Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Frontal Lobe Epilepsy: A New Clinico‐Pathological Entity

Abstract

The histopathological spectrum of human epileptogenic brain lesions is widespread including common and rare variants of cortical malformations. However, 2-26% of epilepsy surgery specimens are histopathologically classified as nonlesional. We hypothesized that these specimens include also new diagnostic entities, in particular when presurgical magnetic resonance imaging (MRI) can identify abnormal signal intensities within the anatomical region of seizure onset. In our series of 1381 en bloc resected epilepsy surgery brain specimens, 52 cases could not be histopathologically classified and were considered nonlesional (3.7%). An increase of Olig2-, and PDGFR-alpha-immunoreactive oligodendroglia was observed in white matter and deep cortical layers in 22 of these patients (42%). Increased proliferation activity as well as heterotopic neurons in white matter were additional histopathological hallmarks. All patients suffered from frontal lobe epilepsy (FLE) with a median age of epilepsy onset at 4 years and 16 years at epilepsy surgery. Presurgical MRI suggested focal cortical dysplasia (FCD) in all patients. We suggest to classify this characteristic histopathology pattern as "mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE)." Further insights into pathomechanisms of MOGHE may help to bridge the diagnostic gap in children and young adults with difficult-to-treat FLE.

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

“…Indeed an occasionally observation in MVNT in this and previous reports has been clustering of VC along vessels, reminiscent of developmental migration patterns of OPC . Recent description of a novel subtype of mild malformation of cortical development in frontal lobe epilepsy, associated with increased OLIG2 cells in the deep cortical layers and superficial white matter with myelin loss also draws comparison with MVNT .…”

Marked accumulation of oligodendroglia‐like cells in temporal lobe epilepsy with amygdala enlargement and hippocampal sclerosis

“…However, there remain few pathological reports on TLE with AE, and no clear consensus has been established. Oligodendroglia or oligodendroglia‐like cells (OLCs) have recently attracted attention in epilepsy studies, especially in pediatric cases and frontal lobe cortical malformation . Here, we report a case of TLE with AE and hippocampal sclerosis, in which histopathological study demonstrated remarkable clustering of OLCs around the uncus.…”

“…OLCs and oligodendroglia have attracted attention in the field of epilepsy . Non‐neoplastic cases with increased oligodendroglial cells were sometimes reported as oligodendroglial hyperplasia, oligodendroglial hamartoma or microdysgenesis .…”

Increased subcortical oligodendroglia‐like cells in pharmacoresistant focal epilepsy in children correlate with extensive epileptogenic zones

“…Increased numbers of oligodendroglia‐like cells (OLCs), oligodendroglial cells, and clusters of oligodendroglia, and oligodendroglial hyperplasia were reported in the surgical specimens from patients with pharmacoresistant epilepsy. We demonstrated previously that OLCs significantly increased from the gray matter and junction of gray–white matter to white matter in pediatric pharmacoresistant focal epilepsy compared to those of normal controls .…”

“…OLCs, however, show strongly positive Olig2 immunoreactivity, whereas, mature oligodendrocytes show weak Olig2 immunoreactivity . Olig2‐positive OLCs were observed in surgical specimens in epilepsy surgery . Olig2 was developed originally as a specific marker of oligodendroglial tumor cells .…”