Temporal Lobe Epilepsy With Hippocampal Sclerosis Research Articles

Identification of gene regulatory networks affected across drug-resistant epilepsies

Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies). This systematic comparison characterized the global molecular signature of epilepsies, elucidating the key underlying mechanisms of disease pathology including neurotransmission and synaptic plasticity, brain extracellular matrix and energy metabolism. In addition, specific dysregulations in neuroinflammation and oligodendrocyte function were observed in TLE-HS and mTORopathies, respectively. The aforementioned mechanisms are proposed as molecular hallmarks of DRE with the identified upstream regulators offering opportunities for drug-target discovery and development.

High-density electric source imaging patterns and outcomes following temporal lobectomy in patients with hippocampal sclerosis.

The objective of this study was to ascertain specific patterns of electrical source imaging (ESI) that are associated with a good surgical outcome (no seizure recurrence) using 256-channel high-density (HD) electroencephalography (EEG) in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) who underwent temporal lobectomy. Adult patients (age ≥ 18 years) were prospectively recruited from September 2016 to May 2020 at the authors' center. All patients underwent phase I presurgical evaluation and were subsequently advised to proceed with surgery based on consensus from a multidisciplinary epilepsy conference, without knowing HD-ESI results. All recruited patients were followed for at least 12 months after surgery. The outcome of interest was a status of no seizure recurrence, which was assessed at the end of the study. The association between ESI patterns and outcome was assessed using the chi-square or Fisher exact test. Associated p values as well as odds ratios and 95% CIs were reported. The diagnostic performance of the significant pattern associated with the outcome was also evaluated. Fifty-eight patients with known predictors for either good or worse surgical outcomes were recruited. The mean postoperative follow-up period was 33.34 (SD 13.88) months. Forty-seven patients had sufficient interictal epileptiform discharges for HD-ESI analysis. Thirteen of these 47 patients experienced seizure recurrence. The most common source localizations were at Brodmann area (BA) 20 (inferior temporal area) and BA 21 (middle temporal area). A specific ESI pattern of BA 21 without extratemporal sources was significantly associated with no seizure recurrence (p = 0.047). This pattern had a high positive predictive value of 100% and false-positive rate of 0% associated with no seizure recurrence following the surgery. A specific ESI pattern that was highly associated with no seizure recurrence following surgery was demonstrated by a 256-channel HD-EEG. If this pattern can be reproducibly proven in further studies, some TLE-HS patients may be able to proceed with surgery without further investigations.

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( = .05) and longer epilepsy duration ( = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.

Risk of suicide and religious or spiritual beliefs in Brazilian adult patients with epilepsy

In epilepsy, suicidal behavior is higher compared with the general population. ObjectiveTo assess the relationship between suicide risk, religiosity or spirituality, and clinical variables in adult patients with epilepsy (PWE). MethodologyThe data from the suicide module of the Mini International Neuropsychiatric Interview (MINI) were related to scores on the Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS-P) and the Hospital Anxiety and Depression Scale (HADS), as well as clinical variables in 96 adults PWE, with a significance level of p < 0.05. ResultsThe study included 49 patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and 47 cases of other epilepsies. The presence of suicide risk in the MINI was observed in 43 (44.7%) cases. Suicide risk was associated with an earlier age of epilepsy onset, higher seizure frequency, neurological abnormalities, and higher scores on the HADS-A and HADS-D scales. Suicide risk was low in 33 (76.7%) cases and moderate or high in 10 (23.2%) cases. Higher suicide risk was associated with higher education levels, focal structural epilepsy, use of ≥2 antiseizure medications, neurological abnormalities, anxiety, and dimensions such as daily spiritual experiences, religious or spiritual coping, organizational religiousness, and total score in the BMMRS-P. DiscussionA high number of patients with epilepsy exhibited suicide risk, with epilepsy-related variables, the presence of anxiety, and perceived lower belongingness and social support from religiosity or spirituality anxiety being associated with a higher risk. The social support provided by religiosity/spirituality may be a non-clinical factor associated with suicidal behavior. Suicide in epilepsy is associated with a complex interaction of multidimensional factors.

Exploring the relationship between amygdala subnuclei volumes and cognitive performance in left-lateralized temporal lobe epilepsy with and without hippocampal sclerosis

Cognitive disruption is a debilitating comorbidity in Temporal Lobe Epilepsy (TLE). Despite recent advances, the amygdala is often neglected in studies that explore cognition in TLE. Amygdala subnuclei are differently engaged in TLE with hippocampal sclerosis (TLE-HS) compared to non-lesional TLE (TLE-MRIneg), with predominant atrophy in the first and increased volume in the latter. Herein, we aim to explore the relationship between the volumes of the amygdala and its substructures with respect to cognitive performances in a population of left-lateralized TLE with and without HS. Twenty-nine TLEs were recruited (14 TLE-HS; 15 TLE-MRIneg). After investigating the differences in the subcortical amygdalae and hippocampal volumes compared to a matched healthy control population, we explored the associations between the subnuclei of the amygdala and the hippocampal subfields with the cognitive scores in TLE patients, according to their etiology. In TLE-HS, a reduced volume of the basolateral and cortical amygdala complexes joined with whole hippocampal atrophy, was related to poorer scores in verbal memory tasks, while in TLE-MRIneg, poorer performances in attention and processing speed tasks were associated with a generalized amygdala enlargement, particularly of the basolateral and central complexes. The present findings extend our knowledge of amygdala involvement in cognition and suggest structural amygdala abnormalities as useful disease biomarkers in TLE.

Analysis of brain volume asymmetry and clinical application in patients with temporal lobe epilepsy with hippocampal sclerosis based on automatic brain segmentation

Objective: To analyze whole brain structural volume asymmetry in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) using automated brain segmentation technology, and to investigate the application value of this technology in the diagnosis of TLE-HS and the performance in determining the location the lateralization of epileptogenic focus. Methods: Twenty-eight patients with TLE-HS were enrolled in the First Affiliated Hospital of Zhengzhou University from April 2019 to October 2020, including 13 females and 15 males, aged ranged from 18 to 63 (30±12) years, and these patients were divided two group according to the epilepsy lateralization, left TLE-HS(LTLE-HS) group (n=11), right TLE-HS(RTLE-HS) group (n=17) and 28 normal controls [aged ranged from 18 to 49 (29±10) years]. All of these subjects underwent three-dimensional T1 weighted image (3D T1WI). The differences of brain structure and volumes in LTLE-HS, RTLE-HS and normal controls group were retrospectively analyzed, and Pearson's correlation coefficient was used to evaluate the left and right volume correlations, and effect size was used for evaluating the differences in left and right volume averages. The asymmetry index (AI) of the left and right lateral volumes in each group was also calculated and compared among the three groups. Results: Standard volumes of all structures within the brain were asymmetric in the normal controls, LTLE-HS, and RTLE-HS groups, with smaller volumes of ipsilateral hippocampus than contralateral hippocampus in both the LTLE-HS and RTLE-HS groups(0.20%±0.03% vs 0.24%±0.02%,0.21%±0.03% vs 0.25%±0.02% respectively;both P<0.001), and smaller volumes of gray and white matter of the ipsilateral temporal lobe than contralateral in the LTLE-HS group(4.41%±0.38% vs 5.01%±0.43%,1.83%±0.22 % vs 2.22%±0.14%;both P<0.001). There was a moderate to strong linear correlation (0.553<r<0. 964,all P<0.05) between left and right lateral volumes in the normal controls, LTLE-HS, and RTLE-HS groups. All three groups showed the largest effect sizes in the cingulate gyrus (The effect sizes were 3.07, 4.85 and 4.22 in control, LTLE-HS and RTLE-HS, respectively.). The AI values of the hippocampus, temporal lobe gray matter, and temporal lobe white matter were statistically different among the three groups (-1.48±8.64 vs 15.91±10.15 vs -17.59±10.00, 7.46±2.67 vs 12.67±6.67 vs 3.67±6.15, 6.53±3.71 vs 19.91±9.85 vs 1.57±8.38;all P<0.001). Conclusion: Volumetric measurements by automated brain segmentation techniques can play an important role in preoperative assessment of TLE, and the asymmetry of brain volume may be of value in determining the localization and extent of the epileptogenic focus.

Lateralizing Characteristics of Morphometric Changes to Hippocampus and Amygdala in Unilateral Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Background andObjective: In the present study, a detailed investigation of substructural volume change in the hippocampus (HC) and amygdala (AMG) was performed and the association with clinical features in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) determined. Methods: The present study included 22 patients with left-sided TLE-HS (LTLE-HS) and 26 patients with right-sided TLE-HS (RTLE-HS). In addition, 28 healthy controls underwent high-resolution T2-weighted image (T2WI) and T1-weighted image (T1WI) MRI scanning. Subfield analysis of HC and AMG was performed using FreeSurfer version 6.0. Results: Patients with TLE-HS showed a decrease in the volume of substructures in both HC and AMG, and this change was observed on the contralateral side and the ipsilateral side with HS. The volume reduction pattern of substructures showed laterality-dependent characteristics. Patients with LTLE-HS had smaller volumes of the ipsilateral subiculum (SUB), contralateral SUB, and ipsilateral cortical nucleus of AMG than patients with RTLE-HS. Patients with RTLE-HS had reduced ipsilateral cornu ammonis (CA) 2/3 and contralateral cortico-amygdaloid transition area (CAT) volumes. The relationship between clinical variables and subregions was different based on the lateralization of the seizure focus. Focal to bilateral tonic-clonic seizures (FTBTCS) was associated with contralateral and ipsilateral side subregions only in LTLE-HS. The abdominal FAS was associated with the volume reduction of AMG subregions only in LTLE-HS, but the volume reduction was less than in patients without FAS. Conclusions: The results indicate that unilateral TLE-HS is a bilateral disease that shows different laterality-dependent characteristics based on the subfield analysis of HC and AMG. Subfield volumes of HC and AMG were associated with clinical variables, and the more damaged substructures depended on laterality in TLE-HS. These findings support the evidence that LTLE-HS and RTLE-HS are disparate epilepsy entities rather than simply identical syndromes harboring a mesial temporal lesion. In addition, the presence of FAS supports good localization value, and abdominal FAS has a high localization value, especially in patients with LTLE-HS.

Brief multidimensional measure of spirituality/religiousness, self-esteem, quality of life, and epilepsy

IntroductionThe relationships between religiousness/spirituality (RS), self-esteem, and quality of life (QoL) in adult people with epilepsy (PWEs) have not been studied in detail. MethodsThis cross-sectional study assessed RS using the brief multidimensional measure of religiousness/spirituality (BMMRS) scores of 86 PWEs. These scores were compared to 58 individuals in the control group (CG). Among the PWEs, the BMMRS data were related with the QOLIE-31 and the Rosenberg self-esteem scale (RSES) scores and clinical variables. ResultsAmong the PWEs, 48 individuals had temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and other epilepsies in 38 cases. Higher “daily spiritual experiences,” “overall self-ranking as a religious/spiritual person,” and lower perception of “religious/spiritual coping” were observed in the TLE-HS group when compared to the CG. Among the PWEs, there was lower “religious/spiritual coping” and higher “overall self-ranking as a religious/spiritual person” in the TLE-HS group. There was a significant difference in the BMMRS dimensions according to the type and frequency of seizures and the number of antiseizure drugs taken. There was a low correlation between the BMMRS, the QOLIE-31, and the RSES. In the network analysis with the Fruchterman-Reingold algorithm, there was no correlation between self-esteem and RS. In the TLE-HS group, there was a correlation between the “forgiveness” dimension of the BMMRS and some dimensions of the QOLIE-31. ConclusionThere was a greater RS in the TLE-HS group when compared to the CG. Regarding the two epilepsy groups, there was a higher “overall self-ranking as a religious/spiritual person” and lower “religious/spiritual coping” in the TLE-HS. The clinical variables and demographic data are related to different BMMRS dimensions according to the type of epilepsy. In the TLE-HS group, a higher RS is related to a better QoL. RS is not related to self-esteem.

Focal cortical dysplasia links to sleep-related epilepsy in symptomatic focal epilepsy

ObjectiveIn sleep-related epilepsy (SRE), epileptic seizures predominantly occur during sleep, but the clinical characteristics of SRE remain elusive. We aimed to identify the clinical features associated with the occurrence of SRE in a large cohort of symptomatic focal epilepsy. MethodsWe retrospectively included patients with four etiologies, including focal cortical dysplasia (FCD), low-grade tumors (LGT), temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and encephalomalacia. SRE was defined as more than 70% of seizures occurring during sleep according to the seizure diary. The correlation between SRE and other clinical variables, such as etiology of epilepsy, pharmacoresistance, seizure frequency, history of bilateral tonic-clonic seizures, and seizure localization was analyzed. ResultsA total of 376 patients were included. Among them 95 (25.3%) were classified as SRE and the other 281(74.7%) as non-SRE. The incidence of SRE was 53.5% in the FCD group, which was significantly higher than the other three groups (LGT: 19.0%; TLE-HS: 9.9%; encephalomalacia: 16.7%; P < 0.001). The etiology of FCD (p < 0.001) was significantly associated with SRE (OR: 9.71, 95% CI: 3.35–28.14) as an independent risk factor. In addition, small lesion size (p = 0.009) of FCD further increased the risk of SRE (OR: 3.18, 95% CI: 1.33–7.62) in the FCD group. SignificanceOur data highlight that FCD markedly increased the risk of sleep-related epilepsy independently of seizure localization. A small lesion of FCD further increased the risk of sleep-related epilepsy by 2.18 times in the FCD group.

Acupuncture, seizure frequency, and quality of life in temporal lobe epilepsy

ObjectiveTo assess seizure frequency and quality of life (QOL) in a group of adults with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) before and after 10 weeks of systemic acupuncture sessions and compare the results with a group of patients with TLE-HS not undergoing acupuncture. MethodsThe Quality of Life in Epilepsy Inventory (QOLIE-31) and the initial and final seizure frequency of 26 adult patients with TLE-HS who underwent acupuncture sessions for 10 consecutive weeks were assessed. The data were compared to those of 26 patients with TLE-HS not submitted to acupuncture, with p < 0.05. ResultsThere was a clinically significant effect in reducing the mean number of seizures per month in the follow-up period of patients submitted or not to acupuncture (no intervention group and intervention group, effect size: −0.94 and −1.01, respectively). In the last four weeks of follow-up, there was a significant difference between the no intervention and intervention groups (0.5 [0–2] and 0 [0–4]; p = 0.018). When using minimally important change (MIC) threshold data for the QOLIE-31 between the final and initial scores, with the Cantril Ladder Scale as anchoring, it was observed that, in the intervention group, large clinically significant effects were seen for all dimensions, except for cognitive function, medication effect, and social function, which presented medium effects. In the follow-up, the variation of the QOLIE-31 scores was positive for both groups; however, it was higher in all dimensions in the intervention group, indicating a better QOL. ConclusionThere was a reduction in the mean number of seizures per month in all patients during the follow-up period. Acupuncture significantly reduced the number of seizures in the intervention group in the final phase of the study. QOL improvements occurred in all patients, however, more significantly in the intervention group.

Anxiety symptoms are the strongest predictor of quality of life in temporal lobe epilepsy

PurposeIt is established that the severity of depressive and anxiety symptoms is associated with poorer quality of life (QOL) in persons with drug-resistant epilepsy. We aimed to verify the presence of subsyndromic depressive episodes (SDEs) and subsyndromic anxiety episodes (SAEs) in persons with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) compared to healthy controls and to determine the impact of depressive and anxiety symptoms on patients' QOL. MethodsWe prospectively evaluated 35 persons with TLE-HS and 90 healthy controls. QOL was assessed by the Epilepsy Surgery Inventory (ESI) and QOL in Epilepsy Inventory-31 (QOLIE-31). The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-X) were used to assess symptoms, and SDEs and SAEs diagnosis were made considering the total scores of BDI (<9) and STAI-Trait (<49), respectively. ResultsPersons with TLE-HS had higher symptoms on BDI, STAI-S, and STAI-T. They have 3.011 greater odds of presenting SDEs and 7.056 times odds, SAEs. The depressive and anxiety symptoms, added in the model with epilepsy-related factors, accounted for a significant increase in the variance in several aspects of QOL. Anxiety-trait symptoms are the most critical individual determinant of the QOL. ConclusionOur results demonstrated that persons with TLE-HS had greater odds of presenting SDE and SAE than healthy controls. Besides, there was a relationship between anxiety and depressive symptoms and worse QOL in TLE-HS. It is essential to be aware of psychiatric symptoms, even though these symptoms do not meet the criteria to be considered a "disorder."

Serotonin and dopamine receptors profile on peripheral immune cells from patients with temporal lobe epilepsy

The role of inflammation and immune cells has been demonstrated in neurological diseases, including epilepsy. Leukocytes, as well as inflammatory mediators, contribute to abnormal processes that lead to a reduction in seizure threshold and synaptic reorganization. In this sense, identifying different phenotypes of circulating immune cells is essential to understanding the role of these cells in epilepsy. Immune cells can express a variety of surface markers, including neurotransmitter receptors, such as serotonin and dopamine. Alteration in these receptors expression patterns may affect the level of inflammatory mediators and the pathophysiology of epilepsy. Therefore, in the current study, we evaluated the expression of dopamine and serotonin receptors on white blood cells from patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Blood samples from 17 patients with TLE-HS and 21 controls were collected. PBMC were isolated and stained ex vivo for flow cytometry. We evaluated the expression of serotonin (5-HT1A, 5-HT1B, 5-HT2, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4), and dopamine receptors (D1, D2, D3, D4, and D5) on the cell surface of lymphocytes and innate immune cells (monocytes and granulocytes). Our results demonstrated that innate cells and lymphocytes from patients with TLE-HS showed high mean fluorescent intensity (MFI) for 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 compared to controls. No difference was observed for 5-HT2B. For dopamine receptors, the expression of D1, D2, D4, and D5 receptors was higher on innate cells from patients with TLE-HS when compared to controls for the MFI. Regarding lymphocytes population, D2 expression was increased in patients with TLE-HS. In conclusion, there are alterations in the expression of serotonin and dopamine receptors on immune blood cells of patients with TLE-HS. Although the biological significance of these findings still needs to be further investigated, these changes may contribute to the understanding of TLE-HS pathophysiology.

Epilepsy characteristics and cognitive, social, and mood functions in relation to intrinsic religiosity

PurposeThe purpose of the study was to relate the Intrinsic Religiosity Inventory (IRI) with clinical epilepsy variables, the occurrence of depressive symptoms, and the quality of life (QoL) of 169 adult people with epilepsy (PWEs). Data were compared with those of a similar control group (CG) without psychiatric disorders, with p < 0.05. ResultsA higher intrinsic religiosity (IR) was observed in PWEs when compared with the CG. Impairment in multiple cognitive domains was found in 41 (24.2%) cases, and a score >15 in the Neurological Disorders Depression Inventory for Epilepsy was observed in 44 (26%) cases. In PWE, a greater IR was associated with the use of more than one antiepileptic drug (AED), epileptiform activity (EA) in the left hemisphere, temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and the absence of depressive disorders. An early age of onset and the social functioning dimension of the Quality of Life in Epilepsy Inventory (QOLIE-31) were the predictive factors for a higher IR in the linear multivariate regression analysis. ConclusionThe IR was significantly higher in PWE. A higher IR was related to TLE-HS, EA in the left hemisphere, later onset of epilepsy, a better performance in the semantic verbal fluency (SVF) test, and the absence of depressive disorders, suggesting a complex neurophysiological relationship involving multiple factors.

Quality of life perception in patients with epilepsy for a period of 4 years

The quality of life (QoL) perception over time in adult people with epilepsy (PWE) is important to define strategies of conduct. ObjectiveThe aim of this study was to assess the minimally important change (MIC) threshold of the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) of PWE over a period of 4 years and its relationship with clinical epilepsy variables. MethodsA total of 129 PWE (46 ± 14.3 years) were included, and the clinical aspects of epilepsy and the QOLIE-31 were assessed in the initial and final assessment, with p < 0.05. ResultsThe emotional well-being (−6.31) and social functioning (−5.36) showed clinically relevant effects between the assessments. Quality of life was compromised by increasing the number of antiepileptic drugs (AED) taken [total score (−8.53), social functioning (−14.70)] or by maintaining the use of polytherapy [social functioning (−12.89)]. Fewer seizures were associated with a better QoL [total score (7.99), social (17.88) and cognitive functioning (16.30)]. The reduction in seizures was not associated with a better QoL [total and social functioning score], and the increase in seizures did not change QoL perception (cognitive functioning). There was a reduction in the QoL perception in medication effects in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) (8.92) and with an increase in age in one year (−0.44). ConclusionsQuality of life was compromised in the emotional well-being and social functioning during the 4-year follow-up period. The increase in the number of AED taken and age and the TLE-HS compromised QoL changes in the frequency of seizures not associated with a significant improvement in QoL.

Cerebrocerebellar structural covariance in temporal lobe epilepsy with hippocampal sclerosis

PurposeThe purpose of the study was to evaluate cerebral morphological changes in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and their relationship to the cerebellum. MethodsThe study cohort included 21 patients with intractable TLE-HS (14 left-sided, 7 right-sided) and 38 healthy controls (HC). All patients later underwent anteromedial temporal lobe resection. All subjects were examined using a 1.5-T magnetic resonance imaging (MRI). Volumes of distinct cerebral and cerebellar structures were measured using voxel-based morphometry. The structural covariance of temporal lobe structures, insula, and thalamus with cerebellar substructures was examined using partial least squares regression. ResultsMorphological changes were more significant in the group with left TLE-HS when comparing left-sided with right-sided structures as well as when comparing patients with controls. The gray matter volume (GMV) of the temporal lobe structures was smaller ipsilaterally to the seizure onset side in most cases. There was a significant amygdala enlargement contralateral to the side of hippocampal sclerosis in both patients with right and left TLE-HS as compared with controls. Selected vermian structures in patients with left but not right TLE-HS had significantly larger GMV than the identical substructures in controls. The structural covariance differed significantly between patients with left and right TLE-HS as compared with HC. The analysis revealed significant negative covariance between anterior vermis and mesial temporal structures in the group with left TLE-HS. No significance was observed for the group with right TLE-HS. ConclusionThere is significant asymmetry in the GMV of cerebral and cerebellar structures in patients with TLE-HS. Morphological changes are distinctly more pronounced in patients with left TLE-HS.The observed structural covariance between the cerebellum and supratentorial structures in TLE-HS suggests associations beyond the mesial temporal lobe structures and thalamus.

Hippocampal microstructural architecture and surgical outcome: Hippocampal diffusivity could predict seizure relapse

PurposeOur aim was to study the microstructural architecture of the contralateral hippocampus to the affected side in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and its relation with surgical outcome. MethodWe included 33 consecutive patients evaluated in our epilepsy surgery program during a five-year period. They underwent a presurgical MRI with volumetric T1 and diffusion weighted sequences. 22 patients with TLE-HS (13 women, 12 right TLE-HS) were finally selected. Median follow-up after surgery was 6.25 years (4.5–8.83 years). We segmented the hippocampal subfields of the contralateral hippocampus using FreeSurfer and calculated the fractional anisotropy (FA) and the mean diffusivity (MD) of each subfield. We also scanned 18 healthy age-matched controls. ResultsAfter surgery, 50 % of the patients (n = 11) remained seizure-free (SF) following surgery. Comparing non-SF to SF patients, the MD showed increased values of the CA1 (p = 0.035), the molecular layer (p = 0.010) and the dentate gyrus (p = 0.041) in the healthy hippocampus. Using a cut-off point for a survival analysis, we found that patients with lower values of MD of the molecular layer and the CA1 remained SF during long-term post-operative follow-up (p < 0.0001). ConclusionsThe contralateral hippocampal internal microstructure may have be implicated in post-surgery seizure freedom in patients with TLE-HS.

Phosphoproteomic analysis reveals Akt isoform-specific regulation of cytoskeleton proteins in human temporal lobe epilepsy with hippocampal sclerosis

Akt is one of the most important downstream effectors of phosphatidylinositol 3-kinase/mTOR pathway. Hyperactivation and expression of this pathway are seen in a variety of neurological disorders including human temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Nevertheless, the expression and activation profiles of the Akt isoforms, Akt1, Akt2, and Akt3 and their functional roles in human TLE-HS have not been studied. We examined the protein expression and activation (phosphorylation) patterns of Akt and its isoforms in human hippocampal tissue from TLE and non-TLE patients. A phosphoproteomic approach followed by interactome analysis of each Akt isoform was used to understand protein-protein interactions and their role in TLE-HS pathology. Our results demonstrated activation of the Akt/mTOR pathway as well as activation of Akt downstream substrates like GSK3β, mTOR, and S6 in TLE-HS samples. Akt1 isoform levels were significantly increased in the TLE-HS samples as compared to the non-TLE samples. Most importantly, different isoforms were activated in different TLE-HS samples, Akt2 was activated in three samples, Akt2 and Akt1 were simultaneously activated in one sample and Akt3 was activated in two samples. Our phosphoproteomic screen across six TLE-HS samples identified 183 proteins phosphorylated by Akt isoforms, 29 of these proteins belong to cytoskeletal modification. Also, we were able to identify proteins of several other classes involved in glycolysis, neuronal development, protein folding and excitatory amino acid transport functions as Akt substrates. Taken together, our data offer clues to understand the role of Akt and its isoforms in underlying the pathology of TLE-HS and further, modulation of Akt/mTOR pathway using Akt isoforms specific inhibitors may offer a new therapeutic window for treatment of human TLE-HS.

Higher transcription alleles of the MAOA-uVNTR polymorphism are associated with higher seizure frequency in temporal lobe epilepsy

BackgroundThere is evidence of an imbalance in the neuromodulatory system mediated by serotonin (5-HT) in patients with drug-resistant temporal lobe epilepsy (TLE). This study analyzed the monoamine oxidase A promoter variable number of tandem repeats (MAOA-uVNTR) polymorphism in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Therefore, we assessed the association between this genetic variant and seizure predisposition and severity in patients with TLE-HS. MethodsOne hundred nineteen patients with TLE-HS and 113 healthy volunteers were assessed. First, we genotyped all individuals for the MAOA-uVNTR genetic polymorphism. Second, we compared patients and controls and evaluated clinical variants of epilepsy. ResultsThere was no difference between the TLE-HS and control groups regarding genotypic and allelic distributions of MAOA-uVNTR polymorphism (p = 1.000). Higher transcription alleles of the MAOA-uVNTR were associated with higher seizure frequency (p = 0.032) and bilateral tonic-clonic seizures (p = 0.016). ConclusionsIn a selected group of patients with TLE-HS, the polymorphism MAOA-uVNTR was associated with some aspects of epilepsy severity, namely seizure frequency and bilateral tonic-clonic seizures.

Volumetric Changes in Hippocampal Subregions and Memory Performance in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

In the present study we explored the different patterns of volumetric atrophy in hippocampal subregions of patients with left and right mesial temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Meanwhile, the memory impairment patterns in Chinese-speaking TLE-HS patients and potential influencing factors were also determined. TLE-HS patients (21 left and 17 right) and 21 healthy controls were recruited to complete T2-weighted imaging and verbal/nonverbal memory assessment. The results showed that both left and right TLE-HS patients had overall reduced hippocampal subregion volumes on the sclerotic side, and cornu ammonis sectors (CA1) exhibited maximum atrophy. The verbal memory of left TLE-HS patients was significantly impaired (P <0.001) and was not associated with the volumes of the left hippocampal subregions. Verbal or nonverbal memory impairment was not found in the patients with right TLE-HS. These results suggested that the atrophy of hippocampal subregion volumes cannot account for the verbal memory impairment, which might be related to the functional network.

Physical activity, stigma, and quality of life in patients with epilepsy

Indication of physical activity (PA) for people with epilepsy (PWE) is debatable. This study investigated whether the International Physical Activity Questionnaire (IPAQ) score is related to the clinical aspects of epilepsy, QOLIE-31, and the Stigma Scale of Epilepsy (SSE) score of 67 PWE at a significance level of 5% (p<0.05).About one-third (32.8%) of the PWE were sedentary/irregularly active. Lower QOLIE-31 scores and higher SSE scores were found in PWE who did not practice PA for fear of seizures and in sedentary/irregularly active PWE. Twenty-three percent of the PWE stopped practicing PA for fear of seizures. The predictive factors in the logistic regression equation for not practicing physical activity for fear of seizures were the presence of depressive disorder (p=0.049) and temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) (p=0.024).Most PWE are sedentary and do not practice PA for fear of seizures. Physical activity is negatively influenced by clinical aspects of epilepsy. Less PA is associated with depressive disorder, worse quality of life, and higher perception of stigma.