Abstracts

Rationale: A novel approach for implanting investigational responsive neurostimulation (RNS)therapy electrodes is presented for potentially interfacing with epileptic circuits that extend beyond the electrode's generated electric field. Juxtacortical white matter pathways are targeted such that the biophysical properties of axons are used to propagate electrical current distant from the source of stimulation. This hypothesis was tested following RNS depth lead implantation in three subjects enrolled in the RNS multi-center clinical trials. Methods: Three subjects (CH, RK and TS) with at least one mesial temporal epileptic source were implanted with a depth electrode in mesial temporal white matter. Stereotactic guidance was used for each subject to place the cylindrical depth lead immediately lateral and adjacent to hippocampal grey matter. The depth electrode followed the longitudinal axis of the hippocampal formation. Delivery of stimulation occurred while employing subtracted activated SPECT (SAS) to capture transient focal blood flow changes. SAS acquisition and analysis (AnalyzeR) for each subject were performed at 12, 18 and 4 months, respectively following implantation of the RNS system. Bipolar stimulation of the posterior two of four depth lead contacts was performed during peripheral intravenous administration of Tc99-HMPAO. The injection of radiotracer occurred during delivery of 6-12 high frequency stimuli (100-200Hz) at 0.5Hz (stimulation intensity=4.5-5 mA, pulse width=160μsec, pulse duration=100msec). No afterdischarges were recorded by electrocorticography during stimulation. A post-stimulation baseline SPECT was acquired for each subject 36 to 48 hours following the stimulation session. The data were normalized, subtracted and co-registered to each respective subject's 3D Fourier tansform SPGR magnetic resonance neuroimaging dataset. Results: Upon repetitive bipolar stimulation of RK's posterior temporal depth contacts, propagation to an ipsilateral epileptic source in primary visual cortex was observed by semiology and blood flow measures. The sensory response overlapped his typical visual aura in distribution, color, form and movement. For CH and TS, transient hypo- and hyperperfusion-related changes were demonstrated both ipsi- and contralaterally, concordant with preoperatively determined epileptic tissue. Conclusions: Direct cortical stimulation of mesial temporal white matter validates influencing distant epileptic sources as determined presurgically. These data ostensibly represent the extent of cortical modulation for a given set of focal stimulation parameters delivered through a specific electrode contact shape, orientation and location in white matter. Presurgical planning can predict axonal pathways that direct the spread of RNS current to distant neural tissue. As a result, a greater extent of the epileptic circuit can be modulated with a minimum number of electrodes. Such data will underscore the need to regard the partial-onset epilepsies as potentially extensive pathological neural networks.