7 research outputs found

    Language assessment in mesial temporal lobe epilepsy : correlations with structural and functional neuroimaging

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    Orientadores: Fernando Cendes, Marcio Luiz Figueredo BalthazarTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A epilepsia de lobo temporal (ELT) é o tipo de epilepsia mais comum no adulto e comorbidades cognitivas podem acompanhá-la, como prejuízos de memória e linguagem. Nesta população é esperada uma maior incidência de pessoas com lateralização atípica para linguagem (LAL), 20% contra 5% da população saudável. Alguns fatores são apontados como preditores: dominância manual, sinistralidade familiar e insulto cerebral precoce e em hemisfério esquerdo. A linguagem nesses pacientes tem sido estudada há décadas, mas ultimamente a técnica de ressonância magnética funcional (fMRI) vem substituindo o teste de WADA e proporcionado uma série de novos métodos e paradigmas para estudar essa função in vivo, inclusive em indivíduos saudáveis. Portanto, o objetivo desse estudo foi delinear os subtipos de ELT, com atrofia esquerda (AHE), direita (AHD) e sem atrofia (negAH) hipocampal comparando-os com controles, quanto a aspectos de linguagem. Os resultados foram dispostos em dois artigos. O primeiro tratou da comparação de dois paradigmas de fMRI de linguagem baseados em decisão semântica. Neste artigo, 24 indivíduos saudáveis foram submetidos a duas versões de tarefa de linguagem: versão complexa e versão fácil. Ambas foram efetivas, porém a versão complexa produziu resultados mais robustos para a avaliação da linguagem. Logo, foi a versão eleita para conduzir o estudo com os pacientes ELT. O segundo resultado, foi exposto no artigo que comparou pacientes com AHD (n=31), AHE (n=32) e negAH (n=30), além de controles (n=101). Esse artigo investigou o impacto da atrofia hipocampal no perfil de linguagem em diferentes subtipos de ELT; avaliando a incidência e fatores preditivos de lateralização de linguagem, sua relação com o padrão de ativação da fMRI em regiões associadas à linguagem; comparação entre os grupos quanto ao padrão de ativação de linguagem e conectividade funcional, além da comparação do desempenho no teste de nomeação de Boston e sua correlação com o padrão de ativação da tarefa. Os resultados apontaram para frequência de LAL semelhante em todos os grupos e somente a dominância manual como preditor de dominância hemisférica para linguagem, porém, de forma distinta em cada grupo de acordo com as regiões de interesse. O padrão de ativação da linguagem e a análise entre regiões de interesse (ROI-to-ROI) apontaram pior desempenho do grupo AHE em relação aos grupos controle e negAH. A análise entre o giro frontal médio esquerdo e o cérebro todo (seed-based-voxel) mostrou que todos os grupos de pacientes apresentam conectividade funcional diminuída em relação aos controles, além de diferenças par a par entre os grupos de pacientes. O melhor desempenho em nomeação se correlacionou com maior ativação em áreas de linguagem nos grupos AHD e negAH. Este estudo concluiu que pacientes com AHE apresentaram pior desempenho em nomeação, ativação e conectividade funcional, seguidos pelos pacientes com AHD, enquanto os pacientes negAH apresentaram alterações discretas em comparação aos controles. Esta tese mostra que apesar dos vários estudos de fMRI sobre linguagem, novos trabalhos com diferentes metodologias e paradigmas são necessários para compreender melhor as alterações de linguagem em subtipos de ELTAbstract: Temporal lobe epilepsy is the most common type of epilepsy in adults and is also associated with cognitive comorbidities, such as memory and language impairments, especially in temporal lobe epilepsy (TLE). In this population, a higher incidence of people with atypical language lateralization (ALL) is expected; 20% against 5% of the healthy people. Some factors are pointed as predictors: manual dominance, left-hand familial history, as well as early insult and left hemisphere lesion. Language in these patients has been studied for decades. Lately functional magnetic resonance (fMRI) technique has been replacing the WADA test and has provided new methods and paradigms to study this function in vivo, including in healthy volunteers. Therefore, the objective of this study was to delineate the language aspects in TLE with left (LHA) and right (RHA) hippocampal atrophy and patients without hippocampal atrophy (nonAH), comparing them to controls. The results were set out in two manuscripts. The first, showed the translation of a well-established language fMRI paradigm based on semantic decision and comparison of two versions: easy and complex task in 24 healthy subjects. Both versions were effective, but the complex version produced more robust results for the evaluation of the language in our patients. Therefore, complex version was chosen to conduct the study with TLE patients. The second result was presented in the manuscript which compared patients with RHA (n=31), LHA (n=32), nonHA (n=30) and controls (n=101). In this paper analyzes were performed to investigate the impact of HA on language to obtain a profile of the language in different subtypes of TLE. Analyzes were conducted to acquire the incidence of language lateralization, predictive factors and correlation with fMRI activation pattern in regions associated with language; comparison between groups regarding language activation pattern and functional connectivity, as well as a comparison of performance on the Boston naming test and its correlation with the task activation pattern. The results pointed to a similar frequency of ALL in all groups and only manual dominance as a predictor of hemispheric dominance for language. However, each group was different according to the specific regions of interest. Language activation pattern and ROI-to-ROI analysis showed that LHA presented reduced activation compared with controls and nonHA groups. Seed-based-voxel analysis showed that all groups of patients had reduced functional connectivity in relation to controls, as well as differences among patients. The higher scores on naming performance was correlated with greater activation in language areas only in RHA and nonHA groups. We concluded that patients with LHA presented worse performance in naming, activation and functional connectivity, followed by RHA, and nonHA patients were more similar to controls. This thesis shows that despite of several language fMRI studies, further investigations using different methodologies and paradigms are necessary for better undestanding of language alterations in different TLE subtypesDoutoradoFisiopatologia MédicaDoutora em Ciências2012/05364-817229/12-0FAPESPCAPESBE

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

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    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

    Neuropsychological profile assessment of patients with spinocerebelar ataxia type 3 : correlations with structural and spectroscopy neuroimaging and CAG lenghts

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    Orientadores: Fernando Cendes, Marcio Luiz Figueredo BalthazarDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Cências MédicasResumo: A doença de Machado Joseph ou ataxia espinocerebelar tipo 3 (DMJ/SCA3) se caracteriza pela marcha atáxica e diversos sinais extracerebelares. Manifestações neuropsiquiátricas e cognitivas já foram descritas, porém não há um consenso quanto aos domínios cognitivos alterados. Portanto nosso objetivo foi investigar os aspectos neuropsicológicos na SCA3 e correlacionar os domínios cognitivos comprometidos com volume de substância cinzenta (SC), integridade de substância branca (FA), metabólitos cerebelares, repetição de CAG, tempo de duração e gravidade da doença. Participaram 32 pacientes com SCA3 pareados por idade, gênero e escolaridade com 32 controles saudáveis. Adquirimos IRM-3T- 3D ponderadas em T1 para análise de morfometria baseada em voxel, processadas e analisadas pelo software SPM8; imagens por tensor de difusão, processadas e analisadas pelo software FSL e espectroscopia por ressonância magnética (single-voxel em cerebelo) processadas pelo software LCModel. Todos os participantes realizaram o mesmo protocolo de avaliação neuropsicológica (NPs). Somente os pacientes com SCA3 se submeteram a escala para avaliação da gravidade da ataxia e pelo inventário neuropsiquiátrico. Utilizamos o teste Mann-Witney para comparação entre grupos quanto à avaliação NPs e correlação de Spearman entre os achados cognitivos e os metabólitos cerebelares, FA, número de CAG, tempo de duração e gravidade da doença. Consideramos p<0.05 não corrigido para múltiplas comparações. Para correlação entre os achados cognitivos e SC usamos cluster-size=50 voxel, p<0.001 (não corrigidos). Encontramos diferença significativa entre grupos nos testes: Rey auditory verbal learning test (RAVLT)-codificação [p=0.001], evocação tardia [p=0.001] e reconhecimento [p=0.027], matrizes progressivas: escala geral [p=0.003]; blocos de Corsi- ordem direta [p=0.002]; blocos de Corsi- ordem inversa [p=0.001]; span de dígitos- ordem direta [p=0.024]; fluência verbal categórica [p=0.029]; sintomas indicativos de depressão [p<0.001] e ansiedade [p<0.001]. A análise qualitativa mostrou prejuízo leve no RAVLT- codificação e médio inferior nos demais achados cognitivos. Houve correlação positiva entre RAVLT-codificação e áreas do córtex temporal, frontal, ínsula e cúlmen cerebelar; RAVLT-evocação tardia e giro précentral, cúlmen, áreas do córtex frontal, temporal e parietal; RAVLTreconhecimento e giro frontal; matrizes progressivas e precúneo e giro temporal; blocos de Corsi- ordem direta e lobo parietal; dígitos- ordem direta e giro temporal e fluência verbal com giro precentral. Todos os p<0.001. Houve correlação entre valor de FA do tronco cerebral de pacientes SCA3 e o teste dígitos- ordem direta [rs=0.485]. Encontramos diferença significativa entre grupos quanto aos metabólitos cerebelares: N-Acetil-Aspartato [p<0.001], N-Acetil-Aspartato-total [p<0.001], glutamato [p=0.017], glutamina [p=0.005], fosfocolina [p=0.019] e compostos de colina [p=0.014], exceto creatina [p=0.522] e inositol [p=0.475]. Houve correlação entre o teste blocos de Corsi- ordem direta e glutamato [rs=- 0.405] e glutamina [rs=-0.419]; fluência verbal semântica fosfocolina [rs= 0.669] e compostos de colina [rs=0.692] e dígitos- ordem direta e N-Acetil-Aspartato [rs=0.418] e N-Acetil-Aspartato-total [rs=0.432]. Não encontramos correlação entre os achados cognitivos e aspectos genético e clínicos. Os resultados sugerem que pacientes com SCA3 apresentam comprometimento de memória episódica e operacional e habilidades visuoespaciais associados a alterações encefálicas. As alterações neuropsiquiátricas apontam para heterogeneidade na doença também referente a esse aspecto e a falta de correlação entre os aspectos cognitivos e os aspectos genéticos e clínicos sugerem que essas variáveis ocorrem independentementeAbstract: The Machado- Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) is characterized by ataxic gait and extracerebellar signs. Neuropsychiatric and cognitive impairment have demonstrated, however there is no consensus on the cognitive domains altered. Therefore, the aim of this study was to investigate the neuropsychological features in SCA3 and correlate the cognitive findings with the gray matter (GM) volume, integrity of white matter, by means of the fractional anisotropy (WM-FA), cerebellar metabolites, CAG lengths, disease duration and severity. Participated 32 SCA3 patients matched by age, gender and educational level with 32 healthy control group. We acquired MRI-3T-3D, T1- weighted for voxel-based-morfometry, processed and analyzed using the SPM8 software, diffusion tensor images (DTI) processed and analyzed by FSL software and magnetic resonance spectroscopy (RMS- single voxel cerebellum) analyzed using LCModel software. All participants underwent the same neuropsychological evaluation. Only SCA3 patients underwent the scale for the assessment and rating of ataxia and Neuropsychiatric inventory. We used the Mann-Whitney test to compare the differences between the groups regarding the NPs and Spearman correlation between the cognitive findings and the cerebellar metabolites, FA values, CAG repeats, disease duration and severity. We used p<0.05 noncorrected for multiple comparison. For GM analysis used cluster-size=50 voxel, p<0.001 (uncorrected). We found significant differences between groups in the tests: Rey auditory verbal learning test (RAVLT)-coding [p=0.001], delayed recall [p=0.001] and recognition [p=0.027], progressive matrices [p=0.003]; Corsi block span-forward [p=0.002]; Corsi block span-backward [p=0.001]; digit span-forward [p=0.024]; semantic verbal fluency [p=0.029]; and symptoms indicative of depression [p<0.001] and anxiety [p<0.001]. The qualitative analysis showed mild impairment in the test RAVLT-coding and inferior medium impairment in the other tests. There were positive correlations between RAVLT-coding and temporal cortex areas, frontal, insula and culmen cerebellar; RAVLT-delayed recall and precentral gyrus, culmen, frontal cortex areas, temporal and parietal lobes; RAVLTrecognition and frontal gyrus; progressive matrices and precuneus and temporal gyrus; Corsi block span- forward and parietal lobe; digit span-forward and temporal gyrus; semantic verbal fluency with precentral gyrus (p<0.001). We found correlation between FA value of brainsteam in SCA3 patients and digits spanforward [rs=0.485]. There were difference between groups related to cerebellar metabolites: N-Acetyl-Aspartate [p<0.001], N-Acetyl-aspartyl-glutamate [p<0.001], glutamate [p=0.017], glutamine [p=0.005], phosphorylcholine [p=0.019] e glycerophosphorylcholine [p=0.014], except creatine [p=0.522] and inositol [p=0.475]. A significant correlation was found between: Corsi block span-forward with glutamate (rs=-0.419) and glutamine (rs=-0.405); verbal fluency with phosphorylcoline (rs=0.661) and glycerophosphorylcholine (rs=0.692); digits spanforward with N-acetyl-Aspartate (rs=0.418) and N-Acetyl-Aspartyl-glutamate (rs=0.432). We found no significant correlation between cognitive findings and clinical variables and CAG lengths. We found no significant correlation between the cognitive findings and clinical and genetic variables. The results suggest there are episodic and working memory dysfunction and visuospatial disabilities in the SCA3 associated with encephalic alterations. The lack of correlation between the neuropsychiatric abnormalities and genetic and clinics features suggest this variables occur independently of primary disease progressionMestradoNeurocienciasMestre em Fisiopatologia Médic

    Effects of task complexity on activation of language areas in a semantic decision fMRI protocol

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    a b s t r a c t Language tasks used for clinical fMRI studies may be too complex for some patients with cognitive impairments, and &quot;easier&quot; versions are sometimes substituted, though the effects on brain activity of such changes in task complexity are largely unknown. To investigate these differences, we compared two versions of an fMRI language comprehension protocol, with different levels of difficulty, in 24 healthy right-handed adults. The protocol contrasted an auditory word comprehension task (semantic decision) with a nonspeech control task using tone sequences (tone decision). In the &quot;complex&quot; version (CV), the semantic decision task required two complex semantic decisions for each word, and the tone decision task required the participant to count the number of target tones in each sequence. In the &quot;easy&quot; version (EV), the semantic task required only a single easier decision, and the tone task required only detection of the presence or absence of a target tone in each sequence. The protocols were adapted for a Brazilian population. Typical left hemisphere language lateralization was observed in 92% of participants for both CV and EV using the whole-brain lateralization index, and typical language lateralization was also observed for others regions of interest. Task performance was superior on the EV compared to the CV (p¼ 0.014). There were many common areas of activation across the two version; however, the CV produced greater activation in the left superior and middle frontal giri, angular gyrus, and left posterior cingulate gyrus compared to the EV, the majority of which are areas previously identified with language and semantic processing. The EV produced stronger activation only in a small area in the posterior middle temporal gyrus. These results reveal differences between two versions of the protocol and provide evidence that both are useful for language lateralization and worked well for Brazilian population. The complex version produces stronger activation in several nodes of the semantic network and therefore is elected for participants who can perform well these tasks

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

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    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. <. 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. © 2014 Elsevier Inc.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 temp36108114FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2010/02492-0Hauser, W.A., Annegers, J.F., Rocca, W.A., Descriptive epidemiology of epilepsy - contributions of population-based studies from Rochester, Minnesota (1996) Mayo Clinic Proceedings, 71, pp. 576-586Yasuda, C.L., Tedeschi, H., Oliveira, E.L., Ribas, G.C., Costa, A.L., Cardoso, T.A., Comparison of short-term outcome between surgical and clinical treatment in temporal lobe epilepsy: a prospective study (2006) Seizure, 15, pp. 35-40. , 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