Central effects of botulinum toxin type A: Evidence and supposition

No convincing evidence exists that botulinum toxin type A (BT-A) injected intramuscularly at therapeutic doses in humans acts directly on central nervous system (CNS) structures. Nevertheless, several studies, using various approaches, strongly suggest that BT-A affects the functional organization of the CNS indirectly through peripheral mechanisms. By acting at alpha as well as gamma motor endings, BT-A could alter spindle afferent inflow directed to spinal motoneurons or to the various cortical areas, thereby altering spinal as well as cortical mechanisms. Muscle afferent input is tightly coupled to motor cortical output, so that the afferents from a stretched muscle go to cortical areas where they can excite neurons capable of contracting the same muscle. The BT-A–induced reduction in spindle signals could, therefore, alter the balance between afferent input and motor output, thereby changing cortical excitability.