O’Brien, Terence J.

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.

AbstractObjectiveVisual assessment of magnetic resonance imaging (MRI) from the Human Epilepsy Project 1 (HEP1) found 18% of participants had atrophic brain changes relative to age without known etiology. Here, we identify the underlying factors related to brain volume differences in people with focal epilepsy enrolled in HEP1.MethodsEnrollment data for participants with complete records and brain MRIs were analyzed, including 391 participants aged 12–60 years. HEP1 excluded developmental or cognitive delay with intelligence quotient <70, and participants reported any formal learning disability diagnoses, repeated grades, and remediation. Prediagnostic seizures were quantified by semiology, frequency, and duration. T1‐weighted brain MRIs were analyzed using Sequence Adaptive Multimodal Segmentation (FreeSurfer v7.2), from which a brain tissue volume to intracranial volume ratio was derived and compared to clinically relevant participant characteristics.ResultsBrain tissue volume changes observable on visual analyses were quantified, and a brain tissue volume to intracranial volume ratio was derived to compare with clinically relevant variables. Learning difficulties were associated with decreased brain tissue volume to intracranial volume, with a ratio reduction of .005 for each learning difficulty reported (95% confidence interval [CI] = −.007 to −.002, p = .0003). Each 10‐year increase in age at MRI was associated with a ratio reduction of .006 (95% CI = −.007 to −.005, p < .0001). For male participants, the ratio was .011 less than for female participants (95% CI = −.014 to −.007, p < .0001). There were no effects from seizures, employment, education, seizure semiology, or temporal lobe electroencephalographic abnormalities.SignificanceThis study shows lower brain tissue volume to intracranial volume in people with newly treated focal epilepsy and learning difficulties, suggesting developmental factors are an important marker of brain pathology related to neuroanatomical changes in focal epilepsy. Like the general population, there were also independent associations between brain volume, age, and sex in the study population.

Abstract Aims The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems‐level analysis. Methods Imaging‐based cortical structural maps from a large‐scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell‐type deconvolution, differential expression analysis and cell‐type enrichment analyses were used to identify differences in cell‐type distribution. These differences were followed up in post‐mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell‐type‐specific depletion was used in a murine model of acquired epilepsy. Results We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post‐mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non‐spatial memory test seen in epileptic mice not depleted of microglia. Conclusions These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Summary To describe the demographics, etiologies, types of status epilepticus ( SE ), and outcomes in people with refractory and super‐refractory SE from around the world, we prospectively collected cases of refractory SE ( RSE ) treated with continuous intravenous anesthetic drugs in an intensive care unit setting through online questionnaires using “active surveillance.” We collected information about 776 cases of RSE in 50 countries over 4 years. Control of SE was achieved in 74% of the cases. Neurologic outcomes were poor in 41% of patients, and 24% died. Good outcome was associated with younger age and a history of epilepsy. Etiology strongly influenced the outcome. Patients from Asia were younger, more frequently presented with convulsive SE , and were more frequently affected by infectious etiologies when compared with patients from Europe and the Americas. Despite these differences, outcomes were similar in all countries. Demographics of patients with RSE in a global audit are similar to those in prior single center series, providing evidence of generalizability of those studies. Important differences exist among patients with RSE from different regions of the world, but these do not seem to significantly influence patient outcomes.

Central processing of visceral information in humans is incompletely understood. We aimed to demonstrate the feasibility of single photon emission computed tomography (SPECT) and to quantitate the changes in regional cerebral blood flow during rectal distension. Ten healthy volunteers underwent randomized sham and active rectal distensions on separate days, during which cerebral blood flow was assessed by intravenous technetium-99m ethyl cysteinate dimer (99mTc-ECD) SPECT. Three-dimensional coregistration of brain images was used to quantitate activation in four preselected cerebral foci and two control regions. Paired analysis compared blood flow during sham and active distensions. There was increased right anterior cingulate gyrus activity (6.5 ± 2.9%, P = 0.03) with active rectal distension. A 5.4 ± 2.4% reduction in blood flow in the superior parieto-occipital control region ( P = 0.04) suggested blood “redistribution” during stimulation. Marked variability in activation of the frontal cortex, thalamus/basal ganglia complex, and mesiotemporal lobe was noted. Thus rectal distension increases activity in the right anterior cingulate gyrus on average; other foci of cerebral activation are quite variable, suggesting a lack of specific cerebral projections during rectal stimulation.

Summary Objective Epilepsy surgery is the most effective treatment for select patients with drug‐resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities. Methods We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers. Results Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis ( MTS ) in 1991, and three had their highest number of MTS surgeries in 2001, only one center achieved its peak number of MTS surgeries in 2011. The most productive year for MTS surgeries varied then by center; overall, the nine centers surveyed performed 48% (95% confidence interval [CI] −27.3% to −67.4%) fewer such surgeries in 2011 compared to either 1991 or 2001, whichever was higher. There was a parallel increase in the performance of surgery for nonlesional epilepsy. Further analysis of 5/9 centers showed a yearly increase of 0.6 ± 0.07% in the performance of invasive electroencephalography ( EEG ) without subsequent resections. Overall, although MTS was the main surgical substrate in 1991 and 2001 (proportion of total surgeries in study centers ranging from 33.3% to 70.2%); it occupied only 33.6% of all resections in 2011 in the context of an overall stable total surgical volume. Significance These findings highlight the major aspects of the evolution of epilepsy surgery across the past two decades in a sample of well‐established epilepsy surgery centers, and the critical current challenges of this treatment option in addressing complex epilepsy cases requiring detailed evaluations. Possible causes and implications of these findings are discussed.