Double-blind, placebo-controlled, pilot trial of botulinum toxin A in restless legs syndrome.

TLDR: Botulinum toxin has been suggested as a potential therapy for refractory RLS, based on its ability to reduce peripheral and central sensitization to pain and demonstrated symptom improvement, reduced medication use, and a reduction in daytime sleepiness in three patients with RLS.

Abstract: The hallmarks of restless legs syndrome (RLS) are a desire to move the limbs due to sensory discomfort, motor restlessness, and worsening of symptoms during rest or at night.1 Sensory symptoms cause the greatest discomfort,2 and are commonly localized to muscle. Sensory and motor symptoms can be improved with dopaminergic medications, some anticonvulsants, opioids, and to a lesser extent with GABA-active hypnotics. Botulinum toxin has been suggested as a potential therapy for refractory RLS, based on its ability to reduce peripheral and central sensitization to pain.3 In an unblinded observational study by Rotenberg and colleagues, IM injections of 70–320 mouse units (mU) of botulinum toxin type A (BTX-A; Botox, Irvine, CA) were injected into the legs of three patients with RLS and demonstrated symptom improvement, reduced medication use, and a reduction in daytime sleepiness.4 Based on these findings, we conducted a randomized, placebo-controlled, double-blind, crossover study. ### Methods. #### Patients. We enrolled six patients from June to July 2007 who were age 18 or older, had a diagnosis of primary RLS based on International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria,1 had a minimum score of 11 (at least moderate severity) on the IRLSSG rating scale (IRLS),5 and were stable on medications for greater than 6 weeks prior to enrollment. Patients were excluded for an abnormal neurologic examination, abnormal laboratory test results, a dermatologic disorder precluding leg injections, pregnancy/lactation, incapacity for informed consent, taking medications which could interact with BTX-A, …