The Role of Botulinum Neurotoxin A in the Conservative Treatment of Fractures: An Experimental Study on Rats.

This paper explores the role of botulinum neurotoxin in aiding fracture recovery through temporary muscle paralysis. Specifically, it investigates the effects of botulinum neurotoxin-induced paralysis of the sternocleidomastoid muscle on clavicle fractures in rats. The research aims to assess safety, effectiveness, and the impact on fracture healing. Healthy male Albino Wistar rats were divided into four groups: clavicle fracture, botulinum neurotoxin injection, both, and control. Surgeries were conducted under anaesthesia, and postoperatively, animals were monitored for 28 days. Euthanasia and radiological assessment followed, examining fracture healing and muscle changes, while tissues were histopathologically evaluated. The modified Lane-Sandhu scoring system was used for the radiographic evaluation of clavicle fractures, and the results varied from complete healing to nonunion. Histopathological examination at 28 days postfracture showed fibrous tissue, mesenchymal cells, and primary callus formation in all groups. Despite varied callus compositions, botulinum neurotoxin administration did not affect clavicle healing, as evidenced by similar scores to the control group. Several studies have explored botulinum neurotoxin applications in fracture recovery. Research suggests its potential to enhance functional recovery in certain types of fractures. Theoretical benefits include managing muscle spasticity, aiding reduction techniques, and preventing nonunion. However, botulinum neurotoxin's transient effect and nonuniversal applications should be considered. The present study found that botulinum toxin had no clear superiority in healing compared to controls, while histological evaluation showed potential adverse effects on muscle tissue. Further research is essential to understand its risk-benefit balance and long-term effects.

Onabotulinumtoxina (craniotomy scar combined with cranial suture line injections) for persistent post craniotomy headache: Case series with long-term follow-up.

BACKGROUND: There is no defined preventive treatment protocol for persistent post-craniotomy headache. In several small case series and individual case reports onabotulinumtoxinA injected into the craniotomy scar has shown possible efficacy. What is lacking is long term follow-up and if focusing on the cranial suture lines along with the craniotomy scar can enhance improvement and provide more sustained benefit. METHODS: Retrospective chart review with case series. RESULTS: Four patients (three women, one man) with ICHD-3 defined persistent post craniotomy headache were treated using a novel onabotulinumtoxinA injection protocol. All the patients presented with continuous head pain of moderate to severe intensity. All had severe allodynia on the side of their craniotomy. All had significant reduction in quality of life. Our application of onabotulinumtoxinA involved injection into both the surgical scar and the transected/irritated cranial suture lines noted on neuroimaging and physical examination. With treatment all patients demonstrated significant benefit including a reduction in daily pain intensity (75%-100%), developing periods of pain freedom (2-7 days per week) and having a dramatic improvement in quality of life (close to 100% in all). The benefit was sustained for at least five years of follow-up. CONCLUSION: From our case series it appears that injection not only along the painful craniotomy scar but into the involved cranial suture lines provides positive efficacy and sustained improvement in patients with persistent post craniotomy headache.

Intradetrusor Versus Suburothelial Onabotulinum Toxin A in Adults with Neurogenic and Non-neurogenic Overactive Bladder Syndrome: A Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor injection for overactive bladder syndrome (OAB). METHODS: This systematic review is registered with PROSPERO (CRD42021237964). A licensed librarian surveyed Medline, EMBASE, Scopus, and Google Scholar databases to conduct a comprehensive search. Studies comparing suburothelial and intradetrusor techniques of OnabotA injection for OAB were included, along with clinical and urodynamic variables and complications. The studies were assessed for quality on the basis of Cochrane Collaboration guidelines and evaluated using statistical analysis via a random-effect model and I2 statistic. Data extraction and analysis were conducted using Covidence systematic review platform and Review Manager software. RESULTS: Six studies with 299 patients were included in the systematic review, with four reporting that suburothelial injection of OnabotA was as effective as intradetrusor injection and two reporting intradetrusor injection to be more effective. The meta-analysis found no significant difference between the suburothelial and intradetrusor groups for mean daily catheter or voiding frequency (mean difference: 2.12 [95% confidence interval (CI): -1.61, 5.84]) and the mean number of urgency/urge incontinence episodes (mean difference: 0.08 [95% CI: -1.42, 1.57]). However, a significant heterogeneity was found among the studies. Only the mean volume at first detrusor contraction showed a significant difference, being higher for suburothelial injection (mean difference: 33.39 [95% CI: 0.16, 66.63]). No significant difference was noted for mean compliance, mean bladder capacity, and mean maximum detrusor pressure. Urinary tract infections (UTIs) (p = 0.24) and acute urinary retention (p = 0.92) showed no significant difference between the two groups. The risk of bias varied among the studies. CONCLUSIONS: Suburothelial injection of OnabotA is as effective as intradetrusor injection in improving OAB symptoms, and it has similar complication rates. A higher mean volume of the first detrusor contraction was found in a urodynamic study with suburothelial injection.

A multicenter, double-blind, randomized, parallel-group, active-controlled, phase 3 clinical trial to compare the effectiveness and safety of two botulinum toxin type A formulations for improving moderate to severe glabellar wrinkles in Asians.

Botulinum toxin type A (BoNT-A) was first isolated in 1946, and since then, several formulations have been developed and widely used to treat wrinkles by inducing muscle paralysis. This multicenter, double-blind, randomized, parallel-group, active-controlled phase 3 clinical trial was designed to evaluate the efficacy and safety of a newly developed BoNT-A formulation, BMI2006, in improving moderate to severe glabellar wrinkles and to compare with existing onabotulinumtoxin A (OBoNT) injections. A total of 276 subjects were enrolled and received 20 units of the randomized material, which was intramuscularly injected into five different locations on the forehead. The primary endpoint, assessed at 4 weeks, showed no statistically significant difference in the improvement rate of glabellar wrinkles between the two groups, with BMI2006 demonstrating non-inferiority to comparator BoNT-A. Secondary endpoints, evaluated by both treating investigators and independent investigators, also exhibited similar improvement rates throughout the study period. Both groups reported high levels of satisfaction with no statistical difference between the two groups. Safety evaluations indicated mild and transient adverse events, with no serious reactions observed. In conclusion, BMI2006 is an effective and safe BoNT-A for treating glabellar wrinkles with an expected duration of action between 8 and 12 weeks.

Positive effect of self-exercise following Botulinum toxin injection on the permanence of the recovery among the patients with HFS and BFS: A clinical trial.

BACKGROUND: Botulinum toxin (BoNT) injection serves as the primary modality for addressing hemifacial spasm (HFS) and blepharospasm (BFS), which are prevalent movement disorders affecting the craniofacial region. However, even though the short-term effectiveness of the botulinum injection may reach over 80%, the long-term effectiveness is still a debatable point Herein, we aim to investigate whether facial self-exercise following the BoNT injection can extend the time period of effectiveness. METHODS: In this study, 51 volunteers who received Onabotilinumtoxin A (BoNTA) treatment for the diagnosis of HFS or BFS, were randomized into 2 groups. A detailed instruction about the self-exercise was given by an experienced physician to the subjects in Group 1. Volunteers were asked to repeat the exercise program afterward and continue to each movement for 5 seconds, to repeat each movement 10 times with a 10-second break, every day, 3 times a week for 1 week. hemifacial spasm grating scale (HSGS) and Jankovic scales were used to assess the efficacy of the treatment. RESULTS: Both groups are similar to each other based on demographic features and the severity of the diseases. According to HSGS and Jankovic scales, at the end of the first month, there was no significant difference between the groups. At the end of the third month, the improvement achieved in the first month remained the same in each parameter in Group 1. On the other hand, in Group 2, most of the values returned to the baseline. CONCLUSION: Facial self-exercise following the botulinum toxin application may extend the period of effectiveness of botulinum toxin treatment the subjects with HFS and BFS.

Subclinical effects of botulinum toxin A and microwave thermolysis for axillary hyperhidrosis: A descriptive study with line-field confocal optical coherence tomography and histology.

Botulinum toxin A (BTX) and microwave thermolysis (MWT) are standard axillary hyperhidrosis treatments, but comparison of their subclinical effects is lacking. Line-field confocal optical coherence tomography (LC-OCT) is a promising non-invasive imaging tool for visualizing tissue-interactions. This study aimed to describe subclinical effects of BTX and MWT for axillary hyperhidrosis with LC-OCT-imaging compared to histology. This study derived from an intra-individual, randomized, controlled trial, treating axillary hyperhidrosis with BTX versus MWT. Subclinical effects based on LC-OCT images from baseline and 6-month follow-up (n = 8 patients) were evaluated and compared to corresponding histological samples. At baseline, LC-OCT visualized eccrine pores at the skin surface and ducts in the upper dermis (500 µm), but not deeper-lying sweat glands. Histology identified entire sweat glands. Six months post-treatment, LC-OCT revealed no detectable morphology changes in any BTX-treated axillae (100%), while recognizing obstructed eccrine pores and atrophy of eccrine ducts in most MWT-treated axillae (75%). Histology corroborated LC-OCT findings, while also showing substantial changes to entire sweat glands. LC-OCT enabled visualization of subclinical alterations of superficial eccrine ducts after MWT and unchanged morphology after BTX. LC-OCT is a promising tool for non-invasive assessment of treatment-specific tissue-interactions that can be complementary to histology.

Trends in American Plastic Surgery Procedures (2005-2019): Observing the Growth Rate of Maxillofacial Surgery and Cosmetic Minimally Invasive Procedures in ASPS Data.

BACKGROUND: This study explores the dynamic changes in plastic surgery practices, focusing on the growth rates across different subcategories, particularly highlighting the trends in the United States. OBJECTIVES: To analyze evolving trends in plastic surgery using statistical methods, providing insights into the changes and growth patterns in various segments over time. MATERIALS AND METHODS: Utilizing data from 2005 to 2019 from the American Society of Plastic Surgeons, the authors, conducted a comprehensive statistical analysis using the SPSS program to investigate trends in plastic surgery procedures. RESULTS: Our analysis revealed no significant differences in year-on-year growth rates between cosmetic and reconstructive surgery. However, in reconstructive surgery subcategories, maxillofacial surgery showed the highest mean growth rate at 11.61%, though this was not statistically significant. In cosmetic minimally invasive procedures, soft tissue filler injections and botulinum toxin A injections experienced notably higher growth trends compared with microdermabrasion. CONCLUSION: The findings suggest that practitioners considering a career in plastic surgery should not focus solely on choosing between reconstructive and cosmetic surgery. Recognizing substantial growth in cosmetic minimally invasive procedures, especially botulinum toxin A injections and fillers, is vital for making informed career decisions.

Combined rehabilitation therapy with botulinum toxin to the upper limbs for acute spinal cord injury: A case report.

INTRODUCTION: Patients with spinal cord injury (SCI) and incomplete paralysis may experience muscle immobilization due to functional impairment of agonist and antagonist muscles. This can induce spasticity and pain, with the risk of contracture increasing as the period of immobilization increases. This could be aggravated by pain, which interferes with rehabilitation. There is no established treatment for pain and joint contractures caused by acute SCI. Botulinum therapy plays a role in relieving muscle tension. Here, we report a case of acute SCI in which botulinum therapy was administered. CASE PRESENTATION: The patient experienced a C5-cervical SCI due to a road traffic accident, with marked paralysis in the upper and lower limbs below the C5 level. The patient had persistent elbow flexion since the SCI and complained of excruciating pain, making adequate rehabilitation difficult. Botulinum toxin was administered to the biceps and brachialis muscles 15 days after the SCI. After administration, the patient experienced a reduction in pain with relaxation of the elbow flexor muscles, and rehabilitation treatment was resumed. This patient's contracture did not worsen, his pain decreased, and he was able to initiate self-feeding training. DISCUSSION: In this case, occupational and physical therapy was administered with botulinum therapy. Together, they successfully reduced pain. Botulinum therapy provides analgesia and muscle relaxation and may lead to functional recovery, and we believe that treatment can be considered even in the acute phase.

The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model.

OBJECTIVE: Migraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA-induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene-related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP-25 through western blot analysis to gain insights into the mechanistic action of BoNT/A. METHODS: BoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post-inflammation, and alterations in CGRP release were evaluated. Changes in SNAP-25 levels were determined using western blot analysis. RESULTS: Upon CFA-induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP-25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A-treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release. CONCLUSION: Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP-25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model.

Sequential administration of peripheral nerve blocks and onabotulinumtoxinA for the treatment of chronic migraine and other headache disorders-A retrospective tolerability and safety study.

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Botulinum toxin and hyperhidrosis of the amputation stump in war amputees.

INTRODUCTION: Stump hyperhidrosis is a common condition after lower limb amputation. It affects the prosthesis use, and the quality of life of patients. Several case reports tried to prove benefit of using Botulinum toxin in its treatment. AIM: This study was to conduct a larger workforce clinical trial and to demonstrate benefits of botulinum toxin injection in the treatment of stump hyperhidrosis. METHODS: A prospective study was conducted. War amputees who complained of annoying excessive sweating of the stump were included. They received intradermal injection of botulinum toxin A in the residual limb area in contact with prosthetic socket. Abundance of sweating and degree of functional discomfort associated with it were assessed before, after 3 weeks, 6 and 12 months. RESULTS: Seventeen male patients, followed for post-traumatic limb amputation were included in the study. Discomfort and bothersome in relation to Hyperhidrosis did decrease after treatment (p<0,001). Reported satisfaction after 3 weeks was 73,33%. Improvement of prothesis loosening up after 3 weeks was 72,5% [±15,6]. Mean injection-induced pain on the visual analogue scale was 5.17/10 (±1.58). The mean interval after the onset of improvement was 5.13 days [min:3, max:8]. The mean time of improvement was 10.4 months after the injection [min:6, max:12]. No major adverse events were reported following treatment. CONCLUSION: Intradermal injections of botulinum toxin in the symptomatic treatment of stump hyperhidrosis are effective and have few adverse effects. It improves the quality of life of our patients thanks to a better tolerance of the prosthesis.

Paradoxical masseteric bulging after botulinum neurotoxin type A injection.

Paradoxical masseteric bulging refers to an unexpected occurrence of masseter muscle bulging or protrusion following the administration of botulinum toxin injections, contrary to the anticipated muscle weakening effect. It may occur secondary to toxin failing to diffuse through the entire masseter muscle due to the presence of an inferior tendon structure within the superficial masseter that divides it into a superficial and deep belly. We report a clinical case of paradoxical masseteric bulging in a female in her late 40s who developed this adverse effect within a week of her masseter botulinum neurotoxin type A injections. We also describe the masseter two-site injection technique for the management of this complication.

Systematic review of the utilization of botulinum toxin in Mohs micrographic surgery.

The use of botulinum toxin for off-label indications has become more prevalent, but the specific benefits in Mohs micrographic surgery (MMS) have not yet been fully elucidated. A systematic review was performed of PubMed, Cochrane, EMBASE, and Scopus databases to identify all articles describing the use of botulinum toxin in MMS. Analysis was subdivided into scar minimization, parotid injury, and pain management. A total of nine articles were included. Scar minimization and treatment of parotid injury were the most reported uses. One case reported the use of botulinum toxin for pain management. Off label uses of botulinum toxin are being explored. Additional research is warranted to determine the efficacy and utility of botulinum toxin in MMS.

Vestibulodynia: Clinical characteristics, first-line treatments, and factors associated with escalation of treatment with EMG-guided injections of botulinum toxin in a retrospective french cohort study.

BACKGROUND: Vestibulodynia is a highly prevalent chronic pain disorder affecting the vulva having a major impact on women's physical, psychological, and sexual well-being. It remains an underrecognized disease that responds insufficiently to therapies such as physiotherapy and medication. AIM: To assess the global efficacy of first-line therapies and factors associated with treatment escalation in women with vestibulodynia. PATIENTS AND METHODS: This retrospective cohort study was conducted at the dermatology outpatient clinic of the University Hospital in Besancon (France) between 2013 and 2017 and follow-up until 2021. RESULTS: Among 132 patients, the mean [standard deviation] age at diagnosis was 27.2 [±9.45] years, with an average duration of symptoms of 42.3 [±37.92] months. Most cases comprised provoked (75.0%) or secondary (72.7%) vestibulodynia. At least one comorbid pain or psychologic condition was identified respectively in 63 (47.7%) and 23 patients (54.5%). Vulvar hyperesthesia associated with pelvic floor muscle dysfunction was present in 121 patients (91.6%) and vulvar erethism was noted in 94 patients (71.2%). First-line treatments consisted of pelvic floor physiotherapy with biofeedback in 85% of patients, associated with amitriptyline in 36% of cases, and of additional lidocaine cream in 17%. Fifty-two patients (39%) presented at least a good response to first-line treatment, with only 21 (15%) being in complete remission, irrespective of therapeutic strategy (p = 0.25). Botulinum toxin injections were performed in 54 patients. Patients with either primary vestibulodynia (p = 0.04) or spontaneous vestibulodynia (p = 0.03) were more likely to receive this treatment. CONCLUSION: Our study highlights the current lack of efficacy of first-line treatments in vestibulodynia. Considering the high prevalence of muscular dysfunction, botulinum toxin injections are of particular interest despite a lack of randomized controlled trials in this indication.

Upper Limb Casting Application Post-Botulinum Toxin Injection for Elbow Spasticity: A Guided Casting Protocol.

ABSTRACT: Casting is an effective adjunctive treatment, which increases the effects of botulinum toxin on patients with spasticity. The evidence for casting as an adjunctive therapy post-botulinum toxin has been well documented in the literature. However, standardized casting protocols are lacking, with no published descriptions of upper limb casting application post-botulinum toxin injection for spasticity. In this article, we will describe our experience regarding the application of upper limb casting as an adjunctive therapy for elbow spasticity, detailing indications, contraindications, and description of our protocol (materials required and technique).

Nerve Block Guided by Anatomic Landmarks Only Reduces Pain in Botulinum Toxin Type A Treatment for Glabellar and Forehead Wrinkles.

BACKGROUND: Botulinum toxin type A is widely used to treat glabellar and forehead wrinkles, but the pain caused by multiple injections often deters patients from receiving long-term treatment. Despite several methods used to alleviate this pain, consistency and effectiveness remain a challenge. Therefore, this study aimed to evaluate the effectiveness and safety of nerve block guided by anatomic landmarks only in reducing pain associated with botulinum toxin type A injections. PATIENTS AND METHODS: Between 2018 and 2022, the study enrolled 90 patients divided into 3 groups: the nerve block group (n = 30), the lidocaine cream group (n = 30), and the control group (n = 30). In the nerve block group, a landmarks-based technique was used to perform the nerve block. The study collected general information and comorbidities, and recorded pain at each point and time spent on preparation and treatment for each patient's forehead and glabellar area on each side. Patient-reported outcomes and complications were followed up at 2, 4, and 12 weeks after the injections. RESULTS: The nerve block group had significantly lower total pain scores in all regions compared to the lidocaine cream and control groups (P < 0.01). There were no significant differences in patient-reported outcomes between the groups at any follow-up point. Additionally, the complication rates related to injection were low and comparable among the 3 groups. CONCLUSIONS: Nerve block guided by anatomic landmarks only is a safe, effective, and consistent approach to reduce pain during botulinum toxin type A treatment for glabellar and forehead lines. This technique may offer advantages over other methods used to alleviate the pain associated with these injections.