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 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized 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. Negative effects of age on atrophy further revealed a strong influence of connectome architecture 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 deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.

Previous imaging studies in the Machado-Joseph disease (MJD/SCA3) have mostly concentrated on the cerebellum and brainstem. Our goal was to perform a whole brain longitudinal evaluation. METHODSWe included 45 patients and 51 controls, who underwent two brain magnetic resonance imaging and magnetic resonance spectroscopy (mean interval of 12.5 ± 1.5 months). We used voxel-based morphometry (VBM) and the MarsBar analysis toolbox to extract grey matter density (GMD) values from regions of interest. We used a linear regression model and a general linear model to correlate GMD with clinical markers, and paired t-test for the longitudinal evaluation. RESULTSWe observed decreased GMD (P < .01) at frontal, parietal, temporal and occipital lobes, subcortical grey matter, cerebellum, and brainstem. White matter atrophy was restricted to the cerebellum. Age, CAG, and disease duration predicted GMD in different areas, but age and CAG were the most important predictors. The longitudinal analysis failed to demonstrate changes. Changes in regions other than the cerebellum appeared to contribute significantly to the final International Cooperative Ataxia Rating Scale score. CONCLUSIONWe confirmed cortical involvement in MJD/SCA3. The most important factors in predicting GMD were age and CAG. The lack of progression of atrophy may indicate floor effect and/or short duration of follow-up.

BACKGROUND AND PURPOSE:TA is a branch of image processing that seeks to reduce image information by extracting texture descriptors from the image. TA of MR images of anatomic structures in mild AD and aMCI is not well-studied. Our objective was to attempt to find differences among patients with aMCI and mild AD and normal-aging subjects, by using TA applied to the MR images of the CC and the thalami of these groups of subjects.

Although white matter damage may play a major role in the pathogenesis of spinocerebellar ataxia 3 (SCA3), available data rely exclusively upon macrostructural analyses. In this setting we designed a study to investigate white matter integrity. We evaluated 38 genetically-confirmed SCA3 patients (mean age, 52.76 ± 12.70 years; 21 males) with clinical scales and brain magnetic resonance imaging (MRI) and 38 healthy subjects as a control group (mean age, 48.86 ± 12.07 years, 20 male). All individuals underwent the same protocol for high-resolution T1 and T2 images and diffusion tensor imaging acquisition (32 directions) in a 3-T scanner. We used Tract-Based Spatial Statistics (FSL 4.1.4) to analyze diffusion data and SPM8/DARTEL for voxel-based morphometry of infratentorial structures. T2-relaxometry of cerebellum was performed with in-house-developed software Aftervoxel and Interactive Volume Segmentation (IVS). Patients' mean age at onset was 40.02 ± 11.48 years and mean duration of disease was 9.3 ± 2.7 years. Mean International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA) scores were 32.08 ± 4.01 and 14.65 ± 7.33, respectively. Voxel-based morphometry demonstrated a volumetric reduction of gray and white matter in cerebellum and brainstem (P <.001). We found reduced fractional anisotropy (P <.05) in the cerebellum and brainstem. There were also areas of increased radial diffusivity (P <.05) in the cerebellum, brainstem, thalamus, frontal lobes, and temporal lobes. In addition, we found decreased T2-relaxation values in the white matter of the right cerebellar hemisphere. Microstructural white matter dysfunction, not previously reported, occurs in the cerebellum and brainstem of SCA3 patients.

Areas of subtle GMA may be related to poorer surgical outcome. In addition, we demonstrated a postoperative relative increase of WM and GM concentration associated with seizure control. These changes may represent neuroplasticity related to improvement of brain function after seizure control. Further studies with a multimodal approach may help to predict surgical outcome and improve selection of patients for surgical treatment of MTLE.

ObjectivePatients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS).MethodsWe evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures.ResultsPatients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions.ConclusionAlthough a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process.

SUMMARYObjective: Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy. Methods: We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. Results: We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. Significance: These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology.

Previous studies demonstrated cognitive impairments in spinocerebellar ataxia type 3 (SCA3/MJD); however, there is no consensus about the cognitive domains affected and the correlation with structural brain abnormalities. We investigated the neuropsychological profile and 3T-MRI findings, including high-resolution T1-images, diffusion tensor imaging and magnetic resonance spectroscopy of 32 patients with SCA3/MJD and 32 age-, gender- and educational level-matched healthy controls. We reviewed patients' clinical history and CAG repeat length, and performed assessment and rating of ataxia (SARA)-Brazilian version and the neuropsychiatric inventory. Patients presented worse performance in episodic and working memory and Beck inventories (depression and anxiety). SCA3/MJD patients had a reduction of gray matter volume (GM) in the cerebellum, putamen, cingulum, precentral and parietal lobe. A positive correlation was identified between the cognitive findings and GM of temporal, frontal, parietal, culmen and insula. We observed positive correlation between the brainstem's fractional anisotropy and digit span-forward. The following cerebellar metabolite groups (measured relative to creatine) were reduced in patients: N-acetyl-aspartate (NAA), NAA + N-acetyl-aspartate-glutamate and glutamate + glutamine (Glx). We found a positive correlation between Corsi's block-tapping task forward with Glx; semantic verbal fluency with phosphorylcholine and glycerophosphorylcholine; digits span-forward with NAA. The cognitive impairments in SCA3/MJD are associated not only with cerebellar and brainstem abnormalities, but also with neuroimaging evidence of diffuse neuronal and axonal dysfunction, particularly in temporal, frontal, parietal and insular areas.