Structural brain lesions, including the broad range of malformations of cortical
development (MCD) and glio-neuronal tumors, are among the most common
causes of drug-resistant focal epilepsy. Epilepsy surgery can provide a curative
treatment option in respective patients. The currently available pre-surgical
multi-modal diagnostic armamentarium includes high- and ultra-high resolution magnetic resonance imaging (MRI) and intracerebral EEG to identify a
focal structural brain lesion as epilepsy's underlying aetiology. However, specificity and accuracy in diagnosing the type of lesion have proven to be limited.
Moreover, the diagnostic process does not stop with the decision for surgery.
The neuropathological diagnosis remains the gold standard for disease classification and patient stratification but is particularly complex with high interobserver variability. Here, the identification of lesion-specific mosaic variants
together with epigenetic profiling of lesional brain tissue became new tools to
more reliably identify disease entities. Also, pathogenic brain somatic variants provide unique insights into disease pathways.