Neuropathological Insights into Unexpected Cognitive Decline in Epilepsy

Objective: Some patients unexpectedly display an unfavorable cognitive course after epilepsy surgery subsequent to any direct cognitive sequelae of the surgical treatment. Therefore, we conducted in-depth neuropathological examinations of resective specimens from corresponding patients to provide insights as to the underlying disease processes. Methods: In this study, cases with significant cognitive deterioration following a previous postoperative assessment were extracted from the neuropsychological database of a longstanding epilepsy surgical program. An extensive reanalysis of available specimens was performed using current, state-of-the-art neuropathological examinations. Patients without cognitive deterioration but matched in regard to basic pathologies served as controls. Results: Among the 355 operated patients who had undergone more than one postoperative neuropsychological examination, 30 (8%) showed significant cognitive decline in the period after surgery. Of the 24 patients with available specimens, 71% displayed further neuropathological changes in addition to the typical spectrum (ie, hippocampal sclerosis, focal cortical dysplasias, vascular lesions, and low-grade tumors), indicating (1) a secondary, putatively epilepsy-independent neurodegenerative disease process; (2) limbic inflammation; or (3) the enigmatic pathology pattern of "hippocampal gliosis " without segmental neurodegeneration. In the controls, the matched individual principal epilepsy-associated pathologies were not found in combination with the secondary pathology patterns of the study group. Interpretation: Our findings indicate that patients who unexpectedly displayed unfavorable cognitive development beyond any direct surgical effects show rare and very particular pathogenetic causes or parallel, presumably independent, neurodegenerative alterations. A multicenter collection of such cases would be appreciated to discern presurgical biomarkers that help with surgical decision-making.