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Dose-dependent, central effects of botulinum neurotoxin type A

A pilot study in the alert behaving cat

From the Laboratorio de Neurociencia, Facultad de Biologia, Universidad de Sevilla, Sevilla, Spain.
Supported by grants PB93-1175 from the Spanish DGICYT and 3,045 from the Junta de Andalucia, Spain.
Received March 5, 1996. Accepted in final form July 5, 1996.
Address correspondence and reprint requests to Prof Delgado-Garcia, MD, Laboratorio de Neurociencia, Facultad de Biologia, Avda. Reina Mercedes, 6, 41012-Sevilla, Spain.

Article abstract-We investigated, in alert behaving cats, the long-term effects of botulinum neurotoxin (BoNT) type A injected into the lateral rectus muscle of the eye. We studied orthodromic field potentials recorded in the injected muscle, eye movements, and the discharge characteristics of the innervating abducens motoneurons. Single BoNT injections at doses from 0.01 to 0.3 ng/kg reduced, or even completely eliminated, eye movements in the abducting direction for up to 2 months without affecting the motoneuron discharge profile that remained related to actual eye movements of the contralateral unparalyzed eye. This result indicates that abducens motoneurons were still under the influence of the ocular motor central control system regardless of their ineffective action on lateral rectus muscle fibers. We also conclude that paralysis per se is not enough to initiate axotomy-like neural responses in ocular motoneurons. The injection of BoNT at a dose of 3 ng/kg produced significant changes in the discharge pattern of abducens motoneurons lasting up to 3 months-the maximum time checked. This finding was probably due to retrograde and, perhaps, transneuronal effects of BoNT when injected in a high dose. The results give some indications of the maximum allowable dose that can be used without the induction of unwanted side effects in the motoneuronal pool innervating the injected muscle.

NEUROLOGY 1997;48: 456-464

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