Single Injection Of Botulinum Toxin A Research Articles

Botulinum Toxin Injection into the Digastric Muscle: Current Clinical Use and a Report of Five Cases.

The present research aimed to review the clinical applications of botulinum toxin-A (BTX-A) injection into the anterior belly of the digastric muscle (ABDM) and to highlight the potential role of the BTX-A injection into ABDM in preventing postsurgical relapse. Five Class II malocclusion patients who underwent orthognathic surgery received BTX-A injections into both ABDM for the prevention of postoperative relapse. The relapse was evaluated using lateral cephalometric radiographs by comparing the postoperative cephalometric analyses at two different time points, postoperatively at 2 weeks (T1), and long-term, at 9 months after the surgical intervention (T2). The results demonstrated no significant differences between T2 and T1 for the Selle-Nasion-point A (SNA) angle, Selle-Nasion-point B (SNB) angle, point A-Nasion-point B (ANB) angle, mandibular length, and sagittal mandibular position. The patients exhibited stable occlusion without any signs of relapse after the surgery. A single BTX-A injection into the ABDM can effectively prevent postoperative relapse in Class II malocclusion patients, following orthognathic surgery. From a clinical perspective, in case of optimal dosage and procedure, BTX-A injection could be considered as the primary option for the prevention of postsurgical relapse for Class II malocclusion patients.

Long-term efficacy of single botulinum toxin-A injection in a relapsing Piriformis syndrome case

Background Piriformis syndrome (PS) has been considered as a complex diagnosis thus often making its management become complicated. Management of PS ranges from conservative therapies to interventional including injection and surgeries. Among interventional methods, local anesthetic and steroid injections are more commonly practiced. However, due to its negative effect, serial botulinum toxin-A (BTX-A) injections has been proposed as an alternative therapy that can provide relief. Aims To report a long term relief of pain in case of persistent PS with single BTX-A injection.

Botulinum toxin-A injection in esotropic Duane syndrome patients up to 2 years of age

To evaluate the role of botulinum toxin-A (BTX) injection as the primary treatment for patients with esotropic Duane retraction syndrome ≤2 years of age. The medical records of patients with esotropic Duane syndrome who underwent unilateral or bilateral BTX injection to the medial rectus muscle at or before 2 years of age were reviewed retrospectively. The following data were extracted from the record: laterality, age at the time of injection, primary position deviation, duction deficit, anomalous head posture, globe retraction before and after injection, further surgeries, and complications. Success was defined as permanent resolution of esotropia and head turn in primary position at final follow-up. A total of 15 patients (14 unilateral, 1 bilateral) were included. Before BTX injection the mean primary esotropia at near with full cycloplegic refraction was 29.3Δ ± 14.4Δ; the mean head turn, 23° ± 11°. Mean duration of follow-up was 37±29months (range, 7-96months). Orthotropia and resolution of head turn was achieved in 7 patients (46.7%). In subgroup analysis, success rate gradually decreased from 100% in patients ≤7months of age to 33.3% in patients 8-12months of age, and 20% in patients >12months of age. Seven patients (46.7%) required surgery (medial rectus recession and/or superior rectus transposition) because of residual head turn and esodeviation following BTX. In this patient cohort, orthotropia in primary position and correction of head turn were achieved with a single BTX injection in about half of the patients ≤2 years of age and all patients ≤7months of age. BTX injection early in infancy can obviate the need for surgery in esotropic Duane syndrome.

PND84 - PATIENT AND CAREGIVER BURDEN OF BOTULINUM TOXIN A INJECTIONS

Botulinum toxin A (BoNT-A) treatment for patients with spasticity requires regular intramuscular injections. We assessed patient- and caregiver-reported burden of injections and perceived benefits of a reduction in injection frequency. Online cross-sectional survey conducted via Carenity platforms. Only patients with spasticity and receiving BoNT-A injections from France, Germany, Italy, Spain, UK and US, as well as their caregivers were invited to complete the questionnaire. 427 patients and 188 caregivers were included (mean age 42 and 39 years respectively, ∼ 50% female). The most common etiologies of spasticity were multiple sclerosis (42%), followed by stroke (20%). On a 0 to 10 scale (0 = not a problem and 10 = very problematic), patients reported cost, availability of timely appointments, and frequency of injections (mean: 5.9-6.3/10) as most problematic, while caregivers reported cost, logistics and availability of timely appointments (mean: 5.6-6.2 /10). The financial burdens reported by both patients and caregivers included transportation, parking, treatments, consultations, and time off work. The mean costs associated with a single BoNT-A injection was 255 (95% CI: 227-284) EUR for patients and 128 (95%CI: 102-155) EUR for caregivers. Overall, 78% of patients and 84% of caregivers who were working had to take time off to receive BoNT- A injections, on average 6.7 (95%CI: 5.8-7.6) and 7.7 (95%CI: 6.4-8.9) days off per year, respectively. Most participants reported they would experience multiple benefits if injections were less frequent. Overall, 92% of patients and 98% of caregivers anticipated less frequent injections to have a positive quality of life impact. Patients with spasticity and their caregivers experience burdens related to BoNT-A treatment that include direct and indirect costs, an impact on quality of life, as well as logistical constraints. Therefore, the frequency of BoNT-A injections can be an important consideration for the treatment of spasticity.

Role of Botulinum Toxin in Post-Stroke Spasticity Related Shoulder Pain

Shoulder pain is a very common complication after stroke, with a reported prevalence varying from 23% to 64%. There are very few treatment options that have been shown to be more effective than placebo for relief of poststroke shoulder pain. One of the factors most frequently associated with shoulder pain is spasticity, especially when the muscles are stretched. Botulinum toxin A (BT-A) is one of the treatments available for the treatment of focal spasticity and its effectiveness in reducing upper limb spasticity in stroke is well documented. In this review, patients with shoulder pain and spasticity after hemiplegia, a single injection of BT-A was associated with a statistically significantly greater reduction in shoulder pain on a numerical rating scale (NRS) from 6/10 at initial assessment; to 1/10 two months post injection. Nine patients (56%) were pain free at 5 and 9 months postinjection. Median Modified Ashworth Scale (MAS) scores for shoulder spasticity in the affected upper limb improved from 3 at the initial assessment to 2, two months post injection and remained as 1+, five and nine months post injection. There was also a significant improvement in median passive shoulder abduction range of motion on the affected upper limb from 80 degrees at the initial assessment to 95 degrees, two months post injection and further improvement to 110 degrees in 9 patients, 5 months post injection. BT-A seems to be effective in managing post- stroke shoulder pain secondary to spasticity.

The Evaluation of the Clinical Effects of Botulinum Toxin on Nocturnal Bruxism.

Objectives Nocturnal bruxism can be managed by botulinum toxin (Botox®) in patients who have not responded to conservative treatment. The aim of this study was to evaluate the efficacy of botulinum toxin A (BTXA) in the treatment of nocturnal bruxism. Material and Methods The retrospective study comprised 25 female patients, aged 23–55 years (mean 35.84 ± 8.41 years). All patients received a single injection of BTXA in the right and left masseters. Evaluation was made by Visual Analogue Scale (VAS) values, complaint duration, onset of effect, and duration of effectiveness. Results BTXA produced significant improvements in pain scores. Only 2 adverse events (8%) were recorded. Conclusion BTX-A is effective in the treatment of nocturnal bruxism.

Analgesic Effect of Botulinum Toxin A in Myofascial Pain Syndrome Patients Previously Treated with Local Infiltration of Anesthetic and Steroids

ABSTRACTThe purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P <.0001. As regards the side effects, 19 (23.2%) patients reported transient soreness at the injection site for 2 to 3 days with BoNTA. The MPS patients previously treated with a local infiltration of anesthetic and steroids who then received a single injection of BoNTA experienced significantly reduced pain for a relatively long time.

Effect of detrusor botulinum toxin a injection on urothelial dysfunction in patients with chronic spinal cord injury: a clinical and immunohistochemistry study before and after treatment.

The objective of this study is to investigate the changes of urothelial junction proteins, apoptosis and suburothelial inflammation after detrusor injection of botulinum toxin A (BoNT-A) in patients with spinal cord injury (SCI) and neurogenic detrusor overactivity (NDO). A total of 26 patients with chronic suprasacral SCI and NDO were enroled. The urothelium was assessed by cystoscopic biopsy at baseline, 3 and 6 months after a single treatment of 300 U BoNT-A into the detrusor. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1) and tryptase for mast cell activity were performed. Urothelial apoptosis was also evaluated. The differences in urothelial dysfunction were compared between baseline and 3 and 6 months after treatment. Bladder biopsies from patients undergoing anti-incontinence surgery served as controls. A single 300-U BoNT-A injection into the detrusor significantly decreased detrusor pressure and increased bladder compliance at 3 and 6 months after treatment. Significantly lower E-cadherin and ZO-1 expressions and increased mast cell and apoptotic cell counts were noted in SCI bladders compared with controls (all P<0.001). Significantly greater distributions of E-cadherin (P<0.001) and ZO-1 (P=0.05) expressions were noted 3 months after BoNT-A injection. However, these changes had declined by 6 months after treatment. Activated mast cells and urothelial apoptosis showed no significant differences between baseline and 3 or 6 months. Urothelial dysfunction and adhesive and junction protein concentrations in SCI patients' bladders recovered after BoNT-A treatment. However, this effect decreased with time. Thus, neurogenic inflammation after SCI was not adequately improved after a single BoNT-A injection.

Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.

Literature provides reports only of a limited follow-up single injection of botulinum toxin-A (BoNT-A) in patients with sialorrhea. The aim of our study is to evaluate the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for severe sialorrhea secondary to neurological dysphagia. We enrolled 38 severe adult sialorrhea patients referred consecutively to the neurology unit and performed bilateral parotid and submandibular gland BoNT-A injections under ultrasound guidance. The outcomes of the study were reduction of sialorrhea, duration of therapeutic effect, and subjective patient- and caregiver-reported satisfaction. A total of 113 BoNT-A administrations were given during the study period with a mean duration of follow-up of 20.2±4.4months. We observed a significant decrease from baseline in mean number of daily aspirations and a significant improvement in patient- and caregiver-reported outcomes following ultrasound-guided BoNT-A injections (p<0.001 vs baseline for all comparisons) and the mean duration of the efficacy was 5.6±1months. No major treatment-related adverse events occurred and a low incidence of minor adverse events was reported. This study confirms the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for sialorrhea, regardless of the causative neurological disorder. These results should encourage the use of BoNT-A in the treatment of severe sialorrhea and highlight the role of ultrasound guidance to obtain optimal results in terms of safety and reproducible outcomes.

Botulinum toxin treatment for oropharyngeal dysphagia in patients with stroke

In a previous pilot study, we demonstrated that a single injection of botulinum toxin A (BTX-A) in the cricopharyngeus muscle is effective in patients with neurologic dysphagia with upper esophageal sphincter (UES) opening dysfunction and presence of some pharyngeal contraction (>25mmHg). The aim of this study was to confirm the long-lasting efficacy of this procedure after stroke. We prospectively studied 23 patients with stroke for at least 6months before administration of a BTX-A injection. Baseline diagnosis of UES opening dysfunction and presence of some pharyngeal contraction were assessed by videofluoroscopy (VFS) and esophageal manometry (EM). Clinical and VFS follow-up was made at 3weeks and 3, 6, and 12months postinjection. Eighteen patients (78%) were fed by gastrostomy tube prior to treatment. Videofluoroscopy showed UES relaxation impairment, residue in pyriform sinuses, and aspiration in all cases. After BTX-A, the number of patients with aspiration and pharyngeal residue decreased to 52% and 70%, respectively (p<0.05 for both); residue was severe in only 4%. Esophageal manometry showed a mean pharyngeal amplitude 66.8mmHg (range: 25-120mmHg). We observed a significant improvement in feeding mode during follow-up: after 3months, 70% of patients were eating exclusively by mouth. Lower residual pressure and minor pharyngeal delay time at baseline were all predictive factors for treatment effectiveness. A single injection of BTX-A is efficacious for a period of at least 12months in improving oropharyngeal dysphagia in stroke patients with UES opening dysfunction and some pharyngeal contraction (>25mmHg).

Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A single set of botulinum toxin A (BoNT-A) injections relieves clinical symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks long-term effect. An inadequate anti-inflammatory effect is likely to cause treatment failure. The study shows that chronic inflammation and apoptotic signalling molecules are significantly reduced after repeated intravesical BoNT-A injection in patients with IC/BPS. It also shows that repeated BoNT-A injections are necessary to achieve greater success in the treatment of IC/BPS. To investigate the mechanisms of action of botulinum toxin A (BoNT-A) treatment on interstitial cystitis/bladder pain syndrome (IC/BPS). A total of 23 women with IC/BPS who received single intravesical BoNT-A injection were studied. Among them, 11 received three repeated injections every 6 months to improve their symptoms. Bladder biopsy was obtained before each BoNT-A injection and the clinical symptoms and urodynamic variables were recorded. Immunohistochemical (IHC) staining for TUNEL and mast cell activity, and western blotting analysis of tryptase, cytokines, Bax and phospho-p38 (p-p38) were carried out. We compared the clinical results and IHC data among baseline, single or repeated BoNT-A treatments. Single BoNT-A injection improved clinical symptoms, pain score and daytime urinary frequency. Mast cell activity and apoptotic cell count did not decrease significantly, while Bax and p-p38, but not tryptase, decreased significantly after a single BoNT-A injection. The 11 patients who received three repeated BoNT-A injections had significantly lower pain scores than the remaining patients (mean [SD]: 5.80 [2.27] vs. 3.03 [2.30], P = 0), glomerulation degree (mean [SD]: 1.80 [1.06] vs. 1.20 [1.06], P = 0.026) and global response scores (mean [SD]: 0.30 [0.92] vs. 1.20 [1.06], P = 0) after treatment. Tryptase, Bax, p-p38 and apoptotic cell counts all decreased significantly. 25-kD synaptosomal-associated protein also decreased after BoNT-A treatments, which confirmed the therapeutic effect of repeated BoNT-A injections. Chronic inflammation and apoptotic signalling molecules were significantly reduced after repeated BoNT-A injections in patients with IC/BPS. The IHC improvement was associated with clinical symptom improvement. Repeated BoNT-A injections are necessary to achieve a greater success rate in the treatment of IC/BPS.

113 DECREASE OF UROTHELIAL CELL APOPTOSIS SIGNAL MOLECULES IS ASSOCIATED WITH IMPROVEMENT OF CLINICAL SYMPTOMS AFTER SINGLE INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR PATIENTS WITH INTERSTITIAL CYSTITIS

INTRODUCTION AND OBJECTIVES: Interstitial cystitis/painful bladder syndrome (IC/PBS) is considered to result from long-standing inflammation of bladder. Currently, no one treatment provides longterm efficacy. Intravesical botulinum toxin A (BoNT-A) injection seems to have promising therapeutic effect on IC/PBS. Several studies indicated that p38 MAPK activation is implicated in inflammation, fibrosis and mediating apoptosis in different cell types in various species. We have found that apoptosis of urothelial cells in IC/PBS could be due to up-regulation of inflammatory signals, including p38 MAPK and TNF . This study aimed to investigate whether the changes of bladder inflammation and apoptotic signal transduction could be modulated by intravesical BoNT-A injection in IC/PBS. METHODS: Twenty three patients with IC/PBS were enrolled. All patients received intravesical 100U BoNT-A injection. The bladder specimens were obtained at baseline and 6 months after the first injection. The double stain, protein array analysis and western blotting were performed to analyze the alterations of tryptase (mast cell activity), Bax, and phospho-p38 . The intensities of proteins in the arrays and Western blots were quantified using Image J processing. Inflammatory molecule treated urothelial cells were analyzed by TUNEL staining and western blotting for level of molecules involved in apoptosis. RESULTS: Clinical results after BoNT-A injection revealed improvement of visual analog score, O’Leary-Sant symptom score, and global response assessment but not glomerulation and maximal bladder capacity in overall patients (Table). Phospho-p38 and TUNEL double staining indicated that inflammatory and apoptotic events were co-existed in IC/PBS bladders. Analysis of the western blot results revealed significant decrease of phospho-p38 and Bax expression after the first time BoNT-A injection. However, the change of tryptase did not reach statistical significance. CONCLUSIONS: Single BoNT-A injection provides clinical improvement and reduce apoptotic signal protein production but mast cell activity did not significantly reduce, suggesting repeat BoNT-A injection is necessary to achieve long-term effect. Table. The changes of clinical measures and western blot measures parameters Baseline 6 months after BoNT-A P values VAS 5.30 2.46 3.78 2.61 0.048

Long-term follow-up after botulinum toxin A (BTX-A) injection into the detrusor for treatment of neurogenic detrusor hyperactivity in children

PurposeTo prove the long-term efficacy of BTX-A injection in the management of children with neurogenic detrusor hyperactivity.Materials and methods28 out of 145 children with neurogenic bladder (15 male and 13 female, mean age 10.7 years) who were treated between 2002 and 2010 and became non-responders to conservative treatment were included into the retrospective study.We injected 10-12 U/kg of BTX-A (Botox®) into the detrusor at 20-30 sites, sparing the trigone. The mean follow-up was 48 months (range 6-84 months).ResultsGroup 1. 14 patients had a single injection of BTX-A. Five of them were successful.Mean bladder reflex volume increased (from 62.9 to 117.5 ml), maximum detrusor pressure decreased (from 59 to 37.5 cm H2O), detrusor compliance increased (from 4.8 to 9.5 ml/cm H2O), and leak-point-pressure decreased (from 46.5 to 24.2 cm H2O). Four patients did not respond and were treated by ileocystoplasty. Another five were lost to follow-up. Group 2. 14 patients had repeated (mean 2.5) injections of BTX-A with a mean interval of 13.7 months. In thirteen patients, urodynamic parameters of the first and last injection were similar to those obtained in Group 1, showing a good response. One patient received an ileocystoplasty.ConclusionBTX-A is a safe alternative in the treatment of detrusor hyperactivity in children with myelomeningocele (MMC). The efficacy lasted a mean of 12 months and urodynamic response was unchanged even after several injections. In our series, 21.7% of children with severe low-compliance bladders were non-responders.

The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

The Use of Botulinum Type A Toxin in the Treatment of Idiopathic Clubfoot: 5-year Follow-up

Continued monitoring and reporting of outcomes in clubfoot patients are important for providing an indicator of functional outcomes and surveillance and treatment for problems or recurrences. The purpose of this study is to report the 5-year outcomes of the updated cohort of 44 patients with 65 idiopathic clubfeet treated with manipulation, casting, and Botulinum toxin A (BTX-A). As part of the original study, the patients underwent the corrective treatment phase of manipulation and casting followed with BTX-A injection and then the maintenance phase of bracing. The patients were seen at regular intervals and a detailed clinical history was maintained for each patient including ankle range of motion, recurrences, and interventions for recurrences. Mean values for range of motion at the 5-year visit were 22.3 and 17.1 degrees for dorsiflexion with the knee in flexion and extension, respectively. Overall, 48% (31 of 65 clubfeet) successfully responded to a single BTX-A injection and experienced no recurrence over the follow-up period. At least 1 repeat BTX-A injection was required in 34 clubfeet, for an overall recurrence rate of 52%. Surgery was required in 10 clubfeet, and the overall surgical rate was 15.4%. Idiopathic clubfeet treated with BTX-A continued to show good outcomes at 2 to 5-year follow-up. The experience with this cohort provides support for the effectiveness of BTX-A in the initial correction and continued management of idiopathic clubfoot. Levels III to IV. This is a prospective, nonexperimental clinical study investigating efficacy of an innovative treatment.