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OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/cirurgia , Eletrodos Implantados , Eletroencefalografia/métodos , Epilepsias Parciais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas Estereotáxicas , Adulto JovemRESUMO
OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.
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INTRODUCTION: There is an emerging interest in the literature about MOGHE (Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia and Epilepsy). We report the case of an epileptic patient with MOGHE. CASE REPORT: A 33-year-old male patient was suffering from refractory focal epilepsy since adolescence. MRI demonstrated increased T2/FLAIR signal intensity of right frontal lobe. Presurgical evaluation led to definition of epileptogenic network in a specific area of right frontal lobe. The resected specimen revealed MOGHE. Discussion. MOGHE appears to be a brain entity which shares some unique histopathological features. Review of the literature is in accordance with our patient's findings. The major neuropathological finding consists of areas with blurred gray-white matter boundaries due to heterotopic neurons in white matter and increased numbers of subcortical oligodendroglial cells with increased proliferation. MR abnormalities are present in T2/FLAIR sequences. It concerns patients with refractory frontal lobe epilepsy and appears to associate with unfavourable postsurgical outcome in seizure control. CONCLUSION: More cases are needed in order to establish more data about this distinct entity in frontal lobe epilepsy. This could be valuable knowledge to patients and doctors concerning expectations or management of undesirable outcome in frontal lobe epilepsy surgery.
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Low-grade epilepsy-associated brain tumours (LEAT) are the second most common cause for drug-resistant, focal epilepsy, that is ganglioglioma (GG) and dysembryoplastic neuroepithelial tumours (DNT). However, molecular pathogenesis, risk factors for malignant progression and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League Against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor inter-rater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web-based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial-like cell patterns prevail, or ganglion cells were difficult to discriminate from pre-existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in four consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular-genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype-genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature.
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Neoplasias Encefálicas/patologia , Epilepsia/patologia , Ganglioglioma/patologia , Glioma/patologia , Oligodendroglia/patologia , Neoplasias Encefálicas/classificação , Epilepsia/classificação , Ganglioglioma/classificação , Ganglioglioma/diagnóstico , Glioma/classificação , Glioma/diagnóstico , Humanos , Oligodendroglia/classificação , FenótipoRESUMO
The Diagnostic Methods commission of the International League against Epilepsy (ILAE) released a first international consensus classification of Focal Cortical Dysplasia (FCD) in 2011. Since that time, this FCD classification has been widely used in clinical diagnosis and research (more than 740 papers cited in Pubmed between 1/1/2012 and 7/1/2017). Herein, we review the new data that will inform and revise the FCD classification. Many recent papers described molecular-genetic characteristics in FCD type II including multiple mutations in the mTOR pathway. In addition, the electro-clinico-imaging phenotype and surgical outcomes of FCD type II (in particular type IIb) were further defined and validated. These results pave the way for the design of an integrated clinico-pathological and genetic classification system, as recently recommended by the WHO for the classification of malignant brain tumours. On the other hand, little new information was acquired on FCD types I and III. Focal cortical dysplasia type I subtypes are still lacking a comprehensive description of clinical phenotypes, reproducible imaging characteristics, and specific molecular/genetic biomarkers. Associated FCD III subtypes also became rare in published literature. Despite temporal lobe epilepsy being the most common focal epilepsy in adults, we have not identified neurophysiological, imaging, histopathological and/or genetic biomarkers to reliably classify FCD III with or without hippocampal sclerosis. In respect of pathogenesis, FCD adjacent to a non-developmental, postnatally acquired lesion is difficult to explain and perhaps does not exist. This update may help foster shared efforts towards a better understanding of FCD, potential future updates of classification and novel targeted treatments.
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Epilepsia/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico , Neuroimagem , Consenso , Epilepsia/classificação , Epilepsia/diagnóstico por imagem , Epilepsia/patologia , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical do Grupo I/classificação , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico por imagem , Malformações do Desenvolvimento Cortical do Grupo I/patologia , Estudos RetrospectivosRESUMO
Approximately 50 million people have epilepsy, making it the most common chronic and severe neurological disease worldwide, with increased risk of mortality and psychological and socioeconomic consequences impairing quality of life. More than 30% of patients with epilepsy have inadequate control of their seizures with drug therapy. Any structural brain lesion can provoke epilepsy. However, progression of seizure activity as well as the development of drug-resistance remains difficult to predict, irrespective of the underlying epileptogenic condition, i.e., traumatic brain injury, developmental brain lesions, brain tumors or genetic inheritance. Mutated DNA sequences in genes encoding for ion channels or neurotransmitter receptors have been identified in hereditary focal or generalized epilepsies, but genotype-phenotype correlations are poor, arguing for additional factors determining the effect of a genetic predisposition. The dynamics of epigenetic mechanisms (e.g. DNA methylation, histone modifications, chromatin remodelling, and non-coding RNAs) provide likely explanations for common features in epilepsy and other complex diseases, including late onset, parent-of-origin effects, discordance of monozygotic twins, and fluctuation of symptoms. In addition, many focal epilepsies, including focal cortical dysplasias (FCDs), glio-neuronal tumors (e.g. ganglioglioma), or temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), do not seem to primarily associate with hereditary traits, suggesting other pathogenic mechanisms. Herein we will discuss the many faces of the epigenetic machinery, which provides powerful tools and mechanisms to propagate epileptogenicity and likely also contribute to the epileptogenic memory in chronic and difficult-to-treat epilepsies.
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Epigênese Genética/genética , Epigenômica , Epilepsia/genética , Malformações do Desenvolvimento Cortical/genética , Animais , Encéfalo/patologia , Metilação de DNA/genética , Humanos , Malformações do Desenvolvimento Cortical/patologia , Neurônios/patologiaAssuntos
Encefalocele/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Lobo Temporal/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Encefalocele/complicações , Encefalocele/patologia , Encefalocele/cirurgia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/etiologia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Humanos , Masculino , Lobo Temporal/patologia , Lobo Temporal/cirurgiaRESUMO
PURPOSE: This study aims to investigate the contributions of magnetoencephalography (MEG) in magnetic resonance imaging (MRI)-negative patients. METHODS: A total of 18 MRI-negative patients diagnosed with refractory epilepsy, subjected to MEG investigation, and subsequently underwent surgery were selected for retrospective analysis. A 1.5-tesla Magnetom Sonata with an eight-channel head array coil was used. MEG data were obtained using a 74/248-channel system. RESULTS: A total of 16 patients (16/18) had positive MEG results, comprising 12 patients with monofocal localizations, five with multifocal localizations, and one with unremarkable results in MEG. In addition, 12 patients had indicative single photon-emission computed tomography (SPECT), five had indicative fluorodeoxyglucose positron emission tomography (FDG-PET), and all the patients had intracranial electroencephalography (EEG) (14 with subdural electrodes and four with electrocorticography). The intracranial EEG recordings of nine patients were guided by MEG informative results. Among these 18 patients, 10 exhibited good postoperative outcomes (Engel I and II), four of which were completely seizure-free. All these ten patients had clear monofocal localization in MEG, including nine with accordant indicative metabolic changes in either SPECT or FDG-PET, or both. None of the five patients with multifocal localizations achieved good postoperative outcomes. CONCLUSION: For cases with negative MRI findings, epilepsy surgery may be an alternative option for pharmaco-resistant patients if epileptogenic focus localizations by MEG are present in multimodal evaluation.
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Encéfalo , Epilepsia/diagnóstico , Imageamento por Ressonância Magnética , Magnetoencefalografia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão , Gravação em Vídeo , Adulto JovemRESUMO
In 2010 the International League against Epilepsy published a new classification of epilepsies. A major advance of this classification system is the acknowledgment of a genetic or pathologic-anatomic basis of epilepsy as important predictors of outcome (cause matters). This applies in particular to structural-metabolic lesions, which were frequently recognized in surgical specimens obtained from patients with drug-resistant focal epilepsy, i.e. hippocampal sclerosis, glioneuronal tumors, focal cortical dysplasias, vascular malformations, ischemia, intracerebral hemorrhage, glial scars or inflammation. A better understanding and classification of the etiopathology as well as the underlying molecular mechanisms will help to anticipate and appreciate the clinical course of a disease as well as to develop new and targeted drug treatment. Surgically available human brain tissue will be most helpful to support this approach but will also need careful neuropathological evaluation with accurate classification systems and use of terminology.
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Epilepsias Parciais/etiologia , Epilepsias Parciais/patologia , Classificação Internacional de Doenças , Terminologia como Assunto , HumanosRESUMO
FCDs are increasingly recognized in patients with drug-resistant epilepsies, and many patients benefit from tailored resection strategies. Yet, postsurgical seizure control cannot be sufficiently predicted and specification of FCD variants remains difficult during presurgical monitoring. The International League against Epilepsy (ILAE) has published a new consensus classification system for focal cortical dysplasias (FCDs). Based on a review of imaging data, electroclinical features and postsurgical seizure control correlation with neuropathological findings specify three clinico-pathological FCD subtypes: FCD Type I is characterized by aberrant radial (FCD Type Ia) or tangential lamination of the neocortex (FCD Type Ib) affecting one or multiple lobes. FCD Type II is characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). It is important to note, that these types should not be associated with any other structural brain lesion (isolated FCD). In contrast, a new FCD Type III is introduced, which occurs in combination with hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with other epileptogenic lesions obtained in early life (i.e., traumatic injury, ischemic injury or encephalitis). Histopathological features are very similar to those observed in FCD Type I, but likely present postnatal development and maturation failures acquired by the principal lesion. This first international consensus classification may encourage neuropathologists to focus their attention onto this important histopathological group. Addressing more precisely defined clinico-pathological entities will also help to clarify underlying pathomechanisms and, thereby, improve treatment strategies for patients with difficult-to-treat epilepsies.
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Consenso , Epilepsia , Cooperação Internacional , Malformações do Desenvolvimento Cortical/classificação , Malformações do Desenvolvimento Cortical/patologia , Encefalopatias/patologia , Europa (Continente) , Humanos , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo I , Neocórtex/patologia , Neurônios/patologiaRESUMO
OBJECTIVE: Surgical tumor resection remains the primary treatment strategy in ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD) and Nelson's syndrome (NS). However, an effective long-term pharmacological regime is not available in patients with persistent ACTH-hypersecretion. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is abundantly expressed in most pituitary adenomas. First encouraging data reported that the PPAR-gamma ligand rosiglitazone antagonizes ACTH hypersecretion and exerts also antiproliferative effects in pituitary cell lines. Herein, we studied the potential therapeutical effects of rosiglitazone in patients with ACTH-secreting pituitary adenomas in vitro and in vivo. MATERIALS AND METHODS: Seven patients with persistent ACTH-hypersecretion (3 with NS, 4 with persistent CD) were treated 5 months with rosiglitazone (4 - 16 mg/day). In vitro assays were performed in primary cell cultures obtained from eight additional patients with ACTH-secreting pituitary adenomas applying 80 microM rosiglitazone repeatedly over a time period of 14 days. RESULTS: Our long-term clinical trial with the PPAR-gamma activator rosiglitazone showed no amelioration of clinical symptoms nor an inhibiting effect on ACTH-secretion in vivo. In vitro, rosiglitazone treatment led to a statistically significant decrease of ACTH levels in 2 out of 8 primary cell cultures after 14 days compared to untreated controls. CONCLUSION: In contrast to the initially promising laboratory data gathered in pituitary cell line experiments and nude mice models, our experimental data obtained in primary human ACTH-expressing pituitary adenoma cell cultures as well as our clinical experience with a long-term rosiglitazone trial in approved antidiabetic doses support the recently reported disappointing reports on acute or short-term medical treatment of ACTH-hypersecretion with PPAR-gamma activators.
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Hormônio Adrenocorticotrópico/metabolismo , Hidrocortisona/metabolismo , Síndrome de Nelson/sangue , PPAR gama/agonistas , Hipersecreção Hipofisária de ACTH/sangue , Tiazolidinedionas/farmacologia , Adenoma/metabolismo , Adenoma/patologia , Adulto , Feminino , Humanos , Técnicas In Vitro , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndrome de Nelson/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Rosiglitazona , Tiazolidinedionas/uso terapêutico , Resultado do Tratamento , Células Tumorais CultivadasRESUMO
The ability to isolate and propagate adult stem/progenitor cells from the human brain opens novel avenues for cell replacement therapy. This will also apply to the pituitary gland, i.e., following tumor induced endocrine deficiency. Herein, we examine autopsy derived pituitaries to unravel a putative stem/progenitor cell population in humans. In tissue sections of the anterior lobe nestin immunoreactive cells co-expressing smooth muscle actin (SMA) were identified in the perivascular space, indicating a pericytic differentiation. Under clonal conditions, this particular cell population generated primary and secondary cell aggregates (spheres). Pituitary cell cultures maintained a stable cell cycle length with a doubling time of 10 days for over eight months. Forskolin treatment induced a prolactin-expressing phenotype in the majority of cell progenies as well as few betaIII-tubulin (Tuj1) expressing cells of putative neuronal lineage. The presence of sphere-forming, nestin-immunoreactive cells and their ability to generate differentiated cell lineages indicates the existence of a progenitor cell population persisting in the adult human pituitary. Further studies are needed to characterize this cell population in more detail and to clarify their potential to initiate neoplastic transformation for example in the cellular pathogenesis of pituitary adenoma.
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Hipófise/citologia , Células-Tronco/citologia , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/fisiologia , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Hipófise/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/metabolismoRESUMO
BACKGROUND: The syndrome of limbic encephalitis (LE) is characterized by subacute onset of temporal lobe epilepsy, loss of short-term memory, cognitive confusion and psychiatric symptoms. AIM: We report a patient with pharmacoresistant epilepsy who underwent presurgical video-electroencephalogram (EEG)-monitoring with normal psychiatric and neuropsychological findings. METHODS: Magnetic resonance imaging (MRI) revealed a hyperintense lesion within the right amygdala but no contrast enhancement. Analysis of cerebrospinal fluid (CSF) showed pleocytosis and positive oligoclonal bands, but all tests for neurotropic viruses or borrelia antibodies were negative. Presurgical evaluation identified a right mesiotemporal focus. RESULTS: As a tumour was the most likely differential diagnosis, we performed selective amygdalohippocampectomy of the right hemisphere. Subsequent histopathological examination revealed the surprising diagnosis of LE. As a consequence, tumour screening was initiated and a testicular carcinoma with high anti-Ma2-antibody titres was detected. Following surgical and chemotherapeutical treatment, the patient was seizure-free and Ma2-antibodies decreased below detection limits. Conclusion - This case report highlights that LE has to be considered even in patients with atypical clinical presentation, i.e. without neuropsychological deficits, if CSF analysis reveals an inflammatory response. When LE is diagnosed, extensive tumour search is mandatory to detect and treat the paraneoplastic origin of LE. Therapeutic strategies of LE include surgical treatment as well as early immunosuppression.
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Neoplasias Encefálicas/diagnóstico , Erros de Diagnóstico/prevenção & controle , Epilepsia do Lobo Temporal/etiologia , Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico , Adulto , Antígenos de Neoplasias/imunologia , Autoanticorpos/imunologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/imunologia , Transtornos Cognitivos/etiologia , Eletroencefalografia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Humanos , Encefalite Límbica/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Transtornos do Humor/etiologia , Proteínas do Tecido Nervoso/imunologia , Procedimentos Neurocirúrgicos , Neoplasias Testiculares/complicações , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/imunologiaRESUMO
OBJECTIVE: Recent reports showed that intraoperative ECoG activities can be analysed with respect to more complex spike patterns. We have systematically investigated different characteristic epileptiform activities in intraoperative ECoG and correlated them to postoperative outcome. METHODS: Intraoperative ECoG findings of patients with non-tumorous epilepsies (20 patients with Engel outcome 1a, 20 patients with Engel outcome 2-4) were analysed in order to differentiate ECoG characteristics in temporal lobe epilepsies (TLE). RESULTS: In addition to focal spiking with or without propagation, focal slowing in the theta or delta range and so-called ictaform ECoG patterns were found. These ictaform patterns occurred in 40% of the patients with TLE. CONCLUSIONS: Leading spikes in combination with focal slowing and ictaform patterns can contribute to a better delineation of mesial temporal epileptic activity in the anterior-posterior alignment. They provide an additional information which can be used for the extent of resection. SIGNIFICANCE: If the resected area included the anterior mesial regions, where interictal spikes, ictaform activity and slowing were localized, the postoperative outcome was good.
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Mapeamento Encefálico , Eletroencefalografia , Epilepsia do Lobo Temporal/fisiopatologia , Potenciais Evocados/fisiologia , Monitorização Intraoperatória , Adulto , Eletrodos Implantados , Epilepsia do Lobo Temporal/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Psicocirurgia/métodos , Resultado do TratamentoRESUMO
We report here a 27-year-old woman who presented with encephalitis of unknown origin. Magnetic resonance imaging (MRI) of the brain revealed leukoencephalopathy, cerebrospinal fluid showed signs of inflammation. Serum and brain biopsy tissue was tested positive for hepatitis C virus (HCV). Neuropathological investigation supported the hypothesis of viral encephalitis. C3, C4 and cryoglobulins as well as cerebral MR-angiography were normal. Neurological complications of HCV infection other than hepatic encephalopathy are generally attributed to parainfectious phenomena. This is the first case of HCV-RNA detection in vivo in human brain in literature and it raises the possibility that HCV is able to induce encephalitis caused by neurotrophism. This is supported by the fact that there is a growing body of literature on HCV-induced cerebral dysfunction and laboratory findings indicating HCV neuroinvasion.
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Encéfalo/virologia , Encefalite/patologia , Encefalite/virologia , Hepacivirus/genética , RNA/isolamento & purificação , Adulto , Feminino , Hepacivirus/isolamento & purificação , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodosRESUMO
AIM: Organotypic slice cultures (OSC) of human brain specimens represent an intriguing experimental model for translational studies addressing, e.g., stem cell transplantation in neurodegenerative diseases or targeting invasion by malignant glioma ex vivo. However, long-term viability and phenomena of structural reorganization of human OSC remain to be further characterized. Here, we report the use of (18)F-deoxyglucose (FDG) for evaluating the viability of brain slice preparations obtained either from postnatal rats or human hippocampal specimens. METHODS: Anatomically well preserved human hippocampi obtained from epilepsy surgery and rat hippocampus slice cultures obtained from six day old Wistar rats were dissected into horizontal slices. The slices were incubated with FDG in phosphate buffered saline up to 1 h, either with or without supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within the medium or slice cultures was measured using a gamma-counter. In addition, distribution of radioactivity was autoradiographically visualized and quantified as counts per mm(2). RESULTS: In rat hippocampal slices, FDG accumulated with 1 300 000 +/- 68 000 counts/mm(2), whereas the incorporation of the radioactive label in human slices was in the order of 1 500 000 +/- 370 000 counts/mm(2). The elevation of glucose concentration within the medium led to a significant three-fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in human specimens. CONCLUSIONS: FDG accumulated in organotypic brain cultures of human or rodent origin. FDG is thus suited to investigate the viability of OSC. Furthermore, these preparations open new ways to study the factors governing cerebral FDG uptake in brain tissue ex vivo.
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Fluordesoxiglucose F18/farmacocinética , Hipocampo/diagnóstico por imagem , Animais , Autorradiografia , Hipocampo/citologia , Humanos , Cinética , Camundongos , Técnicas de Cultura de Órgãos , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , RatosRESUMO
CASE REPORT: We report on a 46-year-old male patient with pharmacoresistant temporal lobe epilepsy (TLE). Based on ictal EEG patterns and MRI scans, Ammon's horn sclerosis (AHS) or an epilepsy-associated tumor was included in the differential diagnosis. RESULTS: Histopathological examination of the surgical specimen revealed the unusual finding of a monomorphous angiocentric neuroepithelial tumor composed of small round cells and bipolar processes with perivascular aggregation. Immunohistochemistry detected perivascular-oriented expression of GFAP and cytoplasmic immunoreactivity of EMA and vimentin. Mitotic or other signs of proliferative activity were lacking. During a 2-year follow-up, the patient was seizure-free. CONCLUSIONS: Albeit AHS is the most frequent finding in TLE specimens, uncommon neuroepithelial tumors with hippocampal growth pattern have to be considered in the differential diagnosis of mesial TLE. The present case meets the criteria of an angiocentric neuroepithelial tumor recently proposed as a new clinicopathological entity. These tumors may be compatible with a maldevelopmental origin during early brain development.