Fisher, Robert S.

AbstractObjectiveFocused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open‐label, single‐center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment‐refractory epilepsy.MethodsTwo adult subjects with treatment‐refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy.ResultsThe patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure‐free at 12 months, and in the second patient, the frequency reduced from 90–100 seizures per month to 3–6 seizures per month.SignificanceThis is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment‐refractory focal onset epilepsy.

Abstract Neuromodulation is a key therapeutic tool for clinicians managing patients with drug‐resistant epilepsy. Multiple devices are available with long‐term follow‐up and real‐world experience. The aim of this review is to give a practical summary of available neuromodulation techniques to guide the selection of modalities, focusing on patient selection for devices, common approaches and techniques for initiation of programming, and outpatient management issues. Vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (DBS‐ANT), and responsive neurostimulation (RNS) are all supported by randomized controlled trials that show safety and a significant impact on seizure reduction, as well as a suggestion of reduction in the risk of sudden unexplained death in epilepsy (SUDEP). Significant seizure reductions are observed after 3 months for DBS, RNS, and VNS in randomized controlled trials, and efficacy appears to improve with time out to 7 to 10 years of follow‐up for all modalities, albeit in uncontrolled follow‐up or retrospective studies. A significant number of patients experience seizure‐free intervals of 6 months or more with all three modalities. Number and location of epileptogenic foci are important factors affecting efficacy, and together with comorbidities such as severe mood or sleep disorders, may influence the choice of modality. Programming has evolved—DBS is typically initiated at lower current/voltage than used in the pivotal trial, whereas target charge density is lower with RNS, however generalizable optimal parameters are yet to be defined. Noninvasive brain stimulation is an emerging stimulation modality, although it is currently not used widely. In summary, clinical practice has evolved from those established in pivotal trials. Guidance is now available for clinicians who wish to expand their approach, and choice of neuromodulation technique may be tailored to individual patients based on their epilepsy characteristics, risk tolerance, and preferences.

Abstract Deep brain stimulation of the anterior nuclei of thalamus (ANT‐DBS) is effective for reduction of seizures, but little evidence is available to guide practitioners in the practical use of this therapy. In an attempt to fill this gap, a questionnaire with 37 questions was circulated to 578 clinicians who were either engaged in clinical trials of or known users of DBS for epilepsy, with responses from 141, of whom 58.2% were epileptologists and 28.4% neurosurgeons. Multiple regions of the world were represented. The survey found that the best candidates for DBS were considered those with temporal or frontal seizures, refractory to at least two medicines. Motivations for renewing therapy upon battery depletion were reduced convulsive, impaired awareness, and severe seizures and improved quality of life. Targeting of leads mainly was by magnetic resonance imaging, sometimes with intraoperative imaging or microelectrode recording. The majority used transventricular approaches. Stimulation parameters mostly imitated the SANTE study parameters, except for initial stimulation amplitudes in the 2–3‐V or ‐mA range, versus 5 V in the SANTE study. Stimulation intensity was most often increased or reduced, respectively, for lack of efficacy or side effects, but changes in active contacts, cycle time, and pulse duration were also employed. Mood or memory problems or paresthesias were the side effects most responsible for adjustments. Off‐label sites stimulated included centromedian thalamus, hippocampus, neocortex, and a few others. Several physicians used DBS in conjunction with vagus nerve stimulation or responsive neurostimulation, although our study did not track efficacy for combined use. Experienced users varied more from published parameters than did inexperienced users. In conclusion, surveys of experts can provide Class IV evidence for the most prevalent practical use of ANT‐DBS. We present a flowchart for one protocol combining common practices. Controlled comparisons will be needed to choose the best approach.