulinum neurotoxin (BoNT) is strongly dependent on its accurate delivery to hyperactive muscles and, ideally, to motor endplate regions. Although guidance techniques such as electromyography (EMG) and ultrasound (US) improve injection precision, each technique provides only partial information—either functional or anatomical. Integrating these techniques could enhance targeting accuracy, optimize dose distribution, and reduce off-target effects. A structured PubMed search was performed using terms related to BoNT, spasticity/dystonia, EMG, and US. Filters included clinical trials, randomized controlled trials, meta-analyses and reviews published within the last decade. Fifty-nine studies met the inclusion criteria. The publications were predominantly in neuroscience and rehabilitation journals. Only 17 studies reported combined EMG–US guidance. These focused mainly on stroke and cervical dystonia. While EMG-US integration is a promising strategy, we emphasize the added value of EMG guidance for US approaches, which is particularly important when treating complex neurological conditions involving complex, overlapping muscle activation patterns, or when targeting structures that are inaccessible to conventional imaging techniques. The EMG-US integrated approach is a promising strategy for optimizing BoNT therapy by combining structural visualization with real-time functional assessment. Despite its promising advantages in terms of accuracy and dose optimization, its clinical adoption is limited by a lack of high-quality evidence. Full article

Background/Objectives: Trigeminal neuralgia (TN) is a debilitating neurological condition characterized by recurrent, severe pain linked to peripheral and central sensitization within trigeminal pathways. Current pharmacologic treatments are limited by inadequate efficacy or dose-limiting side effects, and botulinum neurotoxin type A (BoNT/A) has emerged as a viable option. However, its potential use in the management of TN is hampered by methodological limitations in existing studies and a lack of pivotal clinical trials. This study investigated the efficacy, optimal treatment site, preventive utility, and duration of effect of incobotulinumtoxinA (Inco/A), a BoNT/A, in a model of TN. Methods: An infraorbital nerve chronic constriction injury model was used to induce mechanical allodynia in male Sprague–Dawley rats, reproducing the trigeminal sensitization seen in TN. The effects of subcutaneous Inco/A (1, 2, and 4 U) were measured using the mechanical sensitivity (von Frey) test to evaluate the dose response, effect of injection location, potential preventive nature of treatment, and duration of benefit. Results: Inco/A produced a robust, dose-dependent reduction in mechanical allodynia, predominantly via a local mechanism of action. Both preventive and therapeutic administration of Inco/A was efficacious, with significant reduction in allodynia even when administered up to 28 days before nerve injury. The anti-allodynic effect persisted up to 56 days post-injection. Conclusions: Inco/A is highly effective in alleviating mechanical allodynia in a validated rat model of TN. The findings highlight Inco/A as a promising candidate for clinical translation in TN and related neuropathic pain syndromes and support systematic investigation in well-controlled human trials. Full article

Objectives: To investigate current Canadian physicians’ practice patterns of treating upper limb post-stroke spasticity (PSS) and hemiplegic shoulder pain (HSP) acutely after a stroke. In addition, by examining Canadian physicians’ diagnostic capabilities, time till treatment, minimum criteria to begin treatment, mechanisms of treatment, targeting of muscles, and benefits and adverse effects of treatment, we aim to learn about areas of improvement to optimize PSS management for Canadians. Design: The present study was a cross-sectional survey, polling practicing Canadian physicians. Results: A total of 17 physicians completed the survey, all PM&R specialists, save one neurologist. Four provinces were represented in the responses. Participants had, on average, over ten years of experience managing post-stroke spasticity in outpatient and inpatient clinics. All 17 perform botulinum neurotoxin A (BoNT-A) injections for HSP associated with PSS. Most participants reported that they will begin BoNT-A treatments 2–3 weeks post-stroke, most commonly targeting the pectoralis major, subscapularis, and latissimus dorsi. Participants reported the mean median dosage they use as onabotulinum toxin A (169.12 units, SD = 73.70), incobotulinum toxin A (178.13 units, SD = 65.75), and abobotulinum toxin A (470.83 units, SD = 171.17). For injection guidance, participants responded that they use ultrasound for the largest percentage of their caseload, followed by electromyography, then electrical stimulation, then palpation. Very seldom did participants use palpation alone. Conclusions: From the limited sample included in analyses, the Canadian physicians respondents seem to be treating HSP and associated PSS with variable strategies. Further research is required to align dosages, targets, and guidance strategies as they vary considerably. Full article

Triple-negative breast cancer (TNBC) continues to be a medical challenge requiring multiple treatment options. SV2A, a protein involved in vesicular release, has emerged as a promising biomarker for various cancers. Research shows that botulinum neurotoxin type A (BoNT/A), which binds to SV2A, the BoNT/A receptor, can inhibit the growth of prostate and breast cancer cells, suggesting its potential as an alternative treatment for breast cancer. The purpose of this study was to determine the potential of BoNT/A to inhibit tumor growth in a mouse preclinical model. BoNT/A was evaluated for its effects in an in vitro model employing 4T1 cells and in an in vivo model of orthotopically inoculated 4T1 cells in BALB/c mice. BoNT/A inhibited the proliferation of 4T1 cells, which express the SV2A protein; decreased tumor growth in the preclinical model; and decreased inflammation, associated with fewer blood neutrophils and monocytes, suggesting an immunomodulatory and anti-inflammatory effect. The effect of BoNT/A on the TNBC model supports its use as a repurposed drug for this type of aggressive cancer. Our results emphasize the significance of the SV2A receptor and its interaction with BoNT/A as promising therapeutic targets, particularly for TNBC. Full article

Botulinum neurotoxins (BoNTs) act on peripheral cholinergic nerve terminals, inducing reversible muscle paralysis and profound therapeutic effects. However, their limited cell-type specificity and narrow therapeutic window have motivated the development of engineered variants. Here, a modular strategy was employed to construct full-length chimeric BoNTs, grafting receptor-binding segments from BoNT/B or BoNT/F onto the BoNT/A framework. The novel chimeras AAAF and AAFF efficiently cleaved rSNAP-25 in cell-free assays. Firstly, both toxins showed effective cellular uptake and cleaved endogenous SNAP-25 in Neuro-2a cells, with cleavage efficiencies of approximately 46% for AAAF and 73% for AAFF, highlighting the enhanced activity of AAFF. Secondly, AAAF induced faster recovery from reversible muscle paralysis compared to rBoNT/A-WT, whereas AAFF produced more sustained paralysis, with both exhibiting reduced systemic toxicity. Despite these altered pharmacological profiles, the chimeras required higher doses than rBoNT/A-WT to induce neuromuscular effects. Collectively, this study presents the design of novel chimeric BoNT/A-F proteins, characterizes their functional activities, and provides a preliminary exploration of how domain grafting affects cellular uptake, enzymatic activity, and neuromuscular pharmacodynamics. Full article