Cortical dysplasia: A histopathologic study of 52 cases of partial lobectomy in patients with epilepsy

doi:10.1016/0046-8177(95)90244-9

Human Pathology

Volume 26, Issue 5, May 1995, Pages 493-500

https://doi.org/10.1016/0046-8177(95)90244-9 Get rights and content

Abstract

In utero migrational abnormalities account for most cases of cortical dysplasia. The histopathologic appearance of cortical dysplasia is often varied, making recognition and classification difficult. We studied 52 patients with cortical dysplasia who underwent partial lobectomy for medically intractable seizures in order to devise a simple histopathologic classification schema. The incidence of observed dysplasia in lobectomy specimens over an 11-year period (n = 360) was 14%. Patients ranged in age from 3 months to 47 years at the time of surgery (mean, 19 years; 29 male and 23 female patients). The temporal lobe was involved in 34 patients, frontal lobe in 18, parietal lobe in four, and occipital lobe in three. In three patients multiple lobes showed dysplasia. Dysplasia was right-sided in 29 patients and left-sided in 23 patients. Dysplasia was focal in 23 patients, multifocal in four patients, and diffuse in 25 patients. Three main histologic patterns of cortical dysplasia were observed: (1) a cortical laminar architectural disorganization and/or malalignment of neurons (26 patients), (2) clusters of atypical neurons and glia within the cortex (28 patients), and (3) a hypercellular molecular layer with increased numbers of neurons and glia (31 patients). In 23 patients more than one pattern of dysplasia was identified. Coexistent tumors were present in 13 patients, including ganglioglioma (eight patients), dysembryoplastic neuroepithelial tumor (three patients), and low-grade astrocytoma (two patients). Tuberous sclerosis was present in four patients. We conclude that most types of cortical dysplasia can be divided into three main histologic patterns, facilitating the recognition of dysplasia. In addition to the known association with tuberous sclerosis, tumors may coexist with cortical dysplasia.

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2018, Practical Surgical Neuropathology: A Diagnostic Approach A Volume in the Pattern Recognition Series
There are a wide variety of neuropathologic conditions which may clinically manifest as seizures. The focus of this chapter is to review some of the more commonly encountered lesions associated with medically intractable or pharmacoresistent epilepsy. Among the more common pathologies in this clinical setting are focal cortical dysplasia (developmental architectural abnormalities), hippocampal sclerosis (focal loss of neurons in the hippocampal formation), infarcts, tumors (generally low grade glioneuronal neoplasms that will be addressed elsewhere in this text), and Rasmussen encephalitis (an inflammatory condition associated with cortical neuronal loss). These topics are the focus of this chapter.
Focal cortical dysplasias in temporal lobe epilepsy surgery: Challenge in defining unusual variants according to the last ILAE classification
2015, Epilepsy and Behavior
Citation Excerpt :
Focal cortical dysplasias (FCDs) are a group of highly epileptogenic localized cortical lesions responsible for focal epileptic seizures rarely controlled by pharmacotherapy [1–9].
Focal cortical dysplasias (FCDs) represent a common architectural cortical disorder underlying pharmacoresistant focal epilepsy. The recent ILAE classification defines different types of FCDs based on their histopathological features, MRI imaging, and presumed pathogenesis; however, their clinical features and their prognostic significance are still incompletely defined. In addition, the combination of different histopathological abnormalities can represent “unusual” subtypes that can be difficult to classify. The aim of our study was to analyze the incidence and the significance of these “unusual” subtypes of FCDs in drug-resistant mesial temporal lobe epilepsy (MTLE).
We retrospectively analyzed 133 patients consecutively submitted to tailored anteromesial temporal lobe resection for pharmacoresistant MTLE. Seizure onset, seizure duration, age at surgery, and postoperative seizure outcome were evaluated in relation to the different neuropathological groups defined according to the new ILAE classification.
Focal cortical dysplasias were found in 80 out of 133 patients. Six patients were affected by isolated FCD type I, 12 patients by FCD type II, and 44 patients by FCD type III. Furthermore, we found 18 “atypical” cases (20.5% of all FCD cases and 26.6% of FCDs associated with a principal lesion): 10 cases of associated FCD type II–hippocampal sclerosis (HS) and 8 cases associated with FCD II–epilepsy-associated tumors (EATs).
Our results indicate that “unusual” subtypes of FCDs, in particular associated FCD type II, are not uncommon findings, suggesting that they deserve a classification recognition. Similarities in seizure outcome and immunohistochemical and molecular evidences, shared by FCD type II + EATs and EATs, suggest a common pathogenic link. The choice to create a specific unifying class or, on the contrary, to also include “associated FCD type II” in the definition of the new unifying class FCD type III should be further discussed.
Abnormal maturation and differentiation of neocortical neurons in epileptogenic cortical malformation: Unique distribution of layer-specific marker cells of focal cortical dysplasia and hemimegalencephaly
2012, Brain Research
Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are major causes of intractable epilepsy in children. The probable pathogenesis of FCD and HMG is the abnormal migration and differentiation of neurons. The aim of the present study was to clarify the abnormal cytoarchitecture, based on neuronal immaturation. Tissue samples were obtained from 16 FCD and seven HME patients, aged between 2 months and 12 years, who had been diagnosed as typical FCD and HME, following surgical treatment for intractable epilepsy. Paraffin-embedded sections were stained with the antibodies of three layer-markers that are usually present only during the fetal period, namely SATB2 (expressed in the upper layer of the normal fetal neocortex), FOXP1 (expressed in the 5th layer), and TBR1 (expressed in the 6th layer). In FCD, SATB2-positive (+) cells located in the middle and deep regions of FCD Ia and Ib, but only in the superficial region of FCD IIa and IIb. FOXP1+ cells diffusely located in the neocortex, especially the upper layer of FCD IIa and IIb. TBR1+ cells mainly located in the middle and deep regions, and also white matter. In FCD IIb, TBR1+ cells were in the superficial region. In HME, SATB2+ and FOXP1+ cells were found diffusely. TBR1+ cells were in the middle and deep regions. On the basis of continued expression of fetal cortical layer-specific markers in FCD and HME brains, the abnormal neocortical formation in both is likely to be the result of disrupted neuronal migration and dysmaturation. The expression pattern is different between FCD and HME.
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Decreased glutamate transport enhances excitability in a rat model of cortical dysplasia
2008, Neurobiology of Disease
Citation Excerpt :
Cortical dysplasia is associated with disruption of normal cortical cytoarchitecture and is often observed in pediatric epilepsy (Farrell et al., 1992; Mischel et al, 1995; Prayson et al., 1995).
Glutamate transporters function to maintain low levels of extracellular glutamate and play an important role in synaptic transmission at many synapses. Disruption of glutamate transporter function or expression can result in increased extracellular glutamate levels. Alterations in glutamate transporter expression have been reported in human epilepsy and animal seizure models. Functional electrophysiological changes that occur when transporter expression is disrupted in chronic epilepsy models have not been examined. Here, we used a freeze-induced model of cortical dysplasia to test the role of glutamate transporters in synaptic hyperexcitability. We report that inhibiting glutamate transporters with the non-selective antagonist, dl-threo-β-benzylozyaspartic acid (TBOA) preferentially prolongs postsynaptic currents (PSCs) and decreases the threshold for evoking epileptiform activity in lesioned compared to control cortex. The effect of inhibiting uptake is mediated primarily by the glia glutamate transporter (GLT-1) since the selective antagonist dihydrokainate (DHK) mimicked the effects of TBOA. The effect of uptake inhibition is mediated by activation of N-methyl-d-aspartate (NMDA) receptors since d-(−)-2-amino-5-phosphonovaleric acid (APV) prevents TBOA-induced effects. Neurons in lesioned cortex also have a larger tonic NMDA current. These results indicate that chronic changes in glutamate transporters and NMDA receptors contribute to hyperexcitability in cortical dysplasia.

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^☆: Presented in part at the United States and Canadian Academy of Pathology, International Academy of Pathology 82nd Annual Meeting, Chicago, Illinois, March 1993.

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Original contributionCortical dysplasia: A histopathologic study of 52 cases of partial lobectomy in patients with epilepsy☆

Abstract

Dev Brain Res

Prog Brain Res

Surg Neurol

Epilepsy due to focal cortical dysplasia with macrogyria and the forme fruste of tuberous sclerosis: A study of 15 patients

The neuropathology of temporal lobe epilepsy

J Neuropathol Exp Neurol

Marginal glioneural heterotopias of the central nervous system

Acta Pathol Microbiol Scand

An inherited syndrome with mental deficiency and endocrine disorder

Radial neuronal assemblies, ectopia and necrosis of developing cortex: A case analysis

Acta Neuropathol (Berl)

Microgyria

J Pathol Bacteriol

Pachygyria

J Pathol Bacteriol

Large defects in cerebral hemispheres associated with cortical dysgenesis

J Neuropathol Exp Neurol

Migration of neuroblasts through partial necrosis of the cerebral cortex in newborn rats

Dysplasias of the cortex, in Developmental Neuropathology

Microdysgenesis in resected temporal neocortex: Incidence and clinical significance in focal epilepsy

Neurol

On finding striated muscle in the brain

J Neurol Neurosurg Psychiatry

Agyria-Pachygyria (lissencephaly syndrome)

Neuropadiatrie

Generalized cortical dysplasia manifested by diffusely thick cerebral cortex

Arch Neurol

Pathology of temporal lobe foci

Adv Neurol

The density of dystrophic neurons in the white matter of the gyrus frontalis inferior in epilepsies

J Neurol

Neuropathological findings in primary generalized epilepsy: A study of eight cases

Epilepsia

The significance of microdysgenesia in primary generalized epilepsy: An answer to the considerations of Lyon and Gastaut

Epilepsia

Epilepsy

Tumors of the Central Nervous System

Dysgenetic syndromes (phacomatoses) associated with tumours and hamartomas of the nervous system, in, Pathology of Tumours of the Nervous System

Focal dysplasia of the cerebral cortex in epilepsy

J Neurol Neurosurg Psychiatry

Disorders of cerebral migration

Can J Neurol Sci

Neuropathological findings following temporal lobectomy related to surface and deep EEG patterns

Epilepsia

Original contribution
Cortical dysplasia: A histopathologic study of 52 cases of partial lobectomy in patients with epilepsy☆