CONACyT Vol. 19, issue. 2 (march-april 2018)

Rev Mex Neuroci ahora en Revista Mexicana de Neurociencia Publicación oficial de la Academia Mexicana de Neurología A.C. Revista Mexicana de Neurociencia; 19,2 (2018):86-98 Mexicana Revista

Órgano Oficial de Difusión de la AMN Academia Mexicana de www.revmexneuroci.com / ISSN 1665-5044 Neurología, A.C. 86 Review due to type IIIa dysplasia

Review

René Andrade-Machado,1 due to type IIIa Lina Salazar-Peláez.2 dysplasia. What do we know about this ? 1Neurologist, Epileptologist, Master in Psychology. PhD in Health Sciences, Epilepsia del lóbulo temporal por displasia tipo IIIa. ¿Qué sabemos de Neuropathology Area, CES University. esta entidad? 2PhD in Microbiology, Molecular Biology, Department of Health, CES University. Abstract

In this article we analyze whether there are clinical, radiological and histological findings of temporal lobe epilepsy caused by focal cortical dysplasia type IIIa and with these contribute to its clinical diagnosis. We performed a search in Pubmed and Medline with the following Mesh terms: dysplasia type IIIa, dysplasia type I, dysplasia type I and temporal lobe epilepsy, hippocampal sclerosis and dysplasia type I, reelin, filtered from 2010 to 2017. We considered letters tothe editors, clinical observations, descriptive studies, cases and controls, prospective or retrospective studies, but in which the histological studies were published. We found that mesial temporal lobe epilepsy caused by focal cortical dysplasia type IIIa may be a specific disease with its own clinical, radiological findings and prognostic features. Keywords Perhaps it better individualization will depend on the contributions Malformation of cortical of molecular studies aiming to studying the impact of cell signaling development, cortical dysplasia, pathway abnormalities, which would determine, both the death of Epilepsy, Temporal Lobe, hippocampal and the dispersion of the cells as hippocampal Sclerosis, reelin well as the abnormal neuronal migration with the consequent cortical protein. dislamination, abnormal neurons polarization and final position.

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 Review 87 Temporal lobe epilepsy due to type IIIa dysplasia

Resumen

En este artículo se analiza si existen características clínicas, imagenológicos e histológicas de la epilepsia del lóbulo temporal causada por displasia tipo IIIa y con ello contribuir a incrementar su sospecha clínica. Realizamos una búsqueda en Pubmed y Medline con los siguientes descriptores, Mesh: displasia tipo IIIa, displasia tipo I, displasia tipo I y epilepsia del Lóbulo temporal, esclerosis del hipocampo y displasia tipo I, reelin desde el 2010 hasta el 2017. Se consideraron cartas al editor, comentarios clínicos, estudios descriptivos, casos y controles, prospectivos o retrospectivos, los estudios deberían contener un reporte patológico. Las crisis en pacientes con displasia tipo IIIa debutan en la segunda década de la vida, con frecuencia existen antecedentes de crisis febriles, los estudios de IRM muestran una pobre diferenciación de la interfase sustancia gris sustancia blanca, ausencia de banda de sustancia blanca que separa la amígdala de la corteza entorrinal y los estudios histológicos muestran pérdida de la normal laminación cortical de las capas II, III y IV, con agrupaciones de neuronas heterotópicas en sustancia blanca. Estos hallazgos permiten considerarla una entidad nosológica con identidad propia. Aunque su mejor caracterización Palabras clave dependerá de los aportes de los estudios moleculares encaminados a Malformación del desarrollo estudiar el impacto de las vías de señalización celular, que determinan cortical, displasia cortical, por una parte, la muerte de neuronas hipocampales y la dispersión del epilepsia, lóbulo temporal, giro dentado y por otra, las alteraciones en la migración neuronal y de esclerosis hipocampal, proteína la estructura de la neocorteza. reelina.

Corresponding author: René Andrade-Machado. Neurólogo-Epileptólogo, Neuroclínica SA. Programa de doctorado en Ciencias de La Salud, área de Profundización Neuropatología, Universidad CES, Cl. 10 #22 - 04, Medellín, Antioquia, Colombia. Phone: +57 4 4440555. E-mail: [email protected]

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 88 Review Temporal lobe epilepsy due to type IIIa dysplasia

Introduction Methodology

Focal cortical dysplasia (FCD) is characterized A PubMed and Medline search was performed by disorganization and structural alteration of with the following descriptors: the cerebral cortex due to alterations in cell proliferation, differentiation, and migration during Mesh: dysplasia type IIIa, dysplasia type I, dysplasia cortical development.1 Its presence is associated type I and temporal lobe epilepsy, hippocampal with a high risk of drug-resistant epilepsy in children sclerosis, dysplasia type I and reelin. Published in and adults and postsurgical relapses.2-4 FCD can English or Spanish in the years from 2010 to 2017 appear at any location in the neocortex. It used due to the fact that the ILAE classification proposal to be classified as a dual pathology when located was published in 2010. We did not limit the type specifically in the temporal lobe, which occurred in of article, we considered letters to the editor, about 50% of patients with hippocampal sclerosis clinical comments, descriptive studies, cases and (HS). The clinical importance of this association controls, prospective and retrospective, as long as led to the introduction of the term FCD type IIIa in the histological results were published. Duplicate the International League Against Epilepsy’s (ILAE) cases were excluded. latest revision of the FCD classification.2 The results of the search can be seen in Figure 1. Dysplasia type IIIa is known as mesial temporal sclerosis, defined as neuronal loss and gliosis in the associated with irregularities of the Temporal lobe epilepsy caused temporal cortical lamination and the presence of by dysplasia type iiia neurons with neurofilament protein accumulation 2 in layers II, III, and IV, called hypertrophic neurons. Frequency However, the causal relationship between FCD type IIIa is a disorder whose frequency is FCD and HS remains unknown, as well as the yet to be defined. The study by Jiang Wu et al. etiopathogenesis. reported that FCD type IIIa was present in 60.8% of patients.3 Laura Tassi et al. found in 2010 that We have not found any review that shows the 69% of patients had this type of dysplasia.4 The clinical, imaging, and electrographic characteristics frequency of dysplasia type IIIa does not seem to or a pathogenic approach of this disease. Are be as high as initially thought but is present around there clinical, electroencephalographic, or imaging 16% of cases. This is because the histological elements that could make us suspect the presence criteria are not yet well defined.5 This wide range in of dysplasia type IIIa and determine what we know frequency could also depend on the lack of clinical of its pathogenesis? Answering this question could suspicion, the absence of reliable markers, and the have an impact on the decisions of the epilepsy inherent biases of retrospective studies. surgery groups, on the recognition of the disease, and on the approach of molecular studies aimed at finding markers of the disease or new therapeutic Onset age targets. FCD type IIIa is expressed by epileptic seizures with a greater incidence in the second decade of life. Its mean evolution time is 19.2 years [median 17 years with a range between one year and 50 years of age]. This time is significantly longer than the time of evolution of isolated FCD crises but earlier than FCD type IIIc [median 31, range 4-46]. Figure 2 is constructed from the descriptions

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 Review 89 Temporal lobe epilepsy due to type IIIa dysplasia

Figure 1. Evaluation of the evidence.

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20 ie 22 ie ecle aale wih he ecripr cae repr wih hilical ie cae a crl ae uie an conro 8 ecripive ie cliical characeriai cliical cmmearie 21 wih pe a 6 he paie 81 wih pe a 0 wih pe a 18 ce epilep 29 wih pe a 9 empral le 2 wih pe a 1 21 wih pe a 9 ha plaia pe wih wih pe a 12 ae repr: 2 cmme reari a relaihip 2 amil memer wih plaia ecripive ie ewee hil a pp evli pe a, wih crl 1 cae aciae wih 1 wih pe a 1 cmme repri a Neurofibromatosis type I, 8 wih pe a 8 epilepic ae pp 1 case with histological findings 0 wih pe a 0 aciae wih phlale epi rer i a paie wih pe a oa cae anae n of several studies which compared the time of be an index of suspicion of the syndrome, although evolution of associated with different more prospective studies are needed to consider types of dysplasia.3,6–9 We know that the time of this a key element in the diagnosis. We hope that, evolution depends on the moment in which the with the application of this classification, the next patients were operated on. This could depend on studies will provide data that will allow us to draw whether they are pediatric series or adult patients. conclusions in this regard. This differentiation was only possible after the implementation of the new classification of cortical Crisis frequency dysplasias. So we could point out that studies The mean frequency of seizures before surgery is published on mesial temporal lobe epilepsy (MTLE) 17.7 per month [median 10.0, range 1-330], which evaluating the presence of associated cortical is not significantly different from those occurring dysplasia prior to this classification would have the in isolated FCD or types III b, c, and d.3 bias of evaluating the natural history of epilepsy caused by HS, including cases in which there might have also been patients who suffered dysplasia History of febrile seizures The history of febrile seizures is present in 19.5% type IIIa. of patients with FCD type IIIa. This is significantly more frequent than the other subtypes of FCD of Onset of epilepsy the temporal lobe (IIIb, IIIc, and IIId). Data from Epilepsy in patients with FCD type IIIa debuts Tassi L. et al. suggest that patients with FCD are at 7.8 years [median 6.5, range 1-24], which is more prone to febrile seizures than other patients significantly shorter than that of patients with and that the highest prevalence of febrile seizures isolated FCD. In the case of patients with dysplasia is found in patients with FCD type I at 48%.4 type IIIb, the debut is 3.5 years [median 2.0, range 1-10], which is even shorter than the epilepsy A recent study in patients with temporal lobe 3 debut of FCD subtypes IIIa, IIIc, and IIId. This may sclerosis shows that febrile seizures occur in 73%

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 90 Review Temporal lobe epilepsy due to type IIIa dysplasia

Figure 2. Mean age of onset of epilepsy in different subtypes of focal cortical dysplasias.

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e c

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ae ear of patients, compared to 36% of patients without could suggest the need for a second factor for its sclerosis of the temporal lobe. The study by Faucer definitive development. However, this relationship et al. also documented that the history of febrile will have to be defined in prospective studies and, seizures is more frequent in patients with FCD type at present, we do not have elements to support or IIIa than in other types of temporal lobe epilepsy.10 refute this theory. In the study by Jian Wu et al. the data showed that febrile seizures occurred in 36% of the cohort and Family history that they were significantly more frequent in FCD Only one study has been published of siblings from type IIIa than in other subtypes, which supports a family with epilepsy who developed a similar the results of previous studies and suggests that clinical, electroencephalographic, and histological there is a high susceptibility to the occurrence of picture and had FCD type IIIa. The authors febrile seizures in this type of epilepsy.3 described two siblings with MTLE caused by FCD type IIIa. There was a family history of epilepsy Thus, FCD type IIIa could occur during postnatal (in cousins and the maternal grandmother), and development and the maturation period. It is yet their mother had suffered from febrile seizures in to be determined if FCD Type IIIa is a pathology childhood. These patients also had febrile seizures. acquired from a main lesion or a different They developed epilepsy in the second decade pathological entity, however, clinical studies seem of life characterized by having crisis with initial to delimit that it exists as an entity of its own. In awareness with autonomic, sensory (olfactory or addition, the association with febrile seizures gustatory), and emotional phenomena, followed

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by automatisms, asymmetric tonic postures, and the cortical architecture, which may be related to focal clonias affecting the muscles of the face and the presence of FCD type IIIa.12 hand. In both, the epilepsy was drug-resistant, had HS, and effaced the delineation of the gray- Another important finding from the histological white substance interface in the temporal lobe point of view in patients with FCD type IIIa is the according to the results of the MRI. PET scan presence of lentiform heterotopias. The possible showed temporary hypometabolism. Both patients implication of reelin in this finding comes from the underwent anterior temporal lobectomy and the demonstration that reelin is a glycoprotein acting biopsy showed FCD type Ib associated with HS as a stop signal for neuronal migration during brain [dysplasia type IIIa]. This description suggests that ontogenesis.2 there may be a family component in cases of FCD type IIIa.11 It has been reported that, in adults, reelin is expressed mainly by GABAergic interneurons and regulates the functioning and composition Pathogeny of the glutamate receptor, which could be In a study conducted by Gianluca Marucci et al. of associated with alterations in memory present in 30 patients with drug-resistant MTLE [11 men, 19 patients with MTLE by affecting the mechanisms women] who underwent antero-mesial lobectomy of long-term potentiation mediated by this at the Bellaria Hospital in Bologna, it was shown neurotransmitter.13–15 that in all cases, alterations of the organization and cytoarchitecture of the cortical layers associated However, the molecular mechanisms involved in with HS were present. Of the 30 patients studied, the signaling pathway of reelin, and its relationship 8 had FCD type IIIa without dispersion to the proteolytic fragments and the clinical, in the dentate gyrus (GCD), 7 had HS and GCD type electrophysiological, and histological findings found 1, and 15 had FCD type IIIa and GCD type 2. In the in patients with MTLE and reelin are still unknown. first group, FCD type IIIa without GCD, 53.3% of the neurons of the temporal cortex showed reelin mRNA and in the hippocampus 86.6%. In contrast, Magnetic resonance imaging (mri) in the second group, HS and GCD, only 20% of the studies cortical cells were positive for reelin mRNA and In general, it is known that FCD type I is not only 13.4% in the hippocampus.12 detected by MRI. However, in a 2012 study with 55 patients with MTLE, Robert Kuba et al. found The study by Gianluca Marucci et al. showed that a that patients with FCD type IIIa may have certain global decrease in reelin mRNA is associated with subtle alterations in MRI. These alterations can the dispersion of the granular cells of the dentate be summarized as the existence of an inadequate gyrus in patients with MTLE caused by FCD IIIa.12 delimitation of the gray and white substance, This is due to finding an inverse correlation between temporal lobe FLAIR hyperintensity, and atrophy the number of cells expressing reelin mRNA in the of the temporal lobe. These findings showed high dentate gyrus and the degree of its dispersion of inter-observer concordance [Fleiss’ kappa 0.732, cells. This study suggests that reelin deficiency p <0.0001] and were seen in 52.4% of patients in adulthood could lead to cortical structural with FCD type IIIa [ILAE classification].2 These reorganization. This reorganization could include alterations occurred mainly in the temporal pole an increase in the migratory activity of the neurons (Figure 3 shows one of our patients).16 and of the aberrant plasticity of their dendritic processes, thus the reelin appears to be involved in Inadequate delimitation between the and the maintenance of the architecture in the mature the adjacent cortex with effacement of the white brain.12 Therefore, reelin could play an important matter surrounding it have also been described as role in the remodeling of the hippocampus during indirect signs of FCD type IIIa (see arrows in Figure hippocampal sclerosis [HS] and in the stability of 3, D, E).16

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 92 Review Temporal lobe epilepsy due to type IIIa dysplasia

With the advent of new brain imaging techniques, junction, unequal cortical thickness, probably with the use of ligands, signaling zones of atrophy, and/or thinning of the cortex. A pathways that have not yet been demonstrated, we set of subcortical neuronal heterotopias is usually may, in the future, perhaps elucidate with greater observed. NeuN immunohistochemistry reveals sensitivity and specificity the presence of dysplasia several patterns of abnormal neuronal disposition type IIIa before subjecting the patient to surgical and stratification in the cerebral cortex, including treatment. layers of reduced thickness, predominant vertical columnar structure, and disorganization of the Histological findings cortical structure. This is evident when comparing Architectural abnormalities (histologically the relatively normal hexalaminar structure and equivalent to FCD type I) in the temporal lobe normal thickness.17–19 associated with HS are classified as FCD type IIIa, but not as “dual pathology,” according to the The irregularities of cortical lamination can be current ILA classification of FCD.2 radial (which would classify as dysplasia type Ia), tangential (which would classify as dysplasia Let’s start with the findings in the hippocampi of type Ib), or combined (which would classify as patients with FCD type IIIa, since those of FCD dysplasia type Ic). These alterations are associated type Ia, Ib, and Ic will be explained later. with hypertrophic neurons dispersed outside the V layer, but never with dysmorphic neurons or The representative findings can be better observed globoid cells.17–19 with NeuN immunohistochemistry in fragments of brain tissue obtained after surgical resection of the The following five patterns can be recognized hippocampus.2 as FCD type IIIa variants.2 See Figure 4 which represents a diagram of the different types of FCD Four types of HS have been defined. HS type 1 type IIIa associated with sclerosis of the temporal shows neuronal loss, almost complete in CA1, lobe. moderate to marked in CA4, mild in CA3, sparing the CA2 and region. The granule cell 1. HS with architectural abnormalities in the layer of the dentate gyrus shows both neuronal temporal lobe, Figure 4 A loss and scattering.17–19 2. HS with TLE and heterotopic neurons in the subcortical white matter, Figure 4 B In type 2, what happens is a neuronal loss in CA1 3. HS with small “lentiform” heterotopias in the with no loss of the other sectors.17–19 subcortical white matter, Figure 4 C 4. HS with TLE and small “lentiform” heterotopias In type 3, neuronal loss is marked in the CA4 sector in the subcortical white matter, Figure 4 D and other sectors are spared.17–19 5. HS with TLE, Figure 4 F

A type 4 is accepted in which there is no HS. This Sclerosis of the temporal lobe expresses severe subtype does not belong to the histological findings neuronal loss and laminar gliosis in cortical layers of FCD type IIIa since it shows well-preserved II and III of the cerebral cortex (see Figure 4, the hippocampal neurons.2 loss of layer II neurons in all cases of temporal lobe sclerosis, compare with normal cortex, figure The temporal cortex in patients with HS can show 4C), with cortical reorganization, as suggested by histological alterations, such as irregular cortical observing horizontal lines of aberrant myelinated lamination and the presence of hypertrophic fibers in this area. In fact, TLE can be observed in neurons outside the V layer of the cerebral cortex.2 about 10% of surgical cases of MTLE as an abnormal Cortical structural anomalies can be summarized in band of small “granular” neurons grouped outside the following findings:2 focal blurring of the cortical- the cortical layer II. 2

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 Review 93 Temporal lobe epilepsy due to type IIIa dysplasia

Figure 3. NMR images showing findings associated with dysplasia type IIIa. Magnetic

Resonance 1.5 T of a 38-year-old female patient. A: Coronal section with T2 technique, there is evidence of erasure of the white-gray matter delimitation in the pole of the right temporal lobe. Compare with the contralateral one (see yellow arrow). B: MRI of the same patient. Observe the hyperintensity of the right temporal pole, the white-gray matter interface is not well defined (white arrow). C: Brain PET of the same patient. Observe the marked hypometabolism of the cortex of the right temporal pole. D: FLAIR coronal section showing the typical hyperintensity observed in the hippocampus of patients with hippocampal sclerosis (arrow). E: Shows the subtle loss of a band of white matter that separates the amygdala from the adjacent supra cortex.

Individual heterotopic neurons in subcortical However, reference photographs must be prepared white matter should be considered pathological by each laboratory since the actual enlargement and significant for heterotopias when their of the photographs differs depending on the number in the deep white matter is greater than microscope and the connected digital camera, as 30/mm.2 Although its epileptogenic meaning well as the distance between the optical lens and remains to be determined. For practical purposes, the digital camera.17 immunostaining with NeuN can be useful for estimating the number of heterotopic neurons in The “lentiform” heterotopias are usually the deep white matter.2 undetectable in MRI and are composed

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 94 Review Temporal lobe epilepsy due to type IIIa dysplasia

Figure 4. Diagram of the different types of DCF type IIIa associated with sclerosis of the temporal lobe.

A: > means loss of neurons, * refers to the disorganization of the layered structure of the cerebral cortex, ** means TLE, and + heterotopic neurons in white matter. It shows hippocampal sclerosis (HS) type 1 (loss of neurons in CA4 >>> CA3 >> CA1) associated with dysplasia type Ic, observe the radial and horizontal disorganization of the cortex *. B: HS type 2 (CA1 >>> CA4> CA3), with TLE (**) and heterotopic neurons in the subcortical white matter (+). C: HS type 3 (CA4 >>> CA1) with small “lentiform” heterotopias in the subcortical white matter, without sclerosis of the temporal lobe. D: HS type 3 with TLE and small “lentiform” heterotopias in the subcortical white matter. E: accumulation of heterotopic neurons without sclerosis of the temporal lobe nor of the hippocampus. F: HS with [TLE] with double cellular layer in the dentate gyrus. Sclerosis of the temporal lobe expresses severe neuronal loss and laminar gliosis in cortical layers II and III of the cerebral cortex (see figure 4, loss of neurons in layer II (**) in all cases of sclerosis of the temporal lobe, and the grouping of neurons in the layer I / II interface, compare with the normal cortex, figure 4 C. histologically of projection neurons, and are presence of FCD type IIIa is a factor that affects different from nodular heterotopias which are the postoperative outcome. In recent publications, usually detected by MRI and consist of projection it has been found that patients with MTLE caused neurons and neurons that form local circuits. Due by FCD type IIIa may have a poor postoperative to the similarity between them and to normal prognosis compared with patients with epilepsy structures such as the , special care and isolated HS.4,21,22 must be taken not to confuse them during the histological examination.2 There are few studies that have specifically evaluated post-surgical prognosis in relation For better interpretation of the histological to crisis-free patients operated with refractory findings we recommend reviewing the comments epilepsy caused by dysplasia type IIIa. We did not and the figures of the articles by Blümcke Iet al. and find studies that investigated the prognosis in Miyata H et al. 2,20 relation to the cognitive evolution, memory, and psychiatric complications of these patients. Dysplasia type iiia and post-surgical Regarding the seizure-free postsurgical period, prognosis it has been reported that the shorter the time of Much has been discussed regarding whether the evolution, the time of follow-up of epilepsy, and

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 Review 95 Temporal lobe epilepsy due to type IIIa dysplasia

the age at which the patients operate, the better region of the hippocampal body.24 This may have prognosis regarding freedom from seizures.23,5 The led to errors in the interpretation since the recent controversy is mainly because, although histology classification of HS proposed by the ILAE points out is taken into account to determine the etiology of there can be difficulties classifying the dispersion of epilepsy, the authors rarely take into consideration the granular cells of the dentate gyrus considering the histological alterations that underlie the the dispersion can be focal.25 etiology to determine the postoperative prognosis in epilepsy. Therefore, the main author of the It is also important to note that, when we talk about ILAE’s most recent classification of focal cortical postoperative prognosis in epilepsy, we should dysplasias has pointed out the urgent need to not confine it to the prognosis for the recurrence evaluate the histological subtypes of dysplasias and of epileptic seizures, but we should consider its the cytoarchitectonic alterations of the specimens relationship with cognitive, neuropsychiatric, and obtained in epilepsy surgery as possible predictors behavioral prognosis. In this sense, there are no of postsurgical prognosis in patients undergoing studies that relate these elements to histology. surgery for epilepsy.18 Neither have the different combinations of FCD, kind of HS (type 1,2,3), and pathology of the Giulioni opines that other factors he calls “crucial” dentate gyrus (with double layer, with neuronal should be considered to explain the worst migration, or with thinning) been analyzed. postoperative outcome in the group of patients Different associations may occur which can relate with FCD IIIa, suggesting that the HS subtype to different forecasts; this is yet to be determined. and the pathology of the dentate gyrus may play a The authors of the classification of dysplasias preponderant role.24 of the ILAE expressed that the dispersion of the granular cells has no clear association with the In a study published by Blümcke et al. the HS subtype clinical result.2 did not show an influence on postoperative results. Patients with atypical patterns of HS (according The comments of Giulioni et al. and Blümcke et al. to ILAE type 3) and those where mesial structures enhance the practical use and the importance of were not present in the sample did not have a the pathological classification as well as the need worse postoperative outcome.25 for a greater correlation of results in this important area. This was corroborated in a recent publication by Giulioni et al. where they clearly defined that the In general, it would be worthwhile not only to isolated HS subtype, compared to the presence evaluate the relationship between the histological of FCD IIIa, did not influence the postoperative findings and the likelihood of relapse of the seizures outcome. The only patient with FCD IIIa and but also to determine the relationship between atypical HS (TLE type 2) was crisis-free after histological findings and the presence of cognitive surgery (Engel Ia).26 deficits and psychiatric complications, even if the neural networks involved in the processing of However, Giulioni et al. did find a difference in memory and language of these patients vary when post-surgical outcome when they considered the compared with other pathologies of the temporal presence of granular cell pathology of the dentate lobe. gyrus in patients with isolated HS. In this study, the authors did not present data regarding the presence of FCD type IIIa.

It is important to note that in these studies the examination of the hippocampus and presumably the dentate gyrus only took place in the middle

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 96 Review Temporal lobe epilepsy due to type IIIa dysplasia

Conclusions

Seizures in patients with dysplasia type IIIa debut in the second decade of life. There is often a history of febrile seizures, MRI studies show a poor differentiation of the gray- white matter interface, absence of white substance band that separates the amygdala from the entorhinal cortex associated with histological studies showing irregularities of cortical lamination of layers II, III, and IV, with groupings of heterotopic neurons in white matter. These findings allow us to consider it a nosological entity with its own identity. Although a better characterization will be favored by the contributions of molecular studies aimed at studying the impact of cell signaling pathways which determine, on the one hand, the death of hippocampal neurons and the dispersion of the dentate gyrus, and on the other hand, alterations in neuronal migration and the structure of the neocortex.

Conflicts of interest Funding sources Los autores declaramos que no tenemos Los autores declaramos que no recibimos conflicto de interés. financiamiento para la realización del artículo.

Revista Mexicana de Neurociencia march-april, 2018; 19(2):86-98 Review 97 Temporal lobe epilepsy due to type IIIa dysplasia

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24. Giulioni M., Marucci G., Martinoni M., Volpi L., Riguzzi P., Marliani AF., et al. Seizure outcome in surgically treated drug- resistant mesial temporal lobe epilepsy based on the recent histopathological classifications.J Neurosurg. 2013;119(1):37- 47, doi: 10.3171/2013.3.JNS122132. 25. Blümcke I., Thom M., Aronica E., Armstrong DD., Bartolomei F., Bernasconi A., et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia. 2013;54(7):1315-29, doi: 10.1111/epi.12220. 26. Rubboli G., Giulioni M., Volpi L., Martinoni M., Riguzzi P., Marucci G., et al. Seizure outcome and pathological correlation in drug-resistant temporal lobe epilepsy surgically treated. EpilepsiaConference 29th Int Epilepsy Congr IEC 2011 Rome ItalyConference Start 20110828 Conf End 20110901Conference Publ. 2011;52(Journal Article):191, doi: http://dx.doi. org/10.1111/j.1528-1167.2011.03207.x.

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