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1.
Hum Brain Mapp ; 45(13): e70020, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39225128

RESUMO

Hemispherotomy is an effective surgery for treating refractory epilepsy from diffuse unihemispheric lesions. To date, postsurgery neuroplastic changes supporting behavioral recovery after left or right hemispherotomy remain unclear. In the present study, we systematically investigated changes in gray matter volume (GMV) before and after surgery and further analyzed their relationships with behavioral scores in two large groups of pediatric patients with left and right hemispherotomy (29 left and 28 right). To control for the dramatic developmental effect during this stage, age-adjusted GMV within unaffected brain regions was derived voxel by voxel using a normative modeling approach with an age-matched reference cohort of 2115 healthy children. Widespread GMV increases in the contralateral cerebrum and ipsilateral cerebellum and GMV decreases in the contralateral cerebellum were consistently observed in both patient groups, but only the left hemispherotomy patients showed GMV decreases in the contralateral cingulate gyrus. Intriguingly, the GMV decrease in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in the right but not the left hemispherotomy patients. Importantly, the preoperative voxelwise GMV features can be used to significantly predict postoperative behavioral scores in both patient groups. These findings indicate an important role of the contralateral cerebellum in the behavioral recovery following right hemispherotomy and highlight the predictive potential of preoperative imaging features in postoperative behavioral performance.


Assuntos
Epilepsia Resistente a Medicamentos , Substância Cinzenta , Hemisferectomia , Imageamento por Ressonância Magnética , Humanos , Hemisferectomia/métodos , Feminino , Masculino , Criança , Pré-Escolar , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Adolescente , Cerebelo/diagnóstico por imagem , Cerebelo/cirurgia , Cerebelo/patologia , Plasticidade Neuronal/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Encéfalo/patologia , Lateralidade Funcional/fisiologia
2.
Neuroimage Clin ; 43: 103658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39178601

RESUMO

OBJECTIVE: In drug-resistant temporal lobe epilepsy (TLE), it is not well-established in how far surgery should target morphological anomalies to achieve seizure freedom. Here, we assessed interactions between structural brain compromise and surgery to identify region-specific predictors of seizure outcome. METHODS: We obtained pre- and post-operative 3D T1-weighted MRI in 55 TLE patients who underwent selective amygdalo-hippocampectomy (SAH) or anterior temporal lobectomy (ATL) and 40 age and sex-matched healthy subjects. We measured surface-based morphological alterations of the mesiotemporal lobe structures (hippocampus, amygdala, entorhinal and piriform cortices), the neocortex and the thalamus on both pre- and post-operative MRI. Using precise co-registration, in each patient we mapped the surgical cavity onto the MRI acquired before surgery, thereby quantifying the amount of pathological tissue resected; these features, together with the preoperative morphometric data, served as input to a supervised classification algorithm for postsurgical outcome prediction. RESULTS: On pre-operative MRI, patients who became seizure-free (TLE-SF) presented with severe ipsilateral amygdalar and hippocampal atrophy, while not seizure-free patients (TLE-NSF) displayed amygdalar hypertrophy. Stratifying patients based on the surgical approach, post-operative MRI showed similar patterns of mesiotemporal and thalamic changes, but divergent neocortical thinning affecting the parieto-temporo-occipital regions following ATL and the frontal lobes after SAH. Irrespective of the surgical approach, hippocampal atrophy on pre-operative MRI and its extent of resection were the most predictive features of seizure-freedom in 89% of patients (selected 100% across validations). SIGNIFICANCE: Our study indicates a critical role of the extent of resection of MRI-derived hippocampal morphological anomalies on seizure outcome. Precise pre-operative quantification of the mesiotemporal lobe provides non-invasive prognostics for individualized surgery.


Assuntos
Epilepsia do Lobo Temporal , Imageamento por Ressonância Magnética , Humanos , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Adulto Jovem , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/cirurgia , Tonsila do Cerebelo/patologia , Lobectomia Temporal Anterior/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Encéfalo/patologia
3.
Neurology ; 103(3): e209524, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-38981074

RESUMO

BACKGROUND AND OBJECTIVES: Temporal lobe epilepsy (TLE) is assumed to follow a steady course that is similar across patients. To date, phenotypic and temporal diversities of TLE evolution remain unknown. In this study, we aimed at simultaneously characterizing these sources of variability based on cross-sectional data. METHODS: We studied consecutive patients with TLE referred for evaluation by neurologists to the Montreal Neurological Institute epilepsy clinic, who underwent in-patient video EEG monitoring and multimodal imaging at 3 Tesla, comprising 3D T1 and fluid-attenuated inversion recovery and 2D diffusion-weighted MRI. The cohort included patients with drug-resistant epilepsy and patients with drug-responsive epilepsy. The neuropsychological evaluation included Wechsler Adult Intelligence Scale-III and Leonard tapping task. The control group consisted of participants without TLE recruited through advertisement and who underwent the same MRI acquisition as patients. Based on surface-based analysis of key MRI markers of pathology (gray matter morphology and white matter microstructure), the Subtype and Stage Inference algorithm estimated subtypes and stages of brain pathology to which individual patients were assigned. The number of subtypes was determined by running the algorithm 100 times and estimating mean and SD of disease trajectories and the consistency of patients' assignments based on 1,000 bootstrap samples. Effect of normal aging was subtracted from patients. We examined associations with clinical and cognitive parameters and utility for individualized predictions. RESULTS: We studied 82 patients with TLE (52 female, mean age 35 ± 10 years; 11 drug-responsive) and 41 control participants (23 male, mean age 32 ± 8 years). Among 57 operated, 43/37/20 had Engel-I outcome/hippocampal sclerosis/hippocampal isolated gliosis, respectively. We identified 3 trajectory subtypes: S1 (n = 35), led by ipsilateral hippocampal atrophy and gliosis, followed by white-matter damage; S2 (n = 27), characterized by bilateral neocortical atrophy, followed by ipsilateral hippocampal atrophy and gliosis; and S3 (n = 20), typified by bilateral limbic white-matter damage, followed by bilateral hippocampal gliosis. Patients showed high assignability to their subtypes and stages (>90% bootstrap agreement). S1 had the highest proportions of patients with early disease onset (effect size d = 0.27 vs S2, d = 0.73 vs S3), febrile convulsions (χ2 = 3.70), drug resistance (χ2 = 2.94), a positive MRI (χ2 = 8.42), hippocampal sclerosis (χ2 = 7.57), and Engel-I outcome (χ2 = 1.51), pFDR < 0.05 across all comparisons. S2 and S3 exhibited the intermediate and lowest proportions, respectively. Verbal IQ and digit span were lower in S1 (d = 0.65 and d = 0.50, pFDR < 0.05) and S2 (d = 0.76 and d = 1.09, pFDR < 0.05), compared with S3. We observed progressive decline in sequential motor tapping in S1 and S3 (T = -3.38 and T = -4.94, pFDR = 0.027), compared with S2 (T = 2.14, pFDR = 0.035). S3 showed progressive decline in digit span (T = -5.83, p = 0.021). Supervised classifiers trained on subtype and stage outperformed subtype-only and stage-only models predicting drug response in 73% ± 1.0% (vs 70% ± 1.4% and 63% ± 1.3%) and 76% ± 1.6% for Engel-I outcome (vs 71% ± 0.8% and 72% ± 1.1%), pFDR < 0.05 across all comparisons. DISCUSSION: Cross-sectional MRI-derived models provide reliable prognostic markers of TLE disease evolution, which follows distinct trajectories, each associated with divergent patterns of hippocampal and whole-brain structural alterations, as well as cognitive and clinical profiles.


Assuntos
Progressão da Doença , Epilepsia do Lobo Temporal , Imageamento por Ressonância Magnética , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Eletroencefalografia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/patologia , Adulto Jovem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Testes Neuropsicológicos
4.
Neurology ; 103(3): e209528, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39008785

RESUMO

BACKGROUND AND OBJECTIVES: Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables. METHODS: We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning. RESULTS: Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients (r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds. DISCUSSION: Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.


Assuntos
Circulação Cerebrovascular , Epilepsia do Lobo Temporal , Substância Cinzenta , Substância Branca , Humanos , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/irrigação sanguínea , Adulto , Circulação Cerebrovascular/fisiologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/irrigação sanguínea , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Imagem de Difusão por Ressonância Magnética , Aprendizado de Máquina Supervisionado , Adulto Jovem , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia
5.
Artigo em Russo | MEDLINE | ID: mdl-38881015

RESUMO

OBJECTIVE: Assessing the diagnostic significance of MR morphometry in determining the localization of focal cortical dysplasias (FCD). MATERIAL AND METHODS: The study included 13 children after surgery for drug-resistant epilepsy caused by FCD type II and stable postoperative remission of seizures (Engel class IA, median follow-up 56 months). We analyzed the results of independent expert assessment of native MR data by three radiologists (HARNESS protocol) and MR morphometry data regarding accuracy of FCD localization. We considered 2 indicators, i.e. local cortical thickening and gray-white matter blurring. RESULTS: FCD detection rate was higher after MR morphometry compared to visual analysis of native MR data using the HARNESS protocol. MR morphometry also makes it possible to more often identify gray-white matter blurring as a sign often missed by radiologists (p<0.05). CONCLUSION: MR morphometry is an additional non-invasive method for assessing the localization of FCD.


Assuntos
Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Criança , Adolescente , Pré-Escolar , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia , Malformações do Desenvolvimento Cortical/patologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/patologia , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico por imagem , Malformações do Desenvolvimento Cortical do Grupo I/cirurgia , Displasia Cortical Focal
6.
Epilepsy Res ; 203: 107367, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38703703

RESUMO

BACKGROUND: Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. OBJECTIVE: We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. METHODS: This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. RESULTS: Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. CONCLUSIONS: Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.


Assuntos
Epilepsia Resistente a Medicamentos , Hipocampo , Esclerose , Humanos , Hipocampo/patologia , Hipocampo/cirurgia , Esclerose/cirurgia , Masculino , Feminino , Criança , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/patologia , Adolescente , Estudos Retrospectivos , Resultado do Tratamento , Pré-Escolar , Imageamento por Ressonância Magnética , Eletroencefalografia/métodos , Testes Neuropsicológicos , Lobectomia Temporal Anterior/métodos , Esclerose Hipocampal
7.
Brain ; 147(7): 2483-2495, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38701342

RESUMO

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and interindividual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.


Assuntos
Lobectomia Temporal Anterior , Conectoma , Epilepsia do Lobo Temporal , Lobo Temporal , Humanos , Feminino , Masculino , Adulto , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Lobo Temporal/patologia , Lobo Temporal/cirurgia , Lobo Temporal/diagnóstico por imagem , Lobectomia Temporal Anterior/métodos , Pessoa de Meia-Idade , Adulto Jovem , Imagem de Tensor de Difusão , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/patologia
8.
Zhonghua Bing Li Xue Za Zhi ; 53(5): 419-424, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38678320

RESUMO

With rapid development of genetic testing techniques, neuroimaging and neuroelectrophysiological technologies, our understanding of malformations of cortical development continues to be deepened and updated. In particular, mutations in genes related to the mammalian target of rapamycin (mTOR) signaling pathway have been successively discovered in focal cortical dysplasia (FCD). At the same time, the classification consensus on FCD issued by the International League Against Epilepsy (ILAE) in 2011 has encountered problems and challenges in diagnostic practice. Therefore, in 2022, ILAE proposed an updated version of the FCD classification based on the progress in molecular genetics over the past decade. The main addition to the classification system is "white matter lesions, " and it is also suggested to integrate histopathological, neuroimaging, and molecular testing results for multi-level integrated diagnosis to achieve reliable, clinically relevant, and therapeutic targeted final diagnosis.


Assuntos
Malformações do Desenvolvimento Cortical , Serina-Treonina Quinases TOR , Humanos , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical/patologia , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/genética , Mutação , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Substância Branca/patologia , Substância Branca/diagnóstico por imagem , Neuroimagem/métodos
9.
Epilepsia ; 65(6): 1709-1719, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38546705

RESUMO

OBJECTIVES: Amygdala enlargement is detected on magnetic resonance imaging (MRI) in some patients with drug-resistant temporal lobe epilepsy (TLE), but its clinical significance remains uncertain We aimed to assess if the presence of amygdala enlargement (1) predicted seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) and (2) was associated with specific histopathological changes. METHODS: This was a case-control study. We included patients with drug-resistant TLE who underwent ATL-AH with and without amygdala enlargement detected on pre-operative MRI. Amygdala volumetry was done using FreeSurfer for patients who had high-resolution T1-weighted images. Mann-Whitney U test was used to compare pre-operative clinical characteristics between the two groups. The amygdala volume on the epileptogenic side was compared to the amygdala volume on the contralateral side among cases and controls. Then, we used a two-sample, independent t test to compare the means of amygdala volume differences between cases and controls. The chi-square test was used to assess the correlation of amygdala enlargement with (1) post-surgical seizure outcomes and (2) histopathological changes. RESULTS: Nineteen patients with and 19 patients without amygdala enlargement were studied. Their median age at surgery was 38 years for cases and 39 years for controls, and 52.6% were male. There were no statistically significant differences between the two groups in their pre-operative clinical characteristics. There were significant differences in the means of volume difference between cases and controls (Diff = 457.2 mm3, 95% confidence interval [CI] 289.6-624.8; p < .001) and in the means of percentage difference (p < .001). However, there was no significant association between amygdala enlargement and surgical outcome (p = .72) or histopathological changes (p = .63). SIGNIFICANCE: The presence of amygdala enlargement on the pre-operative brain MRI in patients with TLE does not affect the surgical outcome following ATL-AH, and it does not necessarily suggest abnormal histopathology. These findings suggest that amygdala enlargement might reflect a secondary reactive process to seizures in the epileptogenic temporal lobe.


Assuntos
Tonsila do Cerebelo , Epilepsia do Lobo Temporal , Imageamento por Ressonância Magnética , Humanos , Tonsila do Cerebelo/cirurgia , Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Masculino , Feminino , Adulto , Estudos de Casos e Controles , Resultado do Tratamento , Adulto Jovem , Pessoa de Meia-Idade , Lobectomia Temporal Anterior/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/cirurgia , Adolescente
10.
Epilepsia ; 65(6): 1631-1643, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38511905

RESUMO

OBJECTIVE: We aim to improve focal cortical dysplasia (FCD) detection by combining high-resolution, three-dimensional (3D) magnetic resonance fingerprinting (MRF) with voxel-based morphometric magnetic resonance imaging (MRI) analysis. METHODS: We included 37 patients with pharmacoresistant focal epilepsy and FCD (10 IIa, 15 IIb, 10 mild Malformation of Cortical Development [mMCD], and 2 mMCD with oligodendroglial hyperplasia and epilepsy [MOGHE]). Fifty-nine healthy controls (HCs) were also included. 3D lesion labels were manually created. Whole-brain MRF scans were obtained with 1 mm3 isotropic resolution, from which quantitative T1 and T2 maps were reconstructed. Voxel-based MRI postprocessing, implemented with the morphometric analysis program (MAP18), was performed for FCD detection using clinical T1w images, outputting clusters with voxel-wise lesion probabilities. Average MRF T1 and T2 were calculated in each cluster from MAP18 output for gray matter (GM) and white matter (WM) separately. Normalized MRF T1 and T2 were calculated by z-scores using HCs. Clusters that overlapped with the lesion labels were considered true positives (TPs); clusters with no overlap were considered false positives (FPs). Two-sample t-tests were performed to compare MRF measures between TP/FP clusters. A neural network model was trained using MRF values and cluster volume to distinguish TP/FP clusters. Ten-fold cross-validation was used to evaluate model performance at the cluster level. Leave-one-patient-out cross-validation was used to evaluate performance at the patient level. RESULTS: MRF metrics were significantly higher in TP than FP clusters, including GM T1, normalized WM T1, and normalized WM T2. The neural network model with normalized MRF measures and cluster volume as input achieved mean area under the curve (AUC) of .83, sensitivity of 82.1%, and specificity of 71.7%. This model showed superior performance over direct thresholding of MAP18 FCD probability map at both the cluster and patient levels, eliminating ≥75% FP clusters in 30% of patients and ≥50% of FP clusters in 91% of patients. SIGNIFICANCE: This pilot study suggests the efficacy of MRF for reducing FPs in FCD detection, due to its quantitative values reflecting in vivo pathological changes. © 2024 International League Against Epilepsy.


Assuntos
Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical , Humanos , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Adulto , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/patologia , Adolescente , Adulto Jovem , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/patologia , Pessoa de Meia-Idade , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Imageamento Tridimensional/métodos , Criança , Reações Falso-Positivas , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Processamento de Imagem Assistida por Computador/métodos , Displasia Cortical Focal
11.
Epilepsia ; 65(5): 1451-1461, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38491957

RESUMO

OBJECTIVE: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy. METHODS: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy. Participants were subdivided based on histopathology of the resected brain. Paired blood- and brain-derived DNA samples were sequenced using high-coverage targeted next generation sequencing to high depth (585× and 1360×, respectively). Variants were identified using Genome Analysis ToolKit (GATK4) MuTect-2 and confirmed using high-coverage Amplicon-EZ sequencing. RESULTS: Sequence data on 41 patients passed quality control. Four somatic variants were validated following amplicon sequencing: within CBL, ALG13, MTOR, and FLNA. The diagnostic yield across 41 patients was 10%, 9% in mesial temporal lobe epilepsy with hippocampal sclerosis and 20% in malformations of cortical development. SIGNIFICANCE: This study provides novel insights into the etiology of mesial temporal lobe epilepsy with hippocampal sclerosis, highlighting a potential pathogenic role of somatic variants in CBL and ALG13. We also report candidate diagnostic somatic variants in FLNA in focal cortical dysplasia, while providing further insight into the importance of MTOR and related genes in focal cortical dysplasia. This work demonstrates the potential molecular diagnostic value of variants in both germline and somatic epilepsy genes.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Esclerose Hipocampal , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/patologia , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/patologia , Filaminas/genética , Variação Genética , Esclerose Hipocampal/genética , Esclerose Hipocampal/patologia , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/patologia
12.
Epilepsia ; 65(4): 1092-1106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38345348

RESUMO

OBJECTIVE: Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data-driven alternative for grouping of patients. In this work, we leverage ultra-high-field 7-T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug-resistant focal epilepsy. METHODS: Forty-two drug-resistant epilepsy patients and 13 controls with 7-T structural neuroimaging were included in this study. We measured hippocampal subfield and thalamic nuclei volumetry, and applied an unsupervised machine learning algorithm, Latent Dirichlet Allocation (LDA), to estimate atrophy patterns across the hippocampal subfields and thalamic nuclei of patients. We studied the association between predefined clinical groups and the estimated atrophy patterns. Additionally, we used hierarchical clustering on the LDA factors to group patients in a data-driven approach. RESULTS: In patients with mesial temporal sclerosis (MTS), we found a significant decrease in volume across all ipsilateral hippocampal subfields (false discovery rate-corrected p [pFDR] < .01) as well as in some ipsilateral (pFDR < .05) and contralateral (pFDR < .01) thalamic nuclei. In left temporal lobe epilepsy (L-TLE) we saw ipsilateral hippocampal and some bilateral thalamic atrophy (pFDR < .05), whereas in right temporal lobe epilepsy (R-TLE) extensive bilateral hippocampal and thalamic atrophy was observed (pFDR < .05). Atrophy factors demonstrated that our MTS cohort had two atrophy phenotypes: one that affected the ipsilateral hippocampus and one that affected the ipsilateral hippocampus and bilateral anterior thalamus. Atrophy factors demonstrated posterior thalamic atrophy in R-TLE, whereas an anterior thalamic atrophy pattern was more common in L-TLE. Finally, hierarchical clustering of atrophy patterns recapitulated clusters with homogeneous clinical properties. SIGNIFICANCE: Leveraging 7-T MRI, we demonstrate widespread hippocampal and thalamic atrophy in epilepsy. Through unsupervised machine learning, we demonstrate patterns of volumetric atrophy that vary depending on disease subtype. Incorporating these atrophy patterns into clinical practice could help better stratify patients to surgical treatments and specific device implantation strategies.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Imageamento por Ressonância Magnética/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Lobo Temporal/patologia , Atrofia/patologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Esclerose/patologia
13.
Ann Neurol ; 95(5): 984-997, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38391006

RESUMO

OBJECTIVE: In temporal lobe epilepsy (TLE), a taxonomy classifying patients into 3 cognitive phenotypes has been adopted: minimally, focally, or multidomain cognitively impaired (CI). We examined gray matter (GM) thickness patterns of cognitive phenotypes in drug-resistant TLE and assessed potential use for predicting postsurgical cognitive outcomes. METHODS: TLE patients undergoing presurgical evaluation were categorized into cognitive phenotypes. Network edge weights and distances were calculated using type III analysis of variance F-statistics from comparisons of GM regions within each TLE cognitive phenotype and age- and sex-matched healthy participants. In resected patients, logistic regression models (LRMs) based on network analysis results were used for prediction of postsurgical cognitive outcome. RESULTS: A total of 124 patients (63 females, mean age ± standard deviation [SD] = 36.0 ± 12.0 years) and 117 healthy controls (63 females, mean age ± SD = 36.1 ± 12.0 years) were analyzed. In the multidomain CI group (n = 66, 53.2%), 28 GM regions were significantly thinner compared to healthy controls. Focally impaired patients (n = 37, 29.8%) showed 13 regions, whereas minimally impaired patients (n = 21, 16.9%) had 2 significantly thinner GM regions. Regions affected in both multidomain and focally impaired patients included the anterior cingulate cortex, medial prefrontal cortex, medial temporal, and lateral temporal regions. In 69 (35 females, mean age ± SD = 33.6 ± 18.0 years) patients who underwent surgery, LRMs based on network-identified GM regions predicted postsurgical verbal memory worsening with a receiver operating curve area under the curve of 0.70 ± 0.15. INTERPRETATION: A differential pattern of GM thickness can be found across different cognitive phenotypes in TLE. Including magnetic resonance imaging with clinical measures associated with cognitive profiles has potential in predicting postsurgical cognitive outcomes in drug-resistant TLE. ANN NEUROL 2024;95:984-997.


Assuntos
Disfunção Cognitiva , Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Fenótipo , Humanos , Feminino , Masculino , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/patologia , Adulto , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Pessoa de Meia-Idade , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/patologia , Imageamento por Ressonância Magnética , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Adulto Jovem , Espessura Cortical do Cérebro
14.
Seizure ; 115: 28-35, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183825

RESUMO

BACKGROUND: We aimed to explore the prevalence of autoimmune antibodies (Abs) in a large consecutive series with "chronic" epilepsy and without symptoms of autoimmune encephalitis; and to compare the immunopathology of brain tissue from drug-resistant epilepsy (DRE) with and without Abs positivity. METHODS: Neuronal and glial antibodies were detected in the serum of patients who were admitted to the wards of West China Hospital from October 2016 to September 2019 and had epilepsy by cell-based assays and tissue-based assays. RESULTS: Twenty-one (6.8 %) of 328 patients had positive Ab findings for the following: dipeptidyl-peptidase-like protein-6 (n = 7), contactin-associated protein-like 2 (n = 5), glutamic acid decarboxylase 65 (n = 4), gamma aminobutyric acid beta receptor (n = 2), N-methyl-d-aspartate receptor (n = 2), and dopamine D2 receptor (n = 1). Antibodies were detected in 6.9 % (13/187) of epilepsy people with unknown etiology and 5.6 % (8/141) of patients with known etiology, respectively. Among 190 patients with DRE, 14 (7.3 %) patients were Abs-positive. There was no significant difference between individuals with seropositive and seronegative results in clinical manifestations, except that the history of febrile seizure was significantly more frequent in the seropositive group. Moreover, brain samples from 3 patients with Abs-positive DRE (with DPPX in 2 patients, and CASPR2 in 1 patient) and 18 patients with Abs-negative DRE were analyzed for immunopathology. We found higher expression of CD8-positive T-cells in the hippocampus of Abs-positive DRE group. CONCLUSIONS: Neuronal antibodies are potentially involved in the process of "chronic" epilepsy, and CD8-positive T-cells may play an important role in this process.


Assuntos
Epilepsia Resistente a Medicamentos , Encefalite , Epilepsia , Humanos , Autoanticorpos , Prevalência , Epilepsia/diagnóstico , Encéfalo/patologia , Epilepsia Resistente a Medicamentos/patologia
15.
Histol Histopathol ; 39(9): 1179-1195, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38293776

RESUMO

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.


Assuntos
Displasia Cortical Focal , Malformações do Desenvolvimento Cortical do Grupo I , Proteínas do Tecido Nervoso , Semaforinas , Esclerose Tuberosa , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia Resistente a Medicamentos/patologia , Epilepsia , Displasia Cortical Focal/metabolismo , Displasia Cortical Focal/patologia , Células Gigantes/metabolismo , Células Gigantes/patologia , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , Malformações do Desenvolvimento Cortical do Grupo I/patologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Neurônios/metabolismo , Neurônios/patologia , Semaforinas/metabolismo , Semaforinas/genética , Semaforinas/biossíntese , Esclerose Tuberosa/metabolismo , Esclerose Tuberosa/patologia
16.
Am J Clin Pathol ; 161(5): 469-482, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38217527

RESUMO

OBJECTIVES: We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. METHODS: Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. RESULTS: Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P = .015). CONCLUSIONS: Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS.


Assuntos
Epilepsia Resistente a Medicamentos , Síndrome de Sturge-Weber , Humanos , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/patologia , Masculino , Feminino , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/etiologia , Criança , Adolescente , Estudos Retrospectivos , Adulto , Pré-Escolar , Adulto Jovem , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Mutação , Hipocampo/patologia , Lactente , Pessoa de Meia-Idade
17.
Neuropediatrics ; 55(1): 9-15, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37798920

RESUMO

OBJECTIVE: Describing spectrum, evolution, and clinical relationship of brain magnetic resonance imaging (MRI) findings in a large case series of children with febrile infection-related epilepsy syndrome (FIRES). METHODS: This retrospective study included 31 children with FIRES. Clinical data and MRI findings of the brain were evaluated. Poor clinical outcome was defined as severe disability, persistent vegetative state or stupor, very low intelligence quotient (<80), or death (modified Rankin scale 4-6 and Glasgow Outcome Score 1-3). RESULTS: Seventeen (54.8%) children with FIRES showed no abnormalities in the initial MRI, whereas 28 (90.3%) children showed MRI abnormalities at follow-up. The most frequent abnormalities were brain atrophy (74.2%) and T2/fluid-attenuated inversion recovery changes (64.5%), mostly hippocampal (45.2%). Generalized brain atrophy was the most frequent type of atrophy (58%). The earliest atrophy was recorded 9 days after the onset of disease. It progressed even beyond the acute phase in most children (51.6%). The exploratory data analysis revealed nominal significance between all MRI abnormalities considered together and poor outcome (p = 0.049) and between generalized brain atrophy and anesthesia (p = 0.024). After adjustment for multiple testing, the p-values were not significant. The outcome in four (12.9%) children was not poor despite generalized brain atrophy. CONCLUSION: In contrast to the uniform clinical course, MRI demonstrated a broad spectrum of findings. Initially, these were mostly normal and therefore indicative of FIRES but then changed rapidly and were mostly progressive despite the stable chronic course. The cause may be ongoing disease, treatment intensity, or both. Future studies should focus on what process underlies the onset and the progression of brain atrophy. However, brain atrophy was not always related to poor outcomes in children despite FIRES.


Assuntos
Epilepsia Resistente a Medicamentos , Encefalite , Síndromes Epilépticas , Criança , Humanos , Estudos Retrospectivos , Convulsões , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética , Atrofia/patologia
18.
Acta Neuropathol Commun ; 11(1): 129, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559109

RESUMO

Focal Cortical Dysplasia (FCD) is a frequent cause of drug-resistant focal epilepsy in children and young adults. The international FCD classifications of 2011 and 2022 have identified several clinico-pathological subtypes, either occurring isolated, i.e., FCD ILAE Type 1 or 2, or in association with a principal cortical lesion, i.e., FCD Type 3. Here, we addressed the DNA methylation signature of a previously described new subtype of FCD 3D occurring in the occipital lobe of very young children and microscopically defined by neuronal cell loss in cortical layer 4. We studied the DNA methylation profile using 850 K BeadChip arrays in a retrospective cohort of 104 patients with FCD 1 A, 2 A, 2B, 3D, TLE without FCD, and 16 postmortem specimens without neurological disorders as controls, operated in China or Germany. DNA was extracted from formalin-fixed paraffin-embedded tissue blocks with microscopically confirmed lesions, and DNA methylation profiles were bioinformatically analyzed with a recently developed deep learning algorithm. Our results revealed a distinct position of FCD 3D in the DNA methylation map of common FCD subtypes, also different from non-FCD epilepsy surgery controls or non-epileptic postmortem controls. Within the FCD 3D cohort, the DNA methylation signature separated three histopathology subtypes, i.e., glial scarring around porencephalic cysts, loss of layer 4, and Rasmussen encephalitis. Differential methylation in FCD 3D with loss of layer 4 mapped explicitly to biological pathways related to neurodegeneration, biogenesis of the extracellular matrix (ECM) components, axon guidance, and regulation of the actin cytoskeleton. Our data suggest that DNA methylation signatures in cortical malformations are not only of diagnostic value but also phenotypically relevant, providing the molecular underpinnings of structural and histopathological features associated with epilepsy. Further studies will be necessary to confirm these results and clarify their functional relevance and epileptogenic potential in these difficult-to-treat children.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Displasia Cortical Focal , Malformações do Desenvolvimento Cortical , Criança , Adulto Jovem , Humanos , Pré-Escolar , Estudos Retrospectivos , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/genética , Metilação de DNA , Epilepsia/genética , Epilepsia Resistente a Medicamentos/patologia , Imageamento por Ressonância Magnética
19.
World Neurosurg ; 180: e37-e45, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37495100

RESUMO

OBJECTIVE: To investigate the surgical outcomes of patients with drug-resistant epilepsy and bilateral brain magnetic resonance imaging (MRI) abnormalities who had undergone various epilepsy surgeries. METHODS: Patients with drug-resistant epilepsy and bilateral brain abnormalities on MRI who underwent epilepsy surgery at the Severance Children's Hospital between October 2003 and December 2021 were included. The age of seizure onset was 18 years or younger. Engel's classification was used to assess seizure outcomes at 1, 2, and 5 years after surgery. RESULTS: A total of 40 patients met the inclusion criteria. The median age at surgery was 10.9 years (interquartile range [IQR] 6.9-15.1); the median interval to surgery was 7.1 years (IQR 2.7-11.5). One year after surgery, a favorable outcome of Engel class I-II was observed in 53% (21/40) of patients. At the 2- and 5-year follow-ups, 56% (20/36) and 63% (17/27) of patients showed good postoperative outcomes, respectively. CONCLUSIONS: Approximately, half of the patients with bilateral brain MRI abnormalities achieved seizure freedom after epilepsy surgery. The existence of bilateral brain MRI abnormalities should not hinder resective epilepsy surgery.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Criança , Humanos , Adolescente , Resultado do Tratamento , Eletroencefalografia/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Epilepsia/patologia , Convulsões/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/patologia , Imageamento por Ressonância Magnética , Estudos Retrospectivos
20.
Brain ; 146(9): 3913-3922, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37018067

RESUMO

Epilepsy surgery consists of surgical resection of the epileptic focus and is recommended for patients with drug-resistant focal epilepsy. However, focal brain lesions can lead to effects in distant brain regions. Similarly, the focal resection in temporal lobe epilepsy surgery has been shown to lead to functional changes distant from the resection. Here we hypothesize that there are changes in brain function caused by temporal lobe epilepsy surgery in regions distant from the resection that are due to their structural disconnection from the resected epileptic focus. Therefore, the goal of this study was to localize changes in brain function caused by temporal lobe epilepsy surgery and relate them to the disconnection from the resected epileptic focus. This study takes advantage of the unique opportunity that epilepsy surgery provides to investigate the effects of focal disconnections on brain function in humans, which has implications in epilepsy and broader neuroscience. Changes in brain function from pre- to post-epilepsy surgery were quantified in a group of temporal lobe epilepsy patients (n = 36) using a measure of resting state functional MRI activity fluctuations. We identified regions with significant functional MRI changes that had high structural connectivity to the resected region in healthy controls (n = 96) and patients based on diffusion MRI. The structural disconnection from the resected epileptic focus was then estimated using presurgical diffusion MRI and related to the functional MRI changes from pre- to post-surgery in these regions. Functional MRI activity fluctuations increased from pre- to post-surgery in temporal lobe epilepsy in the two regions most highly structurally connected to the resected epileptic focus in healthy controls and patients-the thalamus and the fusiform gyrus ipsilateral to the side of surgery (PFWE < 0.05). Broader surgeries led to larger functional MRI changes in the thalamus than more selective surgeries (P < 0.05), but no other clinical variables were related to functional MRI changes in either the thalamus or fusiform. The magnitude of the functional MRI changes in both the thalamus and fusiform increased with a higher estimated structural disconnection from the resected epileptic focus when controlling for the type of surgery (P < 0.05). These results suggest that the structural disconnection from the resected epileptic focus may contribute to the functional changes seen after epilepsy surgery. Broadly, this study provides a novel link between focal disconnections in the structural brain network and downstream effects on function in distant brain regions.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Lobo Temporal/patologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/patologia
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