BOTULINUM TOXIN PARALYSIS OF THE ORBICULARIS OCULI MUSCLE - TYPES ANDTIME-COURSE OF ALTERATIONS IN MUSCLE STRUCTURE, PHYSIOLOGY AND LID KINEMATICS

In chronically prepared guinea pigs, we investigated the time course o f botulinum toxin A's (Bot A) effect on the blink reflex by monitoring lid movements and EMG activity prior to and after Bot A injection int o the orbicularis oculi muscle (OOemg), or after nerve crush of the zy gomatic nerve. We correlated these alterations with the morphological changes of the orbicularis oculi (lid-closing) muscles of the same ani mals. After Bot A treatment there was a profound reduction of OOemg ac tivity and blink amplitudes as well as a slowing of maximum blink down -phase velocity. Blink up-phases, however, remained unchanged. Gradual recovery of OOemg magnitude and blink amplitude started around day 6; a functioning blink reflex appeared on day 21, and full recovery of b link amplitude occurred by day 42. Crushing the zygomatic branch of th e facial nerve produced similar changes in blink parameters, but recov ery was much more rapid (15 days) than for Bot A-treated guinea pigs. The morphological analysis demonstrated that Bot A produced a denervat ion-like atrophy in the orbicularis oculi. No fiber type-specific alte rations were noted, and all muscle fiber types ultimately recovered, w ith no long-standing consequences of the transient denervation. Our fi ndings support the notion that functional recovery was the result of p reterminal and terminal axonal sprouting that subsequently re-establis hes functional innervation. Moreover, differences between the present findings and those seen after injection of Bot A into the extraocular muscles strongly support the hypothesis that the composition in terms of muscle fiber type and the properties of the motor control system of a given muscle greatly influence both how the particular muscle respo nds to toxin injection, and how effective the toxin is in resolution o f neuromuscular disorders that affect a particular muscle. The present findings were consistent with clinical observations that Bot A produc es only temporary relief in patients with essential blepharospasm. It is likely that the efficacy of Bot A in treatment of blepharospasm cou ld be improved by using agents that suppress terminal sprouting. The c lose correspondence of the changes in blink physiology between human p atients and guinea pigs after Bot A treatment demonstrate that the gui nea pig is an excellent model system for testing strategies to prolong the beneficial effects of Bot A treatment in relieving lid spasms in human subjects.