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

Abstract

Immunoresistance (Ab+) to botulinum toxin type A (BTX‐A) has been a serous 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 antibodynegative (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 revertedd 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 Ab+ 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.

Clinical Features of Antibody-Induced Complete Secondary Failure of Botulinum Toxin Therapy

“…Antibody failure often persists for several years [15], thus effectively terminating BT therapy and depriving patients from one of their most promising therapy options. Detection of BT antibodies can either be tried by direct BT antibody tests, such as the mouse protection bioassay [11], the mouse diaphragm bioassay [12], or a radioimmunoprecipitation assay [16], or by indirect tests monitoring the electromyographic activity of a target muscle before and after BT application [17].…”

Toxina botunílica tipo B no manejo de distonia não-responsiva a toxina botunílica tipo A

“…Uma vez alguém tendo se tornado não-respondedor secundário, há muito pouco que se pode fazer no sentido de reverter esta situação. Suspender o tratamento com BTX-A em prazo de 12 meses ou mais pode levar a volta da resposta mas rapidamente e ela costuma ser perdida de novo 7 . Tentativas de interromper a resposta imune anôma-la com medidas como plasmaferese ou imunossupressores também não costumam ser eficientes 8 .…”

“…On 8 sessions of BTX-A injections he received a cumulative dosage of 550U with a mean interval between sessions of 8.8 weeks (range [6][7][8][9][10][11][12]. Decline of response was noticed after the fifth session.…”

The Emerging Role of Botulinum Toxin in the Treatment of Orofacial Disorders: Literature Update

“…The antinociceptive and analgesic properties of BTX-A are also much discussed in the literature and have suggested that the BTX-A can play an independent role in peripheral nociceptors by blocking the release of certain neurotransmitters such as substance P, glutamate, and calcitonin gene-related peptide [14]. Resistance is most likely associated with increased doses and frequency of treatment sessions [15,16]. Repeat doses of 300 U and above have been associated with resistance [17].…”