Botulinum toxin A: new hope for RLS?

279 D r. Justinus Kerner first studied the effects of botulinum toxin during the Napoleonic Wars when increased deaths attributed to food poisoning were observed in individuals consuming blood sausages. 1 Its first therapeutic use was as a treatment for strabis-mus and blepharospasm, which was explored in the 1960s and approved by the Food and Drug Administration (FDA) in 1989. Since then, botulinum toxin type A (BTX-A) has been tested in a wide array of potential applications. The FDA approved the use of BTX-A for the treatment of cervical dystonia in 2000 and for the cosmetic improvement of facial wrinkles in 2002. The new study by Joshua Rotenberg and colleagues explores the use of BTX-A in the treatment of persistent restless legs syndrome (RLS). This case series describes 3 adult RLS patients whose symptoms are refractory to conventional treatment or who refused oral medication. The investigators found that the 3 patients given intramuscular injections of BTX-A had symptom relief, less daytime sleepiness by the Epworth Sleepiness Scale (ESS), and/or reduced their medication use. Any new therapy or an existing medication used for a new indication (i.e., off-label use of an FDA-approved medication) should always warrant the exploration of several key questions: Is it safe? Coté et al reviewed the adverse events regarding BTX-A reported to the FDA between 1989 and 2003. 1 The majority of these longitudinal data was related to therapeutic use, with a 33-fold higher proportion of serious adverse events for therapeutic use observed compared with cosmetic use. 1,2 This is not too surprising because patients given BTX-A for therapeutic reasons tend to receive higher doses of BTX-A and are generally less healthy. Of the 406 adverse event reports related to therapeutic use, 217 met the FDA's definition of serious and included a wide spectrum of events, including 28 deaths and 17 seizures. 1 However, of the 28 patients who died, 26 had underlying systemic diseases with elevated risk of mortality, and 15 out of the 17 patients with seizures had either a history of seizures or a preexisting condition that may have elevated their risk for seizures. The majority of the remaining serious adverse events corresponded to potential risks described in the FDA-approved labeling (e.g., dysphagia, muscle weakness). Is it effective? This study represents the first report of BTX-A in the management of RLS, so it would be a large leap to infer effectiveness of BTX-A in …