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Updated: May 29, 2026
A Model of Epileptogenesis in Rhinal Cortex-Hippocampus Organotypic Slice Cultures
Published on: March 18, 2021
Refractory epilepsy associated with microglial activation
Souhel Najjar1, Daniel Pearlman, Douglas C Miller
1Department of Neurology, NYU Comprehensive Epilepsy Center, USA. mna1024231@aol.com
Background:
Experimental and clinical studies support a pathogenic role of microglial activation and proliferation (MAP) in epileptogenesis.
Methods:
From a consecutive series of 319 surgically treated epilepsy cases, we retrospectively reviewed the histopathological sections of 92 cases to define the prevalence and severity of MAP after excluding the other 227 because of coexisting disorders that might contribute to MAP. Severity of MAP was compared with underlying abnormalities. We assessed the response to intravenous immunoglobulin and plasmapheresis in one patient with severe MAP who had failed multiple antiepileptic drugs and epilepsy surgery.
Results:
MAP was detected with routine (hematoxylin and eosin) stain in 46 of 92 cases (50%). MAP was mild in 32 cases (69.6%), moderate in 12 (26.1%), and severe in 2 (4.3%). The prevalence and severity of MAP were independent of underlying abnormalities. Immunomodulatory therapy was followed by a greater than 90% reduction in seizure activity in the treated patient.
Conclusion:
MAP is prevalent in resected human epilepsy tissue. Failure to down-regulate MAP contributes to chronic neuronal hyperexcitability. We hypothesize that MAP initiates a cycle of inflammation-induced seizures and seizure-induced inflammation. Microglia-driven epilepsy may be a primary pathogenic process in a small number of cases, as suggested by the pathology and therapeutic response in our patient, but may contribute to epileptogenesis in many more.
Insights
Microglial activation and proliferation (MAP) is common in epilepsy tissue and may drive chronic seizures. Immunomodulatory therapy showed promise in a severe case, suggesting a potential new treatment avenue for epilepsy.
Area of Science:
- Neuroscience
- Pathology
- Immunology
Background:
- Experimental and clinical studies suggest microglial activation and proliferation (MAP) plays a role in epileptogenesis.
- Microglia are the primary immune cells of the central nervous system.
Purpose of the Study:
- To determine the prevalence and severity of MAP in surgically treated epilepsy patients.
- To investigate the relationship between MAP and underlying abnormalities in epilepsy.
- To assess the efficacy of immunomodulatory therapy in a patient with severe MAP.
Main Methods:
- Retrospective review of histopathological sections from 92 epilepsy cases.
- Exclusion of 227 cases with coexisting disorders that could cause MAP.
- Comparison of MAP severity with underlying abnormalities and assessment of treatment response.
Main Results:
- MAP was detected in 50% of epilepsy tissue samples.
- MAP prevalence and severity were independent of underlying abnormalities.
- A single patient with severe MAP experienced over 90% seizure reduction with immunomodulatory therapy.
Conclusions:
- MAP is prevalent in resected human epilepsy tissue and may contribute to chronic neuronal hyperexcitability.
- MAP may initiate a cycle of inflammation-induced seizures and seizure-induced inflammation.
- Microglia-driven epilepsy may be a primary pathogenic process in some cases and contribute to epileptogenesis in many others.
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