Haferkamp A, Schurch B, Reitz A, Krengel U, Grosse J, Kramer G, Schumacher S, Bastian P J, Büttner R, Müller S C, Stöhrer M
Department of Urology, University of Bonn, Bonn, Germany.
Eur Urol. 2004 Dec;46(6):784-91. doi: 10.1016/j.eururo.2004.07.011.
Endoscopical injections of Botulinum toxin type A into the detrusor muscle are gaining clinical acceptance in the treatment of neurogenic detrusor overactivity. Structural effects of Botulinum toxin type A are only known from studies on striated muscles, where a widespread nerve sprouting occurs temporarily. The aim of this study was to evaluate the ultrastructural effects of Botulinum toxin type A injections on the human detrusor.
30 detrusor biopsies were obtained from 24 patients with neurogenic detrusor overactivity. Patients were divided into two groups: Group I included 13 biopsies from patients before the first Botulinum toxin type A injection. Group II included 6 biopsies from patients within 3 months after the first injection and 11 biopsies at the time of decreasing efficacy of Botulinum toxin type A. The biopsies were processed by standard procedure for detailed electron microscopic study and evaluated by 2 examiners without prior knowledge of clinical/urodynamic data.
No statistically significant detrusor changes have been found concerning muscle cell fascicle structure (p = 0.445), width of intercellular space (p = 0.482) and number/kind of muscle cell junctions (p = 0.443). A median of 70% of intrinsic axon terminals presented with signs of degeneration in group I, a median of 66% in group II (p = 0.840). Out of 309 evaluated axon terminals in both groups, 1 sprouting axon was found in group I, 3 sprouting axons in group II (p = 0.864). Specimen from group I and group II showed only limited collagen deposits within the detrusor. No changes in the ultrastructure of the detrusor have been observed in those biopsies obtained before and after the Botulinum toxin type A injection of the same patient.
This study verifies our earlier report of severe intrinsic axon degeneration in the detrusor of patients with neurogenic detrusor overactivity. It also shows nearly no structural differences of the detrusor before and after Botulinum toxin type A injections. Contrary to reports of striated muscle, axonal sprouting within the detrusor was very limited after Botulinum toxin type A injections indicating pathophysiologically different reactions to the toxin either between striated muscle and smooth muscle or between different treated diseases.
向逼尿肌内镜注射A型肉毒杆菌毒素在神经源性逼尿肌过度活动的治疗中逐渐获得临床认可。A型肉毒杆菌毒素的结构效应仅在对横纹肌的研究中可知，在横纹肌中会暂时出现广泛的神经发芽。本研究的目的是评估A型肉毒杆菌毒素注射对人逼尿肌的超微结构影响。
从24例神经源性逼尿肌过度活动患者中获取30份逼尿肌活检标本。患者分为两组：第一组包括13份来自首次注射A型肉毒杆菌毒素前患者的活检标本。第二组包括6份来自首次注射后3个月内患者的活检标本和11份在A型肉毒杆菌毒素疗效减退时的活检标本。活检标本按标准程序处理以进行详细的电子显微镜研究，并由2名对临床/尿动力学数据不知情的检查人员进行评估。
在肌肉细胞束结构（p = 0.445）、细胞间隙宽度（p = 0.482）和肌肉细胞连接的数量/种类（p = 0.443）方面，未发现逼尿肌有统计学意义的变化。第一组中，70%的内在轴突终末出现变性迹象，中位数为70%；第二组中，66%的内在轴突终末出现变性迹象，中位数为66%（p = 0.840）。在两组共309个评估的轴突终末中，第一组发现1个发芽轴突，第二组发现3个发芽轴突（p = 0.864）。第一组和第二组的标本在逼尿肌内仅显示有限的胶原沉积。在同一患者注射A型肉毒杆菌毒素前后获取的活检标本中，未观察到逼尿肌超微结构的变化情况。
本研究证实了我们早期关于神经源性逼尿肌过度活动患者逼尿肌中严重内在轴突变性的报告。它还表明在注射A型肉毒杆菌毒素前后逼尿肌几乎没有结构差异。与横纹肌报告相反，注射A型肉毒杆菌毒素后逼尿肌内的轴突发芽非常有限，这表明横纹肌和平滑肌之间或不同治疗疾病之间对该毒素的病理生理反应不同。
