Architectural (Type IA) Focal Cortical Dysplasia and Parvalbumin Immunostaining in Temporal Lobe Epilepsy

Abstract

Summary:Purpose: We analyzed 26 surgically treated patients operated on for intractable epilepsy associated with type IA (architectural) cortical dysplasia, to investigate neuropathologic and immunocytochemical features, particularly of the γ -aminobutyric acid (GABA)ergic system, and to compare the findings with those observed in normal cortex.Methods:. Routinely stained slides and serial sections immunostained for neurofilaments (SMI 311), microtubuleassociated protein-2 (MAP-2), neuron-specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), parvalbumin (PV), calbindin (CB), and calretinin (CR) were processed. Some sections were processed by using single-immunoperoxidase procedures; others were processed for double immunofluorescence labelling and observed by confocal microscopy. The density of inhibitory PV-immunoreactive interneurons was quantitatively assessed in all patients and control cases by using a two-dimensional cell-counting technique on PV immunostained sections.Results: The density of PV-immunoreactive interneurons was significantly reduced in this group of patients, whereas CB-and CR-positivity appeared similar to those in normal cortex. In five cases, architectural abnormalities, in addition to those that defined type 1A dysplasia, were present and characterized by abnormal clusters of neurons and laminar cellular loss in superficial cortical laminate.Conclusions: The reduction of PV expression in type IA cortical dysplasia suggests an impairment of the GABAergic system as a possible mechanism for the epileptogenicity; in addition, PV immunoreactivity can be helpful in the neuropathologic characterization of this form of cortical dysplasia. Key Words: Temporal lobe epilepsy-ParvalbuminImmunocytochemistry.Focal cortical dysplasias (FCDs) result from a disturbance in cortical development and are characterized by focal anomalies of cortical structure. Such malformations are often associated with intractable epilepsy (1), and some of the affected patients are referred for surgical treatment. Some forms of FCD have been clearly defined (2) and, particularly the type IA (architectural) cortical dysplasia, represent an increasingly recognized cause of temporal lobe epilepsy (3). Neuronal hyperexcitability is attributed to lack of balanced excitatory and inhibitory mechanisms (4). Neuropathologic findings suggest that alterations of the γ -aminobutyric acid (GABA)ergic (inhibitory) cortical neuronal system play a role in focal epilepsies secondary to cor-

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…Downregulation of several GABA A R subunits, as well as a reduction in the number of inhibitory cells, has been shown in FCD, supporting the impairment of GABAergic inhibition [107,[156][157][158][159]. In addition, electrophysiological studies performed in brain slices from FCD tissue show immature GABA receptor-mediated responses, and GABA receptormediated synchronization appears to be involved in the mechanism leading to in vitro ictal activity in FCD [147,148,160].…”

“…Histopathologically, FCD type III subtypes are often characterized by alterations in cortical dyslamination similar to those described in FCD type I. However, a distinct pattern can be identified in FCD type IIIa, consisting of an abnormal band of small and clustered "granular" neurons in the outer part of layer II [107][108][109]. Recent data indicate a reduction of myelinated axons in the white matter of FCD type II rather than dysmyelination as the primary pathologic process underlying the white matter abnormalities observed in this FCD type [110].…”

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

“…Interneuron-related disorders may arise when cortical development goes awry (Levitt et al, 2004;Di Cristo, 2007). An aberrant number and/or distribution of specific subsets of cortical interneurons have been linked to several major neurological disorders, including epilepsy (Powell et al, 2003;Garbelli et al, 2006), schizophrenia (Reynolds et al, 2002;Lewis et al, 2005;Daskalakis et al, 2007), and depression (Rajkowska et al, 2007). In a rat model of fetal alcohol syndrome, one outcome of ethanol exposure during the first postnatal week is an increase in the number of cortical calretinin-IR neurons in the adult (Granato, 2006).…”

“…The heterogeneity of cortical interneuron morphology and neurochemistry presents a complex, incompletely understood picture of neural development (Wonders and Anderson, 2006). Moreover, cortical interneuron dysfunction has been implicated in several neurological disorders with developmental origins (Levitt et al, 2004;Di Cristo, 2007), including epilepsy (Powell et al, 2003;Garbelli et al, 2006), schizophrenia (Reynolds et al, 2002;Lewis et al, 2005;Daskalakis et al, 2007), and depression (Rajkowska et al, 2007). The current study examined a subpopulation of rat cortical interneurons that produced tyrosine hydroxylase (TH), the first, rate-limiting catecholaminergic enzyme.…”

Epileptic baboons have lower numbers of neurons in specific areas of cortex

“…1-6), and partial epilepsies (i.e., seizures originating from a brain region) may lead to loss of neurons (7) and altered connectivity (8). The cerebral cortex is a heterogeneous structure comprised of multiple sensory and motor information-processing systems (e.g., refs.…”