Neurophysiological effects of botulinum toxin type a

Abstract

Botulinum toxin type A (BoNT-A) acts peripherally by inhibiting acetylcholine release from the presynaptic neuromuscular terminals, thus weakening muscle contraction, and its clinical benefit depends primarily on the toxin's peripheral action. In addition to acting directly at the neuromuscular junction, the toxin alters sensory inputs to the central nervous system, thus indirectly inducing secondary central changes. Some of the long-term clinical benefits of BoNT-A treatment may also reflect plastic changes in motor output after the reorganization of synaptic density.

Long-Distance Retrograde Effects of Botulinum Neurotoxin A

“…These central effects of BoNT/A have been usually ascribed to (1) plastic rearrangements subsequent to denervation or (2) alterations in sensory input (Priori et al, 1995;Giladi, 1997;Abbruzzese and Berardelli, 2006). The data presented in our study indicate that they may be consequences of a direct central action of BoNT/A.…”

“…Several papers have described changes at the level of the CNS in man and animals treated intramuscularly with BoNT/A (Garner et al, 1993;Giladi, 1997;Moreno-Lopez et al, 1997a,b;Kanovsky et al, 1998;Wohlfarth et al, 2001;Abbruzzese and Berardelli, 2006;Kim et al, 2006). For example, delivery of BoNT/A into the lateral rectus muscle of cats dramatically reduces the firing rates of abducens motoneurons projecting to the injected muscle (Moreno-Lopez et al, 1997a,b).…”

Endoscopic Ultrasound-Guided Gastric Botulinum Toxin Injections in Obese Subjects: A Pilot Study

“…We noted that gradual body weight loss continued throughout the 16 week study period, and satiation was increased at 16 weeks compared to baseline. This apparently continued efficacy of antral muscularis BTA is beyond the presumed duration of action of BTA in skeletal muscle [28,29], although similar prolonged responses to BTA have been reported in the treatment of achalasia. The mechanism underlying these continued benefits at 16 weeks is unclear; they may be because of a biological effect of BTA on gastrointestinal smooth muscle that is prolonged relative to its effects on skeletal muscle, inflammation (e.g., myenteric ganglionitis) induced by BTA injection, a behavioral benefit of BTA injection persisting after the pharmacological action has resolved, or a placebo effect.…”

Absorption and Transport of Botulinum Neurotoxins

“…Moreover, although BoNT remains relatively localized at the site of injection by binding to the local nerve endings, side effects of BoNT therapy have been observed due to toxin diffusion [26]. Most often, the undesired effects are related to local toxin diffusion to the adjacent muscles, but in rare cases, adverse effects occur in distant muscles or result in central effects or generalized intoxication [1,63,66,67,87,146,185]. Systemic spreading and autonomic side effects, including mouth dryness, blurred vision, swallowing difficulties and constipation, are more often observed with BoNT/B than BoNT/A [44].…”