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8 pages, 3098 KB  
Case Report
Pattern Changes and Recurrent Remissions in Cervical Dystonia: Insights from a Long-Term Treated Case
by Simone Aloisio, Massimiliano Passaretti, Luca Angelini, Martina De Riggi, Francesca Santachiara, Anna Sofia Grandolfo, Daniele Birreci and Matteo Bologna
Toxins 2026, 18(6), 243; https://doi.org/10.3390/toxins18060243 - 25 May 2026
Viewed by 237
Abstract
Cervical dystonia (CD) is increasingly recognized as a disorder with a dynamic clinical course rather than a fixed phenomenological profile. This report describes the long-term observation of a man with isolated CD followed for nearly 12 years from symptom onset. The course was [...] Read more.
Cervical dystonia (CD) is increasingly recognized as a disorder with a dynamic clinical course rather than a fixed phenomenological profile. This report describes the long-term observation of a man with isolated CD followed for nearly 12 years from symptom onset. The course was characterized by multiple pattern changes, including a clear shift from left- to right-sided torticollis in 2019, followed by alternating and mixed dystonic patterns. Three remission phases were documented during follow-up: two prolonged periods in 2017–2018 and 2020–2021, and a further phase from March to November 2022. Over time, treatment requirements decreased from higher initial doses (500–700 U abobotulinumtoxinA and up to 130 U onabotulinumtoxinA) to lower maintenance doses of 30–50 U incobotulinumtoxinA/onabotulinumtoxinA, with longer injection intervals and no obvious documented need for dose adjustment to maintain clinical responsiveness. This case highlights the coexistence of pattern changes and recurrent remissions within a single continuously followed patient over an unusually long period. Although a treatment-related mechanism remains speculative and alternative explanations cannot be excluded, the observation underscores the value of prolonged follow-up and individualized treatment strategies in CD. Full article
(This article belongs to the Section Bacterial Toxins)
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11 pages, 744 KB  
Review
Muscle-Specific Dosing of OnabotulinumtoxinA in Post-Stroke Upper-Limb Spasticity: A Descriptive Literature Review
by Małgorzata Cisowska-Adamiak, Magdalena Mackiewicz-Milewska and Elżbieta Dorota Miller
Toxins 2026, 18(4), 192; https://doi.org/10.3390/toxins18040192 - 21 Apr 2026
Viewed by 520
Abstract
Background: Botulinum neurotoxin type A is widely used in the management of post-stroke upper-limb spasticity; however, many studies report total injected doses rather than muscle-specific dosing, limiting clinical applicability. This study aimed to evaluate how frequently muscle-level dosing protocols of onabotulinumtoxinA are reported [...] Read more.
Background: Botulinum neurotoxin type A is widely used in the management of post-stroke upper-limb spasticity; however, many studies report total injected doses rather than muscle-specific dosing, limiting clinical applicability. This study aimed to evaluate how frequently muscle-level dosing protocols of onabotulinumtoxinA are reported and to assess consistency of dosing patterns across published studies. Methods: A literature search was conducted in PubMed, Wiley/Cochrane Library, and EBSCO/CINAHL using a structured search strategy informed by PRISMA guidelines. Studies published within the last 10 years reporting on onabotulinumtoxinA treatment in post-stroke upper-limb spasticity with muscle-specific dosing data were included. Studies not providing muscle-level dosing or not allowing extraction of post-stroke upper-limb data were excluded. Data were summarized descriptively and compared across studies. Results: Twenty-seven full-text articles were assessed, and five studies met the inclusion criteria. Muscle-specific dosing was consistently reported for commonly treated muscles such as biceps brachii and wrist and finger flexors, whereas other muscles were less frequently targeted. Variability in dosing between studies was observed, particularly in multicenter real-world datasets. Standardized high-dose protocols contrasted with individualized dosing strategies, which generally showed more moderate dose ranges. Expert recommendations often suggest higher doses than those observed in routine clinical practice. Conclusions: Muscle-specific dosing of onabotulinumtoxinA in post-stroke upper-limb spasticity is reported infrequently, and substantial variability exists between studies and clinical practice. Standardized reporting of muscle-level dosing and its relationship to baseline spasticity severity is needed to improve clinical applicability and reproducibility. Full article
(This article belongs to the Special Issue Botulinum Toxin Application in Post-Stroke Rehabilitation)
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10 pages, 238 KB  
Review
Botulinum Toxin for Chronic Migraine: Beyond Headache Reduction and Toward Possible Cognitive Benefits
by Mauro Silvestrini, Giovanna Viticchi, Sergio Salvemini, Gioacchino De Vanna, Marco Bartolini and Simona Luzzi
Toxins 2026, 18(4), 153; https://doi.org/10.3390/toxins18040153 - 24 Mar 2026
Viewed by 928
Abstract
Chronic migraine (CM) is a debilitating neurological disorder characterized not only by persistent and severe pain, but also by substantial cognitive dysfunction that affects attention, working memory, processing speed, and executive functions. These neuropsychological disturbances are likely influenced by overall disease burden and [...] Read more.
Chronic migraine (CM) is a debilitating neurological disorder characterized not only by persistent and severe pain, but also by substantial cognitive dysfunction that affects attention, working memory, processing speed, and executive functions. These neuropsychological disturbances are likely influenced by overall disease burden and are further modulated by affective comorbidities, sleep disturbances, and medication overuse. OnabotulinumtoxinA (BoNT-A) is an established preventive therapy for CM, supported by strong evidence of both efficacy and safety. This narrative review synthesizes findings from studies examining the relationship between BoNT-A treatment and domain-specific cognitive improvements in CM. It also outlines the potential pathophysiological mechanisms underlying these effects, summarizes the limitations of the existing literature, and highlights priorities for future research. Current evidence suggests that BoNT-A may confer neurocognitive benefits, particularly in working memory and processing speed, and that these improvements may occur partly independently of reductions in headache frequency. These favorable cognitive effects appear to be plausibly linked to decreased nociceptive “noise” and improved cortical inhibition, potentially mediated through modulation of central sensitization, nociceptive signaling, and affective states. Full article
(This article belongs to the Special Issue Efficacy of Botulinum Toxin in Orofacial Pain)
17 pages, 4712 KB  
Article
Botulinum Toxin Treatment Can Enlarge Eye Appearance in Asian Patients and Improves Social and Emotional Attributes
by Maurício de Maio, Kiyoko Kato, Momoko Sato, Yuki Horiuchi, Takuya Toyama, Akiko Imaizumi and Hidenori Ishii
Toxins 2026, 18(3), 145; https://doi.org/10.3390/toxins18030145 - 15 Mar 2026
Viewed by 1578
Abstract
Aesthetic patients in East Asia are commonly concerned about small apparent eye size. Simultaneous treatment of the glabellar and lateral canthal areas with botulinum neurotoxin has potential to provide improvements. This case series evaluated changes in eye size following treatment of these two [...] Read more.
Aesthetic patients in East Asia are commonly concerned about small apparent eye size. Simultaneous treatment of the glabellar and lateral canthal areas with botulinum neurotoxin has potential to provide improvements. This case series evaluated changes in eye size following treatment of these two areas using standard on-label doses of onabotulinumtoxinA in patients from Japan or China. Outcomes were assessed based on standardised frontal photographs taken before and after treatment (at rest, maximum smile, and maximum frowning). Changes in eye size were examined using a 4-point Likert scale, as evaluated by three independent groups: six injectors; six non-injecting observers; and treated patients. Furthermore, improvements in overall facial impression were analysed using two established tools: ‘emotional attributes’ and ‘social attributes’. Twenty East Asian subjects were included (n = 17 women; mean age: 37.5 ± 6.4 years). The majority of evaluators in all three groups rated patients’ eye size as ‘significantly’ or ‘mildly’ improved post-treatment, whether assessed at rest, when smiling, or during frowning. Furthermore, almost all evaluators noted improvements in one or more emotional and social attributes. This approach has significant potential as a culturally adapted aesthetic technique for improving eye size in East Asian patients. Larger multicentre studies are warranted. Full article
(This article belongs to the Special Issue Application of Botulinum Toxin in Facial Diseases)
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11 pages, 644 KB  
Article
OnabotulinumToxinA Reduces Pharmacological Burden in Chronic Migraine Patients: A Two-Center Prospective Cohort Study
by Danilo Antonio Montisano, Alessandra Parisi, Alberto Raggi, Claudia Altamura, Luigi D’Onofrio, Marilena Marcosano, Luisa Fofi, Alessia Marcassoli, Fabrizio Vernieri and Licia Grazzi
Toxins 2026, 18(3), 143; https://doi.org/10.3390/toxins18030143 - 14 Mar 2026
Viewed by 944
Abstract
Background: Chronic migraine (CM) is a highly disabling and difficult-to-manage condition with a high pharmacological and economic burden. OnabotulinumtoxinA (BTx) was the first treatment specifically approved for CM. The main aim of this study was to assess whether the initiation of BTx is [...] Read more.
Background: Chronic migraine (CM) is a highly disabling and difficult-to-manage condition with a high pharmacological and economic burden. OnabotulinumtoxinA (BTx) was the first treatment specifically approved for CM. The main aim of this study was to assess whether the initiation of BTx is associated with discontinuation of previously prescribed preventive therapies. Methods: This study was a prospective cohort investigation conducted in two headache centers: Carlo Besta (Milan) and Policlinico Campus Bio-Medico (Rome). We included patients with CM and previous oral preventive treatments initiating BTx. We analyzed persistence with preventive therapies over 12 months of follow-up and evaluated the conversion rate from chronic to episodic migraine (EM), along with change in migraine days, symptomatic intake, and HIT-6. Results: A total of 95 patients were included in the main analysis, showing a discontinuation of treatment in 28.4% of patients at 12 months. In the exploratory analysis, a CM to EM conversion rate of 58.9% was achieved at 12 months; meanwhile, HIT-6, migraine days, and symptomatic intake showed a sizeable improvement. Conclusion: Treatment with BTx was associated with a reduction in drug burden at 12 months and a CM to EM conversion rate of almost 60% at 12 months, also contributing to a reduction in the economic burden of the disease. Full article
(This article belongs to the Section Bacterial Toxins)
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10 pages, 826 KB  
Review
Botulinum Toxin Treatment of Stiff Person Syndrome—A Critical Review and Update
by Ava Grace Tohidian, Samira Marie Comtesse, Shahroo Etemadmoghadam and Bahman Jabbari
Toxins 2026, 18(3), 130; https://doi.org/10.3390/toxins18030130 - 5 Mar 2026
Viewed by 1214
Abstract
Stiff person syndrome (SPS) is an autoimmune disorder with muscle stiffness and spasms, for which current therapies provide incomplete relief. Botulinum neurotoxin (BoNT) has been explored as an adjunctive symptomatic treatment. The aim of this review was to critically evaluate the clinical evidence [...] Read more.
Stiff person syndrome (SPS) is an autoimmune disorder with muscle stiffness and spasms, for which current therapies provide incomplete relief. Botulinum neurotoxin (BoNT) has been explored as an adjunctive symptomatic treatment. The aim of this review was to critically evaluate the clinical evidence for BoNT therapy in SPS. Using Medline, Scopus and Google Scholar, we identified nine reports that were published up to 1 January 2026. English articles and articles with information on study type, type/dose of BoNT and treatment results were included. One study was double-blind and placebo-controlled, one was retrospective and seven were single-case reports, comprising 46 patients. Open-label trials used botulinumtoxin-A (Botox, Dysport or Xeomin), while the blind study applied abobotulinumA (Dysport). All but one study (a case report) demonstrated motor improvement and a reduction in painful spasms associated with patient satisfaction. Reported doses ranged from 300 to 800 units for onabotulinumtoxinA and incobotulinumtoxinA and from 700 to 1000 units for abobotulinumtoxinA. The literature highlights the need for randomized clinical trials in larger cohorts, with careful selection of dose, injection sites, and adjunct physiotherapy, as well as an evaluation of early BoNT therapy in SPS. The novelty of this review lies in its critical synthesis of reported data and inclusion of most recent reports. Full article
(This article belongs to the Special Issue Botulinum Toxin: Advancing Treatments for Spasticity)
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9 pages, 403 KB  
Communication
Cross-Induction of Anti-Complexing Antibodies in Patients Treated with Botulinum Toxin Formulations Containing Complexing Proteins
by Yuttana Srinoulprasert, Surachet Sirisuthivoranunt, Chattip Sripatumtong, Tunsuda Tansit, Pornsuk Yamlexnoi, Onjira Meethong and Rungsima Wanitphakdeedecha
Toxins 2026, 18(2), 99; https://doi.org/10.3390/toxins18020099 - 14 Feb 2026
Viewed by 1141
Abstract
Botulinum toxin type A (BoNT/A) formulations differ in their content of non-toxic accessory proteins, also known as complexing proteins (CPs), which may influence immunogenicity. Some BoNT/A products share structurally similar CPs, potentially leading to antibody cross-reactivity among formulations. This prospective study investigated whether [...] Read more.
Botulinum toxin type A (BoNT/A) formulations differ in their content of non-toxic accessory proteins, also known as complexing proteins (CPs), which may influence immunogenicity. Some BoNT/A products share structurally similar CPs, potentially leading to antibody cross-reactivity among formulations. This prospective study investigated whether patients treated with different BoNT/A products develop cross-reactive anti-CP antibody responses. One hundred participants were allocated into five treatment groups, each receiving a single BoNT/A formulation: incobotulinumtoxinA (IncoA), onabotulinumtoxinA (OnaA), abobotulinumtoxinA (AboA), letibotulinumtoxinA (LetiA), or prabotulinumtoxinA (PraboA). Each participant received 50 units or equivalent dosing. Serum samples were collected 180 days post-injection, and anti-CP antibodies were quantified using an absorption ELISA and compared with a toxin-naïve control group. IncoA did not induce significant anti-CP antibody responses. In contrast, higher antibody levels were observed in the OnaA, LetiA, and PraboA groups against multiple CPs, suggesting structural similarity and cross-reactivity. AboA primarily induced antibodies directed against its own CPs and those of PraboA. These findings demonstrate that CP-containing formulations can induce cross-reactive antibody responses, whereas CP-free incobotulinumtoxinA exhibits minimal immunogenicity. This study highlights the importance of CP composition in guiding clinical product selection, particularly in patients requiring repeated BoNT/A administration. Full article
(This article belongs to the Special Issue Antibodies for Innovative Studies of Bacterial Toxins)
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13 pages, 3293 KB  
Article
Gender Differences in Post-Stroke Spasticity Patients Treated with OnabotulinumtoxinA: Insights from the BOTOX Economic Spasticity Trial (BEST)
by Monica Verduzco-Gutierrez, Reema Kaloti, Akinpelumi A. Beckley, Adil Syed Hussain, Sima A. Desai, Kimberly Becker Ifantides and Natasha L. Romanoski
Toxins 2026, 18(2), 64; https://doi.org/10.3390/toxins18020064 - 26 Jan 2026
Viewed by 1151
Abstract
Limited data are available on gender differences in patients with post-stroke spasticity (PSS) treated with onabotulinumtoxinA (onabotA). This subgroup analysis of data from the BOTOX® Economic Spasticity Trial (BEST) focused on onabotA-treated patients stratified by gender. BEST was a double-blind, placebo-controlled, randomized [...] Read more.
Limited data are available on gender differences in patients with post-stroke spasticity (PSS) treated with onabotulinumtoxinA (onabotA). This subgroup analysis of data from the BOTOX® Economic Spasticity Trial (BEST) focused on onabotA-treated patients stratified by gender. BEST was a double-blind, placebo-controlled, randomized study with an open-label extension that allowed for up to five treatments. It evaluated the effectiveness of onabotA + Standard of Care (SC) vs. placebo + SC for the treatment of PSS. At baseline, out of 139 patients treated with onabotA, females (n = 54) had a slightly higher body mass index (BMI) compared to males (n = 85) (28.3 vs. 26.9 kg/m2), and a greater percentage of females (40.7%) took analgesic medications compared to males (31.8%). Scores from baseline assessments for pain, spasticity severity, and stroke recovery were comparable between groups. Despite these similarities at baseline, females received an average lower dose (range, 337–365 U) of onabotA compared to males (range, 343–421 U) across treatment sessions. Females also had lower changes from baseline compared to males on pain, spasticity severity, stroke recovery, and functional goal achievement assessments across most onabotA treatment sessions. There is a need for further investigation into treatment approaches to optimize outcomes for both males and females with PSS. Full article
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8 pages, 710 KB  
Review
Botulinum Toxin Treatment of Notalgia Paresthetica—A Critical Review and Update
by Ava Grace Tohidian, Shahroo Etemadmoghadam and Bahman Jabbari
Toxins 2026, 18(1), 50; https://doi.org/10.3390/toxins18010050 - 19 Jan 2026
Viewed by 1122
Abstract
Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December [...] Read more.
Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Full article
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51 pages, 2219 KB  
Review
Integrative Migraine Therapy: From Current Concepts to Future Directions—A Plastic Surgeon’s Perspective
by Cristian-Sorin Hariga, Eliza-Maria Bordeanu-Diaconescu, Andrei Cretu, Dragos-Constantin Lunca, Catalina-Stefania Dumitru, Cristian-Vladimir Vancea, Florin-Vlad Hodea, Stefan Cacior, Vladut-Alin Ratoiu and Andreea Grosu-Bularda
Medicina 2026, 62(1), 50; https://doi.org/10.3390/medicina62010050 - 26 Dec 2025
Cited by 1 | Viewed by 2149
Abstract
Migraine is a prevalent and disabling neurological disorder with multifactorial origins and complex clinical manifestations. While pharmacologic therapies remain the cornerstone of management, a growing body of evidence highlights the role of extracranial peripheral nerve compression as a significant contributor to migraine pathophysiology [...] Read more.
Migraine is a prevalent and disabling neurological disorder with multifactorial origins and complex clinical manifestations. While pharmacologic therapies remain the cornerstone of management, a growing body of evidence highlights the role of extracranial peripheral nerve compression as a significant contributor to migraine pathophysiology in selected patients. This recognition has expanded the therapeutic role of plastic surgery, offering anatomically targeted interventions that complement or surpass traditional medical approaches for refractory cases. From a plastic surgeon’s perspective, optimal migraine care begins with accurate identification of clinical patterns, trigger-site mapping, and the judicious use of diagnostic tools such as nerve blocks and botulinum toxin. Surgical decompression techniques, including endoscopic and open approaches, address compression of the supraorbital, supratrochlear, zygomaticotemporal, greater and lesser occipital, auriculotemporal, and intranasal contact-point trigger sites. Adjunctive strategies such as autologous fat grafting further enhance outcomes by providing neuroprotective cushioning and modulating local inflammation through adipose-derived stem cell activity. Recent advances, including neuromodulation technologies, next-generation biologics, and innovations in surgical visualization, underscore the ongoing shift toward precision-based, mechanism-driven therapy. As understanding of migraine heterogeneity deepens, the integration of surgical expertise with modern neuroscience offers a comprehensive and personalized therapeutic framework. Plastic surgeons, equipped with detailed knowledge of peripheral nerve anatomy and minimally invasive techniques, play an increasingly pivotal role in the multidisciplinary management of refractory migraine. Full article
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12 pages, 795 KB  
Systematic Review
Intracavernosal Botulinum Toxin Injection for Erectile Dysfunction: A Comprehensive Systematic Review
by Vanessa Talavera Cobo, Carlos Andres Yanez Ruiz, Mario Daniel Tapia Tapia, Andres Calva Lopez, Carmina Alejandra Muñoz Bastidas, Francisco Guillen-Grima, Francisco Javier Ancizu Marckert, Luis Labairu Huerta, Marcos Torres Roca, Fernando Jose Diez-Caballero Alonso, Daniel Sanchez Zalabardo, Bernardino Miñana Lopez and Jose Enrique Robles Garcia
Life 2025, 15(12), 1826; https://doi.org/10.3390/life15121826 - 28 Nov 2025
Viewed by 3870
Abstract
Background: Erectile dysfunction (ED) affects approximately 20% of men worldwide, significantly affecting their quality of life. While phosphodiesterase type 5 inhibitors (PDE5-Is) are the standard first-line treatment, a substantial number of patients are non-responders. Second-line treatments, such as intracavernosal alprostadil, are effective but [...] Read more.
Background: Erectile dysfunction (ED) affects approximately 20% of men worldwide, significantly affecting their quality of life. While phosphodiesterase type 5 inhibitors (PDE5-Is) are the standard first-line treatment, a substantial number of patients are non-responders. Second-line treatments, such as intracavernosal alprostadil, are effective but often limited by their invasive nature and the need for frequent injections. Intracavernosal onabotulinumtoxinA (BoNT-A) offers a promising new option. By inhibiting acetylcholine release and norepinephrine, as well as other neurotransmitters involved in detumescence, it facilitates cavernosal smooth muscle relaxation and enhances penile blood flow. Its effects may persist for up to six months following a single injection, potentially reducing treatment burden and improving adherence among men with refractory ED. Methods: A systematic review was performed in accordance with the PRISMA guidelines. Literature searches were conducted in PubMed, Embase, Cochrane Library, Scopus, and Clinicaltrials.gov from inception until August 2025 using a combination of keywords and MeSH terms related to ‘erectile dysfunction’ and ‘botulinum toxin’. After screening, 51 studies met the inclusion criteria. Due to significant heterogeneity in interventions (e.g., BoNT-A dosage, co-therapies), patient populations, and reported outcomes, the data were not suitable for meta-analysis. Consequently, a narrative synthesis was performed to summarize the findings. Results: Among the included studies, intracavernosal BoNT-A was associated with improvements in validated erectile function scores. Reported response rates, variably defined across studies, ranged from 40% to 77.5%. Several studies suggested that efficacy was higher in patients with mild-to-moderate ED and with repeated administration of 100 U doses. The treatment exhibited a favorable safety profile. The most common adverse event was mild, transient penile pain (reported incidence 1.5–6%). No studies reported serious systemic adverse events. The overall strength of the evidence was limited by significant heterogeneity among the included studies and their generally small sample sizes. Conclusions: Based on this systematic review, intracavernosal onabotulinumtoxinA (BoNT-A) may be a beneficial therapeutic option for patients with refractory ED, offering potential improvements in sexual function while reducing the need for invasive therapies. Future large-scale, placebo-controlled studies are essential to confirm these benefits and standardize their clinical application. Full article
(This article belongs to the Section Medical Research)
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13 pages, 377 KB  
Article
OnabotulinumtoxinA to Prevent Chronic Migraine with Comorbid Bruxism: Real-World Data from the GRASP Study Group
by Andreas A. Argyriou, Emmanouil V. Dermitzakis, Maria Chondrogianni, Aikaterini Foska, Dimitrios Rikos, Georgia Xiromerisiou, Panagiotis Soldatos, Pantelis Litsardopoulos and Michail Vikelis
Toxins 2025, 17(11), 547; https://doi.org/10.3390/toxins17110547 - 3 Nov 2025
Cited by 1 | Viewed by 1569
Abstract
Background: This study, designed by the Greek Research Alliance for the Study of Headache and Pain (GRASP), sought to prospectively examine whether the treatment with two consecutive OnabotulinumtoxinA (BoNTA) cycles might improve the frequency and severity of chronic migraine (CM) with comorbid bruxism. [...] Read more.
Background: This study, designed by the Greek Research Alliance for the Study of Headache and Pain (GRASP), sought to prospectively examine whether the treatment with two consecutive OnabotulinumtoxinA (BoNTA) cycles might improve the frequency and severity of chronic migraine (CM) with comorbid bruxism. We also explored whether the potential BoNTA-related alleviation of bruxism can directly influence the improvements in migraine efficacy outcomes. Methods: A total of 58 CM patients with comorbid bruxism at baseline, attaining two consecutive (quarterly given) BoNTA cycles, were studied. The changes in bruxism-related pain were assessed with the 0–10 numeric scale PI-NRS. Bruxism was clinically diagnosed using the self-report Bruxscreen-Q questionnaire. Any phenotypic changes in bruxism, according to Bruxscreen-Q, from baseline (T0) to the last efficacy evaluation follow-up (T1), were analyzed and then compared. Migraine-related efficacy and disability outcomes, mostly mean headache days (MHD), were also compared between T0 and T1. Results: BoNTA exerted significant improvements in bruxism-related pain, with PI-NRS median scores being significantly reduced from 7 at T0 to 3 at T1 (p < 0.001). The rates of masseter hypertrophy at T1 significantly dropped, compared to T0 (chi-square: 16; p < 0.001). Patients also self-reported significant improvements in the Bruxscreen-Q items at T1, compared to T0. At T1, 41/58 (70.7%) patients responded to BoNTA. The significant decrease in MHD frequency at T1 was positively correlated with improvements in bruxism-related pain severity (Pearson’s correlation: 0.710; p < 0.001). Conclusions: BoNTA exerts dual beneficial effects towards both the reduction of migraine frequency and the alleviation of bruxism-related pain and disability. Both of these effects seem closely interrelated in our study. Full article
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14 pages, 855 KB  
Article
Beyond Glycemic Control: Concurrent GLP-1 Receptor Agonist Use Is Associated with Reduced Urinary Adverse Events Following OnabotulinumtoxinA Treatment in Non-Diabetic Adults with Overactive Bladder
by Muhammed A. M. Hammad, Sophia G. Quesada, Aimee L. Belczyk and Gamal M. Ghoniem
Toxins 2025, 17(11), 542; https://doi.org/10.3390/toxins17110542 - 1 Nov 2025
Cited by 1 | Viewed by 4194
Abstract
Semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist, is widely prescribed for weight loss in non-diabetic populations. Given the link between obesity and overactive bladder (OAB), we explored whether GLP-1 use would improve adverse urinary events beyond its weight loss benefit for non-diabetic adults [...] Read more.
Semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist, is widely prescribed for weight loss in non-diabetic populations. Given the link between obesity and overactive bladder (OAB), we explored whether GLP-1 use would improve adverse urinary events beyond its weight loss benefit for non-diabetic adults undergoing onabotulinumtoxin A (BTX-A) treatment for OAB. Using the TriNetX database, we conducted a retrospective cohort study of non-diabetic OAB patients treated with BTX-A alone or with concurrent GLP-1 therapy. Propensity score matching (1:1) was adjusted for age, race, ethnicity, hypertension, and BMI/obesity. After matching, 992 patients were included in each group. GLP-1 use was associated with a lower incidence of urinary retention (8.6% vs. 4.9%, risk difference 3.66%, p = 0.0044) and urinary tract infection (13.3% vs. 8.8%, risk difference 4.54%, p = 0.00224), with corresponding improved one-year retention-free and UTI-free survival on Kaplan–Meier (KM) analysis. Antispasmodic initiation rates were similar (11.8% vs. 10.3%, risk difference 1.55%, p = 0.6921), and KM analysis showed no significant difference. These findings suggest that GLP-1 receptor agonist use may improve select urinary adverse events in non-diabetic adults undergoing BTX-A treatment for OAB and support further investigation into its potential adjunctive role in OAB management with longer follow-up. Full article
(This article belongs to the Special Issue Botulinum Toxins in Lower-Urinary-Tract Diseases and Dysfunctions)
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15 pages, 18289 KB  
Article
Mapping Dural and Periosteal SV2C, a Botulinum Toxin A Receptor, in the Mouse
by Anisa Dehghani, Agustin Melo-Carrillo, Andrew M. Strassman, Ron S. Broide, Aubrey Manack Adams, Brett Dabruzzo, Mitchell F. Brin and Rami Burstein
Toxins 2025, 17(10), 509; https://doi.org/10.3390/toxins17100509 - 17 Oct 2025
Viewed by 1238
Abstract
Objectives: There has been a long-standing debate over the presence or absence of receptors for botulinum toxin A (BoNT/A) in cephalic areas relevant to migraine pathophysiology and onabotulinumtoxinA (onabotA) sites of action in migraine prevention. To address this issue, we sought to investigate [...] Read more.
Objectives: There has been a long-standing debate over the presence or absence of receptors for botulinum toxin A (BoNT/A) in cephalic areas relevant to migraine pathophysiology and onabotulinumtoxinA (onabotA) sites of action in migraine prevention. To address this issue, we sought to investigate for the first time whether synaptic vesicle protein 2C (SV2C), one member of the SV2 receptor family, is present in axons innervating the dura and periosteum. Methods: Single- and double- labeling immunohistochemical techniques were used to map and characterize the distribution of axons containing SV2C, the third isoform of the SV2 glycoprotein, in the mouse dura and periosteum. Results: Dense networks of axons containing SV2C receptors were distributed throughout all regions of the dura and periosteum. In the dura, SV2C-LIR axons were found in 43% of all peripherin-LIR fibers, 49% of all CGRP-LIR fibers, and 75% of all NaV1.8-LIR fibers. In the periosteum, SV2C-LIR was found in 38% of all peripherin-LIR fibers, 53% of all CGRP-LIR fibers, and 68% of all NaV1.8-LIR fibers. Conclusions: We interpret these findings as suggesting that many of the labeled axons are peripheral nerve axons (peripherin-positive) of unmyelinated sensory and possibly parasympathetic origin (CGRP-positive), and that some of these sensory axons are nociceptors (NaV1.8-positive). Clinically, these findings demonstrate an abundance of axons containing onabotA receptors in the vicinity of scalp structures commonly injected with onabotA for the treatment of chronic migraine. Dense labeling in the periosteum provides another rationale for the possibility that onabotA injections in this layer of the scalp may be advantageous. Full article
(This article belongs to the Section Bacterial Toxins)
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Review
Botulinum Toxin Treatment in Hereditary Spastic Paraplegia—A Comprehensive Review and Update
by Bahman Jabbari, Samira Comtesse and Fattaneh Tavassoli
Toxins 2025, 17(10), 503; https://doi.org/10.3390/toxins17100503 - 13 Oct 2025
Viewed by 2473
Abstract
Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 September 2025) on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP). Nine studies were conducted in adults and one in children. Only one of the [...] Read more.
Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 September 2025) on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP). Nine studies were conducted in adults and one in children. Only one of the ten studies was double-blind and placebo-controlled. The search strategy included only articles published in English and articles providing basic information such as the type of the study, type and dose of the toxin and results of the treatment. Articles not in English, case reports and review articles were excluded. A total of 258 patients were included across all studies. The injected toxin in the open-label studies was botulinumtoxin-A (Botox or Dysport or Xeomin), whereas in the blinded study, the investigators used Prosigne. All open-label studies, which used FDA approved botulinumtoxin-A neurotoxins, demonstrated a degree of motor and non-motor improvement, whereas treatment with Prosigne did not improve patients’ function. The possible reasons for this discrepancy between the blinded study and the open-label studies are discussed. We found no studies on the effect of BoNTs on bladder dysfunction in HSP. There is a need for double-blind, placebo-controlled studies assessing the efficacy of FDA-approved botulinum neurotoxins in children and adults affected by hereditary spastic paraparesis. Such studies should also investigate the effect(s) of early botulinum neurotoxin therapy in this disorder. The novelty of this review is that it represents a comprehensive and critical literature review on this subject, with no other studies of this kind published previously. It also includes data not present in previous reviews of this subject. Full article
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