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Crow's feet lines in the lateral canthal region are a common concern among aging patients, initially appearing as dynamic wrinkles during facial expressions and becoming more pronounced with age. Botulinum neurotoxin temporarily paralyzes muscles by inhibiting acetylcholine release, smoothing wrinkles and enhancing skin's youthful appearance. Effective treatment requires tailored approaches considering individual anatomy and muscle activity. Recent cadaveric studies identified the tear trough muscle, emphasizing its role in infraorbital support and aging. Clinically, patients often present medial eye wrinkles after BoNT treatment for crow's feet, prompting exploration of underlying mechanisms and management strategies. Three cases demonstrated that medial BoNT injections in the orbicularis oculi muscle significantly improve medial eye wrinkles and tear trough appearance. The study underscores the importance of understanding muscle hyperactivity and anatomical variations for precise treatment. Enhanced injection techniques targeting specific areas can achieve better outcomes and minimize complications, particularly in culturally sensitive regions where facial expressions are valued. This research highlights the necessity for comprehensive anatomical knowledge and patient‐specific treatment strategies to address medial eye wrinkles effectively. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (BoNT) has been in use since the 1970's. Its effect is reached mainly by inhibiting the release of acetylcholine in the synaptic gap of motor neurons or at the motor end plate and the parasympathetic ganglia. In the case of Parkinson's disease, it is used to treat several motor and non-motor symptoms. Within recent years increasingly numerous possible fields of application of BoNT have been found for the treatment of Parkinson's disease, and for some specific symptoms it has in fact become the therapy of choice, while for others it is but one of the therapeutic options that come into consideration when others are not sufficiently effective. In the following, we intend to outline the indications, the possible side effects and also the approvals for therapies with botulinum toxin in the primary and secondary symptoms of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Hemifacial spasm (HFS) is a neuromuscular disorder characterized by unilateral facial muscle spasms, negatively impacts quality of life due to social embarrassment. Botulinum Neurotoxin (BoNT) injections have emerged as a viable therapeutic approach. This systematic review evaluated the efficacy and safety of BoNT injections for HFS management, along with effects on patients' quality of life and mental health. Materials and methods: A systematic search for studies on BoNT treatment for HFS published between January 1, 2000, and May 1, 2024, was performed across major databases. Study quality was evaluated using Cochrane and Joanna Briggs Institute (JBI) tools, with data management handled by EndNote X9 and statistical analyses conducted via Review Manager (RevMan 5.4) and STATA 14.0. Results: Thirty-five studies met the inclusion criteria: 2 RCTs comprising 83 HFS patients compared the efficacy of perioral injections of botulinum toxin and placebo, while 33 single-arm studies reported outcomes for 2786 patients post-BoNT injection. The selection of 17 single-arm studies focused on the effectiveness rate as the key outcome metric. Pooled estimate signified a remarkably high effectiveness (ES: 0.882, 95% CI: 0.830, 0.926, P < 0.001). Analysis of depression scale (SMD: -0.85, 95% CI: -1.34, -0.35, P < 0.001), anxiety scale (SMD: -1.50, 95% CI: -2.19, -0.80, P < 0.001) and total scale of quality of life (SMD: -0.64, 95% CI: -0.87, -0.41, P = 0.766) showed that BoNT therapy worked well especially in improving mental state and quality of life. Ptosis was considered as the most common adverse reaction during BoNT injections (OR: 0.30, 95% CI: 0.11, 0.81, P = 0.843). Conclusion: BoNT injection showed validity and clinical safety in the treatment of HFS, particular for depression relief. Injections around the mouth were only effective for HFS cases with severe symptoms. A standardized strategy for BoNT injections in managing HFS, detailing parameters such as injection sites, doses, and frequencies, remained elusive. Additional RCTs are necessary to further elucidate the interplay between efficacy and these components. [ABSTRACT FROM AUTHOR]

Background: Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI. Methods: We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany. Results: Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits. Conclusion: Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism. [ABSTRACT FROM AUTHOR]

Spasticity management should be provided within the context of a comprehensive person-centered rehabilitation program. Furthermore, active goal setting for specific spasticity interventions is also important, with a well-established "more is better" approach. It is critical to consider adjunctive therapy and multimodal approaches if patients are not attaining their treatment goals. Often used interchangeably, there may be confusion between the terms adjunctive and multimodal therapy. Yet it is imperative to understand the differences between these approaches to achieve treatment goals in spasticity management. Addition of a secondary pharmacologic or non-pharmacologic treatment to optimize the efficacy of the initial modality, such as adding electrical stimulation or casting to BoNT-A, is considered an adjunctive therapy. Adjunctive therapy is time-specific and requires the added therapy be initiated within a specific period to enhance the primary treatment; usually within 2 weeks. Multimodal therapy is an integrated, patient-centric program of pharmacologic and nonpharmacologic strategies utilized in a concurrent/integrated or sequential manner to enhance the overall treatment effect across a variety of spasticityassociated impairments (e.g., neural and non-neural components). Moreover, within a multimodal approach, adjunctive therapy can be used to help enhance the treatment effect of one specific modality. The objectives of this paper are to clarify the differences between adjunctive and multimodal therapies, provide a brief evidence-based review of such approaches, and highlight clinical insights on selecting multimodal and adjunctive therapies in spasticity management. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusions and Implications Botulinum neurotoxin type A1 (BoNT/A) is one of the most potent neurotoxins known. At the same time, it is also one of the safest therapeutic agents used for the treatment of several human disorders and in aesthetic medicine. Notwithstanding great effectiveness, strategies to accelerate the onset and prolong BoNT/A action would significantly ameliorate its pharmacological effects with beneficial outcomes for clinical use.Here, we combined BoNT/A with two fast‐acting inhibitors of excitation–contraction coupling inhibitors (ECCI), either the μ‐conotoxin CnIIIC or dantrolene, and tested the effect of their co‐injection on a model of hind‐limb paralysis in rodents using behavioural, biochemical, imaging and electrophysiological assays.The BoNT/A‐ECCI combinations accelerated the onset of muscle relaxation. Surprisingly, they also potentiated the peak effect and extended the duration of the three BoNT/A commercial preparations OnabotulinumtoxinA, AbobotulinumtoxinA and IncobotulinumtoxinA. ECCI co‐injection increased the number of BoNT/A molecules entering motoneuron terminals, which induced a faster and greater cleavage of SNAP‐25 during the onset and peak phases, and prolonged the attenuation of nerve‐muscle neurotransmission during the recovery phase. We estimate that ECCI co‐injection yields a threefold potentiation in BoNT/A pharmacological activity.Overall, our results show that the pharmacological activity of BoNT/A can be combined and synergized with other bioactive molecules and uncover a novel strategy to enhance the neuromuscular effects of BoNT/A without altering the neurotoxin moiety or intrinsic activity, thus maintaining its exceptional safety profile. [ABSTRACT FROM AUTHOR]

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Botulinum neurotoxins (BoNTs), including serotypes A and E, are potent biotoxins known to cause human poisoning. In addition to the critical protective antigen found in the full BoNT molecule, the receptor binding domain (Hc domain), BoNTs also harbour another essential protective antigen—the light chain‐translocation domain (L‐HN domain). Leveraging these pivotal protective antigens, we genetically engineered a series of inactivated chimeric molecules incorporating L‐HN and Hc domains of BoNT/A and E. The structure of these chimeric molecules, mirror BoNT/A and E, but are devoid of enzyme activity. Experimental findings demonstrated that a lead candidate mEL‐HN‐mAHc harnessing the inactivated protease LCHN/E with the mutated gangliosides binding site Hc/A (mE‐mA) elicited robust immune protection against BoNT/A and E simultaneously in a mouse model, requiring low immune dosages and minimal immunisations. Moreover, mE‐mA exhibited high protective efficacy against BoNT/A and E in guinea pigs and New Zealand white rabbits, resulting in elevated neutralising antibody titres. Furthermore, mE‐mA proved to be a more stable and safer vaccine compared to formaldehyde‐inactivated toxoid. Our data underscore the genetically engineered mE‐mA as a highly effective bivalent vaccine against BoNT/A and E, paving the way for the development of polyvalent vaccines against biotoxins. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine. Mice vaccinated with CS-Hc/E exhibited superior antibody titers compared to those receiving Hc/E alone. To develop a trivalent vaccine against BoNT/A, BoNT/B, and BoNT/E--key contributors to the vast majority of human botulism--we conjugated CS-Hc/E with a biotinylated atoxic chimeric protein incorporating neutralizing epitopes from BoNT/A and BoNT/B. This chimeric protein includes the binding domain of BoNT/A, along with the protease-inactive light chain and translocation domains of BoNT/B. The interaction between CS and biotin formed a stable tetrameric antigen, EBA. Vaccination with EBA in mice elicited robust antibody responses and provided complete protection against lethal doses of BoNT/A, BoNT/B, and BoNT/E. Our findings highlight EBA's potential as a stable and effective broadspectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies. [ABSTRACT FROM AUTHOR]

One of the aims of diagnostic nerve blocks is to identify the overactive muscles that lead to a specific spasticity pattern. However, to date, there is no evidence on how nerve blocks may affect botulinum neurotoxin-A (BoNT-A) dose in patients with spasticity. This case-control study aims to assess the role of diagnostic nerve block in defining BoNT-A starting dose at first treatment. Patients with upper and lower limb spasticity treated for the first time with BoNT-A were retrospectively divided into two groups: Group 1 (n = 43) was evaluated with clinical assessment and diagnostic nerve block; Group 2 (n = 56) underwent clinical assessment only. Group 1 was injected with higher BoNT-A doses in some muscles (i.e., flexor digitorum profundus, soleus), and received a higher BoNT-A cumulative dose with a larger number of injected muscles for some spasticity patterns (i.e., "clenched fist", "flexed fingers", "adducted thigh"). Diagnostic nerve block may help the clinician to optimize and personalize the BoNT-A dose since the first BoNT-A treatment. [ABSTRACT FROM AUTHOR]

Background: Botulinum neurotoxin injections are the most frequently performed cosmetic procedures, but conventional blind injection for glabellar wrinkles remains to have some limitations. Aims: We intend to directly inject botulinum neurotoxin into the glabella complex guided by real time ultrasound. We aim to propose a more efficient and safer botulinum neurotoxin injection strategy for glabellar wrinkles. Methods: A total of 40 subjects with moderate to severe glabellar lines were enrolled in this study to receive botulinum neurotoxin injection, either through ultrasound‐guided real time injection or conventional blind injection. Facial Wrinkle Scale (ranging from 0 = none to 3 = severe) and inter‐brow distance (from 3D scanned face images) were used to evaluate the glabellar wrinkles improvement. Paired t test and two‐sample t test were performed to analyze the within‐group and between‐group differences. Results: The wrinkle score reduction was significant (p < 0.0001) immediately after the injection in ultrasound‐guided injection group, but not in blind injection group (p = 0.163). Ultrasound‐guided injection also showed a higher performance of wrinkle score reduction and more effective inter‐brow distance increase over blind injection at Day 0 (p < 0.0001), Day 1 (p < 0.0001), Day 21 (p < 0.01) and Day 35 (p < 0.01) after initial treatment. Conclusions: The results of the study confirmed that botulinum neurotoxin injection for glabellar wrinkles under ultrasound guidance achieves quicker onset of action and better final outcomes compared to conventional blind injection. [ABSTRACT FROM AUTHOR]

This article discusses the use of botulinum neurotoxin (BoNT) for the treatment of glabellar lines (GL), which are the lines between the eyebrows that contribute to the appearance of aging. The primary muscle involved in GL is the corrugator supercilii muscle (CSM). The article highlights the importance of understanding the specific contraction patterns of the CSM in order to tailor treatment approaches and achieve precise and natural outcomes. The article also provides an improved injection protocol for the safe and effective administration of BoNT for GL treatment, taking into account the anatomical interconnectedness of the glabellar muscles. The authors emphasize the need for careful attention to dosage, injection sites, and other factors that can influence treatment outcomes and patient satisfaction. [Extracted from the article]

Botulinum neurotoxins are the most lethal and category 'A' bioterrorism agent. Despite all efforts, there is no drug available for intoxicating human. The 8-HQ is a well-known privileged scaffold which possesses metal chelation properties and its derived compounds are reported to inhibit the catalytic activity of BoNTs. Novel derivatives of NSC1012 were designed and synthesized via Mannich reaction. After characterization by NMR & mass spectrometry, compounds were studied for its toxicity profiling by in vitro and in vivo experiments. The designed compounds were screened and validated against BoNTs using molecular docking and FTS assay. The derived derivatives displayed no significant hemolytic activity (upto 500 µM) and low cytotoxicity with the CC50 value ranging from 105.94–80.97 µM. The in vivo assay reveals, 25 mM concentration is a NOAEL dose with no observed significant difference in biochemical parameters between the control and treated groups. Molecular docking study showed "hits" with the binding energies for BoNT/A found in the range of −11.65 to −7.24 kcal/mol, BoNT/B between −10.69 to −6.91 kcal/mol, BoNT/E it was −8.18 to −5.30 kcal/mol and for BoNT/F were −8.94 to −6.86 kcal/mol. The FTSA result reveals the binding efficiency of the compounds with the shift in ΔTm from 8.10 to −7.15 °C for serotypes under study. Synthesized compounds are less toxic to the cells, not significantly affect the biochemical profile of the animals, and have shown high binding affinity as well as inhibited the catalytic activity of the BoNTs. These molecules can pave the way for the development of therapeutics against the neurotoxins. [ABSTRACT FROM AUTHOR]

Abstract Background Hemifacial spasm (HFS) is a neuromuscular disorder characterized by unilateral facial muscle spasms, negatively impacts quality of life due to social embarrassment. Botulinum Neurotoxin (BoNT) injections have emerged as a viable therapeutic approach. This systematic review evaluated the efficacy and safety of BoNT injections for HFS management, along with effects on patients’ quality of life and mental health. Materials and methods A systematic search for studies on BoNT treatment for HFS published between January 1, 2000, and May 1, 2024, was performed across major databases. Study quality was evaluated using Cochrane and Joanna Briggs Institute (JBI) tools, with data management handled by EndNote X9 and statistical analyses conducted via Review Manager (RevMan 5.4) and STATA 14.0. Results Thirty-five studies met the inclusion criteria: 2 RCTs comprising 83 HFS patients compared the efficacy of perioral injections of botulinum toxin and placebo, while 33 single-arm studies reported outcomes for 2786 patients post-BoNT injection. The selection of 17 single-arm studies focused on the effectiveness rate as the key outcome metric. Pooled estimate signified a remarkably high effectiveness (ES: 0.882, 95% CI: 0.830, 0.926, P

Abstract Background Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI. Methods We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany. Results Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits. Conclusion Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.

INTRODUCTION. The outbreak of foodborne botulism that occurred in Russia in June 2024 once again demonstrated the danger of this rather rare but severe infectious disease caused by ingesting botulinum neurotoxin. The only aetiological treatment for botulism is currently the administration of antitoxins against various serotypes of botulinum toxin. However, antitoxins do not provide rapid regression of neurological symptoms, which may raise doubts about the effectiveness of the selected treatment option. It is impossible to assess the potential of specific treatment without understanding the mechanisms of action of botulinum toxin and antitoxin.AIM. This study aimed to systemise information on the mechanism underlying the damaging effect of botulinum neurotoxin, aetiological antitoxin treatment, and the patient recovery process.DISCUSSION. The mechanism underlying the damaging effect of botulinum neurotoxin consists in the destruction of SNARE proteins in presynaptic cholinergic nerve terminals, which disrupts the release of acetylcholine into the synaptic cleft and the transmission of excitation between neurons. The lack of acetylcholine at the neuromuscular junction results in a distinctive form of persistent flaccid paralysis. The specific mechanism of action of botulinum toxin determines the treatment strategy, which includes a set of life-sustaining measures and the earliest possible antiserum administration. If used within 48 hours from the onset of symptoms, botulinum antitoxin binds botulinum toxin circulating in the blood, which stops the progression of paralysis and prevents further disorders in patients. However, botulinum antitoxin cannot neutralise the effect of the toxin that has already bound to nerve receptors, so clinical symptoms may worsen within 12 hours after antiserum administration. Restoration of normal neuronal transmission occurs through the formation of new axonal sprouts and can take a long time.CONCLUSIONS. Antitoxin administration is effective and irreplaceable in the aetiological treatment of botulism. Nevertheless, the duration of recovery depends on the speed of reinnervation and restoration of transmission at the neuromuscular junction.

Introduction Migraine is a common disease that a large part of the population struggles with. Stressful work and poor eating habits increase the risk of headaches. The basic therapy is lifestyle change, and when this does not bring results, medications are used. The choice of the appropriate preparation depends on the characteristics of the pain and the patient's condition. Knowledge about different treatment methods can improve patients' lives. Aim of the study The aim of the article was to present current guidelines for migraine therapy depending on the individual patient's requirements. Materials and methods The article is the result of a review of recent scientific literature using PubMed, Scopus and Google Scholar databases. The literature was reviewed using the keywords. Results Many clinical trials have examined the effects of different classes of drugs on migraine headaches. The final effect depends on the dose used, the moment of drug administration, and the patient's age, gender and health condition. Doctors often have to modify therapy within the same group of drugs to find a drug that will work for a given patient. Conclusions Clinical trials have proven the effectiveness of, among others, non-steroidal anti-inflammatory drugs, triptans and botulinum neurotoxin. A clinically significant analgesic effect is sometimes characterized by side effects, therefore careful selection of the preparation and patient observation are important. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, have been used for the treatment of various central and peripheral neurological conditions. Recent studies have suggested that BoNTs may also have a beneficial effect on pain conditions. It has been hypothesized that one of the mechanisms underlying BoNTs' analgesic effects is the inhibition of pain-related receptors' transmission to the neuronal cell membrane. BoNT application disrupts the integration of synaptic vesicles with the cellular membrane, which is responsible for transporting various receptors, including pain receptors such as TRP channels, calcium channels, sodium channels, purinergic receptors, neurokinin-1 receptors, and glutamate receptors. BoNT also modulates the opioidergic system and the GABAergic system, both of which are involved in the pain process. Understanding the cellular and molecular mechanisms underlying these effects can provide valuable insights for the development of novel therapeutic approaches for pain management. This review aims to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions by inhibiting the transmission of pain-related receptors. [ABSTRACT FROM AUTHOR]

Recombinant mutant holotoxin BoNTs (rBoNTs) are being evaluated as possible vaccines against botulism. Previously, several rBoNTs containing 2–3 amino acid mutations in the light chain (LC) showed significant decreases in toxicity (2.5-million-fold–12.5-million-fold) versus wild-type BoNT/A1, leading to their current exclusion from the Federal Select Agent list. In this study, we added four additional mutations in the receptor-binding domain, translocation domain, and enzymatic cleft to further decrease toxicity, creating 7M rBoNT/A1. Due to poor expression in E. coli, 7M rBoNT/A1 was produced in an endogenous C. botulinum expression system. This protein had higher residual toxicity (LD50: 280 ng/mouse) than previously reported for the catalytically inactive rBoNT/A1 containing only three of the mutations (>10 µg/mouse). To investigate this discrepancy, several additional rBoNT/A1 constructs containing individual sets of amino acid substitutions from 7M rBoNT/A1 and related mutations were also endogenously produced. Similarly to endogenously produced 7M rBoNT/A1, all of the endogenously produced mutants had ~100–1000-fold greater toxicity than what was reported for their original heterologous host counterparts. A combination of mutations in multiple functional domains resulted in a greater but not multiplicative reduction in toxicity. This report demonstrates the impact of production systems on residual toxicity of genetically inactivated rBoNTs. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the intramuscular distribution pattern of the medial plantar nerve and determine its motor nerve ending territories within the abductor hallucis muscle using modified Sihler's staining and external anatomical landmarks. The study included 40 specimens of the abductor hallucis muscle (13 men and seven women) from formalin-fixed (ten cadavers) and fresh cadavers (ten cadavers), with a mean age of 77.6 years. The entry point of the medial plantar nerve into the muscle was examined, followed by Sihler's staining to analyze the intramuscular distribution pattern and motor nerve ending location within the abductor hallucis muscle. Ultrasound- and palpation-guided injections were performed to verify the applicability of motor nerve ending location-based injections. The areas with the highest concentrations of nerve entry points and nerve endings were identified in the central portion of the muscle. Ultrasound- and palpation-guided injections were safely positioned near the densest nerve ending region of the muscle. These detailed anatomical data and injection methods would be beneficial for proceeding with safe and effective injection treatments using various analgesic agents to alleviate abductor hallucis muscle-associated pain disorders. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative review explores the role of US in BoNT administration, particularly in complex anatomical regions, highlighting its impact on treatment customization, real-time visualization, and complication reduction. Materials and methods: A comprehensive literature search was conducted using PubMed, MEDLINE, Embase, and Cochrane Library for articles published from January 2018 to December 2023. Search terms included "Botulinum neurotoxin," "facial anatomy," "ultrasonography guided injection," and "facial muscle sonoanatomy." Studies focusing on US-guided BoNT injections in facial muscles were included. Data extraction and synthesis were performed independently by two reviewers, focusing on study design, ultrasonography techniques, outcomes, and conclusions. Results: The review found that US guidance significantly enhances the precision of BoNT injections by providing real-time visualization of facial muscles and blood vessels, thereby reducing the risk of adverse events. US enables tailored injection strategies, ensuring symmetrical facial expressions and minimizing over-treatment. The technique also offers immediate feedback, allowing for on-the-spot adjustments to improve treatment efficacy and safety. However, the review identified limitations, including potential selection bias and variability in US techniques across different studies. Conclusion: US guidance for BoNT injections into facial muscles offers substantial benefits in terms of precision, safety, and treatment customization. Despite the identified limitations, the integration of US into clinical practice is poised to enhance patient outcomes in aesthetic and therapeutic procedures. Further research is needed to standardize US techniques and broaden the inclusivity of studies to validate these findings comprehensively. [ABSTRACT FROM AUTHOR]

Our objective was to provide expert consensus on best practices for anatomy teaching and training on ultrasound-guided botulinum neurotoxin type A (BoNT-A) injection for specialists involved in treating spasticity and dystonia. Nine experts (three neurologists; six physical medicine and rehabilitation physicians) participated in a three-round modified Delphi process. Over three rounds, experts reached consensus on 15 of 16 statements describing best practices for anatomy and BoNT-A injection training. They unanimously agreed that knowledge of the target audience, including their needs and current competency, is crucial when designing training programs. Experts also agreed that alignment between instructors is essential to ensure consistency of approach over time and between regions, and that training programs should be simple, adaptable, and "hands-on" to enhance engagement and learning. Consensus was also reached for several other key areas of training program development. The best-practice principles identified by expert consensus could aid in the development of effective, standardized programs for anatomy teaching and BoNT-A injection training for the purposes of treating spasticity and dystonia. This will enhance the exchange of knowledge, skills, and educational approaches between global experts, allowing more specialists to treat important movement disorders and ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Due to its heterogeneous manifestation an individualized approach to reach therapeutic goals in cervical dystonia (CD) is advantageous. Objectives: The aim of the current study was to adapt goal attainment scaling (GAS) to drive the management of CD. Methods: 38 patients with CD, regularly treated with botulinum neurotoxin (BoNT), were involved in the current exploratory observational pilot study. GAS, including domains of motor, pain, disability, and psychiatric features, was applied to set up individualized goals with the calculation of initial GAS T‐scores. Following at least 4 BoNT injection cycles, patients were reassessed whether they reached the pre‐set goals. Results: The initial GAS T‐scores (median: 36.9, range: 22.8–40) significantly improved (P < 0.001) to the end of the study (the median of final GAS T‐scores: 50, range: 25.5–63.6). Conclusions: The applicability of GAS in CD patients was confirmed, but further large‐scale studies are needed refining this innovative approach. [ABSTRACT FROM AUTHOR]

Cervical dystonia (CD) causes involuntary movements and postures of the head, neck, and shoulders, as well as nonmotor symptoms including pain, mood, and sleep dysfunction, and impacts quality of life. The first-line treatment for CD is botulinum neurotoxin (BoNT) injections. The clinical presentation and diagnosis of CD, as well as where BoNT resides in the treatment landscape, is reviewed first. Next, the mechanism of action and the pharmacological differences in the available preparations of BoNT products are explained. The evidence base for motor and nonmotor efficacy and safety of the available BoNT formulations is reviewed, with attention to duration of benefit as a driver of patient satisfaction. Practical determinants of BoNT efficacy are reviewed including muscle selection, accurate muscle injection, factors related to poor or deteriorating response, and immunogenicity. BoNT represents a significant advancement in the treatment of CD. More accurate diagnosis, muscle selection and targeting, and dosing can improve outcomes with existing BoNT formulations. Further refinement of BoNT potency, duration of action, safety, and immunogenicity will help reduce unmet needs in the magnitude and duration of benefit. Additional validation of DBS and MRI-guided focused ultrasound may expand options for patients with toxin nonresponse. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Complex abdominal wall hernias represent a significant reconstructive challenge to the general surgeon. In patients with loss of abdominal domain, standard surgical techniques such as anterior component separation or transversus abdominus muscle release may not allow for primary fascial closure. In complex ventral wall hernias, visceroabdominal disproportion may need to be addressed prior to an attempt at hernia repair. Tissue expanders placed in the intermuscular space is a novel technique used to increase intraabdominal volume and safely allow reduction of viscera with subsequent closure of the myofascia. We present the case of an adult patient with complications of an untreated congenital omphalocele who underwent a successful two stage operation using tissue expanders in the abdominal wall combined with anterior component separation.

Abstract Background Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. Case presentation To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. Conclusion This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.

Hypertrophic scars (HS) and keloids are challenging dermatological conditions that often lead to physical and psychological distress in affected individuals. Current therapeutic approaches have limitations, prompting the exploration of novel treatments. Botulinum Neurotoxin BoNT-A has emerged as a promising candidate in managing these scars. This comprehensive review delves into the pathophysiology of HS and keloids, the shortcomings of existing treatments, and the mechanisms underlying BoNT-A's potential efficacy. Through an analysis of clinical studies and evidence, the review evaluates BoNT-A's impact on scar formation and patient outcomes. Safety and side effects and the potential influence of BoNT-A on quality of life are also considered. Comparative analysis with traditional therapies underscores the advantages and challenges of BoNT-A use. The review concludes by suggesting future research directions and emphasizing the significance of Botulinum Neurotoxin BoNT-A as a promising therapeutic option. This article provides valuable insights for clinicians, researchers, and patients seeking innovative solutions for HS and keloids.

Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations. As such, the development of more promising botulism prevention and treatment modalities is warranted. Here, we designed an mRNA encoding B9-hFc – a heavy-chain antibody fused to VHH and human Fc that can neutralize BoNT serotype B (BoNT/B) effectively – and assessed its expression in vitro and in vivo. The results confirmed that our mRNA demonstrates good expression in vitro and in vivo. Moreover, a single mRNA lipid nanoparticle injection effectively prevents BoNT/B intoxication in vivo, with effects comparable to those of protein antibodies. In conclusion, we explored and clarified whether mRNA drugs encoding neutralizing antibodies prevent BoNT/B intoxication. Our results provide an efficient strategy for further research on the prevention and treatment of intoxication by botulinum toxin.

ABSTRACTBotulism is a fatal neurologic disease caused by the botulinum toxin (BoNT) produced by Clostridium botulinum. It is a rare but highly toxic disease with symptoms, such as cramps, nausea, vomiting, diarrhea, dysphagia, respiratory failure, muscle weakness, and even death. Currently, two types of antitoxin are used: equine-derived heptavalent antitoxin and human-derived immunoglobulin (BabyBIG®). However, heptavalent treatment may result in hypersensitivity, whereas BabyBIG®, has a low yield. The present study focused on the development of three anti-BoNT monoclonal antibodies (mAbs), 1B18, C25, and M2, in Nicotiana benthamiana. The plant-expressed mAbs were purified and examined for size, purity and integrity by SDS-PAGE, western blotting and size-exclusion chromatography. Analysis showed that plant-produced anti-BoNT mAbs can fully assemble in plants, can be purified in a single purification step, and mostly remain as monomeric proteins. The efficiency of anti-BoNT mAbs binding to BoNT/A and B was then tested. Plant-produced 1B18 retained its ability to recognize both mBoNT/A1 and ciBoNT/B1. At the same time, the binding specificities of two other mAbs were determined: C25 for mBoNT/A1 and M2 for ciBoNT/B1. In conclusion, our results confirm the use of plants as an alternative platform for the production of anti-BoNT mAbs. This plant-based technology will serve as a versatile system for the development botulism immunotherapeutics.

Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A-G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1-OrfX3 complex, which are encoded in the orfX cluster of a BoNT/E1-producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.

Equine-derived antitoxin (BAT®) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT® is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with KD values ranging from 3.86 nM to 103 nM (median KD 20.9 nM). Five mAb-binding non-overlapping epitopes were humanized and affinity matured to create antibodies hu6G6.2, hu6G7.2, hu6G9.1, hu6G10, and hu6G11.2, with IgG KD values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD50s of BoNT/G at a total mAb dose of 6.25 μg per mouse. The mAb combinations have the potential for use in the diagnosis and treatment of botulism due to serotype G and, along with antibody combinations to BoNT/A, B, C, D, E, and F, provide the basis for a fully recombinant heptavalent botulinum antitoxin to replace the legacy equine product.

Background: Graves' ophthalmopathy (GO) is characterized by upper eyelid retraction (UER), the most prevalent clinical sign. We aimed to assess the clinical efficacy of a multimodal combination of steroids, 5-fluorouracil (5-FU), and botulinum neurotoxin A (BoNT-A) injections in managing UER with GO and analyze the clinical factors in relation to the injection response. Methods: A total of 37 eyes from 23 patients were enrolled for UER with GO. At the endocrinology clinic, the patients were referred to the ophthalmology clinic after taking antithyroid medication for an average of 5.76 months (13 patients), while 10 patients were initially diagnosed with GO and referred to the endocrinology clinic for management of the thyroid hormone function. They performed an orbital computed tomography (CT) scan and measured the cross-sectional area of the orbit, orbital fat, and each extra ocular muscle (EOM) except for the inferior oblique muscle 4 mm behind the eyeball. Each of the EOMs and orbital fat were calculated as a ratio to the total orbit area. A total of 0.1 cc of triamcinolone (40 mg/mL), dexamethasone (5 mg/mL), 5-FU, and BoNT-A (2.5 units) was injected transconjunctivally. Medical records were examined and photographs were utilized to assess MRD1, inferior palpebral fissure (IPF), and lid lag during down gaze before and after the injection. The patients were divided into two groups: responders (more than 1 mm decrease in MRD1 after injection) and non-responders. During the follow-up period (11.0 ± 11.6 months), any potential adverse effects were monitored. Results: CAS decreased from 3.0 ± 0.8 to 1.4 ± 0.5 after the injection, and MRD1 decreased from 5.0 ± 0.9 mm to 4.5 ± 1.3 mm. Sixty percent of the patients were responders. Before and after the injection, the difference between IPF and MRD1 in responders was 0.60 ± 1.10 mm and 0.90 ± 0.90 mm, respectively, whereas, in non-responders, it was −0.57 ± 0.88 mm and −0.15 ± 0.75 mm, respectively. In the responders, pre-injection IPF and FT4 were significantly higher (p < 0.05). Responders had a larger EOM cross-sectional area (153.5 ± 18.0 mm2), including a larger lateral rectus muscle cross-sectional area (37.6 ± 9.7 mm2) than non-responders (132.0 ± 27.9 mm2; 29.1 ± 8.1 mm2). In responders, the treatment effect on IPF and MRD1 remained consistent at 1.2 ± 3.4 mm and 1.2 ± 1.6 mm, respectively, during the latest follow-up assessment. Conclusions: The combination injection of corticosteroids, 5-FU, and BoNT-A would be effective, especially, in patients with hyperthyroidism and an elongated IPF. Additionally, an increase in EOM cross-sectional area on CT, up to 150 mm2, may serve as an additional positive indicator for the use of multimodal injections in UER with GO. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin serotype A (BoNT/A) is widely used in therapeutics and cosmetics. The effects of multi‐dosed BoNT/A treatment are well documented on the peripheral nervous system (PNS), but much less is known on the central nervous system (CNS). Here, the mechanism of multi‐dosed BoNT/A leading to CNS neurodegeneration is explored by using the 3D human neuron‐glia model. BoNT/A treatment reduces acetylcholine, triggers astrocytic transforming growth factor beta, and upregulates C1q, C3, and C5 expression, inducing microglial proinflammation. The disintegration of the neuronal microtubules is escorted by microglial nitric oxide, interleukin 1β, tumor necrosis factor α, and interleukin 8. The microglial proinflammation eventually causes synaptic impairment, phosphorylated tau (pTau) aggregation, and the loss of the BoNT/A‐treated neurons. Taking a more holistic approach, the model will allow to assess therapeutics for the CNS neurodegeneration under the prolonged use of BoNT/A. [ABSTRACT FROM AUTHOR]

Background: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. Case presentation: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. Conclusion: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies. [ABSTRACT FROM AUTHOR]

Botulinum Neurotoxin Type A (BoNT-A) injections using Ultrasound (US) guidance have led to research evaluating changes in muscle architecture. Controversy remains as to what constitutes increased Echo-Intensity (EI) in spastic muscles and whether this may affect outcomes. We aim to provide a narrative review of US muscle architecture changes following Central Nervous System (CNS) lesions and explore their relationship to spasticity. Medline, CINAHL, and Embase databases were searched with keywords: ultrasonography, hypertonia, spasticity, fibrosis, and Heckmatt. Three physicians reviewed the results of the search to select relevant papers. Reviews identified in the search were used as a resource to identify additional studies. A total of 68 papers were included. Four themes were identified, including histopathological changes in spastic muscle, effects of BoNT-A on the muscle structure, available US modalities to assess the muscle, and utility of US assessment in clinical spasticity. Histopathological studies revealed atrophic and fibrofatty changes after CNS lesions. Several papers described BoNT-A injections contributing to those modifications. These changes translated to increased EI. The exact significance of increased muscle EI remains unclear. The Modified Heckmatt Scale (MHS) is a validated tool for grading muscle EI in spasticity. The use of the US may be an important tool to assess muscle architecture changes in spasticity and improve spasticity management. Treatment algorithms may be developed based on the degree of EI. Further research is needed to determine the incidence and impact of these EI changes in spastic muscles. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs), derived from Clostridium botulinum, have been employed to treat a range of central and peripheral neurological disease. Some studies indicate that BoNT may be beneficial for pain conditions as well. It has been hypothesized that BoNTs may exert their analgesic effects by preventing the release of pain‐related neurotransmitters and neuroinflammatory agents from sensory nerve endings, suppressing glial activation, and inhibiting the transmission of pain‐related receptors to the neuronal cell membrane. In addition, there is evidence to suggest that the central analgesic effects of BoNTs are mediated through their retrograde axonal transport. The purpose of this review is to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions. Most of the studies reviewed in this article were conducted using BoNT/A. The PubMed database was searched from 1995 to December 2022 to identify relevant literature. [ABSTRACT FROM AUTHOR]

This review discusses the expanding application of botulinum neurotoxin in treating neurological conditions. The article specifically explores novel approaches to using non-paralytic botulinum molecules. These new molecules, such as BiTox or el-iBoNT, offer an alternative for patients who face limitations in using paralytic forms of botulinum neurotoxin due to concerns about muscle function loss. We highlight the research findings that confirm not only the effectiveness of these molecules but also their reduced paralytic effect. We also discuss a potential cause for the diminished paralytic action of these molecules, specifically changes in the spatial parameters of the new botulinum molecules. In summary, this article reviews the current research that enhances our understanding of the application of new botulinum neurotoxins in the context of common conditions and suggests new avenues for developing more efficient molecules. [ABSTRACT FROM AUTHOR]

Introduction: This study explores the effects of botulinum neurotoxin (BoNT) on the relationship between dystonia and tremor, specifically focusing on cervical dystonia (CD) and its connection to head tremor. Methods: Fourteen CD patients were recruited; eight (57%) with clinically observable head oscillations were included in further analysis. A highresolution magnetic search coil system precisely measured head movements, addressing two questions: 1) BoNT's effects on head movement amplitude, frequency, and regularity, and 2) BoNT's influence on the relationship between head position and head oscillations. For the first question, temporal head position measurements of three patients were analyzed before and after BoNT injection. The second question examined the effects of BoNT injections on the dependence of the oscillations on the position of the head. Results: Three distinct trends were observed: shifts from regular to irregular oscillations, transitions from irregular to regular oscillations, and an absence of change. Poincaré analysis revealed that BoNT induced changes in regularity, aligning oscillations closer to a consistent "set point" of regularity. BoNT injections reduced head oscillation amplitude, particularly in head orientations linked to high-intensity pre-injection oscillations. Oscillation frequency decreased in most cases, and overall variance in the amplitude of head position decreased post-injection. Discussion: These findings illuminate the complexity of CD but also suggest therapeutic potential for BoNT. They show that co-existing mechanisms contribute to regular and irregular head oscillations in CD, which involve proprioception and central structures like the cerebellum and basal ganglia. These insights advocate for personalized treatment to optimize outcomes that is based on individual head oscillation characteristics. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (BoNT) injection for the treating plunged nose, post-rhinopasty and hyaluronic filler migration is common procedures in clinical settings. However, the lack of thorough anatomical understanding makes it difficult to locate the nose region muscles. The anatomical considerations concerned with BoNT injection into the nasalis, levator labii superioris alaeque, and depressor septi nasi muscles were reviewed in this study. The injection spots have been presented for the nasalis, levator labii superioris alaeque, and depressor septi nasi muscles, with the recommended injection technique for each muscle. We have suggested the ideal injection sites in association with outer anatomical landmarks of the nose region. Moreover, these proposals would support a more accurate procedure of BoNT injection in relieving plunged nose, preventing post-rhinoplasty deviation, and migration of the hyaluronic acid filler. [ABSTRACT FROM AUTHOR]

Background: The concept of "skin boosters" has evolved, marking a shift from traditional uses of hyaluronic acid (HA) fillers primarily for augmenting skin volume to a more diverse application aimed at improving dermal conditions. Restylane Vital and other HA fillers have been repurposed to combat skin aging and wrinkles by delivering HA directly to the dermis. Objectives: This review aims to define the term "skin booster" and to discuss the various components that constitute skin boosters. It seeks to provide a comprehensive overview of the different ingredients used in skin boosters, their roles, and their impact on enhancing dermal conditions. Methods: A comprehensive review was conducted, focusing on representative skin booster ingredients. The approach involved analyzing the different elements used in skin boosters and their specific roles in enhancing dermal improvement. Results: The findings indicate that skin boosters, encompassing a range of ingredients, are effective in improving the condition of the skin's dermis. The review identifies key ingredients in skin boosters and their specific benefits, including hydration, elasticity improvement, and wrinkle reduction. Conclusions: Skin boosters represent a significant development in dermatological treatments, offering diverse benefits beyond traditional HA fillers. This review provides valuable insights into the constituents of skin boosters and their effectiveness, aiding readers in making informed decisions about these treatments. The potential of skin boosters in dermatological practice is considerable, warranting further research and application. [ABSTRACT FROM AUTHOR]

Spasticity management should be provided within the context of a comprehensive person-centered rehabilitation program. Furthermore, active goal setting for specific spasticity interventions is also important, with a well-established “more is better” approach. It is critical to consider adjunctive therapy and multimodal approaches if patients are not attaining their treatment goals. Often used interchangeably, there may be confusion between the terms adjunctive and multimodal therapy. Yet it is imperative to understand the differences between these approaches to achieve treatment goals in spasticity management. Addition of a secondary pharmacologic or non-pharmacologic treatment to optimize the efficacy of the initial modality, such as adding electrical stimulation or casting to BoNT-A, is considered an adjunctive therapy. Adjunctive therapy is time-specific and requires the added therapy be initiated within a specific period to enhance the primary treatment; usually within 2 weeks. Multimodal therapy is an integrated, patient-centric program of pharmacologic and non-pharmacologic strategies utilized in a concurrent/integrated or sequential manner to enhance the overall treatment effect across a variety of spasticity-associated impairments (e.g., neural and non-neural components). Moreover, within a multimodal approach, adjunctive therapy can be used to help enhance the treatment effect of one specific modality. The objectives of this paper are to clarify the differences between adjunctive and multimodal therapies, provide a brief evidence-based review of such approaches, and highlight clinical insights on selecting multimodal and adjunctive therapies in spasticity management.

Introduction Migraine is a common disease that a large part of the population struggles with. Stressful work and poor eating habits increase the risk of headaches. The basic therapy is lifestyle change, and when this does not bring results, medications are used. The choice of the appropriate preparation depends on the characteristics of the pain and the patient's condition. Knowledge about different treatment methods can improve patients' lives. Aim of the study The aim of the article was to present current guidelines for migraine therapy depending on the individual patient's requirements. Materials and methods The article is the result of a review of recent scientific literature using PubMed, Scopus and Google Scholar databases. The literature was reviewed using the keywords. Results Many clinical trials have examined the effects of different classes of drugs on migraine headaches. The final effect depends on the dose used, the moment of drug administration, and the patient's age, gender and health condition. Doctors often have to modify therapy within the same group of drugs to find a drug that will work for a given patient. Conclusions Clinical trials have proven the effectiveness of, among others, non-steroidal anti-inflammatory drugs, triptans and botulinum neurotoxin. A clinically significant analgesic effect is sometimes characterized by side effects, therefore careful selection of the preparation and patient observation are important.

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies.

One of the aims of diagnostic nerve blocks is to identify the overactive muscles that lead to a specific spasticity pattern. However, to date, there is no evidence on how nerve blocks may affect botulinum neurotoxin-A (BoNT-A) dose in patients with spasticity. This case-control study aims to assess the role of diagnostic nerve block in defining BoNT-A starting dose at first treatment. Patients with upper and lower limb spasticity treated for the first time with BoNT-A were retrospectively divided into two groups: Group 1 (n = 43) was evaluated with clinical assessment and diagnostic nerve block; Group 2 (n = 56) underwent clinical assessment only. Group 1 was injected with higher BoNT-A doses in some muscles (i.e., flexor digitorum profundus, soleus), and received a higher BoNT-A cumulative dose with a larger number of injected muscles for some spasticity patterns (i.e., “clenched fist”, “flexed fingers”, “adducted thigh”). Diagnostic nerve block may help the clinician to optimize and personalize the BoNT-A dose since the first BoNT-A treatment.

As one of the most fatal substances, botulinum neurotoxins (BoNTs) have never acted solo to accomplish their formidable missions. Most notably, nontoxic nonhemagglutinin (NTNH), a protein co‐secreted with BoNT by bacteria, plays critical roles to stabilize and protect BoNT by tightly associating with it to form the minimal progenitor toxin complex (M‐PTC). A new cryo‐EM structure of the M‐PTC of a BoNT‐like toxin from Weissella oryzae (BoNT/Wo) reveals similar assembly modes between M‐PTC/Wo and that of other BoNTs, yet also reveals some unique structural features of NTNH/Wo. These findings shed new light on the potential versatile roles of NTNH during BoNT intoxication. [ABSTRACT FROM AUTHOR]

Objective: In the esthetic field, the masseter muscle is commonly targeted by botulinum neurotoxin for facial contouring. However, multiple botulinum neurotoxin injections have been reported to cause muscle fibrosis. Ultrasonography can be useful for clinical consideration in such cases. Materials and Methods: This study presents nine cases of masseteric fibrosis caused by repeated botulinum neurotoxin injections with ultrasonographic analysis of full and partial masseteric fibrosis. Results: Repetitive botulinum neurotoxin injections resulted in reduced masseter muscle volume, which frequently appeared hyperechoic on ultrasonography. The hyperechoic region was mostly located in the deep and posterior portions; however, in some cases, it was observed throughout the muscle, including the superficial, deep, or both areas. Conclusion: The fibrotic masseter muscles appear hyperechoic, and ultrasonography is necessary to analyze the degree and location of fibrosis. Predictions can be made for cases in which botulinum neurotoxin injections may have less of an effect after ultrasonography. Because muscle fibrosis can be localized, it is necessary to confirm the degree and location of fibrosis before determining the effective area of injection. In clinical practice, muscle fibrosis may be visible in a specific area where blind injections are administered. [ABSTRACT FROM AUTHOR]