Search Results (506)

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

Background: Spasticity is a major contributor to pain, impaired mobility, contractures, and caregiver burden in children with cerebral palsy. Intrathecal baclofen (ITB) is an established treatment for severe generalized spasticity when rehabilitation, oral medications, and focal interventions are insufficient or poorly tolerated. Methods: This critical review synthesizes current evidence on ITB in children with cerebral palsy, focusing on patient selection, screening, rehabilitation goals, functional outcomes, complications, and long-term management. Results: Available evidence consistently demonstrates substantial and sustained tone reduction with ITB, with associated improvements in comfort, positioning, ease of care, pain, and selected quality-of-life domains. However, gains in gross motor function are variable and depend on baseline motor phenotype, individualized treatment goals, and careful dose titration. Device-related complications, infections, catheter dysfunction, overdose, and withdrawal remain clinically significant risks requiring specialized multidisciplinary follow-up. Compared with selective dorsal rhizotomy and botulinum toxin injections, ITB provides a reversible and programmable option particularly suited to children with severe, generalized spasticity and high caregiving needs. Conclusions: ITB represents an important component of comprehensive, goal-directed spasticity management in appropriately selected children. Further high-quality longitudinal and comparative studies are needed to define long-term functional and cost-effectiveness outcomes better. Full article

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

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

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: Post-stroke neuropathic pain, particularly central post-stroke pain and facial pain syndromes, continues to be challenging to manage with conventional pharmacological approaches. While botulinum toxin A (BoNT-A) is well established for treating spasticity after stroke, its use in the management of central neuropathic pain remains less well established. Methods: This report presents two cases of patients with refractory neuropathic pain following ischemic cerebrovascular accidents who achieved significant pain relief through subcutaneous botulinum toxin administration, after failure of multiple conventional and intramuscular BoNT-A approaches. Results: Case 1 involves a 66-year-old patient with 18 years of post-stroke hemicorporeal pain who responded dramatically to subcutaneous BoNT-A injections after extensive prior treatment failures. Case 2 describes a 54-year-old with trigeminal-region and mandibular pain following ICA dissection who achieved complete pain resolution at facial sites with subcutaneous administration of BoNT-A. Conclusions: These cases demonstrate the potential efficacy of subcutaneous botulinum toxin for managing post-stroke neuropathic pain in selected patients and suggest a mechanism of action related to peripheral pain sensitization rather than motor denervation. Our findings support further investigation of subcutaneous administration techniques for pain management in specialized centers. 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

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

Introduction: As multimodal therapy for esophageal cancer advances, addressing immediate and long-term functional outcomes following surgery has become more important. Despite surgical advancements, delayed gastric conduit emptying (DGCE) remains a primary cause of functional impairment after esophageal cancer resection. The literature addressing pylorus management following minimally invasive esophagectomy (MIE) is scarce. The effects of pyloric drainage with pyloromyotomy or postoperative approaches such as intrapyloric Botox injection or dilatation on the incidence and course of DGCE were the focus of this study. Methods: A retrospective analysis of consecutive patients after minimally invasive esophagectomy with thoracic esophagogastric anastomosis and gastric tube reconstruction between 2014 and 2023 was performed. Univariate analyses were used to identify significant patient-, tumor-, and procedure-related factors affecting DGCE. Results: A total of 276 patients were included. DGCE was observed in 80 (28.9%) patients. Demographics did not differ with statistical significance. Postoperative complications were not increased in patients with DGCE. Pyloric intervention (PI) did not reduce postoperative occurrence of DGCE (PI: n = 19/23.75% compared to no PI: n = 62 (30.5%), p = 0.342). Median length of hospital stay was significantly longer, and total costs were significantly higher in patients with DGCE (p = 0.03 and p = 0.047, respectively). Analysis of endoscopic approaches was not associated with a statistically significant difference between botulinum toxin injection and pyloric dilatation with regard to reinterventions. Conclusions: While DGCE is frequent after esophagectomy, it is not associated with short-term morbidity but with prolonged total hospital stay and increased costs. Intraoperative pyloric intervention does not influence the incidence of DGCE after esophagectomy and endoscopic management was associated with therapeutic success, but choice of specific, optimal approach remains elusive. Novel concepts, including preoperative dilatation should be investigated. Full article

Purpose: This study compared the therapeutic efficacy of different bladder monotherapies and multimodal therapy in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Materials and methods: In total, 190 patients with a confirmed diagnosis of IC/BPS were treated with different bladder therapies. The bladder monotherapies included intravesical platelet-rich plasma (PRP) injection (n = 60), intravesical botulinum toxin A (BoNT-A) injection (n = 33), intravesical hyaluronic acid (HA) instillation (n = 36), and low-energy shock wave (LESW) bladder therapy (n = 61). Multimodal therapy (MMT) was provided to patients who had unsuccessful initial bladder treatment targeting chronic inflammation, urothelial dysfunction, bladder pain, pelvic floor muscle pain, psychological stress, and lower urinary tract dysfunction. The treatment outcome was assessed using self-reported Global Response Assessment scores at 3 months and during the follow-up time points after bladder treatment. Results: Thirty-one patients received MMT. The 3-month success rates of bladder therapy were 55.0% for PRP injection, 57.6% for BoNT-A injection, 50.0% for HA instillation, 46.7% for LESW bladder therapy, and 58.1% for MMT. The success rates of bladder monotherapy decreased after 6 months. However, the success rate of MMT increased at 9 (67.7%) and 12 (73.1%) months. Patients treated with MMT exhibited improvement in glomerulation grade after cystoscopic hydrodistention. Only patients with successful treatment outcomes after MMT had improvement in bladder pain severity and pelvic floor muscle pain parameters. Conclusions: Bladder monotherapy such as PRP injection, BoNT-A injection, HA instillation, and LESW bladder therapy had successful treatment outcomes in patients with IC/BPS. In patients who had unsuccessful initial bladder therapy, the 3-month success rate of MMT was 58.1% and sustained improvement with time, particularly in the improvement of bladder pain and PFM pain severity. Full article

Botulinum neurotoxin injections are used off-label to treat chronic pain, but their efficacy is limited and paralytic effects restrict clinical utility in these applications. Here, we investigated whether combining the light chain and translocation domains of botulinum neurotoxin A (BoNT/A) with the GM1-binding B subunit of cholera toxin would be beneficial in silencing pain-associated sensory neurons. Chimeric ChoBot was assembled via a coiled-coil linking technology and was shown to retain the enzymatic activity of BoNT/A in vitro and in vivo. In cultured dorsal root ganglion neurons, ChoBot cleaved SNAP25 in a calcitonin gene-related peptide (CGRP)-rich subpopulation of sensory neurons, resulting in marked inhibition of CGRP release. ChoBot had a lesser effect on the compound muscle action potentials of the rat gastrocnemius muscle than BoNT/A following subcutaneous injections. In rat models of pain, including chemotherapy-induced peripheral neuropathy, intraplantar administration of ChoBot significantly attenuated mechanical allodynia. Immunohistochemical analysis confirmed SNAP25 cleavage in NF200- and CGRP-expressing sensory fibres in the epidermis following a single injection. ChoBot also mediated SNAP25 cleavage in human neuroblastoma cells in culture. Together, these findings indicate that ChoBot enables a silencing of pain-associated sensory pathways, providing a new strategy for the development of new long-lasting analgesics for chronic pain. 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