Search Results (123)

Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin^®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration–Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Full article

Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An umbrella review was conducted following PRISMA guidelines and registered in PROSPERO. High-quality systematic reviews with meta-analysis evaluating BoNT-A efficacy were identified through five databases up to August 2024. Primary outcomes included monthly headache frequency and severity. Methodological quality and risk of bias were assessed using the umbrella review checklist. Fourteen articles were included. Overall, quantitative evidence indicated favorable effects of BoNT-A compared with placebo for chronic migraines, across headache frequency, headache severity, and acute medication use, but less efficacy than topiramate and the CGRP monoclonal antibodies (CGRPmAbs) galcanezumab and fremanezumab. Though the adverse events were frequent, BoNT-A was generally well-tolerated. Comparative data suggested superior tolerability versus topiramate and a safety profile like CGRPmAbs. Although botulinum toxin type A is widely used as a preventive treatment for chronic migraines, the available evidence supports its efficacy at a moderate level. Further head-to-head and long-term analyses are needed to clarify its comparative role alongside newer biologic treatments. Full article

Temporomandibular disorders (TMDs) are common musculoskeletal chronic orofacial pain conditions involving peripheral and central sensitization within trigeminal nociceptive pathways, manifesting as mechanical allodynia and functional impairment. Botulinum toxin type A (BoNT-A) has been explored as a treatment targeting both muscle hyperactivity and nociceptive modulation. Preclinical and clinical evidence demonstrate that BoNT-A reduces peripheral neurotransmitter release, neurogenic inflammation, and central neuronal excitability, leading to attenuation of mechanical allodynia in TMD models and patients. Clinical trials show modest and variable analgesic effects, with patients displaying sensory sensitization appearing to respond more favorably, though methodological heterogeneity limits definitive conclusions. Safety concerns related to muscle weakening, changes in bone density, and structural changes underscore the need for standardized protocols optimizing dosing and monitoring, in addition to prospective studies. These findings suggest that BoNT-A may serve as an adjunctive, mechanism-based therapy within multimodal TMD management. Future research should focus on standardized sensory phenotyping and trial design to clarify BoNT-A’s role in modulating central sensitization and improving patient outcomes. Full article

While distinguishing between collis and caput patterns in cervical dystonia (CD) has clear clinical and therapeutic relevance, the effects of botulinum toxin type A (BoNT-A) on segmental spinal excitability and inhibitory function in caput-pattern CD have not been previously investigated. This study aimed to advance understanding of the effects of BoNT-A and its broader neurophysiological impact in cervical dystonia, particularly in the caput subtype. The study utilised non-invasive neurophysiological methods to assess F-wave and cutaneous silent period (CSP or CuSP) parameters in 21 CD patients with caput motor patterns at waning and peak response phases of BoNT-A therapy. Significant prolongation of Fmin latency, increased F–M interlatency, reduced F-wave amplitude, and a marked increase in CSP duration and onset latencies were observed following BoNT-A administration, indicating that BoNT-A not only reduces spinal motoneuron excitability and strengthens spinal inhibitory processes, but also highlights its capacity to modulate central sensorimotor pathways beyond local chemodenervation. Together, the observed changes in CSP support its use as a potential biomarker for nervous system effects of BoNT-A in dystonia; however, further validation in controlled studies is warranted. Full article

Facial palsy affects millions worldwide. Botulinum toxin Type A (BoNT-A) is an established treatment for non-flaccid facial palsy, yet objective evidence remains limited. This study evaluates the effects of BoNT-A using AI-based tools and patient-reported outcome measures (PROMs). In this prospective observational study, patients with non-flaccid facial palsy received individualized BoNT-A injections. Exclusion criteria included age < 18, hypersensitivity to BoNT-A, or lack of follow-up. Assessments were conducted before and 3 weeks after treatment, including facial symmetry (Emotrics^®), emotion expression (FaceReader™), and PROMs (FaCE and FDI). Eleven patients (mean age 50.1 ± 18 years) were included. BoNT-A significantly improved dynamic facial symmetry: eyebrow raising (p = 0.032), smile angle (p = 0.005), and lower lip height (p = 0.042). Emotion analysis showed no significant changes. PROMs revealed improvements in social well-being (FDI, p = 0.004) and aesthetic satisfaction (FaCE, p = 0.035), while functional FDI scores remained unchanged (p = 0.406). BoNT-A improves objective symmetry and patient satisfaction in non-flaccid facial palsy. The lack of change in emotional expression may reflect improved symmetry at the cost of dynamic muscle activation. Full article

Background: Erectile dysfunction (ED) affects approximately 20% of men worldwide, significantly affecting their quality of life. While phosphodiesterase type 5 inhibitors (PDE5-Is) are the standard first-line treatment, a substantial number of patients are non-responders. Second-line treatments, such as intracavernosal alprostadil, are effective but often limited by their invasive nature and the need for frequent injections. Intracavernosal onabotulinumtoxinA (BoNT-A) offers a promising new option. By inhibiting acetylcholine release and norepinephrine, as well as other neurotransmitters involved in detumescence, it facilitates cavernosal smooth muscle relaxation and enhances penile blood flow. Its effects may persist for up to six months following a single injection, potentially reducing treatment burden and improving adherence among men with refractory ED. Methods: A systematic review was performed in accordance with the PRISMA guidelines. Literature searches were conducted in PubMed, Embase, Cochrane Library, Scopus, and Clinicaltrials.gov from inception until August 2025 using a combination of keywords and MeSH terms related to ‘erectile dysfunction’ and ‘botulinum toxin’. After screening, 51 studies met the inclusion criteria. Due to significant heterogeneity in interventions (e.g., BoNT-A dosage, co-therapies), patient populations, and reported outcomes, the data were not suitable for meta-analysis. Consequently, a narrative synthesis was performed to summarize the findings. Results: Among the included studies, intracavernosal BoNT-A was associated with improvements in validated erectile function scores. Reported response rates, variably defined across studies, ranged from 40% to 77.5%. Several studies suggested that efficacy was higher in patients with mild-to-moderate ED and with repeated administration of 100 U doses. The treatment exhibited a favorable safety profile. The most common adverse event was mild, transient penile pain (reported incidence 1.5–6%). No studies reported serious systemic adverse events. The overall strength of the evidence was limited by significant heterogeneity among the included studies and their generally small sample sizes. Conclusions: Based on this systematic review, intracavernosal onabotulinumtoxinA (BoNT-A) may be a beneficial therapeutic option for patients with refractory ED, offering potential improvements in sexual function while reducing the need for invasive therapies. Future large-scale, placebo-controlled studies are essential to confirm these benefits and standardize their clinical application. Full article

(1) Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (2) Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively. (3) Results: Seven trials (n = 229) were included. Across all studies, toxin treatment reduced spasticity within groups, whereas additional spasticity reduction with RAT versus conventional rehabilitation was inconsistent. In contrast, several lower-limb trials reported greater improvements in walking capacity and balance when RAT was added, while upper-limb trials showed comparable motor recovery across treatment arms with occasional advantages in strength and movement quality. A pilot four-arm study suggested that starting RAT around four weeks after injection may maximize upper-limb motor gains. (4) Conclusions: The combination of BoNT-A with RAT appears safe and is particularly promising for gait rehabilitation, but further research is needed to define optimal timing and protocols. Full article

Background/Objectives: To investigate the impact of a routine botulinum toxin type A (BoNT-A) injection in combination with outpatient therapy on the daily activities of stroke survivors with upper extremity spasticity and to facilitate patient-centred assessment focusing on individual needs during daily life. Methods: Design: Observational study across one treatment cycle (3 months). Setting: Spasticity outpatient clinic of a neurorehabilitation hospital in Germany. Participants: Adult stroke survivors (n = 27) with upper extremity spasticity receiving routine BoNT-A treatment. Interventions: Participants received one BoNT-A injection and outpatient therapies as part of their routine management. Augmented assessment was conducted directly before the injection (T0), and at 4 to 6 weeks (Tmax1) and 12 to 14 weeks (T2) following the injection. Main outcome measures: The Canadian Occupational Performance Measure (COPM), Goal Attainment Scaling (GAS), and Arm Activity Measure (ArmA). Secondary outcome measures: The Resistance to Passive Movement Scale (REPAS), Motricity Index (MI), SF-12v2 Health Survey (SF-12v2), Global Clinical Impression (GCI), and importance of and satisfaction with the BoNT-A treatment. Results: Performance of individually selected daily activities and satisfaction with their performance (COPM), passive care tasks (ArmA, part A), and resistance to passive movement (REPAS) significantly improved from T0 to Tmax1. Improvements largely remained at T2. Individual goals were all set at the activities and participation levels of the International Classification of Functioning, Disability and Health. These improved for 75% of participants and were fully attained by 33.3% at Tmax1. Responder analysis indicated that COPM and ArmA improvements were clinically significant for up to 50% of participants. Active upper extremity use (ArmA, part B), health-related quality of life (SF-12v2), and upper extremity strength (MI) remained unchanged. Conclusions: Our results indicate that BoNT-A in combination with routine outpatient therapy positively influenced the individually valued daily activities of stroke survivors. COPM, GAS, and ArmA are suitable for facilitating a patient-centred and daily life-oriented spasticity management post-stroke. Full article

Pediatric torticollis, predominantly resulting from congenital muscular torticollis, is characterized by unilateral shortening of the sternocleidomastoid muscle, leading to head tilt and limited cervical mobility. Conventional management primarily involves physical therapy and repositioning strategies, with most infants achieving full recovery. However, a subset of patients exhibits persistent symptoms despite conservative treatment. Botulinum toxin type A (BoNT-A) has emerged as a minimally invasive adjunct intervention that targets muscular hypertonicity by inhibiting acetylcholine release at neuromuscular junctions. This scoping review synthesizes clinical evidence from six studies, including randomized controlled trials and case reports, assessing the efficacy and safety of BoNT-A in pediatric torticollis. Results indicate consistent improvements in range of motion, head posture correction, and patient satisfaction, with rare and mild adverse events such as local bruising and transient muscle weakness. Despite promising outcomes, variability in dosing, injection protocols, and follow-up durations underscores the need for standardized treatment guidelines and further high-quality research. These findings support BoNT-A as a valuable therapeutic option for refractory pediatric torticollis, warranting integration into multidisciplinary care frameworks. Full article

Bruxism, defined as a repetitive jaw-muscle activity characterized by clenching or grinding of teeth and/or by bracing or thrusting of the mandible, is a prevalent behavior affecting up to 22% of adults worldwide. While traditionally viewed as a disorder, current understanding recognizes bruxism as a behavior that may have both positive and negative consequences. Objective assessment methods for evaluating the effectiveness of interventions in symptomatic patients remain limited. This article presents the first longitudinal study using myotonometry to quantify changes in masseter muscle following botulinum toxin type A (BoNT-A) treatment in patients with symptoms of bruxism. In total, 57 patients were recruited and their masseter muscle tone, stiffness, elasticity, relaxation time, and creep parameters were measured. Measurements were performed at baseline, 3 weeks, and 3 months post-injection during both rest and maximum voluntary contraction. BoNT-A treatment produced significant improvements in all biomechanical parameters, with the greatest effects observed in patients with the highest baseline muscle values. The objective biomechanical changes correlated with the duration of BoNT-A’s therapeutic effects. These findings establish myotonometry as a valuable tool for objective assessment of masticatory muscle function and demonstrate that BoNT-A produces measurable, long-lasting biomechanical changes in masseter muscle parameters, supporting its possible clinical application in this challenging condition. Full article

This study investigated bite force changes after botulinum toxin type A (BoNT-A) injection into different masticatory muscles. Thirty-five male participants were divided into three groups: masseter only (M), masseter and temporalis (MT), and masseter, temporalis, and medial pterygoid (MTP). Bite force was measured before and up to 6 months after injection with the Dental Prescale II system. Baseline values showed no significant group differences. Group M exhibited significant reduction at 1 and 2 weeks, with recovery within 1 month. Group MT showed a similar transient decrease, also recovering after 1 month. In contrast, Group MTP demonstrated a more pronounced and prolonged reduction, persisting up to 4 months before recovery. These results indicate that the extent and duration of BoNT-A effects depend on the number of muscles injected. Multi-muscle injections, including the medial pterygoid, provide more durable suppression. However, further research involving patient populations is needed to clarify whether multi-muscle injection strategies provide therapeutic benefits in clinical conditions such as temporomandibular disorders or oromandibular dystonia. Full article

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸–2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs. Full article

Anecdotal reports have recently circulated suggesting that intramuscular injection of bacteriostatic saline (BS)—which contains benzyl alcohol (BnOH)—can reverse botulinum toxin type A (BoNTA)-induced brow ptosis. Given the well-established intracellular persistence of BoNTA’s light chain and its irreversible cleavage of SNAP-25, such rapid functional recovery challenges existing pharmacological understanding. This study employed high-resolution pharmacokinetic/pharmacodynamic (PK/PD) modelling using the AesthetiSim™ platform to systematically evaluate this hypothesis. A total of 30,000 virtual patients were randomized to receive BoNTA alone, BoNTA followed by BS injection, or BoNTA followed by normal saline (NS) at Day 7. The model incorporated BoNTA diffusion, internalization, SNAP-25 cleavage, neuromuscular output, and transient BS effects on membrane permeability and endosomal trafficking. Simulated recovery trajectories were tracked over 90 days. The primary outcome, time to 80% restoration of baseline frontalis muscle force (T₈₀), averaged 42.0 days in the BoNTA-only group and 35.5 days in the BS group (Δ = −6.5 days; p < 0.001). Only 13.9% of BS-treated patients reached the T₈₀ threshold by Day 30. Partial reactivation (T₃₀) occurred earlier with BS (21.8 ± 5.3 days vs. 27.3 ± 4.9 days), and the area under the effect curve (AUEC) was increased by 9.7%, reflecting higher overall muscle function over time. In molecular simulations, BnOH produced a minor rightward shift in the BoNTA–SNAP-25 dissociation curve, but receptor occupancy remained above 90% at therapeutic toxin concentrations, suggesting no meaningful impairment of binding affinity. A global Sobol sensitivity analysis demonstrated that the primary driver of recovery kinetics was intracellular LC degradation (49% of T₈₀ variance), while BS-modulated extracellular parameters collectively contributed less than 20%. These findings indicate that BS does not reverse the molecular action of BoNTA but may transiently influence recovery kinetics via non-receptor-mediated pathways such as increased membrane permeability or altered vesicular trafficking. The magnitude and variability of this effect do not support the notion of a true pharmacologic reversal. Instead, these results emphasize the need for mechanistic scrutiny when evaluating rapid-reversal claims, particularly those propagated through anecdotal or social media channels without supporting biological plausibility. Full article

Background/Objectives: Major depressive disorder (MDD) represents a leading cause of global disability, with approximately one-third of patients exhibiting treatment resistance (TRD) despite adequate pharmacological interventions. This treatment gap underscores the urgent need for novel therapeutic strategies. Recently, a series of data suggests that botulinum neurotoxin of type A (BoNT-A), traditionally used for neuromuscular and cosmetic indications, could constitute a potential antidepressant tool. This narrative review critically examines the current preclinical and clinical findings of BoNT-A in MDD. Methods: A comprehensive search of PubMed, Scopus, and Web of Science was conducted up to June 2025, including randomized controlled trials, observational studies, animal models, and mechanistic investigations. Search terms included “Botulinum Toxin,” “BoNT type A”, “Depression”, “Major Depressive Disorder”, “Facial Feedback”, and “Neurobiology”. Results: Some randomized and observational studies would indicate that glabellar BoNT-A injections might lead to significant reductions in depressive symptoms in patients with MDD and TRD. Proposed mechanisms include both peripheral modulation of emotional expression and brain effects, such as reduced amygdala hyperactivity, increased BDNF expression, and enhanced monoaminergic transmission. Preclinical studies confirm that BoNT-A modulates limbic and brainstem circuits, possibly implicated in affective regulation. The few comparative studies suggest therapeutic efficacy comparable to that of SSRIs, with a more rapid onset. Preliminary data also support its application in bipolar depression and comorbid anxiety disorders. Conclusions: The available literature would indicate that BoNT-A might constitute a promising candidate at least as an adjunctive treatment in MDD, although the impact of current findings is limited due to the methodological heterogeneity and the small sample sizes of patients examined. Further large-scale, placebo-controlled trials are warranted to elucidate the mode of action of BoNT-A and to validate or not its clinical effectiveness. Full article

The neurotoxin BoNT/B2 is the predominant Clostridium parabotulinum subtype in foodborne and infant botulism cases in Spain. This study characterizes a novel case of foodborne botulism in Spain caused by a dual-toxin A1(B5) strain. A 64-year-old male presented with acute, progressive flaccid paralysis including diplopia, dysphagia, and respiratory failure. Although botulism was not initially suspected, the patient recovered with supportive care and without antitoxin administration. Genomic characterization confirmed the presence of both bont/A1 and silent bont/B5 genes. The bont/A1 gene was associated with an orfX+ neurotoxin gene cluster, while the silent bont/B5 gene was in an ha+ cluster. Phylogenetic analysis of both bont/A1 and bont/B5 sequences showed 100% amino acid identity, respectively, to previously reported A1(B5) strains (e.g., CDC_69094, FE9504ACG). Multi-locus sequence typing (MLST) assigned the ST10, a genotype previously undetected in Spanish botulism cases, yet found in other European countries. This case highlights the importance of considering botulism in differential diagnosis due to its varied presentation and the significance of timely laboratory confirmation for effective management. The identification of this dual-toxin BoNT/A1(B5) orfX+/ha+ ST10 strain expands our understanding of C. botulinum epidemiology and genetic diversity in Spain. Full article