Differential diagnosis of a failure to respond to an injection of botulinum toxin:
(1) reduced toxin activity in the preparation (inactivation due to conformational change, contamination, etc)
(2) injection of too small a dose
(3) improper injection (leakage of fluid, wrong site injected, etc)
(4) diffusion of toxin into adjacent tissue, reducing dose at the intended site
(5) development of neutralizing antibodies (active immunization, antibody-induced therapy failure or ABTF)
(6) circulating antitoxin antibodies from passive administration
(7) misinterpretation of clinical findings (clinical error in diagnosis of toxin failure)
Development of neutralizing antibodies is the most important reason if future therapy is anticipated.
Factors associated with development of neutralizing antibodies:
(1) total dose of toxin administered at each session (sum of doses at all administration sites)
(2) short interval between repeated injection series
(3) amount of antigenic material in the preparation (sum of active and inactive toxin and toxin protein fragments)
(4) immunocompetence of host
Antibodies to the toxin can be measured. Antibodies from antitoxin administration should be IgG and should be unmeasurable after 3 months.
