Intravesical botulinum toxin: Practice patterns from a survey of Canadian urologists

IntroductionThe objectives of this study were to conduct a survey of intravesical botulinum toxin administration practices in Canada, to compare practices based on level of training, and to identify barriers to delivery.MethodsA voluntary online survey was sent to all members of the Canadian Urological Association. Respondents who provide intravesical botulinum toxin were questioned on training, surgical volume, workup, technique, and followup practices. Those with formal training in functional urology were compared to those without. Barriers to treatment delivery were identified.ResultsThe overall response rate was 26% (148/570). Most providers (59%) perform 1–10 treatments/month. Preoperatively, 51% perform cystoscopy and 43% perform urodynamics. A majority (66%) give routine antimicrobial prophylaxis; however, regimen and duration varied. Most (79%) perform some treatments under local anesthetic, and 66% instill lidocaine solution for analgesia. There was a wide variation in technique with regards to the number of injections administered (range <10 to >20), volume administered per injection (range 0.5–2 mL), location of injections (bladder body vs. trigone vs. both), and depth of injection. Postoperative followup ranged from three days to three months. Respondents with fellowship training in functional/reconstructive urology performed more treatments per month and administered fewer injections per treatment. Common barriers to delivery included lack of experience/training among non-providers (45%), lack of resources (34%), and lack of medication funding (32%).ConclusionsDespite intravesical botulinum toxin being a widely accepted treatment, significant variability in practices and several barriers to delivery exist in Canada. Further study is required to optimize treatment access and quality.

KEY MESSAGES

• No formal guidelines exist on intravesical botulinum toxin evaluation, administration, or followup, and as such, there is a wide range of practice patterns among Canadian urologists.
• Further research is required to identify appropriate, evidence-based practices for patients undergoing intravesical botulinum toxin injections.
• Several barriers to administration of intravesical botulinum toxin exist among providers and nonproviders within the Canadian healthcare system.

     

Frey syndrome treatment with botulinum toxin

The goal of this work is to present our results of the intradermic infiltration with botulinum toxin in patients with Frey syndrome. Sixteen hemifaces in 15 patients were studied. Gustatory stimulation was evoked by sucking on a slice of lemon while measurements were done on both hemifaces, with the normal side being used as a control. Skin temperature and color (erythema) were measured with a digital surface thermometer and a skin chromameter, respectively. Sweat quantity and surface were measured by using the previously described blotting paper and iodine-sublimated paper histogram methods, respectively. Testing was repeated 2 weeks after skin infiltration with botulinum toxin (dilution of 50 U/mL). The interinjection distances were 1 cm, and 0.1 mL (5 U) was infiltrated at each injection site. Frey syndrome complaints disappeared in all patients. Small residual amounts of sweat were measurable. The difference in sweat quantity before and after botulinum toxin infiltration was significant in every patient (P < 0.001). Skin temperature and color measurement gave inconclusive results. In conclusion, Frey syndrome treatment with botulinum toxin is an efficient and well-tolerated technique. Further work should address the optimal injection parameters.     

Anatomic considerations for treatment with botulinum toxin

Botulinum toxin A treatment continues to increase in popularity and number. Many more patients are undergoing cosmetic Botox procedures and many, diverse practitioners are providing them. The best results are obtained from a careful history and physical examination of the patient combined with a detailed understanding of facial and neck anatomy. Understanding the dynamic anatomic relationships, such as agonist-antagonist muscles and contraction force vectors, is key to providing the patient with an excellent outcome.     

Vocal fold granuloma: successful treatment with botulinum toxin.

Vocal fold granulomas are benign but frequently recurrent lesions that can cause frustration for both the patient and the treating physician. Etiologic factors include endotracheal intubation, vocal abuse, and gastroesophageal reflux. Conventional treatment for granulomas has included medical, voice, and surgical therapy, none with uniform success. In this study 8 patients with vocal fold granulomas were treated with intralaryngeal injection of botulinum toxin. The resultant temporary paresis of the vocal folds allowed for a window of time during which the vocal process could heal and the granulomas could resolve without being exposed to ongoing intermittent contact and friction with the opposing arytenoid. Although the underlying cause of a granuloma must also be addressed, we have found that botulinum toxin can be a useful adjunct to traditional therapy and can lead to avoidance of repetitive surgical procedures.     

肉毒杆菌素治疗膝骨性关节炎有效性的荟萃分析

[目的]荟萃分析A型肉毒杆菌素治疗膝骨性关节炎(KOA)的有效性和安全性。[方法]检索PubMed、Embase、The Cochrane Library、Web of Science、CBM、万方数据库和CNKI数据库,搜集A型肉毒杆菌素治疗膝骨性关节炎的研究。经由2名评价员独立筛选文献、提取资料并评价偏倚风险后,采用Stata14.0软件进行荟萃分析。[结果]经过初检、筛选和精读全文后共纳入7个RCT,包括535例患者。荟萃分析结果显示:与对照组相比,A型肉毒杆菌素可显著降低KOA 4周WOMAC疼痛评分[WMD=-9.83,95%CI (-11.79,-7.88),P0.001]、4周WOMAC僵硬程度评分[WMD=-5.44,95%CI (-7.10,-3.78),P0.001]、4周WOMAC功能障碍评分[WMD=-4.43,95%CI (-6.00,-2.87),P0.001],8周WOMAC疼痛评分[WMD=-14.29,95%CI (-25.04,-3.54),P=0.009]、8周WOMAC僵硬程度评分[WMD=-5.33,95%CI (-8.54,-2.12),P0.001]和8周WOMAC功能障碍评分[WMD=-7.99,95%CI (-12.71,-3.27),P0.001],差异均有统计学意义。[结论]当前证据表明A型肉毒杆菌素可减轻膝关节疼痛,有效治疗膝骨性关节炎,受纳入研究质量的限制,上述结论尚需更多临床随机对照试验予以验证。     

Clinical results of botulinum toxin type a treatment of migraine headache

Clinical trials, retrospective studies, and case studies indicate that botulinum toxin type A is safe and effective for prophylactic and acute treatment of migraine headache. Further studies are needed to scientifically determine the optimum dosage and administration sites, and which patients are most likely to benefit from this treatment. (Aesthetic Surg J 2002;22:91-93.)     

Botulinum toxin: a new tool in the treatment of focal hyperhidrosis

Focal hyperhidrosis is a quantitative disturbance of sweat function which may involve multiple areas. It is a chronic condition and can cause the patient severe problems in social and professional relationships. Conventional treatments have proved to be marginally effective, impractical and/or with potentially significant side effects. Botulinum toxin type A is capable of blocking the cholinergic transmission to the eccrine glands, thus inhibiting sweat production. A series of 53 patients treated with Botulinum toxin for focal hyperhidrosis of multiple areas is reported. Intradermal injections of 2 mU were performed every 1.5 cm², with an average dose of 40 mU for each axilla, 50–60 mU for each palm and sole. The treatment has proved to be very effective in most cases, with the best results in the axilla. The mean duration of the effect was 6 months. Received: 26 August 1999 / Accepted: 10 January 2000     

Evaluation of botulinum toxin A in treatment of tinnitus

OBJECTIVES: The purpose of this study was to evaluate the potential benefit of botulinum toxin A in treatment of tinnitus with a prospective, double-blinded study design. STUDY DESIGN: Double-blinded, prospective clinical study. METHODS: Thirty patients with tinnitus were randomly placed into 1 of 2 treatment arms. Patients either received botulinum toxin A (20 to 50 units) or saline injection at the first treatment, and the opposite treatment 4 months later. Prospective data including tinnitus matching test, tinnitus handicap inventory (THI), tinnitus rating scale (TRS), and patient questionnaires were obtained over a 4-month period after each injection. RESULTS: Twenty-six patients completed both injections and follow-up and were included in data analysis. After botulinum toxin A, subjective tinnitus changes included 7 patients improved, 3 worsened, and 16 unchanged. Following placebo, 2 patients were improved, 7 worsened, and 17 unchanged. Comparison of the treatment and placebo groups was statistically significant (P < 0.005) when including better, worse, and same effects. A significant decrease in THI scores between pretreatment and 4 month postbotulinum toxin A injection (P = 0.0422) was recorded. None of the other comparisons of pretreatment to 1 month, or pretreatment to 4 months were significantly different. CONCLUSIONS: This small study found improvement in THI scores and patient subjective results after botulinum toxin A injection compared with placebo, suggesting a possible benefit of botulinum toxin A in tinnitus management. Larger studies need to be completed to further evaluate potential benefits of botulinum toxin A in treatment of this difficult problem.     

A型肉毒毒素对兔植皮后皮片收缩相关因素的影响

／目的研究A型肉毒毒素对兔植皮术后皮片收缩的相关因素影响。方法于兔背部沿脊柱两侧对称地制备两排共4个2cm×2cm正方形供皮区,切取全厚皮片,共形成20个创面。每只兔背部随机选取2个创面皮下注射A型肉毒毒素5U,此为A组,共10个创面;其余未注射A型肉毒毒素的创面为B组。术后12d,大体观察切口愈合及植皮成活情况。观察组织的HE染色标本中炎症细胞、成纤维细胞、胶原纤维的变化及免疫组织化学染色标本中α-SMA表达;测量每张图片α-SMA的积分光密度值。结果大体观察A组与B组切口愈合及皮片成活无明显差异。光镜下,观察A组较B组真皮中炎症细胞减少,胶原纤维相对细小、致密度下降,排列较规则,大体走向一致;成纤维细胞数量减少,较分散。A组与B组α-SMA的积分光密度值组间差异具有统计学意义（P=0．003）,A组α-SMA的表达较B组明显减少。结论A型肉毒毒素的注射不影响植皮的正常成活及切口愈合。可通过减少收缩过程中的成纤维细胞的数量、胶原的合成与沉积及炎症细胞的生成,以减少肌成纤维细胞中α-SMA的表达,达到抑制皮片收缩的目的。     

Injectable neuromodulatory agents: botulinum toxin therapy

Botulinum toxin therapy is a diverse treatment option for various dysfunctions of the lower urinary tract. The limited but growing clinical experience reveals that temporary chemodenervation with reduction or loss of neuronal activity at the target organ may be achieved with minimal risk. This highly favorable risk-benefit ratio in urology is derived from the clinical ability to treat an end-organ condition effectively with controllable site-specific delivery (eg, subcutaneous, intramuscular, or instillation) combined with high affinity for toxin uptake by the peripheral cholinergic nerves. Although many questions remain regarding the optimal use of this minimally invasive option for urologic applications, the opportunity for expanding indications will provide urologists with more options for addressing difficult challenges in voiding dysfunction.     

Transcutaneous needle-free injection of botulinum toxin: a novel treatment of childhood constipation and anal fissure

Purpose

Constipation is a common problem in children, and when it becomes chronic fecal impaction, overflow soiling and megarectum may develop. Children with chronic idiopathic constipation (IC) may not respond to conventional treatments of laxatives, enemas, and toilet training. The aims of the study were to evaluate the long-term outcome of transcutaneous needle-free injection of botulinum toxin (TNFBT) into the external anal sphincter (EAS) and to assess the extent of the toxin penetration into the sphincter.

Method

Children were recruited if symptomatic with chronic constipation, soiling, painful defecation, and withholding behavior requiring disimpaction of stool and rectal biopsy under general anesthesia. A total dose of 200 U of botulinum toxin (BT) (Dysport; Ipsen Limited, Slough, United Kingdom) was injected transcutaneously into the EAS at 3 and 9-o'clock positions using J-tip needle-free syringes (National Medical Products Inc, Irvine, Calif). The depth and width of toxin penetration was assessed by endosonography. Outcome was measured by a validated symptom severity (SS) score questionnaire. The total SS score ranged between 0 (best) and 65 (worst). The outcome was compared with 31 children in a comparable historical control group at 3 and 12-month follow-up.

Results

Sixteen children were recruited with median age of 6.11 (range, 3-14.85) years and median duration of symptoms of 3.9 years (1.6-11.5). On endosonography, the median depth and width of BT penetration was 8 (7-10) mm and 8 (6-10) mm, respectively. At 3-month follow-up, the median SS score improved in all children after TNFBT from 32.50 (5-57) to 7.50 (0-26) (Wilcoxon's P < .0001).There were significant improvements in symptoms of constipation, soiling, painful defecation, general health and behavior, and fecal impaction of rectum (P < .05). Anal fissures healed in all 4 children. The SS score in the control group improved from 33 (12-49) to 15 (0-40) (P < .0001). At 12-month follow-up, the improvement of SS score in TNFBT group was significantly more than the control group as follows: 4 (0-25) vs 15 (0-51), respectively (Mann-Whitney U P < .002). Three patients had a second TNFBT injection for relapsed symptoms. There were no complications. The transcutaneous needle-free injection of botulinum toxin eliminates the risk of intravascular injection or needlestick injury. The transcutaneous needle-free injection of botulinum toxin also has other therapeutic applications including an alternative therapy to biofeedback training for dyssynergia of the EAS, treatment of muscle limb spasticity in cerebral palsy, and cosmetic treatment of overactive facial muscles and wrinkles and hyperhydrosis.

Conclusion

Transcutaneous needle-free injection of botulinum toxin into the external anal sphincter is a novel and safe new treatment of chronic idiopathic constipation and anal fissure in children. A second injection may be required in 20% of patients.     

超声引导下肉毒杆菌毒素治疗环咽肌功能障碍的进展

环咽肌功能障碍是环咽肌不能完全松弛而导致以吞咽困难为主要症状的常见疾病。可能病因包括神经肌肉性，医源性，炎症性，肿瘤性和特发性疾病。治疗方法包括环咽肌切开术，食管扩张，注射肉毒杆菌毒素等。随着技术的发展，微创治疗凭借其安全、便捷、微创及美观等优点而逐步取代传统手术治疗，成为环咽肌功能障碍的首选临床治疗方案。其中，超声引导下肉毒杆菌毒素注射治疗作为近年来的热点治疗措施而备受关注，成为临床治疗环咽肌功能障碍的首选。本文就超声引导下肉毒杆菌毒素治疗与其他方法治疗环咽肌功能障碍作一比较。     

Use and mechanism of botulinum toxin in overactive bladder treatment

Overactive bladder is very frequent in central neurogenic patients; it is a major cause of refractory incontinence despite anticholinergic treatment. In non-neurogenic patients it results in very distressing symptoms that associate urgency with or without incontinence and frequency. Botulinum toxin A is a well known agent used previously in the treatment of striated muscle spasmodism, which blocks the release of acetylcholine from nerve endings and neuro-muscular transmission. Its recent use in urology revealed a dramatic improvement in clinical and urodynamic parameters of the overactive bladder, associated with a long lasting effect over 6 to 9 months and an excellent tolerance. In neurogenic patients, the efficacy of botulinum injection was demonstrated over a placebo control group. Toxin was injected at 20 to 30 different sites in the detrusor muscle, with cystoscopy guidance. Recent studies showed a sub-epithelial mechanism of action on neuropeptides, which could explain an inhibitory effect of both efferent and afferent arms of the micturition reflex. Further studies remain necessary regarding the respective doses of Dysport and Botox toxin, selection of patients, combination with anticholinergic treatment, effects of repeated injections.     

Long-term prospective follow-up of botulinum toxin treatment for facial rhytides

Some wrinkles and unsightly facial expressions are due to hyperactivity of the underlying facial musculature. Clostridium botulinum type A exotoxin reversibly paralyzes selected muscles and is a safe, helpful adjunct to many other treatments for facial rejuvenation. Fifty-two patients were treated and all data recorded in a prospective fashion. Only areas requested by the patient were treated. The dosage and dilution given in each area were carefully noted and all patients had pretreatment and posttreatment photographs. The effect of botulinum toxin injections on the horizontal brow rhytides was recorded by measuring the distance from the frontal hairline to the superior edge of the eyebrow in the mid-pupillary line. Patients were followed for one to three years (mean 16.3 months). One patient was not responsive to botulinum toxin in spite of repeated injections. Three further patients required touch-up injections two weeks after the initial treatment due to a weak initial response. Repeat injections were required every three to six months (mean 4.05) to maintain the desired improvement. Asymmetry of the brow was seen in two patients and corrected with further administration of botulinum toxin. Twenty-five patients had their forehead rhytides injected and the appropriate measurements taken. Brow ptosis occurred in 22 of the 25 patients and varied 1–6 mm with a mean value of 2.3 mm. This difference was statistically significant (paired t-test p <0.001). Two patients reported dryness and flakiness of the frontal area after injections. No cases of eyelid ptosis or hypersensitivity were seen. Botulinum toxin injections are safe and all undesired effects are reversible. Great care has to be taken not to aggravate the degree of brow ptosis. Injection of the forehead depressors minimizes the risk of brow ptosis. Careful planning of injection sites and doses avoids a mask-like upper face. The use of botulinum toxin provides a useful adjunct to laser and surgical procedures for facial rejuvenation.     

超声引导下肉毒杆菌毒素治疗环咽肌功能障碍的进展

环咽肌功能障碍是环咽肌不能完全松弛而导致以吞咽困难为主要症状的常见疾病。可能病因包括神经肌肉性,医源性,炎症性,肿瘤性和特发性疾病。治疗方法包括环咽肌切开术,食管扩张,注射肉毒杆菌毒素等。随着技术的发展,微创治疗凭借其安全、便捷、微创及美观等优点而逐步取代传统手术治疗,成为环咽肌功能障碍的首选临床治疗方案。其中,超声引导下肉毒杆菌毒素注射治疗作为近年来的热点治疗措施而备受关注,成为临床治疗环咽肌功能障碍的首选。本文就超声引导下肉毒杆菌毒素治疗与其他方法治疗环咽肌功能障碍作一比较。