Qualitative Assessment of Activated Microglia and Astrocytes in Focal Cortical Dysplasia: Case Series of Pediatric Patients

Abstract

Epilepsy is the most common neurologic condition seen in children. Focal cortical dysplasia (FCD), a seizure disorder characterized by abnormal cortical laminar development, comprises approximately 75% of medically intractable epilepsies in the pediatric population. A greater appreciation of the pathology and intrinsic properties of the epileptogenic zone may help in understanding why FCD lesions are drug‐resistant, and could potentially lead to more effective treatments in the pediatric population. Neuronal support cells such as microglia and astrocytes have shown to have a role in FCD pathology. These cells are also activated during aging and traumatic brain injury as evidence by morphological change. This study aims to characterize the spatial distribution of microglia and astrocytes using immunohistochemistry in dysplastic tissue of eight male pediatric patients diagnosed with FCD. Cortical specimens from patients who underwent surgical resection of focally dysplastic cortex at Phoenix Children’s Hospital between 2008 and 2014 were examined using immunohistochemistry. Primary antibodies against GFAP and Iba1, as well as structural staining using hematoxylin and eosin (H&E), were incubated on sections and further analyzed using bright‐field microscopy. A pattern of perivascular activated microglia was observed in five patients around at least one blood vessel, while a pattern of non‐localized ramified microglia was observed in the other three patients. No identifiable pattern of astrocytic distribution was found. Thus, distinct patterns of microglia, rather than astrocytes, suggest dual underlying mechanisms of epileptogenesis.