Botulinum Toxin Research Articles

Botulinum Toxin A for the management of temporomandibular myofascial pain - a cohort study

Myofascial pain represents the largest subgroup of TMD (Temporomandibular Disorders), which accounts for a common cause of non-dental orofacial pain. The management of TMD is complex, due to the chronic nature of the condition, alongside acute episodes presenting to the clinician. A fundamental part of TMD management is consideration of the bio-psycho-social element in the aetiology of TMD. First-line treatment of myofascial TMD includes; early diagnosis, explanation and education and conservative self-care measures. More recently, Botulinum Toxin A (BTX-A) is being used increasingly as an adjunct to conservative management of muskulo-skeletal pain disorders, due to its muscle-relaxant and analgesic properties. However, the scientific evidence regarding this is conflicting and it has been suggested that there is insufficient evidence to support the efficacy of BTX-A. A mixed method analysis of a TMD-myofascial pain cohort who underwent BTX-A injections to assess the effectiveness of masseteric BTX-A was carried out. 149 patients completed one round of masseteric BTX-A treatment, of whom 61 completed an additional round of BTX-A. In total, 398 masseter muscles were injected. The average VAS pain score pre-operatively was 8/10, compared with a postoperative mean score of 3/10 at 6 weeks after treatment. The mean percentage reduction in pain was 50%. Pain scores were classified as mild (≤4) , moderate (≤7) or severe (≥8). Pain scores and quality of life scores were found to improve considerably more in the severe pain group in comparison to the mild group. Complete resolution of symptoms was reported in 21% of patients (n=31). The treatment significantly improved patients’ reported pain and quality of life scores, highlighting key beneficial effects for the myofascial pain subgroup of TMD.

Impact of botulinum toxin type A on tooth movement and bone remodeling in male Wistar rats

ObjectiveWe evaluated whether the use of botulinum neurotoxin type A (BTX-A) in masticatory muscles influences tooth movement and bone remodeling. DesignSeventy-seven male Wistar rats were allocated to the groups: S - Saline (n=20); SM - Saline with movement (n=20); BT - Botulinum toxin (n=18); BTM - Botulinum toxin with movement (n=19). On day 1, 0.02mL of sterile 0.9% saline was administered to groups S and SM and BTX-A (1U in 0.02mL of saline) to groups BT and BTM, in the masseter and temporal muscles laterally. On day 30, a nickel titanium spring was installed to move the first maxillary molar and euthanasia was performed on days 32 and 51. Tooth displacement, maxillary and mandibular bone volumes, collagen neoformation, bone and root resorptions, and masseter morphometry were assessed. Statistical analysis was conducted (p < 0.05). ResultsA higher percentage of type I collagen was observed in the BT than in the S group on day 51 and lower mass, length, and diameter of the masseter fibers in BT and BTM (p < 0.05). Tooth displacement, bone volume, bone and root resorptions, hyaline area, and masseter height showed no difference among groups with and without BTX-A, regardless of tooth movement (p > 0.05). ConclusionsBTX-A did not interfere with tooth displacement, bone volume, and dental and periodontal tissues related to tooth movement in rats; it increased mature collagen in animals without tooth movement; and it caused a decrease in the mass, length, and diameter of the masseter fibers.

Real-World Use of Intradetrusor Botulinum Toxin Injections: A Population-Based Study from France.

In recent decades, intradetrusor injections of botulinum toxin A (BoNT-A) have been widely applied to treat incontinence in both idiopathic overactive bladder (iOAB) and neurogenic detrusor overactivity incontinence (NDOI). This analysis, based on the French National Hospital Discharge Database (PMSI), aims to describe real-world trends in intradetrusor BoNT-A use between 2014 and 2022. Among 32,864 patients who received at least one intradetrusor BoNT-A injection, 18,320 (55.7%) had conditions coded under iOAB, 13,376 (40.7%) under NDOI, and 1168 (3.6%) under other indications. The overall mean interval between two intradetrusor BoNT-A injections was 9.7 months, ranging from 8.7 months in patients with multiple sclerosis (MS) to 11.5 months in patients with cerebral pathologies. The median number of injections was two (quartile 1-quartile 3, 1-4) in patients with spina bifida, whereas it was five (2-10) in those with MS. Only 31% of patients with iOAB received more than two intradetrusor BoNT-A injections. Regardless of its indication, BoNT-A was well tolerated. Adverse events occurring during or requiring hospitalization included infections (3.8%), hematuria (0.53%), and bleeding episodes necessitating transfusions (0.11%), all recorded within the initial month following BoNT-A injection. Our analysis of the PMSI database highlights a broad spectrum of intradetrusor BoNT-A injection practices.

Safety and Effectiveness of Synchronized Monopolar Radiofrequency and HIFES in Patients Injected With Botulinum Toxin.

Botulinum toxin (BT) has become one of the most frequently sought aesthetic procedures for wrinkle reduction. This study investigated the effectiveness and safety of a novel device using radiofrequency (RF) and high-intensity facial muscle stimulation (HIFES) in patients injected with BT. Twelve patients were divided into an Active (N=10) and a Control group (N=2), where the Active received four treatments and the Control none. The facial expressions documented by digital photographs (neutral) and videos (frown, smile, surprise expressions) were taken at all visits (baseline, after last Tx, 1 and 3-month follow-ups) and were evaluated using the Global Aesthetic Improvement Scale (GAIS) and 3D automated analysis. The subject's therapy comfort and satisfaction were assessed. The Active group reported high satisfaction with treatment comfort (6.3&plusmn;0.2 points on the 7-point Likert scale). 3D analysis showed reduced wrinkle severity (37.4%) and volume increase (+1.5 mL) on the cheeks at 3 months. GAIS evaluation demonstrated the most prominent improvement in smiling facial expression by 2.2&plusmn;0.1 points. No adverse events were observed. The study results suggest that the combination of HIFES and synchronized RF is a safe and effective treatment for improving facial appearance and muscle tone in patients injected with BT. J Drugs Dermatol. 2024;23(11):937-942.&nbsp; doi:10.36849/JDD.7938.

Investigating the impact of botulinum toxin type a on the migration of normal human dermal fibroblasts: An invitro wound healing assay.

Botulinum toxin A (BoNT-A) is widely utilized in the management of hypertrophic and keloid scars. One proposed mechanism for scar prevention involves the inhibition of fibroblast migration in scars by BoNT-A. However, the data regarding the effect of BoNT-A on the migration of normal human dermal fibroblasts (NHDF) is limited. The aim of this study was to investigate the inhibitory effect of different types and dilutions of BoNT-A on the migration of NHDF. In vitro scratch wound assay, NHDF cells were cultured, incubated, and subjected to scratching using a sterile tip. Subsequently, the scratched NHDF monolayer was treated with different types of BoNT-A, including onabotulinumtoxinA (ONA), incobotulinumtoxinA (INCO), prabotulinumtoxinA (PRABO), or letibotulinumtoxinA (LETI), at varying concentrations of 10, 20, 25, 40, 50, and 100 units/milliliter (U/mL). Additionally, abobotulinumtoxinA (ABO) was administered at concentrations of 33, 50, 66, 71, 100, 150, 300, and 500 U/mL. Normal saline solution (NSS) served as a negative control. The extent of NHDF migration was evaluated by comparing each dilution of BoNT-A with the controls using high-content imaging at the 48-h time point. Furthermore, the viability of the of NHDF was assessed. The concentrations of 25, 40, and 50 U/mL of ONA (p < 0.001) and 25 U/mL of LETI (p < 0.05) demonstrated significantly inhibited NHDF migration in comparison to the control group. Conversely, all dilutions of PRABO, INCO, and ABO exhibited comparable NHDF migration to that of the control group. Regarding NHDF viability, no significant decrease was observed across any of the BoNT-A types and dilutions. Different types and dilutions of BoNT-A demonstrated variable inhibitory effects on NHDF migration invitro. The selection of BoNT-A formulation may significantly impact the clinical outcome of scar prevention related to fibroblast migration.

Evaluation of craniocervical posture after myofascial pain treatment in adults with bruxism: A randomized clinical trial

BackgroundDespite numerous clinical studies on bruxism management, critical evaluation parameters, including the impact of bruxism pain on quality of life and secondary issues like changes in craniocervical posture, are often disregarded. Research questionEvaluate the effect of two treatments on the craniocervical posture of adult patients with myofascial pain. MethodsThis parallel randomized clinical trial included 60 patients with myofascial pain due to probable bruxism that fulfilled the study requirements. A computer-generated random sequence was used to allocate treatments: botulinum toxin-A or occlusal appliance. Follow-up time was 3 and 6 months. Kyphosis angle (α) and head posture measurement by cervical radiograph were assessed using two-way repeated measures ANOVA (alpha = 0.05). ResultsSixty patients were randomized (mean age 30 ± 7.6) and 6 were excluded from the analysis (did not attend follow-up). No statistically significant difference was observed for the head posture measure (p = 0.98) and kyphosis angle (p = 0.74). Mild pain was reported by one patient after botulinum toxin-A application. SignificanceResults indicate that craniofacial posture does not seem to be influenced by the treatment of pain in bruxers. If a better posture is desired, this should probably be targeted with other therapies. Trial registrationClinical Trials NCT03456154.

Sexual Dysfunction in Patients with Overactive Bladder Syndrome Treated with Botulinum Toxin

Introduction: Overactive bladder (OAB) is a syndrome of the lower urinary tract characterized by urinary urgency, frequency, and nocturia, with or without urgency urinary incontinence. OAB significantly impacts all aspects of life—social, psychological, physical, professional, domestic, and sexual—for both women and men. The aim of this study was to investigate sexual dysfunction in both women and men with OAB treated with intravesical onabotulinumtoxinA (Botox) injections using the Sexual Quality of Life questionnaire in two versions: female (SQoL-F) and male (SQoL-M). Methods: Forty sexually active patients (thirty women and ten men) with idiopathic OAB were recruited. Patients completed the SQoL-F or SQoL-M questionnaire before treatment, and again at 3 and 6 months after treatment with intravesical onabotulinumtoxinA injections. Results: All 40 patients completed the study (30 women and 10 men). There were no statistically significant differences in SQoL results before the procedure or at 3- and 6-months post-treatment. Conclusions: OAB treatment with onabotulinumtoxinA did not significantly affect the quality of sexual life in either women or men. Further research is needed using questionnaires specifically designed to assess the sexual life of patients with OAB, especially in men.

Smile Dessigning with Botulinum Toxin A in Dentistry

Smile Dessigning with Botulinum Toxin A in Dentistry

Immediately Injections of Botulinum Toxin A After Surgical Excision for Ear Keloids: A Retrospective Study.

Ear keloids are pathologic scar hyperplasia in the ear region. The most therapeutic approach was surgical shave excision with radiation therapy. However, radiation therapy is easily delivered to healthy surrounding tissues. In the last years, injections with botulinum toxin type A (BTX-A) have been proven to improve surgical scars effectively in clinical trials. This study aimed to evaluate the effect of immediate injections of BTX-A after surgical excision for ear keloids. From January 2020 to January 2023, 33 consecutive patients with ear keloids were enrolled. All patients underwent scar excision and revision at the same time when they needed BTX-A. It was injected into surgical wound closure immediately after surgery. The results of this study were evaluated at follow-up from 7 to 18 months using the Vancouver Scar Scale (VSS) and the Visual Analogue Scale (VAS). From January 2020 to January 2023, 33 patients received concomitant therapy of immediate injections of BTX-A after surgery for ear keloids. The patients were evaluated at follow-ups lasting 7 to 18 months. Only one case recurred within the follow-up period, and no adverse effects were reported. This study demonstrates that significant cosmetic outcomes in ear keloid treatment were achieved after early postsurgical BTX-A injections. The patients reported high satisfaction and few complications.

Implications of the non-neuronal cholinergic system for therapeutic interventions of inflammatory skin diseases.

The pivotal roles of acetylcholine (ACh) in physiological processes encompass both the nervous and non-neuronal cholinergic systems (NNCS). This review delineates the synthesis, release, receptor interactions, and degradation of ACh within the nervous system, and explores the NNCS in depth within skin cells including keratinocytes, endothelial cells, fibroblasts, macrophages, and other immune cells. We highlight the NNCS's essential functions in maintaining epidermal barrier integrity, promoting wound healing, regulating microcirculation, and modulating inflammatory responses. The potential of the NNCS as a therapeutic target for localized ACh regulation in the skin is discussed, though the translation of these findings into clinical practice remains uncertain due to the complexity of cholinergic signalling and the lack of comprehensive human studies. The review progresses to therapeutic modulation strategies of the NNCS, including AChE inhibitors, nicotinic and muscarinic receptor agonists and antagonists, choline uptake enhancers, and botulinum toxin, highlighting their relevance in dermatology. We highlight the impact of the NNCS on prevalent skin diseases such as psoriasis, atopic dermatitis, rosacea, acne, bullous diseases, hyperhidrosis and hypohidrosis, illustrating its significance in disease pathogenesis and therapy. This comprehensive overview aims to enhance understanding of the NNCS's role in skin health and disease, offering a foundation for future research and therapeutic innovation.

Dermatologic Procedures for the Treatment of Seborrheic Dermatitis.

This paper examines alternative procedural interventions for Seborrheic Dermatitis (SD), aiming to offer clinicians more treatment options and encourage further research. A search was conducted on PubMed using specific search terms related to SD and various dermatological procedures. Studies in English, focusing on SD in human patients, and in-office treatments were included. Data were analyzed for procedure type, effectiveness, and side effects. Nine studies were reviewed, covering phototherapy, indole-3-acetic acid photodynamic therapy (IAA-PDT), Picosecond Nd:YAG laser, botulinum toxin (BoNT) injections, triamcinolone injections, hair growth factor therapy, and precision cryotherapy. Most showed significant efficacy in small cohorts with high patient satisfaction. Hair growth factor therapy had long-term benefits, while narrow-band ultraviolet B phototherapy showed relapse within one month. Intense pulsed light with supramolecular salicylic acid, IAA-PDT, and laser therapy reduced sebum output and Malassezia furfur. Triamcinolone injections were effective against SD's immunological aspects. Hair growth factor therapy and precision cryotherapy have been successfully used to treat scalp SD. The role of BoNT in SD is still being explored; however, current evidence does not support its use. Limited data reveal the need for further research on dermatological procedures for SD. These methods show promise for better patient compliance but face challenges such as cost, variable effectiveness, and unknown long-term safety. Future research should focus on protocol standardization and comprehensive evaluation of long-term outcomes. J Drugs Dermatol. 2024;23(10):819-824. doi:10.36849/JDD.8116.

Botulinum Toxin Treatment in a Patient with Facial Paralysis

Botulinum Toxin Treatment in a Patient with Facial Paralysis

Bilateral hand dystonia following high-velocity thrust manipulation: a case report.

Thrust manipulation is one of the most commonly used techniques for managing musculoskeletal pain in clinical practice. This involves the application of a high-velocity, low-amplitude force directed to the joints with the intent of achieving joint cavitation. This current case report describes a female in her mid-20s who presented with excessive bilateral and involuntary hand muscle contractions after bilateral thrust manipulation. Dystonia appeared both at rest and during voluntary movements but was aggravated by actions such as finger flexion or spreading and disappeared during sleep. A diagnosis of complex regional pain syndrome (CRPS) type I combined with dystonia was made. Prednisolone administered between 2 and 5 weeks after symptom onset significantly reduced CRPS symptoms, but intramuscular botulinum toxin injection 5 weeks after symptom onset was ineffective at controlling her symptoms. Seven weeks after symptom onset, the patient was administered 2 mg trihexyphenidyl oral twice a day, 2.5 mg diazepam oral twice a day and 5 mg baclofen oral three times a day for 1 month and this significantly reduced dystonia, but complete resolution was not achieved. Clinicians should be aware that dystonia is a rare complication of thrust manipulation.

Pharmacological Treatment of Tourette Disorder in Children.

Background: Tourette disorder (TD) is a neurodevelopmental disorder characterized by childhood onset of tics lasting more than one year, with multiple motor tics and at least one phonic tic at some point during the course of the symptoms. Treatment of tics may include psychoeducation, non-pharmacologic treatment, or pharmacologic treatment. We review pharmacologic treatment here. Methods: We performed a literature review on pharmacologic treatments for TD. Results: There is no current evidence to suggest that medications impact the prognosis of tic disorders, so current clinical guidelines recommend reassurance of the patient and family and monitoring if there is no change in function or quality of life due to tics. If treatment is indicated, it must be chosen based on the needs of each individual patient. Comprehensive behavioral intervention for tics (CBIT) is considered first-line management for most individuals with bothersome tics, especially if they are mild to moderate in severity. Pharmacotherapy should be considered when tics are impairing daily functioning, causing social problems, accompanied by other neuropsychiatric symptoms, or when the patient is not likely to benefit from CBIT. Current recommended pharmacotherapy options include alpha-2 adrenergic agonists, dopamine modulators, GABAergic medications, dopamine depleters, and botulinum toxin injections. Additionally, there are other novel medications that are being studied in ongoing clinical trials. Conclusions: This review summarizes available pharmacotherapy options for TD in children. It provides an overview of new medications and offers guidance to physicians when selecting appropriate treatments. If medications are indicated for tic management, treatment should be chosen based on the needs of the individual patient.

Antegrade Continence Enema Alone for the Management of Functional Constipation and Segmental Colonic Dysmotility (ACE-FC): A Pediatric Colorectal and Pelvic Learning Consortium Study.

The purpose of the study was to determine if antegrade continence enema (ACE) alone is an effective treatment for patients with severe functional constipation and segmental colonic dysmotility. A retrospective study of patients with functional constipation and segmental colonic dysmotility who underwent ACE as their initial means of management. Data was collected from six participating sites in the Pediatric Colorectal and Pelvic Learning Consortium. Patients who had a colonic resection at the same time as an ACE or previously were excluded from analysis. Only patients who were 21 years old or younger and had at least 1-year follow-up after ACE were included. All patients had segmental colonic dysmotility documented by colonic manometry. Patient characteristics including preoperative colonic and anorectal manometry were summarized, and associations with colonic resection following ACE were evaluated using Fisher's exact test and Wilcoxon rank-sum test. p-Values of less than 0.05 were considered significant. Statistical analyses and summaries were performed using SAS version 9.4 (SAS Institute Inc., Cary, North Carolina, United States). A total of 104 patients from 6 institutions were included in the study with an even gender distribution (males n = 50, 48.1%) and a median age of 9.6 years (interquartile range 7.4, 12.8). At 1-year follow-up, 96 patients (92%) were successfully managed with ACE alone and 8 patients (7%) underwent subsequent colonic resection for persistent symptoms. Behavioral disorder, type of bowel management, and the need for botulinum toxin administered to the anal sphincters was not associated with the need for subsequent colonic resection. On anorectal manometry, lack of pelvic floor dyssynergia was significantly associated with the need for subsequent colonic resection; 3/8, 37.5% without pelvic dyssynergia versus 1/8, 12.5% (p = 0.023) with pelvic dyssynergia underwent subsequent colonic resection. In patients with severe functional constipation and documented segmental colonic dysmotility, ACE alone is an effective treatment modality at 1-year follow-up. Patients without pelvic floor dyssynergia on anorectal manometry are more likely to receive colonic resection after ACE. The vast majority of such patients can avoid a colonic resection.

175 - Long term effectiveness and treatment adherence of botulinum toxin injections for neurogenic detrusor overactivity

175 - Long term effectiveness and treatment adherence of botulinum toxin injections for neurogenic detrusor overactivity

Diagnosis and Management of Retrograde Cricopharyngeal Dysfunction: A Systematic Review.

Retrograde cricopharyngeal dysfunction (R-CPD) is a syndrome with rapidly increasing awareness since being first described in March 2019. As such, few cases of R-CPD are currently reported in the literature. The goal of this study is to provide a comprehensive systematic review of the available literature on R-CPD, including patient characteristics, diagnosis, and management. PubMed, Scopus, EMBASE. A systematic review of the available English literature was conducted using the data sources PubMed, Scopus, and EMBASE. Studies with original data of patients experiencing classic symptoms of R-CPD were included. Independent abstract screening followed by full-text screening was performed to assess study eligibility. Data extraction of patient demographics, symptoms, treatment, and follow-up were subsequently performed. Common presentations of R-CPD include abelchia (100%), abdominal bloating (83%), and gurgling noises (75%). 554 (86.9%) patients had improved symptoms after initial treatment with BTX. The most common initial dose was 50 units in 204 (37.3%) patients. Subsequent BTX injections resolved symptoms in 40 (80%) patients. Six patients ultimately received CP myotomy for recurrent symptoms, resulting in long-term resolution in 4 (67%) patients. R-CPD is a newly recognized syndrome with effective treatment options including botulinum toxin injections and cricopharyngeal myotomy, where appropriate. Diagnostic modalities including esophageal manometry may aid in the initial work up of R-CPD, however further studies are required to assess its diagnostic utility.

172 - Selective Bladder Denervation with Radiofrequency Ablation vs Intramuscular Botulinum Toxin Injection in Patients with Refractory Overactive Bladder: A Preliminary Report of Prospective Randomized Comparative Study

172 - Selective Bladder Denervation with Radiofrequency Ablation vs Intramuscular Botulinum Toxin Injection in Patients with Refractory Overactive Bladder: A Preliminary Report of Prospective Randomized Comparative Study

A randomized, double-blind, placebo-controlled trial of DaxibotulinumtoxinA for Injection for the treatment of upper limb spasticity in adults after stroke or traumatic brain injury.

Intramuscular injection of botulinum toxin type A is a first-line pharmacotherapy for adults with upper limb spasticity (ULS). However, reemergence of symptoms within 12 weeks of treatment is common and longer-lasting treatments are needed. To evaluate the efficacy and safety of three doses of DaxibotulinumtoxinA for Injection (DAXI) for treatment of ULS in adults with stroke or traumatic brain injury. Intramuscular injections of placebo (N = 24), DAXI 250 U (N = 22), DAXI 375 U (N = 19), or DAXI 500 U (N = 18) to the suprahypertonic muscle (SMG) and other muscle groups. Randomized, double-blind, placebo-controlled study. Twenty-six study centers across the United States. Eighty-three adult patients with ULS were randomly assigned to each treatment group and followed for up to 36 weeks. Co-primary endpoints were the Modified Ashworth Scale (MAS) score change from baseline in the designated SMG and Physician Global Impression of Change (PGIC) at Week 6. The mean changes from baseline in MAS score for the designated SMG for placebo and the DAXI 250 U, 375 U, and 500 U groups were -0.6, -0.9, -0.9, and -1.8, respectively, at Week 4 and -0.8, -0.9, -1.0, and -1.5, respectively, at Week 6. Statistically significant improvement in MAS score compared with placebo was reported only for the 500 U dose (Week 4: p < .001; Week 6: p = .049). Significant improvements in PGIC ratings compared with placebo were reported for DAXI 375 U (p = .015) and DAXI 500 U (p = .009) at Week 4 but not for any DAXI doses at Week 6. All DAXI doses were well tolerated with no trend toward more adverse events with increased dose. Results from this Phase 2 study indicate that DAXI 500 U is effective and well tolerated for treatment of adults with ULS.

Long-term effects of different number of botulinum toxin injections into the gastrocnemius muscle on function and muscle morphology in children with cerebral palsy

BackgroundBotulinum toxin (BoNT) injections are used to reduce spasticity, and sometimes repeated injections of the toxin are required. The aim of this study is to investigate the effects of the number of injections of BoNT into the gastrocnemius muscle on function, muscle morphology, muscle stiffness and muscle vascularization in children with cerebral palsy (CP). MethodsThe study included 22 children with unilateral or bilateral spastic type CP aged 5-13 years who had previously received one, two, or three BoNT injections into the gastrocnemius muscle. A total of 29 gastrocnemius muscles were evaluated. Gastrocnemius muscle morphology (muscle cross-sectional area, thickness, fascicle length and pennation angle) was examined by ultrasonography, muscle stiffness by shear wave ultrasound elastography and muscle vascularization by Superb Microvascular Imaging. The functional status of the children was evaluated by the Gross Motor Function Measurement, the Timed-Up-and-Go Test, the Squat Test, the Vertical Jumping Test and the Sit-and-Reach Test. ResultsIn the motor functions and muscle morphology values were similar in all three groups (p>0.05). Muscle stiffness values were higher (p=0.035) and vascularization values were lower (p=0.03) in the group that received three injections compared to the groups that received one injection. There was a moderate positive correlation of the number of BoNTs with muscle stiffness (p<0.05, r=0.454) and a moderate negative correlation with muscle vascularization (p<0.05, r=-0.497). ConclusionsRepeated BoNT applications have no effect on motor functions and muscle morphology in children with CP, whereas BoNT injections administered three times increase muscle stiffness and decrease vascularization.