Botulinum toxin for the lower urinary tract

Botulinum toxins (BoNTs) are known for their ability to potently and selectively modulate neurotransmission for successful long-term treatment of muscle hypercontractility. Recent studies suggest that BoNT has effects on modulation of sensory processing, inflammation and glandular function. Urologists and urogynaecologists have become interested in the potential application of BoNTs in patients with lower urinary tract symptoms, including detrusor and sphincter overactivity, bladder hypersensitivity, interstitial cystitis/painful bladder symptoms and benign prostatic hyperplasia. We review the biological action of BoNT in bladder and prostate, and present the techniques and results of the clinical studies with BoNT in the lower urinary tract.     

Botulinum toxin A for the management of vulvodynia

Clinically, botulinum toxin A blocks the cholinergic innervation of the target tissue. Recently, it has been proved effective not only at a neuromuscular junction but also within parasympathetic or sympathetic neural synapses. Seven women with pain on genitalia that could not be controlled with conventional pain managements were enrolled in this study. Twenty to 40 U of botulinum toxin A were used in each injection. Injection sites were the vestibule, levator ani muscle or the perineal body. Repeat injections were administered every 2 weeks if the patient's symptoms had not fully subsided. In all patients, pain had disappeared with botulinum toxin A injections. Five patients needed to be injected twice; the other two patients needed only one injection. We did not observe complications related to botulinum toxin A injections, such as pain, hemorrhage, infection, muscle paralysis or other complications. The subjective pain score improved from 8.3 to 1.4, and no one has experienced a recurrence (the follow-up period was four to 24 months, with a mean follow-up of 11.6 months). Botulinum toxin A is effective in blocking nociception. Even though further investigation and well-controlled study will be necessary, we suggest that the botulinum toxin therapy would be useful and safe in managing vulvodynia of muscular or neuroinflammatory origins.     

Botulinum toxin for the treatment of anal fissure

BACKGROUND: The classic treatment for uncomplicated anal fissure is surgical sphincterotomy, i.e. cutting of the internal anal sphincter, thus eliminating spasm of this muscle and breaking the vicious circle of pain, spasm and inflammation. Recently, however, botulinum toxin has become available for the treatment of muscular dystonias, and thus for anal fissure. In the present study, we investigated the effectiveness of treatment with botulinum toxin in 76 patients with uncomplicated anal fissure. MATERIAL AND METHOD: The 76 patients received an injection of 40 U of botulinum toxin on each side of the fissure. Response was monitored 7, 30 and 90 days later. All patients who did not show clear improvement after 30 days received a second dose of 40 U on each side. RESULTS: After 90 days, 51 patients (67%) showed complete recovery, 19 patients (25%) substantial improvement though not complete recovery, and 6 patients (8%) no significant improvement. Transitory gas incontinence was reported by 2 patients (2.6%), and 1 patient presented hemorrhoidal thrombosis. DISCUSSION: Botulinum toxin enables chemical denervation of the internal sphincter, facilitating healing of the anal fissure. Its principal advantages with respect to surgical sphincterotomy are the absence of the general risks of surgery, and reduced incidence of incontinence, which even if it occurs tends to be transitory. The technique does not require hospitalization and is well tolerated. It appears suitable for the initial treatment of uncomplicated anal fissure, reserving surgical treatment for those cases which fail to response adequately.     

Botulinum toxin for the treatment of essential blepharospasm

Twenty-six patients with essential blepharospasm were treated with botulinum toxin by injection. The onset of protractor weakness in all patients ranged from one to five days following treatment. Maximal weakness developed within 12 days. There was a variable and gradual return of protractor strength over eight to 29 weeks in most patients and, with it, a return of spasm. Twenty-five patients received some degree of functional relief following initial injection. In most patients, however, the post-injection result could not be stabilized and repeat injections have been necessary to control recurrent spasms. There was one treatment failure. Three patients treated by injection following previous neurectomy and myectomy appeared to have a reduced requirement for subsequent injections. Complications included transient ptosis in six patients and mild exposure symptoms in four patients. Extraocular muscle paresis did not occur. There were no systemic side effects from the botulinum toxin injections.     

Botulinum toxin treatment for bladder dysfunction

Botulinum toxin A is available under three different protein complexes that are not interchangeable until appropriate comparative studies are undertaken. The best studied for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity and overactive bladder/idiopathic detrusor overactivity is onabotulinum toxin A. This brand is only approved for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity at a dose of 200 U and idiopathic detrusor overactivity at a dose of 100 U. In patients with detrusor overactivity as a result of spinal cord injury or multiple sclerosis, 200 U of onabotulinum toxin A should be injected in 30 different sites above the trigone. It was shown to be highly effective in curing or decreasing urinary symptoms of incontinence, increasing quality of life, increasing bladder capacity and decreasing maximal detrusor pressure. This effect was independent of the concomitant use of oral anticholinergic drugs. Adverse events were mild, mainly urinary tract infections and high postvoid residual requiring clean intermittent catheterization. In patients with overactive bladder/idiopathic detrusor overactivity, 100 U of onabotulinum toxin A should be injected in 20 sites above the trigone. It markedly decreases urinary incontinence and improves quality of life. Frequency and urgency episodes are also decreased. Adverse events are mild, mainly urinary tract infections and urinary retention. The latter occurred in just 5% of the patients. Candidates for onabotulinum toxin A treatment should be warned that the effect of the toxin is transient and that repeated injections will be required to maintain the effect in the long term. There is no evidence that repeated injections will have a decreased efficacy.     

Botulinum toxin injections for paediatric incontinence

PURPOSE OF REVIEW: This review highlights a recent innovation in the medical treatment of children with neurogenic detrusor overactivity. Anticholinergics are usually the main way to treat bladder overactivity. Side effects and lack of efficacy are the two main causes for considering alternative treatment. Up to recently, invasive surgery, mainly bladder augmentation, was the only available treatment for these intractable bladders. Here, we report on botulinum A toxin injection as an alternative to surgery in children with neurogenic detrusor overactivity. RECENT FINDINGS: There are only four published articles on the use of botulinum A toxin in children with neurogenic detrusor overactivity. However, an increasing number of reports indicate clinical benefit and a good safety profile of botulinum A toxin in neurogenic and idiopathic detrusor overactivity. Extrapolation of the data published in adults treated with botulinum A toxin injections and understanding the mechanism of action on the detrusor muscle are worthwhile to encourage paediatric physicians to propose this option to their patients. Furthermore, the literature does not seem to warn against drug resistance or ultrastructural changes of the detrusor after repeated injection. SUMMARY: Botulinum A toxin appears to be a reasonable alternative to surgery in the management of intractable overactive bladder in children. However, studies of the delivery method, site of injection, dose and long-term follow-up are required to confirm the good safety profile/clinical benefit of this new, minimally invasive approach.     

Botulinum toxin and pregnancy

The overall use of botulinum toxin type A in cosmetic procedures continues to rise, and the incidental exposures of pregnant women to the drug can occur. The author describes 2 patients who received botulinum toxin type A injections during pregnancy. The first patient was a 34-year-old woman who received 54 units of botulinum toxin type A to treat periorbital lines (crow's feet) unaware that she was 6 weeks pregnant. She had a healthy term baby delivered by cesarean section; Apgar scores were 9/10. The second patient was a 37-year-old woman who received 65 units of botulinum toxin type A to treat facial dynamic lines (forehead, glabelar, and periorbital), unaware that she was 5 weeks pregnant. She had a healthy term baby delivered by cesarean section; Apgar scores were 9/10. The 2 patients were injected only once in the first trimester. Both cases did not have any complications or detectable adverse effects on the fetuses.     

Botulinum toxin therapy for neurogenic detrusor overactivity

Detrusor injection of botulinum toxin (BTX) has shown great promise in the treatment of neurogenic detrusor overactivity (NDO) refractory to conservative therapy. Despite a paucity of prospective evidence, there exists a growing consensus that BTX injection therapy is a well-tolerated, low-risk therapy. Injections result in substantial subjective improvement in continence and quality of life. Moreover, assessment of urodynamic parameters demonstrates objective changes: (1) an increase in maximum cystometric capacity; (2) when applicable, a reduction in maximal detrusor voiding pressures; and (3) an increase in bladder compliance in cases where baseline bladder compliance measures were abnormal. While BTX bladder injection offers both objective and subjective measures of incontinence control, treatment duration is limited by the gradual reinnervation of injected tissue over an approximately 6- to 9-month interval. However, repeat injection cycles do appear to achieve similar levels of efficacy. The objective of this review is to provide a focused summary of the current body of literature, investigating the safety and efficacy of bladder BTX injection in patients with NDO.     

Botulinum toxin in the management of dystonia

Dystonia is a neurologic disorder that can occur at any age and often results in significant disability. The therapeutic application of botulinum toxin has revolutionized the treatment of this disorder, particularly for the adult-onset focal forms such as cervical dystonia and blepharospasm. The two available commercial preparations, botulinum toxin types A and B, have been shown to be equally efficacious in cervical dystonia and are both reasonable first-line choices for treating other forms of focal dystonia. Preliminary studies have suggested that differences in tolerability and immunogenicity may exist between the two preparations, but this has not been adequately evaluated. Because of high cost, complicated administration, potentially serious side effects, and the risk of developing immunoresistance, this treatment should be administered only by a physician with sufficient background in the diagnosis and treatment of dystonia, to ensure optimal outcomes.     

A型肉毒毒素在新疆维吾尔族女性眼周除皱中的应用

目的 探讨A型肉毒毒素去除维吾尔族女性眼周皱纹个性化治疗方法.方法 用生理盐水将100 U/支A型肉毒毒素稀释至4-5 ml,对维吾尔族女性求美者行定位、定点、定量注射的眼周除皱.在定位注射时,以眉毛、眼睛、眶周骨骼的解剖位置为标示,定出安全区域.在定点时,以肌肉的解剖分布及皱纹收缩时的外彤、长度为参照,较汉族人增加注射点.在定量注射时,较汉族人每点增加1、2 U.每个部化注射2、3次,每次间隔6～8个月.自2003年7月至2008年3月,对178例维吾尔族女性求美者进行治疗,并对其中的60例进行了临床观察.结果 对维吾尔族女性进行了个性化的注射后,7～14 d效果最佳,可维持6～8个月.注射后除出现疼痛、出血、红肿、瘀斑、两侧眉不对称,个别求美者出现了暂时性头痛,但均无须特殊处理,于1～2周自行缓解外,未发现过敏、中毒等全身症状.结论 正确掌握维吾尔族女性眼周软组织的解剖特点及皱纹分型,并进行个件化的注射治疗,是A型肉毒毒素除去维吾尔族女性眼周皱纹的关键.     

Botulinum toxin for treatment of glandular hypersecretory disorders

SUMMARY: The use of botulinum toxin to treat disorders of the salivary glands is increasing in popularity in recent years. Recent reports of the use of botulinum toxin in glandular hypersecretion suggest overall favourable results with minimal side-effects. However, few randomised clinical trials means that data are limited with respect to candidate suitability, treatment dosages, frequency and duration of treatment. We report a selection of such cases from our own department managed with botulinum toxin and review the current data on use of the toxin to treat salivary gland disorders such as Frey's syndrome, excessive salivation (sialorrhoea), focal and general hyperhidrosis, excessive lacrimation and chronic rhinitis.     

Botulinum toxin A for the treatment of lateral periorbital rhytids

The lateral periorbital area represents one of the earliest and most bothersome facial stigmata of aging. Although traditional techniques have had limited success in treating the static cutaneous component to rhytid formation in this region, they have been largely unsuccessful in addressing the dynamic hyperkinetic lines that are created by the activity of the lateral orbicularis oculi muscle. Botox A injection represents a safe and reproducible technique to selectively denervate muscle activity in this troublesome area. This minimally invasive technique has led to significant improvement of periorbital lines, either when used as a single agent or in combination with other methods (Fig. 3). As more experience is gained with this toxin, as well as other Botox serotypes, continued progress is likely to occur in this area, as well as in other facial regions.     

Botulinum toxin: future developments

The proposed mechanisms of action of botulinum neurotoxin-A (BoNT-A) in the bladder provide new insights that might help to understand better the complex machinery of the bladder wall and the importance of the afferent signalling mechanisms. BoNT-A might thus become to be considered a small revolution in the understanding and treatment of bladder overactivity. However, substantially more clinical and basic scientific data are needed before we can truly claim to comprehend how it influences lower urinary tract function, or its role in managing urological problems.     

Botulinum toxin therapy in orthopaedics

Botulinum toxin A plays an important role in the conservative management of problems of the musculoskeletal system. The main indications for its use are disorders of muscle tone and spasticity of various origins, which makes botulinum toxin an important focal treatment in many neurological conditions. Nevertheless, every orthopaedic surgeon who is involved in the conservative management of muscular problems should be familiar with the indications as well as the pharmacology of the substance and its proper injection techniques. By a combination of botulinum toxin injections with a variety of other conservative measures, such as orthotics and plaster cast treatment, its effect can be enhanced and prolonged. Due to the reversibility of its action, exact dose adjustment to the individual is possible.     

Botulinum toxin in urinary incontinence

PURPOSE OF REVIEW: In recent years, botulinum toxin has been investigated for treatment of lower urinary tract dysfunction. This review discusses recently published literature related to the role of botulinum toxin in treating incontinence, including the place for repeated treatment, the differing types of toxin available and the side effects of its use. RECENT FINDINGS: Botulinum toxin is safe and effective in improving both urodynamic and subjective parameters. The A serotype has a longer duration of action than the B serotype and has fewer systemic side effects; hence, it is more likely to gain favour as a suitable treatment, both in patients with neurogenic detrusor overactivity and those with idiopathic detrusor overactivity. It is especially effective in reducing incontinence associated with detrusor overactivity, and repeated treatments appear safe and efficacious. A better understanding of urothelial physiology suggests that botulinum toxin not only has efferent effects but also acts on afferent pathways. The existing data as they stand at present would also suggest it to be safe in patients of all age groups. SUMMARY: Botulinum toxin is awaiting approval for use in lower urinary tract dysfunction. Studies have been carried out in varying populations, but few have used reduction in incontinence episodes as a primary end point. The short-term and long-term efficacy and safety of botulinum toxin as a treatment modality for those with lower urinary tract dysfunction, especially for those with detrusor overactivity refractory to anticholinergics, is, however, evidenced increasingly. Further investigation is needed, specifically large randomized placebo-controlled trials, to determine the ideal conditions for the use of botulinum toxin. Some such trials are underway and we look forward to their findings with interest.     

Botulinum toxin treatment for symptomatic Frey's syndrome.

Gustatory sweating, or Frey's syndrome, usually occurs after surgery or trauma to the parotid gland as a result of inappropriate parasympathetic cholinergic innervation of cutaneous sympathetic receptors. Numerous medical and surgical treatments have been proposed to prevent or treat this condition. The results, overall, have been unsatisfactory. Botulinum toxin is a relatively new treatment modality for Frey's syndrome. We review the literature and present our experience with 7 patients successfully treated with intradermal injections of botulinum toxin (Botox). Our technique and dosing are described. In all treated patients gustatory sweating ceased in the area injected with botulinum toxin. In 6 patients, symptoms reappeared, and additional injections were needed up to 4 times, at 6- to 8-month intervals. All patients now have been free of symptoms for a long period of time (mean 12.1 months). We strongly recommend intradermal injections of botulinum toxin as a safe, efficacious treatment for gustatory sweating.