Assessing interindividual variability of brain activation is of practical importance to the use o... more Assessing interindividual variability of brain activation is of practical importance to the use of functional magnetic resonance imaging (fMRI) in the clinical context. The main objective of this study is to analyze the variability of the oculomotor system through horizontal optokinetic, pursuit and saccadic eye movement stimulations by means of fMRI. We found significant activation of many cortical and subcortical structures. The frequency of activation demonstrates a high variability between subjects. However, the most frequent activation regions were located in frontal areas and in regions comprising the middle temporal and medial superior temporal areas. Our study allowed the characterization of the most frequently involved foci in optokinetic stimulation, pursuit and saccadic eye movement tasks. The combination of these tasks constitutes a suitable tool for mapping major areas involved in the oculomotor system.
Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters i... more Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n ؍ 16), non-HS (n ؍ 10), and autopsy hippocampi (n ؍ 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.
Purpose: To characterize perfusion patterns of periictal single-photon emission tomography (SPECT... more Purpose: To characterize perfusion patterns of periictal single-photon emission tomography (SPECT) in patients with unilateral temporal lobe epilepsy (TLE) and to determine their relationship to the epileptogenic zone (EZ).
Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequence... more Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was sign...
Como postulado inicialmente na década de 50 por Hebb (1), a associação de diferentes padrões de a... more Como postulado inicialmente na década de 50 por Hebb (1), a associação de diferentes padrões de atividade neuronal é capaz de promover mudanças específicas na eficiência da transmissão sináptica que compõe uma circuitaria neural, determinando uma plasticidade sináptica. Tais mudanças levam a alterações no processamento de informações de caráter sensorial, motor, emocional, cognitivo ou motivacional, podendo gerar novos modos de comportamento, e assim propiciar uma plasticidade comportamental. Acredita-se hoje que estes sejam importantes mecanismos celulares envolvidos em diversos comportamentos adaptativos como a formação de memórias e formação de hábitos, assim como de comportamentos patológicos, vício em drogas, epilepsia e transtornos neuropsiquiátricos. Além disso, inúmeras evidências se 1. A ordem dos quatro primeiros autores foi colocada de maneira alfabética (pelo sobrenome), pois todos estes autores tiveram igual participação na redação deste capítulo. acumulam indicando modificações eletrofisiológicas e moleculares que correlacionam plasticidade sináptica e plasticidade comportamental.
Journal of Neurology, Neurosurgery & Psychiatry, 2006
Background: Neurocysticercosis is a major cause of epilepsy in developing countries and is endemi... more Background: Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy. Methods: A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non-contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non-neurocysticercosis groups according to previous diagnostic criteria. Results: The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p,0.001). Isolated neurocysticercosis was found in only eight patients (1.56%). Conclusions: These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause-effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co-vary with a missing variable, such as socio-economic status.
In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of ictal semi... more In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of ictal semiology and ictal EEG is better for patients with unilateral interictal spikes (UIS) than for patients with bilateral interictal spikes (BIS), possibly due to rapid seizure propagation patterns associated with bilateral epileptogenesis. In this study, the authors investigated if ictal SPECT is a reliable diagnostic test for both UIS and BIS patients. Video-EEG recording was used as the gold standard to examine the accuracy of ictal SPECT and its relationship with interictal and ictal EEG. Ninety-three consecutive patients with MTLE associated with hippocampal sclerosis were included in the analysis. Ictal SPECT was considered accurate if two blinded observers independently lateralized the scan correctly. Ictal SPECT correctly lateralized 75 (80.6%) of 93 scans. The rate of correct seizure lateralization was 87.6% for the UIS group and only 55.0% for the BIS group (p = 0.0027). In the EEG epochs, 66.7% of BIS patients vs 43.4% of UIS patients had nonlateralized ictal EEG (p < 0.001). The authors conclude that the accuracy of ictal SPECT is worse for MTLE patients with BIS than for those with UIS. The role of ictal SPECT in presurgical evaluation of patients with BIS must be reviewed.
Neurocysticercosis (NCC) is the most common parasitic disease of the human central nervous system... more Neurocysticercosis (NCC) is the most common parasitic disease of the human central nervous system and a major health problem for most developing countries. The most common clinical manifestations of NCC are epileptic seizures. Whenever epilepsy and NCC coexist in the same patient, an uncertainty may rise about a causal relationship between them. We described a female patient with disseminated calcified NCC lesions and intractable epilepsy. Her medical history included cysticercotic meningoencephalitis and status epilepticus caused by active NCC. Fundoscopy showed the ocular presence of parasite; computed tomography of the brain showed evidence of cystic lesions with the scolex and calcified lesions; enzyme-linked immunosorbent assay of the cerebrospinal fluid was positive for cysticercosis. Epileptic seizures started after an 8-year silent period. Magnetic resonance imaging showed left hippocampal sclerosis. Plain x-ray film showed calcifications in muscles and subcutaneous tissue. Video-electroencephalography and ictal and interictal single-photon emission computed tomography disclosed left mesial temporal lobe epilepsy. The patient underwent left temporal lobectomy and has been seizure free since surgery, for a follow-up of 4 years. This case report highlights and supports surgical therapy in patients with epileptic seizures and calcified NCC, even when there are several calcifications, provided that clear localization of epilepsy has been determined by means of a presurgical workup.
Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgi... more Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP(c)) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP(c) might be related to epilepsy. To evaluate the genetic contribution of PRNP to MTLE-HS. The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. A variant allele at position 171 (Asn-->Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.
Purpose: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated wit... more Purpose: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) submitted to presurgical investigation with scalp sphenoidal, followed by foramen ovale electrodes (FO), and, when necessary, with depth temporal electrodes. We sought to evaluate the clinical utility of FO in patients with MTLE-HS.
The development of newer diagnostic technologies has reduced the need for invasive electroencepha... more The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.
Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment o... more Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for ≥4 years of postsurgical follow-up.
Purpose: To analyze the patterns of brain activation in polymicrogyric cortex in epilepsy patient... more Purpose: To analyze the patterns of brain activation in polymicrogyric cortex in epilepsy patients by blood oxygenation level-dependent (BOLD) functional MRI (f MRI), during language and motor activation tasks.
Introdução: A estruturação do ensino médico nas escolas médicas brasileiras ao longo do século XX... more Introdução: A estruturação do ensino médico nas escolas médicas brasileiras ao longo do século XX sofreu grande influência das idéias de Abrahan Flexner, educador americano que julgava ser o ensino indissociável da pesquisa. Para tanto, o ensino deveria ser desenvolvido em escolas com adequada infra-estrutura de hospitais e laboratórios para o estudo das doenças. Este trabalho tem por objetivo apresentar o cenário atual da pesquisa em epilepsia no âmbito do ensino de graduação e pós-graduação das escolas médicas brasileiras. Material e métodos: Busca a análise de informações obtidas em bancos de dados governamentais (MEC e CAPES), de declarações de diretorias de instituições representativas dos órgãos médicos (AMB e CFM) além de informações obtidas no Encontro Nacional de Pós-Graduação em Medicina. Resultados e discussão: O número crescente de escolas médicas nos últimos anos, associado a um ainda questionável sistema de avaliação, tem contribuído para que muitas escolas se estabeleçam sem o perfil adequado para a pesquisa em neurologia. Assim, a pesquisa em epilepsia brasileira, no âmbito da graduação, esta praticamente restrita a instituições vinculadas às principais Universidades Federais, Estaduais (principalmente as Estaduais Paulistas), e algumas do sistemas das PUCs. Nestas instituições observa-se a presença de Professores/Pesquisadores que ministram aulas nos cursos de medicina, mas que também atuam em Programas de Pós-Graduação. Em contraste com a graduação, a plena autonomia conferida ao sistema de avaliação da CAPES para o descredenciamento de programas com avaliação insuficiente, tem permitido uma melhora significativa na qualidade dos Programas de Pós-Graduação.
The pathologically synchronized neuronal activity in temporal lobe epilepsy (TLE) can be triggere... more The pathologically synchronized neuronal activity in temporal lobe epilepsy (TLE) can be triggered by network events that were once normal. Under normal conditions, hippocampus and medial prefrontal cortex (mPFC) work in synchrony during a variety of cognitive states. Abnormal changes in this circuit may aid to seizure onset and also help to explain the high association of TLE with mood disorders. We used a TLE rat model generated by perforant path (PP) stimulation to understand whether synchrony between dorsal hippocampal and mPFC networks is altered shortly before a seizure episode. We recorded hippocampal and mPFC local field potentials (LFPs) of animals with spontaneous recurrent seizures (SRSs) to verify the connectivity between these regions. We showed that SRSs decrease hippocampal theta oscillations whereas coherence in theta increases over time prior to seizure onset. This increase in synchrony is accompanied by a stronger coupling between hippocampal theta and mPFC gamma o...
Assessing interindividual variability of brain activation is of practical importance to the use o... more Assessing interindividual variability of brain activation is of practical importance to the use of functional magnetic resonance imaging (fMRI) in the clinical context. The main objective of this study is to analyze the variability of the oculomotor system through horizontal optokinetic, pursuit and saccadic eye movement stimulations by means of fMRI. We found significant activation of many cortical and subcortical structures. The frequency of activation demonstrates a high variability between subjects. However, the most frequent activation regions were located in frontal areas and in regions comprising the middle temporal and medial superior temporal areas. Our study allowed the characterization of the most frequently involved foci in optokinetic stimulation, pursuit and saccadic eye movement tasks. The combination of these tasks constitutes a suitable tool for mapping major areas involved in the oculomotor system.
Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters i... more Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n ؍ 16), non-HS (n ؍ 10), and autopsy hippocampi (n ؍ 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.
Purpose: To characterize perfusion patterns of periictal single-photon emission tomography (SPECT... more Purpose: To characterize perfusion patterns of periictal single-photon emission tomography (SPECT) in patients with unilateral temporal lobe epilepsy (TLE) and to determine their relationship to the epileptogenic zone (EZ).
Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequence... more Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was sign...
Como postulado inicialmente na década de 50 por Hebb (1), a associação de diferentes padrões de a... more Como postulado inicialmente na década de 50 por Hebb (1), a associação de diferentes padrões de atividade neuronal é capaz de promover mudanças específicas na eficiência da transmissão sináptica que compõe uma circuitaria neural, determinando uma plasticidade sináptica. Tais mudanças levam a alterações no processamento de informações de caráter sensorial, motor, emocional, cognitivo ou motivacional, podendo gerar novos modos de comportamento, e assim propiciar uma plasticidade comportamental. Acredita-se hoje que estes sejam importantes mecanismos celulares envolvidos em diversos comportamentos adaptativos como a formação de memórias e formação de hábitos, assim como de comportamentos patológicos, vício em drogas, epilepsia e transtornos neuropsiquiátricos. Além disso, inúmeras evidências se 1. A ordem dos quatro primeiros autores foi colocada de maneira alfabética (pelo sobrenome), pois todos estes autores tiveram igual participação na redação deste capítulo. acumulam indicando modificações eletrofisiológicas e moleculares que correlacionam plasticidade sináptica e plasticidade comportamental.
Journal of Neurology, Neurosurgery & Psychiatry, 2006
Background: Neurocysticercosis is a major cause of epilepsy in developing countries and is endemi... more Background: Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy. Methods: A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non-contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non-neurocysticercosis groups according to previous diagnostic criteria. Results: The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p,0.001). Isolated neurocysticercosis was found in only eight patients (1.56%). Conclusions: These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause-effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co-vary with a missing variable, such as socio-economic status.
In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of ictal semi... more In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of ictal semiology and ictal EEG is better for patients with unilateral interictal spikes (UIS) than for patients with bilateral interictal spikes (BIS), possibly due to rapid seizure propagation patterns associated with bilateral epileptogenesis. In this study, the authors investigated if ictal SPECT is a reliable diagnostic test for both UIS and BIS patients. Video-EEG recording was used as the gold standard to examine the accuracy of ictal SPECT and its relationship with interictal and ictal EEG. Ninety-three consecutive patients with MTLE associated with hippocampal sclerosis were included in the analysis. Ictal SPECT was considered accurate if two blinded observers independently lateralized the scan correctly. Ictal SPECT correctly lateralized 75 (80.6%) of 93 scans. The rate of correct seizure lateralization was 87.6% for the UIS group and only 55.0% for the BIS group (p = 0.0027). In the EEG epochs, 66.7% of BIS patients vs 43.4% of UIS patients had nonlateralized ictal EEG (p < 0.001). The authors conclude that the accuracy of ictal SPECT is worse for MTLE patients with BIS than for those with UIS. The role of ictal SPECT in presurgical evaluation of patients with BIS must be reviewed.
Neurocysticercosis (NCC) is the most common parasitic disease of the human central nervous system... more Neurocysticercosis (NCC) is the most common parasitic disease of the human central nervous system and a major health problem for most developing countries. The most common clinical manifestations of NCC are epileptic seizures. Whenever epilepsy and NCC coexist in the same patient, an uncertainty may rise about a causal relationship between them. We described a female patient with disseminated calcified NCC lesions and intractable epilepsy. Her medical history included cysticercotic meningoencephalitis and status epilepticus caused by active NCC. Fundoscopy showed the ocular presence of parasite; computed tomography of the brain showed evidence of cystic lesions with the scolex and calcified lesions; enzyme-linked immunosorbent assay of the cerebrospinal fluid was positive for cysticercosis. Epileptic seizures started after an 8-year silent period. Magnetic resonance imaging showed left hippocampal sclerosis. Plain x-ray film showed calcifications in muscles and subcutaneous tissue. Video-electroencephalography and ictal and interictal single-photon emission computed tomography disclosed left mesial temporal lobe epilepsy. The patient underwent left temporal lobectomy and has been seizure free since surgery, for a follow-up of 4 years. This case report highlights and supports surgical therapy in patients with epileptic seizures and calcified NCC, even when there are several calcifications, provided that clear localization of epilepsy has been determined by means of a presurgical workup.
Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgi... more Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP(c)) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP(c) might be related to epilepsy. To evaluate the genetic contribution of PRNP to MTLE-HS. The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. A variant allele at position 171 (Asn-->Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.
Purpose: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated wit... more Purpose: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) submitted to presurgical investigation with scalp sphenoidal, followed by foramen ovale electrodes (FO), and, when necessary, with depth temporal electrodes. We sought to evaluate the clinical utility of FO in patients with MTLE-HS.
The development of newer diagnostic technologies has reduced the need for invasive electroencepha... more The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.
Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment o... more Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for ≥4 years of postsurgical follow-up.
Purpose: To analyze the patterns of brain activation in polymicrogyric cortex in epilepsy patient... more Purpose: To analyze the patterns of brain activation in polymicrogyric cortex in epilepsy patients by blood oxygenation level-dependent (BOLD) functional MRI (f MRI), during language and motor activation tasks.
Introdução: A estruturação do ensino médico nas escolas médicas brasileiras ao longo do século XX... more Introdução: A estruturação do ensino médico nas escolas médicas brasileiras ao longo do século XX sofreu grande influência das idéias de Abrahan Flexner, educador americano que julgava ser o ensino indissociável da pesquisa. Para tanto, o ensino deveria ser desenvolvido em escolas com adequada infra-estrutura de hospitais e laboratórios para o estudo das doenças. Este trabalho tem por objetivo apresentar o cenário atual da pesquisa em epilepsia no âmbito do ensino de graduação e pós-graduação das escolas médicas brasileiras. Material e métodos: Busca a análise de informações obtidas em bancos de dados governamentais (MEC e CAPES), de declarações de diretorias de instituições representativas dos órgãos médicos (AMB e CFM) além de informações obtidas no Encontro Nacional de Pós-Graduação em Medicina. Resultados e discussão: O número crescente de escolas médicas nos últimos anos, associado a um ainda questionável sistema de avaliação, tem contribuído para que muitas escolas se estabeleçam sem o perfil adequado para a pesquisa em neurologia. Assim, a pesquisa em epilepsia brasileira, no âmbito da graduação, esta praticamente restrita a instituições vinculadas às principais Universidades Federais, Estaduais (principalmente as Estaduais Paulistas), e algumas do sistemas das PUCs. Nestas instituições observa-se a presença de Professores/Pesquisadores que ministram aulas nos cursos de medicina, mas que também atuam em Programas de Pós-Graduação. Em contraste com a graduação, a plena autonomia conferida ao sistema de avaliação da CAPES para o descredenciamento de programas com avaliação insuficiente, tem permitido uma melhora significativa na qualidade dos Programas de Pós-Graduação.
The pathologically synchronized neuronal activity in temporal lobe epilepsy (TLE) can be triggere... more The pathologically synchronized neuronal activity in temporal lobe epilepsy (TLE) can be triggered by network events that were once normal. Under normal conditions, hippocampus and medial prefrontal cortex (mPFC) work in synchrony during a variety of cognitive states. Abnormal changes in this circuit may aid to seizure onset and also help to explain the high association of TLE with mood disorders. We used a TLE rat model generated by perforant path (PP) stimulation to understand whether synchrony between dorsal hippocampal and mPFC networks is altered shortly before a seizure episode. We recorded hippocampal and mPFC local field potentials (LFPs) of animals with spontaneous recurrent seizures (SRSs) to verify the connectivity between these regions. We showed that SRSs decrease hippocampal theta oscillations whereas coherence in theta increases over time prior to seizure onset. This increase in synchrony is accompanied by a stronger coupling between hippocampal theta and mPFC gamma o...
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Papers by João Leite