Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections

Immunoresistance (Ab+) to botulinum toxin type A (BTX-A) has been a serious concern since the introduction of BTX-A in the treatment of dystonia and other disorders associated with abnormal muscle contractions. We studied seven patients who developed Ab+ and later reverted to antibody-negative (Ab-) status. These seven patients, six women (mean age, 56 years; range, 41-80 years), with an average duration of dystonia for all patients of 197 months (range. 84-360 months), received a total mean cumulative dose of 1659 units (U) (range, 810-1975 U), with an average dose of 207 U per visit. All of these patients became unresponsive to BTX-A treatment and became Ab+ as determined by mouse bioassay. Their response to BTX-A after they reverted to Ab-was analyzed, The average latency between the initial BTX-A treatment and development of Ab+ was 27 months (range, 15-43 months). The average duration between the detection of Abt status and subsequent reversal to Ab-status was 30 months (range, 10-78 months). Six of these Ab-patients were reinjected with BTX-A, and all six benefited from repeat injections comparable with their earlier response. Three patients lost their clinical response to subsequent injections and were found to be again Ab+. Two of the five patients who became immunoresistant to BTX-A. received botulinum toxin type F (BTX-F) injections and one patient received a single session of BTX-B with improvement in their symptoms. In conclusion, this unique group of patients who were Ab+ and became Ab-responded favorably to repeat BTX-A injections, but some lost the benefit with subsequent injections, These observations suggest that the anamnestic immunologic response to BTX-A can wane, but can be reactivated by repeat BTX-A treatments. The presence of antibodies did not interfere with the response to BTX-F or BTX-B injections, thus confirming the antigenic specificity of various BTX serotypes.