OBJECTIVE To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER NCT00572195. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

https://n.neurology.org/content/neurology/early/2020/07/20/WNL.0000000000010154.full.pdf

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Objective Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. Methods This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. Results Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. Significance LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

/pdf/effects-of-surgical-targeting-in-laser-interstitial-thermal-2lywx3reqx.pdf

Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients

Laser interstitial thermal therapy (LITT): Seizure outcomes for refractory mesial temporal lobe epilepsy

Background For patients with focal drug-resistant epilepsy (DRE), surgical resection of the epileptogenic zone (EZ) may offer seizure freedom and benefits for quality of life. Yet, concerns remain regarding invasiveness, morbidity, and neurocognitive side effects. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a less invasive option for stereotactic ablation rather than resection of the EZ. Objective To provide an introduction to MRgLITT for epilepsy, including historical development, surgical technique, and role in therapy. Methods The development of MRgLITT is briefly recounted. A systematic review identified reported techniques and indication-specific outcomes of MRgLITT for DRE in human studies regardless of sample size or follow-up duration. Potential advantages and disadvantages compared to available alternatives for each indication are assessed in an unstructured review. Results Techniques and outcomes are reported for mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasia, nonlesional epilepsy, tuberous sclerosis, periventricular nodular heterotopia, cerebral cavernous malformations, poststroke epilepsy, temporal encephalocele, and corpus callosotomy. Conclusion MRgLITT offers access to foci virtually anywhere in the brain with minimal disruption of the overlying cortex and white matter, promising fewer neurological side effects and less surgical morbidity and pain. Compared to other ablative techniques, MRgLITT offers immediate, discrete lesions with real-time monitoring of temperature beyond the fiber tip for damage estimates and off-target injury prevention. Applications of MRgLITT for epilepsy are growing rapidly and, although more evidence of safety and efficacy is needed, there are potential advantages for some patients.

Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for Epilepsy: Systematic Review of Technique, Indications, and Outcomes.

Introduction: Epilepsy affects more than 1% of the US population, and over 30% of adults with epilepsy do not respond to antiseizure medications without life-impacting medication-related side effects. Resection of the seizure focus is not an option for many patients because it would cause unacceptable neurological or cognitive harm. For these patients, neuromodulation has emerged as a nondestructive, effective, and safe alternative. The NeuroPace® RNS® System, the only brain-responsive neurostimulation device, records neural activity from leads placed at one or two seizure foci. When the neurostimulator detects epileptiform activity, as defined for each patient by his or her physician, brief pulses of electrical stimulation are delivered to normalize the activity.Areas covered: This review describes the RNS System, the results of multi-year clinical trials, and the research discoveries enabled by the chronic ambulatory brain data collected by the RNS System.Expert commentary: Brain-responsive neurostimulation could potentially be used to treat any episodic neurological disorder that's accompanied by a neurophysiological biomarker of severity. Combining advanced machine learning approaches with the chronic ambulatory brain data collected by the RNS System could eventually enable automatic fine-tuning of detection and stimulation for each patient, creating a general-purpose neurotechnological platform for precision medicine.

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy.

Objectives Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique for focal epilepsy. A major appeal of LITT is that it may result in fewer cognitive deficits, especially when targeting dominant hemisphere mesial temporal lobe (MTL) epilepsy. To evaluate this, as well as to determine seizure outcomes following LITT, we evaluated the relationships between ablation volumes and surgical or cognitive outcomes in 43 consecutive patients undergoing LITT for MTL epilepsy. Methods All patients underwent unilateral LITT targeting mesial temporal structures. FreeSurfer software was used to derive cortical and subcortical segmentation of the brain (especially subregions of the MTL) using preoperative magnetic resonance imaging (MRI). Ablation volumes were outlined using a postablation T1-contrasted MRI. The percentages of the amygdala, hippocampus, and entorhinal cortex ablated were quantified objectively. The volumetric measures were regressed against changes in neuropsychological performance before and after surgery, RESULTS: A median of 73.7% of amygdala, 70.9% of hippocampus, and 28.3% of entorhinal cortex was ablated. Engel class I surgical outcome was obtained in 79.5% and 67.4% of the 43 patients at 6 and 20.3 months of follow-up, respectively. No significant differences in surgical outcomes were found across patient subgroups (hemispheric dominance, hippocampal sclerosis, or need for intracranial evaluation). Furthermore, no significant differences in volumes ablated were found between patients with Engel class IA vs Engel class II-IV outcomes. In patients undergoing LITT in the dominant hemisphere, a decline in verbal and narrative memory, but not in naming function was noted. Significance Seizure-free outcomes following LITT may be comparable in carefully selected patients with and without MTS, and these outcomes are comparable with outcomes following microsurgical resection. Failures may result from non-mesial components of the epileptogenic network that are not affected by LITT. Cognitive declines following MTL-LITT are modest, and principally affect memory processes.

Lauren Moss

Papers

Laser ablation for mesial temporal lobe epilepsy: Surgical and cognitive outcomes with and without mesial temporal sclerosis.