Botulinum Toxin Injection Research Articles

Painful Legs and Moving Toes Syndrome: Case Report and Review

Introduction: Painful legs and moving toes (PLMT) syndrome is a rare movement disorder characterized by defuse lower limb neuropathic pain and spontaneous abnormal, involuntary toe movements. Objective: The objective was to present a rare case of PLMT syndrome with a triggering area in an adult patient due to multilevel discogenic pathology, to make a thorough review of this disorder and to provide a practical approach to its management. Case presentation: A 59-years-old male was admitted to the neurology ward with symptoms of defuse pain in the lower-back and the right leg accompanied by involuntary movements for the right toes intensified by tactile stimulation in the right upper thigh. Magnetic resonance imaging (MRI) revealed a multilevel discogenic pathology of the lumbar and cervical spine, with myelopathy at C5-C7 level. A medication with Pregabalin 300 mg/daily significantly improved both the abnormal toe movements and the leg pain. The clinical effect was constant during the 90-day follow-up without any adverse effects. Conclusion: Painful legs and moving toes (PLMT) is a condition that greatly affects the quality of life of patients, but which still remains less known by clinicians. Spontaneous resolution is rare, and oral medications are the first-line treatment. Pregabalin is a safe and effective treatment option for PLMT that should be considered early for the management of this condition. Other medication interventions, such as botulinum toxin injections, spinal blockade, or non-pharmacological treatment options like spinal cord stimulation, and surgical decompressions, are also recommended when the conservative treatment is ineffective in well-selected patients.

The effectiveness and safety of botulinum toxin injections for managing motor disorders of patients with Parkinson's disease: A meta-analysis of randomized controlled trials.

This study aimed to assess the effectiveness and safety of botulinum toxin (BTX) injections for managing motor disorders in patients with Parkinson's disease (PD). An electronic search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from available randomized controlled trials (RCTs) assessing BTX injections for motor disorders in PD patients were extracted for meta-analysis. Ultimately, 215 patients from eight RCTs were enrolled. Pooled analyses indicated that BTX was more effective than placebo in improving tremor (standardized mean difference [SMD] = 0.96, 95% CI [0.34, 1.58], p < 0.01), whereas no notable differences were observed between BTX and placebo regarding freezing of gait (SMD = 0.66, 95% CI [-0.26, 1.58], p = 0.162), United Parkinson's Disease Rate Scale (UPDRS) III score (SMD = -0.20, 95% CI [-1.17, 0.76], p = 0.68) and clinical global impression (CGI) score (SMD = 0.84, 95% CI [-0.74, 2.42], p = 0.298). Adverse events related to BTX injections were comparable to placebo (OR = 1.74, 95% CI [0.59, 5.14], p = 0.32). The current evidence suggests that BTX is effective and safe in treating PD tremor but fails to provide therapeutic benefits for freezing of gait and motor functional scores in PD patients. Furthermore, the limited number of included studies and heterogeneity in BTX intervention protocols suggest more research is needed, with additional standardized RCTs, to better understand and optimize BTX injections for motor disorders in PD.

Depressive symptoms and quality of life in patients with benign essential blepharospasm under long-term therapy with botulinum toxin.

Regular and long-term injections of botulinum toxin (BoNT) are considered the first line therapy for essential blepharospasm (BEB), but no data exists on the long-term effect of this therapy on depressive symptoms and quality of life. This study aims to prospectively evaluate the long-term effects of BoNT therapy on depressive symptoms as well as on daily activities, emotional well-being and quality of life using validated questionnaires (BEB-scale, Beck`s Depression Inventory (BDI)). 86 patients diagnosed with BEB were followed up for a median of 4 years. Clinical symptoms improved significantly after BoNT-injections. Everyday activities and subjective assessment of the overall situation improved gradually under long-term BoNT therapy. Significant correlations (p < 0.0001; r-values between 0.498 and 0.706) were found between the BDI and items of the BEB-scale. No significant antidepressive effect of long-term BoNT therapy was found with a low median BDI total score (5/max. 63), but up to 31.3% of BEB patients had a BDI score ≥ 11, indicating clinically relevant depressive symptoms. Of these, 65.4% had no known history of depression. Although, several studies reported an antidepressant effect of botulinum toxin injections in patients with major depression, this effect does not seem to be present in patients with BEB despite clinical improvement of symptoms. A high prevalence of previously undetected depressive symptoms was found in BEB patients. As this may influence BoNT therapy success, identifying potential depressive symptoms at the time of BEB diagnosis and initiating appropriate treatment seems important.

Comparison of The Postoperative Outcomes of Surgical Lateral Internal Sphincterotomy and Botulinum Toxin Injection in Patients Presenting With Chronic Anal Fissure At CMH, Rawalpindi

Objective: To compare the postoperative outcomes in Lateral Internal Sphincterotomy Group and in Botulinum toxin injection Group in patients managed for chronic anal fissure. Study Design: Quasi-experimental study. Place and Duration of Study: Department of Surgery, Combined Military Hospital, Rawalpindi Pakistan, from Aug 2021 to Feb 2022. Methodology: All patients of either gender, aged 30 to 70 years, who had presented to CMH, were included in this study. Block randomization was done to allocate half of them to Lateral Internal Sphincterotomy and half to Botulinum toxin injection. Patients in both Groups were followed for four weeks to assess and compare various short and long term post-surgical outcomes. Results: There were 82 patients in total with 41 in each treatment arm. In the Lateral Internal Sphincterotomy Group, 35 85(37%) of the patients reported postoperative pain relief at 24 hours, 39(95.12%) patients healed, only 2(4.88%) patients had a recurrence. In the Botulinum toxin Group, 29(70.73%) reported postoperative pain relief at 24 hours, 35(85.37%) patients healed, whereas 6(4.63%) had a recurrence. There was no statistical difference in any parameter between either Group. Conclusion: Both methods did not show any statistically significant difference in post-operative outcomes thus other parameters like patient’s choice, cost and expertise may be considered in treatment of chronic anal fissure.

INTERCORRÊNCIAS NO USO ESTÉTICO DA TOXINA BOTULÍNICA FACIAL

Botulinum toxin, the causal agent of botulism, is the fermentation product of the bacteria Clostridium Botulinum. Toxins exist in 8 types, although in Brazil, only type A has ANVISA approval for cosmetic and therapeutic purposes. Due to its versatility and specific mechanism of action, it has become a great option for both therapeutic and cosmetic use worldwide, given the great potential in relation to its minimally invasive technique. Botulinum toxin injections treat aesthetic problems induced or aggravated by muscle contraction, controlling local neurotransmission. However, there are some risks and possible complications arising from its use. The present study, carried out in the form of a narrative review, aimed to describe the possible complications arising from the therapeutic and cosmetic use of the toxin for facial rejuvenation. To this end, studies published in the last 10 years were selected, retrieved from the Google Scholar and CAPES databases that addressed the topic. In addition to complications at the injection site, such as erythema, edema, pain, ptosis of the eyelid or eyebrow and ecchymosis, there is a group of aesthetic and functional adverse effects associated with different muscular responses to botulinum toxin or its migration. These complications occur less frequently than injection-associated reactions, but their risks and consequences are potentially greater. There are no reports of serious or fatal complications resulting from the cosmetic use of botulinum toxin. Complications depend on the technique used, so it is important to have adequate knowledge and training on the application technique.

Staggered botulinum toxin-a injections into parotid and submandibular glands prior to four-duct ligation for pediatric sialorrhea.

This study aimed to assess the effectiveness of four-duct ligation following Botulinum toxin-A injections into the parotid and submandibular glands in pediatric patients with sialorrhea resistant to nonsurgical treatments. Prior research has individually explored either surgical or Botulinum toxin interventions; however, the safety and efficacy of the combined approach to these treatments have yet to be documented. Patients were assessed before surgery and 6, 12, and 24months post-operatively. Evaluations involved interviews with parents and caregivers, conducted face-to-face or by telephone, using the Drooling Severity and Frequency Scales. Additionally, metrics such as the daily count of bib changes and the hourly frequency of saliva wiping were recorded. Quality-of-life assessments were performed before and after the surgical procedures. All complications associated with the interventions were carefully recorded. The study group consisted of 25 participants, with a median age of 6years (range 2-17years). Each participant was diagnosed with a neurological, metabolic, or genetic disorder. Evaluations were conducted periodically, culminating in a final follow-up at 24months. The treatment demonstrated a 100% success rate at six months post-operation (25/25 patients), which slightly decreased to 96% at the 12-month mark (24/25 patients) and further to 84% by the 24-month follow-up (21/25 patients). Major complications were not observed. However, minor complications were reported in six patients (24%): three exhibited temporary facial swelling (12%), two encountered minor bleeding (8%), and one experienced excessive dryness (4%). The combination of Botulinum toxin-A injection 3 weeks prior to the four-duct ligation procedure demonstrated high success rates and substantially reduced the incidence of infectious and cosmetic complications. Consequently, this staggered approach to combination treatment is recommended for managing pediatric sialorrhea cases that are resistant to non-surgical interventions.

Use of a ticket punch and adhesive transparent dressings for injecting botulinum toxin in hyperhidrosis

This article describes a novel modification in marking the sites of botulinum toxin injection in patients with axillary hyperhidrosis using a ticket punch and an adhesive occlusive sticker.

Resolving the Controversy Surrounding the Function of the Corrugator Supercilii Muscle.

The corrugator supercilii muscle (CSM) has traditionally been recognized as a primary depressor of the eyebrows, playing a key role in expressing negative emotions and contributing to the formation of glabellar lines. However, recent studies indicate that the CSM may exhibit movements contrary to those previously documented, suggesting a more complex functional role. This research re-evaluates the anatomical and functional roles of the CSM and discusses their implications for botulinum toxin treatments. A prospective, intrapersonal comparative, and split-face study was conducted over a five-year period, from January 6, 2019, to January 6, 2024, involving 298 patients who underwent botulinum toxin injections. The study divided participants into seven groups, each targeting specific anatomical areas of the CSM and associated muscles. Injection techniques were varied to assess their impact on brow dynamics, with outcomes measured by changes in eyebrow position and expression lines. The study demonstrated that targeting specific portions of the CSM and depressor supercilii muscle (DSM) leads to distinct outcomes in brow elevation and the reduction of expression lines. However, this approach was also frequently associated with the development of omega-shaped wrinkles. Split-face evaluations further validated that the modified injection techniques achieved superior eyebrow elevation compared to traditional methods. This study challenges the traditional view of the CSM as primarily a brow depressor, highlighting its role in medial brow elevation. These findings underscore the need for a nuanced approach in esthetic medicine, particularly in botulinum toxin injections, to achieve balanced and natural facial expressions. Understanding the full range of CSM functions is crucial for optimizing esthetic outcomes and enhancing patient satisfaction. 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 .

Ultrasound visualization of Botulinum toxin injection: Identifying clinical correlates to optimize outcomes in spasticity management.

Botulinum toxin injections are well established and commonly used for spasticity management. Clinicians strive to optimize outcomes from toxin injections. One potential complication is toxin spread beyond the intended muscle, which can lead to unwanted weakness. The utilization of ultrasound allows direct visualization of target muscles and identification of toxin leakage from the target muscle. Ultrasound evaluation of clinical factors that correlate to toxin leakage have not been studied. To identify cases of botulinum toxin injectate leak beyond the targeted muscle during ultrasound-guided spasticity injections and associate cases of leak with predictive clinical factors, which include muscle size, fibroadipose changes, and number of previous injections. This was a prospective observational study. An outpatient clinic in an academic medical center. Patients who demonstrated wrist flexor spasticity warranting intervention were invited to participate. Patients received standard-of-care spasticity management with injection of onabotulinumtoxinA into the flexor carpi radialis muscle based upon clinical presentation and prescribing guidelines. Ultrasound video was recorded, and a blinded review was conducted by the study team. The primary outcome measure was visualized leak of injectate on recorded ultrasound video. Documented leak was then associated with clinical factors including diameter of the flexor carpi radialis, volume of injectate used, history of prior injections, and fibrotic change of the muscle. The study included 54 patients, 77.8% of whom had an underlying diagnosis of cerebrovascular accident. Injectate leak was observed in 18.5% of injections and could not be confirmed in 9.3% of injections. Multivariable analysis demonstrated increased odds of leak with higher Modified Heckmatt Scale score. No statistically significant increase in leak was noted with higher volume of injectate or smaller muscle diameter. Extramuscular leak of botulinum toxin injection may be associated with fibroadipose muscle change.

Intragastric botulinum toxin injection: a promising alternative for obesity treatment?

Intragastric botulinum toxin injection: a promising alternative for obesity treatment?

Impact of Bell's palsy in facial emotion recognition: a prospective observational study of 60 patients.

Patients with Bell's palsy suffer from functional deficits and cannot convey their emotions through the face as well as they used to. According to embodied cognition, automatic mimicry and facial feedback modulate emotion perception. The aim of our study was to determine the impact of Bell's palsy on facial emotion perception. Facial motor skills, the use of botulinum toxin injections, and anxiety were studied. 60 patients completed Emotest-VA, an assessment tool of facial emotion perception, facial motor assessment and affective questionnaires. Facial perception scores of patients were compared to the normative data provided by Emotest-VA. Relationships between facial motor skills, anxiety and perceptual abilities were carried out with Pearson's correlations. Perception accuracy scores were abnormal in 12% of patients. Patients were more ambiguous than normative population to perceive emotion (t(23) = 4.14, p < .001). Happiness arousal was negatively correlated to smile asymmetry (n = 60, r=-.294 p = .022). Patients who received botulinum toxin were more accurate to perceive disgust (Z = 3.60, p < .001). State anxiety decreased when patients could improve their horizontal smile (r = - 440, p < .001). Bell's palsy impaired sensorimotor simulation, thereby reducing emotional contagion. Smile measures could indicate patients' recovery and patients' anxiety. It could also predict patient's perceptual abilities. These results provide new directions in the management of Bell's palsy. Additionally to physical therapy, it is relevant to improve emotional contagion both in its productive and perceptive aspects through facial feedback.

Botulinum Toxin Treatment of Psoriasis-A Comprehensive Review.

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

When Should Headache Specialists Hold a Needle? The Role of Botulinum Toxin Injections and Occipital Nerve Blocks

When Should Headache Specialists Hold a Needle? The Role of Botulinum Toxin Injections and Occipital Nerve Blocks

Combination of pretarsal and preseptal botulinum toxin injections in the treatment of blepharospasm: A prospective nonrandomized clinical trial

PurposeTo compare the efficacy of two botulinum toxin (BoNT) injection methods, pretarsal (PT) combined with preseptal (PS) injection (PT-PS) and conventional PT injection, in the treatment of benign essential blepharospasm (BEB). DesignProspective nonrandomized clinical trial. MethodsFrom January 2023 to April 2024, 95 BoNT injections into orbicularis oculi were performed in 45 BEB patients, including 52 PT-PS injections s and 43 PT injections. Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI) were used to assess motor symptoms. The efficacy of two injection methods for BEB was compared in terms of latency to response (LTR), latency to the peak response (LPR), duration of peak response (DPR), duration of response (DOR), satisfaction degree, and possible complications. ResultsBoth injection methods significantly improved JRS and BSDI scores in patients with BEB. However, PT-PS injections showed a shorter LTR [(4.00(3.00,6.00) vs 5.00(4.00,7.00) days, p=0.024] and LPR [23.50(16.00,26.00) vs 26.00(20.00,30.00) days, p=0.040], a longer DPR [88.00(80.50,104.75) vs 75.00(65.00,92.00) days, p=0.003] and DOR [135.00(118.50,153.75) vs 121.00(107.00,135.00) days, p=0.003] than PT injections. Patients with PT-PS injections were more satisfied than those with PT injections [9.50(8.50,10.00) vs 8.00(7.50,9.00), p<0.001], and around 2/3 of patients were more willing to receive the combined injection method later. Among patients receiving PT-PS injections, only one case experienced ptosis, and there were no significant differences in other complications such as lacrimation, dry eyes, and blurred vision between the two injection methods. ConclusionsPT-PS injections of BoNT showed more advantages in the treatment of BEB than PT injections in terms of both their efficacy and patients’ satisfactions.

The Use of Botulinum Toxin to Treat Infantile Esotropia

Injection of botulinum toxin type A into both rectus muscles is an alternative to surgery and has given good results in children with infantile esotropia. Reducing the angle of deviation can help restore binocular vision, which in turn will promote motor fusion and allow better control of the strabismus and may even lead to eventual healing. We report the result after 6 months of injection of botulinum toxin in the medial rectus in 6 children with infantile esotropia.

An Alternative Approach for Treating Female Underactive Bladders with Chronic Urine Retention: A Pilot Study on Combined Transvaginal Ultrasound-Guided Botulinum Toxin A External Sphincter Injection and Transurethral Incision of the Bladder Neck.

Background: Treating an underactive bladder (UAB) is challenging. Previously, we introduced a more precise method of transvaginal ultrasound-guided botulinum toxin A (BoNT-A) injection into the external urethral sphincter as a treatment option for patients with UABs. Although many patients experience good results, those with an UAB and excessive residual urine still require catheterization. Therefore, we developed a new method that combines transvaginal ultrasound-guided BoNT-A injection with a transurethral bladder neck incision. Methods: A prospective study was conducted on 16 patients who experienced symptoms of UAB and chronic urine retention. The treatment consisted of a combination of transvaginal ultrasound-guided BoNT-A injection and a transurethral incision of the bladder neck (TUI-BN). The primary objective was to assess the efficacy of this combined treatment in improving symptoms in women with UABs. Results: Our study demonstrated significant improvements after treatment, including increased voiding volume, decreased post-void residual (PVR) urine, and improved voiding efficiency. The frequency of clean intermittent catheterization (CIC) decreased at 1 and 3 months post-surgery, along with improvements in the AUA symptoms score and the Patient Perception of Bladder Condition (PPBC) score. Conclusions: Our study showed significant improvements in the surgical treatment of UABs using a combination of transvaginal ultrasound-guided BoNT-A and TUI-BN.

Endoscopic Management of Post-Esophagectomy Delayed Gastric Conduit Emptying (DGCE): Results from a Cohort Study in a Tertiary Referral Center with Comparison between Procedures

Background/Objectives: Delayed gastric conduit emptying (DGCE) occurs in 15–39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods: We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. A Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20 mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. Results: A total of 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma) with a median age of 62 years (IQR 55–70) were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group, and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p = 0.02), and a Kaplan–Meier analysis with a log–rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8–1.5; p = 0.001) and a shorter median time to discharge of one day (95% CI 1–3; p = 0.0001). Conclusions: Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged.

Variety of therapeutic approaches to primary hyperhidrosis (HH) and botulinum toxin priority over other treatment options in this condition - a review

Introduction and purpose Hyperhidrosis (HH) is a medical conditions that affects more and more people every year. It is characterized by undue sweating without any temperature changes and significantly above the body’s thermoregulation needs. Primary hyperhidrosis is associated with genetic and psychological factors, as the etiology is not yet found. Treatment is aimed at the symptoms. Secondary hyperhidrosis happens as an adverse event of drugs taken by patient or is a part of neurological, endocrine or oncological diseases. Teratment should be focused on the main underlying disease. The quality of life of these patients is reduced and it affects their psychological health.This study inevstigates currently available methods of treatment. State of knowledge Various treatment options for hyperhidrosis range from topical aluminum salts for mild cases to oral anti-cholinergic agents for more severe conditions. Additional methods include iontophoresis, lasers like Nd:Yag, and botulinum toxin injections, known for their effectiveness. Surgical procedures such as Endoscopic Thoracic Sympathectomy, local skin excision, liposuction-curettage are also available for severe cases. Consultation with a healthcare provider is crucial to determine the most suitable treatment based on individual needs and preferences. Conclusions Literature provides valuable insights into hyperhidrosis and its treatments, emphasizing the importance of patient expectations and safety. Starting with topical aluminum salts for mild cases, treatments need to be reapplied regularly. Surgical options are considered if conservative treatments fail, but they come with potential risks. Botulinum toxin injections stand out for their efficacy, quick procedure, and the convenience of one or two annual sessions, making them a popular choice in many aesthetic clinics. Consulting with healthcare professionals is key to selecting the most suitable treatment approach for individual needs.

Doses of Botulinum Toxin in Cervical Dystonia: Does Ultrasound Guidance Change Injection Practices?

Cervical dystonia is widely understood to benefit from botulinum toxin injections. The injection practices may be influenced by specific factors, including the method of injection. Three main guidance methods can be used: palpation of anatomical landmarks, ultrasound, and electromyography. We investigated how target muscles and doses of botulinum toxin were modified after the transition from surface anatomy (non-guided) to ultrasound (US-guided), in patients with cervical dystonia. We also determined the long-term dose trend. We studied a group of 82 patients, who received non-guided injections (median: 16.5 cycles/5.1 years) followed by US-guided injections (median: 12.0 cycles/3.8 years). More muscles, and especially deep muscles, were injected during the US-guided period. The total dose and number of injected muscles were higher when US guidance was used, but the mean dose per muscle was lower. Over the long term, the total dose stabilized, and the mean dose per muscle decreased during the US-guided period. According to our results, the guidance method has a strong impact on the botulinum toxin injection strategy in cervical dystonia (target muscles and dose). Also, the treatment appeared more stable when using US guidance; this could be explained by the good precision of such injections.

Reduced Injection Site Pain with Altered pH in 24-h Reconstituted Botulinum Toxin: Findings from a Randomized Controlled Study on Cosmetic Applications.

Botulinum toxin (BTX) injections are widely recognized for many cosmetic applications, but still commonly encounter a challenge: injection site pain (ISP). This discomfort can impact the overall patient experience and satisfaction, highlighting a need for innovative solutions to this problem. This randomized controlled study aimed to determine whether adjusting the pH levels in a 24-h reconstituted botulinum toxin can serve as a strategy to mitigate ISP. A controlled trial involving 24 volunteers was executed. Participants received incobotulinum toxin A. One side of each participant's face was treated with fresh toxin, while the other received a 24-h reconstituted version. Pain perceptions post-injection were assessed using the visual analogue scale (VAS). pH values of the fresh toxin were more acidic (6.17) than the 24-h reconstituted toxin (7.17). Out of 24 patients, 13 reported reduced ISP with the 24-h reconstituted toxin. The mean VAS score for the fresh toxin was 5.92, in contrast to 4.17 for the reconstituted toxin, indicating a significant difference (p<0.01). Limitations include the use of a VAS and a relatively small sample size. Altering the pH of BTX demonstrates potential in ISP reduction. However, broader, large-scale investigations are important for comprehensive validation. 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.