60 research outputs found
Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study
Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 Ă 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 Ă 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 Ă 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 Ă 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 Ă 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 Ă 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 Ă 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed
Network-based atrophy modelling in the common epilepsies: a worldwide ENIGMA study
SUMMARY Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided novel insights into the macroscale features that shape the pathophysiology of common epilepsies
Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study
Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-Analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = \uc3\ua2 '0.24 to \uc3\ua2 '0.73; P < 1.49 \uc3\u97 10 \uc3\ua2 '4), and lower thickness in the precentral gyri bilaterally (d = \uc3\ua2 '0.34 to \uc3\ua2 '0.52; P < 4.31 \uc3\u97 10 \uc3\ua2 '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = \uc3\ua2 '1.73 to \uc3\ua2 '1.91, P < 1.4 \uc3\u97 10 \uc3\ua2 '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = \uc3\ua2 '0.36 to \uc3\ua2 '0.52; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = \uc3\ua2 '0.29 to \uc3\ua2 '0.54; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = \uc3\ua2 '0.27 to \uc3\ua2 '0.51; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < \uc3\ua2 '0.0018; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed
A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy
The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control
Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy
Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.11Nsciescopu
COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
Background:
The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms.
Methods:
International, prospective observational study of 60â109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms.
Results:
âTypicalâ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (â€â18 years: 69, 48, 23; 85%), older adults (â„â70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each Pâ<â0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country.
Interpretation:
This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
Contribution to the developments of rapid acquisition schemes in magnetic resonance imaging
LâImagerie par RĂ©sonance MagnĂ©tique (IRM) est une belle application de la physique et constitue sans aucun doute lâune des techniques les plus performantes dâimagerie mĂ©dicale. BasĂ©e sur le phĂ©nomĂšne de la RĂ©sonance MagnĂ©tique NuclĂ©aire (RMN) du proton contenu dans les molĂ©cules dâeau, lâIRM permet dâinvestiguer en coupes les tissus mous du corps, sur base de contrastes diffĂ©rents. La mĂ©thode est non-invasive et nâutilise pas de radiations ionisantes. En plus des donnĂ©es morphologiques, lâIRM permet Ă©galement dâobtenir des informations fonctionnelles et physiologiques.De nos jours, plus de 10 000 unitĂ©s IRM existent dans le monde et des millions dâexamens sont rĂ©alisĂ©s chaque annĂ©e. La technique est en constant dĂ©veloppement et le domaine de recherches est multidisciplinaire. Il concerne aussi bien les dĂ©veloppements mĂ©thodologiques (imagerie rapide, imagerie de diffusion, etc.) que technologiques (imagerie Ă haut champ, systĂšmes de gradients Ă commutation rapide, etc.), le point central des recherches Ă©tant lâamĂ©lioration de la qualitĂ© des images et la diminution du temps dâacquisition. Ceci implique l'optimisation des diffĂ©rentes sĂ©quences IRM (sĂ©ries d'impulsions radiofrĂ©quence et de gradients de champ magnĂ©tique) tenant compte des contraintes imposĂ©es par le matĂ©riel, ainsi que le dĂ©veloppement et l'optimisation du matĂ©riel lui-mĂȘme. Cette thĂšse est consacrĂ©e au design avancĂ© des sĂ©quences dâimpulsions et contribue donc Ă l'optimisation des schĂ©mas dâacquisition en IRM.En particulier, le prĂ©sent travail est focalisĂ© sur la comprĂ©hension et lâamĂ©lioration dâun certain type de sĂ©quences rapides, employant des Ă©chos de gradients :les sĂ©quences Steady-State Free Precession (SSFP) et plus prĂ©cisĂ©ment les sĂ©quences dites balanced-SSFP. Dans ce genre de schĂ©ma dâacquisition, le systĂšme est excitĂ© rapidement et pĂ©riodiquement, conduisant Ă lâĂ©tablissement dâun Ă©tat stationnaire de lâaimantation. La premiĂšre partie de la thĂšse est consacrĂ©e Ă une analyse approfondie des propriĂ©tĂ©s du signal dans une sĂ©quence balanced-SSFP, Ă la fois Ă lâĂ©tat stationnaire et Ă lâĂ©tat transitoire. Ensuite, de nouveaux schĂ©mas dâacquisition sont dĂ©veloppĂ©s sur base de calculs analytiques et de simulations numĂ©riques et sont ensuite testĂ©s expĂ©rimentalement. Dâune part, une manipulation de lâĂ©tat stationnaire est prĂ©sentĂ©e en vue de supprimer le signal de la graisse sur les images (qui peut ĂȘtre gĂȘnant pour le diagnostic de certaines lĂ©sions ou maladies). Dâautre part, lâapplication dâune phase de prĂ©paration en vue dâobtenir un contraste basĂ© sur le degrĂ© de diffusion des molĂ©cules dâeau dans les tissus est analysĂ©e en dĂ©tails, afin dâamĂ©liorer la qualitĂ© dâimage produite par des sĂ©quences de diffusion existantes.La prĂ©sente thĂšse constitue donc un travail de recherches thĂ©oriques et expĂ©rimentales, allant de la conception de nouveaux schĂ©mas dâacquisition Ă leur expĂ©rimentation sur volontaires, en passant par leur implĂ©mentation sur un imageur IRM. Ce travail a Ă©tĂ© rĂ©alisĂ© au sein de lâUnitĂ© dâIRM â Radiologie de lâHĂŽpital Erasme, sous la direction de Thierry Metens, Docteur en Sciences et Physicien IRM.Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe
Editorial for âCardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy ( REFMAP ) MRI in Healthy Human Kidneyâ
info:eu-repo/semantics/publishe
Dual steady-state sequence with periodic variable flip angles
401info:eu-repo/semantics/nonPublishe
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