Botulinum Toxin Treatment in Neurology

Bahman Jabbari, MD

The agent responsible for botulism was discovered and isolated by Belgian bacteriologist Emile Van Ermengem in 1895 from spoiled smoked ham. Justinus Kerner, a German physician, first commented on the therapeutic potentials of botulinum toxin in clinical medicine after studying several outbreaks of botulism in Germany (1917–1922). American investigators Carl Lamanna and Edward Schantz purified, isolated, and produced this toxin in the U.S. Army facility of Fort Detrick, Maryland (1944–1946), a work that was continued by Schantz and Eric Johnson later at the University of Wisconsin. Allan Scott, an ophthalmologist, investigated the clinical application of the toxin with a focus on its potential value for correcting strabismus. His first paper on weakening of the extraocular muscles (in monkeys) was published in 1973, followed by U.S. Food and Drug Administration (FDA) approval to conduct human studies (1979). Ultimately, botulinum toxin-A (BOTOX, Allergan, Inc.) for the treatment of strabismus, blepharospasm, and hemifacial spasm was approved in 1989.

Over the next 26 years, several other indications were approved by the FDA, including cervical dystonia, sialorrhea, hyperhidrosis, cosmetic use (2002), chronic migraine (2010), upper limb spasticity (BOTOX in 2010, Dysport, Galderma Laboratories, L.P., in 2015), and neurogenic bladder (2011). Additional potential applications have been continuously explored; the published, blinded studies show promising results in alleviation of many kinds of pain, such as neuropathic pain, trigeminal neuralgia, posttraumatic neuralgia, and plantar fasciitis to name a few, as well as to relieve symptoms of spasticity associated with stroke, cerebral palsy, multiple sclerosis, and posttraumatic states involving the brain and spinal cord. Few therapeutic agents have been so successful in the treatment of so many diverse symptoms, and thus made such an impact in the lives of a large population of patients.

In this issue of Seminars of Neurology, a group of internationally known experts discuss different indications of botulinum toxin therapy in clinical medicine. Two manuscripts in this issue cover molecular structure, mechanism of action, types of toxins, immunogenesis, and side effects, while nine focus on and discuss multiple clinical indications. Most of the senior authors of the clinical manuscripts are pioneers in this field; their vision and efforts have led to the development of new indications and FDA approvals. I am grateful to them for sharing their knowledge and expertise with us. I am thankful to Professor David Greer, the Editor-in-Chief of Seminars of Neurology, for agreeing to devote this issue of the journal to botulinum toxin and its therapeutic utility, as well as to Ms. Ashley Stahle for helping with the collection and publication of the manuscripts. I am confident that the information presented in this issue will be useful to clinicians and researchers alike, ultimately resulting in enhanced management and better care of our patients.