An Update on the Neurologic Applications of Botulinum Toxins

Abstract

Initially used to treat strabismus in the 1970s, botulinum toxin now has more than a hundred possible medical applications. Its utility in neurologic conditions has largely involved treating movement disorders (particularly dystonia and conditions with muscle hyperactivity), although practically any hyperkinetic movement disorder may be relieved by botulinum toxin, including hemifacial spasm, tremor, tics, myoclonus, and spasticity. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neurotransmitters involved in pain regulation. Thus, their use in neurology has been expanded to include headache and other pain syndromes, as well as hypersecretory disorders. This article highlights some of the common neurologic conditions currently improved by botulinum toxins and reviews the scientific evidence from research studies and clinical experience with these conditions.

Evidence for Anterograde Transport and Transcytosis of Botulinum Neurotoxin A (BoNT/A)

“…In the clinic, the long-lasting effects of BoNT/A at peripheral nerve terminals have been exploited for the treatment of several neuromuscular and autonomic disorders, such as dystonia, spasticity, and hyperhidrosis (Johnson, 1999;Davletov et al, 2005;Montecucco and Molgo, 2005;Naumann et al, 2008;Simpson et al, 2008a,b). BoNT/A has proven very effective in the treatment of these conditions, and the range of possible clinical applications of BoNT/A is continuously increasing (Evidente and Adler, 2010). Of particular interest, the action of BoNT/A on nociceptive neurons has prompted its use in the management of different types of pain (Casale and Tugnoli, 2008;Pavone and Luvisetto, 2010), and this is currently an area of very active investigation.…”

Characterization of Botulinum Neurotoxin A Subtypes 1 Through 5 by Investigation of Activities in Mice, in Neuronal Cell Cultures, and In Vitro

“…Currently, the Food and Drug Administration (FDA) has approved two serotypes, A1 (abo-, ona-, and incobotulinumtoxin A) and B1 (rimaotulinumtoxin B), for treatment of various indications in humans. BoNT/A1 is the predominant serotype of botulinum neurotoxin used for pharmaceutical applications (8,9) and is the best-studied BoNT. Its extraordinary potency (10), its long duration of action, and its localized activity in the inhibition of neuromuscular activity upon intramuscular injection have contributed to the use of BoNT/A as a valuable pharmaceutical for treatment of a variety of clinical as well as aesthetic applications (reviewed in reference 11).…”

Botulinum neurotoxins: new questions arising from structural biology

“…On the basis of sequence differences, 10 different BoNT/A subtypes have been identified [2], some of which differ in their intoxication properties [6,7]. BoNT/A1 is the best-characterized BoNT/A subtype and many of its properties, including its potency and its utility for pharmaceutical applications, have been extensively studied (Box 1) [8,9]. Moreover, BoNT/E and BoNT/F are also produced by some strains of Clostridium butyricum and Clostridium baratii, respectively [4,5].…”

“…BoNTs: clinical and cosmetic applications As a result of their muscle-relaxing properties BoNT/A (including trade names Botox, Dysport and Xeomin) and BoNT/B (marketed as Myobloc in the USA and Neurobloc in Europe) have emerged, despite their toxicity, as effective and powerful reagents for the treatment of a wide and increasing range of medical conditions [8,9]. They include treatment of migraine, ocular motility disorders including strabismus or eyelid twitching, and a variety of movement disorders such as dystonias, tremors, and hemifacial spasms.…”