Kuzniecky, Ruben

AbstractRacial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug‐resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05–.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

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 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.