Diagnosing Epilepsy with Normal Interictal EEG Using Dynamic Network Models

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Abstract
Objective: Whereas a scalp electroencephalogram (EEG) is important for diagnosing epilepsy, a single routine EEG is limited in its diagnostic value. Only a small percentage of routine EEGs show interictal epileptiform discharges (IEDs) and overall misdiagnosis rates of epilepsy are 20% to 30%. We aim to demonstrate how network properties in EEG recordings can be used to improve the speed and accuracy differentiating epilepsy from mimics, such as functional seizures – even in the absence of IEDs.Methods: In this multicenter study, we analyzed routine scalp EEGs from 218 patients with suspected epilepsy and normal initial EEGs. The patients’ diagnoses were later confirmed based on an epilepsy monitoring unit (EMU) admission. About 46% ultimately being diagnosed with epilepsy and 54% with non‐epileptic conditions. A logistic regression model was trained using spectral and network‐derived EEG features to differentiate between epilepsy and non‐epilepsy. Of the 218 patients, 90% were used for training and 10% were held out for testing. Within the training set, 10‐fold cross validation was performed. The resulting tool was named “EpiScalp.”Results: EpiScalp achieved an area under the curve (AUC) of 0.940, an accuracy of 0.904, a sensitivity of 0.835, and a specificity of 0.963 in classifying patients as having epilepsy or not.Interpretation: EpiScalp provides an accurate diagnostic aid from a single initial EEG recording, even in more challenging epilepsy cases with normal initial EEGs. This may represent a paradigm shift in epilepsy diagnosis by deriving an objective measure of epilepsy likelihood from previously uninformative EEGs. ANN NEUROL 2025;97:907–918
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  • National Institute of Neurological Disorders and Stroke (R35NS132228)

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