SCN1A rs3812718 polymorphism modulates structural and functional brain networks in TLE: A multimodal imaging-genomics study.

Neuropsychology/Language/Behavior: Adult

Extratemporal abnormalities of brain parenchyma in young adults with temporal lobe epilepsy: A diffusion tensor imaging study

Compromised Memory Function in Schizophrenia and Temporal Lobe Epilepsy

Introduction: Depression is a common condition in epilepsy patients, especially temporal lobe epilepsy both before and after epilepsy surgery. However, not many studies have examined the depression status of patients undergoing surgery outside the temporal lobe (extratemporal resection). Differences in levels of depression between temporal lobe epilepsy (TLE) and extra-TLE patients are also not well known, so the effect of surgery on mood disorders in this group of epilepsy patients needs to be further investigated. Aim: This study aims to study whether there are differences in depression rates for TLE and extra-TLE patients in case studies of post-epileptic surgery patients. Method: The design of this study was cross sectional by conducting research on patients with temporal lobe epilepsy (n = 29) and extra temporal epilepsy patients (n = 24) from 1999 to 2019. The study was conducted at the Hospitals in Semarang. Researchers recorded depression levels using the Beck Depression Inventory - II (BDI-II) after the patient had surgery. The collected data will be analyzed using the parametric 2 independent samples t test. Results: 53 patients who were subject were 29 TLE patients (54.7%) and 24 Extra TLE patients (45.3%). TLE patients who had normal BDI-II results were 14 patients (48.3%), mild depression by 6 patients (20.7%), moderate depression by 8 patients (27.6%) and severe depression by 1 patient (3,4%) while the Extra TLE patients showed normal results of 11 patients (45.8%), mild depression of 8 patients (33.3%), moderate depression of 4 patients (16.7%) and severe depression of 1 patient ( 4.2%). 2 independent samples t test showed insignificant results, namely p = 0.831. Conclusion: There are differences of depression level between TLE and Extra TLE cannot be confirmed, because there are many factors such as the duration of epilepsy and seizure frequency that influence patients. Multifactorial explanation for the depression in patients with TLE and extra TLE must be investigated. Keywords: TLE (Temporal Lobe Epilepsy), extra-TLE, Depression

Headache is one of the most common symptoms of epilepsy comorbidities. However, the relationship between the epilepsy and headache still needs clarification. Previous studies mostly investigated the overall incidence and clinical features of the headache in patients with the epilepsy. Temporal lobe epilepsy (TLE) and juvenile myoclonic epilepsy (JME) are the common types of focal epilepsy and generalized epilepsy, respectively. Nevertheless, there was no study comparing the clinical features of headache between TLE and JME. This study aimed to analyze the headache features of these two types of epilepsy. Patients with either TLE or JME diagnosed with headache and referred to the West China Hospital of Sichuan University were consecutively recruited from June 2021 to June 2022. The duration of epilepsy was longer than 6 months in these patients. Data on headache and epilepsy were obtained through face-to-face questionnaires. The headache was classified according to the International Classification Headache Disorders-3rd edition (ICHD-III) criteria. χ2-test, t-test, rank-sum test, logistic regression modeling and Mann Whitney test were used to compare the clinical differences of the headache in TLE and JME. A total of 151 TLE patients and 30 JME patients were enrolled in this study. There was no significant difference in the family history of headache, epilepsy durations, headache types, proportion receiving analgesic therapy, the frequency of inter-ictal headache (inter-IH), and the quality of life in epilepsy -10 inventory (QOLIE-10) between the TLE and JME patients. Patients in the TLE group were significantly older (p = 0.004), and a lower percentage of them had a family history of epilepsy (p = 0.007) compared with the JME patients. The proportion of cases with refractory epilepsy was higher in the TLE group than that in the JME group (p < 0.001). The types of seizures in the TLE group varied from those in the JME group (p < 0.001). The composition of the antiseizure medications (ASM) applied in the TLE group differed from that in the JME group (p = 0.047), and the usage of oxcarbazepine was more frequently in the TLE group than in the JME group (p = 0.003). There was no difference in the headache types among patients with TLE or JME. Specifically, 67 (44.37%), 12 (7.95%), and 118 (7.95%) patients were found with inter-IH, pre-ictal headache (Pre-IH) and post-ictal headache (Post-IH) in the TLE group; while 8 (26.67%), 4 (13.33%) and 26 (86.67%) patients had inter-IH, Pre-IH and Post-IH in the JME group. Thirty-nine patients in the TLE group and 4 patients in the JME group were identified with more than one type of headaches, respectively. Tension-type headache (TTH) were found in 38 patients (25.17%) in the TLE group and 3 patients (10.00%) in the JME group, respectively; migraines were found in 10 patients (6.62%) in the TLE group and in 2 patients (6.67%) in the JME group. Patients in the TLE group had a higher headache-attributed lost time-90 days (HLT-90) score than those in the JME group (p = 0.019). The proportion of patients with inter-IH accompanied by nausea in the TLE group was higher than that in the JME group (p = 0.029), while the proportion of patients with frontal headache was lower than that in the JME group (p < 0.05). There was no significant difference in headache severity, quality, headache nature, unilateral/bilateral, and headache duration either in inter-IH or peri-ictal headache (Peri-IH) between the two groups. The logistic regression analysis suggested that except for HLT-90 (AUC = 0.622, p = 0.027), other factors were not found to be correlated with refractory epilepsy. The clinical features of headache differed between TLE and JME patients. TLE patients had a higher ratio of refractory epilepsy, more headache time loss compared with JME patients. HLT-90 was associated with the occurrence of refractory epilepsy in TLE patients. Taken together, we suggested that the comorbid headache may essentially be different between TLE and JME patients.

ObjectiveTo investigate the changes in the cerebellar-cerebral language network in temporal lobe epilepsy (TLE) patients from the cerebellar perspective, the research analyzes the changes of language and cognitive network in terms of functional connectivity (FC), as well as their efficiency of the reorganization were evaluated basing on relationship between the network metrics and neuropsychological scale scores.Methods30 TLE patients and 30 healthy controls were recruited. Brain activity was evaluated by voxel-mirrored homotopic connectivity analysis (VMHC). Two groups were analyzed and compared in terms of language FC using the following methods: Seed-to-Voxel analysis, pairwise correlations [region of interest(ROI)-to-ROI] and graph theory. Correlation analysis was performed between network properties and neuropsychological score.ResultsCompared with healthy participants, VMHC values in the Cerebellum Anterior Lobe, Frontal Lobe, Frontal_Sup_R/L, Cingulum_Ant_R/L, and Cingulum_Mid_R/L were decreased in TLE patients. Decreased FC was observed from the Cerebelum_10_R to the left inferior frontal gyrus, from the Cerebelum_6_R to the left Lingual Gyrus, from the Cerebelum_4_5_R to left Lingual Gyrus, left Cuneal Cortex and Precuneous Cortex, from the Cerebelum_3_R to Brain-Stem, and from the Cerebelum_Crus1_L to Cerebelum_6_R in TLE patients. The FC was enhanced between bilateral Cingulum_Mid and angular gyrus and frontoparietal insular cranium, between Frontal_Sup_Med L and left/right superior temporal gyrus (pSTG l/r), while it was decreased between left middle temporal gyrus and pSTG l/r. Compared with controls, the Betweenness Centrality (BC) of the right superior marginal gyrus (SMG), Temporal_Pole_Mid_R and Temporal_Mid_L as well as the Degree Centrality (DC) and Nodal Efficiency (NE) of the right SMG were lower in TLE patients. Further analysis showed that decreased VMHC in bilateral Cerebellum Anterior Lobe was positively correlated with the Boston Naming Test score in TLE patients, but it was negatively correlated with the Verbal Fluency Test score. The NE and DC of SMG_R were both negatively correlated with visual perception score in Montreal Cognitive Assessment.ConclusionOur results suggest that presence of abnormalities in the static functional connectivity and the language and cognitive network of TLE patients. Cerebellum potentially represents an intervention target for delaying or improving language and cognitive deficits in patients with TLE.

We hypothesized that temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS) showed differences in their limbic networks. This study aimed to evaluate the role of the thalamus in TLE patients with HS. Twenty-nine TLE patients with HS and 30 controls were enrolled in this study. In addition, we included eight TLE patients without HS as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the limbic structures, including the hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. Moreover, we quantified correlations between epilepsy duration and the volumes of these structures. There was a statistically significant effective connectivity from the hippocampus to the thalamus in TLE patients with HS. Moreover, the volumes of the left and right thalamus were negatively correlated with epilepsy duration (r=-.42, P=.0315 and r=-.52, P=.0062, respectively). However, neither TLE patients without HS nor normal controls had a significant effective connectivity from the hippocampus to the thalamus. The limbic networks of TLE patients with and without HS could be different, and the thalamus might play a critical role in TLE patients with HS.

ObjectiveThis study aimed to evaluate glymphatic system function in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS) in comparison to healthy controls, using diffusion tensor imaging (DTI)‐analysis along the perivascular space (ALPS) method. We hypothesized that there is glymphatic system dysfunction in TLE patients with HS.MethodsWe retrospectively enrolled 25 TLE patients with HS and 26 age‐ and sex‐matched healthy controls. All participants underwent DTI with the same 3T magnetic resonance imaging scanner, and the DTI‐ALPS index was calculated. We evaluated the differences in the DTI‐ALPS index between TLE patients with HS and healthy controls. Moreover, we evaluated the correlation between the DTI‐ALPS index and clinical characteristics of epilepsy, including age, age at seizure onset, duration of epilepsy, and number of anti‐seizure medications (ASMs).ResultsThere was a difference in the DTI‐ALPS index between TLE patients with HS and healthy controls. The DTI‐ALPS index in TLE patients with HS was lower than that in healthy controls (1.497 vs. 1.668, P = .015). However, there was no difference in the DTI‐ALPS index between the newly diagnosed TLE patients with HS and the chronic TLE patients with HS. The DTI‐ALPS index was negatively correlated with age (r = −0.420, P = .036). However, the DTI‐ALPS index was not correlated with other clinical characteristics, including age at seizure onset, duration of epilepsy, and number of ASMs.SignificanceOur findings showed that the DTI‐ALPS index was significantly lower in TLE patients with HS than in healthy controls, indicating the presence of glymphatic system dysfunction in TLE patients with HS. Our study also suggests that the DTI‐ALPS method may be useful for evaluating glymphatic system function in epilepsy.

A meta-analysis of voxel-based morphometry studies on unilateral refractory temporal lobe epilepsy

Background: The aim of this study was to identify the differences of intrinsic amygdala, hippocampal, or thalamic networks according to surgical outcomes in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS).Methods: We enrolled 69 pathologically confirmed TLE patients with HS. All patients had pre-operative three-dimensional T1-weighted MRI using a 3.0 T scanner. We obtained the structural volumes of the amygdala nuclei, hippocampal subfields, and thalamic nuclei. Then, we investigated the intrinsic networks based on volumes of these structures using structural covariance and graph theoretical analysis.Results: Of the 69 TLE patients with HS, 21 patients (42.1%) had poor surgical outcomes, whereas 40 patients (57.9%) had good surgical outcomes. The volumes in the amygdala nuclei, hippocampal subfields, and thalamic nuclei were not different according to surgical outcome. In addition, the intrinsic amygdala and hippocampal networks were not different between the patients with poor and good surgical outcomes. However, there was a significant difference in the intrinsic thalamic network in the ipsilateral hemisphere between them. The eccentricity and small-worldness index were significantly increased, whereas the characteristic path length was decreased in the patients with poor surgical outcomes compared to those with good surgical outcomes.Conclusion: We successfully demonstrated significant differences in the intrinsic thalamic network in the ipsilateral hemisphere between TLE patients with HS with poor and good surgical outcomes. This result suggests that the pre-operative intrinsic thalamic network can be related with surgical outcomes in TLE patients with HS.

To characterize possible metabolic changes of the dorsolateral prefrontal cortex (DLPFC) in patients with temporal lobe epilepsy (TLE). Quantitative proton magnetic resonance spectroscopy (1H-MRS) studies were performed on 24 TLE patients and 22 healthy controls. Metabolite concentrations were calculated using a linear combination model (LCModel) and corrected for cerebrospinal fluid contamination. Comparisons were performed between the TLE patients and the controls and between the left DLPFC and right DLPFC in each group. Pearson correlation coefficients were calculated between the metabolite concentrations and epilepsy duration and between the metabolite concentrations and voxel tissue composition: [gray matter (GM)/(GM+white matter (WM))]. Metabolic asymmetry was found in controls between the left and right DLPFC, i.e., the NAA concentration of the left DLPFC was significantly higher than that of the right. However, such metabolic asymmetry was not observed in TLE patients. Compared with the controls, TLE patients showed significantly decreased NAA and Ins, and the reductions were greater in the left DLPFC. No significant correlation was found between the metabolite concentrations and epilepsy duration or between the metabolite concentrations and voxel tissue composition [GM/(GM+WM)]. This study suggests that TLE can produce metabolic changes to DLPFC that is remote from the seizure focus. • Magnetic resonance spectroscopy probes the brain metabolism noninvasively. • Dorsolateral prefrontal reductions in NAA (a neuronal marker) and Ins are observed in TLE. • Temporal lobe epilepsy can result in metabolic changes remote from the seizure focus.

The aim of this study was to investigate the differences in structural connectivity based on diffusion tensor imaging (DTI) and functional connectivity based on arterial spin labeling (ASL) MRI between temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS). We enrolled 50 patients with TLE, including 25 patients with HS and 25 patients without HS, who underwent brain MRI, including DTI and ASL. We calculated the network parameters of structural connectivity based on DTI and functional connectivity based on ASL using a graph theoretical analysis. The parameters included global network measures (radius, diameter, characteristic path length, global efficiency, local efficiency, mean clustering coefficient, transitivity, assortative coefficient, and small-worldness index) and a local network measure (betweenness centrality). The global and local network measures of structural connectivity were not different between TLE patients with and without HS. However, significant differences in functional connectivity existed between the two groups. The radius and diameter of the global network measures in the TLE patients with HS were significantly increased compared with those without HS (4.140 vs. 3.140, p = 0.045; 6.812 vs. 5.132, p = 0.049; respectively). No differences were detected between other global network measures of functional connectivity and local network measure. Significant differences in global network measures of functional connectivity based on ASL existed between TLE patients with and without HS. These findings suggest that TLE patients with HS exhibit a more disconnected functional brain network than those without HS.

Abnormal functional brain networks of temporal lobe epilepsy (TLE) patients with structural abnormalities may partially reflect structural lesions rather than either TLE per se or functional compensatory processes. In this study, we sought to investigate the brain-network properties of intractable TLE patients apart from the effects of structural abnormalities. The brain network properties of 20 left and 23 right MRI-negative TLE patients and 22 healthy controls were evaluated using magnetoencephalographic recordings in six main frequency bands. A slowing of oscillatory brain activity was observed for the left or right TLE group vs. healthy controls. The TLE groups presented significantly increased functional connectivity in the delta, theta, lower alpha and beta bands, and significantly greater values in the normalized clustering coefficient and path length, and significantly smaller values in the weighted small-world measure in the theta band when compared to healthy controls. Alterations in global and regional band powers can be attributed to spectral slowing in TLE patients. The brain networks of TLE patients displayed abnormally high synchronization in multi-frequency bands and shifted toward a more regular architecture with worse network efficiency in the theta band. Without the contamination of structural lesions, these significant findings can be helpful for better understanding of the pathophysiological mechanism of TLE. The theta band can be considered as a preferred frequency band for investigating the brain-network dysfunction of MRI-negative intractable TLE patients.

ObjectiveReduced deactivation within the default mode network (DMN) is common in individuals with primary affective disorders relative to healthy volunteers (HVs). It is unknown whether similar network abnormalities are present...

The degree to which depression interacts with the cognitive deficits of epilepsy to alter cognitive skill and general functioning is unknown. Depression has significant negative effects on adaptive functioning including cognitive skills. Temporal lobe epilepsy (TLE) patients are known to possess cognitive dysfunction. Thus, TLE patients who are depressed may suffer a double burden of cognitive deficits. We examined whether depressed patients show increased cognitive deficits relative to nondepressed TLE patients (n = 59). We then sought to determine if this effect varied for left versus right TLE patients utilizing preoperative depression and neuropsychological data. To accurately study the lateralization of any observed effects, we selected only patients with definitive evidence of unilateral pathology and seizure focus and utilized a two-year seizure-free postsurgical outcome to capture this. The data suggested that cognitive performance was not related to depression, and that depression did not reliably mediate the cognitive presentation of either our left or right TL patients. The notion of a double burden on cognition did not receive support from our data. The data did produce the expected advantage on verbal memory measures for right TLE patients. The reasons for the limited statistical effects are discussed and issues in unraveling the causal relationships between depression, cognition, and TLE are considered. We discussed the potential role depression may play in the cognitive skills of TLE patients, but the major implication is that depression and neurocognitive performance appear to bear a limited relationship in the context of TLE.