Safety and efficacy of botulinum toxin in primary orthostatic tremor

Primary orthostatic tremor (POT) is a rapid 13-18 Hertz tremor that produces a subjective feeling of unsteadiness when standing, and is absent when seated or supine. It predominantly affects the legs during isometric contraction though a similar tremor can be seen in the arms and jaw. When present in the jaw this rapid tremor has been successfully treated with botulinum toxin. We sought to test whether symptoms of POT improved following injection of abobotulinumtoxinA to muscles in the legs. This randomised, double blind, placebo controlled cross-over design study enrolled eight patients with electrophysiologically confirmed POT. Each patient received injections of either 200 mU abobotulinumtoxinA or 0.9% saline in the tibialis anterior bilaterally, with cross-over after 20 weeks. Electrophysiological and clinical assessments were performed before and 6 weeks after each injection. Seven patients completed the study. No significant differences were seen in the primary outcome measures of time from standing to unsteadiness or symptom diary scores. Electrophysiological characteristics of POT remained remarkably constant throughout the study in all patients with variability of less than 1 Hertz in the frequency recorded. Falls were common, with one patient experiencing a fall with upper limb fracture whilst on the placebo. The frequency of falls correlated with both the severity of the self-rated symptoms and a shorter time to feeling unsteady with eyes closed. In conclusion, treatment with 200 mU of abobotulinumtoxinA in the tibialis anterior does not alter subjective experience of unsteadiness in POT. Postural instability and falls are common.