A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies. Methods: We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility. Results: ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-ß and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs. Conclusions: Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS)-Does it Really Exist?

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS) is a rare variant of the CLIPPERS spectrum with less than ten reports published so far. There is ongoing discussion regarding whether SLIPPERS is a disease entity on its own or just an acronym encompassing many underlying diagnoses, such as sarcoidosis, vasculitis and anti-glial fibrillary acidic protein (GFAP)-associated disease. A 40-year-old woman presented with episodes of language and attention impairment. Magnetic resonance imaging (MRI) revealed T2/FLAIR hyperintense lesions in the subcortical white matter associated with a micronodular, curvilinear perivascular contrast-enhancement. Alternative diagnoses were excluded. There was a remarkable response to steroids. A relapse occurred after six years, and the biopsy showed perivascular T-cell lymphocytic infiltrate, without granulomas, vasculitis, or neoplasia. There was complete resolution of the relapse after steroids. This case represents the longest reported follow-up of a patient diagnosed with SLIPPERS, and brain biopsy after 6 years did not suggest alternative diagnoses. This report contributes to the discussion regarding the possibility that exclusive supratentorial CLIPPERS-like pathology might be an isolated disease entity, but more biopsy-proven cases with a longer follow-up are needed to support this hypothesis. Recently, GFAP astrocytopathy has been characterized and might correspond to a significant number of cases previously diagnosed as CLIPPERS or SLIPPERS.

Case Report: Evolutionary Clinical-Radiological Features of a Diffuse Hemispheric Glioma, H3 G34 Mutant with Over 5 Years of Survival.

Diffuse hemispheric glioma (DHG), H3 G34 mutant was included in the 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System recently published. Given the recent inclusion in the current classification and its rarity in adult patients, there are scarce data on clinical-radiological characteristics, survival, and outcome. The authors report the case of a 35-year-old female with DHG, H3 G34-mutant characteristics and outcomes with an unusual presentation, recurrence, and prolonged survival. In conclusion, our case report demonstrates relevant details that should be observed in patients with suspicion or confirmation of the diagnosis of DHG, H3 G34 mutant, not only in the initial presentation but also in the evolution to ensure more personalized treatment.

Granule cell dispersion is associated with hippocampal neuronal cell loss, initial precipitating injury, and other clinical features in mesial temporal lobe epilepsy and hippocampal sclerosis.

PURPOSE: To characterize a 10-year series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) and determine the histopathological characteristic of the association between granule cell dispersion (GCD) and hippocampal neuronal loss. METHODS: The study included 108 MTLE/HS patients. Histopathological analyses were performed in NeuN-stained hippocampal sections for HS pattern, neuronal density, dentate gyrus (DG) pathology, and granule cell layer width. Statistical tests investigated the association between DG pathologies and HS patterns, as well as the correlation of DG width with total hippocampal and subfield-specific neuronal densities. RESULTS: Fifty-six patients (51.9%) presented right HS. All the four ILAE HS patterns were represented (90 Type 1, 11 Type 2, 2 Type 3, and 5 no-HS). Sixty-seven patients (62.0%) presented GCD, 39 (36.1%) normal DG, and 2 (1.9%) narrow DG. GCD was associated with initial precipitating injury, higher numbers of monthly focal seizures and lifetime bilateral tonic-clonic seizures, longer epilepsy duration, and older age at surgery. GCD was prevalent in all HS patterns, except for Type 2 (81.8% normal versus 18.2% GCD, p = 0.005). GCD was associated with total hippocampal and subfield-specific neuronal loss, except for CA1. DG width correlated with total hippocampal (r = -0.201, p = 0.037) and CA4 neuronal densities (r = -0.299, p = 0.002). Patients with HS Type 1 had better surgical outcomes, with 51 (61.4%) seizure-free in the first year post-surgery. CONCLUSIONS: This study confirmed that seizure control in MTLE/HS patients submitted to surgical treatment is comparable worldwide. Moreover, histopathological analyses showed an association between GCD and hippocampal neuronal loss, especially in the CA4 subfield.

An atypical case of neurotoxoplasmosis in immunocompetent patient.

Toxoplasmosis is an infection caused by Toxoplasma gondii, an intracellular protozoan that is often associated with immunocompromised patients and is rare in immunocompetent. A 60-year-old man was admitted with a history of 2 days of headache and right-sided weakness. There was no history of fever, surgeries, or any other comorbid illness. Cerebrospinal fluid showed just mild pleocytosis with 15 cells/mm3, predominantly lymphomononuclear. MRI showed Peripheral enhancing lesion with central diffusion restriction and perivascular enhancing lesion with restricted diffusion with vasogenic edema and leptomeningeal enhancement in the white matter. Viral serologies, tumor markers, protein electrophoresis were normal. The patient was submitted to brain biopsy, revealing necrotic brain parenchyma with predominantly acute inflammation, with diffuse encephalitis pattern, and cysts with bradyzoites (cystozoites) of Toxoplasma gondii in the brain parenchyma. The central nervous system infection by Toxoplasma gondii can present as meningoencephalitis during primary infection in an immunocompetent, although it is rare. Central nervous system lymphoma is the main differential diagnosis of neurotoxoplasmosis by imaging, especially in our case.

Temporal horns subependymomas: A report of two cases of an intraventricular neoplasm in an atypical location.

Slow-growing intraventricular masses are sometimes imaging findings in asymptomatic patients. The neuroimaging characteristics frequently help making the correct diagnosis and the treatment decision. Subependymomas usually present as single lesions poorly vascularized, without invasion into adjacent brain parenchyma or cerebrospinal fluid dissemination. Ependymoma is considered the main differential diagnosis. We report two cases of this tumour who share the unusual location: The temporal horns. The lack of enhancement (or heterogeneous when present) and advanced neuroimaging techniques can be very useful in differentiating them from other lesions.

Genetic Variants Related to Cell Cycle and Stability of Telomere in Patients with Glioma.

Background: Glioma, most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. Evaluate the association of polymorphisms related of to the cell cycle, integrity and DNA repair with gliomas, as well as lifestyle habits, comorbidities, survival and response to treatment. Methods: Were studied 303 individuals distributed into: Study Group - 100 patients with gliomas, regardless of the degree of malignancy, and Control Group - 203 individuals without clinical signs of the disease. These polymorphisms were genotyped by TaqMan® SNP Genotyping Assay. Significance level was set at 5%. Results: Smoking, alcohol consumption, systemic arterial hypertension (SAH) and diabetes mellitus (DM) prevailed in patients, compared to controls (P=0.0088, P=0.0001, P=0.0001, P=0.0011, respectively). In the logistic regression analysis, alcohol consumption and SAH were identified as independent risk factors for gliomas (P=0.0001, P=0.0027, respectively). Patients with low-grade gliomas showed survival in one year (92.0±6.8%), compared to patients with high-grade gliomas (24.0±5.3; P=0.011). Conclusion: Polymorphisms involved in cell cycle, telomere protection and stability and DNA repair are not associated with gliomas. On the other hand, alcohol consumption and SAH stand out as independent risk factors for the disease. Low-grade gliomas, response to treatment and the combination of chemotherapy with Temozolomide and radiation therapy show increased survival of patients.

The impact of epilepsy duration in a series of patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis.

PURPOSE: To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). METHODS: Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus - normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. RESULTS: Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = -0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). CONCLUSION: Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis.

OBJECTIVE: The objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield. METHODS: The hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36). RESULTS: There were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p=0.048). The groups with HS presented different memory performance - the right HS were worse in visual memory test [Complex Rey Figure, immediate (p=0.001) and delayed (p=0.009)], but better in one verbal task [RAVLT delayed (p=0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p=0.050) and Logical Memory and RAVLT delayed recalls (p=0.004 and p=0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p=0.006) and epilepsy duration (p=0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p<0.001). SIGNIFICANCE: Cornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS.

Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. METHODS: Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. RESULTS: Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). CONCLUSION: This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS.

Anaplastic Ganglioglioma of the Pineal Region ­ A Case Report

Introduction Gangliogliomas are tumors commonly found in the temporal lobe and related to seizures; their appearance in the pineal region is rarely described. This report characterizes the first case of anaplastic ganglioglioma of the pineal region. Case Report The authors describe the case of a 32-year-old woman that developed progressive headache. An MRI investigation revealed a pineal tumor. The patient tested negative for biomarkers and underwent surgery through supracerebellar infratentorial approach and achieved gross total resection of the tumor in a challenging location. Pathological analysis revealed a biphasic neoplasm with the following two distinct phenotypes in separate fields: an immature neuronal component with several atypical mitoses and a mature astrocytic component with bipolar cells, microcysts, and eosinophilic bodies. The Ki67/MIB1 proliferation index was 20­30% in localized hotspots. Based on the pathological findings, the tumor was defined as an anaplastic ganglioglioma World Health Organization (WHO) grade III. Discussion/Conclusion Gangliogliomas are classified as glioneural neoplasms based on the histologic findings described as a mixture of neoplastic astrocytes and neurons. Moreover, these tumors represent 0.4­1.3% of tumors of the central nervous system. Authors describe de novo anaplastic ganglioglioma as 1% of the largest series. Gross total resection and adjuvant treatment may play important role in patients' prognostic. In this case, due to the malignant anaplastic component of her tumor, the patient received treatment with temozolamide and radiotherapy after gross total resection of the lesion.

Introdução Gangliogliomas são tumores comumente encontrados no lobo temporal e se relacionam com crises epilépticas; o aparecimento desses tumores na região da pineal é raramente descrito. Este relato caracteriza o primeiro caso de ganglioglioma anaplásico da região da pineal. Relato de Caso Paciente do sexo feminino, 32 anos, apresentou-se com cefaleia de piora progressiva. Investigação com ressonância magnética revelou tumor na região da pineal. Os biomarcadores para tumores da pineal foram negativos e a paciente foi submetida a microcirurgia com o acesso supracerebelar e infratentorial atingindo ressecção total da lesão. A análise patológica revelou neoplasia bifásica com dois fenótipos distintos em campos separados: um componente era composto por células neuronais imaturas com inúmeras mitoses atípicas e o segundo componente era composto por astrócitos maduros, microcistos e corpos eosinofílicos. Foi encontrado um índice proliferativo Ki67/M1B1 de 20­30%. Baseado nos achados anatomopatológicos, o tumor foi definido como ganglioglioma anaplásico grau III da OMS. Discussão/Conclusão Gangliogliomas são classificados como neoplasias glioneurais baseado nos achados histológicos descritos como misto de neoplasia neuronal e glial; esses tumores representam 0,4­1,3% de todos os tumores do sistema nervoso central. Ganglioglioma anaplásico de novo tem sido descrido em 1% nas maiores series de gangliogliomas. Ressecção total da lesão e tratamento adjuvante desempenham um papel importante no prognóstico dos pacientes. Devido ao componente anaplásico do tumor em questão, a paciente foi tratada com temozolamida e radioterapia após ressecção total da lesão.

Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms.

OBJECTIVE: The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer. METHODS: The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin-eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases. RESULTS: The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of high-grade lesions (cervical intraepithelial neoplasm - CIN - 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68. CONCLUSION: Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry.

Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms / Reprodutibilidade do diagnóstico das neoplasias intraepiteliais cervicais e a influência dos marcadores imuno-histoquímicos p16 e Ki-67 como ferramentas auxiliares

Objective The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer. Methods The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin-eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases. Results The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of highgrade lesions (cervical intraepithelial neoplasm - CIN - 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68. Conclusion Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry.

Objetivo Observar a expressão dos marcadores imuno-histoquímicos p16 e Ki-67 em neoplasias intraepiteliais cervicais e sua influência na concordância entre observadores diferentes e, entre o mesmo observador. Métodos Foram incluídas no estudo 184 pacientes com neoplasias cervicais intraepiteliais confirmadas por biópsia realizadas durante os anos de 2005 e 2006. As biópsias foram revistas, primeiramente, por três patologistas utilizando-se apenas a coloração de Hematoxilina-Eosina. Foi realizado um consenso acerca do diagnóstico. Posteriormente, foi realizado o estudo imuno-histoquímico e analisada a expressão de p16 e Ki- 67 nesses casos. Resultados A comparação entre os patologistas revisoresmostrou uma concordância apenas regular (k = 0,44. A concordância foi melhor quando analisada apenas a capacidade de diferenciar lesões de alto grau (NIC 3) (k = 0,59). A marcação de p16 mostrou alto valor preditivo negativo e sensibilidade, porém baixa especificidade. Em geral, tanto p16 qualitativo, quanto p16 quantitativo e Ki-67 quantitativo mostraram baixa acurácia geral. A concordância entre os diagnósticos antes da imuno-histoquímica obteve k = 0,47, e após o auxílio da imuno-histoquímica houve um aumento do Kappa para 0,68. A marcação de p16 mostrou alto valor preditivo negativo e sensibilidade, porém baixa especificidade. Em geral, tanto p16 qualitativo, quanto p16 quantitativo e Ki-67 quantitativo mostraram baixa acurácia geral. Conclusão Nosso estudo mostrou que a concordância no diagnóstico tradicional de lesões intraepiteliais cervicais é regular e que pode ser melhorada como o auxílio da imuno-histoquímica.

Atypical Teratoid Rhabdoid Tumor in a Child: Case Report / Tumor teratóide rabdóide atípico emuma criança: relato de caso

Atypical teratoid/rhabdoid tumor (ATRT) is a rare and aggressive type of embryonal tumor of the central nervous system (CNS) occurring in childhood. The present study aims to describe the case of a 16-year-old girl who presented with an occipital mass lesion that was diagnosed as ATRT.We present a brief review of the current knowledge of the treatment of this rare neoplasm. A previously healthy 16-year-old girl was referred after two episodes of partial complex seizure 2 weeks before admission. MRI showed a right parieto-occipital lesion with homogeneous contrast-enhancing and significant surrounding brain edema. The patient underwent uneventful surgical resection of the lesion and was discharged home on the fifth postoperative day. Pathologic examination revealed it to be ATRT. The patient was referred to chemotherapy and radiotherapy. After 6 months of follow-up, the patient remains free of seizure and disease progression. ATRT is a rare and aggressive disease. Therefore, early diagnosis and treatment may improve the patient's prognosis and quality of life.

O tumor teratoide rabdoide atípico (TTRA) é um tipo de neoplasia rara, com comportamento maligno, que atinge o sistema nervoso central (SNC) de crianças. O objetivo do presente estudo é relatar o caso de uma paciente de 16 anos de idade admitida no nosso serviço com uma lesão occipital que revelou tratar-se de TTRA em estudo anatomopatológico. Uma paciente previamente hígida foi admitida no nosso serviço referindo ocorrência de dois episódios de crises convulsivas nas últimas 2 semanas. A ressonância magnética de crânio mostrou a presença de lesão occipital direita com captação homogênea do meio de contraste. A paciente foi submetida a cirurgia de ressecção da lesão expansiva sem intercorrências. A análise histopatológica e imuno-histoquímica revelou tratar-se de TTRA. A paciente foi encaminhada para a realização de quimioterapia e radioterapia complementares ao tratamento cirúrgico. Após 6 meses de seguimento ambulatorial, a paciente encontra-se assintomática, sem recorrência das crises convulsivas e/ou progressão radiológica da doença. TTRA é uma doença rara e agressiva. Com isso, diagnóstico e tratamento antecipados podem aprimorar prognóstico e qualidade de vida dos pacientes.

Surgical and postmortem pathology studies: contribution for the investigation of temporal lobe epilepsy / Patologia cirúrgica e post mortem: contribuição para a investigação da epilepsia do lobo temporal

Pathology studies in epilepsy patients bring useful information for comprehending the physiopathology of various forms of epilepsy, as well as aspects related to response to treatment and long-term prognosis. These studies are usually restricted to surgical specimens obtained from patients with refractory focal epilepsies. Therefore, most of them pertain to temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and malformations of cortical development (MCD), thus providing information of a selected group of patients and restricted regions of the brain. Postmortem whole brain studies are rarely performed in epilepsy patients, however they may provide extensive information on brain pathology, allowing the analysis of areas beyond the putative epileptogenic zone. In this article, we reviewed pathology studies performed in epilepsy patients with emphasis on neuropathological findings in TLE with MTS and MCD. Furthermore, we reviewed data from postmortem studies and discussed the importance of performing these studies in epilepsy populations.

Estudos de patologia em pacientes com epilepsia trazem informações úteis para compreender a fisiopatologia de várias formas de epilepsia, bem como aspectos relacionados ao tratamento e ao prognóstico a longo prazo. Esses estudos são usualmente restritos a espécimes cirúrgicos obtidos de pacientes com epilepsias focais refratárias. Portanto, a maioria diz respeito à epilepsia do lobo temporal (ELT) com esclerose mesial temporal (EMT) e às malformações do desenvolvimento cortical (MDC). Desse modo, fornecem informações sobre um grupo selecionado de pacientes e sobre regiões restritas do cérebro. Raramente são realizados estudos post mortem do cérebro inteiro em pacientes com epilepsia; entretanto, eles podem prover informações relevantes sobre patologia cerebral, permitindo a análise de áreas além da zona epileptogênica putativa. Neste artigo, foram revisados estudos de patologia feitos em pacientes com epilepsia, com ênfase nos achados neuropatológicos em ELT com EMT e MDC. Foram revisados, ainda, dados de estudos post mortem e discutiu-se a importância da realização desses estudos em populações de pessoas com epilepsia.

Expressão de mediadores neurotróficos e pró-inflamatórios na endometriose de reto e sigmoide / Expression of neurotrophic and inflammatory mediators in rectosigmoid endometriosis

OBJETIVO: Avaliar a expressão de mediadores neurotróficos (NGF, NPY E VIP) e pró-inflamatórios (TNF-α) em fragmentos de reto e sigmoide comprometidos por endometriose. MÉTODOS: Foram selecionadas 24 pacientes submetidas ao tratamento cirúrgico de endometriose de reto e sigmoide com técnica de ressecção segmentar, seguido de anastomose mecânica término-terminal, com grampeador circular, no período de janeiro de 2005 a dezembro de 2007. Neste estudo incluímos mulheres no menacme que se submeteram a tratamento cirúrgico por endometriose profunda infiltrativa com acometimento do reto e sigmoide, atingindo o nível da camada muscular, submucosa ou mucosa. Para o grupo de estudo foram utilizados 24 fragmentos de reto e sigmoide com endometriose confirmada histologicamente, sendo um fragmento de cada uma das 24 pacientes selecionadas. Para o grupo controle, utilizou-se um fragmento da margem distal da ressecção, denominado anel de anastomose, de cada uma das 24 pacientes selecionadas e incluídas no estudo. As amostras foram agrupadas em blocos de Tissue Micro Array (TMA) e submetidas à reação imunoistoquímica para avaliar a expressão do fator de necrose tumoral alfa (TNF-α), do fator de crescimento neural (NGF), do neuropeptídeo Y (NPY) e do peptídeo intestinal vasoativo P (VIP), e posterior análise semiquantitativa da imunomarcação por meio da leitura da densidade ótica relativa (DO). RESULTADOS: Observou-se maior densidade ótica relativa da imunomarcação para TNF-α e NGF no grupo de estudo (amostras com endometriose intestinal), DO= 0,01, respectivamente, para as duas proteínas (p<0,05), em relação aos controles sem endometriose. Não houve diferença estatística na densidade ótica da imunomarcação do NPY e VIP. CONCLUSÃO: Identificou-se o aumento da imunomarcação dos anticorpos TNF-α e NGF em fragmentos de reto e sigmoide comprometidos por endometriose em relação aos controles livres da doença. Não identificamos diferença estatística na imunomarcação das proteínas NPY e VIP.

PURPOSE: To evaluate the expression of neurotrophic (NGF, NPY and VIP) and pro-inflammatory (TNF-α) mediators in the rectum and sigmoid fragments compromised by endometriosis. METHODS: Twenty-four patients were selected to undergo surgical treatment of endometriosis of the rectum and sigmoid colon with a segmental resection technique, followed by end-to-end anastomosis with a circular stapler from January 2005 to December 2007. The study included premenopausal women who underwent surgical treatment for deep endometriosis infiltrating the rectum with involvement of the rectum and sigmoid, reaching the level of the muscle layer, submucosa or mucosa. Twenty-four rectum and sigmoid fragments with histologically confirmed endometriosis, one from each of the 24 selected patients, were used for the study group. For the control group, we used a fragment of the distal resection margin called anastomosis ring from each of the 24 patients enrolled in the study. Samples were grouped into Tissue Micro Array (TMA) blocks and subjected to immunohistochemistry to evaluate the expression of tumor necrosis factor alpha (TNF-α), nerve growth factor (NGF), neuropeptide Y (NPY) and P vasoactive intestinal peptide (VIP), followed by semiquantitative analysis of immunostaining by reading the relative optical density (OD). RESULTS: There was higher optical density relative to TNF-α immunostaining and NGF in the study group (samples with intestinal endometriosis), DO=0.01, for the two proteins, respectively (p<0.05), compared to controls without endometriosis. There was no statistically significant difference in the optical density of immunostaining of NPY and VIP. CONCLUSION: We identified increased immunostaining of TNF-α antibodies and fragments of NGF in the rectum and sigmoid compromised by endometriosis compared to disease-free controls. We did not identify any statistical difference in immunostaining of NPY and VIP proteins.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome.

OBJECTIVE: To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD: Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. RESULTS: Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). CONCLUSION: Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome / Epilepsia do lobo temporal com esclerose mesial temporal: o padrão da perda neuronal hipocampal como preditor do prognóstico cirúrgico

OBJECTIVE: To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD: Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. RESULTS: Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). CONCLUSION: Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

OBJETIVO: Analisar retrospectivamente uma série de pacientes com epilepsia do lobo temporal (ELT) e esclerose mesial temporal (EMT), bem como correlacionar os padrões de esclerose hipocampal com os dados clínicos e o prognóstico cirúrgico. MÉTODOS: Foram incluídos neste estudo 66 pacientes com ELT refratária a tratamento medicamentoso e com EMT unilateral submetidos à lobectomia temporal anterior. A análise neuropatológica quantitativa foi realizada em seções hipocampais imunomarcadas com NeuN. Dados clínicos e resultados do acompanhamento pós-cirúrgico foram revisados. RESULTADOS: Ocorrência de evento precipitante inicial e melhor controle de crises após a cirurgia (i.e. classe 1 de Engel) foram associados aos padrões clássico (EMT tipo 1a) e severo (EMT tipo 1b) de esclerose hipocampal. CONCLUSÃO: A análise quantitativa do padrão de perda neuronal do hipocampo é capaz de predizer o prognóstico cirúrgico em pacientes com ELT-EMT.