Improved treatments for medication refractory Tourette's Syndrome (TS) are needed to address a subset of severely affected patients. Chronic high frequency deep brain stimulation (DBS) has recently emerged as a possible therapeutic option in refractory cases incapacitated by their tics. Although DBS has been utilized for addressing basal ganglia disorders such as Parkinson disease, essential tremor, and dystonia, these diseases differ fundamentally from TS. The symptoms of TS are characteristically paroxysmal and change their character over time. TS can also include a wide spectrum of behavioral symptoms. One brain area, the centromedian thalamus (CM) has shown the most promise (N> 20) as a therapeutic target for DBS in refractory TS. Nevertheless, there is room for improvement. One drawback of previous studies may be that stimulation was delivered in a """"""""continuous"""""""" mode. We hypothesize that a different stimulation pattern, either """"""""scheduled"""""""" (delivered at specific intervals and for specified amounts of time) or """"""""responsive"""""""" (timed to coincide with occurrence of tics), may produce more optimal results. Potential advantages of scheduled and responsive brain stimulation over continuous DBS include: 1) the ability to address the paroxysmal nature of the symptoms of TS; 2) a strategy that may prevent or limit tolerance; and 3) not negatively impact normal inter-tic functioning. This pilot study will investigate the efficacy and tolerability/safety bilateral """"""""scheduled"""""""" CM stimulation using a novel DBS device, the Responsive NeuroStimulator (RNS), in six adult subjects with severe and intractable TS (specific aim 1). Activation of the device will be at either one or two months (staggered onset) following implantation under randomized double-blind conditions. Outcome will be assessed at six months of chronic stimulation using standardized tic and related functional measures by blinded evaluators. The RNS device is currently under testing for epilepsy and was selected primarily because of its flexibility in delivering different stimulation patterns including the potential for responsive stimulation based on ongoing intracranial recordings. An additional advantage of RNS for the TS patient is that it is self-contained in the skull and brain and the system contains no tunneled neck connector wire and no chest pacemaker device. This feature may help to limit device related fractures due to tics involving the neck region as well as lessen provocation of self-injurious behaviors aimed at the pacemaker site. Using the recording mode of the device, we will study intra-operative and post-operative physiology of tics in specific aim 2. The data gleaned from these studies will be used for an exploratory trial of """"""""responsive"""""""" brain stimulation (specific aim 3) in the same cohort of subjects. This is a pilot study of the benefits and safety of a novel deep brain stimulation (DBS) device in six adult subjects with severe and intractable Tourette Syndrome (TS). Although neurosurgery should be considered a last resort in TS, refinements in DBS as proposed herein may better tailor the stimulation parameters to the symptoms of patients with TS who are otherwise incapacitated or at risk of further injury by their tics. ? ? ?
