gms | German Medical Science

Objective: The pathomechanisms of chronic temporal lobe epilepsy (TLE) leading to hippocampal sclerosis (or vice versa) are unknown. Yet, it seems clear that hippocampal sclerosis is associated with neuropsychological deficits, even worsening the patient’s already dreadful situation. The role of microglia (MG) in various pathologies has been studies within the past years, showing beneficial as well as detrimental effects – including direct neuronal injury via inflammatory pathways. To study the relation between MG driven inflammation and hippocampal sclerosis, we evaluated human tissue data of patients suffering from TLE.

Methods: Resected brain tissue of 27 patients suffering from drug-resistant TLE were immunohistochemically evaluated for the grade of hippocampal sclerosis and the grade of MG activation and accumulation within the hippocampus. A blinded observer categrorized MG activation using an arbitrary grading system (none[0] – mild focal[1] – mild global[2] – moderate[3] – strong[4] – intense[5]). Correlation with the respective Wyler grading of the tissue was then done by another observer.

Results: MG accumulation was seen in all resected tissue samples – most probably due to the operative procedure. Notably, the extent of MG invasion in the hippocampus was significantly more pronounced in tissue with high grade sclerosis (Wyler 4, n=10, Grading 3.9±0.6), than in tissue with lower grade sclerosis (Wyler 1-3, n=8, Grading 2.4±1.3) or in tissue without pathological changes (no sclerosis, n=8, Grading 2.4±1.3). The differences were statistically significant (p=0.007 Wyler 4vs both other groups). In two patients with focal cortical dysplasia, an intense accumulation of MG was seen as well (FCD, n=2, Grading 4.0±0).

Conclusion: Inflammatory mechanisms – such as MG accumulation and activation – might contribute to hippocampus sclerosis in chronic TLE patients. Counteracting MG accumulation might therefore propose a potential salvage strategy against neuropsychological deficits.