Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) can reduce seizures in patients with drug-resistant epilepsy. However, seizure freedom is rare, and there is no early response biomarker to predict long-term seizure suppression. To evaluate a short-term biomarker of therapeutic response to DBS, we studied 18-minute trials of ANT stimulation in patients with drug-resistant epilepsy undergoing intracranial electroencephalography. We compared a standard high-frequency periodic versus a non-periodic pulse pattern. We found that short-term ANT stimulation within the clinically used amplitude range preferentially altered the first 150 ms of anterograde ANT to anterior cingulate and superior frontal connectivity. Non-periodic ANT stimulation selectively modified early cortico-cortical evoked potentials more than periodic stimulation, and these changes were driven by the response phase. These pattern-specific changes in connectivity between the ANT and spatially restricted cortical areas suggest differing mechanisms and are a promising biomarker for patients being treated with ANT-DBS.

OBJECTIVE:This study was undertaken to evaluate the safety and effectiveness of responsive thalamic stimulation as adjunctive therapy for drug-resistant idiopathic generalized epilepsy (IGE) with generalized tonic-clonic seizures (GTCSs). METHODS:NAUTILUS is a prospective, multicenter, single-blind, randomized sham-controlled pivotal trial. Patients were ≥12 years of age with drug-resistant IGE and ≥2 GTCSs over a 3-month baseline. Bilateral depth leads were targeted to the centromedian thalamus. One month later, patients were randomized to Active (responsive stimulation, n = 44) or Sham (no stimulation, n = 43). The effectiveness evaluation period (EEP) began 3 months postimplant through 1 year. After a second GTCS in the EEP, patients transitioned to open-label active stimulation. The primary safety endpoint was the serious adverse device-related event (SADE) rate at 84 days postimplant. The primary effectiveness endpoint was time-to-second-GTCS during the EEP. Additional endpoints included median percent change in days with any generalized seizure, GTCS frequency, and responder rate (RR). RESULTS:Eighty-seven patients were implanted across 23 US centers. The SADE rate was significantly below the performance goal (6.9%, p < .0001), with no adverse effects on cognition, mood, or sleep. The prespecified primary effectiveness endpoint was not significant. However, a post hoc mixed-effects model considering all EEP days demonstrated greater GTCS reduction in the originally randomized Active group (61%) compared to patients originally randomized to Sham (49%, p = .030). Eighteen-month outcomes included 76.8% median GTCS reduction, 62.5% RR, 40% GTCS-free at that timepoint, and 77.8% median reduction in days with any generalized seizure. More than 90% of patients and 86% of physicians reported improvement on Global Impression of Change scales. SIGNIFICANCE:NAUTILUS is the first randomized controlled neuromodulation trial in IGE. Responsive thalamic stimulation provided a clinically meaningful and durable reduction in seizures with an acceptable safety profile, offering a much-needed option for drug-resistant IGE.

BACKGROUND AND OBJECTIVES:Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT. METHODS:This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will be conducted at 5 years. RESULTS:Across 32 US epilepsy centers, 324 patients (mean age 37.1, 59.6% female individuals) were implanted and 271 completed 3 years of follow-up. The median percent reduction in seizure frequency at 6 months was 62% and 82% at 3 years (p < 0.0001; Wilcoxon signed-rank test); 41% had a ≥90% reduction in seizure frequency at 3 years, 42.5% of participants had at least 1 seizure-free period of 6 months or more, and 22.0% experienced seizure freedom for 12 months or more. Observed effectiveness was similar across patients with 1 or 2 seizure onsets and across onset locations (mesial temporal, neocortical, or both mesial temporal and neocortical). No serious stimulation-related adverse events were reported. Combining data from all RNS System trials (n = 645), the sudden unexplained death in epilepsy (SUDEP) rate was 2.3/1,000 patient years, which was significantly lower than predefined comparators (p < 0.05; 1-tailed χ2). DISCUSSION:This prospective real-world study contributes to the body of evidence that adjunctive direct brain-responsive neurostimulation provides significant and sustained reductions in the frequency of focal seizures. Seizure reductions were greater and were achieved faster than in the RCT and long-term treatment trials but were similar to a more recent retrospective multicenter real-world study. As in the preapproval studies, treatment was well-tolerated and safe, and the SUDEP rate was low. The RNS System showed similar safety and improved seizure outcomes in real-world use compared with the RCT. Improvements in efficacy may reflect changes in programming practices. Future research efforts will focus on using the brain data obtained by the device to optimize detection and stimulation paradigms for each patient. TRIAL REGISTRATION INFORMATION:ClinicalTrials.gov, NCT02403843, submitted March 26, 2015. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that in adults with refractory focal-onset seizures, direct brain-responsive neurostimulation reduces seizure frequency without serious adverse events up to 3 years.

RATIONALE:VNS is an efficacious therapy for people with epilepsy (PwE), but personalized implementation of VNS dosing and titration could be improved by measuring therapeutic engagement of cortical and subcortical physiology. METHODS:People with Drug-Resistant Epilepsy (DRE) were enrolled into a feasibility study using investigational microburst VNS (NCT03446664). An investigational VNS system with conditional approval for stimulation in the magnetic environment was titrated using an fMRI-guided titration approach to determine VNS therapy settings for each individual participant over 6 months. Stimulation parameter combinations that evoked the highest thalamic BOLD response were chosen in an individual participant as the preferred VNS therapy setting. RESULTS:Thirty-two participants were implanted and 31 participants attended the 6-month study visit and at least one prior fMRI study visit. In all participants, significant VNS-evoked thalamic BOLD responses were found. Participants who experienced significant thalamic BOLD signal among multiple stimulation parameter combinations over multiple visits were most likely to respond to µVNS. Participants responded to µVNS with a median reduction in seizure frequency of 42.6 % at 6 months. There were no MRI-related safety issues associated with active VNS during scanning. CONCLUSION:Titration of VNS using an fMRI-guided approach is feasible and safe in PwE (when using appropriate investigational devices), but our specific biomarker, used in this specific study design, was ultimately too variable to be used for patient-specific titration. An increase in thalamic BOLD signal that occurred across multiple stimulation parameter combinations and multiple visits with microburst settings was associated with seizure response that could be visualized early in the titration process.

BACKGROUND:Chimeric antigen receptor (CAR) T-cell therapy revolutionized cancer treatment, though has potential for neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS). EEG has been proposed as a predictive and prognostic tool in ICANS. OBJECTIVE:Evaluate pre-treatment EEG, neuroimaging, and clinical features in predicting ICANS, and EEG in prognosis in ICANS. METHODS:Retrospective multicenter study involving adult patients who underwent CAR T-cell therapy at Mayo Clinic Florida, Minnesota, and Arizona between October 2019 and July 2024. Univariable, multivariable and survival analyses were performed. RESULTS:We included 207 patients (111 female). Pre-treatment EEG was performed in 50.2 % of patients. Multivariable analysis of EEG, imaging, and clinical data demonstrated older age (roughly 1 % increased odds per 1 year of increased age, p = 0.006) and generalized slowing on pre-treatment EEG being associated with ICANS (p = 0.021). There were no factors predictive of hospital duration or survival in ICANS using multivariable analysis. Patients with ICANS had longer hospitalization (p < 0.001) and were less likely to survive at 12- and 24-months (p = 0.001, p < 0.001 respectively). CONCLUSION:ICANS is associated with longer hospitalization and worse survival. ICANS risk increases with older age. Generalized slowing on pre-treatment EEG may identify patients at risk of ICANS. SIGNIFICANCE:ICANS is associated with worse outcomes and may be predicted by pre-treatment EEG and older age.

OBJECTIVES:Pivotal trials have established the effectiveness of the Responsive Neurostimulation System (RNS® System) in treating focal epilepsy. In clinical trials, depth leads were primarily used to treat mesial temporal seizure onsets while cortical strip leads were used to treat neocortical seizure onsets. Here, we systematically analyze the safety and efficacy of stereoelectroencephalography (sEEG)-guided depth leads to provide responsive stimulation to neocortical gray matter. METHODS:Patients were stratified as strong responders (>median cohort seizure reduction %), weak responders (>0% and ≤median cohort seizure reduction %), and anti-responders (≤0%) based on percent seizure reduction at 1 year post-implant (1-Y). Pre-operative T1-weighted magnetic resonance imaging and post-operative computed tomography images were merged, and the Euclidean distance between the sEEG epileptic focus (sEEG-EF) and the nearest RNS System depth lead contacts was calculated. RESULTS:A total of 87 depth leads were implanted in 55 patients across neocortical brain regions. The median reduction in clinical seizures improved from 66.7% at 1-Y to 77.5% at long-term follow-up (LTFU: 2.35 ± 0.95 years), with 10 patients (18.2%) achieving complete seizure freedom. Seven patients (12.7%) experienced six serious adverse events. At 1-Y, shorter Euclidean distance between the sEEG-EF and RNS System depth leads predicted improved seizure outcome in strong responders (β = -0.84, p = 0.008) but not in weak responders (β = 0.21, p = 0.9) or anti-responders (β = -20.34, p = 0.11). At LTFU, there was no significant relationship between Euclidean distance and seizure reduction in strong responders (β = 0.77, p = 0.18), weak responders (β = 2.05, p = 0.54), or anti-responders (β = 0.24, p = 0.99). Exploratory analyses at 1-Y showed nominal associations between older age (ρ = 0.32), longer epilepsy duration (ρ = 0.27), and non-mesial temporal sEEG-EFs and greater seizure reduction; however, none survived Bonferroni correction (adjusted α = 0.0027; all post-correction p > 0.0027), and no associations were observed at LTFU. SIGNIFICANCE:In this series, neocortical depth leads for RNS therapy had favorable safety and efficacy and proximity to the sEEG-EF drove initial outcomes for strong responders to RNS therapy. PLAIN LANGUAGE SUMMARY:In this multi-center study, patients with difficult-to-treat seizures received brain-responsive stimulation using a device called responsive neurostimulation (RNS), which delivers small electrical pulses to reduce seizures. We focused on patients treated with electrodes placed in the brain's outer regions (the neocortex) and guided by a mapping procedure called sEEG. On average, patients had their seizures cut by two-thirds after one year and by more than three-quarters with longer follow-up, with about one in five becoming seizure-free. The treatment was safe, and closer electrode placement to the seizure source helped explain early-but not long-term-improvements.

Background and ObjectivesInvasive neurostimulation is rapidly becoming an established option for treatment of neurologic disorders, particularly those that are refractory to pharmacologic treatment. However, there is limited information on the use of neuromodulation during pregnancy. This study explores the safety and clinical outcomes of invasive neuromodulation-specifically vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS)-in pregnant patients with epilepsy and movement disorders.MethodsPregnant patients treated with VNS, DBS, or RNS were identified, and charts were reviewed to extract data on maternal epilepsy/movement disorder, treatment, and pregnancy.ResultsA total of 14 patients (9 VNS, 3 DBS, 2 RNS) had 22 pregnancies. Neuromodulation indications included focal epilepsy (n = 6: 3 VNS, 2 RNS, 1 DBS), generalized epilepsy (n = 6: all VNS), and Tourette syndrome (n = 2: both DBS). The average age at implantation was 24.7 years for VNS, 29.6 years for DBS, and 28 years for RNS. Pregnancy complications included miscarriages (n = 4 pregnancies; 1 VNS, 2 DBS, 1 RNS), pre-eclampsia with fetal growth restriction (n = 3: 2 VNS, 1 DBS), and gestational diabetes (2 VNS). In addition, 10 pregnancies (8 VNS, 2 RNS) were complicated by seizure exacerbations. Delivery of eight of the pregnancies (5 VNS, 1 DBS, 2 RNS) was by cesarean section. There were no cases of maternal or neonatal mortality, and there were no major congenital malformations. Owing to exacerbated shortness of breath during the third trimester, 1 patient had her VNS turned off.DiscussionPregnancy complications were consistent with previous reports of patients with neurologic disorders. Despite limitations in sample size and confounding factors related to medication use and neurologic diagnosis, our study suggests that implanted neuromodulation devices do not seem to pose a risk of neuromodulation-related teratogenicity. While these data are promising and may provide some reassurance for patient counseling regarding pregnancy, further studies with larger sample sizes are necessary.

Background and Objectives:Invasive neurostimulation is rapidly becoming an established option for treatment of neurologic disorders, particularly those that are refractory to pharmacologic treatment. However, there is limited information on the use of neuromodulation during pregnancy. This study explores the safety and clinical outcomes of invasive neuromodulation-specifically vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS)-in pregnant patients with epilepsy and movement disorders. Methods:Pregnant patients treated with VNS, DBS, or RNS were identified, and charts were reviewed to extract data on maternal epilepsy/movement disorder, treatment, and pregnancy. Results:A total of 14 patients (9 VNS, 3 DBS, 2 RNS) had 22 pregnancies. Neuromodulation indications included focal epilepsy (n = 6: 3 VNS, 2 RNS, 1 DBS), generalized epilepsy (n = 6: all VNS), and Tourette syndrome (n = 2: both DBS). The average age at implantation was 24.7 years for VNS, 29.6 years for DBS, and 28 years for RNS. Pregnancy complications included miscarriages (n = 4 pregnancies; 1 VNS, 2 DBS, 1 RNS), pre-eclampsia with fetal growth restriction (n = 3: 2 VNS, 1 DBS), and gestational diabetes (2 VNS). In addition, 10 pregnancies (8 VNS, 2 RNS) were complicated by seizure exacerbations. Delivery of eight of the pregnancies (5 VNS, 1 DBS, 2 RNS) was by cesarean section. There were no cases of maternal or neonatal mortality, and there were no major congenital malformations. Owing to exacerbated shortness of breath during the third trimester, 1 patient had her VNS turned off. Discussion:Pregnancy complications were consistent with previous reports of patients with neurologic disorders. Despite limitations in sample size and confounding factors related to medication use and neurologic diagnosis, our study suggests that implanted neuromodulation devices do not seem to pose a risk of neuromodulation-related teratogenicity. While these data are promising and may provide some reassurance for patient counseling regarding pregnancy, further studies with larger sample sizes are necessary.

Anterior thalamic (ANT) deep brain stimulation (DBS) can reduce seizure frequency by 75% in patients with medication-resistant focal epilepsy. However, a third of patients experience <50% seizure reduction and 10% no measurable reduction. Accurate mammillothalamic tract (MTT) targeting does not explain most observed seizure suppression variability. We suggest uniform application of high frequency (145 Hz) regularly spaced stimulation pulses may not be effective for all patients. A systematic investigation of alternative patterns, including irregularly spaced stimulation pulses (hypothesized to weaken hyperexcitability) is needed. Patients were consented and underwent a research thalamic stimulation protocol after completion of seizure mapping and anti-epileptic medication resumption. Bipolar continuous ANT rhythmic (RS) or non-rhythmic stimulation (NRS) was delivered spanning the two contacts closest to the MTT during 18-minute blocks. Rates of high frequency oscillations (HFOs) and epileptic spikes were detected, quantified, and compared using the KS test (p-value <0.05). ANT stimulation was performed on three subjects (n=2 right ANT, n=1 left ANT). Rhythmic stimulation modulated HFO rates in 4.8%, 1.5%, and 1.5% of channels and epileptic spike rate in 68%, 49%, and 2% of channels across subjects, respectively. Non rhythmic stimulation modulated HFO rates in 2.4%, 2.6%, and 2.5% of channels, and modified epileptic spike rate in 45% and 6% of channels in subjects 2 and 3, respectively. In a seizure onset zone (SOZ) specific analysis, we found differential effects of RS and NRS on HFO and spiking rates. Epileptiform biomarkers are modulated in a significant fashion by short-term thalamic stimulation. Ongoing studies will explore an expanded library of non-rhythmic stimulation patterns to identify those with optimal epileptiform activity suppression. Future clinical trials of chronic thalamic stimulation directed by short-term trial stimulation are needed to validate this approach.

[This corrects the article DOI: 10.1212/CPJ.0000000000200498.].

BACKGROUND AND OBJECTIVES: Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide. Our study aims to analyze the national trends in different treatment modalities for individuals with drug-resistant epilepsy and investigate the outcomes associated with these procedural trends in the United States. METHODS: Using the National Inpatient Sample database from 2010 to 2020, patients with drug-resistant focal epilepsy who underwent laser interstitial thermal therapy (LITT), open surgical resection, vagus nerve stimulation (VNS), or responsive neurostimulation (RNS) were identified. Trend analysis was performed using piecewise joinpoint regression. Propensity score matching was used to compare outcomes between 10 years prepandemic before 2020 and the first peak of the COVID-19 pandemic. RESULTS: This study analyzed a total of 33 969 patients with a diagnosis of drug-resistant epilepsy, with 3343 patients receiving surgical resection (78%), VNS (8.21%), RNS (8%), and LITT (6%). Between 2010 and 2020, there was an increase in the use of invasive electroencephalography monitoring for seizure zone localization ( P = .003). There was an increase in the use of LITT and RNS ( P < .001), while the use of surgical resection and VNS decreased over time ( P < .001). Most of these patients (89%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (11%) underwent treatment during the COVID pandemic (2020). After propensity score matching, the rate of pulmonary complications, postprocedural hematoma formation, and mortality were slightly higher during the pandemic compared with the prepandemic period ( P = .045, P = .033, and P = .026, respectively). CONCLUSION: This study indicates a relative decrease in the use of surgical resections, as a treatment for drug-resistant focal epilepsy. By contrast, newer, minimally invasive surgical approaches including LITT and RNS showed gradual increases in usage.

Background: Vagus nerve stimulation (VNS) at low frequencies (<= 30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. Objective: To examine the initial safety and efficacy performance of an investigational, high-frequency (>= 250 Hz) VNS paradigm herein called "Microburst VNS" (mu VNS). mu VNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. Methods: Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of mu VNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. Results: The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of mu VNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (>= 50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (>= 80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). Conclusion: Overall, mu VNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.

INTRODUCTION: Responsive neurostimulation (RNS) is efficacious in treating medically refractory epilepsy arising from neocortical foci. During clinical trials, most patients with neocortical seizure foci received cortical strip leads, perhaps due to intracranial monitoring with subdural grids/strips. Stereo-electroencephalography (sEEG) has become more widely utilized since the trials, resulting in increased placement of neocortical RNS depth leads. This is also an appealing approach when dural adhesions make strip lead implantation difficult. METHODS: We conducted retrospective chart review of adult patients with refractory epilepsy at seven institutions who underwent placement and connection of at least one RNS depth lead in the neocortex. RESULTS: 61 neocortical depth leads were connected to the RNS neurostimulator in 53 patients. 33 patients had additional depth leads in a non-neocortical focus, and 12 had an additional neocortical strip lead. Median follow-up was 2.2 years (range: 0.4 – 5.2 years). Median clinical seizure reduction in seizures was 63% at 1 y and 75% at last follow-up. 12 patients (23%) were seizure-free at last follow-up; a majority of these (83%) were seizure-free for >6 mo, with five patients seizure-free for >1 y. There were two (3.8%) scalp infections. One patient (1.9%) had each of the following: chemical meningitis, epidural hematoma, post-surgical status epilepticus (resolved with stimulation), new-onset non-epileptic seizures, and stimulation-related nausea (resolved with programming). CONCLUSIONS: Our multicenter series of 53 patients with neocortical-onset epilepsy treated with neocortical RNS depth leads demonstrated 75% median seizure reduction at 2 y of follow-up with a similar safety profile to placement of deep brain electrodes for movement disorders. Neocortical depth leads may be preferred with the RNS system following sEEG evaluation and/or if strip placement poses increased surgical risk.

Objective: Drug-resistant epilepsy can be difficult to cure and may pose emotional challenges for epilepsy providers. Neuropalliative care (NPC) can augment quality of life (QOL) in persons with neurological dis-eases and may add meaningful elements to the treatment repertoire of epilepsy specialists even if sei-zures continue. However, NPC has not been widely implemented in epilepsy. Our study aimed to determine whether physicians of persons with drug-resistant epilepsy (PWDRE) experience distress when faced with treatment failure (Engel class >= 2), either failure of medications-only (PWDREmo) or of both medications and surgery (procedures with curative intent (PWDREms)). Furthermore, we evalu-ated physician knowledge about and referrals to NPC following treatment failures to help improve patient QOL despite ongoing seizures.Methods: An anonymous online survey was distributed to US epilepsy physicians through the American Epilepsy Society website and personal email to assess levels of distress experienced when caring for PWDREmo and PWDREms (7-point Likert scale ["1" = "no distress", "7" = "most distress ever felt"]), and knowledge and use of NPC.Results: Eighty-two physicians completed the survey. Most experienced distress when epilepsy treat-ments failed: 59% felt moderate distress (>= 4) with PWDREmo (median "4", mean 3.74, range 1-7), 90% suffered moderate to severe distress (5, 5.17, 1-7) with PWDREms. Distress over PWDREms was sig-nificantly greater than distress over PWDREmo (p < 0.0001). Forty-three percent reported confidence in their knowledge about NPC. Only 15% were likely to refer PWDREmo to NPC, while 44% would consider it for PWDREms.Conclusion: Among survey responders, physician distress was high when confronted with treatment fail-ures, especially the failure of epilepsy surgery. Fewer than half of responders were likely to refer patients to NPC. Further research is necessary to determine extent, reasons, and effects of physician distress and whether improved understanding of and patient access to NPC would help alleviate physician distress when faced with treatment failures in PWDRE.(c) 2022 Elsevier Inc. All rights reserved.

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia.