Search Results (365)

Botulinum toxin suppresses neurotransmitter release, thereby inhibiting muscle contraction and inducing flaccid paralysis. Botulinum toxin type A (BoNT/A) is widely used for neuromuscular blockade but, upon repeated administration, may cause long-lasting muscle atrophy, fibrosis, and inflammation. It is produced as a single peptide chain that becomes activated through cleavage into a heavy and light chain. BoNT/E, like BoNT/A, is produced as a single-chain polypeptide and requires cleavage to generate the active dichain form. Although BoNT/E is known to have a faster onset and shorter duration of action compared with BoNT/A, its efficacy and safety have not been thoroughly investigated. We compared BoNT/E and BoNT/A in SKH-1 hairless mice. Neuromuscular blockade, recovery pattern, and changes in muscle weight, volume, fiber size, fibrosis, mast cell infiltration, and diffusion to adjacent muscles were evaluated over time. BoNT/E induced maximal neuromuscular blockade on day 3 and fully recovered by day 35, whereas BoNT/A reached maximal effect on day 7 and showed only 20% recovery of the vehicle group by day 35. BoNT/E caused transient, dose-dependent reductions in muscle weight, volume, fiber size, and fibrosis, which largely normalized by day 35. In contrast, BoNT/A, administered at a dose of 0.5 U per injection site, induced persistent muscle atrophy, fibrosis, and significantly increased mast cell infiltration under the experimental conditions used in this study. Neither BoNT/E nor BoNT/A showed diffusion to adjacent muscles or changes in body weight. These findings suggest that BoNT/E provides rapid onset, short duration, and favorable safety, supporting its potential as an alternative therapeutic option for indications requiring temporary muscle relaxation with minimized long-term adverse effects. Full article

Objective: The aim of the study was to evaluate the dynamics of skin temperature at the injection points of botulinum toxin type A in the forehead area at different time stages as a marker of the vasomotor response and restoration of microcirculation after aesthetic botulinum therapy. Methods: The prospective study included 126 patients (19–59 years old, mean age 34.4 ± 1.2 years) who underwent injections of botulinum toxin type A at standard points of m. frontalis, m. procerus, and m. corrugator supercilii. Skin temperature was recorded with an infrared thermal imager at nine standardized points (P1–P9) at the following stages: before the procedure (T0), immediately after (T1), after 30 min (T2), after 14 (T14) and 30 (T30) days. The analysis was performed using analysis of variance with repeated measures and post hoc tests (p < 0.05). Results: A typical three-phase pattern of temperature response was revealed: an immediate decrease in temperature at all points immediately after injections (T1, −1.7–4.8% relative to the baseline, p < 0.001), subsequent reactive hyperemia after 30 min (T2, an increase of 2.35–5.8% at points P1, P2, P4–P7) and normalization of indicators by T14–T30. The most pronounced and stable changes were recorded at the interbrow points P7–P9, projecting to m. corrugator supercilii and m. procerus, which reflects their higher functional and vascular activity. Conclusions: Infrared thermography allows for objective recording of the phasic vasomotor response of the skin to injections of botulinum toxin type A, can be used to assess individual vascular response, and may aid in individualized treatment planning for aesthetic botulinum therapy. Full article

Background: Myogenous temporomandibular disorders (TMDs) are a common subtype of orofacial pain. Evidence regarding treatment with botulinum toxin type A (BoNT-A) remains heterogeneous, and its use is generally limited to refractory cases. This study evaluated 12-month clinical outcomes following an incobotulinumtoxinA protocol (the Ângelo Botulinum Toxin Protocol^®) in adults with DC/TMD-confirmed myogenous TMD unresponsive to conservative therapy. Methods: This retrospective observational study reviewed records from 98 adults treated with incobotulinumtoxinA following the predefined injection protocol. All patients had failed ≥ 3 months of conservative management and completed ≥ 12 months of follow-up. Outcomes included myalgia severity (0–3), patient-reported orofacial pain intensity (VAS 0–10), and maximum mouth opening (MMO). Favorable outcome criteria required myalgia 0–1 or VAS ≤ 2 and MMO ≥ 35 mm. Results: Myalgia significantly decreased at 12 months (2.69 ± 0.64 to 0.43 ± 0.85; p < 0.001). Patient-reported orofacial pain intensity also improved (2.44 ± 2.54 to 0.37 ± 1.33; p < 0.001). MMO remained stable, indicating preserved mandibular mobility. Overall, 79.6% of patients met the predefined favorable outcome criteria. Reintervention was required in 12 patients; 7 received additional incobotulinumtoxinA injections, and 5 underwent TMJ arthrocentesis. No complications were observed. Conclusion: This protocol was associated with improvements in muscular pain and orofacial discomfort while preserving mandibular mobility. However, given the retrospective design and absence of a control group, these findings should be interpreted as hypothesis generating. Full article

Background/Objectives: Percutaneous cryoneurolysis (CNL) has emerged as a minimally invasive neuromodulatory technique for focal spasticity management, with growing international clinical adoption since 2018. Its application to upper limb motor nerve targets—including branches of the musculocutaneous, radial, median, ulnar, pectoral, and thoracodorsal nerves—is of direct relevance to clinicians involved in the surgical and non-surgical management of hand and upper extremity spasticity. The existing literature lacks a comprehensive systematic appraisal of its evidence base. This systematic scoping review aimed to map all published evidence on CNL for spasticity across all aetiological groups and anatomical regions, with particular attention to upper limb and hand-relevant targets; appraise methodological quality using design-appropriate tools; characterise the safety profile; apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to key outcome domains; and identify critical evidence gaps. Methods: A systematic scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines (search through February 2026). PubMed/MEDLINE, Embase (via Ovid), Scopus, and the Cochrane Library were searched. Methodological quality was assessed using JBI Critical Appraisal Checklists, Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I), and A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2). Certainty of evidence was evaluated using GRADE. Results: Twenty-five studies met inclusion criteria; no randomised controlled trials (RCTs) were identified. In the largest prospective observational cohort (n = 59, 12-month follow-up), CNL produced statistically significant improvements in passive range of motion (ROM), Modified Ashworth Scale (MAS) scores, and pain in patients with upper limb spasticity refractory to botulinum toxin type A (BoNT-A). A prospective safety study (n = 113 patients; 277 nerves) documented that 96.75% of nerve treatments produced no post-procedural sensory disturbance; the risk was approximately 10-fold higher for mixed sensorimotor than purely motor nerve targets (7.1% vs. 1.1%). Certainty of evidence was Very Low (⊕◯◯◯) for all efficacy outcomes and Low (⊕⊕◯◯) for safety. Conclusions: CNL represents a mechanistically sound second-line or complementary intervention for refractory focal spasticity. In the upper extremity context, it may additionally serve as a reversible functional evaluation tool before irreversible surgical decisions—including selective neurotomy—are made. The evidence base is critically constrained by the absence of RCTs, confirmed cohort overlap between the two largest primary studies, financial conflicts of interest with the primary device manufacturer identified in ≥48% of included studies (≥12/25), and single-institution concentration of primary evidence (≥69% of primary clinical studies from one research group). Multiple ongoing controlled trials are expected to provide higher-quality evidence to inform guideline development. 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

Background: Sleep bruxism involves repetitive jaw-muscle activity, including teeth clenching, grinding, or mandibular bracing. Despite the growing interest in botulinum toxin type A (BTX-A) as a therapeutic intervention for bruxism, evidence remains limited, particularly regarding studies using portable electromyography (EMG) monitoring devices. This study evaluated the effects of BTX-A injections into the masseter muscle on the reduction of bruxism activity, as measured using the portable electromyographic Holter Bruxoff system. Methods: Adult patients with diagnosed sleep bruxism were monitored for two nights using the Bruxoff device to record masseter EMG activity, respiratory rate, and heart rate. After receiving standardized bilateral masseter BTX-A injections, participants underwent the same monitoring protocol 40 days later. Statistical analyses compared pre- and post-treatment values, and effect sizes were calculated. Results: Ten participants (60% women; mean age 47.6 ± 4.4 years) completed the study. The Bruxism Index showed a marked reduction, dropping from 12.2 ± 1.32 at baseline to 7.4 ± 1.35 after 40 days, a statistically significant change (t (9) = 10.23, p < 0.001; Cohen’s d = 3.25). Average heart rate also decreased significantly, from 64.4 ± 2.99 to 62.6 ± 2.63 (t (9) = 2.86, p = 0.018; Cohen’s d = 0.91). However, the respiratory rate measurement remains stable. Conclusions: BTX-A injections into the masseter muscles produced a marked reduction in sleep-related bruxism activity as measured by portable EMG. These findings support BTX-A as a promising and effective treatment option for sleep bruxism. Full article

Benign parotid tumors are increasingly treated with parenchyma-sparing extracapsular enucleation, yet postoperative salivary collections and Frey syndrome can still generate clinically relevant morbidity; we evaluated whether a standardized intraoperative bundle combining intraparotid botulinum toxin A (BTX-A) and bovine collagen membrane interposition is associated with fewer complications than standard enucleation alone. In this retrospective comparative cohort at a tertiary Head and Neck Surgery Unit, consecutive adults undergoing extracapsular enucleation for pleomorphic adenoma or Warthin tumor (2010–2025) were allocated by institutional era-based protocol to Group A (2010–2017, standard enucleation) or Group B (2018–2025, enucleation plus intraoperative intraparotid BTX-A 50 IU and bovine collagen membrane placement over the repaired parotid fascia). Prespecified endpoints were sialocele/salivary fistula, surgical-site infection (SSI) within 30 days, and clinically recorded Frey syndrome within 6 months; effect sizes with 95% confidence intervals were reported. A total of 188 patients were analyzed (94 per group). Sialocele occurred in 20/94 (21.3%) in Group A versus 2/94 (2.1%) in Group B [Relative Risk (RR) 0.10]. SSI occurred in 14/94 (14.9%) versus 2/94 (2.1%) (RR 0.143), and clinically recorded Frey syndrome in 18/94 (19.1%) versus 4/94 (4.3%) (RR 0.222). This combined protocol was associated with lower complication rates through 6 months; prospective controlled studies with standardized Frey assessment and longer follow-up are warranted. Full article

Background: Excessive gingival display is frequently associated with upper lip hypermobility and represents a common aesthetic concern. Several therapeutic approaches have been proposed, including botulinum toxin type A injections, lip repositioning surgery (LRS), and combined techniques; however, no clear consensus exists regarding the most effective and stable treatment option. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) guidelines. A comprehensive search of multiple electronic databases was performed, leading to the inclusion of 17 human studies that met predefined PICOS criteria. The review protocol was registered in PROSPERO (CRD420261281920). Results: Most included studies reported favorable outcomes in terms of reduction in gingival display, improvement in smile aesthetics, and patient satisfaction. No major adverse effects were reported, suggesting acceptable safety profiles for all therapeutic modalities. Outcomes varied depending on the type of intervention, surgical technique, botulinum toxin dosage and injection protocol, and the initial severity of upper lip hypermobility. Conclusions: Both botulinum toxin injections and LRS demonstrated effectiveness in reducing excessive gingival display. Botulinum toxin provided a rapid but temporary improvement, whereas modified LRS showed greater stability over time. Combined approaches appeared to offer the most consistent long-term results by limiting postoperative relapse. Further standardized protocols and long-term clinical studies are needed to confirm these findings and support evidence-based clinical decision-making. Full article

Botulinum toxin type A (BoNT/A) injection into the bladder wall is a milestone in the treatment of urinary incontinence in patients with neurogenic detrusor overactivity (NDOi) or overactive bladder syndrome (OABi) who are refractory to or unable to tolerate oral or transdermal therapies. However, the efficacy of BoNT/A is hampered by the low long-term adherence of patients to a treatment that requires repeated bladder injections under cystoscopy control. The discontinuation is particularly evident among incontinent patients with spontaneous voluntary voiding, regardless of whether the cause is NDOi or OABi, although clearly more marked among the latter group. In addition to the bother and pain associated with repeated cystoscopies, these patients show low tolerance to the high incidence of urinary tract infections (UTIs) and transient urinary retention, the two most common adverse events. Fewer injection points may render treatments less painful, apparently without reducing efficacy, but will not avoid the need for repeated cystoscopies, and no studies have demonstrated that such modification increases adherence. Eventually, accessing the bladder wall for BoNT/A administration via a transabdominal approach, under real-time ultrasound guidance, may overcome trans-urethral limitations, but the technique’s reproducibility remains unknown. An intensive investigation is ongoing to identify aids that facilitate the passage of the large, fragile BoNT/A molecule across the urothelium to reach the bladder nerves without injections. Electromotive Drug Administration (EMDA) of BoNT/A demonstrated efficacy and safety over a 6-year follow-up in NDOi patients at a single center, but the results were not reproduced at other institutions. The application of shock waves to the bladder using shock waves generated by Extracorporeal Shock Wave Lithotripsy (ESWL) machines to tear the urothelium and facilitate the passage of BoNT/A instilled in the bladder is ingenious, but the experience is very limited. Dimethyl sulfoxide, liposomes, and thermal-reversal hydrogel to deliver the toxin failed in pilot trials. BoNT/A in nano-formulations has high heat stability, resistance to pH changes, and to enzymatic degradation. Extended efficacy in dermal and intramuscular pilot applications is promising but needs to be replicated in the bladder. Full article

Post-stroke upper limb pain is prevalent and challenging to manage once established. Early use of botulinum toxin can reduce spasticity and contracture development and has potential to prevent or reduce pain. A secondary analysis of the EUBoSS study was undertaken to report pain prevalence in people post-stroke with severe upper limb impairment and spasticity in a hyper/acute setting, identify if botulinum toxin Type-A (BoNTA) could prevent pain developing and reduce pain if already present and evaluate differences in analgesic use between BoNTA and placebo groups. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ninety-three participants (48F:45M) were randomised at a median of 11 days post-stroke (IQR 8–19) and included in the intention-to-treat analysis. Pain prevalence increased from 29.0% (95% CI [20.1–37.9%]) to 63.4% (95% CI [54.0–72.9%]) at six months. BoNTA treatment may prevent the development of pain at six months (OR = 0.42, 95% CI [0.18 to 1.01]) but not at three months (OR = 0.57, 95% CI [0.25 to 1.32]). The odds ratio for being on at least one analgesic at six months in the BoNTA group was 0.35 ([95% 0.14 to 0.87]). This secondary analysis suggests that early treatment of spasticity with BoNTA may potentially help prevent post-stroke upper limb pain and reduce analgesic use but appears less effective once pain is established. Further prospective studies are required to verify the hypotheses generated from this secondary analysis. Full article

Excessive gingival display (EGD) is most commonly attributed to vertical upper lip elevation, short lip length, or dentoalveolar disproportion. However, some patients exhibit gingival or mucosal visibility during smiling despite minimal vertical upper lip displacement, suggesting the presence of alternative dynamic patterns. This exploratory case series examined an inversion-dominant smile presentation and its documented modulation in association with conservative intraoral chemodenervation directed toward the marginal region of the orbicularis oris. Ninety-four patients with dynamic inversion during smiling were assessed using a qualitative rating aid (Armenti Inversion Scale, AIS) and a quantitative composite proportional measure of vermilion loss (ΔLv%). All patients received low-dose intraoral Onabotulinum toxin A (4–6 U) as part of routine aesthetic care. At Day 15 follow-up, a shift toward lower inversion grades was observed across the cohort, with a large proportion of patients showing minimal residual inversion. Quantitative ΔLv% values showed proportional changes that were directionally consistent with shifts in AIS grade. The functional alterations were mild, transient, and self-resolving. Preliminary inter-rater agreement for AIS and measurement repeatability for ΔLv% suggested acceptable internal consistency for exploratory reporting tools. These findings suggest that inward vermilion inversion may represent a potentially distinct dynamic contributor to gingival or mucosal exposure in selected individuals, and that conservative marginal chemodenervation was associated with transient modulation of this pattern with generally preserved oral competence. AIS and ΔLv% are preliminary documentation tools. Further studies incorporating objective neuromuscular assessment, three-dimensional imaging, and comparative designs are required to refine phenotypic characterization. Full article

Botulinum neurotoxin type A (BoNT/A) is intramuscularly injected for the treatment of, e.g., spasticity, cervical dystonia or facial lines. Several BoNT/A products with or without complexing proteins, with non-interchangeable dose units and various duration of effect claims, are approved but hard to compare. The goal of this study was to compare the complexing protein-free approved BoNT/A products IncobotulinumtoxinA (INCO), DaxibotulinumtoxinA (DAXI) and RelabotulinumtoxinA (RELA) in vitro and in vivo. BoNT/A protein content per 100 U was lowest in INCO and highest in DAXI (INCO 0.44, RELA 0.46, DAXI 0.58 ng/100 U). Relative bioactivity of INCO, DAXI and RELA was comparable (116, 104 and 117 U/100 labeled units). INCO and DAXI caused a maximum mouse digit abduction score (DAS) 2–3 days after IM injection of 20 or 40 U/kg. The DAS after 20 U/kg INCO was higher and showed a 10 days longer paralysis than DAXI at equivalent dosing. The in vivo spread of DAXI in the mouse gastrocnemius muscle was indistinguishable from that after INCO, and the spread of RELA ex vivo in porcine muscle was larger than INCO but equal to 0.9% NaCl. These results show the differences between 150 kDa botulinum type A toxin products beyond the published claims. Full article

Purpose: Giant inguinal hernias (GIHs) are rare and technically demanding conditions, associated with loss of domain and abdominal wall compliance. Preoperative botulinum toxin type A (BtxA) has been increasingly used in complex ventral hernia repair to facilitate abdominal wall relaxation; however, its role in GIHs surgery remains poorly defined. This scoping review aimed to map the literature on preoperative BtxA use in GIHs repair, focusing on technical protocols, patient selection, and areas of variability. Methods: A scoping review was conducted in accordance with PRISMA-ScR guidelines. MEDLINE, Embase, Web of Science, and Scopus were searched from inception to 10 October 2025. Studies reporting preoperative BtxA administration in adult patients undergoing GIHs repair were included. Data were extracted descriptively and synthesized narratively. Results: Seven observational and non-comparative studies published between 2019–2025 were included, comprising a total of 16 patients. Substantial heterogeneity was observed in BtxA protocols, with total doses ranging from 100 to 450 units, injection timing between 2 and 8 weeks preoperatively, and injection sites varying from 6 to 18. In several reports, BtxA was used as part of a multimodal preoperative strategy including progressive pneumoperitoneum. All studies targeted the lateral abdominal wall musculature, employed imaging guidance, and performed bilateral injections. Patient selection criteria and outcome reporting were inconsistent. Conclusions: Preoperative BtxA use in GIHs repair is limited and heterogeneous. No standardized protocol can be identified. Further anatomically focused and systematically designed studies are required to clarify the role of BtxA and to establish standardized preoperative protocols for this challenging surgical condition. Full article

Botulism is a neuroparalytic disease caused by exposure to botulinum neurotoxins produced by anaerobic spore-forming bacteria of the genus Clostridium. This disease occurs in both humans and wild and domestic animals, and is currently becoming an increasingly serious problem worldwide due to high animal mortality and economic losses. The clinical signs observed during the progression of botulism are nonspecific and difficult to unequivocally associate with this disease entity. The aim of this study is to present laboratory diagnostics of suspected botulism cases reported in Poland in 2022–2024, as well as to present the challenges encountered during laboratory investigations. The material for the study consisted of samples of liver, serum, digestive tract, feed, feces, straw, and water from drinking lines, sent to the National Veterinary Research Institute (NVRI) in relation to thirteen suspected cases of botulism, predominantly reported in poultry, but also in mink and cattle farms. The samples were analyzed using a mouse bioassay and conventional culture methods, as well as real-time PCR methods aimed at detecting the ntnh and bont genes, which determine the production of botulinum neurotoxins. Of the thirteen suspected cases analyzed, ten were confirmed by the detection of botulinum toxin (BoNTs) and/or the presence of the ntnh and bont genes in the tested material. Based on the results obtained, it was concluded that botulinum toxin type C was the etiological factor of botulism poisoning in most of the analyzed cases. In one case reported in cattle, poisoning occurred as a result of the mosaic variant of BoNT D/C. Due to the nonspecific signs of botulism and the time required for them to appear, laboratory diagnostics play a key role in detecting the disease. However, this process is complicated due to the high heterogeneity observed among Clostridium spp. strains, as well as difficulties encountered during the isolation of the microorganism and the possibility of loss of toxin-producing capacity at later stages of analysis. Full article

Facial neuromodulation with botulinum toxin has traditionally been approached from the perspective of wrinkle correction. However, facial expressions primarily arise from coordinated muscular interactions that convey both positive and negative emotional valence. A conceptual framework focused on muscular equilibrium rather than wrinkle severity may therefore offer a more comprehensive, reproducible, and clinically meaningful approach. In this article, we propose the Index of Muscular Equilibrium (IME) Framework, a conceptual model for aesthetic neuromodulation that integrates functional muscle mapping, validated severity scales, and a composite IME score to support personalized treatment planning and outcome assessment. The framework is derived from a narrative review of PubMed-indexed literature on facial muscle activity, emotional expression, and validated clinical assessment tools. It combines a Valence Map to classify positive- and negative-valence muscle groups, a standardized evaluation of static and dynamic hypertonus, a conceptual Plan Score to guide selective neuromodulation, and a feedback-based longitudinal workflow (the IME Loop). Together, these components enable structured assessment of muscular imbalance, integration of established wrinkle severity scales, and translation into individualized, function-oriented treatment strategies, with intended benefits including improved objectivity, reproducibility, and patient communication. By reframing treatment success from the duration of muscle blockade to the duration of expressive harmony, the IME Framework introduces testable constructs for future validation and offers a functional perspective on facial neuromodulation aligned with contemporary affective science. Full article