Hogan, R Edward

Abstract Objective To measure the relative levels of signal and noise in expert diagnosis of epilepsy. Methods Twenty multinational epileptologists independently reviewed 50 vignettes of adult and pediatric patients presenting with suspected seizure(s) on two separate occasions with a ≥30‐day washout period. Experts provided a diagnosis of epilepsy or non‐epilepsy based on clinical information and, if requested, routine EEG and neuroimaging data. Cases had an established clinical diagnosis of epilepsy or non‐epilepsy based on capture of habitual paroxysmal events on video‐EEG or long‐term clinical follow‐up. Experts' judgments were analyzed to decompose variability into different sources: signal (objective differences between cases), level noise (experts' bias toward over/under‐diagnosis), pattern noise (experts' idiosyncratic reactions to specific case features), and occasion noise (inconsistency across occasions). Results The probability of an expert making a different diagnosis for a given case on two different occasions was 16%. The probability of two different experts making a different diagnosis for the same case was 26%. Signal (case “difficulty”) accounted for 66–69% of total variation, with 31–34% attributable to noise. Level noise was the largest contributor in the absence of EEG/neuroimaging results (23%), while pattern noise dominated when test results were available (24%). Occasion noise contributed relatively little (1%) but was still sufficient to cause diagnostic reversals in 16–22% between occasions. Significance The degree of noise in expert diagnosis of epilepsy is substantial, stemming primarily from physicians' idiosyncratic interpretations of case features and variable dispositions toward over‐ or under‐diagnosis. Strategies to improve reliability are needed, including standardized data collection protocols and structured decision algorithms. For “difficult cases,” where expert reliability and accuracy are lowest, our findings support current clinical practice which favors early referral for video‐EEG monitoring over reliance on diagnostic anchoring. This diagnostic pathway may become more accessible with advances in EEG technology (e.g., wearable devices) and artificial intelligence.

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.

AbstractFocal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD.We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization.FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques.Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.