Estudo comparativo entre os tratamentos clinico e cirurgico para pacientes com epilepsia do lobo temporal mesial

Orientador: Helder TedeschiDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A epilepsia é uma doença crônica que acomete 0,5% a 2% da população em geral, sendo considerada a segunda patologia neurológica mais freqüente. A epilepsia de lobo temporal mesial (ELTM) com atrofia hipocampal é a forma mais freqüente das epilepsias parciais refratárias ao tratamento medicamentoso. Nestes pacientes, o tratamento cirúrgico é capaz de proporcionar uma redução da freqüência ou o controle total de crises. Com o objetivo de comparar a eficácia dos tratamentos cirúrgico e clínico realizamos um estudo prospectivo com 26 pacientes com ELTM que foram submetidos a tratamento cirúrgico e 75 pacientes com ELTM submetidos a tratamento medicamentoso entre agosto de 2002 e outubro de 2004 . Todos os pacientes apresentavam critérios de refratariedade, ou seja, controle inadequado de crises parciais com uso em doses máximas toleradas de pelo menos duas drogas antiepilépticas, durante pelo menos um ano. Utilizamos a análise de curva de sobrevivência de Kaplan-Meier em função do tempo de recorrência das crises para obter o intervalo de confiança dos pacientes sem crises e o teste log-rank para comparação do estado de controle de crises entre os grupos. A proporção acumulada dos pacientes sem crise (classe IA de Engel) foi maior no grupo submetido ao tratamento cirúrgico (73.1%) comparando-se com o grupo clínico (12%) (p<0.0001). No grupo cirúrgico, 2 de 26 pacientes (7.7%) apresentaram alterações neurológicas transitórias e 2 dos 26 (7.7%), alterações neurológicas permanentes relacionados ao procedimento cirúrgico. No grupo clínico, sete pacientes (9.3%) apresentaram eventos adversos graves durante o seguimento, tais como queimaduras e estado de mal epiléptico. O tratamento cirúrgico para ELTM refratária ao tratamento clínico prévio com duas DAEs foi mais eficiente que o tratamento clínico, incluindo novas tentativas de mono ou politerapiaAbstract: Epilepsy is a chronic disease that affects 0.5% to 2% of the general population, and is considered the second most frequent neurological condition in outpatient clinics. Mesial temporal lobe epilepsy (MTLE) associated to hippocampal sclerosis is the most frequent type of partial epilepsy in adult. A significant proportion of these patients do not respond to antiepileptic drugs (AEDs). For patients with MTLE and refractory seizures, surgery is considered an efficient treatment option. We prospectively studied 26 patients with MTLE who underwent surgical treatment and 75 patients with MTLE who underwent medical treatment between August 2002 and October 2004. All patients failed to achieve seizure control with at least two first line AED for partial seizures before entering the study. We used Kaplan-Meier survival analysis as a function of time of seizure recurrence to obtain estimates of 95% confident interval of seizure freedom and log-rank test to compare the status of seizure control between the two groups. The cumulative proportion of patients free of all seizures (Engel¿s class IA) was higher in the surgical group (73.1%) compared to the clinical group (12%) (p<0.0001). In the surgical group, 2 of 26 patients (7.7%) had transient adverse effects and 2 of 26 patients (7.7%) had a permanent deficit related to the surgical procedure. In the clinical group 7 patients had (9.3%) major adverse events during follow-up, including burns and status epilepticus. Surgical treatment for patients with MTLE who failed to achieve seizure control with two previous AED regimens was more efficient than medical treatment with further trials of AEDMestradoNeurologiaMestre em Ciências Médica

[chronic Subdural Hematoma: Study Of 161 Patients And The Relationship With Coagulation Abnormalities].

The chronic subdural hematoma represents one of the most frequent types of intracranial hemorrhage. One hundred sixty one patients operated in the Clinical Hospital of State University of Campinas-SP (UNICAMP) from April 1994 to May 2000, were analyzed retrospectively in order to characterize the population and to study the importance of the pre-operative coagulation analysis in the outcome. The majority of the population was male (86%), white (85.1%) and in the fifth decade (median age: 57 years). A high mortality index in the postoperative period was found in patients with INR (international normalized ratio) values greater than 1.25 and/or thrombocytopenia (p<0.001 and p=0.004 respectively). Patients with previous head injury history (76%) showed a lower mortality (p=0.044). The results stand out the importance of the pre-operative evaluation with coagulation studies in order to correct possible abnormalities.611011-

Chronic subdural hematoma: study of 161 patients and the relationship with coagulation abnormalities

The chronic subdural hematoma represents one of the most frequent types of intracranial hemorrhage. One hundred sixty one patients operated in the Clinical Hospital of State University of Campinas - SP (UNICAMP) from April 1994 to May 2000, were analyzed retrospectively in order to characterize the population and to study the importance of the pre-operative coagulation analysis in the outcome. The majority of the population was male (86%), white (85.1%) and in the fifth decade (median age: 57 years). A high mortality index in the postoperative period was found in patients with INR (international normalized ratio) values greater than 1.25 and/or thrombocytopenia (p<0.001 and p=0.004 respectively). Patients with previous head injury history (76%) showed a lower mortality (p=0.044). The results stand out the importance of the pre-operative evaluation with coagulation studies in order to correct possible abnormalities.O objetivo deste estudo é analisar a evolução de pacientes com hematoma subdural crônico em relação aos achados do coagulograma. Foram analisados 161 pacientes operados no Hospital das Clínicas-UNICAMP entre abril de 1994 e 2000. Foi detectado um predomínio do sexo masculino (86,3%), da cor branca (85,1%) e da faixa etária na quinta década (mediana 57 anos). O estudo mostrou mortalidade maior no período pós-operatório entre os pacientes com valores de RNI (international normalized ratio) superiores a 1,25 e/ou trombocitopenia (p<0,001 e p=0,004, respectivamente) e mortalidade menor para os pacientes com antecedente de traumatismo cranioencefálico (76%) (p=0,044). Os resultados ressaltam a importância da avaliação pré-operatória com o coagulograma a fim de se corrigir possíveis alterações.1011101

Artifacts in brain magnetic resonance imaging due to metallic dental objects

Objective: Artifacts caused by metallic objects, such as dental crowns, dental implants and metallic orthodontic appliances, are a common problem in head and neck MRI. The aim of this retrospective study was to identify the main metal dental objects that produce artifacts on brain MRIs.Study design: Imaged metallic artifacts and their sources were identifi ed. Artifact image plane was rated on a score of 0 or 1 (0 - distinguishable for diagnosis and 1 - not distinguishable for diagnosis).Results: Seventy-eight percent of the artifacts appearing in images were caused by orthodontic appliances, followed by dental titanium implants (18%) and metallic crowns (4%). Orthodontic appliances obtained the highest scores in all planes.Conclusions: We concluded that is diffi cult to avoid the effect of metallic artifacts in the maxillofacial regions on brain scan. Removing metallic parts of the orthodontic appliance should ensure diagnostically useful quality scans

Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome

BackgroundThe expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis.Case presentationHere, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells.ConclusionsFatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity

Long-term postoperative atrophy of contralateral hippocampus and cognitive function in unilateral refractory MTLE with unilateral hippocampal sclerosis

Objective: This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). Methods: We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. Results: The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p b 0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (±2.5 SD; median = 8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. Conclusions: We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms

Recovery of white matter atrophy after epilepsy surgery: structural evidences through voxel-based morphometry

OBJECTIVES: To study pre and postoperative WMA in MTLE patients. METHODS: We performed Voxel-Based Morphometry (VBM) with volume of interest (VOI) in 69 controls (mean age, 34.3±11.1 years) and 67 operated patients (mean age, 34.1±10.4 years) with unilateral MTLE. 34 became seizure-free (SzFree-Group), 23 improved (Engel IB-IIA [Partial recovery-group]) and 10 did not improve (Engel III-IV [Failure-Group]). All had pre and postoperative MRIs (one year minimum). We flipped MRIs of right MTLE patients in order to avoid right-to-left analysis cancelation. VBM was performed on SPM2/MATLAB7.0 with individual masks for surgical lacunae and 1% false-discovery-rate to control for multiple comparisons. We used MARSbar routine to select ROIs and t-test for statistical analyses. RESULTS: Mean postoperative follow-up was 60.2 (±SD 30.7) months. On baseline MRI, SzFree-Group showed White Matter Atrophy (WMA) involving temporal lobes [TL], ipsilateral occipital, parietal and frontal regions, with areas of significant recovery of WMA on postoperative MRI. Partial recovery-Group presented a more restricted pattern of WMA, involving ipsilateral temporal lobe, contralateral superior temporal gyrus and few areas in bilateral cingulated and orbitofrontal areas. In this group we also identified areas with relative increase of WM after surgery. By contrast, Failure-Group showed more widespread bi-hemispheric areas of WMA on baseline MRI without postoperative improvement. CONCLUSIONS: Although we have identified some differences in baseline WMA, we were unable to correlate a more widespread pattern with a worse prognosis, as SzFree-Group, also presented a bilateral distribution of WMA. The recovery of WMA in SzFree-Group and Partial recovery-group is in agreement with previous MRS and PET studies and suggests that a network of neuronal dysfunction in MTLE can be, at least in part, reversible after successful postoperative seizure control.071

The ENIGMA-Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy

Event-based modelling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multi-centre cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area and subcortical brain volumes from T1-weighted (T1W) MRI scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1,625 healthy controls from 25 centres. Features with a moderate case-control effect size (Cohen's d≥0.5) were used to train an Event-Based Model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age of onset and anti-seizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume and, finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated to duration of illness (Spearman's ρ=0.293, p=7.03x10-16 ), age of onset (ρ=-0.18, p=9.82x10-7 ) and ASM resistance (AUC=0.59, p=0.043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM stage zero, which represents MTLE-HS with mild or non-detectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features