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.

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.

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.

Third-Line Therapeutic Interventions for Non-Neurogenic Bladder Dysfunction in Children.

PURPOSE OF REVIEW: The aim of this article is to review considerations and efficacy of third-line treatments for pediatric non-neurogenic bladder dysfunction, including Botulinum toxin A (BoTNA), Posterior Tibial Nerve Stimulation (PTNS), and Sacral Neuromodulation (SNM). RECENT FINDINGS: Federal Drug Administration approval for use of beta-3-agonists in overactive detrusor activity in pediatric patients may provide an additional step prior to third-line therapies. New long-term data on pediatric SNM efficacy, complications, and revision rates will provide valuable information for counseling families. BoTNA offers a safe and efficacious treatment to decrease detrusor contractility and improve bladder capacity but is limited by the half-life of BoNTA agent. Percutaneous or transcutaneous PTNS offers improved voided volumes or cure in some patients but is time-intensive. SNM can be utilized in a variety of LUTD pathology with high success rate and cure but should consider cumulative anesthetic and fluoroscopic exposures for battery replacements and re-positioning for patient growth.

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 enemy at the gate: Botulism.

Botulism, caused by Clostridium botulinum, continues to pose a significant threat to public health. This review explores the historical context and contemporary relevance of botulism, emphasizing its potential lethality and evolving medical applications. In recent years, the use of botulinum toxin in medical procedures, particularly in cosmetic and therapeutic applications, has increased the risk of iatrogenic botulism. The rise in iatrogenic cases underscores the importance of vigilance among health-care providers, especially those in emergency departments, where prompt diagnosis and intervention are critical. This review underscores the necessity for health-care professionals to consider botulism in the differential diagnosis of patients presenting with relevant symptoms, given the potential severity of the condition.

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.

New approach to generating of human monoclonal antibodies specific to the proteolytic domain of botulinum neurotoxin A.

Introduction: Botulinum neurotoxins (BoNTs) cause botulism and are the most potent natural toxins known. Immunotherapy with neutralizing monoclonal antibodies (MAbs) is considered to be the most effective immediate response to BoNT exposure. Hybridoma technology remains the preferred method for producing MAbs with naturally paired immunoglobulin genes and with preserved innate functions of immune cells. The affinity-matured human antibody repertoire may be ideal as a source for antibody therapeutics against BoNTs. In an effort to develop novel BoNT type A (BoNT/A) immunotherapeutics, sorted by flow cytometry plasmablasts and activated memory B cells from a donor repeatedly injected with BoNT/A for aesthetic botulinum therapy could be used due to obtain hybridomas producing native antibodies. Methods: Plasmablasts and activated memory B-cells were isolated from whole blood collected 7 days after BoNT/A injection and sorted by flow cytometry. The sorted cells were then electrofused with the K6H6/B5 cell line, resulting in a producer of native human monoclonal antibodies (huMAbs). The 3 antibodies obtained were then purified by affinity chromatography, analyzed for binding by Western blot assay and neutralization by FRET assay. Results: We have succeeded in creating 3 hybridomas that secrete huMAbs specific to native BoNT/A and the proteolytic domain (LC) of BoNT/A. The 1B9 antibody also directly inhibited BoNT/A catalytic activity in vitro. Conclusion: The use activated plasmablasts and memory B-cells isolated at the peak of the immune response (at day 7 of immunogenesis) that have not yet completed the terminal stage of differentiation but have undergone somatic hypermutation for hybridization allows us to obtain specific huMAbs even when the immune response of the donor is weak (with low levels of specific antibodies and specific B-cells in blood). A BoNT/A LC-specific antibody is capable of effectively inhibiting BoNT/A by mechanisms not previously associated with antibodies that neutralize BoNT. Antibodies specific to BoNT LC can be valuable components of a mixture of antibodies against BoNT exposure.

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.

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.

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.

Botulinum toxin intoxication requires retrograde transport and membrane translocation at the ER in RenVM neurons.

Botulinum neurotoxin A (BoNT/A) is a highly potent proteolytic toxin specific for neurons with numerous clinical and cosmetic uses. After uptake at the synapse, the protein is proposed to translocate from synaptic vesicles to the cytosol through a self-formed channel. Surprisingly, we found that after intoxication proteolysis of a fluorescent reporter occurs in the neuron soma first and then centrifugally in neurites. To investigate the molecular mechanisms at play, we use a genome-wide siRNA screen in genetically engineered neurons and identify over three hundred genes. An organelle-specific split-mNG complementation indicates BoNT/A traffic from the synapse to the soma-localized Golgi in a retromer-dependent fashion. The toxin then moves to the ER and appears to require the Sec61 complex for retro-translocation to the cytosol. Our study identifies genes and trafficking processes hijacked by the toxin, revealing a new pathway mediating BoNT/A cellular toxicity.

Botulinum toxin type A injection into the masticatory muscles and its effects on mandibular bone resorption and density. A systematic review.

OBJECTIVE: This systematic review aims to summarize and synthesize the evidence that investigates the secondary effects of the application of botulinum toxin (BT) into the masticatory muscles and its effects on bone density. MATERIALS AND METHODS: Database searches were conducted until March 19th, 2024. The quality of the studies was assessed by the Cochrane tool risk of bias for the randomized controlled trials and the ROBINS-I tool for non-randomized studies. The Cochrane Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the confidence in the overall evidence. RESULTS: Five studies looking at the effects of botulinum toxin on bone density and resorption when applied to masticatory muscles were found. No significant changes were observed in most of the studies when looking at the effects of botulinum toxin on mandibular condyle volume, density, mandibular angle thickness, and coronoid process volume. The only finding that was statistically and clinically relevant was the difference between patients who received a double application of BT when compared with patients who received a single application (SMD: -0.99 [95%CI: -1.94,-0.05]) on the volume of the mandibular angle. CONCLUSIONS: There is no clear pattern on whether the application of botulinum toxin is associated with bone resorption or not. Although some studies show statistical significance of the findings, the magnitude of the changes in bone density and their clinical significance are not completely clear. CLINICAL RELEVANCE: To understand the effectiveness of the use of botulinum toxin into the masticatory muscles and its possible secondary adverse effects on the density of the mandible.

Tirbanibulin (KX2-391) analog KX2-361 inhibits botulinum neurotoxin serotype A mediated SNAP-25 cleavage in pre- and post-intoxication models in cells.

Botulinum neurotoxins (BoNT) inhibit neuroexocytosis, leading to the potentially lethal disease botulism. BoNT serotype A is responsible for most human botulism cases, and there are no approved therapeutics to treat already intoxicated patients. A growing body of research has demonstrated that BoNT/A can escape into the central nervous system, and therefore, identification of BoNT/A inhibitors that can penetrate BBB and neutralize the toxin within intoxicated neurons would be important. We previously identified an FDA-approved, orally bioavailable compound, KX2-391 (Tirbanibulin) that inhibits BoNT/A in motor neuron assays. Recently, a structural analog of KX2-391, KX2-361, has been shown to exhibit good oral bioavailability and cross BBB with high efficiency in mouse experiments. Therefore, in this work, we evaluated the inhibitory effects of KX2-361 against BoNT/A. Toward this goal, we first evaluated the compound for its effects on cell viability in PC12 cells, via MTT assay, and in mouse embryonic stem cell (mESC)-derived motor neurons, with imaging-based assays. Following, we tested KX2-361 in mESC-derived motor neurons intoxicated with BoNT/A holotoxin, and the compound exhibited activity against the toxin in both pre- and post-intoxication conditions. Excitingly, KX2-361 also inhibited BoNT/A enzymatic component (light chain; LC) in PC12 cells transfected with BoNT/A LC. Furthermore, our molecular docking analyses suggested that KX2-361 can directly bind to BoNT/A LC. Medicinal chemistry approaches to develop structural analogs of KX2-361 to increase its efficacy against BoNT/A may provide a critical lead compound with BBB penetration capacity for drug development efforts against BoNT/A intoxication.

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.

Short- medium- and long-term effects of botulinum toxin on upper limb spasticity in children with cerebral palsy: A meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin (BTX) is an effective management method for spasticity in children with cerebral palsy (CP), but the short- medium- and long-term effects remain unclear. OBJECTIVE: The primary objective was to quantify the effects of BTX injections on upper limb spasticity over time in children with CP. The secondary objective was to evaluate efficacy according to the International Classification of Functioning, Disability, and Health-Children & Youth version framework. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that included control/comparison groups treated with a placebo or other treatments. We searched CINAHL, Embase, PubMed, Scopus, Web of Science, and PsycINFO from their inception to April 2024. The pooled mean difference (MD) or standard mean difference (SMD) with 95 % CI was calculated using a random effects model at the short-term (up to 3 months), medium-term (3 to 6 months), and long-term (over 6 months). RESULTS: A total of 658 children with CP aged 1.8 to 19 years old in 12 eligible trials were involved. The primary outcome of the Melbourne Assessment percentile showed a significant increase in the medium- (MD = 2.63, 95 % CI 0.22 to 5.04, I² = 0 %) and long-term (MD = 4.72, 95 % CI 0.93 to 8.51, I² = 0 %) in favor of BTX. Pooled effects also showed that BTX significantly improved Modified Ashworth Scale scores in the short- (MD = -0.44, 95 % CI -0.88 to -0.01, I² = 88 %) and medium-term (MD = -0.20, 95 % CI -0.28 to -0.13, I² = 0 %), and individual goals and bimanual performance up to 6-months. No significantly higher risk of adverse events was observed with BTX. CONCLUSIONS AND IMPLICATIONS: BTX injections sustainably improved the quality of affected upper limb function and temporarily improved individual goals and bimanual performance in children with CP. Our findings cautiously support a time interval of 3 to 6 months between BTX injections in the upper limbs of children with CP. TRIAL REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration ID: CRD42022323672).

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.