| Intramuscular injection of Botox type A is largely successful in the treatment of focal dystonias, however, patients who become immunoresistant to Botox A no longer benefit from therapy. For these individuals, the shorter-acting Botox F may provide a reasonable treatment alternative. The present investigation compared the time course and extent of neuromuscular blockade and recovery of Botox A and F.;Thirty-three rats were implanted with a stimulus cuff around the sciatic nerve and recording electrodes in the gastrocnemius muscle and near its origin and insertion, the Achilles tendon and knee. Evoked potentials (EPs) were recorded three times weekly. The gastrocnemius muscle of implanted animals was injected with 0.625, 1.25, 2.5, 5 or 10 units of Botox type A or type F, or a saline placebo. EPs were recorded tri-weekly over 22 weeks time until EMG values recovered maximally and were stable for one month. Gastrocnemius muscles were weighed and evaluated histologically.;Results determined that the degree of neuromuscular blockade significantly differed between A and F, with more complete blockade observed with type A. Regardless of toxin type, doses of 2.5-10 units depressed neurotransmission by 75-97%. The effect of type A lasted three months, while type F animals recovered within 30 days. The extent of final recovery was dependent on both type and dose of Botox. EMG activity fully recovered to baseline in all type F and low-dose type A animals. EPs recorded from animals injected with 2.5 or more units of type A never recovered to preinjection values. Delayed onset of recovery in high-dose type A animals may have allowed time for denervative changes to prevent a full reversal of toxin effect. Histological analysis confirmed atrophy in higher-dose type A muscles. The rapid recovery of type F animals made questionable nerve terminal sprouting as the mechanism by which neurotransmission was restored. Clinical implications and applications of findings are discussed. |
