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1.
Cereb Cortex ; 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31867595

RESUMO

Focal epilepsy can be conceptualized as a network disorder, and the functional epileptic network can be described as a complex system of multiple brain areas that interact dynamically to generate epileptic activity. However, we still do not fully understand the functional architecture of epileptic networks. We studied a cohort of 21 patients with extratemporal focal epilepsy. We used independent component analysis of functional magnetic resonance imaging (fMRI) data. In order to identify the epilepsy-related components, we examined the general linear model-derived electroencephalography-fMRI (EEG-fMRI) time courses associated with interictal epileptic activity as intrinsic hemodynamic epileptic biomarkers. Independent component analysis revealed components related to the epileptic time courses in all 21 patients. Each epilepsy-related component described a network of spatially distributed brain areas that corresponded to the specific epileptic network in each patient. We also provided evidence for the interaction between the epileptic activity generated at the epileptic network and the physiological resting state networks. Our findings suggest that independent component analysis, guided by EEG-fMRI epileptic time courses, have the potential to define the functional architecture of the epileptic network in a noninvasive way. These data could be useful in planning invasive EEG electrode placement, guiding surgical resections, and more effective therapeutic interventions.

2.
Front Neurol ; 10: 380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057476

RESUMO

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p < 0.05 and cluster size k = 50 and at uncorrected p < 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p < 0.05) than that obtained with the SPM threshold p < 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p < 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization.

4.
Br J Haematol ; 185(3): 480-491, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30793290

RESUMO

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

5.
J Neurol Neurosurg Psychiatry ; 90(1): 108-110, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29986904

RESUMO

OBJECTIVE: To describe an adult patient with Rasmussen's disease with focal dystonia as the most disabling symptom and the good response to unilateral globus pallidus internus (GPi) deep brain stimulation (DBS). METHODS: Retrospective review of clinical records and diagnostic tests. RESULTS: The patient had displayedmild focal seizures with sensory and motor symptoms on the left arm and hemiface since the age of 22. Ten years later she experienced abrupt onset of focal left dystonia involving mainly the leg. Brain MRI showed progressive right hemisphere atrophy, and  18 fluorodeoxyglucose-positron emission tomography (18FDG-PET) showed right hypometabolism mainly over the frontal and insular regions. Brain biopsy confirmed chronic encephalitis. The dystonia became very severe and made walking extremely difficult. Different treatments including dopaminergic, anticholinergic, immunomodulatory drugs and botulinum toxin were ineffective. Finally the patient was treated with unilateral GPi DBS. Shortly after the onset of the stimulation, the dystonia started to improve. Parameters have been adjusted, and 18 months after surgery the patient is able to walk and run unaided, although a mild left leg dystonia persists. CONCLUSION: Rasmussen's disease may be difficult to diagnose in adult patients. Associated movement disorders may be more disabling than seizures. Focal dystonia may be treated successfully with DBS.


Assuntos
Estimulação Encefálica Profunda/métodos , Distonia/terapia , Encefalite/fisiopatologia , Globo Pálido , Adulto , Anticonvulsivantes/uso terapêutico , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Doença Crônica , Distonia/etiologia , Distonia/fisiopatologia , Eletroencefalografia , Eletromiografia , Encefalite/complicações , Feminino , Humanos , Perna (Membro) , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Convulsões/tratamento farmacológico , Convulsões/etiologia , Convulsões/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único
6.
Neuroimage Clin ; 20: 742-752, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30238918

RESUMO

Chronic exposure to seizures in patients with left hemisphere (LH) epileptic focus could favor higher activation in the contralateral hemisphere during language processing, but the cognitive effects of this remain unclear. This study assesses the relationship between asymmetry in hemispheric activation during language fMRI and performance in verbal and non-verbal tasks. Whereas prior studies primarily used fMRI paradigms that favor frontal lobe activation and less prominent activation of the medial or superior temporal lobes, we used a verbal comprehension paradigm previously demonstrated to activate reliably receptive language areas. Forty-seven patients with drug-resistant epilepsy candidates for surgery underwent a multidisciplinary assessment, including a comprehensive neuropsychological evaluation and an fMRI verbal comprehension paradigm. Patients were distributed in two groups depending on laterality indexes (LI): typical hemispheric asymmetry (unilateral left activation preponderance; n = 23) and atypical hemispheric asymmetry (bilateral or unilateral right preponderance; n = 24). Right-handedness and right hemisphere (RH) focus were significant predictors of typical asymmetry. Patients with typical activation pattern presented better performance intelligence quotient and verbal learning than patients with atypical hemispheric asymmetry (for all, p < 0.014). Patients with LH focus had more frequently atypical hemispheric asymmetry than patients with RH focus (p = 0.05). Specifically, they showed lower LI and this was related to worse performance in verbal and non-verbal tasks. In conclusion, an increased activation of homologous RH areas for verbal comprehension processing could imply a competition of cognitive resources in the performance of the same task, disrupting cognitive performance.


Assuntos
Compreensão , Epilepsia/fisiopatologia , Epilepsia/psicologia , Linguagem , Adolescente , Adulto , Mapeamento Encefálico , Cognição , Feminino , Lateralidade Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
7.
Eur J Nucl Med Mol Imaging ; 45(13): 2358-2367, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30069576

RESUMO

PURPOSE: We present a modified version of the SISCOM procedure that uses interictal PET instead of interictal SPECT for seizure onset zone localization. We called this new nuclear imaging processing technique PISCOM (PET interictal subtracted ictal SPECT coregistered with MRI). METHODS: We retrospectively studied 23 patients (age range 4-61 years) with medically refractory epilepsy who had undergone MRI, ictal SPECT, interictal SPECT and interictal FDG PET and who had been seizure-free for at least 2 years after surgical treatment. FDG PET images were reprocessed (rFDG PET) to assimilate SPECT features for image subtraction. Interictal SPECT and rFDG PET were compared using statistical parametric mapping (SPM). PISCOM and SISCOM images were evaluated visually and using an automated volume of interest-based analysis. The results of the two studies were compared with each other and with the known surgical resection site. RESULTS: SPM showed no significant differences in cortical activity between SPECT and rFDG PET images. PISCOM and SISCOM showed equivalent results in 17 of 23 patients (74%). The seizure onset zone was successfully identified in 19 patients (83%) by PISCOM and in 17 (74%) by SISCOM: in 15 patients (65%) the two techniques showed concordant successful results. The volume of interest-based analysis showed no significant differences between PISCOM and SISCOM in identifying the extension of the seizure onset zone. However, PISCOM showed a lower amount of indeterminate activity due to propagation, background or artefacts. CONCLUSION: Preliminary findings of this initial proof-of-concept study suggest that perfusion and glucose metabolism in the cerebral cortex can be correlated and that PISCOM may be a valid technique for identification of the seizure onset zone. However, further studies are needed to validate these results.


Assuntos
Epilepsia/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Imagem Multimodal/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único , Adulto Jovem
8.
Neurotherapeutics ; 15(4): 1082-1092, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30066084

RESUMO

Psychiatric morbidity in drug-resistant epilepsy is frequent. Surgery is the best therapeutic alternative for treating seizures, but the current evidence concerning the effects of surgery on psychiatric disorders (PDs) is inconclusive. We aim to clarify surgery's role in long-term PDs. Using a prospective controlled study, we analyzed the psychopathologic outcomes of patients with drug-resistant epilepsy, comparing those who underwent surgery to those who did not due to not being suitable. Surgical candidates were paired (n = 84) with the immediately following nonsurgical candidates (n = 68). Both groups continued their usual medical treatment. We studied psychiatric changes for each group and analyzed de novo and remission cases. The assessments were made during the presurgical evaluation, and at 6 months (6-M) and 12 months (12-M) after surgery. Finally, we determined associated factors for postsurgical PDs. At 12 months, using the Hospital Anxiety and Depression Scale (HADS), anxiety improved in both groups (p = 0.000), while depression improved only in the surgical group (p = 0.016). Moreover, all symptom dimensions on the Symptom Checklist-90-R (SCL-90), as well as severity, distress, and total symptoms, decreased only in the surgical group. These ameliorations reached not only statistical significance but also clinical significance for depression (HADS) (p = 0.014) and the interictal dysphoric disorder (p = 0.013). The main predictors for PDs after surgery were as follows: the presurgical and 6-month psychiatric symptoms, the absence of surgery, seizure outcomes, and some antiepileptic and psychiatric drugs. This study provides evidence that surgery for epilepsy could have a role in improving some symptoms of psychiatric disorders 12-M after the surgery.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Transtornos Mentais/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Adulto , Eletroencefalografia , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos Mentais/diagnóstico por imagem , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos
9.
Epilepsy Res ; 129: 101-105, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28043058

RESUMO

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients.


Assuntos
Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Epilepsia Resistente a Medicamentos/imunologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/imunologia , Epilepsia do Lobo Temporal/cirurgia , Adolescente , Adulto , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/cirurgia , Criança , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico por imagem , Europa (Continente) , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Estados Unidos , Adulto Jovem
10.
Neuroimage Clin ; 12: 976-989, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27995064

RESUMO

OBJECTIVES: Several studies using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) or diffusion tensor imaging (DTI) have found both temporal and extratemporal abnormalities in patients with mesial temporal lobe epilepsy with ipsilateral hippocampal sclerosis (MTLE-HS), but data are lacking about the findings of both techniques in the same patients. We aimed to determine whether the extent of 18F-FDG-PET hypometabolism is related to DTI abnormalities. METHODS: Twenty-one patients with MTLE-HS underwent comprehensive preoperative evaluation; 18 (86%) of these underwent epilepsy surgery. We analyzed and compared the pattern of white matter (WM) alterations on DTI and cortical hypometabolism on 18F-FDG-PET. RESULTS: We found widespread temporal and extratemporal 18F-FDG-PET and DTI abnormalities. Patterns of WM abnormalities and cortical glucose hypometabolism involved similar brain regions, being more extensive in the left than the right MTLE-HS. We classified patients into three groups according to temporal 18F-FDG-PET patterns: hypometabolism restricted to the anterior third (n = 7), hypometabolism extending to the middle third (n = 7), and hypometabolism extending to the posterior third (n = 7). Patients with anterior temporal hypometabolism showed DTI abnormalities in anterior association and commissural tracts while patients with posterior hypometabolism showed WM alterations in anterior and posterior tracts. CONCLUSIONS: Patients with MTLE-HS have widespread metabolic and microstructural abnormalities that involve similar regions. The distribution patterns of these gray and white matter abnormalities differ between patients with left or right MTLE, but also with the extent of the 18F-FDG-PET hypometabolism along the epileptogenic temporal lobe. These findings suggest a variable network involvement among patients with MTLE-HS.


Assuntos
Imagem de Tensor de Difusão/métodos , Epilepsia do Lobo Temporal , Substância Cinzenta , Hipocampo , Tomografia por Emissão de Pósitrons/métodos , Substância Branca , Adolescente , Adulto , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Feminino , Fluordesoxiglucose F18 , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Esclerose/diagnóstico por imagem , Esclerose/metabolismo , Esclerose/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Substância Branca/patologia , Adulto Jovem
11.
Epilepsia ; 57(10): 1680-1690, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27562413

RESUMO

OBJECTIVE: Psychiatric morbidity in drug-resistant epilepsy is frequent and has a negative influence on quality of life. Surgery is proven to be the best therapeutic alternative for treating seizures. However, it is inconclusive with the current evidence whether surgery, per se, is a risk factor or promotes amelioration of psychiatric disorders. Until now, most studies have been cross-sectional with small or heterogeneous groups. In addition, the few prospective studies did not have an identical control group. The present study aims to clarify the role of surgery in psychopathologic alterations. METHODS: We analyzed, through a prospective case-control study, the psychopathologic outcomes of patients with drug-resistant epilepsy, comparing those who underwent surgery and those who continued with pharmacologic treatment due to not being suitable for surgery. The assessments were performed during presurgical evaluation and 6 months after surgery. We studied psychiatric changes for each group, compared differences between groups, and also analyzed de novo and remission cases. Finally, we determined associated factors for postsurgical psychiatric disturbances. RESULTS: The surgical group experienced a significant decrease in psychopathologic alterations in comparison with the control group. In addition, distress perception of surgical patients also improved, whereas it did not decrease in the control group. Patients who underwent surgery presented a decrease in depressive and anxiety symptoms, whereas the nonsurgical group increased its anxiety levels. De novo disturbances that appeared after surgery were less frequent than in nonsurgical patients. We observed significant favorable outcomes considering de novo versus remission cases for anxiety, depression, and total symptoms only in the surgical group. The two main predictors for psychiatric disorders after surgery were presurgical psychiatric functioning and surgery. SIGNIFICANCE: Provides evidence that surgery improves psychiatric functioning in drug-resistant epilepsy through a prospective controlled study.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Transtornos Mentais/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/fisiopatologia , Adulto , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Eletroencefalografia , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Transtornos Mentais/diagnóstico por imagem , Pessoa de Meia-Idade , Testes Neuropsicológicos , Complicações Pós-Operatórias/diagnóstico por imagem , Escalas de Graduação Psiquiátrica , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
12.
Epilepsia ; 57(8): 1236-44, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27286896

RESUMO

OBJECTIVE: Neuroimaging is crucial in the presurgical evaluation of patients with medically refractory epilepsy. To improve the moderate sensitivity of [(18) F]fluorodeoxyglucose-positron emission tomography ((18) F-FDG-PET), our aim was to evaluate the usefulness of statistical parametric mapping (SPM) to localize the seizure-onset zone (SOZ) in PET studies deemed normal by visual assessment. METHODS: Fifty-five patients with medically refractory epilepsy whose (18) F-FDG-PET was visually evaluated as normal were retrospectively included. Twenty of these patients had undergone surgical intervention. PET images were analyzed by SPM8 using a corrected p-value of p < 0.05 and three uncorrected p-values of p < 0.0001, p < 0.001, and p < 0.005, matched with minimum cluster sizes of k > 0, k > 20, k > 100, and k > 200, respectively. The SPM-identified potential seizure zone (SZ) was compared to the SOZ, which was determined by consensus during patient management meetings in the epilepsy unit, taking into account presurgical tests. Studies in which the SPM-identified potential SZ was concordant with the SOZ were considered "correctly localizing." RESULTS: The SPM threshold combination with the least restrictive p-value and greatest minimum cluster size achieved the highest rate of correctly localizing studies. When p < 0.005/k > 200 was used, 40% (22/55) of studies were correctly localizing, and the concordance obtained in the surgically intervened subgroup was substantial (к = 0.607, 95% confidence interval [CI] 0.258-0.957), which was comparable to the concordance obtained by magnetic resonance imaging (MRI) (к = 0.783, 95% CI 0.509-1.000). SIGNIFICANCE: SPM offers improved SOZ localization in (18) F-FDG-PET studies that are negative on visual assessment. For this purpose, statistical parametric maps could be thresholded with liberal p-values and restrictive cluster sizes.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Adulto , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/metabolismo , Adulto Jovem
14.
Diagn Pathol ; 10: 158, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26369323

RESUMO

We report an unusual case of a 70-year-old male with history of hereditary spherocytosis (HS) and secondary paraspinal extramedullary hematopoiesis with a concurrent follicular lymphoma. The lesion presented as a thoracic paraspinal mass of 9 cm, extending longitudinally between T6 and T9 vertebral bodies. Incisional biopsy revealed that this mass included mature hematopoietic tissue compatible with extramedullary hematopoiesis (EMH). The tissue also presented an extensive and diffuse infiltration by an atypical lymphoid population composed predominantly by small cells. The immunohistochemical study revealed that the atypical lymphoid population had a germinal center phenotype, consistent with the diffuse variant of follicular lymphoma (FL). The simultaneous presence of both EMH and FL in the same lesion made the interpretation and the final diagnosis of this case difficult. The presence of EMH in this clinical context may eclipse the diagnosis of the underlying lymphoproliferative neoplasm. The close association between the tumor cells and extramedullary hematopoietic tissue in the absence of lymphadenopathies or other tissue involvement suggests a relationship of this tumor with the recently described primary FL of the bone marrow.


Assuntos
Hematopoese Extramedular , Linfoma Folicular/complicações , Linfoma Folicular/patologia , Esferocitose Hereditária/complicações , Idoso , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Masculino
15.
Ann Hematol ; 94(5): 803-12, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25501975

RESUMO

A retrospective study was performed to assess the outcome of patients with diffuse large B cell lymphoma (DLBCL) who did not achieve complete response or who relapsed before and after the use of rituximab. Clinical features and outcome of 816 (425 M/391 F; median age 63 years) patients diagnosed from 1991 to 2001 (pre-rituximab era, N = 348) and from 2002 to 2012 (rituximab era, N = 468) in a single institution were evaluated. Five hundred fifty-three patients achieved complete remission (CR), 57 partial response (PR), and 206 were refractory with a median overall survival of 15, 1.5, and 0.4 years, respectively. Patients receiving rituximab had lower risk of refractoriness or relapse. In primarily refractory and PR patients, there was not a difference in survival depending on whether patients received or not rituximab-containing frontline treatment. Early death rate was 11%, including 3.6% due to infectious complications. Rituximab did not modify these figures. In the relapse setting, 5-year survival from relapse was 25% for patients who never received rituximab, 54% for those who received rituximab only at relapse, and 48% for those treated with immunochemotherapy both as frontline and at relapse. In conclusion, relapsed/refractory patients with DLBCL show poor prognosis despite the use of frontline immunochemotherapy. New therapeutic approaches are needed in this group of patients.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Rituximab , Adulto Jovem
16.
J Nucl Med ; 55(7): 1099-105, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24799620

RESUMO

UNLABELLED: A precise assessment of the drug-resistant epileptic pediatric population for surgical candidacy is often challenging, and to date there are no evidence-based guidelines for presurgical identification of the epileptogenic zone. To evaluate the usefulness of radionuclide imaging techniques for presurgical evaluation of epileptic pediatric patients, we compared the results of video-electroencephalography (EEG), brain MR imaging, interictal SPECT, ictal SPECT, subtraction ictal SPECT coregistered to MR imaging (SISCOM), and interictal PET with (18)F-FDG. METHODS: Fifty-four children with drug-resistant epilepsy who had undergone video-EEG monitoring, brain MR imaging, interictal and ictal brain perfusion SPECT, SISCOM, and (18)F-FDG PET were included in this study. All abnormal findings revealed by these neuroimaging techniques were compared with the presumed location of the epileptogenic zone (PEZ) as determined by video-EEG and clinical data. The proportion of localizing studies for each technique was statistically compared. In the 18 patients who underwent resective brain surgery, neuroimaging results were compared with histopathology results and surgical outcome. RESULTS: SISCOM and (18)F-FDG PET concordance with the PEZ was significantly higher than MR imaging (P < 0.05). MR imaging showed localizing results in 21 of 54 cases (39%), SISCOM in 36 of 54 cases (67%), and (18)F-FDG PET in 31 of 54 cases (57%). If we consider SISCOM and (18)F-FDG PET results together, nuclear medicine imaging techniques showed coinciding video-EEG results in 76% of patients (41/54). In those cases in which MR imaging failed to identify any epileptogenic lesion (61% [33/54]), SISCOM or (18)F-FDG PET findings matched PEZ in 67% (22/33) of cases. CONCLUSION: SISCOM and (18)F-FDG PET provide complementary presurgical information that matched video-EEG results and clinical data in three fourths of our sample. SISCOM was particularly useful in those cases in which MR imaging findings were abnormal but no epileptogenic lesion was identified. Radionuclide imaging techniques are both useful and reliable, extending the possibility of surgical treatment to patients who may have been discouraged without a nuclear medicine approach.


Assuntos
Epilepsia/diagnóstico , Imagem por Ressonância Magnética , Imagem Multimodal , Técnica de Subtração , Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Criança , Pré-Escolar , Resistência a Medicamentos , Epilepsia/diagnóstico por imagem , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
IEEE Trans Med Imaging ; 33(10): 1931-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24876110

RESUMO

Monte Carlo (MC) simulation provides a flexible and robust framework to efficiently evaluate and optimize image processing methods in emission tomography. In this work we present Brain-VISET (Voxel-based Iterative Simulation for Emission Tomography), a method that aims to simulate realistic [ (99m) Tc]-SPECT and [ (18) F]-PET brain databases by including anatomical and functional information. To this end, activity and attenuation maps generated using high-resolution anatomical images from patients were used as input maps in a MC projector to simulate SPECT or PET sinograms. The reconstructed images were compared with the corresponding real SPECT or PET studies in an iterative process where the activity inputs maps were being modified at each iteration. Datasets of 30 refractory epileptic patients were used to assess the new method. Each set consisted of structural images (MRI and CT) and functional studies (SPECT and PET), thereby allowing the inclusion of anatomical and functional variability in the simulation input models. SPECT and PET sinograms were obtained using the SimSET package and were reconstructed with the same protocols as those employed for the clinical studies. The convergence of Brain-VISET was evaluated by studying the behavior throughout iterations of the correlation coefficient, the quotient image histogram and a ROI analysis comparing simulated with real studies. The realism of generated maps was also evaluated. Our findings show that Brain-VISET is able to generate realistic SPECT and PET studies and that four iterations is a suitable number of iterations to guarantee a good agreement between simulated and real studies.


Assuntos
Encéfalo/diagnóstico por imagem , Neuroimagem Funcional/métodos , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Algoritmos , Simulação por Computador , Bases de Dados Factuais , Epilepsia/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Método de Monte Carlo
18.
Epilepsia ; 54(12): 2143-50, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24304437

RESUMO

OBJECTIVE: Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity. METHODS: We included 12 patients (six male, 4-53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[(11) C]methyl-l-tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG recording. AMT uptake in each tuber was visually evaluated on PET coregistered with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also calculated. Sensitivity and specificity values of AMT-PET in the detection of epileptogenic lesions were obtained, using the available electroclinical and neuroimaging evidence as the gold standard for epileptogenicity. RESULTS: A total of 126 tubers were identified. Two of 12 patients demonstrated a tuber with clearly increased AMT uptake, one of whom also showed a subtle increased AMT uptake in another contralateral tuber. Four other patients showed only subtle increased AMT uptake. The only two tubers with clearly increased AMT uptake proved to be epileptogenic based on intracerebral EEG data, whereas none of the tubers associated with subtle increased AMT uptake were involved at ictal onset. In a per-patient approach, this yielded a sensitivity of clearly increased AMT uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3-34%) and 100% (95% CI: 97-100%), respectively. SIGNIFICANCE: AMT-PET is a specific neuroimaging technique in the identification of epileptogenic tubers in TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still deserves to be considered according to the challenging complexity of epilepsy surgery in tuberous sclerosis.


Assuntos
Epilepsia/etiologia , Esclerose Tuberosa/complicações , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia por Emissão de Pósitrons/métodos , Triptofano/análogos & derivados , Esclerose Tuberosa/diagnóstico por imagem , Adulto Jovem
19.
Epilepsy Res ; 107(1-2): 75-81, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24054426

RESUMO

PURPOSE: While there is solid experimental evidence of brain oxidative stress in animal models of epilepsy, it has not been thoroughly verified in epileptic human brain. Our purpose was to determine and to compare oxidative stress markers in the neocortex of epileptic and non-epileptic humans, with the final objective of confirming oxidative stress phenomena in human epileptic brain. METHODS: Neocortical samples from drug-resistant epilepsy patients submitted to epilepsy surgery (n=20) and from control, non-epileptic cortex samples (n=11) obtained from brain bank donors without neurological disease, were studied for oxidative stress markers: levels of reactive oxygen species (ROS), such as superoxide anion (O2(-)); activity of antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR); and markers of damage to biomolecules (lipid peroxidation and DNA oxidation). RESULTS: Compared with non-epileptic controls, the neocortex of epileptic patients displayed increased levels of superoxide anion (P≤0.001), catalase (P≤0.01), and DNA oxidation (P≤0.001); a decrease in GPx (P≤0.05), and no differences in SOD, GR and lipid peroxidation. CONCLUSIONS: Our findings in humans are in agreement with those found in animal models, supporting oxidative stress as a relevant mechanism also in human epilepsy. The concurrent increase in catalase and decrease in GPx, together with unchanged SOD levels, suggests catalase as the main antioxidant enzyme in human epileptic neocortex. The substantial increase in the levels of O2(-) and 8-oxo-dG in epileptic patients supports a connection between chronic seizures and ROS-mediated neural damage.


Assuntos
Epilepsia/metabolismo , Neocórtex/metabolismo , Estresse Oxidativo/fisiologia , Adulto , Anticonvulsivantes/uso terapêutico , Biomarcadores/metabolismo , Catalase/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Feminino , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/cirurgia , Psicocirurgia , Retratamento , Superóxido Dismutase/metabolismo , Falha de Tratamento
20.
Epilepsia ; 54(4): 678-90, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23362864

RESUMO

PURPOSE: The aim of this study was to apply sequential analysis of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data to study the cortical substrates related to the generation of the interictal epileptiform activity (IEA) in patients with pharmacoresistant extratemporal epilepsy. METHODS: We analyzed fMRI data from 21 children, adolescents, and young adults patients who showed frequent bursts or runs of spikes on EEG, by using the sequential analysis method. We contrasted consecutive fixed-width blocks of 10 s to obtain the relative variations in cerebral activity along the entire fMRI runs. Significant responses (p < 0.05, family-wise error (FWE) corrected), time-related to the IEA recorded on scalp EEG, were considered potential IEA cortical sources. These results were compared with those from the fluorodeoxyglucose-positron emission tomography (FDG-PET), intracranial EEG (two patients), and surgery outcome (eight patients). KEY FINDINGS: The typical IEA was recorded in all patients. After the sequential analysis, at least one significant blood oxygen level-dependent (BOLD) response spatially consistent with the presumed epileptogenic zone was found. These IEA-related activation areas coincided when superimposed with the hypometabolism depicted by the FDG-PET. These data were also consistent with the invasive EEG findings. Epileptic seizures were recorded in eight patients. A subset of IEA-associated fMRI activations was consistent the activations at seizure-onset determined by sequential analysis. The inclusion of the IEA-related areas in the resection rendered the patients seizure-free (five of eight operated patients). SIGNIFICANCE: The EEG-fMRI data sequential analysis could noninvasively identify cortical areas involved in the IEA generation. The spatial relationship of these areas with the cortical metabolic abnormalities depicted by the FDG-PET and their intrinsic relationship regarding the ictal-onset zone could be useful in epilepsy surgery planning.


Assuntos
Córtex Cerebral/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Oxigênio/sangue , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Resultado do Tratamento , Adulto Jovem
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