TLE Groups Research Articles

Inflammation-related genes and immune infiltration landscape identified in kainite-induced temporal lobe epilepsy based on integrated bioinformatics analysis.

Temporal lobe epilepsy (TLE) is a common brain disease. However, the pathogenesis of TLE and its relationship with immune infiltration remains unclear. We attempted to identify inflammation-related genes (IRGs) and the immune cell infiltration pattern involved in the pathological process of TLE via bioinformatics analysis. The GSE88992 dataset was downloaded from the Gene Expression Omnibus (GEO) database to perform differentially expressed genes screening and weighted gene co-expression network analysis (WGCNA). Subsequently, the functional enrichment analysis was performed to explore the biological function of the differentially expressed IRGs (DEIRGs). The hub genes were further identified by the CytoHubba algorithm and validated by an external dataset (GSE60772). Furthermore, the CIBERSORT algorithm was applied to assess the differential immune cell infiltration between control and TLE groups. Finally, we used the DGIbd database to screen the candidate drugs for TLE. 34 DEIRGs (33 up-regulated and 1 down-regulated gene) were identified, and they were significantly enriched in inflammation- and immune-related pathways. Subsequently, 4 hub DEIRGs (Ptgs2, Jun, Icam1, Il6) were further identified. Immune cell infiltration analysis revealed that T cells CD4 memory resting, NK cells activated, Monocytes and Dendritic cells activated were involved in the TLE development. Besides, there was a significant correlation between hub DEIRGs and some of the specific immune cells. 4 hub DEIRGs (Ptgs2, Jun, Icam1, Il6) were associated with the pathogenesis of TLE via regulation of immune cell functions, which provided a novel perspective for the understanding of TLE.

The local neural markers of MRI in patients with temporal lobe epilepsy presenting ictal panic: A resting resting-state postictal fMRI study

ObjectivesTemporal lobe epilepsy (TLE) is one of the most common focal epilepsies. Some patients with TLE have ictal panic (IP), which is often confused with panic attack (PA) in panic disorder (PD). Previous studies have described temporal lobe epilepsy with ictal panic (TLEIP), but the specific mechanisms remain unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate local brain abnormalities in patients with TLEIP and tried to find neural markers to explore the mechanism of IP in patients with TLE. MethodsA total of 40 patients with TLE, including 28 patients with TLE and 12 patients with TLEIP along with 30 age- and gender-matched healthy controls were included. We collected clinical/physiological/neuropsychological and rs-fMRI data. Fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated. ANOVA was used to find different areas and t-tests used to compare differences among fALFF, ReHo, and DC. Correlation analyses explored the relationship between local brain abnormalities and patient characteristics. ResultsNo significant differences in age and gender were found among the three groups, nor were there differences in education level, Montreal Cognitive Assessment (MOCA) and Hamilton Anxiety Scale (HAMA) between the TLEIP and TLE groups. All the onset sites of patients with TLEIP were on the right. In addition to fear, other symptoms observed included nausea, palpitations, rising epigastric sensation, and dyspnea. There were no correlations between duration of IP and HAMA (p = 0.659). Moreover, all IP durations were <2 min and most <1 min. Compared to the HCs group, the ReHo value of the TLEIP group in the right middle frontal gyrus was significantly decreased (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). Compared to the HCs and TLE groups, the DC value of the TLEIP group in the left middle temporal gyrus (MTG) was significantly increased (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). No regions showed any significant fALFF difference between HCs and TLE groups (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). ConclusionsThis research describes local brain abnormalities in patients with TLE presenting as IP. These results will be preliminarily conducive to understand the seizure mechanism of IP in patients with TLE, find out the MRI neural markers, and to further explore the neurophysiological mechanisms of IP in patients with TLE.

DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures

BackgroundTemporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS.ResultsWe found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls.ConclusionTogether, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted.

The relationship of seizure focus with depression, anxiety, and health-related quality of life in children and adolescents with epilepsy.

For youth with epilepsy, comorbid psychiatric conditions, such as depression and anxiety, require further examination as they carry increased risk for reduced health-related quality of life (HRQOL). The current study assessed whether rates of depression, anxiety, and withdrawal behaviors differed based on seizure location. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 132 children and adolescents (mean age=11.34, SD=3.95) with generalized or partial (i.e., frontal [FLE] or temporal lobe epilepsy [TLE]) epilepsy. Our results identified clinically significant internalizing psychopathology in nearly half of our sample (41%). Although rates of internalizing behavior were similar between generalized and partial groups, children and adolescents with TLE demonstrated higher rates of depression compared to youth with FLE. No effects of laterality on internalizing behaviors were identified between TLE and FLE groups. Finally, for youth with TLE, parental depression ratings along with current number of antiepileptic medications (AEDs) were found to be significant barriers to HRQOL above and beyond anxiety, withdrawal, and epilepsy-specific variables. Temporal lobe epilepsy was associated with a two-fold risk of clinically significant depression ratings. These findings highlight the high prevalence of internalizing psychopathology features in pediatric epilepsy and offer further support for the relationship between depression and TLE in children and adolescents with epilepsy.

Study of absence of theta oscillation of working memory dysfunction in temporal lobe epilepsy

Objective Temporal lobe epilepsy (TLE), frequently accompanied by working memory dysfunction, is an important form of adult epilepsy syndrome. Study on neural mechanisms of TLE with working memory dysfunction has important scientific value and clinical significance. Theta oscillations are synchronous activity of the brain in the 4-8 Hz frequency range. It is well recognized that there is a close relationship between the theta oscillations and working memory behavior. TLE patients with working memory dysfunction were taken as the research subjects, and the theta oscillations absence in TLE with working memory behavioral disorder was carried out, which provide the reference for further research into the neural mechanisms of TLE with working memory dysfunction. Methods The 34-channel electroencephalographs (EEGs) were recorded from TLE group (18 TLE patients) and control groups (18 healthy subjects) while subjects were performing visual working memory (delayed matching-to-sample) tasks. The EEGs during the 3 s delay period was analyzed as experimental data. Fourier transform was used to assess the EEGs spectrum. The channel with the strongest spectrum was selected as the feature channel. Short-time Fourier transform algosiths was employed to calculate the time-frequency representation of the feature channel for the TLE and control groups. Frequency band with the strongest spectrum was selected for control group as the feature frequency band in working memory. Then, the topographical maps of the feature frequency band spectrum were calculated for the TLE and control groups. Results Compared with the control group, the working memory behavioral performance of the TLE group was lower: accuracy of the TLE group was significantly lower than that of the control group (P<0.05), and reaction time of the TLE group was significantly longer than that of the control group (P<0.001). The feature channel in working memory was frontal midline (Fz) and the feature frequency band was theta band. The Fz spectrum of the feature frequency for TLE was lower than that for control (P<0.05). The frontal spectrum (seven channels) of the feature frequency for TLE was lower than that of control (P<0.01). Conclusions Theta oscillations for TLE with working memory behavioral disorder is absent, which maybe one of the possible neural mechanism of TLE with working memory dysfunction. Key words: Temporal lobe epilepsy; Working memory dysfunction; Multi-channel electroencephalographs; Theta oscillations

Memory, executive function and language function are similarly impaired in both temporal and extra temporal refractory epilepsy—A prospective study

Cognitive impairment has long been recognized as a co-morbidity or sequel to refractory epilepsy. This study was conducted to evaluate the degree and selectivity of involvement of memory, language and executive functions performance among patients with temporal (TLE) versus extratemporal epilepsy (ETLE). We prospectively enrolled adolescent and adult patients with medically refractory focal epilepsy, who had undergone pre-surgical evaluation. Language, memory and executive function assessment was done using Western Aphasia Battery, PGI memory scale and battery of four executive function tests (trail making test A & B, digit symbol test, Stroop Task and verbal fluency test), respectively. Among102 patients enrolled (TLE-59, ETLE-43), mean age of patients 23.0 4± 8.3 years, 83 (82%) had impairment of more than one cognitive domain and 21 (21%) had all three domains involved. Severely impaired memory scores were found in 8.6% patients with MTLE-HS, 8% of the rest of the patients with TLE and 7% patients with ETLE. The differences in the mean scores were also not found statistically significant (p=0.669). Naming impairment was the most common language abnormality, although all aphasia subscores were similar for the ETLE and TLE groups. Executive function impairment was the most common cognitive domain affected. Overall performance on executive function tests was found impaired in almost all patients of both groups without any significant inter-group difference, except on Trail-A test, which revealed better results in patients with mTLE-HS as compared to all other sub-groups. Our study shows that impairment of memory, language and executive function is common among patients with drug refractory epilepsy. The most prevalent impairment is in executive function. There is no significant difference in the degree, prevalence or selectivity of impairment in either of the three domains, between the TLE versus ETLE groups.

Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy

Topiramate (TPM) is well recognized for its negative effects oncognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (−TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. −TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls — all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. −TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization.

Mesial temporal sclerosis is linked with more widespread white matter changes in temporal lobe epilepsy

Temporal lobe epilepsy patients with unilateral mesial temporal sclerosis (TLE + uMTS) have been demonstrated to have extensive white matter abnormalities both ipsilateral and contralateral to the seizure onset zone. However, comparatively less is known about the white matter integrity of TLE patients without MTS (non-lesional TLE, nl-TLE). The purpose of the study was to investigate the diffusion properties of thirteen major white matter tracts in patients with TLE + uMTS and nl-TLE. Diffusion tensor imaging (DTI) was performed on 23 TLE + uMTS (15 left MTS and 8 right MTS), 15 nl-TLE and 21 controls. Thirteen tracts were delineated by tractography and their diffusion parameters compared for the two TLE groups relative to controls, with left and right hemispheres combined per tract. A subgroup analysis investigated left and right MTS separately. Compared to controls, reduced anisotropy was detected in ten tracts for TLE + uMTS, but only the parahippocampal cingulum and tapetum for nl-TLE. Right MTS subgroup showed reduced anisotropy in 7 tracts bilaterally (3 limbic, 3 association, 1 projection) and 2 tracts ipsilaterally (1 association, 1 projection) and the body of the corpus callosum whereas the left MTS subgroup showed reduced anisotropy in 4 tracts bilaterally (2 limbic, 1 association, 1 projection) and 2 tracts ipsilaterally (1 limbic, 1 association). Diffusion abnormalities in tracts were observed within and beyond the temporal lobe in TLE + uMTS and were more widespread than in nl-TLE. Patients with right MTS had more extensive, bilateral abnormalities in comparison to left MTS. These findings suggest different dysfunctional networks in TLE patients with and without MTS.

Drawing from memory in focal epilepsy: A cognitive and neural perspective

This study provides evidence of non-verbal cognitive functioning in temporal (TLE) and frontal lobe epilepsy (FLE) patients by exploring the mechanisms and neural correlates of drawing abilities. Sixty-six patients with left (n=32) or right TLE (n=34), 30 patients with left (n=18) or right FLE (n=12), and 30 healthy subjects were compared. The Drawing from Memory (DfM) test required participants to design 16 living or non-living items; the total score was the sum of all scores blindly provided by three judges who had to identify the drawings. The verbal and visual Pyramid and Palm Trees Test (PPTT), Raven Colored Progressive Matrices (Raven CPM), Cube Analysis, Token Test, Word Fluency, Card Classification, and Rey Complex Figure Test Copy trial (Rey CFC) assessed different verbal and non-verbal functions. Non-parametric statistics indicated that, with respect to controls, both TLE groups and the left FLE patients had significantly lower DfM scores. In the TLE group, hierarchical regression analyses revealed that the DfM score was predicted by the Raven CPM and PPTT scores, while, in the FLE group, it was predicted by the Rey CFC. Thus, drawing abilities may be impaired by TLE or FLE owing to different mechanisms that involve semantic or executive abilities. Implying cooperation between temporal and frontal areas that support these functions, DfM may be a sensitive index of integrity of cortical areas or neural pathways damaged by focal epilepsy.

Widespread extrahippocampal NAA/(Cr+Cho) abnormalities in TLE with and without mesial temporal sclerosis

MR spectroscopy has demonstrated extrahippocampal NAA/(Cr+Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/(Cr+Cho) reductions? (2) Do extrahippocampal NAA/(Cr+Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI. Statistical parametric mapping (SPM2) was used to identify regions of significantly decreased NAA/(Cr+Cho) in TLE groups and in individual patients. TLE-MTS and TLE-no had widespread extrahippocampal NAA/(Cr+Cho) reductions. NAA/(Cr+Cho) reductions had a bilateral fronto-temporal distribution in TLE-MTS and a more diffuse, less well defined distribution in TLE-no. Extrahippocampal NAA/(Cr+Cho) decreases in the single subject analysis showed a large inter-individual variability and did not provide additional focus lateralizing information. Extrahippocampal NAA/(Cr+Cho) reductions in TLE-MTS and TLE-no are neither focal nor homogeneous. This reduces their value for focus lateralization and suggests a heterogeneous etiology of extrahippocampal spectroscopic metabolic abnormalities in TLE.

Voxel‐based morphometry of sporadic epileptic patients with mesiotemporal sclerosis

In refractory temporal lobe epilepsy (rTLE), gray matter (GM) abnormalities are not confined to the hippocampus but also are found in extrahippocampal structures. Very recently we observed in mild TLE (mTLE) with or without mesiotemporal sclerosis (MTS), GM reductions in regions outside the presumed epileptogenic focus. To date, there are no studies that directly investigate whether whole-brain GM volume differs between rTLE and mTLE. Herein, we used optimized voxel-based morphometry (VBM) to identify GM abnormalities beyond the hippocampus in both rTLE and mTLE with evidence of MTS. Brain magnetic resonance imaging (MRI) and optimized VBM were performed in 19 unrelated patients with mTLE, 19 patients with rTLE, and 37 healthy controls. MRI diagnosis of MTS was based on the atrophy of the hippocampal formation and/or mesiotemporal hyperintensity on fluid-attenuated inversion recovery (FLAIR) or T(2) images, or both. No patients (rTLE and mTLE) had generalized tonic-clonic or complex partial seizures for at least 3 weeks before scanning. Both mTLE and rTLE patients showed GM volume reduction of the bilateral thalamus, left hippocampus, and sensorimotor cortex compared with controls. No significant GM difference was found between rTLE and mTLE groups. In both rTLE and mTLE, VBM shows GM reductions not confined to the hippocampus involving mainly the thalamus bilaterally. This finding together with the lack of significant GM differences between the two TLE groups supports the hypothesis that mTLE and rTLE might lie along a biologic continuum, suggesting a pathophysiologic role of the thalamus in partial epilepsy.

Thalamic changes in temporal lobe epilepsy with and without hippocampal sclerosis: A diffusion tensor imaging study

The seizure network may be different between temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) and without HS (TLE-HS). Chronic seizure activity may alter the diffusion properties of a seizure network. The thalamus is known to have an anatomical connection to the medial temporal area and to play a role in seizure modulation. This study aimed to evaluate differences in thalamic changes between TLE+HS and TLE-HS with diffusion tensor imaging (DTI). Nine patients with TLE+HS and nine patients with TLE-HS were included in the study. All patients underwent surgery with good seizure outcomes. Hippocampal sclerosis was verified pathologically. Sixteen right-handed, normal subjects were enrolled as controls. DTI was acquired using 3.0 T MRI. The mean diffusivity (MD) and fractional anisotropy (FA) were calculated in the center of the bilateral thalamus with the DTIstudio program. The MD of bilateral thalami increased in both TLE groups compared to controls (p<0.05), while FA values did not differ from controls. The MD of the thalamus ipsilateral to the epileptogenic side was higher in the TLE+HS group than in the TLE-HS group (p=0.007). Onset age, seizure duration, seizure frequency and total seizure number were not correlated with FA and MD changes (p>0.05). Bilateral thalamic diffusion properties are altered in temporal lobe epilepsy. The presence of hippocampal sclerosis enhances the change ipsilaterally.

Decision making under ambiguity and under risk in mesial temporal lobe epilepsy

Decision making is essential in everyday life. Though the importance of the mesial temporal lobe in emotional processing and feedback learning is generally recognized, decision making in mesial temporal lobe epilepsy (mTLE) is almost unexplored so far. Twenty-eight consecutive epilepsy patients with drug resistant mTLE and fifty healthy controls performed decision tasks under initial ambiguity (participants have to learn by feedback to make advantageous decisions) and under risk (advantageous choices may be made by estimating risks and by rational strategies). A subgroup analysis compared the performance of patients affected by MRI-verified abnormalities of the hippocampus or amygdala. The effect of lesion side was also assessed. In decision under ambiguity, mTLE patients showed marked deficits and did not improve over the task. Patients with hippocampus abnormality and patients with amygdala abnormality showed comparable deficits. No difference was found between right and left TLE groups. In decision under risk, mTLE patients performed at the same level as controls. Results suggest that mTLE patients have difficulties in learning from feedback and in making decisions in uncertain, ambiguous situations. By contrast, they are able to make advantageous decisions when full information is given and risks, possible gains and losses are exactly defined.

Global/local scoring modifications for the Rey-Osterrieth Complex Figure: Relation to unilateral temporal lobe epilepsy patients

Observation of figural reproductions of right temporal lobe epilepsy (RTLE) patients have revealed overall configuration errors, whereas in left temporal lobe epilepsy (LTLE) patients, the global aspect of performance is generally preserved. This study compared performance of individuals with temporal lobe epilepsy (LTLE, n=83; RTLE, n=63) on a global/local modification of the Rey-Osterrieth Complex Figure Test (RCFT). In Phase I, neuropsychologists (n=6) and neuropsychology fellows (n=3) completed a survey identifying the global and local aspects of the RCFT. Questionnaire responses were used to categorize a list of global and local items (five global, five local) for re-scoring the protocols of TLE patients during study Phase II. Results showed that the RTLE and LTLE groups were not differentiated according to the global or local indices F(1,141) = .385; p = not significant. There were lower local scores for both groups in the copy F(1,142) = 5.23; p = .024, immediate F(1,142) = 445.26; p < .001, and delay trials F(1,142) = 427.82; p < .001, indicating less retention of local information over time. Results suggest general declines in figural memory for local stimulus properties in both unilateral TLE groups. However, this relationship was weakened after controlling for global and local item verbalizability.

Time Perception Following Unilateral Amobarbital Injection in Patients with Temporal Lobe Epilepsy

Estimates of elapsed time were obtained from 53 patients with unilateral temporal lobe epilepsy (Left TLE = 27; Right TLE = 26) following Wada (intracarotid amobarbital) assessment. After resolution of drug effects, patients were asked to estimate how much time had passed since amobarbital administration. Estimates were also obtained from 24 healthy control subjects using the same cognitive tasks over a similar time frame. Elapsed time was significantly underestimated by both left and right TLE groups following right hemisphere injection. In addition, there was an interaction effect involving patient group, side of injection, and sequence of injection. Left TLE patients, consistent with normal controls, made more accurate time estimates when they could anticipate the estimation task following the second amobarbital administration. More accurate time estimates, however, occurred only when left hemisphere injection was second in sequence. In contrast, right TLE patients did not improve regardless of the order of injection. These results suggest that right hemisphere function plays a critical role in the accuracy of time estimations of intermediate temporal duration and that interhemispheric interaction may be required to make accurate retrospective temporal judgments. These findings are discussed in the context of the growing evidence for a right-hemispheric attentional network.