Development of resistance to botulinum toxin type A in patients with torticollis.

Between 1984 and 1992, 559 patients with torticollis were treated with botulinum toxin type A (btx) injections. Twenty-four of these 559 patients (4.3%) had serological evidence of antibodies to btx by mouse neutralization assay. Some of the 559 patients had only one or two injection series, whereas others were lost to follow-up, so that the actual prevalence of serologically detectable antibodies may be higher than 4%. In addition, some patients who improved after btx injections lost benefit and stopped developing muscle atrophy from adequate doses of btx, without serological evidence of antibodies. To evaluate the risk factors for btx resistance (loss of benefit and muscle atrophy after injections with or without serological evidence of antibodies), we reviewed the records of a cohort of torticollis patients injected over 2-45 months (mean, 23 months) beginning in 1988. Eight of 76 patients (10.5%) developed btx resistance. Compared to nonresistant patients from the same cohort, these eight patients received more frequent injections, had more "booster injections" 2-3 weeks after an initial injection, and received higher doses of btx per treatment. In order to minimize the risk of developing btx resistance, therefore, we recommend that physicians wait as long as possible (at least 1 month) between btx injections, avoid booster injections, and use the smallest possible doses.