Cortical Dysplasia: Electroclinical, Imaging, and Neuropathologic Study of 13 Patients

Abstract

Summary:Purpose: The aim of this study was to correlate the electroclinical and radiologic data with the neuropathologic findings and surgical outcome in epileptic patients with epilepsy and Taylor's focal cortical dysplasia (TFCD) and to characterize further the abnormal intermediate filaments expression in the balloon cell present in the peculiar dysplasia.Methods: We retrospectively selected 13 TFCD patients who underwent surgery for intractable epilepsy with the aim of removing the magnetic resonance (MR)-detectable lesion and/or the epileptogenic zone defined by stereoelectroencephalographic recordings. The surgical specimens were analyzed by means of routine neuropathologic and immunocytochemical studies. Antisera against different intermediate filaments also were used in serial adjacent sections to evaluate their coexpression in balloon cells.Results: Histopathologic abnormalities typical of TFCD were found not only within the MR-visible lesions but also in most of the epileptogenic zones with no MR signal alterations. Furthermore, the MR-visible lesions contained a high proportion of cells with an abnormal expression of intermediate filament proteins. After a long follow-up, 10 of the patients are now seizure free. Conclusions: Our findings indicate that highly epileptogenic zones may correspond to tissue alterations not revealed by neuroimaging. Furthermore, the immunocytochemical data show that the dysplastic tissue detected by MR contained high concentrations of cells filled with abnormal intermediate filaments.The detected colocalization of neuronal and glial markers in balloon cells indicates a failure of cellular commitment during development.

Pediatric Cortical Dysplasia: Correlations between Neuroimaging, Electrophysiology and Location of Cytomegalic Neurons and Balloon Cells and Glutamate/GABA Synaptic Circuits

“…For example, interictal and ictal epileptiform EEG and MEG activity has been associated with CD structural lesions as assessed by MRI that contained cytomegalic neurons and balloon cells [Colombo et al, 2003;Morioka et al, 1999;Palmini et al, 1995;Tassi et al, 2002;Urbach et al, 2002;Usui et al, 2001]. In addition, interictal and ictal epileptic discharges observed with acute or chronic intracranial electrode recordings have been associated with the presence of cytomegalic and balloon cells in the pathologic specimen near the recording site, and authors have reported better postsurgery seizure control in CD patients if surgical specimens contained balloon cells compared with cases without these cells [Boonyapisit et al, 2003;Chassoux et al, 2000;Colombo et al, 2003;Rosenow et al, 1998;Tassi et al, 2001]. Furthermore, previous in vitro studies on adult CD tissue have shown that application of the convulsant drug, 4-aminopyridine, can induce seizure-like discharges in the slice involving glutamate and GABA receptormediated mechanisms [Avoli et al, 1999;D'Antuono et al, 2004;Mattia et al, 1995].…”

“…Due to their dramatic cytologic abnormalities, balloon cells and cytomegalic neurons have been proposed as candidate 'epileptic' cells possibly acting as 'pacemakers' capable of spontaneous depolarizations that would drive local neurons and circuits into seizures [Schwartzkroin and Walsh, 2000]. This hypothesis is supported by circumstantial anatomic and correlative electrocorticography (ECoG) studies demonstrating an association between the presence of dysmorphic cells with interictal and ictal abnormalities in CD patients [Boonyapisit et al, 2003;Palmini, 2000;Rosenow et al, 1998;Spreafico et al, 1998;Tassi et al, 2001]. Similarly, in CD tissue investigators have noted a qualitative reduction in GABAergic neurons and changes in the coassembly of AMPA, NMDA and GABA A receptor subunits in and around human dysplastic lesions, suggesting the possibility of enhanced excitation and partial loss of inhibition leading to seizures [Crino et al, 2001;Kerfoot et al, 1999;Mikuni et al, 1999;Najm et al, 2000;Ying et al, 1998].…”

Metabolic characteristics of cortical malformations causing epilepsy

“…Several electrophysiological and neurohistochemical studies have shown that some CM can possess an intrinsic epileptogenicity [22]. Furthermore, subtle histological and electrophysiological disturbances are sometimes also found in normal appearing tissue surrounding the MRI visible malformation [29]. 1 H MR spectroscopy (MRS) is able to identify the neuronal dysfunction/neuron loss associated with epileptic activity by a reduction of the neuronal marker N-acetylaspartate (NAA) [30] even in the absence of structural abnormalities on MRI [11].…”

Focal cortical dysplasia: a review of pathological features, genetics, and surgical outcome

“…Many of these cells are immunopositive for vimentin, and others are immunopositive for glial fibrillary acidic protein, neuron-specific enolase, microtubule-associated protein, or neuronal-specific nuclear protein. 42,44,45,48 …”