Botulinum toxin and hyperhidrosis of the amputation stump in war amputees.

INTRODUCTION: Stump hyperhidrosis is a common condition after lower limb amputation. It affects the prosthesis use, and the quality of life of patients. Several case reports tried to prove benefit of using Botulinum toxin in its treatment. AIM: This study was to conduct a larger workforce clinical trial and to demonstrate benefits of botulinum toxin injection in the treatment of stump hyperhidrosis. METHODS: A prospective study was conducted. War amputees who complained of annoying excessive sweating of the stump were included. They received intradermal injection of botulinum toxin A in the residual limb area in contact with prosthetic socket. Abundance of sweating and degree of functional discomfort associated with it were assessed before, after 3 weeks, 6 and 12 months. RESULTS: Seventeen male patients, followed for post-traumatic limb amputation were included in the study. Discomfort and bothersome in relation to Hyperhidrosis did decrease after treatment (p<0,001). Reported satisfaction after 3 weeks was 73,33%. Improvement of prothesis loosening up after 3 weeks was 72,5% [±15,6]. Mean injection-induced pain on the visual analogue scale was 5.17/10 (±1.58). The mean interval after the onset of improvement was 5.13 days [min:3, max:8]. The mean time of improvement was 10.4 months after the injection [min:6, max:12]. No major adverse events were reported following treatment. CONCLUSION: Intradermal injections of botulinum toxin in the symptomatic treatment of stump hyperhidrosis are effective and have few adverse effects. It improves the quality of life of our patients thanks to a better tolerance of the prosthesis.

Combined rehabilitation therapy with botulinum toxin to the upper limbs for acute spinal cord injury: A case report.

INTRODUCTION: Patients with spinal cord injury (SCI) and incomplete paralysis may experience muscle immobilization due to functional impairment of agonist and antagonist muscles. This can induce spasticity and pain, with the risk of contracture increasing as the period of immobilization increases. This could be aggravated by pain, which interferes with rehabilitation. There is no established treatment for pain and joint contractures caused by acute SCI. Botulinum therapy plays a role in relieving muscle tension. Here, we report a case of acute SCI in which botulinum therapy was administered. CASE PRESENTATION: The patient experienced a C5-cervical SCI due to a road traffic accident, with marked paralysis in the upper and lower limbs below the C5 level. The patient had persistent elbow flexion since the SCI and complained of excruciating pain, making adequate rehabilitation difficult. Botulinum toxin was administered to the biceps and brachialis muscles 15 days after the SCI. After administration, the patient experienced a reduction in pain with relaxation of the elbow flexor muscles, and rehabilitation treatment was resumed. This patient's contracture did not worsen, his pain decreased, and he was able to initiate self-feeding training. DISCUSSION: In this case, occupational and physical therapy was administered with botulinum therapy. Together, they successfully reduced pain. Botulinum therapy provides analgesia and muscle relaxation and may lead to functional recovery, and we believe that treatment can be considered even in the acute phase.

Effectiveness of Extracorporeal Shock Wave Therapy after Botulinum Toxin Injection for Post-Stroke Upper Extremity Spasticity: A Randomized Controlled Study.

Post-stroke spasticity is a common complication that limits the functional performance of patients. Botulinum toxin (BTx) is an effective treatment for spasticity. Numerous researchers have applied extracorporeal shock wave therapy (ESWT) to address post-stroke spasticity, yielding positive clinical outcomes. We aimed to clarify the add-on effects of ESWT on BTx therapy for spasticity in patients with post-stroke. Sixteen eligible patients with upper extremity spasticity after stroke were recruited for this study. They were randomized to either a BTx with focused ESWT treatment group or a BTx alone group. Spasticity, measured using the modified Ashworth score (MAS) and modified Tardieu scale (MTS), showed statistically significant improvements in the elbow and wrist flexor muscles in both BTx + ESWT group and BTx alone groups. However, no significant differences were observed between the two groups with time flow. The BTx + ESWT group showed significantly decreased MAS of the finger flexors at follow-up and increased R1 (MTS) of the finger flexors at 3 weeks after treatment, which was not observed in the BTx alone group. This is the first study to identify the add-on effect of ESWT on BTx injections to improve post-stroke upper limb spasticity.

Nerve Block Guided by Anatomic Landmarks Only Reduces Pain in Botulinum Toxin Type A Treatment for Glabellar and Forehead Wrinkles.

BACKGROUND: Botulinum toxin type A is widely used to treat glabellar and forehead wrinkles, but the pain caused by multiple injections often deters patients from receiving long-term treatment. Despite several methods used to alleviate this pain, consistency and effectiveness remain a challenge. Therefore, this study aimed to evaluate the effectiveness and safety of nerve block guided by anatomic landmarks only in reducing pain associated with botulinum toxin type A injections. PATIENTS AND METHODS: Between 2018 and 2022, the study enrolled 90 patients divided into 3 groups: the nerve block group (n = 30), the lidocaine cream group (n = 30), and the control group (n = 30). In the nerve block group, a landmarks-based technique was used to perform the nerve block. The study collected general information and comorbidities, and recorded pain at each point and time spent on preparation and treatment for each patient's forehead and glabellar area on each side. Patient-reported outcomes and complications were followed up at 2, 4, and 12 weeks after the injections. RESULTS: The nerve block group had significantly lower total pain scores in all regions compared to the lidocaine cream and control groups (P < 0.01). There were no significant differences in patient-reported outcomes between the groups at any follow-up point. Additionally, the complication rates related to injection were low and comparable among the 3 groups. CONCLUSIONS: Nerve block guided by anatomic landmarks only is a safe, effective, and consistent approach to reduce pain during botulinum toxin type A treatment for glabellar and forehead lines. This technique may offer advantages over other methods used to alleviate the pain associated with these injections.

Botulinum Toxin Injections for Psychiatric Disorders: A Systematic Review of the Clinical Trial Landscape.

Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.

Intravesical Injection of OnabotulinumtoxinA (Botulinum Toxin Type A) in Japanese Patients With Refractory Overactive Bladder.

BACKGROUND/AIM: Botulinum toxin intravesical injection therapy (hereafter, botulinum therapy) is approved in Japan for treating urinary urgency, frequency, and urinary incontinence due to refractory overactive bladder or neurogenic bladder. Although botulinum therapy is classified as urinary incontinence surgery, it is minimally invasive, effective, and safe. However, there are few reports on the actual use of botulinum therapy and examination of its effects and side-effects. Herein, we report real-world data on botulinum therapy. PATIENTS AND METHODS: Patients who received botulinum therapy for refractory overactive bladder at the Nara Medical University and affiliated facilities from May 2020 to May 2022 were enrolled. The patient background, treatment efficacy, and safety were retrospectively reviewed. RESULTS: Twenty-three cases of refractory overactive bladder (age: 68.4±14.1 years; 7 males, 16 females; 17 outpatient, 6 hospitalized) were enrolled. Pretreatment, the overactive bladder symptom score (OABSS) was 10.1±2.7, and post-void residual urine volume was 27.1±31.6 ml. Botulinum was administered once, twice, thrice, and four times in 11, eight, three, and one cases, respectively. OABSS decreased to 6.1±3.2 2 weeks after botulinum therapy (p<0.0001), and the effect persisted at 6.6±3.2 after 12 weeks (p<0.0001). Post-void residual urine volume increased to 74.6±79.2 ml after 2 weeks (p=0.0010), but subsequently improved to 33.9±42.0 ml after 12 weeks (p=0.0002). Adverse events included post-void residual urine volume of 200 ml or more in three patients (7.5%) and urinary retention grade 2 in two (5.0%). CONCLUSION: Botulinum therapy is effective and relatively safe for refractory overactive bladders.

In-vivo assessment of application of folinic acid and botulinum toxin A in cleft lip surgical defects.

INTRODUCTION: Folinic acid and botulinum toxin A have shown promising results in wound healing in different studies. This study aimed to compare the effects of these approaches on wound healing after simulating cleft lip surgery in rats. METHODS: In this experimental animal study, after creating lip defects, 30 rats were randomly divided into three groups and received normal saline (CTL), botulinum toxin A (BOT), and folinic acid (FOL). Biopsy from the skin wounds was performed after 14- and 28-days. These samples were stained with haematoxylin and eosin and Masson trichrome staining. Finally, each pathological parameter of wound healing was rated in this study. RESULTS: While the inflammatory response was not different among the study groups, fibroblast proliferation and collagen deposition were significantly higher in FOL group compared to BOT group. Moreover, both BOT and FOL facilitated epithelial healing and 14-day angiogenesis as compared with normal saline. CONCLUSIONS: Improved wound healing was observed using both botulinum toxin A and folinic acid in rat animal models. However, the application of botulinum toxin A caused less fibroblast proliferation and collagen deposition which can potentially lead to less scar formation, which can be particularly important in the aesthetic zone.

OnabotulinumtoxinA as a promising treatment for primary trochlear headache: A retrospective case series.

OBJECTIVES: To report the efficacy of onabotulinumtoxinA (BoNTA) injections in relieving pain in patients with primary trochlear headache (PRTH). METHODS: Examination of medical records for patients diagnosed with PRTH according to the International Classification of Headache Disorders, 3rd edition criteria and treated with BoNTA. Data were collected for variables related to pain relief, duration of effectiveness, and adverse effects. RESULTS: Six patients were included in the study. All had previously undergone standard care interventions, including infiltrations or oral treatments, yet experienced treatment failure or symptom recurrence. All patients received 20 units of BoNTA, administered in the corrugator and procerus muscles. Subsequent to the BoNTA injections, all six patients reported substantial pain relief, with five achieving complete remission of symptoms. The analgesic effect persisted for a duration of 3 months. No adverse events were reported in any of the cases. CONCLUSIONS: Our case series presents the first evidence of the potential of BoNTA as a safe and effective treatment option for PRTH. From a clinical standpoint, having a safer alternative is of paramount significance for patients with limited treatment options, such as those with PRTH. Further research is warranted to validate these findings and explore the long-term efficacy of BoNTA in PRTH management.

Botulinum neurotoxin type A responders among children with spastic cerebral palsy: Pattern-specific effects.

AIM: To identify short-term effects of botulinum neurotoxin type A (BoNT) injections on gait and clinical impairments, in children with spastic cerebral palsy (CP), based on baseline gait pattern-specific subgroups. METHOD: Short-term effects of BoNT injections in the medial hamstrings and gastrocnemius were defined in a retrospective convenience sample of 117 children with CP (median age: 6 years 4 months; GMFCS I/II/III: 70/31/16; unilateral/bilateral: 56/61) who had received gait analyses before and 2 months post-BoNT. First, baseline gait patterns were classified. Statistical and meaningful changes were calculated between pre- and post-BoNT lower limb sagittal plane kinematic waveforms, the gait profile score, and non-dimensional spatiotemporal parameters for the entire sample and for pattern-specific subgroups. These gait waveforms per CP subgroup at pre- and post-BoNT were also compared to typically developing gait and composite scores for spasticity, weakness, and selectivity were compared between the two conditions. RESULTS: Kinematic improvements post-BoNT were identified at the ankle and knee for the entire sample, and for subgroups with apparent equinus and jump gait. Limbs with baseline patterns of dropfoot and to a lesser extent true equinus showed clear improvements only at the ankle. In apparent equinus, jump gait, and dropfoot, spasticity improved post-BoNT, without leading to increased weakness or diminished selectivity. Compared to typical gait, knee and hip motion improved in the crouch gait subgroup post-BoNT. CONCLUSION: This comprehensive analysis highlighted the importance of investigating BoNT effects on gait and clinical impairments according to baseline gait patterns. These findings may help identify good treatment responders.

Addressing limitations of single GON blockade treatment and repetitive intervention with GON block or onabotulinum toxin A in chronic migraine- part 2 of three men in a boat study.

This study investigated the effectiveness of three treatment interventions for managing migraine symptoms over a three-month assessment period: single greater occipital nerve block (GON), repetitive GON block, and single GON block combined with onabotulinium toxin A (BoNT-A) treatment. Significant improvements were observed across all treatment groups in various migraine-related parameters, including medication usage, frequency and severity of attacks, and subjective measures such as Headache Impact Test-6 scores and Pittsburgh Sleep Quality Index scores. Notably, all groups showed reductions in NSAID and triptan usage, total number of attacks with VAS>4, and number of headache days. However, slight differences in the magnitude of improvements were observed between the groups, with GON block combined with BoNT-A treatment demonstrating slightly greater reductions compared to single GON block treatment. Additionally, the integration of BoNT-A therapy alongside GON blockade appeared to confer supplementary benefits in migraine prophylaxis. These findings highlight the importance of implementing comprehensive treatment approaches to address various aspects of migraine management and improve patient outcomes.

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.

The Use of Botulinum Toxin Type A in Medically Refractory Pediatric Patients With Chronic Daily Headaches and Its Impact on the Quality of Life.

Background: Chronic migraine in children has been a challenging condition to treat, prompting the investigation of alternative therapies. This retrospective single-center chart review aimed to evaluate the efficacy and safety of Botox injections for managing chronic migraine in children. Methods: The study included children with chronic daily headaches and chronic migraine who were medically refractory to previous treatments at OSF Healthcare/Illinois Neurological Institute, Peoria, between 2015 and 2021. Botox injections were administered quarterly following a specific protocol. Data were obtained from electronic medical records by manual review. Results: Twenty-four patients met the inclusion criteria (median age 15.4 years, 87% female). Comorbidities included depression (41.6%) and sleep disturbances (33.2%). Prior to Botox treatment, patients had been tried on a median number of 5 (interquartile range [IQR] 4, 7) medications. Botox injections resulted in a significant reduction in headache frequency, with a mean difference (6 months vs pretreatment) in the Headache Impact Test (HIT 3) scores of -19.6 (95% CI -24.8, -14.3), P < .001, and mean difference in the Migraine Disability Assessment (MIDAS) scores of -50.8 (95% CI -62.6, -39.0, P < .001). Subjective improvements included mood enhancement (13/24, 54.2%) and improved concentration (12/24, 50%). Treatment-related side effects were reported by 5/24 (20%) of patients and were mostly mild to moderate. Conclusions: Botox injections offer a promising therapeutic option for managing chronic migraine in children who have not responded to traditional medications. Future controlled trials and long-term follow-up studies are needed to further evaluate Botox treatment's benefits and adverse effects in children with chronic migraine.

Efficacy and safety of botulinum toxin for rosacea with positive impact on quality of life and self-esteem.

BACKGROUND: Rosacea is a prevalent chronic inflammatory skin disease with a multifactorial pathophysiology. It compromises several skin structures, including the proliferation and dilation of dermal blood vessels, primarily in the central areas of the face, accompanied by significant psychosocial impairment, leading to reduced quality of life (QoL) and self-esteem. There are consensus guidelines for its treatment, but few options for the erythema. This study hypothesizes that treating rosacea skin lesions with botulinum toxin (BTX) could improve signs and symptoms, resulting in enhanced QoL and self-esteem. METHODS: This interventional, open, uncontrolled, and prospective study, conducted at a single center, included 33 individuals diagnosed with rosacea, treated with standard therapeutic options according to the rosacea subtype plus superficial injections of BTX, and followed up for 90 days. Botulinum toxin injections were applied on Days 1 and 14. Clinical features and side effects were assessed at each visit; QoL, self-esteem, and medication adherence questionnaires were administered on Days 1 and 90. RESULTS: Treatment with BTX yielded improvement in the clinical signs of rosacea, registered by the investigators, and reported by 94% of the participants. Improved QoL scores (P < 0.05) and a notable increase in self-esteem scores (P < 0.001) were demonstrated. Rare adverse events were observed. CONCLUSIONS: The utilization of BTX superficial injections in patients with rosacea was safe and effective, improving the clinical appearance of the lesions. Despite some limitations, to our knowledge, this is the first study that showed the positive impact of this treatment modality on both QoL and self-esteem.

Trial Design for Mixed Urinary Incontinence: Midurethral Sling Versus Botulinum Toxin A.

IMPORTANCE: Mixed urinary incontinence (MUI) is common and can be challenging to manage. OBJECTIVES: We present the protocol design and rationale of a trial comparing the efficacy of 2 procedures for the treatment of women with MUI refractory to oral treatment. The Midurethral sling versus Botulinum toxin A ( MUSA) trial compares the efficacy of intradetrusor injection of 100 U of onabotulinimtoxinA (an office-based procedure directed at the urgency component) versus midurethral sling (MUS) placement (a surgical procedure directed at the stress component). STUDY DESIGN: The MUSA is a multicenter, randomized trial of women with MUI electing to undergo procedural treatment for MUI at 7 clinical centers in the NICHD Pelvic Floor Disorders Network. Participants are randomized to either onabotulinumtoxinA 100 U or MUS. OnabotulinimtoxinA recipients may receive an additional injection between 3 and 6 months. Participants may receive additional treatment (including crossover to the alternative study intervention) between 6 and 12 months. The primary outcome is change from baseline in Urogenital Distress Inventory (UDI) at 6 months. Secondary outcomes include change in UDI at 3 and 12 months, irritative and stress subscores of the UDI, urinary incontinence episodes, predictors of poor treatment response, quality of life and global impression outcomes, adverse events, use of additional treatments, and cost effectiveness. RESULTS: Recruitment and randomization of 150 participants is complete and participants are currently in the follow-up phase. CONCLUSIONS: This trial will provide information to guide care for women with MUI refractory to oral treatment who seek surgical treatment with either onabotulinumtoxinA or MUS.

Subcutaneous infection caused by Mycobacterium abscessus following botulinum toxin injections: A case report and literature review.

BACKGROUND: The rapid development of cosmetic injections has led to an increased incidence of nontuberculous mycobacterial (NTM) infection. PATIENTS AND METHODS: Here, we presented a case of cutaneous Mycobacterium abscessus infection subsequent to botulinum toxin injection for treating masseter hypertrophy, and reviewed the literature on skin and soft tissue infections caused by NTM after cosmetic injections. RESULTS AND CONCLUSIONS: The patient underwent surgical excision and regular antibiotic therapy and has had nearly 2 months of follow-up without any signs of infection. The diagnosis and treatment of NTM infection have always been challenging, and further research is needed to standardize and guide the treatment.

Advanced Injection of Botulinum Toxin in the Nasal Muscles: A Novel Dynamic Change in Facial Expression.

BACKGROUND: Among the nasal muscles, the levator labii superior alaeque nasi (LLSAN) acts as a transitional muscle that conjugates with other nasal and perinasal muscles. Thus, when treating the nasal region with Botulinum toxin (BTX), it is important to understand local nasal muscular dynamics and how they can influence the muscular dynamics of the entire face. METHODS: This is a retrospective analysis of cases treated by an injection pattern encompassing the face, including nasal muscles. Photographs were taken at rest and during motion (frontal and oblique views), before and after treatment. RESULTS: A total of 227 patients have been treated in the last 18 months with the following results: eyebrow tail lifting, softness of crow's feet, improvement of the drooping of the tip of the nose, and shortening of the lip philtrum when smiling. We present cases illustrating the use of this approach. CONCLUSIONS: Treating the facial muscles globally (including the frontal, corrugators, procerus, orbicularis oculi, platysma, DAO, and nasal muscles) can improve the smile and facial expressions. This is believed to occur because the elevated portion of the upper lip muscle becomes stronger as the nasal part of the LLSAN is paralyzed. LEVEL OF EVIDENCE IV: 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 .