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 × 10⁻⁴), and lower thickness in the precentral gyri bilaterally (d = −0.34 to −0.52; P < 4.31 × 10⁻⁶). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = −1.73 to −1.91, P < 1.4 × 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 × 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 × 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 × 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 × 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.

To grade brain gliomas by using a data-driven analysis of multiparametric magnetic resonance (MR) imaging, taking into account the heterogeneity of the lesions at MR imaging, and to compare these results with the most widespread current radiologic reporting methods. One hundred eighteen patients with histologically confirmed brain gliomas were evaluated retrospectively. Conventional and advanced MR sequences (perfusion-weighted imaging, MR spectroscopy, and diffusion-tensor imaging) were performed. Three evaluations were conducted: semiquantitative (based on conventional and advanced sequences with reported cutoffs), qualitative (exclusively based on conventional MR imaging), and quantitative. For quantitative analysis, four volumes of interest were placed: regions with contrast material enhancement, regions with highest and lowest signal intensity on T2-weighted images, and regions of most restricted diffusivity. Statistical analysis included t test, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), leave-one-out cross-validation, and Kendall coefficient of concordance. Significant differences were noted in age, relative cerebral blood volume (rCBV) in contrast-enhanced regions (cutoff > 2.59; sensitivity, 80%; specificity, 91%; area under the ROC curve [AUC] = 0.937; P = .0001), areas of lowest signal intensity on T2-weighted images (>2.45, 57%, 97%, 0.852, and P = .0001, respectively), restricted diffusivity regions (>2.61, 54%, 97%, 0.808, and P = .0001, respectively), and choline/creatine ratio in regions with the lowest signal intensity on T2-weighted images (>2.07, 49%, 88%, 0.685, and P = .0007, respectively). DFA that included age; rCBV in contrast-enhanced regions, areas of lowest signal intensity on T2-weighted images, and areas of restricted diffusivity; and choline/creatine ratio in areas with lowest signal intensity on T2-weighted images was used to classify 95% of patients correctly. Quantitative analysis showed a higher concordance with histologic findings than qualitative and semiquantitative methods (P < .0001). A quantitative multiparametric MR imaging evaluation that incorporated heterogeneity at MR imaging significantly improved discrimination between low- and high-grade brain gliomas with a very high AUC (ie, 0.95), thus reducing the risk of inappropriate or delayed surgery, respectively.

Background: Early exposure to nociceptive events may cause brain structural alterations in preterm neonates, with long-lasting consequences on neurodevelopmental outcome. Little is known on the extent to which early pain may affect brain connectivity. We aim to evaluate brain functional connectivity changes in preterm neonate that underwent multiple invasive procedures during the postnatal period, and to correlate them with the neurodevelopmental outcome at 24 months. Methods: In this prospective case-control study, we collected information about exposure to painful events during the early postnatal period and resting-state BOLD-fMRI data at term equivalent age from two groups of preterm neonate: 33 subjected to painful procedures during the neonatal intensive care (mean gestational age 27.9 ± 1.8 weeks) and 13 who did not require invasive procedures (average gestational age 31.2 ± 2.1 weeks). A data-driven principal-component-based multivariate pattern analysis (MVPA) was used to investigate the effect of early pain exposure on brain functional connectivity, and the relationship between connectivity changes and neurodevelopmental outcome at 24 months, assessed with Griffiths, Developmental Scale-Revised: 0–2. Results: Early pain was associated with decreased functional connectivity between thalami and bilateral somatosensory cortex, and between the right insular cortex and ipsilateral amygdala and hippocampal regions, with a more evident effect in preterm neonate undergoing more invasive procedures. Functional connectivity of the right thalamocortical pathway was related to neuromotor outcome at 24 months (P = 0.003). Conclusion: Early exposure to pain is associated with abnormal functional connectivity of developing networks involved in the modulation of noxious stimuli in preterm neonate, contributing to the neurodevelopmental consequence of preterm birth.