Search Results (157)

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

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

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

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

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

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

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸–2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs. Full article

Background: Refractory overactive bladder (OAB) poses a significant clinical burden, often severely impacting quality of life (QoL). While intradetrusor onabotulinumtoxinA (BoNT-A) and sacral neuromodulation (SNM) are established therapeutic options, a direct comparison of their efficacy and safety profiles is essential to guide clinical decision-making. This study compares BoNT-A against placebo and SNM for the management of refractory OAB in women. Methods: Following PRISMA guidelines, PubMed, Scopus, CENTRAL, and Google Scholar were searched until February 2025 for randomized controlled trials (RCTs) and cohort studies on treatment alternatives for refractory OAB. Treatment outcomes at 3- (BoNT-A vs. placebo) and 6-month (BoNT-A vs. SNM) follow-up were analyzed. Odds ratios (ORs) and mean differences (MDs) were calculated for dichotomous and continuous variables, respectively, with heterogeneity assessed via I² test. Study quality was evaluated using CASP tools. Results: Pooled data from 12 studies (2645 patients) indicated that BoNT-A significantly reduced urgency urinary incontinence (UUI) episodes compared to placebo (p = 0.02) and SNM (p = 0.0008). Additionally, a ≥75% reduction in UUI episodes was more likely with BoNT-A compared to both placebo (p < 0.00001) and SNM (p < 0.00001). Complete resolution of UUI was more likely with BoNT-A compared to placebo (p < 0.00001); however, when compared to SNM, the latter demonstrated a higher rate of complete UUI resolution (p < 0.00001). Patient-reported QoL did not show significant differences between BoNT-A and SNM (p = 0.2). Urinary tract infection (UTI) risk was higher with BoNT-A than both comparators. Conclusions: While BoNT-A offers robust symptom control, its safety profile necessitates careful patient selection. SNM remains a viable alternative for those prioritizing fewer adverse events. The study highlights the need for standardized outcome reporting, long-term cost-effectiveness analyses, and personalized treatment approaches. Full article

Chronic migraine (CM) in childhood and adolescence is associated with a high disease burden, including impaired quality of life, school absenteeism, and reduced daily functioning. OnabotulinumtoxinA (ONA) is approved for prophylactic treatment of CM in adults, but its use in pediatric patients remains off-label, with evidence still limited. This narrative review summarizes current data on the efficacy, safety, and tolerability of ONA in pediatric CM, drawing from randomized controlled trials, prospective cohorts, and retrospective series. In addition to summarizing efficacy and safety data, our review aims to focus on potential practical clinical implications and on discussion points and research questions that remain open. Full article

Interictal burden (IB), defined as the symptoms and impairments that occur between migraine attacks, including cognitive dysfunction, photophobia, and fatigue, is recognized as a significant determinant of quality of life in patients. A prospective observational study was conducted. Patients diagnosed with chronic migraine (CM) and under treatment with OnabotulinumtoxinA (OnabotA) according to the PREEMPT protocol (every 12 weeks) were assessed at baseline and at 3, 6, 9, and 12 months. The primary endpoint was to evaluate the change in the IB measured with the Migraine Interictal Burden Scale (MIBS-4) and in the monthly migraine days (MMD). The secondary endpoint was acute medication use. This single-center study included 150 patients (91.3% female; median age 44 years). MIBS-4 scores were decreased by 29.1% at 3 months (8.47 to 5.97) and by 41.6% at 12 months (to 4.86; p < 0.001). IB-free status was achieved by 16 patients (10.7%). The most disabling baseline symptoms were photophobia (37%), fatigue (20%), and allodynia (18%), which reduced by 52%, 43%, and 39% at 12 months, respectively. MMD were reduced from 18.6 to 8.3 days at 12 months and triptan and analgesic intake decreased by 58.7% and 55.4%. OnabotA significantly reduced both IB and migraine frequency over 12 months, underscoring its relevance in CM management. Full article

Many patients with spasticity report pain which can be debilitating. Numerous studies have shown onabotulinumtoxinA (onabotA) is efficacious in the management of spasticity but comprehensive data on its impact on spasticity-associated pain is limited. This systematic review aimed to assess the published evidence on the efficacy of onabotA in the management of pain in adults with spasticity. Search strategies were conducted from 1990 to 2023 for journal publications and from 2020 to 2023 for congress proceedings to identify relevant studies on onabotA in adults with spasticity where pain was a reported outcome. Of 665 records identified, 31 unique studies from 33 publications were included (2740 patients). Twenty-seven studies demonstrated a reduction in pain compared to baseline following treatment with onabotA in adults with spasticity (n = 2740). Of these, 12 studies reported a statistically significant reduction in pain with onabotA versus baseline. Sixteen studies reported a clinically meaningful reduction in pain (≥30% reduction). The reduction in pain with onabotA was consistent across etiologies and a range of pain measures. There was a high level of heterogeneity in the design and quality of the studies identified, which limited statistical analysis; however, the published evidence overall shows a consistent positive trend for the use of onabotA in reducing spasticity-related pain in adults. Full article

Purpose: Detrusor sphincter dyssynergia (DSD), a common lower urinary tract condition in patients with suprasacral spinal cord injury (SCI), can lead to urological complications and reduced quality of life. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to promote spontaneous voiding, albeit with limited success. This study aimed to identify predictive factors for treatment success. Methods: This retrospective analysis included 207 patients (157 males and 50 females) with chronic SCI and varying DSD grades treated with urethral sphincter BoNT-A injection. Each received 100 U of onabotulinumtoxinA via transurethral sphincter injection. The primary outcome was voiding efficiency (VE) and symptom improvement, assessed via global response evaluation 3 months post-treatment. Baseline videourodynamic parameters were used to predict success. Results: Successful outcomes were observed in 33.8% of patients. These patients were older and had higher voiding pressure, maximum flow rate (Qmax), voided volume, bladder contractility index, and VE, as well as lower post-void residual (PVR) volume and bladder outlet obstruction index. Patients with SCI and DSD grade 1 had the highest success rate (65.7%) compared to those with DSD grade 2 (14.3%) or 3 (7.1%). Patients with DSD grade 3 had the highest failure rate (55.8%). Multivariate analysis showed that higher Qmax and lower PVR significantly predicted success, consistent with lower DSD grades. Conclusion: Grade 1 DSD, higher Qmax, and lower PVR were associated with higher success after urethral BoNT-A injection, whereas grade 3 DSD predicted failure. Thus, careful patient selection is essential for effective DSD treatment with urethral BoNT-A injection. Full article

Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies. Full article

Background/Objectives: Intradetrusor botulinum toxin injection is a well-established third-line therapy for patients with refractory overactive bladder (OAB) and detrusor overactivity (DO). Botulinum toxin type A (BoNT-A) is most commonly used due to its prolonged therapeutic duration. We aimed to evaluate the effectiveness of intradetrusor BoNT-A injection therapy in managing refractory OAB by performing a urodynamic study (UDS). Methods: The patients were prospectively enrolled between February 2020 and March 2021. The patients received treatment regimens comprising behavioral modification therapy, pelvic floor muscle physiotherapy, and/or OAB medications for at least three months. The UDS procedure was carried out by a single examiner, in accordance with the International Continence Society standards for good urodynamic practice. A total of 100 units of BoNT-A was dissolved in 10 mL of saline, and 0.5 mL (5 units) was injected at 20 sites on the posterior wall of the bladder. The primary endpoint was the change in DO, which was measured using the UDS from the baseline to two months after treatment with BoNT-A. Results: Prior to treatment initiation, DO was observed in all the patients during the UDS. The occurrence of DO during the filling phase demonstrated a significant decrease following treatment, with DO no longer identified in 27.3% of the patients. The first sensation of bladder filling, maximum cystometric capacity, DO, and terminal DO all demonstrated significant improvement after intradetrusor BoNT-A injection, based on the UDS. The OAB symptom scores also significantly decreased after BoNT-A therapy. Conclusions: The present study demonstrated that intradetrusor BoNT-A injection significantly improved symptoms in patients with OAB who had been unresponsive to various treatments. This study also demonstrated the usefulness of performing a UDS before and after treatment to prove the efficacy of BoNT-A. Full article

OnabotulinumtoxinA (OnaBoNT-A) is approved for chronic migraine prevention and follows the PREEMPT protocol with injections in the glabellar and forehead regions. While aesthetic changes are considered a side effect, their effect on patient satisfaction has not been thoroughly assessed. This study evaluated patient satisfaction with facial aesthetic outcomes after repeated OnaBoNT-A treatment for chronic migraine. Conducted at specialist headache centers, it included adult patients with chronic migraine who had received at least three OnaBoNT-A cycles. Participants completed a structured questionnaire on demographics, migraine history, facial wrinkles and age perception, appearance satisfaction, psychological impact, treatment satisfaction, and adverse aesthetic events. A total of 124 patients (92.7% female; median age 42.5 years) participated. OnaBoNT-A reduced wrinkle severity (p < 0.0001). Most patients (74.2%) reported aesthetic improvement post-treatment. The majority of patients (76.7%) declared that treatment met or exceeded expectations. 32% reported looking younger post-treatment, with a median perceived age difference of 5 years. Adverse event frequency was similar to pivotal trial outcomes, mostly mild, with no treatment discontinuations. OnaBoNT-A for chronic migraine, following the PREEMPT protocol, provides significant therapeutic benefits and high patient satisfaction regarding aesthetic outcomes. Although aesthetic side effects were generally mild, they were not uncommon. Full article