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Multicenter Study
. 2023 Mar;93(3):536-550.
doi: 10.1002/ana.26557. Epub 2022 Dec 5.

Neuropathological Insights into Unexpected Cognitive Decline in Epilepsy

Annika Reimers  1 , Christoph Helmstaedter  2 , Christian E Elger  2 , Julika Pitsch  2 , Motaz Hamed  3 , Albert J Becker  1 , Juri-Alexander Witt  2
Affiliations
Multicenter Study

Neuropathological Insights into Unexpected Cognitive Decline in Epilepsy

Annika Reimers et al. Ann Neurol. 2023 Mar.

Abstract

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. ANN NEUROL 2023;93:536-550.

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References

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