The Central Effects of Botulinum Toxin in Dystonia and Spasticity

Abstract

In dystonic and spastic movement disorders, however different in their pathophysiological mechanisms, a similar impairment of sensorimotor control with special emphasis on afferentation is assumed. Peripheral intervention on afferent inputs evokes plastic changes within the central sensorimotor system. Intramuscular application of botulinum toxin type A (BoNT-A) is a standard evidence-based treatment for both conditions. Apart from its peripheral action on muscle spindles, a growing body of evidence suggests that BoNT-A effects could also be mediated by changes at the central level including cerebral cortex. We review recent studies employing electrophysiology and neuroimaging to investigate how intramuscular application of BoNT-A influences cortical reorganization. Based on such data, BoNT-A becomes gradually accepted as a promising tool to correct the maladaptive plastic changes within the sensorimotor cortex. In summary, electrophysiology and especially neuroimaging studies with BoNT-A further our understanding of pathophysiology underlying dystonic and spastic movement disorders and may consequently help develop novel treatment strategies based on neural plasticity.

Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy

“…Overall, the studies briefly summarized here demonstrate a correlation between the peripheral effects, i.e., muscle relaxation after BoNT/A injection, and indirect central effects. Furthermore, what emerges from these and other studies [33,50] is that the central effects induced by the peripheral injection of BoNT/A are not limited to the cortical and subcortical representations of the treated muscles, but they extend beyond the circuits that underlie the control of the affected parts of the body.…”

“…injection of BoNT/A. Due to the vastness of the topic and the large amount of studies in the literature, only a selection of the most significant studies will be briefly summarized in the next paragraphs (for a more detailed review, see Hok et al [33]).…”

Effect of Botulinum Toxin on Non-Motor Symptoms in Cervical Dystonia

“…BoNT-A is known to inhibit acetylcholine release from neuromuscular junctions, resulting in biochemical denervation of the treated muscle [ 26 , 27 ]. In addition to a primary peripheral clinical site of action, evidence also suggests that pharmacological properties of BoNT-A include central effects [ 27 , 28 , 29 ], including the modulation of glutamate, noradrenaline, dopamine, and glycine transmission and changes in the electrophysiologic and morphologic properties of central neurons [ 30 ]. A few studies have investigated the effect of BoNT-A on NMS in CD, though they focused on only one non-motor domain [ 31 , 32 ].…”

Postmarketing safety surveillance data reveals protective effects of botulinum toxin injections against incident anxiety

“…More likely, the peripheral action of BoNT may initiate a chain of neurochemical and neuroplastic changes that may be propagated to remote sites within the CNS 55 . Such neuronal reorganisation has been observed in patients treated for dystonia and spasticity 45 , 56 – 58 . It may also explain anxiolytic effects of BoNT applied at various injection sites in rats or mice 30 – 32 .…”

“…However, the amount of circulating BoNT may be very low, and the anti-anxiety effect shows no dose-dependence across the investigated indications with large vs. small muscles/muscle groups 54 . More likely, the peripheral action of BoNT may initiate a chain of neurochemical and neuroplastic changes that may be propagated to remote sites within the CNS 55 www.nature.com/scientificreports/ has been observed in patients treated for dystonia and spasticity 45,[56][57][58] . It may also explain anxiolytic effects of BoNT applied at various injection sites in rats or mice [30][31][32] .…”