Anatomical connectivity and efficacy of electro-therapy for seizure control: A SANTE's single-center regression analyses.

OBJECTIVE: To assess based on a single-center data from a multicenter trial (Stimulation of the Anterior Nucleus for the Thalamus for Epilepsy (SANTE)), the role of anatomical connectivity and other factors (e.g., stimulating electrode placement) on efficacy of electro-therapy of the anterior thalamic nuclei (ATN), a node in Papez network, on pharmaco-resistant seizures. DATA SOURCE: Adults with at least 6 seizures /month were enrolled in this trial. Percent seizure reduction was compared between subjects with seizures emerging inside Papez's network (IPN) to those with seizures outside it (OPN). Statistical analyses were performed on the first year of the trial. RESULTS: Data from 11 subjects were analyzed. At Year 1, median seizure reduction was 80.5% (-100% to -40.3%) in 8/11 subjects with seizures IPN, vs. 52.8% (-61.4% to -23.7%) for 3/11 subjects with seizures OPN (2-sided Wilcoxon p = 0.08). At year 7, 3/11 subjects with seizures IPN had been seizure free for several years vs. 0/11 subjects with seizures OPN. Addition of 4 subjects from a pilot trial with nearly identical protocol to SANTE's, increased to 12/15 the number of subjects with seizures IPN. A 2-sided Fisher's exact test applied to seizure frequency reduction in the 12/15 cohort compared to the 3/15 with seizures OPN, showed significant (p = 0.04) differences in efficacy at the 70% seizure reduction rate. Median quality of life (QOL) scores for subjects with seizures IPN improved by 81% vs. 53% for subjects with seizures OPN. No other factors (e.g., current intensity) had a statistically significant effect on efficacy. CONCLUSIONS: Degree of anatomical connectivity between stimulation targets and epileptogenic networks (ENs) plays an important role in therapeutic efficacy. This may be explained by the minimization of signal attenuation inherent in impulse transmission in nervous tissue partly as a function of fiber tract length, tissue anisotropy, and number of synaptic relays between stimulation target and epileptogenic networks.

Placement of deep brain electrodes in the dog using the Brainsight frameless stereotactic system: a pilot feasibility study.

BACKGROUND: Deep brain stimulation (DBS) together with concurrent EEG recording has shown promise in the treatment of epilepsy. A novel device is capable of combining these 2 functions and may prove valuable in the treatment of epilepsy in dogs. However, stereotactic implantation of electrodes in dogs has not yet been evaluated. OBJECTIVE: To evaluate the feasibility and safety of implanting stimulating and recording electrodes in the brain of normal dogs using the Brainsight system and to evaluate the function of a novel DBS and recording device. ANIMALS: Four male intact Greyhounds, confirmed to be normal by clinical and neurologic examinations and hematology and biochemistry testing. METHODS: MRI imaging of the brain was performed after attachment of fiducial markers. MRI scans were used to calculate trajectories for electrode placement in the thalamus and hippocampus, which was performed via burr hole craniotomy. Postoperative CT scanning was performed to evaluate electrode location and accuracy of placement was calculated. Serial neurologic examinations were performed to evaluate neurologic deficits and EEG recordings obtained to evaluate the effects of stimulation. RESULTS: Electrodes were successfully placed in 3 of 4 dogs with a mean accuracy of 4.6 ± 1.5 mm. EEG recordings showed evoked potentials in response to stimulation with a circadian variation in time-to-maximal amplitude. No neurologic deficits were seen in any dog. CONCLUSIONS AND CLINICAL IMPORTANCE: Stereotactic placement of electrodes is safe and feasible in the dog. The development of a novel device capable of providing simultaneous neurostimulation and EEG recording potentially represents a major advance in the treatment of epilepsy.

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.