In the area of dystonia treatment, we continue to provide botulinum toxin injections to our patients while training physicians to perform these injections. We have conducted a therapeutic trial of transcranial direct current stimulation (tDCS) of the brain in patients with focal hand dystonia, but this was not effective. For patients with blepharospasm, we have been evaluating the efficacy of various types of non-invasive brain stimulation. Low frequency repetitive TMS, theta burst stimulation and tDCS have been compared. We are also conducting a therapeutic trial in blepharospasm of a cream that has an action similar to botulinum toxin. Past studies from our group have shown that certain rehabilitation techniques, such as motor training and sensory training can be therapeutic. We are trying to develop other methods of rehabilitation that might be more efficacious. We are trying to develop non-invasive brain stimulation methods for improvement in Parkinson disease (PD). A past study showed that this could be done with 25 Hz repetitive transcranial magnetic stimulation (rTMS). We have now completed addtional trials of tDCS, intermittent theta burst stimulation (iTBS), and rTMS at 50 Hz. In other studies, we are evaluating a new device to see if it can provide objective evidence of motor deterioration in early PD. New treatments are needed for essential tremor. One promising agent is 1-octanol which we continue to develop. We have characterized this drugs pharmacokinetics and compared the efficacy of different formulations in a dose escalation and cross-over study in patients with ET. In addition to characterizing the pharmacokinetics of 1-octanol, we have tested its efficacy in a double-blind placebo-controlled trial in patients with essential tremor. We are currently conducting trials with 1-octanoic acid, a metabolite of 1-octanol. Other similar agents might also be examined in the future.

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