Dressler Dirk, Bigalke Hans
Dept. of Neurology, Rostock University, Gehlsheimer Str. 20, 18147 Rostock, Germany.
J Neurol. 2005 Aug;252(8):904-7. doi: 10.1007/s00415-005-0774-3. Epub 2005 Mar 11.
Botulinum toxin induced therapy failure type B antibody (BT-B, BT-B-AB) has so far only been reported after previous formation of antibodies against botulinum toxin type A (BT-A, BTA- AB). We wanted to explore the risk of BT-B-AB-induced therapy failure in patients who were exposed to botulinum toxin for the first time. For this purpose we followed nine patients with cervical dystonia receiving BT-B (NeuroBloc/Myo- Bloc, Elan Pharmaceuticals) in a dose of 11435 +/- 2977MU during 4.9 +/- 3.0 injection series. All patients showed a satisfactory initial therapeutic response as documented by a Toronto Western Spasmodic Torticollis Rating Scale score reduction from 17.7 +/- 9.4 to 5.3 +/- 4.8 and an overall subjective improvement of 56.1 +/- 28.3%. Seven patients experienced systemic anticholinergic side effects. Five patients had stable therapeutic responses over subsequent injection series. Four patients experienced complete therapy failure with BT-B-AB titres in excess of 10 mU/ml on the mouse diaphragm assay. Doubling the last effective BT-B dose produced neither therapeutic effects nor side effects. Subsequent applications of botulinum toxin type A produced a continued therapeutic response in one patient and complete therapy failure in the other.Despite the small sample size a frequency of 44 % indicates a high risk for BT-B-AB-induced complete therapy failure. The high amount of neurotoxin administered when NeuroBloc/MyoBloc is used might be a contributory factor. Further prospective comparative studies are necessary to monitor the frequency and time course of BT-B-AB formation.
迄今为止,仅在先前形成抗A型肉毒毒素(BT - A,BTA - AB)抗体后才报告了肉毒毒素诱导的B型治疗失败抗体(BT - B,BT - B - AB)。我们想探讨首次接触肉毒毒素的患者中由BT - B - AB诱导治疗失败的风险。为此,我们对9例颈部肌张力障碍患者进行了随访,这些患者接受了剂量为11435±2977MU的BT - B(NeuroBloc/Myo - Bloc,伊兰制药公司),共进行了4.9±3.0次注射。所有患者最初均显示出令人满意的治疗反应,多伦多西部痉挛性斜颈评定量表评分从17.7±9.4降至5.3±4.8,总体主观改善率为56.1±28.3%。7例患者出现全身性抗胆碱能副作用。5例患者在随后的注射系列中治疗反应稳定。4例患者出现完全治疗失败,小鼠膈膜试验中BT - B - AB滴度超过10 mU/ml。将最后一次有效的BT - B剂量加倍既未产生治疗效果也未产生副作用。随后应用A型肉毒毒素,1例患者持续有治疗反应,另1例患者完全治疗失败。尽管样本量小,但44%的频率表明BT - B - AB诱导完全治疗失败的风险很高。使用NeuroBloc/MyoBloc时给予的神经毒素量高可能是一个促成因素。需要进一步的前瞻性比较研究来监测BT - B - AB形成的频率和时间进程。