A novel diagnostic intracranial EEG biomarker in MOGHE

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Abstract

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently recognized cause of drug-resistant focal epilepsy. It is often MRI-negative or shows imaging features mimicking focal cortical dysplasias, which makes recognition difficult and limits presurgical counseling. We aimed to identify an intracranial EEG (iEEG) biomarker that distinguishes MOGHE from other developmental brain lesions encountered in epilepsy surgery. In a retrospective multicenter test cohort of 38 patients (18 MOGHE, 20 non-MOGHE), we analyzed long-term stereo-EEG and subdural recordings. Only MOGHE patients showed highly stereotyped clusters of very brief low-voltage fast activity (LVFA) events, organized into status-like 3 to 12-minute episodes that often lacked clear clinical symptoms. LVFA clusters were present in 16/18 MOGHE and 0/22 non-MOGHE patients. We then tested diagnostic performance in an independent, blinded single-center validation cohort of 22 patients (11 MOGHE, 11 non-MOGHE), in which visual identification of LVFA clusters correctly classified 10/11 MOGHE and 10/11 non-MOGHE cases (Cohen’s κ=0.82). Penalized logistic regression further confirmed MOGHE histology as the strongest predictor of LVFA clusters, independent of age and lobe localization. Because LVFA clusters can be recognized visually on routine intracranial EEG recordings without specialized software, this biomarker is readily applicable in clinical practice and may improve presurgical identification of MOGHE. Future prospective studies should determine whether its recognition influences surgical planning, improves outcome prediction, or facilitates selection of patients for mechanism-based therapies.

Highlights

  • Clusters of brief LVFA in intracranial EEG are a lesion-specific biomarker of MOGHE compared to mMCD and FCD2

  • LVFA clusters reliably distinguished MOGHE from non-MOGHE lesions (mMCD and FCD2) in both a multicenter test cohort and an independent blinded validation cohort.

  • Younger age at seizure onset is a secondary independent modifier, while frontal localization and age at intracranial recording are not.

  • Clinicians can detect LVFA clusters on continuous intracranial EEG using routine montages and ≥60-second review windows, without any specialized software.

  • LVFA clusters show a characteristic temporal organization and burden in MOGHE, indicating a distinct pattern of pathological network activity in this lesion type.

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