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Objective: We aimed to clarify the pathophysiology of epilepsy involving seizures with apparently generalized onset, progressing to focal ictal rhythm through stereotactic EEG (SEEG) implantation, recording, stimulation and high-frequency oscillation (HFO) analysis., Methods: We identified two patients with seizures with bilateral electrographic onset evolving to focal ictal rhythm, who underwent SEEG implantation. Patients had pre-surgical epilepsy work-up, including prolonged video scalp EEG, brain MRI, PET, ictal/interictal SPECT, MEG, and EEG-fMRI prior to SEEG implantation., Results: Both patients had childhood-onset seizures involving behavioural arrest and left versive head and eye deviation, evolving to bilateral tonic-clonic convulsions. Seizures were electrographically preceded by diffuse, bilateral 3-Hz activity resembling absence seizures. Both had suspected focal lesions based on neuroimaging, including 3T MRI and voxel-based post-processing in one patient. Electrode stimulation did not elicit any habitual electroclinical seizures. HFO analysis showed bilateral focal regions with high fast-ripple rates., Significance: “Generalized-to-focal” seizures may occur due to a diffuse, bilateral epileptic network, however, both patients showed ictal evolution from a generalized pattern to a single dominant focus which may explain why the focal aspect of their seizures had a consistent clinical semiology. Patients such as these may have a unique form of generalized epilepsy, but focal/multifocal cerebral abnormalities are also a possibility.

The ILAE Neuroimaging Task Force aims to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Previous quantitative MRI studies have established important imaging markers of epilepsy-related pathology, including features sensitive to hippocampal cell loss and reactive astrogliosis. Here, we review the case of a female with pediatric drug-resistant epilepsy. Throughout her course of treatment, she had seven MRI investigations at several centers; the first three did not follow optimized epilepsy imaging protocols whereas the remaining four adhered to HARNESS-MRI protocols ( har monized n euroimaging of e pilepsy s tructural s equences). Visual inspection of a set of HARNESS-MR images revealed conspicuous left hippocampal hyperintensity which may have been initially overlooked on non-optimized MR images. Quantitative analysis of these multimodal imaging data along hippocampal subfields provided clear evidence of hippocampal sclerosis, with increased atrophy, increased mean diffusivity, increased T2-FLAIR signal, and lower qT1 values observed in the anterior portions of the left, compared to the right hippocampus. The patient underwent a left anterior temporal lobectomy with amygdalohippocampectomy at age 16 years. Histopathology of the resected specimen also confirmed hippocampal sclerosis with widespread gliosis and focal neuronal loss in the hippocampal subfields overlapping with regions of multimodal quantitative alterations. The patient remains seizure-free one year after surgery. Collectively, this case highlights the need for optimized data acquisition protocols early in the treatment of epilepsy and supports quantitative analysis of MRI contrasts to enhance personalized diagnosis and prognosis of drug-resistant patients with epilepsy.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n = 102, age range = 30-89 years) with MRI and Aβ PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aβ deposition. In addition to carrying out surface-based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aβ deposition occurred across the entire cortical topography, increased Aβ deposition was especially pronounced toward higher-order transmodal regions. Age-related atrophy was greater toward the posterior end of the hippocampal long-axis. No significant effect of age on Aβ deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography-specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain-based biomarkers of aging., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Objectives: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo., Experimental Design: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG., Principal Observations: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy., Conclusion: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology., (© 2015 Wiley Periodicals, Inc.)

In drug-resistant temporal lobe epilepsy (TLE), MRI studies have shown consistent mesiotemporal and neocortical structural alterations when comparing patients to healthy controls. It remains, however, relatively unclear whether the side of seizure focus differentially impacts the degree of structural damage. This work performed a comprehensive surface-based analysis of mesiotemporal and neocortical morphology on preoperative 1.5 T MRI in 25/35 LTLE/RTLE patients that achieved seizure freedom after surgery (i.e., Engel-I outcome; 7 ± 2 years follow-up), an imaging-independent confirmation of focus lateralization. Compared to 46 age- and sex-matched controls, both TLE groups displayed marked ipsilateral atrophy in mesiotemporal regions, while cortical thinning was bilateral. Direct contrasts between LTLE and RTLE did not reveal significant differences. Bootstrap simulations indicated low reproducibility of observing a between-cohort difference; power analysis revealed that more than 110 patients would be necessary to detect subtle differences. No difference between LTLE and RTLE was confirmed when using voxel-based morphometry, an independent proxy of gray matter volume. Similar results were obtained analyzing a separate 3 T dataset (15/15 LTLE/RTLE patients; Engel-I after 4 ± 2 years follow-up; 42 controls). Our results strongly support equivalent gray matter compromise in left and right TLE. The morphological profile of seizure-free patients, presenting with ipsilateral mesiotemporal and bilateral cortical atrophy, motivates the development of neuromarkers of outcome that consider both mesiotemporal and neocortical structures. Hum Brain Mapp 37:515-524, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Accurate tissue classification is a crucial prerequisite to MRI morphometry. Automated methods based on intensity histograms constructed from the entire volume are challenged by regional intensity variations due to local radiofrequency artifacts as well as disparities in tissue composition, laminar architecture and folding patterns. Current work proposes a novel anatomy-driven method in which parcels conforming cortical folding were regionally extracted from the brain. Each parcel is subsequently classified using nonparametric mean shift clustering. Evaluation was carried out on manually labeled images from two datasets acquired at 3.0 Tesla (n = 15) and 1.5 Tesla (n = 20). In both datasets, we observed high tissue classification accuracy of the proposed method (Dice index >97.6% at 3.0 Tesla, and >89.2% at 1.5 Tesla). Moreover, our method consistently outperformed state-of-the-art classification routines available in SPM8 and FSL-FAST, as well as a recently proposed local classifier that partitions the brain into cubes. Contour-based analyses localized more accurate white matter-gray matter (GM) interface classification of the proposed framework compared to the other algorithms, particularly in central and occipital cortices that generally display bright GM due to their highly degree of myelination. Excellent accuracy was maintained, even in the absence of correction for intensity inhomogeneity. The presented anatomy-driven local classification algorithm may significantly improve cortical boundary definition, with possible benefits for morphometric inference and biomarker discovery., (© 2015 Wiley Periodicals, Inc.)

Pregnancy-associated Plasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSAPAM) can be used in vitro to select parasites from nonpregnant donors to express VSAPAM and that this selection for VSAPAM expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.

Our purpose was to quantify structural changes of the temporopolar cortex (TPC) and its white matter (TPWM) in temporal lobe epilepsy (TLE) using MRI volumetry and texture analysis. We studied 23 patients with hippocampal atrophy, and 20 healthy controls. Gradient magnitude and entropy were calculated to model signal intensity blurring on T1-MRI. Two observers assessed signal changes and atrophy visually. Compared to controls, TLE patients had a decrease in TPC and TPWM volume ipsilateral to the seizure focus. The gradient magnitude and entropy were decreased ipsilateral to the focus only in TPWM, indicating blurring of this compartment. Eighty-seven percent of TLE patients had at least one volumetric or textural abnormality. Although sensitivity of visual and quantitative assessment of TPC atrophy was comparable (43 and 39%), specificity was higher for volumetry (54% vs. 95%). Compared to visual analysis of signal changes in TPWM on T1-MRI, texture metrics had higher sensitivity (65% vs. 17%) and specificity (100% vs. 69%). The proportion of patients with blurring of TPWM as determined by texture analysis was higher than that seen on visual inspection of T2 images (78% vs. 43%). We found no clear association between volumetric or textural changes of TPC and TPWM and outcome after surgery. Structural changes of the anatomically distinct TPC and TPWM are found ipsilateral to the seizure focus in the majority of TLE patients with hippocampal sclerosis. MRI post-processing allows dissociating different pathological tissue characteristics and shows that atrophy involves gray and white matter, whereas blurring is confined to white matter., ((c) 2007 Wiley-Liss, Inc.)

Subcortical band heterotopia is a diffuse malformation of cortical development related to pharmacologically intractable epilepsy. On magnetic resonance imaging (MRI), patients with "double cortex" syndrome (DCS) present with a band of heterotopic gray matter separated from the overlying cortex by a layer of white matter. The function and connectivity of the subcortical heterotopic band in humans is only partially understood. We studied six DCS patients with bilateral subcortical band heterotopias and six healthy controls using functional MRI (fMRI). In controls, simple motor task elicited contralateral activation of the primary motor cortex (M1) and ipsilateral activation of the cerebellum and left supplementary motor area (SMA). All DCS patients showed task-related contralateral activation of both M1 and the underlying heterotopic band. Ipsilateral motor activation was seen in 4/6 DCS patients. Furthermore, there were additional activations of nonprimary normotopic cortical areas. The sensory stimulus resulted in activation of the contralateral primary sensory cortex (SI) and the thalamus in all healthy subjects. The left sensory task also induced a contralateral activation of the insular cortex. Sensory activation of the contralateral SI was seen in all DCS patients and secondary somatosensory areas in 5/6. The heterotopic band beneath SI became activated in 3/6 DCS patients. Activations were also seen in subcortical structures for both paradigms. In DCS, motor and sensory tasks induce an activation of the subcortical heterotopic band. The recruitment of bilateral primary areas and higher-order association normotopic cortices indicates the need for a widespread network to perform simple tasks., (Copyright 2005 Wiley-Liss, Inc.)