[Clinical application of botulinum toxin].

The clinical application of botulinum toxin (BoNT) was first proposed by Justinus Kerner in 1822. BoNT was formally accepted as a therapeutic agent in the 1970s, and currently, it is used worldwide for treating diseases as well as for cosmetic conditions. In Japan, Botox® is the only type A formulation that has been officially approved for the treatment of blepharospasm, hemifacial spasm, cervical dystonia, pes equinus of cerebral palsy, adult spasticity of upper and lower limbs, and Botox Vista® is applied for glabellar frown lines. Its effect is symptomatic, but long-lasting remission is noted after treatment in more than 30% of cases with cervical dystonia. Ultrasound guidance is useful and may be even superior to electromyographic monitoring, especially when the obliquus capitis inferior muscle is targeted in rotatocollis, because the vertebral artery or upper cervical nerve root(s) may be injured when the needle penetrates the muscle. BoNT alleviates pain or glandular secretion besides causing a neuromuscular block. After being transported to the axons, BoNT is carried centrally and even to the adjacent neurons via synapses (toxin jump). A direct central action has also been postulated. BoNT is generally safe, but serious adverse reactions may occur very rarely. Individual differences in toxin sensitivity may be considerably greater than assumed, and even the routine clinical dose may be too high in some patients. The future strategy includes clinical application of other types of toxin or chimera toxins, or the use of the toxin as a cargo ("Trojan Horse") carrying some bioactive molecules into the cell. A non-injection procedure for mucosal application or cosmetic use is currently under clinical trials.