Trial of Botulinum Toxin for Isolated or Essential Head Tremor.

BACKGROUND: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. METHODS: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS: A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS: Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).

Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls.

BACKGROUND: Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. METHODS: We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. RESULTS: A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P<0.001 for all comparisons). The most common serious adverse events were pneumonia, bronchiolitis, hypotonia, and respiratory failure. CONCLUSIONS: In this study involving infants with type 1 SMA, risdiplam resulted in higher percentages of infants who met motor milestones and who showed improvements in motor function than the percentages observed in historical cohorts. Longer and larger trials are required to determine the long-term safety and efficacy of risdiplam in infants with type 1 SMA. (Funded by F. Hoffmann-La Roche; FIREFISH ClinicalTrials.gov number, NCT02913482.).

Risdiplam in Type 1 Spinal Muscular Atrophy.

BACKGROUND: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. METHODS: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. RESULTS: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. CONCLUSIONS: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.).

Efficacy and safety of botulinum neurotoxin in the treatment of hemifacial spasms: a systematic review and meta-analysis.

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.

Is chemodenervation with incobotulinumtoxinA an alternative to invasive chronic anal fissure treatments?

BACKGROUND: Botulinum toxin type A is currently strongly recommended for the treatment of anal fissures (AFs). However, there is still no consensus on dosage or injection technique. This study provides further efficacy and safety evidence in a 2-year follow-up. METHOD: Prospective, open-label, single-arm, single-center study carried out in adult patients with AFs non-responsive to previous treatments. Patients were treated with incobotulinumtoxinA (incoBoNT/A) injected in both laterals and posterior intersphincteric groove. Healing rate at 2 years was the primary endpoint. Secondary endpoints included internal anal sphincter pressures, incontinence, and safety. RESULTS: A total of 49 patients were treated with a mean incoBoNT/A dose of 40.5 U (spread across three locations). Healing rate at 2 years was 83.9% with a 24.5% of recurrence throughout the study. Only 7 patients (14.3%) reported adverse events (AEs) that were mild and temporary. Mean reduction in anal resting pressure was -9.1 mmHg at 3 months (p = 0.001). Mean reduction in voluntary squeeze pressure was -27.5 mmHg at 3 months (p < 0.001). Mean pain perception measured with a visual analog scale decreased by -6.5 points at 2 years (p < 0.001). There was an incontinence increase at 1 month of 1.3 points (p = 0.006), but baseline values were restored at 6 months. CONCLUSION: We present results that support the use of incoBoNT/A as a second line for AFs that do not respond to ointment therapy. IncoBoNT/A injection is a less invasive treatment that should be considered before surgery due to its efficacy and its safety which includes no permanent impairment. TRIAL REGISTRATION: ISRCTN90354265; Registered on 16th February 2024. Retrospectively registered.

Sequential administration of peripheral nerve blocks and onabotulinumtoxinA for the treatment of chronic migraine and other headache disorders-A retrospective tolerability and safety study.

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

The Botulinum Toxin Innovation: From Powder to Liquid.

BACKGROUND: Botulinum toxin (BoNT) has evolved as a popular treatment for various medical and aesthetic conditions since the 1980s. The emergence of new liquid formulation BoNT products in the industry highlights the need to evaluate the value and advantages of these modern formulations. OBJECTIVE: The aim of this review was to assess and compare the expected difference in practice between liquid and powder formulation BoNT products. PAITENTS AND METHODS/MATERIALS: This article involves a review of pertinent guidelines, product information from manufacturers, available database for safety reports, and survey results. RESULTS: Guidelines and safety reports have pointed out potential risks in the reconstitution process, while medication preparation steps are simplified in liquid formulation. CONCLUSION: The shift toward ready-to-use liquid products can mitigate risks related with reconstitution errors and potentially enhancing patient care by saving time and cost associated with medication preparation.

Versatility of OnabotulinumtoxinA in Aesthetic Medicine.

BACKGROUND: OnabotulinumtoxinA is an injectable product that was introduced into medicine in the 1970s and has been the subject of thousands of clinical and nonclinical publications. OBJECTIVE: To review the data related to the versatility of onabotulinumtoxinA in medical aesthetics. METHODS: PubMed was searched to identify literature evaluating the effects of onabotulinumtoxinA, with preference given to randomized, placebo-controlled trials and safety meta-analyses. RESULTS: OnabotulinumtoxinA is effective and safe across multiple facial indications, racial and ethnic groups, age groups, genders, and facial line severities. Patient-reported outcomes have been prioritized in aesthetic clinical trials and indicate high patient satisfaction and appearance-related psychological outcomes. Integrated safety meta-analysis and immunogenicity analyses have documented acceptable adverse event rates and low immunogenicity of onabotulinumtoxinA. CONCLUSION: OnabotulinumtoxinA is a versatile aesthetic product supported by a strong literature base and positive physician and patient-reported outcomes that reflect a meaningful impact on patient's quality of life.

Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study.

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.

Post Hoc Analysis Comparing the Safety and Efficacy of PrabotulinumtoxinA in Millennials and Nonmillennials With Moderate to Severe Glabellar Lines.

BACKGROUND: Millennials accept and invest in aesthetic procedures more than older generations. OBJECTIVE: To compare efficacy outcomes between millennial and nonmillennial patients after treatment of glabellar lines with prabotulinumtoxinA. MATERIALS AND METHODS: This was a post hoc analysis of 3 Phase III studies of 20 U prabotulinumtoxinA for the treatment of moderate to severe glabellar lines. Investigator- and/or subject-assessed positive responder rates in the Glabellar Line Scale, Global Aesthetic Improvement Scale, and Subject Satisfaction Scale were compared between millennials (born 1982-2000) and nonmillennials (born ≤1981). RESULTS: Aesthetic outcomes and subject satisfaction of prabotulinumtoxinA treatment were high in nonmillennials (n = 65) and even higher in millennials (n = 668) at all time points. At Days 7, 14, and 30 post-treatment, positive responder rates were >85% and >97% across all scales in nonmillennials and millennials, respectively, with statistical superiority observed in millennials at multiple time points in virtually all scales. The incidence of treatment-related adverse events was similar between groups. CONCLUSION: PrabotulinumtoxinA was highly effective in treating moderate to severe glabellar lines. The greater efficacy seen in millennials may reflect physiological differences related to aging as well as botulinum toxin-mediated effects on mood. The results align well with their aesthetic expectations.

RimabotulinumtoxinB: An Update.

BACKGROUND: Botulinum type-A toxin is a well established aesthetic and medical treatment. While the usage of type-B toxin is less common, there is a growing interest in using type-B toxin, especially in those who are treatment resistant. OBJECTIVE: To evaluate the primary FDA-approved clinical applications of rimabotulinumtoxinB, along with established and emerging off-label clinical indications. MATERIAL AND METHODS: Articles were reviewed from PubMed database and Food and Drug Adminstration guidelines. RESULTS: Facial rhytids tend to use a higher conversion ratio between type A and type B toxin, due to type B toxin's weaker affinity to muscles and higher affinity for sweat glands. Specially, a 1:100 to 1:50 ratio was utilized for glabellar rhytids, a 1:25 to 1:50 ratio for periocular rhytids, a 1:50 to 1:66.6 ratio for cervical dystonia, a 1:20 to 1:50 ratio for hyperhidrosis, and a 1:25 to 30 ratio for sialorrhea. CONCLUSION: Type B toxin has demonstrated its safety and efficacy in treating facial rhytids, cervical dystonia, sialorrhea and hyperhidrosis, with potential for novel applications under investigation. Regardless of injection location and clinical applications, dry mouth and dysphagia remained the most common side effects. Across all indications, type B toxin appeared to have a faster onset of action, a dose-dependent clinical duration, and a dose-dependent adverse effect profile.

Contouring With Neuromodulators.

BACKGROUND AND OBJECTIVE: Botulinum toxins, originally used for facial rejuvenation, have emerged as a promising tool for sculpting and refining contours for both the face and body. METHODS: The peer-reviewed literature on neuromodulator contouring treatments was analyzed, with a particular emphasis on studies and case reports involving the use of botulinum toxin type A. RESULTS: Modification of face, neck, shoulder, arm, and calf contour has been reported. Treatment and dosing protocols vary with the strength and depth of the target muscle. Regional effects of neuromodulator treatment begin to appear approximately 2 weeks after injection and are often most prominent at the 70- to 90-day time point. Although treatments are generally well tolerated, short-term muscle weakness and other side effects may occur. CONCLUSION: The use of neuromodulators to enhance facial and body contours has demonstrated efficacy, but further research is needed to validate their use and explore the full potential of this intervention through larger randomized controlled trials. The application of neuromodulators as a minimally invasive tool to address the rising demand for nonsurgical body sculpting represents a promising frontier in aesthetics.

Safety and Effectiveness of Synchronized Monopolar Radiofrequency and HIFES in Patients Injected With Botulinum Toxin.

BACKGROUND: Botulinum toxin (BT) has become one of the most frequently sought aesthetic procedures for wrinkle reduction. OBJECTIVE: This study investigated the effectiveness and safety of a novel device using radiofrequency (RF) and high-intensity facial muscle stimulation (HIFES) in patients injected with BT. METHODS: Twelve patients were divided into an Active (N=10) and a Control group (N=2), where the Active received four treatments and the Control none. The facial expressions documented by digital photographs (neutral) and videos (frown, smile, surprise expressions) were taken at all visits (baseline, after last Tx, 1 and 3-month follow-ups) and were evaluated using the Global Aesthetic Improvement Scale (GAIS) and 3D automated analysis. The subject's therapy comfort and satisfaction were assessed. RESULTS: The Active group reported high satisfaction with treatment comfort (6.3±0.2 points on the 7-point Likert scale). 3D analysis showed reduced wrinkle severity (37.4%) and volume increase (+1.5 mL) on the cheeks at 3 months. GAIS evaluation demonstrated the most prominent improvement in smiling facial expression by 2.2±0.1 points. No adverse events were observed. CONCLUSION: The study results suggest that the combination of HIFES and synchronized RF is a safe and effective treatment for improving facial appearance and muscle tone in patients injected with BT. J Drugs Dermatol. 2024;23(11):937-942.  doi:10.36849/JDD.7938.

Botulinum Toxin-Induced Parotitis: A Postoperative Complication Following Masseter Muscle Injection.

Botulinum toxin (BTX) injection is a common treatment for bruxism, but there is no literature on potential salivary gland complications. This paper presents a case of acute parotitis in a 60-year-old female following BTX injections to the masseter muscle. This case highlights the possible salivary gland complications after injection of BTX into the masticatory muscles. An electronic search of PubMed and Embase databases was conducted to create a literature review in order to delve into the etiology behind the presented case and suggest potential preventive measures to avoid salivary gland complications. Thirty-one articles are reviewed and discussed. Currently, there is no consensus on the causes of the mentioned complication. However, various factors have been proposed, encompassing anatomical, physiological, biological, and physical aspects. Several methods have been recommended for the safe injection of BTX, which, along with better medical training and knowledge, are warranted to achieve predictable results.

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

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

A Phase III Clinical Study of the Efficacy and Safety of Botulinum Toxin Type A (MASPORT) with DYSPORT for the Treatment of Glabellar Lines.

BACKGROUND: Botulinum toxin type A is a widely used treatment of facial wrinkles. The objective of this study was to compare the efficacy and safety of a new botulinum toxin type A (Masport [abobotulinum toxin A], MasoonDarou Co) with DYSPORT® for the treatment of glabellar lines. METHODS: 262 subjects with moderate-to-severe glabellar lines received either a fixed dose of 50 units of MASPORT® or DYSPORT® (Ipsen Company, England). Subjects were followed up at 14, 30, 60, 90 and 120 days after injection. Efficacy was assessed by investigator at maximum frown and rest and also by Subject Global Assessment of Change (SGA). The responders were defined as persons with +2 grade improvement from baseline for both investigator and patient assessment. The occurrence and duration of adverse effects were recorded up throughout the study. RESULTS: According to the investigator evaluations, the responder rate at maximum frown were 94.5% for MASPORT and 95.6% for DYSPORT group on day 30 and at rest were 85.45% and 85.68% for MASPORT and DYSPORT group, respectively. According to the subject self-assessment, the proportion of responders in MASPORT group at day 30 was 95.28% versus 97.04% for DYSPORT group. No serious drug related adverse effect was recorded in either study groups, and the rates of adverse effects were similar for both groups. CONCLUSION: Abobotulinum toxin A [MASPORT] is equally safe and effective as commercial product [DYSPORT] for the treatment of glabellar lines with the dose of 50 units, up to 120 days. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Subjective Discomfort during Botulinumtoxin Injections Dependent on Injection Site and Needle Size: A Comparison Between 30G, 33G and 34G Needles.

BACKGROUND: Botulinumtoxin application in the face is amongst the most common aesthetic procedures in the head and neck region. It also has numerous medical uses. One of the main reasons for patients to refrain from it is the subjective discomfort that is experienced during injections. OBJECTIVES: The study at hand aimed to determine whether needles with 33G and 34G offer an advantage in terms of individual pain perception during botulinumtoxin injections. METHODS: We conducted a prospective study where patients were asked to grade subjective discomfort on a visual analogue scale for each region (forehead, glabella, temple) that was treated directly after treatment and 15 minutes after. Patients were treated with 30G, 33G or 34G needles, respectively. RESULTS: Ninety-nine patients that underwent treatment of 189 regions were included in the study. Patients were evenly distributed amongst the different needle sizes and regions. Subjective discomfort was greatest in all regions for 30G needles (3.9 ± 1.6 forehead, 4.3 ± 1.7 glabella and 4.0 ± 1.6 temple) followed by 33G (2.7 ± 1.5 forehead, 2.7 ± 1.9 glabella and 2.2 ± 1.2 temple) and 34G (1.7 ± 1.2 forehead, 1.6 ± 1.4 glabella and 1.6 ± 1.4 temple). All differences between needle size were statistically significant (p < 0.05) CONCLUSION: 33G and 34G needles seem to offer smaller discomfort during BTX treatments of the head and neck, with 34G being superior to 33G. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Botulinum Toxin Injection Technique for Reducing the Masseter Size and Enhancing the Jawline.

BACKGROUND: The injection of botulinum toxin into the masseter muscle is an important method for improving hypertrophy. However, some patients may experience adverse reactions, such as sagging of the lower jaw. Therefore, we proposed a method of injecting botulinum toxin into the masseter and platysma muscles that would reduce masseter size and enhance the jawline. OBJECTIVES: The aim of this study was to reduce the masseter size while enhancing the jawline. METHODS: Twenty patients received botulinum toxin injections into the masseter and platysma muscles. Pain levels were evaluated with the visual analog scale. All patients were photographed before and 6 months after treatment. Evaluations were performed based on standardized criteria. The lift index, reduction index, and symmetry index were performed to assess the degree of jawline elevation, masseter size reduction, and jawline symmetry before and after treatment. RESULTS: The mean visual analog scale score of the 20 patients was 2.80 (±1.24). The mean lift index score decreased from 4.93 (±0.34) to 4.53 (±0.37), P < .05. The mean reduction index score decreased from 3.13 (±0.27) to 2.74 (±0.27), P < .05. The mean symmetry index score changed from 0.0393 (±0.0296) to 0.0257 (±0.0246), P < .05. CONCLUSIONS: Botulinum toxin injections into the masseter and platysma muscles through nerve block reduced the masseter size, elevated the jawline, and improved symmetry.

Safety and Duration of Effect of 40-Unit PrabotulinumtoxinA-xvfs for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients: A Phase II, Multicenter, Randomized, Double-Blind, Active-Controlled Trial.

BACKGROUND: Extending the duration of effect of botulinum toxins-by administering doses beyond those of the approved labels-has been an area of increasing interest in the field of aesthetics. OBJECTIVES: The aim of this study was to investigate the safety and duration of effect of 40-unit (U) prabotulinumtoxinA-xvfs (twice the approved dose and concentration) for the treatment of moderate-to-severe glabellar lines. METHODS: A total of 154 adult patients were randomized 1:1:1 to a single treatment of either 40 U prabotulinumtoxinA-xvfs (PRA 40, 5 injections of 8 U/0.05 mL), or 20 U of either prabotulinumtoxinA-xvfs (PRA 20) or onabotulinumtoxinA (ONA 20). Both 20-U controls were administered as 5 injections of 4 U/0.1 mL. Efficacy and safety were assessed on days 2, 7 (by telephone), 30, and every 30 days thereafter up to 365 days or until the patient had returned to baseline. The primary effectiveness endpoint was the duration of effect (estimated by Kaplan-Meier analysis), defined as the number of days from treatment day (baseline) to the day that glabellar line severity at maximum frown by investigator assessment returned to the baseline value. RESULTS: Patients had a mean age of 47 years (20-72 years); 69.5% had severe glabellar lines at baseline. Of the 36 adverse events, 32 (88.9%) were mild and 4 (11.1%) were moderate in severity; none were serious. The median durations of effect were estimated to be 183, 149, and 148 days for PRA 40-, PRA 20-, and ONA 20-treated patients, respectively. CONCLUSIONS: In this phase 2 pilot study, 40 U prabotulinumtoxinA-xvfs was observed to be safe and had a duration of 6 months.

Intravesical injections of botulinum neurotoxin A to treat overactive bladder and/or detrusor overactivity related to multiple sclerosis: 5-Year continuation rate and specific risk factors for discontinuation-A study from the neuro-urology committee of the French Association of Urology.

BACKGROUND: While intravesical injections of botulinum neurotoxin A (BoNT-A) are currently recommended for patients experiencing refractory neurogenic overactive bladder and/or detrusor overactivity (OAB/DO), it is unclear how much this therapy is effective and sustainable in the long-term in patients with multiple sclerosis (MS). OBJECTIVES: To assess the mid-term continuation rate of BoNT-A injections to treat neurogenic OAB/DO in MS patients and to investigate MS-specific risk factors for discontinuation. METHODS: This retrospective study involved 11 French university hospital centers. All MS patients who received BoNT-A to treat neurogenic OAB/DO between 2008 and 2013 and were subsequently followed up for at least 5 years were eligible. RESULTS: Of the 196 MS patients included, 159 (81.1%) were still under BoNT-A 5 years after the first injection. The combination of the Expanded Disability Status Scale (EDSS < 6 or ⩾ 6) and of the MS type (relapsing-remitting vs progressive) predicted the risk of discontinuation. This risk was 5.5% for patients with no risk factor, whereas patients presenting with one or two risk factors were 3.3 and 5.7 times more likely to discontinue, respectively. CONCLUSION: BoNT-A is a satisfying mid-term neurogenic OAB/DO therapy for most MS patients. Combining EDSS and MS type could help predict BoNT-A discontinuation.