Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). METHODS: This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. RESULTS: 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). CONCLUSION: G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

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.).

Botulinum toxin A dissolving microneedles for hyperhidrosis treatment: design, formulation and in vivo evaluation.

Multiple periodic injections of botulinum toxin A (BTX-A) are the standard treatment of hyperhidrosis which causes excessive sweating. However, BTX-A injections can create problems, including incorrect and painful injections, the risk of drug entry into the bloodstream, the need for medical expertise, and waste disposal problems. New drug delivery systems can substantially reduce these problems. Transdermal delivery is an effective alternative to conventional BTX-A injections. However, BTX-A's large molecular size and susceptibility to degradation complicate transdermal delivery. Dissolving microneedle patches (DMNPs) encapsulated with BTX-A (BTX-A/DMNPs) are a promising solution that can penetrate the dermis painlessly and provide localized translocation of BTX-A. In this study, using high-precision 3D laser lithography and subsequent molding, DMNPs were prepared based on a combination of biocompatible polyvinylpyrrolidone and hyaluronic acid polymers to deliver BTX-A with ultra-sharp needle tips of 1.5 ± 0.5 µm. Mechanical, morphological and histological assessments of the prepared DMNPs were performed to optimize their physicochemical properties. Furthermore, the BTX-A release and diffusion kinetics across the skin layers were investigated. A COMSOL simulation was conducted to study the diffusion process. The primary stability analysis reported significant stability for three months. Finally, the functionality of the BTX-A/DMNPs for the suppression of sweat glands was confirmed on the hyperhidrosis mouse footpad, which drastically reduced sweat gland activity. The results demonstrate that these engineered DMNPs can be an effective, painless, inexpensive alternative to hypodermic injections when treating hyperhidrosis.

Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.

Designing an RNA-interacting molecule that displays high therapeutic efficacy while retaining specificity within a broad concentration range remains a challenging task. Risdiplam is an FDA-approved small molecule for the treatment of spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. Branaplam is another small molecule which has undergone clinical trials. The therapeutic merit of both compounds is based on their ability to restore body-wide inclusion of Survival Motor Neuron 2 (SMN2) exon 7 upon oral administration. Here we compare the transcriptome-wide off-target effects of these compounds in SMA patient cells. We captured concentration-dependent compound-specific changes, including aberrant expression of genes associated with DNA replication, cell cycle, RNA metabolism, cell signaling and metabolic pathways. Both compounds triggered massive perturbations of splicing events, inducing off-target exon inclusion, exon skipping, intron retention, intron removal and alternative splice site usage. Our results of minigenes expressed in HeLa cells provide mechanistic insights into how these molecules targeted towards a single gene produce different off-target effects. We show the advantages of combined treatments with low doses of risdiplam and branaplam. Our findings are instructive for devising better dosing regimens as well as for developing the next generation of small molecule therapeutics aimed at splicing modulation.

Unparallel improvement patterns of dynamic wrinkles and skin quality after botulinum toxin type A treatment on the upper face.

BACKGROUND: Botulinum toxin type A (BoNT-A) can not only reduce the dynamic wrinkles but also improve the skin quality. This study aims to quantitaively and comprehensively assess the improvement of dynamic wrinkles and skin quality following BoNT-A treatment on the upper face. METHODS: Patients were recruited to receive BoNT-A treatment of the glabellar, frontal, and lateral periorbital wrinkles. Antera 3D camera was used to evaluate the skin quality and dynamic wrinkle severity. Follow-up visits were at 1 week, 1 month, 3 months, and 6 months after treatment. Different filters were utilized to quantitatively detect the severity of fine wrinkles (FWS), the volume of pores (PV), the roughness of skin texture (STR), and the severity of dynamic wrinkles (DWS). RESULTS: Twenty-four participants (average 30.5 ± 7.2 years) were recruited. The significant improvement of PV, FWS, and STR in different areas usually maintained from 1 to 6 months after injections but of DWS only existed within 3 months. For each area, the improvement rates of FWS, PV, and STR peaked at 3 months or 6 months after treatment while the maximal improvement of DWS was observed at 1 month posttreatment. CONCLUSION: After BoNT-A treatment for dynamic wrinkles on the upper face, the skin quality of target regions can also be ameliorated. The improvement of skin quality and dynamic wrinkles presented unparallel patterns. The former is with a slower onset but longer duration while the latter exhibits a more rapid onset but shorter duration.

A computed tomography study investigating the effects of botulinum toxin injections prior to complex abdominal wall reconstruction.

OBJECTIVE: To explore how intramuscular injection of botulinum toxin A (BTA) affects the lateral abdominal wall (LAW) musculature, abdominal- and hernia dimensions, and muscle structure on computed tomography (CT) in patients scheduled for complex abdominal wall reconstruction (CAWR). METHODS: Retrospective analysis of prospectively registered patients who received bilateral intramuscular BTA injections into all three muscles of the LAW. Only patients for which a CT was available before and 3-6 weeks after BTA treatment prior to surgery were analyzed. RESULTS: Fifty-two patients were analyzed. Median hernia width in all patients decreased with 0.4 cm (IQR - 2.1;0.6) (p = 0.023). Median intra-abdominal transverse diameter increased with 0.9 cm (IQR - 0.2;3.3) (p = 0.001) and the intra-abdominal anterior-posterior diameter decreased with 0.5 cm (IQR - 1.3;0.5) (p = 0.017), making the abdomen more oval. Median LAW muscle length increased with 0.9 cm (IQR 0.0;2.4) per side (p < 0.001), muscle thickness decreased with 0.5 cm (IQR - 0.8;- 0.2) (- 25.0%) per side (p < 0.001), and muscle mass decreased with 3.9 cm2 (IQR - 6.4;-1.5) (- 15.8%) per side (p < 0.001). Median HU of the psoas muscles (density) increased with 4.8 HU (IQR 0.4;9.7) (10.3%) per side (p < 0.001). Effects of BTA were more pronounced in patients with a loss of domain (LoD) ≥ 20%. CONCLUSIONS: The main effect of BTA injections is elongation and thinning of the LAW muscles, more than a decrease in hernia width. Concomitantly, the abdomen becomes more oval. An increase of psoas muscles density is seen, associated with offloading of the LAW muscles. Patients with large LoD have a proportionally higher effect of BTA.

Clinical effects of glabellar botulinum toxin injections on borderline personality disorder: A randomized controlled trial.

BACKGROUND: Inhibition of frowning via injections of botulinum toxin A (BTX) into the glabellar region has shown beneficial effects in the treatment of major depression. Preliminary research suggests that improvements in the affective domain are not depression-specific, but may also translate to other psychiatric disorders. AIM: This 16-week, single-blind, two-center randomized controlled trial investigated the influence of BTX on clinical symptoms of borderline personality disorder (BPD). METHODS: Fifty-four patients with BPD were randomly assigned to treatment with BTX (n = 27) or a minimal acupuncture (ACU) control condition (n = 27). Clinical outcomes were followed at 2, 4, 6, 8, 12, and 16 weeks. Primary endpoint was the relative score change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) 8 weeks after baseline relative to the control group and adjusted for treatment center. Secondary and additional outcome variables were self-rated borderline symptoms, comorbid symptoms of depression, psychological distress, and clinical global impression. RESULTS: Participants showed significant improvements at the primary efficacy endpoint in both treatment groups (BTX: M = -0.39, SD = 0.39; ACU: M = -0.35, SD = 0.42), but no superior effect of the BTX condition in comparison with the control intervention was found-F(1,5323) = 0.017, p = 0.68). None of the secondary or additional outcomes yielded significant group differences. Side effects were mild and included headache, transient skin or muscle irritations, and dizziness. CONCLUSION: Evidence regarding the efficacy of BTX for BDP remains limited, and the design of adequate control conditions presents an opportunity for further research.ClinicalTrials.gov registry: Botulinum Toxin A for Emotional Stabilization in Borderline Personality Disorder (BPD), NCT02728778, https://clinicaltrials.gov/ct2/show/NCT02728778.

OnabotulinumtoxinA for the treatment of headache: an updated review.

Botulinum toxin (BT) is a neurotoxin produced by Clostridium botulinum, a gram-positive anaerobic bacterium. Systemic human intoxication from BT following oral ingestion results in acute and life-threatening muscle paralysis called botulism. BT has a wide scope of therapeutic uses, including conditions associated with increased muscle tone, smooth muscle hyperactivity, salivation, sweating, and allergies, as well as for cosmetic purposes. Several commercial forms of BT are available for medical use, including Botox (onabotulinumtoxinA). Multiple studies have found evidence of an analgesic effect of onabotulinumtoxinA and demonstrated the benefits of its use for the treatment of various chronic pain disorders. In this review, we provide an update on the use of onabotulinumtoxinA for the treatment of headache disorders.

Comprehensive Assessment of the Time Course of Biomechanical, Electrophysiological and Neuro-Motor Effects after Botulinum Toxin Injections in Elbow Flexors of Chronic Stroke Survivors with Spastic Hemiplegia: A Cross Sectional Observation Study.

Botulinum neurotoxin (BoNT) is commonly used to manage focal spasticity in stroke survivors. This study aimed to a perform comprehensive assessment of the effects of BoNT injection. Twelve stroke subjects with spastic hemiplegia (age: 52.0 ± 10.1 year; 5 females) received 100 units of BoNT to the spastic biceps brachii muscles. Clinical, biomechanical, electrophysiological, and neuro-motor assessments were performed one week (wk) before (pre-injection), 3 weeks (wks) after, and 3 months (mons) after BoNT injection. BoNT injection significantly reduced spasticity, muscle strength, reflex torque, and compound muscle action potential (CMAP) amplitude of spastic elbow flexors (all p < 0.05) during the 3-wks visit, and these values return to the pre-injection level during the 3-mons visit. Furthermore, the degree of reflex torque change was negatively correlated to the amount of non-reflex component of elbow flexor resistance torque. However, voluntary force control and non-reflex resistance torque remained unchanged throughout. Our results revealed parallel changes in clinical, neurophysiological and biomechanical assessment after BoNT injection; BoNT injection would be more effective if hypertonia was mainly mediated by underlying neural mechanisms. BoNT did not affect voluntary force control of spastic muscles.

An indirect comparison meta-analysis of noninvasive intravesical instillation and intravesical injection of botulinum toxin-A in bladder disorders.

BACKGROUND: Botulinum toxin type A (BTX-A) intravesical instillation and BTX-A intravesical injection are both effective treatments or overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS), but direct comparative studies of the two treatments are lacking. METHODS: We conducted a pairs-comparison meta-analysis and an adjusted indirect comparison meta-analysis extracting published data from randomized controlled trials in literature databases from the inception of each database to Aug. 31, 2021, evaluating efficacy and safety of BTX-A intravesical instillation and BTX-A intravesical injection. We also carried out a subgroup analysis. RESULTS: We identified 24 trials in 21 studies were included in our study, of which 18 trials in 17 studies were BTX-A intravesical injections, 6 trials in 4 studies were BTX-A intravesical instillation. Compared with the normal saline injection, BTX-A intravesical injections for patients with OAB and IC/ BPS can obviously improve the symptoms of urinary frequency, urgency episode, UI and UUI, but BTX-A significantly increased the rate of urinary retention and urinary tract infection and increased PVR (p < 0.05). Adjusted indirect comparison meta-analysis showed that BTX-A intravesical injections was more effective than BTX-A intravesical instillation (p > 0.05). Surprisingly, BTX-A intravesical instillation had fewer side effects than BTX-A intravesical injections (p < 0.05). CONCLUSIONS: Although BTX-A intravesical injections of OAB and IC/BPS has been significantly superior the BTX-A intravesical instillation, it has major side effects, but this needs to be confirmed by more large-scale, multicenter, direct comparison randomized controlled trials.

Botulinum Toxin Type A for Lumbar Sympathetic Ganglion Block in Complex Regional Pain Syndrome: A Randomized Trial.

BACKGROUND: The present study was designed to test the hypothesis that botulinum toxin would prolong the duration of a lumbar sympathetic block measured through a sustained increase in skin temperature. The authors performed a randomized, double-blind, controlled trial to investigate the clinical outcome of botulinum toxin type A for lumbar sympathetic ganglion block in patients with complex regional pain syndrome. METHODS: Lumbar sympathetic ganglion block was conducted in patients with lower-extremity complex regional pain syndrome using 75 IU of botulinum toxin type A (botulinum toxin group) and local anesthetic (control group). The primary outcome was the change in the relative temperature difference on the blocked sole compared with the contralateral sole at 1 postoperative month. The secondary outcomes were the 3-month changes in relative temperature differences, as well as the pain intensity changes. RESULTS: A total of 48 participants (N = 24/group) were randomly assigned. The change in relative temperature increase was higher in the botulinum toxin group than in the control group (1.0°C ± 1.3 vs. 0.1°C ± 0.8, respectively; difference: 0.9°C [95% CI, 0.3 to 1.5]; P = 0.006), which was maintained at 3 months (1.1°C ± 0.8 vs. -0.2°C ± 1.2, respectively; P = 0.009). Moreover, pain intensity was greatly reduced in the botulinum toxin group compared with the control group at 1 month (-2.2 ± 1.0 vs. -1.0 ± 1.6, respectively; P = 0.003) and 3 months (-2.0 ± 1.0 vs. -0.6 ± 1.6, respectively; P = 0.003). There were no severe adverse events pertinent to botulinum toxin injection. CONCLUSIONS: In patients with complex regional pain syndrome, lumbar sympathetic ganglion block using botulinum toxin type A increased the temperature of the affected foot for 3 months and also reduced the pain.

Safety and Efficacy of Botulinum Toxin in the Treatment of Self-Biting Behavior in Lesch-Nyhan Disease.

BACKGROUND: Lesch-Nyhan disease (LND) is a disease of purine metabolism linked to chromosome X due to the absence or near-absence of enzyme hypoxanthine-guanine phosphoribosyltransferase. Patients with LND have a compulsive autoaggressive behavior that consists of self-mutilation by biting. METHODS: The objective of this study was to explore the safety and efficacy of botulinum toxin (BoNT) injected into the masticatory muscles and biceps brachii to reduce self-mutilation in patients with LND. We retrospectively analyzed six patients with LND who were treated with BoNT to prevent automutilatory behavior. RESULTS: The patient ages when started on treatment with BoNT were 4, 4.5, 6.6, 7.9, 13.9, and 32.3 years. Patients received a mean number of injections of 20, ranging from 3 to 29, over a period that ranged from 1.5 to 7.1 years. The maximum total dose of Botox was 21.3 units/kg mean and the maximum total dose of Dysport was 37.5 units/kg mean. A total of 119 injections were performed. Of these 113 (95%) were partially or completely effective. Only three of 119 injections (2.5%) produced adverse effects. CONCLUSIONS: Botulinum toxin is useful and safe for the treatment of self-biting behavior in patients with LND.

Investigating Inducible Muscle Overactivity in Acquired Brain Injury and the Impact of Botulinum Toxin A.

OBJECTIVE: To investigate the pattern of change in muscle overactivity during repetitive grasp/release using dynamic computerized dynamometry (DCD; objective 1) and the effect of botulinum toxin A (BTX-A; objective 2). DESIGN: Secondary analysis of an observational cohort study. SETTING: Hospital outpatient spasticity management service. PARTICIPANTS: A convenience sample (N=65), comprising adults with upper motor neuron syndrome affecting the arm after acquired brain injury (ABI; n=38) and participants without ABI (n=27). INTERVENTIONS: After clinical assessment, a subgroup of participants with ABI (n=28) underwent BTX-A injections as part of their spasticity management. MAIN OUTCOME MEASURES: Post hoc DCD data processing extracted the values of minimum force generation between 10 sequential contractions. The pattern of change was analyzed. RESULTS: The ABI injected group exerted greater force at baseline than both other groups (ABI injected=1.04 kg, ABI noninjected=0.74 kg, participants without ABI=0.53 kg; P=.011). After the first contraction, minimum force values increased for all groups and were greatest in the ABI injected group. With subsequent cycles, the group without ABI showed a linear pattern of decreasing force generation, whereas both ABI groups showed a quadratic increasing pattern, which was of greater magnitude in the ABI injected group. After injection, values for the ABI injected group showed a 51% reduction in inducible muscle overactivity (P=.003) to magnitudes similar to those of the ABI noninjected group. CONCLUSIONS: This study showed that hand relaxation deteriorated during repetitive movements in people with spasticity, a feature hypothesized to adversely influence everyday hand function. After BTX-A injection, the magnitude but not the pattern of this inducible muscle overactivity improved.

Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins.

All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed that its efficacy is superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (LL type A1 toxin, or onabotulinumtoxinA) and a low-molecular-weight (150 kD) A1 neurotoxin (A1NTX). Those who had been using A1LL (n = 90; 50-360 mouse LD50 units) or A1NTX (n = 30; 50-580 units) were switched to A2NTX (n = 120; 25-600 units) from 2010 to 2018 (number of sessions ~27, cumulative doses ~11,640 units per patient). The adverse events for A2NTX included weakness (n = 1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), and spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness (n = 2, A1NTX), dysphagia (8), ptosis (6), local weakness (7), and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had clinical safety up to the dose of 500 units and was well tolerated compared to A1 toxins.

Ultrasonographic Evaluation of Three Approaches for Botulinum Toxin Injection into Tibialis Posterior Muscle in Chronic Stroke Patients with Equinovarus Foot: An Observational Study.

Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to achieving maximum accuracy for the BoNT-A injection. In current clinical practice, there are three approaches to target the TP: an anterior, a posteromedial, and a posterior. To date, previous studies have failed to identify the best approach for needle insertion into TP. To explore the ultrasonographic characteristics of these approaches, we investigated affected and unaffected legs of 25 stroke patients with SEV treated with BoNT-A. We evaluated the qualitative (echo intensity) and quantitative (muscle depth, muscle thickness, overlying muscle, subcutaneous tissue, cross-sectional area) ultrasound characteristics of the three approaches for TP injection. In our sample, we observed significant differences among almost all the parameters of the three approaches, except for the safety window. Moreover, our analysis showed significant differences in cross-sectional area between treated and untreated. Advantages and disadvantages of each approach were investigated. Our findings can thus provide a suitable reference for clinical settings, especially for novice operators.

Overview of DaxibotulinumtoxinA for Injection: A Novel Formulation of Botulinum Toxin Type A.

Botulinum toxin type A (BoNTA) products are widely used for therapeutic and aesthetic indications, but there is a need for longer-lasting treatments that maintain symptom relief between injections and reduce the frequency of re-treatment. DaxibotulinumtoxinA for Injection (DAXI) is a novel BoNTA product containing highly purified 150-kDa core neurotoxin and is the first to be formulated with a proprietary stabilizing excipient peptide (RTP004) instead of human serum albumin. The positively charged RTP004 has been shown to enhance binding of the neurotoxin to neuronal surfaces, which may enhance the likelihood of neurotoxin internalization. DAXI produces robust, extended efficacy across both aesthetic and therapeutic indications. In an extensive glabellar lines clinical program, DAXI showed a high degree of efficacy, a consistent median time to loss of none or mild glabellar line severity of 24 weeks, and median time until return to baseline of up to 28 weeks. In adults with cervical dystonia, DAXI at 125 U and 250 U significantly improved Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores, with a median duration of efficacy of 24 and 20 weeks, respectively, which compares favorably with the 12-14 weeks' duration reported for approved BoNTA products. Overall, DAXI was well tolerated, and the consistent extended duration of effect suggests that DAXI has the potential to improve the management of both aesthetic and therapeutic conditions.

Botulinum toxin is used to block the nerve signals that cause muscles to contract. Products containing botulinum toxin are commonly given by injection to treat muscle spasms (such as cervical dystonia, a painful condition where the neck muscles contract involuntarily) and for cosmetic treatment of frown lines. However, the effects of the currently approved botulinum toxin products typically wear off about 3­4 months after injection and so the injections must be repeated regularly. A new product called DAXI (DaxibotulinumtoxinA for Injection) has been developed. In this product, the botulinum toxin is formulated with a unique protein (called RTP004) that has been designed to help deliver the botulinum toxin to the nerve cells. Research suggests that the RTP004 protein in DAXI adheres the botulinum toxin to the nerves close to the injection site, potentially making its effect last longer. To date, DAXI has been studied in over 3800 patients. The studies have shown that DAXI is effective for treating neck spasms (cervical dystonia) and for reducing the appearance of frown lines. Importantly, the effects of DAXI lasted up to 6 months, which is longer than seen with other botulinum toxin products. The side effects seen with DAXI are consistent in nature and frequency with those seen with other botulinum toxin products. These findings suggest that DAXI can improve both medical and cosmetic treatments due to its longer-lasting effect.

OnabotulinumtoxinA injection towards the SPG for treating symptoms of refractory chronic rhinosinusitis with nasal polyposis: a pilot study.

BACKGROUND AND OBJECTIVE: The main objective of this prospective, open, uncontrolled pilot study was to investigate the safety of administering onabotulinumtoxinA (BTA) towards the sphenopalatine ganglion (SPG) in 10 patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) using a novel injection tool, the MultiGuide®. MATERIAL AND METHODS: A one-month baseline period was followed by bilateral injections of 25 U BTA in the SPG and a follow-up of 12 weeks. The primary outcome was adverse events (AE), and the main efficacy outcome was a 50% reduction in visual analogue scale (VAS) symptoms for nasal obstruction and rhinorrhea in months 2 and 3 post-treatment compared to baseline. RESULTS: We registered 13 AEs, none of which were serious, however, one patient experienced diplopia which moderately affected his daily activities. The symptoms slowly improved and resolved 4 weeks after injection. Five patients were treatment responders with at least 50% median reduction in the nasal obstruction, and four were treatment responders concerning rhinorrhea. CONCLUSIONS: Injection of BTA toward the SPG using the MultiGuide® in patients with CRSwNP appears to be safe but with a potential for moderately disabling side effects. The study indicates a beneficial effect on nasal obstruction.

A Novel Injection Technique to the Lateral Pterygoid Muscle for Temporomandibular Disorders: A Cadaveric Study.

BACKGROUND: Lateral pterygoid muscle activity is associated with the pathological mechanisms of some temporomandibular disorders. The authors aimed to define and demonstrate a novel, practical, and safe technique for botulinum toxin type A injection to the lateral pterygoid muscle based on their findings. Their secondary aims were to standardize the injection pattern according to the variations of the lateral pterygoid muscle and its surrounding anatomical structures, and to establish its advantages over intraoral injection. METHODS: Twenty cadaver heads were dissected. The lateral pterygoid muscle and its surrounding structures were investigated for anatomical variations. Based on these findings, a standardized extraoral injection protocol was defined and compared with the intraoral technique for accuracy and safety. RESULTS: The average depth of the lateral pterygoid plate from the skin surface was 49.9 ± 2.2 mm, and the mean width of the lateral pterygoid plate was 10.5 ± 3.9 mm. The extraoral injection approach based on the location of the maxillary tuberosity, tragus, and lateral pterygoid plate was consistent in all dissections for the accuracy of the intramuscular injection. In the intraoral approach, standardization of the entry point of the needle through the oral mucosa is difficult, which makes adjustment of the depth of the injection challenging while increasing the risk of neurovascular injury. CONCLUSIONS: The clinical significance of the lateral pterygoid muscle makes it worthwhile to implement minimally invasive treatments before considering more invasive options. The authors define a safe, accurate, and reliable approach with ease of administration in patients with temporomandibular disorders.

Ultrasound-guided five-point injection of botulinum toxin for patients with trapezius hypertrophy.

OBJECTIVES: Our study aimed to explore the clinical therapeutic effects of ultrasound-guided five-point injection of botulinum toxin type A for patients with trapezius hypertrophy. METHODS: Twenty female patients diagnosed with trapezius hypertrophy were enrolled in this study. The thicknesses of the trapezius muscle were measured by using the ultrasound scanner to locate the thickest point of trapezius, followed by labelling the other four points around the first point. Botulinum toxin type A was injected bilaterally (50 IU/side, 5 points/side) in the trapezius muscle of these patients. The surgery effects were evaluated by thicknesses of the trapezius muscle, intramuscular needle electromyographic and electroneurographic examinations, appearance changes and patients' satisfactions. RESULTS: Statistically significant differences in thicknesses of the trapezius muscle were observed at 4 weeks (p < 0.001), 12 weeks (p < 0.001), 20 weeks (p < 0.001), 28 weeks (p = 0.011), 36 weeks (p = 0.022), and 44 weeks (p = 0.032) after surgery. The latencies of trapezius muscle became longer at 12 weeks after surgery (left: 2.40 ms, right: 2.53 ms vs. left: 1.75 ms, right: 2.00 ms). Electroneurographic results showed amplitude reduction of compound muscle action potentials (CMAPs) at 12 weeks after surgery (left: 1.91 uV, right: 3.10 uV vs. left: 15.00 uV, right: 15.40 uV). Obvious appearance changes were revealed at 12 weeks after surgery. All of 80% patients were very satisfied, 15% patients were relatively satisfied, and 5% patients were not satisfied with the surgery. CONCLUSION: Ultrasound-guided five-point injection of botulinum toxin type A might be effective for patients with trapezius hypertrophy.

Ultrasound-Guided BoNT-A (Botulinum Toxin A) Injection Into the Subscapularis for Hemiplegic Shoulder Pain: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND AND PURPOSE: This study aimed to assess the efficacy of an ultrasound-guided lateral approach for BoNT-A (botulinum toxin A) injections into the subscapularis in patients with hemiplegic shoulder pain. METHODS: This single-center trial used a randomized, double-blind, placebo-controlled design. The key inclusion criteria were a visual analogue scale score of ≥4 cm and a modified Ashworth scale score of ≥1+. The patients were randomized to receive either BoNT-A injections or a placebo. The outcomes included the visual analogue scale score, modified Ashworth scale score, pain-free passive range of motion of the hemiplegic shoulder, Fugl-Meyer assessment score for the upper extremities, and Stroke-Specific Quality-of-Life score. RESULTS: A total of 49 hemiplegic shoulder pain patients were screened, and 36 were included. The participants receiving the BoNT-A injection reported a significant decrease in pain (visual analogue scale, -1.39 [95% CI, -2.41 to -0.36]; P=0.002) and spasticity (modified Ashworth scale score for shoulder internal rotation, -0.72 [95% CI, -1.10 to -0.35]; P=0.001; modified Ashworth scale score for shoulder abduction, -0.44 [95% CI, -0.90 to -0.01]; P=0.026) and improved pain-free passive shoulder internal rotation range of motion (14.56 [95% CI, 6.70-21.41]; P<0.001) and quality of life (Stroke-Specific Quality-of-Life upper extremity subscale, P=0.025) compared with those receiving the placebo at the end point. The shoulder abduction range of motion did not significantly improve after the BoNT-A injection at the end point (P=0.127). In addition, the patients in the BoNT-A group showed significant improvements in the visual analogue scale score and shoulder external rotation range of motion at the 12-week follow-up. No injection-related adverse events were observed during or after the interventions in either group. CONCLUSIONS: The ultrasound-guided lateral approach for BoNT-A injections into the subscapularis is a precise and reliable method for reducing pain and spasticity and improving quality of life in stroke survivors with hemiplegic shoulder pain. Registration: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900023513.