Aims
Generalised epilepsy is thought to involve distributed brain networks. However, the molecular and cellular factors that render different brain regions more vulnerable to epileptogenesis remain ...largely unknown. We aimed to investigate epilepsy‐related morphometric similarity network (MSN) abnormalities at the macroscale level and their relationships with microscale gene expressions at the microscale level.
Methods
We compared the MSN of genetic generalised epilepsy with generalised tonic–clonic seizure patients (GGE‐GTCS, n = 101) to demographically matched healthy controls (HC, n = 150). Cortical MSNs were estimated by combining seven morphometric features derived from structural magnetic resonance imaging for each individual. Regional gene expression profiles were derived from brain‐wide microarray measurements provided by the Allen Human Brain Atlas.
Results
GGE‐GTCS patients exhibited decreased regional MSNs in primary motor, prefrontal and temporal regions and increases in occipital, insular and posterior cingulate cortices, when compared with the HC. These case–control neuroimaging differences were validated using split‐half analyses and were not affected by medication or drug response effects. When assessing associations with gene expression, genes associated with GGE‐GTCS‐related MSN differences were enriched in several biological processes, including ‘synapse organisation’, ‘neurotransmitter transport’ pathways and excitatory/inhibitory neuronal cell types. Collectively, the GGE‐GTCS‐related cortical vulnerabilities were associated with chromosomes 4, 5, 11 and 16 and were dispersed bottom‐up at the cellular, pathway and disease levels, which contributed to epileptogenesis, suggesting diverse neurobiologically relevant enrichments in GGE‐GTCS.
Conclusions
By bridging the gaps between transcriptional signatures and in vivo neuroimaging, we highlighted the importance of using MSN abnormalities of the human brain in GGE‐GTCS patients to investigate disease‐relevant genes and biological processes.
The molecular and cellular factors that render different brain regions more vulnerable to epileptogenesis remain largely unknown. Li et al. investigated epilepsy‐related morphometric similarity network (MSN) from MRI data. And then, we linked these macroscale morphometric abnormalities to microscale brain‐wide gene expression from cell types to chromosomes to pathways. We thus highlighted chromosome‐ and cell‐type‐specific transcriptomic signatures of cortical morphometric vulnerability to patients with genetic generalized epilepsy.
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, affecting 2%-3% of the world's population. Mental and emotional stress, as well as some mental health conditions (e.g., ...depression) have been shown to significantly impact the heart and have been suggested to act both as independent risk factors and triggers in the onset of AF. In this paper, we review the current literature to examine the role that mental and emotional stress have in the onset of AF and summarise the current knowledge on the interaction between the brain and heart, and the cortical and subcortical pathways involved in the response to stress. Review of the evidence suggests that mental and emotional stress negatively affect the cardiac system, potentially increasing the risk for developing and/or triggering AF. Further studies are required to further understand the cortical and sub-cortical structures involved in the mental stress response and how these interact with the cardiac system, which may help in defining new strategies and interventions to prevent the development of, and improve the management of AF.
Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique ...opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole‐brain voxel‐based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10 (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty‐four controls were also studied. Right‐handed controls and right‐handed patients with left HLD had comparable structural brain asymmetries in cortical, subcortical, and cerebellar regions that have previously been documented in healthy people. However, these patients and controls differed in structural asymmetry of the mesial temporal lobe and a circumscribed region in the superior temporal gyrus, suggesting that only asymmetries of these regions were due to brain alterations caused by epilepsy. Additional comparisons between patients with left and right HLD, matched for type and location of epilepsy, revealed that structural asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal cortex, ventral temporo‐occipital cortex, mesial somatosensory cortex, and mesial cerebellum were significantly associated with the side of HLD. Patients with right HLD and bilateral language representation were significantly less right‐handed. These results suggest that structural asymmetries of an insular‐fronto‐temporal network may be related to HLD.
A detailed understanding of white matter tract alterations in patients with temporal lobe epilepsy (TLE) is important as it may provide useful information for likely side of seizure onset, cognitive ...impairment and postoperative prognosis. However, most diffusion-tensor imaging (DTI) studies have relied on manual reconstruction of tract bundles, despite the recent development of automated techniques. In the present study, we used an automated white matter tractography analysis approach to quantify temporal lobe white matter tract alterations in TLE and determine the relationships between tract alterations, the extent of hippocampal atrophy and the chronicity and severity of the disorder.
We acquired preoperative T1-weighted and DTI data in 64 patients with well-characterized TLE, with imaging and histopathological evidence of hippocampal sclerosis. Identical acquisitions were collected for 44 age- and sex-matched healthy controls. We employed automatic probabilistic tractography DTI analysis using TRActs Constrained by UnderLying Anatomy (TRACULA) available in context of Freesurfer software for the reconstruction of major temporal lobe tract bundles. We determined the factors influencing probabilistic tract reconstruction and investigated alterations of DTI scalar metrics along white matter tracts with respect to hippocampal volume, which was automatically estimated using Freesurfer's morphometric pipelines. We also explored the relationships between white matter tract alterations and duration of epilepsy, age of onset of epilepsy and seizure burden (defined as a function of seizure frequency and duration of epilepsy).
Whole-tract diffusion characteristics of patients with TLE differed according to side of epilepsy and were significantly different between patients and controls. Waypoint comparisons along each tract revealed that patients had significantly altered tissue characteristics of the ipsilateral inferior-longitudinal, uncinate fasciculus, superior longitudinal fasciculus and cingulum relative to controls. Changes were more widespread (ipsilaterally and contralaterally) in patients with left TLE while patients with right TLE showed changes that remained spatially confined in ipsilateral tract regions. We found no relationship between DTI alterations and volume of the epileptogenic hippocampus. DTI alterations of anterior ipsilateral uncinate and inferior-longitudinal fasciculus correlated with duration of epilepsy (over and above effects of age) and age at onset of epilepsy. Seizure burden correlated with tissue characteristics of the uncinate fasciculus.
This study shows that TRACULA permits the detection of alterations of DTI tract scalar metrics in patients with TLE. It also provides the opportunity to explore relationships with structural volume measurements and clinical variables along white matter tracts. Our data suggests that the anterior temporal lobe portions of the uncinate and inferior-longitudinal fasciculus may be particularly vulnerable to pathological alterations in patients with TLE. These alterations are unrelated to the extent of hippocampal atrophy (and therefore potentially mediated by independent mechanisms) but influenced by chronicity and severity of the disorder.
•The lower basal ganglia structures located in and adjacent to the midbrain should not be overlooked in people with IGE.•Both structural and functional alterations of these anatomical regions were ...found in patients with IGE.•Functional alterations included brain regions which participate in prominent motor and cognitive pathways.
Structural and functional neuroimaging studies often overlook lower basal ganglia structures located in and adjacent to the midbrain due to poor contrast on clinically acquired T1-weighted scans. Here, we acquired T1-weighted, T2-weighted, and resting-state fMRI scans to investigate differences in volume, estimated myelin content and functional connectivity of the substantia nigra (SN), subthalamic nuclei (SubTN) and red nuclei (RN) of the midbrain in IGE.
Thirty-three patients with IGE (23 refractory, 10 non-refractory) and 39 age and sex-matched healthy controls underwent MR imaging. Midbrain structures were automatically segmented from T2-weighted images and structural volumes were calculated. The estimated myelin content for each structure was determined using a T1-weighted/T2-weighted ratio method. Resting-state functional connectivity analysis of midbrain structures (seed-based) was performed using the CONN toolbox.
An increased volume of the right RN was found in IGE and structural volumes of the right SubTN differed between patients with non-refractory and refractory IGE. However, no volume findings survived corrections for multiple comparisons. No myelin alterations of midbrain structures were found for any subject groups. We found functional connectivity alterations including significantly decreased connectivity between the left SN and the thalamus and significantly increased connectivity between the right SubTN and the superior frontal gyrus in IGE.
We report volumetric and functional connectivity alterations of the midbrain in patients with IGE. We postulate that potential increases in structural volumes are due to increased iron deposition that impacts T2-weighted contrast. These findings are consistent with previous studies demonstrating pathophysiological abnormalities of the lower basal ganglia in animal models of generalised epilepsy.
Radiological identification of temporal lobe epilepsy (TLE) is crucial for diagnosis and treatment planning. TLE neuroimaging abnormalities are pervasive at the group level, but they can be subtle ...and difficult to identify by visual inspection of individual scans, prompting applications of artificial intelligence (AI) assisted technologies.
We assessed the ability of a convolutional neural network (CNN) algorithm to classify TLE vs. patients with AD vs. healthy controls using T1-weighted magnetic resonance imaging (MRI) scans. We used feature visualization techniques to identify regions the CNN employed to differentiate disease types.
We show the following classification results: healthy control accuracy = 81.54% (SD = 1.77%), precision = 0.81 (SD = 0.02), recall = 0.85 (SD = 0.03), and F1-score = 0.83 (SD = 0.02); TLE accuracy = 90.45% (SD = 1.59%), precision = 0.86 (SD = 0.03), recall = 0.86 (SD = 0.04), and F1-score = 0.85 (SD = 0.04); and AD accuracy = 88.52% (SD = 1.27%), precision = 0.64 (SD = 0.05), recall = 0.53 (SD = 0.07), and F1 score = 0.58 (0.05). The high accuracy in identification of TLE was remarkable, considering that only 47% of the cohort had deemed to be lesional based on MRI alone. Model predictions were also considerably better than random permutation classifications (p < 0.01) and were independent of age effects.
AI (CNN deep learning) can classify and distinguish TLE, underscoring its potential utility for future computer-aided radiological assessments of epilepsy, especially for patients who do not exhibit easily identifiable TLE associated MRI features (e.g., hippocampal sclerosis).
•Tractography approaches showed moderate to good agreement for tract morphology.•Along- and whole-tract diffusivity was significantly correlated across approaches.•Whole-tract AFQ but not manual ...tract diffusivity correlated with clinical variables.•Absence of excellent agreement between approaches warrants caution.
To investigate the agreement between manually and automatically generated tracts from diffusion tensor imaging (DTI) in patients with temporal lobe epilepsy (TLE). Whole and along-the-tract diffusivity metrics and correlations with patient clinical characteristics were analyzed with respect to tractography approach.
We recruited 40 healthy controls and 24 patients with TLE who underwent conventional T1-weighted imaging and 60-direction DTI. An automated (Automated Fiber Quantification, AFQ) and manual (TrackVis) deterministic tractography approach was used to identify the uncinate fasciculus (UF) and parahippocampal white matter bundle (PHWM). Tract diffusion scalar metrics were analyzed with respect to agreement across automated and manual approaches (Dice Coefficient and Spearman correlations), to side of onset of epilepsy and patient clinical characteristics, including duration of epilepsy, age of onset and presence of hippocampal sclerosis.
Across approaches the analysis of tract morphology similarity revealed Dice coefficients at moderate to good agreement (0.54 - 0.6) and significant correlations between diffusion values (Spearman's Rho=0.4–0.9). However, within bilateral PHWM, AFQ yielded significantly lower FA (left: Z = 4.4, p<0.001; right: Z = 5.1, p<0.001) and higher MD values (left: Z=-4.7, p<0.001; right: Z=-3.7, p<0.001) compared to the manual approach. Whole tract DTI metrics determined using AFQ were significantly correlated with patient characteristics, including age of epilepsy onset in FA (R = 0.6, p = 0.02) and MD of the ipsilateral PHWM (R=-0.6, p = 0.02), while duration of epilepsy corrected for age correlated with MD in ipsilateral PHWM (R = 0.7, p<0.01). Correlations between clinical metrics and diffusion values extracted using the manual whole tract technique did not survive correction for multiple comparisons. Both manual and automated along-the-tract analyses demonstrated significant correlations with patient clinical characteristics such as age of onset and epilepsy duration. The strongest and most widespread localized ipsi- and contralateral diffusivity alterations were observed in patients with left TLE and patients with HS compared to controls, while patients with right TLE and patients without HS did not show these strong effects.
Manual and AFQ tractography approaches revealed significant correlations in the reconstruction of tract morphology and extracted whole and along-tract diffusivity values. However, as non-identical methods they differed in the respective yield of significant results across clinical correlations and group-wise statistics. Given the absence of excellent agreement between manual and AFQ techniques as demonstrated in the present study, caution should be considered when using AFQ particularly when used without reference to benchmark manual measures.
Seizures can occur unpredictably in patients with acute encephalitis syndrome (AES), and many suffer from poor long-term neurological sequelae. Establishing factors associated with acute seizures ...risk and poor outcomes could support clinical care. We aimed to conduct regional and volumetric analysis of cerebral oedema on magnetic resonance imaging (MRI) in patients with AES. We assessed the relationship of brain oedema with acute seizure activity and long-term neurological outcome.
In a multi-centre cohort study, adults and children presenting with an AES were recruited in the UK. The clinical and brain MRI data were retrospectively reviewed. The outcomes variables were inpatient acute seizure activity and neurological disability at six-months post-discharge. A poor outcome was defined as a Glasgow outcome score (GOS) of 1-3. We quantified regional brain oedema on MRI through stereological examination of T2-weighted images using established methodology by independent and blinded assessors. Clinical and neuroimaging variables were analysed by multivariate logistic regression to assess for correlation with acute seizure activity and outcome.
The study cohort comprised 69 patients (mean age 31.8 years; 53.6% female), of whom 41 (59.4%) had acute seizures as inpatients. A higher Glasgow coma scale (GCS) score on admission was a negative predictor of seizures (OR 0.61 0.46-0.83, p = 0.001). Even correcting for GCS on admission, the presence of cortical oedema was a significant risk factor for acute seizure activity (OR 5.48 1.62-18.51, p = 0.006) and greater volume of cerebral oedema in these cortical structures increased the risk of acute seizures (OR 1.90 1.12-3.21, p = 0.017). At six-month post-discharge, 21 (30.4%) had a poor neurological outcome. Herpes simplex virus encephalitis was associated with higher risk of poor outcomes in univariate analysis (OR 3.92 1.08-14.20, p = 0.038). When controlling for aetiology, increased volume of cerebral oedema was an independent risk factor for adverse neurological outcome at 6 months (OR 1.73 1.06-2.83, p = 0.027).
Both the presence and degree of cerebral oedema on MRIs of patients with AES may help identify patients at risk of acute seizure activity and subsequent long-term morbidity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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