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Focal Cortical Dysplasia (focal + cortical_dysplasia)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Intraoperative Ultrasound to Define Focal Cortical Dysplasia in Epilepsy Surgery

EPILEPSIA, Issue 1 2008
Dorothea Miller
Summary Focal cortical dyplasia (FCD) is a frequent cause of medication-resistant focal epilepsy. Patients with FCD may benefit from epilepsy surgery. However, it is difficult to intraoperatively define lesion boundaries. In this case report we present a novel tool to identify FCD intraoperatively. A patient with frontal lobe epilepsy underwent resection of a left frontomesial FCD. Image guidance was achieved by intraoperative ultrasound, which depicted the lesion with a higher resolution than preoperative MRI. Postoperatively the patient remained seizure free. Intraoperative ultrasound may be helpful in identifying and targeting subtle epileptogenic lesions, which are difficult to visualize. [source]

Neuroradiologic Findings in Focal Cortical Dysplasia: Histologic Correlation with Surgically Resected Specimens

EPILEPSIA, Issue 2001
Kazumi Matsuda
Summary: ,Purpose: We investigated the neuroradiologic characteristics of focal findings of surgically resected specimens obtained from 47 patients with focal cortical dysplasia (FCD). Methods: Forty cases were detected by magnetic resonance imaging (MRI), and two cases were detected only by single-photon emission computed tomography (SPECT), but five cases could not be detected before operation. Results: MRI revealed abnormal gyri and sulci in 34 patients (pachygyric in 18, polymicrogyric in 10, both in six), and blurring of the gray matter,white matter junction in 29 (72%) patients. Signal abnormalities were found in 36 (90%) patients, in the gray matter in 32, with white matter in 30, and at the gray matter,white matter junction in 13. Moreover, peculiar patterns of abnormal signals in the white matter were recognized, including remarkably abnormal subcortical signals of T2 hyperintensity and T1 hypointensity adjacent to the dysplastic cortex in 15 cases, high radiated T2 signals extending from the ependymal surface of the lateral ventricle to the overlying cortex in 11 cases, and widespread abnormal signals in the white matter with gray matter involvement in four cases. Histologically, these abnormal signals corresponded to various degrees of dyslamination and morphologic abnormalities of neurons and glial cells in the gray matter, and to dysmyelination, ectopic clustering of dysplastic neurons, glial proliferation, and necrotic change in the white matter. Regional cerebral blood flow SPECT showed interictal hypoperfusion in 29 (62%) of the 47 patients, interictal hyperperfusion in two, and ictal hyperperfusion in 28 of the 34 patients associated with FCD. [123I]iomazenil SPECT demonstrating the distribution of central benzodiazepine receptors showed low accumulations localized spatially corresponding to the epileptogenic foci associated with FCD in seven of eight patients. Conclusions: These results demonstrate that neuroimaging reflects various structural and functional changes closely related to epileptogenesis in FCD. [source]

Focal Cortical Dysplasia: Improving Diagnosis and Localization With Magnetic Resonance Imaging Multiplanar and Curvilinear Reconstruction

JOURNAL OF NEUROIMAGING, Issue 3 2002
Maria Augusta Montenegro MD
ABSTRACT Objective. To establish the contribution of multiplanar reconstruction (MPR) and curvilinear reformatting (CR) to the MRI investigation of focal cortical dysplasia (FCD). Methods. From a group of patients with intractable frontal lobe epilepsy, we selected patients with neuroimaging diagnosis of FCD. The diagnosis of FCD was based on the neuroimaging findings after a three step evaluation, always in the same order: (a) plain MRI films, (b) MPR, and (c) CR. After the selection of patients, the process of reviewing all the images in the three stages described above was performed by one of us, who did not take part on the selection of patients nor on the initial evaluation, and who was blind to the clinical and EEG findings of the patients. For data analysis, we first assessed the contribution of the additional findings of MPR analysis compared to the results of the evaluation using only plain MRI films, as is usually done in routine practice. Second, we assessed the contribution of CR to the findings of plain MRI films plus MPR. After completing the multistep evaluation, we all went back to review the plain MRI films with knowledge of lesion topography, in order to identify possible subtle features associated with FCD. Results. Seventeen patients met the inclusion criteria. Twelve had imaging diagnosis of FCD and were included in the second step of this project. Plain films of high resolution MRI showed the lesion in 6 (50%) of the 12 patients. By adding MPR to the plain MRI films, we identified lesions in all 12 patients. Furthermore, we found that MPR provided a better lesion localization and ascertainment of its relationship to other cerebral structures in 5 of 6 (83%) patients who had a lesion identified on plain films. By adding CR to the plain MRI films plus MPR analysis, we observed that (a) CR also allowed the identification of the dysplastic lesion in all patients, (b) CR improved lesion localization in one patient, and (c) CR provided a better visualization of the lesion extent in 4 patients (33%), showed a larger lesion in 3, and demonstrated that part of the area suspected as abnormal was more likely volume averaging in 2. Conclusion. MPR and CR analysis add to the neuroimaging evaluation of FCD by improving the lesion diagnosis and localization. CR helps to establish the extent of the lesion more precisely, allowing the visualization of some areas not shown on high resolution MRI and MPR. These techniques are complementary and do not replace the conventional wisdom of MRI analysis. [source]

Neuronal migration disorders: clinical, neuroradiologic and genetics aspects

ACTA PAEDIATRICA, Issue 3 2009
Alberto Spalice
Disorders of neuronal migration are a heterogeneous group of disorders of nervous system development. One of the most frequent disorders is lissencephaly, characterized by a paucity of normal gyri and sulci resulting in a ,smooth brain'. There are two pathologic subtypes: classical and cobblestone. Six different genes could be responsible for this entity (LIS1, DCX, TUBA1A, VLDLR, ARX, RELN), although co-delection of YWHAE gene with LIS1 could result in Miller,Dieker Syndrome. Heterotopia is defined as a cluster of normal neurons in abnormal locations, and divided into three main groups: periventricular nodular heterotopia, subcortical heterotopia and marginal glioneural heterotopia. Genetically, heterotopia is related to Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2) genes mutations. Polymicrogyria is described as an augmentation of small circonvolutions separated by shallow enlarged sulci; bilateral frontoparietal form is characterized by bilateral, symmetric polymicrogyria in the frontoparietal regions. Bilateral perisylvian polymicrogyria results in a clinical syndrome manifested by mild mental retardation, epilepsy and pseudobulbar palsy. Gene mutations linked to this disorder are SRPX2, PAX6, TBR2, KIAA1279, RAB3GAP1 and COL18A1. Schizencephaly, consisting in a cleft of cerebral hemisphere connecting extra-axial subaracnoid spaces and ventricles, is another important disorder of neuronal migration whose clinical characteristics are extremely variable. EMX2 gene could be implicated in its genesis. Focal cortical dysplasia is characterized by three different types of altered cortical laminations, and represents one of most severe cause of epilepsy in children. TSC1 gene could play a role in its etiology. Conclusion: This review reports the main clinical, genetical and neuroradiological aspects of these disorders. It is hoped that accumulating data of the development mechanisms underlying the expanded network formation in the brain will lead to the development of therapeutic options for neuronal migration disorders. [source]

Epilepsy with dual pathology: Surgical treatment of cortical dysplasia accompanied by hippocampal sclerosis

EPILEPSIA, Issue 8 2010
Dong W. Kim
Summary Purpose:, The presence of two or more epileptogenic pathologies in patients with epilepsy is often observed, and the coexistence of focal cortical dysplasia (FCD) with hippocampal sclerosis (HS) is one of the most frequent clinical presentations. Although surgical resection has been an important treatment for patients with refractory epilepsy associated with FCD, there are few studies on the surgical treatment of FCD accompanied by HS, and treatment by resection of both neocortical dysplastic tissue and hippocampus is still controversial. Methods:, We retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with the pathologic diagnosis of FCD and the radiologic evidence of HS. We evaluated the prognostic roles of clinical factors, various diagnostic modalities, surgical procedures, and the severity of pathology. Results:, A total of 40 patients were included, and only 35.0% of patients became seizure free. Complete resection of the epileptogenic area (p = 0.02), and the presence of dysmorphic neurons or balloon cells on histopathology (p = 0.01) were associated with favorable surgical outcomes. Patients who underwent hippocampal resection were more likely to have a favorable surgical outcome (p = 0.02). Conclusions:, We show that patients with complete resection of epileptogenic area, the presence of dysmorphic neurons or balloon cells on histopathology, or resection of hippocampus have a higher chance of a favorable surgical outcome. We believe that this observation is useful in planning of surgical procedures and predicting the prognoses of individual patients with FCD patients accompanied by HS. [source]

Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development)

EPILEPSIA, Issue 12 2009
Wendy A. Chamberlain
Summary Purpose:, Malformations of cortical development (MCD) (cortical dysplasias) are well-recognized causes of intractable epilepsy. Although a histologic classification system for MCD has been proposed by Palmini et al. (Neurology; 2004; 62:S2), studies to date have not assessed reproducibility. The purpose of this study was to analyze inter- and intraobserver agreement among eight experienced neuropathologists (NPs) with respect to this classification system. Methods:, Sections from 26 epilepsy resections were selected to represent the range of pathologies described by Palmini et al. Recuts of single sections from each case were sent to the NPs to classify. The slides were resent at a later date for reclassification. Kappa analysis for both inter- and intraobserver concordance was performed. Results:, Interobserver agreement was moderate (, = 0.4968). There was ,62.5% (5 of 8 NPs) agreement for 19 of 26 cases. The greatest concordance was present when making focal cortical dysplasia (FCD) types IIA/B classifications (12 of the 14 cases with ,75% consensus). Mild MCD (types I/II) and FCD types IA/B classifications were the least reproducible, and used most frequently in cases without consensus. Intraobserver concordance was moderate to very good (range , = 0.4654,0.8504). The category with the fewest classification changes made on reevaluation was FCD type IIB (4.2%), whereas that with the most changes was mild MCD (types I/II) (52.9%). Discussion:, Interobserver concordance using this approach was moderate. The classification categories with the greatest concordance were FCD type IIA/B, and the least, mild MCD and FCD types IA/B. In addition, difficulty in differentiating Mild MCD/FCD type I lesions from normal and/or gliotic tissue was noted. [source]

Mechanisms of Epileptogenesis in Tuberous Sclerosis Complex and Related Malformations of Cortical Development with Abnormal Glioneuronal Proliferation

EPILEPSIA, Issue 1 2008
Michael Wong
Summary Malformations of cortical development (MCDs) are increasingly recognized as causes of medically intractable epilepsy. In order to develop more effective, rational therapies for refractory epilepsy related to MCDs, it is important to achieve a better understanding of the underlying mechanisms of epileptogenesis, but this is complicated by the wide variety of different radiographic, histopathological, and molecular features of these disorders. A subset of MCDs share a number of characteristic cellular and molecular abnormalities due to early defects in neuronal and glial proliferation and differentiation and have a particularly high incidence of epilepsy, suggesting that this category of MCDs with abnormal glioneuronal proliferation may also share a common set of primary mechanisms of epileptogenesis. This review critically analyzes both clinical and basic science evidence for overlapping mechanisms of epileptogenesis in this group of disorders, focusing on tuberous sclerosis complex, focal cortical dysplasia with balloon cells, and gangliogliomas. Specifically, the role of lesional versus perilesional regions, circuit versus cellular/molecular defects, and nonneuronal factors, such as astrocytes, in contributing to epileptogenesis in these MCDs is examined. An improved understanding of these various factors involved in epileptogenesis has direct clinical implications for optimizing current treatments or developing novel therapeutic approaches for epilepsy in these disorders. [source]

Symptomatic Epilepsies Imitating Idiopathic Generalized Epilepsies

EPILEPSIA, Issue 2005
Hirokazu Oguni
Summary:, The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1,4 years of age at times imitate epilepsy with myoclonic-astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs. [source]

Operative Results without Invasive Monitoring in Patients with Frontal Lobe Epileptogenic Lesions

EPILEPSIA, Issue 10 2001
A. Mariottini
Summary: ,Purpose: To further explore the still controversial issues regarding whether all or most candidates for epilepsy surgery should be investigated preoperatively with invasive long-term video-EEG monitoring techniques (ILTVE). Methods: We studied five patients with intractable seizures since early childhood using the same protocol: clinical evaluation, magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery (FLAIR) sequences, long-term video-EEG (LTVE) monitoring with scalp electroencephalogram (EEG), interictal single photon emission computed tomography (SPECT), positron emission tomography (PET), and neuropsychological testing. The patients' seizures had clinical features suggesting a frontal lobe (FL) origin. MRI scans revealed focal cortical dysplasia (CD) in four patients and a probable gliotic lesion in the fifth. The findings in both PET and SPECT images were congruent with those of the MRI. Scalp LTVE failed to localize the ictal onset, although the data exhibited features suggestive of both CDs and FL seizures. On the basis of these results, surgery was performed with intraoperative corticography, and the cortical area exhibiting the greatest degree of spiking was ablated. Results: Histopathologic study of four of the resected specimens confirmed the presence of CD, whereas in the fifth, there were features consistent with a remote encephaloclastic lesion. There were no postoperative deficits. Seizures in three of the patients were completely controlled at 2,3.5 years of follow-up; a fourth patient is still having a few seizures, which have required reinstitution of pharmacotherapy, and the fifth has obtained 70% control. All patients have had significant improvement in psychosocial measures. For comparison, five patients with generally similar clinical and neuroradiologic features to the previous group underwent preoperative ILTVE monitoring. The surgical outcomes between the two groups have not differed significantly. Conclusions: We conclude that patients with FL epilepsies may be able to undergo successful surgery without preoperative ILTVE monitoring, provided there is high concordance between neuroimaging tests (MRI, SPECT, PET) and the seizure phenotypes, even when routine EEGs and scalp LVTE fail to localize ictal onset unambiguously. The surgical outcomes of these patients generally paralleled those of the other subjects who also had FL epilepsy but who were operated on only after standard ILTVE monitoring. [source]

Neuroradiologic Findings in Focal Cortical Dysplasia: Histologic Correlation with Surgically Resected Specimens

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

EPILEPSIA, Issue 9 2001
Laura Tassi
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. [source]

Ictal Perfusion Changes During Occipital Lobe Seizures in Infancy: Report of Two Serial Ictal Observations

EPILEPSIA, Issue 2 2001
Andras Hollo
Summary: Serial-ictal single-photon-emission computed tomography (SPECT) examinations are presented in two infants (ages 1 and 2 years), with early ictal and ictal in one, and ictal and late ictal images in the other. Both had pharmacoresistant occipital epilepsy, due to focal cortical dysplasia. In the first case, size of ictal hyperperfusion increased in the course of the seizure from early ictal to ictal state. A concomitant ictal hypoperfusion was observed around the hyperperfused area. In the second patient, there was a dramatic difference between ictal and late ictal images. In the late ictal state, the previous occipital ictal hyperperfusion and extraoccipital ictal hypoperfusion disappeared, together with homolateral posterotemporal and contralateral occipital hyperperfusion, corresponding to seizure propagation. Ictal extratemporal blood-flow changes are therefore highly dynamic, particularly in very young children. [source]

Focal Cortical Dysplasia: Improving Diagnosis and Localization With Magnetic Resonance Imaging Multiplanar and Curvilinear Reconstruction

Expression of CD34 as a novel marker for glioneuronal lesions associated with chronic intractable epilepsy

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2006
P. Deb
The spectrum of glioneuronal lesions underlying intractable epilepsies includes malformative pathologies like focal cortical dysplasia (FCD); and neoplastic lesions like gangliogliomas (GG) and dysembryoplastic neuroepithelial tumours (DNT). These may occur either singly or as dual lesions, having simultaneous presence of both elements. Currently, the relationship between the malformative and neoplastic glioneuronal lesions is poorly understood. Recently, CD34, a stem cell marker transiently expressed during early neurulation, has been identified in these tumours. This study was undertaken to (i) evaluate the role of CD34 as a diagnostic marker for glioneuronal lesions of epilepsy, namely, GG, DNT and FCD, and (ii) attempt to define the relationship among these lesions, using CD34 as a marker. Tissues resected from 47 patients with intractable epilepsy due to glioneuronal lesions (GG, FCD, DNT) were studied. These were evaluated for CD34 expression, using immunohistochemistry. Dysplastic or atypically differentiated neural precursors which could not be identified on routine haematoxylin and eosin (H&E) staining were highlighted by CD34 immunostaining. The pattern of immunostaining was diffuse in GGs, unlike FCDs, wherein cells were present singly or in small clusters. However, cases of DNT and control tissue were largely CD34-immunonegative. Based on these findings, we propose a possible common origin of GG and FCD, from a bipotent precursor that undergoes abnormal glioneuronal development, while DNTs possibly have a different origin. The CD34-immunoreactive cells represent dysplastic or undifferentiated neural precursors, which may signify a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathologies in patients with intractable epilepsy. [source]

A Possible Role for Gap Junctions in Generation of Very Fast EEG Oscillations Preceding the Onset of, and Perhaps Initiating, Seizures

EPILEPSIA, Issue 2 2001
Roger D. Traub
Summary: ,Purpose: We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (>,70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. Methods: Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon,axon gap junctions between principal neurons, as supported by recent experimental data. Results: Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30,70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included. Conclusions: Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure-prone brain, but possibly also in normal brain. The anticonvulsant potential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered. [source]

VIQ-PIQ Discrepancies in Partial Epilepsy: On the Relation to Lat- eralities of Focal MRI Lesions, P3 Peaks, and Focal Spikes.

EPILEPSIA, Issue 2000
Osamu Kanazawa
Purpose: A number of previous ncurophysiological studies have indicated that the glutamatergic system is important in the induction of epileptiform activity and the dcvelopment of epileptogenesis. Clutamate transport is the primary mechanism of inactivation of syiiaptically released glutamate. GLAST is classified BS an astrocytic transporter and occurs in high concentrations in the ccrebcllum. The pathophysiologic rolc of GLAST in epilepsy is not known in detail. To investigate the role of thc astroglial glutamatc transporter GLAST in epileptogenesis, we compared amygdalu-kindling and pentylenctetrazolc (PTZ) induced seizures in GLAST-deficient mice (GLAST(-/-)) wild-type mice (GLAST(+/+)), and maternal C57Black6/J mice (C57). Purpose: Subtest IQ such as verbal IQ (VIQ) and performance IQ (PIQ) in WAIS or WISC are thought to represent neuropsychological functions of the left and right hemispheres, respectively. The P300 (P3) event-related potential reflects cognitive processes. We do not ye1 know the brain site of P3 origin or how epileptogenic foci (EF) influ- ence P3 potentials. To examine neuropsychological influence by partial epilepsy (PE), we studied VIQ-PIQ discrepancies in PE in relation to lateralities of focal MRI lesions, P3 peaks, and EF. Methods: Thirteen patients showed VIQ-PIQ discrepancies significant at the p7lt;O.O5 level, represented by a>l2-point spread for the WAIS in adults, and a 15-point spread in the WISC in children. We evoked P3 potentials in the individuals with discrepant IQ differences by asking them to keep a mental count of rare tones, including introduction of oddbail tones. EEGs were recorded by the international 10,20 system and P3 peaks were shown in a topographical view by offline analysis. Patients were divided into normal and abnormal groups according to MRI findings, and were examined for the laterali- ties of the dominant side in subtest IQ (conventionally, we regarded higher VIQ as left hemisphere dominant and higher PIQ as right hemisphere dominant), P3 peaks, and EF. We did not correlate results with lert or right handedness. Results: Five patients (38.5%) were in the normal group and 8 patients (61.5%) were in the abnormal group. Concordance of the lateralities in P3 peaks and dominant side in subtest IQ was shown in 1 patient (20%) in the normal group and 5 patients (62.5%) in the abnormal group. In the normal group, all patients showed contralateral P3 peak shift to EF, and all except I patient showed contralateral P3 peak shift to the dominant side in subtest IQ. The other 3 patients in the abnormal group showed unilateral focal cortical dysplasias (FCD), ipsilateral P3 shift, and contralateral dominant side in subtest IQ to the focal MRI lesions. Conclusion: In our partial epilepsy series with VIQ-PIQ discrepancies, concordance of the lateralities in P3 peaks and dominant side in subtest IQ was shown in < half of the patients. Epileptogenic foci seem to have 3 different grades of influence on P3 peak shift and dominant side in subtest IQ according to the severities of accompanying focal MRI lesions: 1. Without MRI lesions, EF can make P3 peak shift contralaterally, but the dominant side in the subtest IQ shift ipsilaterally; 2. With less severe focal MRI lesions such as hippocampal atrophy etc., EF can make not only P3 peaks but also the dominant side in the subtest IQ shift contralaterally; 3. With severe focal MRI lesions such as FCD, EF can make the dominant side in the subtest IQ shift contralaterally, but the P3 peak may shift ipsilaterally. Epileptogenic foci without MRI lesions seem to control ipsilateral P3 potentials. MRI lesions render a hemisphere unlikely to become dominant, but epileptogenic foci can coexist with apparently normal neuropsychological function. [source]

Mutational and expression analysis of CDK1, cyclinA2 and cyclinB1 in epilepsy-associated glioneuronal lesions

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2007
V. Schick
Gangliogliomas and focal cortical dysplasias (FCDs) constitute glioneuronal lesions, which are frequently encountered in biopsy specimens of patients with pharmacoresistant focal epilepsy and relate to impaired differentiation and migration of neural precursors. However, their molecular pathogenesis and relationship are still largely enigmatic. Recent data suggest several components of the insulin-pathway, including TSC1 and TSC2 mutated in tuberous sclerosis complex (TSC), to be altered in gangliogliomas and FCD with Taylor type balloon cells (FCDIIb). The proteins tuberin (TSC2) and hamartin (TSC1) constitute a tumour suppressor mechanism involved in cell-cycle control. Hamartin and/or tuberin were reported to colocalize and/or interact with CDK1, cyclinB1 and cyclinA2 that are critically involved in cell-size and cell-growth control. Here, we have carried out mutational and expression analyses of CDK1, cyclinB1 and cyclinA2 in gangliogliomas and FCDIIb. Mutational screening was performed by single-strand conformation polymorphism analysis in gangliogliomas (n = 20), FCDIIb (n = 35) and controls. CyclinB1 revealed a polymorphism (G to A, cDNA Position 966, GenBank: NM_031966) in exon 7 with similar frequencies in FCDIIb, gangliogliomas and control specimens (FCD n = 9/35; gangliogliomas n = 5/20; control n = 20/100). We used real-time reverse transcription polymerase chain reaction to determine expression levels of CDK1, cyclinB1 and cyclinA2 in 10 FCDIIb and nine gangliogliomas compared with unaffected adjacent control tissue of the same patients. We observed significantly lower expression of CDK1 and cyclinA2 in FCDIIb vs. controls whereas no significant expression differences were present for CDK1, cyclinB1 and cyclinA2 in gangliogliomas. Our data strongly argue against mutational events of CDK1, cyclinB1 and cyclinA2 to play a role in gangliogliomas or FCDIIb. However, a potential functional significance of lower expression for the cell-size and cell-cycle regulators CDK1 and cyclinA2 in FCDIIb composed of large dysplastic neurones and balloon cells needs to be further resolved. [source]