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A型肉毒杆菌毒素注射用于治疗神经功能正常儿童的外括约肌协同失调。

The use of botulinum toxin A injection for the management of external sphincter dyssynergia in neurologically normal children.

作者信息

Franco Israel, Landau-Dyer Lori, Isom-Batz Ginger, Collett Therese, Reda Edward F

机构信息

Section of Pediatric Urology, New York Medical College, Valhalla, USA.

出版信息

J Urol. 2007 Oct;178(4 Pt 2):1775-9; discussion 1779-80. doi: 10.1016/j.juro.2007.03.185. Epub 2007 Aug 17.

Abstract

PURPOSE

Botulinum toxin A has previously been used for neurogenic and nonneurogenic urgency and urge incontinence. We evaluated the effects of sphincteric botulinum toxin A injection in a series of neurologically normal children with evidence of external sphincter dyssynergia with various voiding problems documented by abnormal voiding electromyography as well as voiding cystourethrography to assess its effectiveness for eliminating post-void residual urine.

MATERIALS AND METHODS

We retrospectively reviewed the charts of 16 dysfunctional voiders who underwent botulinum toxin A injection to the external sphincter between 2002 and 2006, including 1 to 3 injections in 14, 1 and 1, respectively. Of 19 injections 17 were performed with 300 U to the sphincter, while 2 of 19 were done with 200 U. Two patients also received 100 U injected into the detrusor. Mean patient age at surgery was 9.0 years (range 6 to 16). Preoperative clinical data were recorded, including medications, electromyography, uroflowmetry with post-void residual urine, ultrasound and voiding cystourethrography. Before botulinum toxin A injection medical therapies had failed in all patients, including alpha-blockers in 100%, biofeedback in 100%, oxybutynin in 33% and tricyclics in 3 (20%). One patient was on intermittent catheterization. All patients were refractory to bowel regimens and timed voiding. Postoperative parameters consisted of medications, symptoms and post-void residual urine. In the 3 males the resolution of epididymitis symptoms and prevention of recurrence were evidence of success.

RESULTS

Before treatment patients experienced symptoms of urge incontinence (14 of 16), recurrent urinary tract infections (66%), voiding postponement (45%) and epididymitis (3 of 16). All patients had external sphincter dyssynergia, as documented by preoperative electromyography or voiding cystourethrography. Average preoperative post-void residual urine was 107 cc (range 49 to 218). Two patients who underwent preoperative voiding cystourethrography had unilateral grade 1 reflux. Of the 16 children 12 (75%) were dry at the first postoperative visit. The remaining 2 patients had decreased enuresis and 13 of 16 were dry at the second postoperative visit. The last patient became dry after treatment for attention deficit disorder was initiated. Average initial postoperative post-void residual urine volume was 43 cc (range 0 to 141) and the average best postoperative visit post-void residual urine was 8 cc (range 0 to 26). Uroflow data revealed no difference in uroflow before or after injections. Neuropsychiatric problems were present in 9 of the 16 patients, including depression in 4, anxiety in 3 and attention deficit disorder in 2.

CONCLUSIONS

Before our study in the pediatric literature doses between 50 and 100 U were used. We used a significantly higher dose with increased efficacy and no increased morbidity. Endoscopic botulinum toxin A injection of the external sphincter appears to be a safe and efficacious way to treat refractory nonneurogenic voiding dysfunction in children with external sphincter dyssynergia. Long-term followup is necessary and repeat endoscopic injections may be required in select patients.

摘要

目的

肉毒杆菌毒素A此前已用于治疗神经源性和非神经源性急迫性尿失禁及急迫性尿失禁。我们评估了对一系列神经功能正常但存在外括约肌协同失调证据的儿童进行括约肌内注射肉毒杆菌毒素A的效果,这些儿童存在各种排尿问题,通过异常排尿肌电图以及排尿膀胱尿道造影记录,以评估其消除排尿后残余尿的有效性。

材料与方法

我们回顾性分析了2002年至2006年间16例功能失调性排尿患儿的病历,这些患儿接受了外括约肌肉毒杆菌毒素A注射,其中14例注射1至3次,分别为1次和1次。19次注射中,17次向括约肌注射300单位,19次中的2次注射200单位。2例患者还接受了向逼尿肌注射100单位。手术时患者平均年龄为9.0岁(范围6至16岁)。记录术前临床数据,包括用药情况、肌电图、排尿后残余尿的尿流率、超声检查和排尿膀胱尿道造影。在注射肉毒杆菌毒素A之前,所有患者的医学治疗均失败,其中100%使用过α受体阻滞剂,100%接受过生物反馈治疗,33%使用过奥昔布宁,3例(20%)使用过三环类药物。1例患者进行间歇性导尿。所有患者对肠道治疗方案和定时排尿均无效。术后参数包括用药情况、症状和排尿后残余尿。3例男性患者附睾炎症状的缓解及复发的预防证明了治疗的成功。

结果

治疗前,患者出现急迫性尿失禁症状(16例中的14例)、反复尿路感染(66%)、排尿延迟(45%)和附睾炎(16例中的3例)。术前肌电图或排尿膀胱尿道造影记录显示所有患者均存在外括约肌协同失调。术前平均排尿后残余尿为107毫升(范围49至218毫升)。2例术前进行排尿膀胱尿道造影的患者存在单侧1级反流。16例患儿中,12例(75%)在术后首次随访时无尿失禁。其余2例遗尿减少,16例中的13例在术后第二次随访时无尿失禁。最后1例患者在开始治疗注意力缺陷障碍后不再遗尿。术后初始平均排尿后残余尿量为43毫升(范围0至141毫升),术后最佳随访时平均排尿后残余尿为8毫升(范围0至26毫升)。尿流数据显示注射前后尿流无差异。16例患者中有9例存在神经精神问题,包括4例抑郁、3例焦虑和2例注意力缺陷障碍。

结论

在我们的研究之前,儿科文献中使用的剂量为50至100单位。我们使用了显著更高的剂量,疗效提高且发病率未增加。内镜下向外括约肌注射肉毒杆菌毒素A似乎是治疗外括约肌协同失调的儿童难治性非神经源性排尿功能障碍的一种安全有效的方法。需要进行长期随访,部分患者可能需要重复内镜注射。

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