Neglecting Bone Health: A Critical Gap in Management of Muscle Spasticity with Botulinum Toxin in Spinal Cord Injury.

Neuromuscular inhibitors have been quickly advanced from being used only for aesthetic purposes to being used as a treatment for musculoskeletal pain and muscle spasticity. This phenomenon stems from the diminished force exerted by muscles, which are essential for bone remodeling. In this context, it is hypothesized that botulinum toxin (BTX) might exert a direct influence on bone resorption. Although such treatments have the potential to provide patients with significant relief, bone loss occurring due to elective muscle paralysis has yet to be examined in clinical trials. The disuse model resulting from spinal cord injury, characterized by the absence of ground reaction and muscle forces, provides an ideal context for exploring the skeletal ramifications of intramuscular BTX injection. This approach enables an investigation into the intricate interplay between muscle and bone, encompassing the impact of spasticity on bone preservation, the potential positive and negative outcomes of BTX on bone metabolism, and the involvement of the autonomic nervous system in bone remodeling regulation. This paper presents a narrative review of research findings on the disturbance of the typical balance between muscles and bones caused by acute muscle paralysis from BTX, resulting in osteopenia and bone resorption.

Retrograde cricopharyngeal dysfunction (R-CPD): What do we know so far?

Objective: This comprehensive review aims to explain the disease pathophysiology, clinical presentation, and management options. Methods: A review was carried out in the following databases: Medline, Scopus, Web of Science, and Cochrane. The following terms were used alone and combined: Retrograde, Cricopharyngeus muscle, Dysfunction, Abelchia, and inability to burp. Results: A total of 68 articles were identified, and only 11 were found to be relevant and included in writing this review. Retrograde cricopharyngeal dysfunction (R-CPD) is a relatively new disease entity that has recently been described in clinical literature. It is caused by the inability of the cricopharyngeus muscle to relax. Unlike cricopharyngeal dysfunction (CPD), which is well-known and characterized by dysphagia, R-CPD is characterized by the inability to belch in almost all patients, which is considered diagnostic for the condition. Conclusions: High-resolution manometry (HRM) is the definitive diagnostic modality. Most patients reported in the literature responded well to treatment with botulinum toxin injection.

Treatment of Neuropsychiatric Symptoms in Parkinson's Disease With Botulinum Toxin A: A 12 week Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: The study aimed to evaluate the impact of Botulinum toxin A (BoNT/A) on neuropsychiatric symptoms in Parkinson's disease (PD) patients. METHODS: A total of 125 PD patients and an equal number of age- and gender-matched healthy controls were involved. Mental health status was assessed using the Cornell Medical Index (CMI) self-assessment questionnaire. Sixty-four PD patients exhibiting neuropsychiatric symptoms were selected for the controlled study and randomly grouped into treatment and control groups. The treatment group received BoNT/A injections, while the control group received a placebo. The primary outcome measures included depression scores from the CMI and the proportion of patients displaying improvement in neuropsychiatric symptoms at 8 weeks post-treatment. The secondary outcome was other CMI scores at 4, 8, and 12 weeks post-treatment. RESULTS: The outcomes revealed that PD patients had significantly higher scores in various neuropsychiatric factors compared to healthy controls. At 4 weeks post-treatment, the treatment group displayed improvements in depression and tension. At 8 weeks post-treatment, they exhibited significant reductions in depression, anxiety, sensitivity, and tension compared to the control group. Moreover, a notably higher percentage of patients in the treatment group showed improvement in neuropsychiatric symptoms compared to the control group. At 12 weeks post-treatment, the treatment group exhibited significant improvements in somatization, depression, sensitivity, and tension. CONCLUSION: PD patients commonly experience multiple neuropsychiatric symptoms, and BoNT/A has demonstrated efficacy in alleviating these symptoms. Specifically, BoNT/A was found to effectively alleviate somatization, tension, anxiety, depression, and sensitivity in PD patients.

Effectiveness of microneedle fractional radiofrequency combined with transcutaneous delivery of botulinum toxin in the management of post-acne scars.

BACKGROUND: Post-acne scars are a common sequela of acne, especially prevalent among young people. Delayed treatment not only affects self-perception of beauty but also affects the mental health of patients. OBJECTIVE: This study aims to investigate the clinical efficacy of microneedle fractional radiofrequency (MFR) combined with botulinum toxin A (BoNT/A) in managing post-acne scars. METHODS: This retrospective study involved 63 adult patients with post-acne scars, divided into two groups: group 1 (n = 30) and group 2 (n = 33). Group 1 received treatment with MFR combined with transcutaneous delivery of BoNT/A, whereas group 2 received treatment with MFR alone. The study observed the clinical outcomes in both groups. RESULTS: Based on experimental analysis, the combination of MFR with transcutaneous delivery of BoNT/A demonstrated superior clinical efficacy compared with group 2. There were no significant differences in baseline data or treatment-related pain and adverse reactions between the two groups. However, group 1 exhibited a higher effectiveness rate, lower ECCA score after treatment, higher satisfaction levels, and statistically significant differences compared to group 2. CONCLUSION: MFR combined with transcutaneous delivery of BoNT/A represents an effective and safe alternative for treating acne scars with minimal side effects and complications. SUMMARY STATEMENT: Post-acne scars are a common sequela of acne and combination therapy proves beneficial. Microneedle fractional radiofrequency (MFR) combined with transcutaneous delivery of BoNT/A can be considered an effective and safe alternative for the treatment of acne scars with minimal side effects and complications. It works together through microneedles, radiofrequency, and botulinum toxin. MFR combined with transcutaneous delivery of BoNT/A is based on the direct action of MFR on acne scars and the use of microneedle to create a transient skin microchannel, facilitating BoNT/A penetration into the skin.

Evaluation of the effect of botulinum toxin A on the physical and mental health of patients with hemifacial spasm.

BACKGROUND: Hemifacial spasm (HFS) is a debilitating disease characterized by involuntary tonic and clonic contractions of muscles innervated by the facial nerve. Botulinum toxin A (BTX-A) is the first-line option and the most effective medical treatment for HFS. The objective of this study was to evaluate the effect of BTX-A therapy on the physical and mental health of HFS patients. METHODS: Participants included 65 HFS patients and 65 matched healthy controls in the study. Cornell Medical Index (CMI) self-assessment questionnaire was used to detect the psychological health of all participants. Local injection of BTX-A was applied, and the Cohen hierarchical criteria were employed to stratify the degree of spasticity, further evaluating the efficacy of BTX-A before and two months after treatment in HFS patients. The HFS patients at two months post-treatment were re-evaluated by CMI self-assessment questionnaire, and the evaluated factors of these patients were compared with those of patients before treatment. RESULTS: The scores of somatization, depression, anxiety, inadaptation, sensitivity, anger, tension, M-R, and total scores in the HFS group were significantly higher than those in the control group (all P<0.05). Two months post-treatment, among 65 HFS patients who received with BTX-A treatment, 42 (64.6%) were completely relieved, 16 (24.6%) were significantly relieved, 7 (10.8%) were partially relieved, and 0 (0%) cases were invalid, and the total effective rate was 89.2%. Two months after BTX-A treatment, the scores of somatization, tension, anxiety, depression, sensitivity, M-R and total scores of patients with HFS were lower than those before treatment (all P<0.05). CONCLUSIONS: Patients with HFS are often accompanied by somatization, anger, inadaptation, sensitivity, anxiety, depression, and tension. BTX-A can not only alleviate the symptoms of HFS, but also improve the somatization, tension, anxiety, depression, and sensitivity.

Dose-Dependent Effects of Botulinum Toxin Type A on Prevention of Postoperative Scars in Various Regions in the Body: A Prospective, Double-Blind Randomized Controlled Trial.

BACKGROUND: Botulinum toxin type A (BTXA) can improve wound healing and reduce scar formation; however, the exact dose required to prevent postoperative scarring across various anatomical sites remains unclear. This study aimed to investigate the effectiveness and optimal concentrations of BTXA for preventing postoperative scarring across various common surgical sites throughout the body. METHODS: In this prospective randomized controlled trial, 46 patients with benign skin tumors received injections of 1, 2.5, or 5 U/0.1 mL of BTXA or 0.9% saline immediately following surgical tumor excision on both sides of the incisions. Follow-ups were conducted at 7 days, 15 days, and 1, 3, and 6 months postoperatively. Patient-reported adverse events and standardized digital photographs were collected. Scar formation was assessed using the modified Stony Brook Scar Evaluation Scale (mSBSES). RESULTS: All 46 patients completed the trial without severe complications. The mSBSES scores were higher in the experimental groups at all follow-ups. The 5 U/0.1 mL BTXA dose group demonstrated optimal scar prevention at all high-risk sites for scar hyperplasia. No significant difference was observed between the 2.5 U/0.1 mL and 5 U/0.1 mL doses for intermediate-risk sites, while 1 U/0.1 mL dose was sufficient for low-risk sites. Overall, 86.5% of patients were satisfied with their treatments, with 16.3% being very satisfied. CONCLUSIONS: Early postoperative BTXA injection can reduce or prevent hypertrophic scarring, with optimal doses ranging from 1 to 5 U/0.1 mL depending on the surgical site, supporting broader clinical application of BTXA. The effectiveness of different concentrations of botulinum toxin type A (BTXA) in preventing postoperative scarring was compared, expanding the scope of previous research, which focused only on the head, face, and neck regions, to include the trunk and extremity areas. Different optimal injection strategies were determined based on different surgical sites and their risks of developing hypertrophic scars. The study demonstrates that BTXA not only reduces scar formation but also enhances patient satisfaction and reduces postoperative itching and pain, contributing to overall better postoperative outcomes. By establishing the efficacy and optimal dosing of BTXA for various surgical sites, this research supports the potential for broader clinical application of BTXA in aesthetic and reconstructive surgeries. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

O uso da proteína botulínica na correção do sorriso gengival / The use of botulinum protein in the correction of gingival smile

A sociedade está cada vez mais exigente e em busca de excelência quando o assunto é estética facial. O sorriso tem grande impacto na harmonia da face e, atualmente, os pacientes estão mais conscientes sobre a influência da gengiva na beleza do sorriso. A exposição da gengiva em excesso, conhecida como sorriso gengival, afeta a estética, podendo interferir na autoestima e nas relações sociais dos pacientes. Existem diversos procedimentos descritos para solucionar o problema e, para o planejamento do caso e escolha do método, é preciso determinar a etiologia e levar em consideração o desejo do paciente. A injeção da proteína botulínica é uma alternativa minimamente invasiva que está sedo cada vez mais utilizada para a correção do sorriso gengival. Com isso, o objetivo do presente trabalho monográfico foi realizar uma revisão de literatura sobre o uso da toxina botulínica na correção do sorriso gengival, analisando técnicas de injeção, identificando o efeito imediato e a longo prazo da toxina nos músculos elevadores do lábio superior, além de avaliar a relevância desse método na correção do sorriso gengival, sozinho ou em conjunto com outros procedimentos. Foi realizada uma revisão de literatura nas bases de dados PubMed e Scielo, buscando artigos dos anos de 2013 até 2022, utilizando os descritores "botulinum toxin", "botox", "gummy smile", "gingival display" e "gingival exposure". Essa revisão analisa 15 artigos que discorrem sobre o método, durabilidade e eficácia da aplicação de proteína botulínica para correção do sorriso gengival. Algumas variantes diferenciam as técnicas de aplicação, como a marca do produto e recomendações do fabricante, classificação do sorriso e extensão da exposição gengival. Com base na revisão de literatura, pôde-se concluir que, apesar de ser transitório, esse procedimento se mostrou eficaz, tanto ao ser realizado como método principal, quanto como coadjuvante no tratamento. Além de ser comprovadamente seguro, rápido, minimamente invasivo e ser o tratamento de preferência entre os pacientes, com alto índice de satisfação, são raras as complicações relacionadas a aplicação da proteína botulínica para esse fim.

Society is becoming increasingly demanding, seeking excellence in facial aesthetics. The smile greatly impacts facial harmony, and nowadays, patients are more aware of the influence of the gums on smile beauty. Excessive gum exposure, known as gummy smile, affects aesthetics and can interfere with patients' self-esteem and social relationships. There are various procedures described to address this issue, and for case planning and method selection, it is necessary to determine the etiology and take into account the patient's desires. The injection of botulinum protein is a minimally invasive alternative that is increasingly being used for gummy smile correction. Thus, the aim of this monographic work was to conduct a literature review on the use of botulinum toxin in gummy smile correction, analyzing injection techniques, identifying the immediate and long-term effects of the toxin on the upper lip elevator muscles, and evaluating the relevance of this method in gummy smile correction, either alone or in conjunction with other procedures. A literature review was conducted in the PubMed and Scielo databases, seeking articles from 2013 to 2022, using the descriptors "botulinum toxin", "botox", "gummy smile", "gingival display", and "gingival exposure". This review analyzes 15 articles that discuss the method, durability, and effectiveness of botulinum toxin application for gummy smile correction. Some variations differentiate the application techniques, such as the product brand and manufacturer's recommendations, smile classification, and extent of gum exposure. Based on the literature review, it was possible to conclude that, despite being temporary, this procedure proved to be effective, both when performed as the main method and as an adjunct in treatment. In addition to being proven safe, fast, minimally invasive, and the preferred treatment among patients, with a high satisfaction rate, complications related to botulinum toxin application for this purpose are rare.

An Uncommon Culprit: Trapezius Dystonia as a Cause of Thoracic Outlet Syndrome: A Case Report.

Thoracic outlet syndrome (TOS) results from compression of the neurovascular bundle in the thoracic outlet. Several etiologies can contribute to the development of thoracic outlet syndrome, including both congenital and acquired causes. Historically, trapezius pathology has not been considered a cause of TOS; however, here we report a patient with neurogenic TOS plus ipsilateral trapezius hypertonicity and hypertrophy who had significant symptomatic improvement following botulinum toxin injections to trapezius.

Botulinum toxin type A injection combined with biofeedback in the treatment of spastic pelvic floor syndrome.

BACKGROUND: Spastic pelvic floor syndrome (SPFS) is a refractory pelvic floor disease characterized by abnormal (uncoordinated) contractions of the external anal sphincter and puborectalis muscle during defecation, resulting in rectal emptation and obstructive constipation. The clinical manifestations of SPFS are mainly characterized by difficult defecation, often accompanied by a sense of anal blockage and drooping. Manual defecation is usually needed during defecation. From physical examination, it is commonly observed that the patient's anal muscle tension is high, and it is difficult or even impossible to enter with his fingers. AIM: To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome. METHODS: Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome. All patients underwent pelvic floor surface electromyography assessment, anorectal dynamics examination, botulinum toxin type A injection 100 U intramuscular injection, and two cycles of biofeedback therapy. RESULTS: After the botulinum toxin A injection combined with two cycles of biofeedback therapy, the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery (P < 0.05). Moreover, the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery (P < 0.05). CONCLUSION: Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome. Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively. However, randomized controlled trials are needed.

Clinical effect of botulinum toxin type A combined with autologous fat grafting in patients with nasolabial fold depression.

BACKGROUND: Nasolabial fold (NLF) depression can affect the facial appearance of patients to some extent and increase their psychological burdens. In recent years, autologous fat grafting (AFG) combined with botulinum toxin A (BTX-A) injection (AFG + BTX-A injection) has been gradually applied in the treatment of patients with NLF depression. Although studies have been conducted on the efficacy and safety of AFG + BTX-A injection in treating NLF depression, the experimental design, observational indicators, and sample enrollment criteria vary remarkably, making it difficult to draw convincing and consistent conclusions. Thus, further relevant research is warranted. AIM: To assess the esthetic improvement, efficacy, and safety of AFG + BTX-A injections in patients with NLF depression. METHODS: This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021. These patients were categorized into control (n = 30) and observation (n = 30) groups. The observation group received AFG + BTX-A injection, whereas the control group underwent AFG only. All patients were evaluated using the wrinkle severity rating scale (WSRS) and global aesthetic improvement scale. The compactness of facial contours, skin evaluation indexes, adverse reactions, and satisfaction of the two groups were evaluated 3 months postoperatively. RESULTS: The WSRS scores of the observation group at 1, 3, and 6 months postoperatively were lower than those of the control group (P < 0.05). Three months postoperatively, facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group (P < 0.05). The compactness of facial contours was better in the observation group than in the control group (P < 0.05). In addition, no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness, facial asymmetry, facial bruising, and facial concavity inequality (P > 0.05). CONCLUSION: AFG + BTX-A injection is a highly safe, cost-effective, effective, and long-lasting treatment for NLF depression with high esthetic value, which should be promoted in the future.

The use of botulinum toxin type a to prepare patients with large ventral hernias for laparoscopic hernioplasty: Our experience.

OBJECTIVE: Aim: To study the effectiveness of BTA in a total dose of 100 IU as the preparation for patients with primary and incisional ventral hernias (VH). PATIENTS AND METHODS: Materials and Methods: The prospective study included 59 patients with large VH (defect ³10 cm). All patients received 100 IU of BTA in abdominal wall muscles 4-5 weeks before surgery from June 2017 to December 2022. An average age of the patients was 59.13 ± 9.07 years, body mass index - 32.20 ± 4.95 kg/m2. RESULTS: Results: An average width of the hernia defect after BTA decreased by 4.5 ± 1.11 cm (p<0.001). An average length of the hernia defect after BTA also decreased, without clinical significance. A significant increase in the length of the abdominal wall and a decrease in its thickness were observed. The abdominal cavity volume after BTA increased by 4.04 ± 4.55% (p=0.008) and the hernial sac volume decreased by 21.43 ± 16.57% (p=0.005). All patients underwent surgery with hernia defect suturing and without component separation: laparoscopic IPOM hernioplasty - 50 (84.7%) patients, open IPOM hernia repair - 7 (11.9%) patients, open sublay hernioplasty - 2 (3.4%) patients. There was no recurrence of hernia during 12 months after surgery. CONCLUSION: Conclusions: The administration of 100 IU BTA allows to increase the length of the abdominal wall muscles and to perform laparoscopic IPOM hernioplasty for patients with large VH.

Botox: Current and Emerging Trends for Dental Practitioners in Esthetic Dentistry.

There are numerous medical and dental disorders for which there are no effective traditional therapy options. For various medical and dental disorders, botulinum toxin (BT) can be employed as an alternate therapeutic option that uses the chemodenervation approach. The range of dentistry treatment choices is expanding quickly. Applications of non-traditional therapy alternatives, such as the use of BT, are becoming more and more common in this situation. Although BT has been shown to be effective in a number of circumstances, its application in esthetic operations, such as the treatment of facial wrinkles, has gained widespread acceptance. This research is especially interested in applications of BT related to dentistry in the craniofacial region. For many diseases that a dentist would be interested in treating, BT provides a temporary, reversible, and generally safe therapy option. Due to their extensive knowledge of the anatomy of the faciomaxillary region, dental surgeons are a potential pool of operators who, with a small amount of skill enhancement, can use BT in their toolkit. This broadens the scope of minimally invasive alternatives to invasive protocols or refractory conditions. An online search was conducted for the use of BT in dentistry; all studies and articles pertaining to the subject were chosen, and dental-related content was removed and summarized. The fundamentals of BT and some of its applications in dentistry are covered in this article. The comprehensive details of its application in dentistry will be covered in the upcoming sections.

Evaluation of efficacy and safety of Botulinum toxin-A injection at three deferent sites in treatment of premature ejaculation.

BACKGROUND: Premature ejaculation (PE) is a common sexual problem, resulting in adverse effects on the quality of life, of both the patient and the partner. The idea of muscular contraction inhibition during the ejection phase of ejaculation by Botulinum toxin-A injection may delay ejaculation. AIM OF STUDY: This study was performed to assess the efficacy and safety of Botulinum toxin-A injection in PE treatment. MATERIAL AND METHODS: This study included 45 married male patients diagnosed with primary PE. All included patients were injected with 75 units of Dysport equal efficacy of 25 units of Botulinum toxin-A (Botox) into three sites: the root of the penis (Group 1), glans penis (Group 2), and each side of the ischiocavernosus muscle (Group 3). All patients were subjected to an assessment of intravaginal ejaculation latency time (IELT) using a stopwatch and answering the Premature Ejaculation Diagnostic Tool (PEDT) Questionnaire before and after treatment. RESULTS: There was a statistically significant improvement in IELT after treatment in all groups. The most significant improvement was shown in Group 3 (average 108% increase), followed by Group 1 (74%) and Group 2 (40%), respectively. There was a positive correlation between age and the improvement in improved IELT. There was a statistically significant improvement in PEDTq scores in Group 1 and Group 3. CONCLUSION: Botulinum toxin-A injection into the root of the penis and ischiocavernosus muscle could be recommended in the treatment of premature ejaculation.

Ear Dyskinesia in the Absence of Neuroleptics: A Case Report.

Ear dyskinesia, also known as "moving ear syndrome," is a rare movement disorder characterized by involuntary, rhythmic, or semi-rhythmic contractions of the external ear muscles. The condition is not well-documented in the medical literature, with only a few case reports available. We present the case of a 37-year-old teacher from Saudi Arabia who developed a history of sudden, progressive involuntary movement of the posterior head region, provoking movement of the external ears, over the course of one year. The movements were non-rhythmical, more prominent on the right side, and associated with occasional involvement of the face and anterior neck muscles. The patient had no history of neuroleptic use or other relevant medical conditions. Examination confirmed the presence of palpable muscle contractions originating mainly from the posterior region, with the movements not synchronized across the two sides. Investigations, including blood tests and brain MRI, did not reveal any underlying pathology. A diagnosis of ear dyskinesia was made, and botulinum toxin treatment was recommended; however, the treatment showed no results, and then the patient was subsequently lost to follow-up. This case adds to the limited literature on the rare phenomenon of ear dyskinesia, highlighting the clinical presentation and the challenges in the management of this unusual movement disorder. Further research is needed to better understand the underlying mechanisms and optimal treatment approaches for this condition.

Botulinum toxin treatment for hemifacial spasm: harmonising neurological and aesthetic outcomes.

Hemifacial spasm (HFS) represents a challenging cranial movement disorder primarily affecting the facial nerve innervated muscles, with significant prevalence among Asians. Botulinum toxin type A (BoNT/A) injections, established as a primary therapeutic intervention since FDA approval, offer considerable effectiveness in alleviating spasms, albeit accompanied by challenges such as temporary effects and potential adverse events including facial asymmetry. This comprehensive review underscores the crucial need for harmonising neurological benefits and aesthetic outcomes in HFS management. The discussion delves into the interplay between facial aesthetics and neurological objectives in BoNT/A injections, emphasising precise techniques, dosages, and site considerations. Distinct aspects in neurological and aesthetic domains are also examined, including detailing the targeted muscles and injection methodologies for optimal therapeutic and aesthetic results. Importantly, evidence regarding various BoNT/A formulations, recommendations, and reconstitution guidelines in both neurology and aesthetics contexts are provided, along with a schematic approach outlining the stepwise process for BoNT/A injection in HFS treatment, addressing critical areas such as orbicularis oculi muscle sites, eyebrow correction strategies, mid- and lower-face considerations, contralateral injection sites, and post-injection follow-up and complication management. By highlighting the culmination of neurological efficacy and facial esthetics in BoNT/A treatment for HFS patients, this review proposes a holistic paradigm to achieve balanced symptomatic relief and natural aesthetic expression, ultimately enhancing quality of life for individuals grappling with HFS.

Botulinum toxin type A-targeted SPP1 contributes to neuropathic pain by the activation of microglia pyroptosis.

BACKGROUND: Neuropathic pain (NP) is the primary symptom of various neurological conditions. Patients with NP often experience mood disorders, particularly depression and anxiety, that can severely affect their normal lives. Microglial cells are associated with NP. Excessive inflammatory responses, especially the secretion of large amounts of pro-inflammatory cytokines, ultimately lead to neuroinflammation. Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system. AIM: To investigate the effects of botulinum toxin type A (BTX-A) on microglial pyroptosis in terms of NP and associated mechanisms. METHODS: Two models, an in vitro lipopolysaccharide (LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments, were used. Key proteins in the pyroptosis signaling pathway, NLRP3-GSDMD, were assessed using western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence. Inflammatory factors [interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α] were assessed using enzyme-linked immunosorbent assay. We also evaluated microglial cell proliferation and apoptosis. Furthermore, we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation. RESULTS: The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α, IL-6, and IL-1ß were enhanced in LPS-treated microglia. Furthermore, SPP1 expression was also induced in LPS-treated microglia. Notably, BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia. Additionally, depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia, whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin (sh)RNA in LPS-treated microglia. Finally, SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N, NLPRP3, and ASC and suppressed the production of inflammatory factors. CONCLUSION: Notably, BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death. It improves pain perception and inhibits microglial activation in rats with selective nerve pain.

[Five-year follow-up after neurosurgery complicated by facial neuropathy]. / Rezul'taty pyatiletnego nablyudeniya za patsientami s neiropatiei litsevogo nerva posle neirokhirurgicheskikh vmeshatel'stv.

BACKGROUND: Botulinum toxin A (BTA) injections are effective for facial neuropathy. However, there is insufficient number of studies devoted to long-term management of these patients. OBJECTIVE: To evaluate the effectiveness and safety of BTA therapy in patients with facial neuropathy after neurosurgical interventions. MATERIAL AND METHODS: The study included 86 patients with facial neuropathy after surgical treatment of posterior cranial fossa and cerebellopontine angle tumors. All ones were divided into 2 groups: group I (main) - 57 patients with BTA prescribed early after facial nerve injury, group II (control) - 29 people undergoing exercise therapy, as well as special exercises and acupressure of painful muscle cords. The Sunnybrook Facial Grading Scale (SFGS) was used to assess facial symmetry and synkinesis, the Facial Disability Index (FDI scale) - to assess the quality of life. Overall duration of the study was 5 years (control points: 6 months, 1, 2, 3 and 5 years). RESULTS: The SFGS scores after 1, 2, 3 and 5 years were significantly better in the main group (resting symmetry p<0.01, voluntary movement symmetry p<0.01, synkinesis p<0.01, general condition of facial muscles p<0.01). Scores of physical and social functioning were significantly higher in the main group after 1 (p<0.01), 2 (p<0.01), 3 (p<0.01) and 5 years (p<0.01) after surgery. There was no need to change BTA dosage over 5 years. Thus, this form of BTA may be the most effective for synkinesis of facial muscles. CONCLUSION: Correction of synkinesis caused by facial neuropathy requires long-term follow-up and long-term treatment. BTA is effective and may be recommended for long-term treatment of these patients.

Exploring the Biomarkers and Potential Mechanisms of Botulinum Toxin Type A in the Treatment of Microglial Inflammatory Activation through P2X7 Receptors based on Transcriptome Sequencing.

AIMS: This study aims to explore the potential mechanism by which Botulinum toxin type A (BoNT/ A) inhibits microglial inflammatory activation through P2X7 receptors (P2X7R). BACKGROUND: BoNT/A is a promising analgesic drug, and previous studies have established that it alleviates Neuropathic Pain (NP) by inhibiting microglial inflammatory activation. This study examined the biomarkers and potential mechanisms by which BoNT/A relieves neuropathic pain by mediating microglial P2X7R and analyzing transcriptome sequencing data from mouse BV-2 microglial cells. OBJECTIVE: The P2X7R agonist Bz-ATP was used to induce microglial inflammatory activation, whilst RNAseq technology was used to explore the biomarkers and potential mechanisms through which BoNT/A suppresses microglial inflammation. METHODS: RNA sequencing was performed on three BV-2 cell samples treated with a P2X7R specific activator (Bz-ATP) and three BV-2 cell samples pre-treated with BoNT/A. Only data that successfully passed quality control measures were included in subsequent analysis. Initially, Differentially Expressed Genes (DEGs) were identified from BoNT/A and control samples, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Biomarkers were then identified by constructing a Protein- Protein Interaction (PPI) network and utilizing the CytoHubba plug-in in Cytoscape software. Lastly, enrichment analysis and regulatory network analysis were performed to elucidate the potential mechanism of BoNT/A in the treatment of NP. RESULTS: 93 DEGs related to the "cell component size regulation" GO term and enriched in the "axon guidance" KEGG pathway were identified. Subsequently, 6 biomarkers were identified, namely PTPRF, CHDH, CKM, Ky, Sema3b, and Sema3f, which were enriched in pathways related to biosynthesis and metabolism, disease progression, signal transduction, and organelle function, including the "ribosome" and "Wnt signaling pathway." Finally, a competing endogenous RNA (ceRNAs) network was constructed from 6 mRNAs, 66 miRNAs, and 31 lncRNAs, forming a complex relationship network. CONCLUSION: Six genes (PTPRF, Sema3b, Sema3f, CHDH, CKM, and Ky) were identified as biomarkers of microglial inflammatory activation following BoNT/A treatment. This finding may provide a valuable reference for the relief and treatment of neuropathic pain.

Botulinum Toxin Enhanced Foker Process for Long Gap Esophageal Atresia.

BACKGROUND: The traction-induced esophageal growth (Foker) process for the treatment of long gap esophageal atresia (LGEA) relies on applying progressive tension to the esophagus to induce growth. Due to its anti-fibrotic and muscle-relaxing properties, we hypothesize that Botulinum Toxin A (BTX) can enhance traction-induced esophageal growth. METHODS: A retrospective two-center cohort study was conducted on children who underwent a BTX-enhanced Foker process for LGEA repair from 2021 to 2023. BTX (10 units/ml, 2 units/kg, per esophageal pouch) was applied at the time of traction initiation. Time on traction, complications, and anastomotic outcomes were compared against historical controls (Foker process without BTX) from 2014 to 2021. RESULTS: Twenty infants (LGEA type A:12, B:4, C:4; 35% reoperative; median [IQR] age 3 [2-5] months), underwent BTX-enhanced Foker process (thoracotomy with external traction: 9; minimally invasive [MIS] multi-staged internal traction: 11). Mean gap lengths were similar between BTX-enhanced external and external traction control patients (mean [SD], 50.6 mm [12.6] vs. 44.5 mm [11.9], p = 0.21). When compared to controls, the BTX-enhanced external traction process was significantly faster (mean [SD], 12.1 [1.6] days vs. 16.6 [13.2] without BTX, p = 0.04) despite similar preoperative gap lengths. There was no difference in time on traction for those undergoing a minimally invasive process. There were no significant differences in complications or anastomotic outcomes in either cohort. CONCLUSION: Botulinum toxin may play a role in accelerating the traction-induced esophageal growth process for LGEA repair. Minimizing time on traction can decrease sedation and paralysis burden while on external traction. Further studies are needed to elucidate the effects of BTX on the esophagus. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective, Two-center, Cohort study.

The Effects of Botulinum Toxin Type A on the Biological Behavior of Fibroblasts on Silicone Implants.

BACKGROUND: Capsular contracture is one of the most severe complications following breast augmentation surgery. It has been reported that botulinum toxin Type A (BTX-A) can inhibit capsular contracture, but the exact mechanisms remain unclear. Therefore, this study aims to explore the potential mechanisms behind BTX-A's inhibition of capsular contracture by observing its effects on the biological behavior of fibroblasts and its impact on the TGF-ß/Smad signaling pathway. METHODS: In vitro experiments involved culturing fibroblasts on PDMS surfaces, subsequently treating them with various concentrations of BTX-A. Fibroblast proliferation activity was assessed using the CCK-8 assay, while the migration and cytoskeletal morphology of the fibroblasts were meticulously examined. ELISA was utilized to quantify the expression of fibrosis-related cytokines. Gene and protein expressions related to the TGF-ß/Smad pathway were analyzed through real-time PCR and Western blotting techniques. RESULTS: BTX-A moderately enhanced the early proliferation and migration of fibroblasts on the surface of PDMS silicone sheets and reduced the synthesis of collagen types I and III. Furthermore, under the influence of BTX-A, the expression of TGF-ßR2 and α-SMA in the TGF-ß/Smad pathway was significantly inhibited. CONCLUSIONS: This study demonstrates that BTX-A can inhibit fibroblast differentiation by downregulating the expression of TGF-ßR2, thereby suppressing the TGF-ß/Smad pathway. This suggests a possible mechanism through which BTX-A mitigates capsular contracture. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .