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Do the unintended actions of botulinum toxin at distant sites have clinical implications?

From the Department of Neurological Sciences and A. Fiorini Hospital (A.C.), Terracina, LT, Sapienza, University of Rome, Polo Pontino; and Department of Neurological Sciences and INM Neuromed IRCCS (A.B.), Pozzilli, IS, Sapienza, University of Rome, Italy.

Address correspondence and reprint requests to Prof. Alfredo Berardelli, Department of Neurological Sciences, Sapienza University of Rome, Viale dell’Università 30, 00185 Rome, Italy alfredo.berardelli{at}uniroma1.it

Over the past 2 decades, botulinum toxin (BT) has enjoyed phenomenal success as a safe and effective therapeutic tool for neurologic and non-neurologic conditions. Even though recent evidence-based conclusions are limited by the availability of data, clinicians’ practice confidently recommends BT for many clinical conditions. Besides being effective, BT injected locally has also been considered safe, because no evidence showed that the toxin acts also at distant sites. Recent findings from basic scientific research now challenge this conviction and raise concern that the toxin may have a less localized function than previously thought. Studies in rodents show that the toxin is retrogradely transported and even transcytosed to second-order neurons in the CNS. We therefore need to reappraise whether BT injected into muscles, glands, or cutis might induce previously unconsidered central actions, and whether these actions might have clinical implications. In eliciting clinical benefits, BT’s peripheral and central action probably summate. Whether BT acts centrally mainly through retrograde transport, transcytosis, or both remains unclear. Whatever the mechanism, the lack of deleterious central effects implies that while research into action mechanisms continues, physicians can safely use BT for therapy.

Abbreviations: BT = botulinum toxin.

Disclosure: The authors report no disclosures.

Received October 1, 2008. Accepted in final form December 30, 2008.