Unilateral Hippocampal Sclerosis Research Articles

Expression and correlation of the NOD-like receptor family, pyrin domain-containing 3 inflammasome and the silent information regulator 1 in patients with drug-resistant epilepsy

BackgroundThe NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammatory pathway is implicated in the development of epilepsy and can be suppressed by the activation of the silent information regulator 1 (SIRT1). However, the expression and correlation of the NLRP3 pathway and SIRT1 in drug-resistant epilepsy (DRE) remain unknown. MethodsThis study evaluated the histopathology of the cerebral cortex from nine patients with DRE and eight patients with cavernous haemangioma undergoing surgical treatment. It analysed the expression of the NLRP3, interleukin-1β (IL-1β), caspase-1 and SIRT1 using immunohistochemistry. Additionally, the contents of NLRP3, caspase-1, IL-1β and SIRT1 in the serum samples of the included study participants were determined using ELISA method. The correlation between the NLRP3 pathway and the SIRT1 was assessed using Spearman’s correlation analysis. ResultsThe expression of NLRP3, caspase-1 and IL-1β in the cerebral cortex of patients with DRE was elevated, with the NLRP3 expression being negatively correlated with the SIRT1 expression. Furthermore, IL-1β in serum was upregulated in patients with DRE. The correlation between the content of serum SIRT1 and NLRP3, caspase-1 and IL-1β in patients with DRE was not significant. Notably, serum caspase-1 levels were obviously higher in patients with bilateral hippocampal sclerosis than in patients with unilateral hippocampal sclerosis. ConclusionsThe current results indicate that the expression of the NLRP3/caspase-1/IL-1β pathway is significantly upregulated in patients with DRE and that it is partially correlated with the SIRT1 expression. This study is important for understanding the pathophysiology of DRE and developing new treatment strategies for it.

Who are the Better Candidates for Epilepsy Surgery?

The resective epilepsy surgery can be the effective procedure to get seizure-free outcome in these drug resistant epilepsy (DRE) patients. Class I evidence firmly establishes the superiority of epilepsy surgery over medical treatments in both seizure control and quality of life for DRE patients. For the effective identification of optimal surgical candidates, it's essential to understand the prognostic factors of epilepsy surgery based on the surgical methods employed. Established positive prognostic indicators for temporal resection include the presence of hippocampal sclerosis on magnetic resonance imaging (MRI), focal lesions on MRI, unilateral temporal spikes, concordant ictal electroencephalography (EEG), and a history of prolonged febrile convulsion. Potential negative predictors encompass preoperative secondary generalized tonic-clonic seizures, a normal MRI, postoperative EEG spikes, and age at the time of surgery. For neocortical epilepsy, the prognostic factors identified through multivariate analysis were the presence of a discrete lesion, localized hypometabolism on Fluorodeoxyglucose positron emission tomography (FDG-PET), and localized ictal EEG. A significant correlation was found between achieving a seizure-free outcome in no visible lesion on MRI (MR-negative) epilepsy patients and having concordance in two or more presurgical evaluations, specifically in interictal EEG, ictal EEG, FDG-PET, and ictal single-photon emission computed tomography. There was a marked improvement in the seizure-free outcome in MR-negative temporal lobe epilepsy (TLE) by the application of this strategy. The better surgical candidates for epilepsy surgery are the followings: patients displaying a discrete lesion on MRI with concordant video-EEG monitoring (VEM) results, patients diagnosed with unilateral hippocampal sclerosis who have concordant VEM results, patients with unilateral hippocampal sclerosis but discordant VEM results, patients with focal cortical dysplasia and concordant VEM results, and patients diagnosed with MR-negative TLE who exhibit two or more consistent results from presurgical evaluations.

Interhemispheric asymmetrical change in gray matter volume in patients with unilateral hippocampal sclerosis.

To clarify the interhemispheric asymmetrical change in gray matter volume (GMV) in unilateral hippocampal sclerosis (HS), we compared changes in GMV relative to normal subjects between the HS and contralateral or non-HS sides. Forty-five patients with unilateral HS and 30 healthy subjects were enrolled. We quantified changes in GMV in the patients with HS as compared to GMV in the normal subjects by introducing the Z-score (Z-GMV) in each region or region of interest in unilateral HS. Then, we assessed the asymmetrically decreased regions, that is, regions with significantly higher Z-GMV on the HS side than the contralateral or non-HS side. Z-GMV was calculated according to the two templates of 58 regions per hemisphere covering the whole brain by anatomical automatic labeling (AAL) and 78 regions per cerebral hemisphere using the Anatomy Toolbox. Seven and four regions in AAL and 17 and 11 regions in Anatomy Toolbox were asymmetrically decreased in the Left Hand Side (LHS) and Right Hand Side (RHS), respectively. Hippocampus and Caudate in AAL, five subregions of the hippocampus (CA1-3, Dentate Gyrus and hippocampus-amygdala-transition-area and 4 extrahippocampal regions including two subregions in amygdala (CM: Centromedial, SF: Superficial), basal forebrain (BF) (Ch4), and thalamus (temporal) in anatomy toolbox were common among LHS and RHS concerning asymmetrically decreased regions. By introducing Z-GMV, we demonstrated the regions with asymmetrically decreased GMV in LHS and RHS, and found that the hippocampus and extrahippocampal regions, including the BF, were the common asymmetrically decreased regions among LHS and RHS.

Bilateral ictal EEG is associated with better memory outcome after hippocampal sclerosis surgery.

To compare memory outcomes after surgery for unilateral hippocampal sclerosis (HS)-associated epilepsy in patients with unilateral and bilateral ictal electrographic involvement. We prospectively evaluated HS patients, aged 18-55 years and IQ ≥70. Left (L) and right (R) surgical groups underwent noninvasive video-EEG monitoring and Wada test. We classified patients as Ipsilateral if ictal EEG was restricted to the HS side, or Bilateral, if at least one seizure onset occurred contralaterally to the HS, or if ictal discharge evolved to the opposite temporal region. Patients who declined surgery served as controls. Memory was evaluated on two occasions with Rey Auditory-Verbal Learning Test and Rey Visual-Design Learning Test. Baseline neuropsychological test scores were compared between groups. Pre- and postoperative scores were compared within each group. Reliable change index Z-scores (RCI) were obtained using controls as references, and compared between surgical groups. We evaluated 64 patients. Patients were classified as: L-Ipsilateral (9), L-Bilateral (15), L-Control (9), R-Ipsilateral (10), R-Bilateral (9), and R-Control (12). On preoperative evaluation, memory performance did not differ among surgical groups. Right HS patients did not present postoperative memory decline. L-Ipsilateral group presented postoperative decline on immediate (P = 0.036) and delayed verbal recall (P = 0.011), while L-Bilateral did not decline. L-Ipsilateral had lower RCI Z-scores, indicating delayed verbal memory decline compared to L-Bilateral (P = 0.012). Dominant HS patients with bilateral ictal involvement presented less pronounced postoperative verbal memory decline compared to patients with exclusive ipsilateral ictal activity. Surgery was indicated in these patients regardless of memory impairment on neuropsychological testing, since resection of the left sclerotic hippocampus could result in cessation of contralateral epileptiform activity, and, therefore, improved memory function.

Brain volumes and white matter diffusion across the adult lifespan in temporal lobe epilepsy.

Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.

White matter tract abnormalities are associated with executive dysfunction in temporal lobe epilepsy and hippocampal sclerosis (P12-1.010)

<h3>Objective:</h3> To evaluate the role of white-matter tract involvement in executive dysfunction in patients with temporal lobe epilepsy and unilateral hippocampal sclerosis (TLE-HS). <h3>Background:</h3> TLE-HS patients frequently display executive dysfunction (ED). The neuroanatomical substrate of ED in TLE-HS remains poorly understood. In this study, we investigated the role of white-matter tract involvement in ED in TLE-HS. <h3>Design/Methods:</h3> Patients with unilateral TLE-HS, aged 17–55, education&gt;=8 years, IQ&gt;=70, EEG findings of unilateral or bilateral temporal discharges were studied. Patients and healthy controls fulfilling the same inclusion criteria underwent the Stroop Color and Word Test (SCWT) and a 3T MRI with DTI sequences. DTI Fractional Anisotropy (FA) data was extracted and analyzed using FSL. FA maps were compared with Tract-Based Spatial Statistics (TBSS) voxel-wise analysis. Patients were classified as ED if performance in the SCWT was below minus 1.5 (−1.5) Standard Deviations of the mean performance of healthy controls. <h3>Results:</h3> 49 patients (30 left and 19 right HS) underwent the SCWT. Performance did not differ between right and left HS. Patients with normal and impaired executive function did not differ in disease duration, antiseizure medication load, and seizure frequency. Both patient groups showed diffuse FA decrease when compared to healthy controls. Compared to TLE-HS patients with normal SCWT performance, patients with ED had more pronounced FA alterations, showing statistically significant decreased FA in the superior longitudinal fasciculi, body of the corpus callosum, forceps major, corona radiata, inferior frontal-occipital fasciculus, uncinate fasciculus and corticospinal tract, and right thalamic radiations. <h3>Conclusions:</h3> In this TLE-HS patient population, executive dysfunction was associated with more pronounced widespread WM tract damage, in comparison with TLE-HS patients with preserved executive function. This finding underscores the role of microstructural WM damage in executive dysfunction in TLE-HS. <b>Disclosure:</b> Miss Solti has nothing to disclose. Mr. Mahler Ferreira Oliveira has nothing to disclose. Carla Adda has nothing to disclose. Rosa Valerio has nothing to disclose. Dr. Jorge has nothing to disclose. Katarina Lyra has nothing to disclose. Mr. Pastorello has nothing to disclose. Claudia Leite has nothing to disclose. Maria Otaduy has nothing to disclose. Dr. Castro has nothing to disclose.

Differential vulnerability of neuronal subpopulations of the subiculum in a mouse model for mesial temporal lobe epilepsy.

Selective loss of inhibitory interneurons (INs) that promotes a shift toward an excitatory predominance may have a critical impact on the generation of epileptic activity. While research on mesial temporal lobe epilepsy (MTLE) has mostly focused on hippocampal changes, including IN loss, the subiculum as the major output region of the hippocampal formation has received less attention. The subiculum has been shown to occupy a key position in the epileptic network, but data on cellular alterations are controversial. Using the intrahippocampal kainate (KA) mouse model for MTLE, which recapitulates main features of human MTLE such as unilateral hippocampal sclerosis and granule cell dispersion, we identified cell loss in the subiculum and quantified changes in specific IN subpopulations along its dorso-ventral axis. We performed intrahippocampal recordings, FluoroJade C-staining for degenerating neurons shortly after status epilepticus (SE), fluorescence in situ hybridization for glutamic acid decarboxylase (Gad) 67 mRNA and immunohistochemistry for neuronal nuclei (NeuN), parvalbumin (PV), calretinin (CR) and neuropeptide Y (NPY) at 21 days after KA. We observed remarkable cell loss in the ipsilateral subiculum shortly after SE, reflected in lowered density of NeuN+ cells in the chronic stage when epileptic activity occurred in the subiculum concomitantly with the hippocampus. In addition, we show a position-dependent reduction of Gad67-expressing INs by ∼50% (along the dorso-ventral as well as transverse axis of the subiculum). This particularly affected the PV- and to a lesser extent CR-expressing INs. The density of NPY-positive neurons was increased, but the double-labeling for Gad67 mRNA expression revealed that an upregulation or de novo expression of NPY in non-GABAergic cells with a concomitant reduction of NPY-positive INs underlies this observation. Our data suggest a position- and cell type-specific vulnerability of subicular INs in MTLE, which might contribute to hyperexcitability of the subiculum, reflected in epileptic activity.

Changes in the Brain in Temporal Lobe Epilepsy with Unilat-eral Hippocampal Sclerosis: Initial Case Series

Changes in the Brain in Temporal Lobe Epilepsy with Unilat-eral Hippocampal Sclerosis: Initial Case Series

Temporal lobe epilepsy with GAD antibodies: neurons killed by T cells not by complement membrane attack complex.

Temporal lobe epilepsy (TLE) is one of the syndromes linked to antibodies against glutamic acid decarboxylase (GAD). It has been questioned whether 'limbic encephalitis with GAD antibodies' is a meaningful diagnostic entity. The immunopathogenesis of GAD-TLE has remained enigmatic. Improvement of immunological treatability is an urgent clinical concern. We retrospectively assessed the clinical, MRI and CSF course as well as brain tissue of 15 adult patients with GAD-TLE who underwent temporal lobe surgery. Brain tissue was studied by means of immunohistochemistry, multiplex fluorescent microscopy and transcriptomic analysis for inflammatory mediators and neuronal degeneration. In 10 patients, there was a period of mediotemporal swelling and T2 signal increase; in nine cases this occurred within the first 6 years after symptom onset. This resulted in unilateral or bilateral hippocampal sclerosis; three cases developed hippocampal sclerosis within the first 2 years. All CSF studies done within the first year (n = 6) revealed intrathecal synthesis of immunoglobulin G. Temporal lobe surgeries were done after a median disease duration of 9 years (range 3 weeks to 60 years). Only two patients became seizure-free. Brain parenchyma collected during surgery in the first 6 years revealed high numbers of plasma cells but no signs of antibody-mediated tissue damage. Even more dense was the infiltration by CD8+ cytotoxic T lymphocytes (CTLs) that were seen to locally proliferate. Further, a portion of these cells revealed an antigen-specific resident memory T cell phenotype. Finally, CTLs with cytotoxic granzyme B+ granules were also seen in microglial nodules and attached to neurons, suggesting a CTL-mediated destruction of these cells. With longer disease duration, the density of all lymphocytes decreased. Whole transcriptome analysis in early/active cases (but not in late/inactive stages) revealed 'T cell immunity' and 'Regulation of immune processes' as the largest overrepresented clusters. To a lesser extent, pathways associated with B cells and neuronal degeneration also showed increased representation. Surgically treated patients with GAD-TLE go through an early active inflammatory, 'encephalitic' stage (≤6 years) with CTL-mediated, antigen-driven neuronal loss and antibody-producing plasma cells but without signs of complement-mediated cell death. Subsequently, patients enter an apparently immunologically inactive or low-active stage with ongoing seizures, probably caused by the structural damage to the temporal lobe. 'Limbic encephalitis' with GAD antibodies should be subsumed under GAD-TLE. The early tissue damage explains why immunotherapy does not usually lead to freedom from seizures.

Changes in the Brain in Temporal Lobe Epilepsy with Unilateral Hippocampal Sclerosis: An Initial Case Series.

Temporal lobe epilepsy (TLE) is a network disorder of the brain. Network disorders predominately involve dysregulation of hippocampal function caused by neuronal hyperexcitability. However, the relationship between the macro- and microscopic changes in specific brain regions is uncertain. In this study, the pattern of brain atrophy in patients with TLE and hippocampal sclerosis (HS) was investigated using volumetry, and microscopic changes in specific lesions were observed to examine the anatomical correspondence with specific target lesions using diffusion tensor imaging (DTI) with statistical parametric mapping (SPM). This retrospective cross-sectional study enrolled 17 patients with TLE and HS. We manually measured the volumes of the hippocampus (HC), amygdala (AMG), entorhinal cortex, fornix, and thalamus (TH) bilaterally. The mean diffusivity and fractional anisotropy of each patient were then quantified and analyzed by a voxel-based statistical correlation method using SPM8. In right TLE with HS, there was no evidence of any abnormal diffusion properties associated with the volume reduction in specific brain regions. In left TLE with HS, there were significant changes in the volumes of the AMG, HC, and TH. Despite the small sample size, these differences in conditions were considered meaningful. Chronic left TLE with HS might cause structural changes in the AMG, HC, and TH, unlike right TLE with HS.

Seizure Duration and Spread Dynamics in MRI-Defined Subtypes of Temporal Lobe Epilepsy.

MRI and PET imaging enables subgroups of temporal lobe epilepsy (TLE) to be defined on the basis of structural pathology. Few studies have examined the variation in electroclinical seizure spread patterns based on imaging findings. We performed a retrospective cohort study to investigate the electroclinical differences among 3 specific groups of TLE: MRI-negative PET-positive TLE (MRI-negative TLE), temporal lobe lesion TLE (lesional TLE), and unilateral hippocampal sclerosis TLE (HS-TLE). Patients with an electroclinical diagnosis of TLE who had video-scalp EEG recordings of seizures were identified from the retrospective database of the Austin Comprehensive Epilepsy Program between 2005 and 2019. The cohort was further selected into the 3 defined groups based on imaging findings, using MRI and FDG-PET. Timings of clinical and electrographic seizure progression were measured, considering the onset, ipsilateral lobar spread, contralateral spread, and termination. Durations were compared between groups using linear mixed models with inclusion of demographic and clinical covariates. A total of 105 patients (137 seizures) were included, comprising 36 with MRI-negative TLE (54 seizures), 36 with lesional TLE (18 lateral vs 16 mesial lesions; 44 seizures), and 33 with HS-TLE (39 seizures). Seizure duration was similar between MRI-negative TLE and lesional TLE (mean 75.9 vs 71.7 seconds; p = 0.91). Further dividing lesional TLE into medial vs lateral temporal revealed no timing difference. However, the HS-TLE group had longer total seizure duration (114 seconds) compared with both MRI-negative TLE (p < 0.001) and lesional TLE (p < 0.001). Progression of electrographic spread also reflected this pattern, with involvement of extratemporal regions and then the contralateral hemisphere each taking significantly longer in HS-TLE. MRI-negative TLE appears electrographically similar to lesional TLE, whether mesial or lateral, in the duration of seizures and the timing of electrographic spread. Both appear electrographically different from HS-TLE, where propagation is slower, suggesting engagement of different epileptogenic networks or seizure suppression mechanisms. This study provides Class II evidence that the electroclinical features of seizures in HS-TLE are different than MRI-negative TLE and lesional TLE.

Reward-based decision-making in mesial temporal lobe epilepsy patients with unilateral hippocampal sclerosis pre- and post-surgery

BackgroundCorrect functioning of the reward processing system is critical for optimizing decision-making as well as preventing the development of addictions and/or neuropsychiatric symptoms such as depression, apathy, and anhedonia. Consequently, patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis (mTLE-UHS) represent an excellent opportunity to study the brain networks involved in this system. ObjectiveThe aim of the current study was to evaluate decision-making and the electrophysiological correlates of feedback processing in a sample of mTLE-UHS patients, compared to healthy controls. In addition, we assessed the impact of mesial temporal lobe surgical resection on these processes, as well as general, neuropsychological functioning. Method17 mTLE-UHS patients and 17 matched healthy controls completed: [1] a computerized version of the Game of Dice Task, [2] a Standard Iowa Gambling Task, and [3] a modified ERP version of a probabilistic gambling task coupled with multichannel electroencephalography. Neuropsychological scores were also obtained both pre- and post-surgery. ResultsBehavioral analyses showed a pattern of increased risk for the mTLE-UHS group in decision-making under ambiguity compared to the control group. A decrease in the amplitude of the Feedback Related Negativity (FRN), a weaker effect of valence on delta power, and a general reduction of delta and theta power in the mTLE-UHS group, as compared to the control group, were also found. The beta-gamma activity associated with the delivery of positive reward was similar in both groups. Behavioral performance and electrophysiological measures did not worsen post-surgery. ConclusionsPatients with mTLE-UHS showed impairments in decision-making under ambiguity, particularly when they had to make decisions based on the outcomes of their choices, but not in decision-making under risk. No group differences were observed in decision-making when feedbacks were random. These results might be explained by the abnormal feedback processing seen in the EEG activity of patients with mTLE-UHS, and by concomitant impairments in working memory, and memory. These impairments may be linked to the disruption of mesial temporal lobe networks. Finally, feedback processing and decision-making under ambiguity were already affected in mTLE-UHS patients pre-surgery and did not show evidence of clear worsening post-surgery.

Reward-Based Decision Making in Mesial Temporal Lobe Epilepsy Patients with Unilateral Hippocampal Sclerosis Pre- and Post-Surgery

Reward-Based Decision Making in Mesial Temporal Lobe Epilepsy Patients with Unilateral Hippocampal Sclerosis Pre- and Post-Surgery

Reduced myelin in patients with isolated hippocampal sclerosis as assessed by SyMRI.

PurposeSynthetic MRI (SyMRI) enables to quantify brain tissue and morphometry. We aimed to investigate the WM and myelin alterations in patients with unilateral hippocampal sclerosis (HS) with SyMRI.MethodsAdult patients with isolated unilateral HS and age-matched control subjects (CSs) were included in this study. The SyMRI sequence QRAPMASTER in the coronal plane perpendicular to the hippocampi was obtained from the whole brain. Automatic segmentation of the whole brain was processed by SyMRI Diagnostic software (Version 11.2). Two neuroradiologists also performed quantitative analyses independently from symmetrical 14 ROIs placed in temporal and extratemporal WM, hippocampi, and amygdalae in both hemispheres.ResultsSixteen patients (F/M = 6/10, mean age = 32.5 ± 11.3 years; right/left HS: 8/8) and 10 CSs (F/M = 5/5, mean age = 30.7 ± 7 years) were included. Left HS patients had significantly lower myelin and WM volumes than CSs (p < .05). Myelin was reduced significantly in the ipsilateral temporal lobe of patients than CSs, greater in left HS (p < .05). Histopathological examination including luxol fast blue stain also revealed myelin pallor in all of 6 patients who were operated. Ipsilateral temporal pole and sub-insular WM had significantly reduced myelin than the corresponding contralateral regions in patients (p < .05). No significant difference was found in WM values. GM values were significantly lower in hippocampi in patients than CSs (p < .05).ConclusionSyMRI revealed myelin reduction in the ipsilateral temporal lobe and sub-insular WM of patients with HS. Whether this finding correlates with electrophysiological features and SyMRI could serve as lateralization of temporal lobe epilepsy need to be investigated.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00234-021-02824-6.

IL-1\u03b2 and HMGB1 are anti-neurogenic to endogenous neural stem cells in the sclerotic epileptic human hippocampus

BackgroundThe dentate gyrus exhibits life-long neurogenesis of granule-cell neurons, supporting hippocampal dependent learning and memory. Both temporal lobe epilepsy patients and animal models frequently have hippocampal-dependent learning and memory difficulties and show evidence of reduced neurogenesis. Animal and human temporal lobe epilepsy studies have also shown strong innate immune system activation, which in animal models reduces hippocampal neurogenesis. We sought to determine if and how neuroinflammation signals reduced neurogenesis in the epileptic human hippocampus and its potential reversibility.MethodsWe isolated endogenous neural stem cells from surgically resected hippocampal tissue in 15 patients with unilateral hippocampal sclerosis. We examined resultant neurogenesis after growing them either as neurospheres in an ideal environment, in 3D cultures which preserved the inflammatory microenvironment and/or in 2D cultures which mimicked it.Results3D human hippocampal cultures largely replicated the cellular composition and inflammatory environment of the epileptic hippocampus. The microenvironment of sclerotic human epileptic hippocampal tissue is strongly anti-neurogenic, with sustained release of the proinflammatory proteins HMGB1 and IL-1β. IL-1β and HMGB1 significantly reduce human hippocampal neurogenesis and blockade of their IL-1R and TLR 2/4 receptors by IL1Ra and Box-A respectively, significantly restores neurogenesis in 2D and 3D culture.ConclusionOur results demonstrate a HMGB1 and IL-1β-mediated environmental anti-neurogenic effect in human TLE, identifying both the IL-1R and TLR 2/4 receptors as potential drug targets for restoring human hippocampal neurogenesis in temporal lobe epilepsy.

Single-subject gray matter networks in temporal lobe epilepsy patients with hippocampal sclerosis

ObjectivePrevious studies have demonstrated structural brain network abnormalities in patients with temporal lobe epilepsy (TLE) using cortical thickness or gray matter (GM) volume. However, no studies have applied single-subject GM network analysis. Here, we first applied an analysis of similarity-based single-subject GM networks to individual patients with TLE. Materials and methodsWe recruited 51 patients with TLE and unilateral hippocampal sclerosis (22 left, 29 right TLE) and 51 age- and gender- matched healthy controls. Single-subject structural networks were extracted from three-dimensional T1-weighted magnetic resonance images for each subject. In this method, nodes were defined as small cortical regions and edges representing connecting regions that have high statistical similarity. The constructed graphs were analyzed using the graph theoretical approach. The following global and local network properties were calculated: betweenness centrality, clustering coefficient, and characteristic path length. In addition, small world properties (normalized path length λ, normalized clustering coefficient γ, and small-world network value σ) were obtained and compared with those for the controls. ResultsAlthough the small-world configurations were retained, impaired global clustering coefficient was observed in left and right TLE. At a regional level, patients with left TLE showed a widespread decrease of the clustering coefficient beyond the ipsilateral temporal lobe and a decreased characteristic path length in the ipsilateral temporal pole. On the other hand, patients with right TLE showed a localized decrease of the clustering coefficient in the ipsilateral temporal lobe. ConclusionsOur findings suggest that global and local network properties disrupted and moved toward randomized networks in TLE patients in comparison to controls. This network alteration was more extensive in left TLE than in right TLE patients. Single-subject GM networks may contribute to a better understanding of the pathophysiology of TLE.

EEG-based P300 in mesial temporal lobe epilepsy and its correlation with cognitive functions: A case-control study

ObjectiveP300 is an event-related potential, being explored as an objective tool to assess cognition. This study aimed to investigate the characteristics of auditory and visual P300 in patients with TLE having unilateral HS using electroencephalography (EEG) and to study its correlation with cognition. MethodsThis is a cross-sectional case-control study, where P300 characteristics in thirty patients with unilateral hippocampal sclerosis with refractory epilepsy were compared with fifteen age-, gender-, and years of education-matched healthy controls (M: F-10:5, mean age-28 ± 4.76 years). Among patients, 15 belonged to the right HS group (M: F-9:6, age at onset-12.92 ± 10.22 years, duration of epilepsy-16.67 ± 9.38 years) and 15 to the left HS group (M: F-8:7, age at onset-10.62 ± 7.18 years, duration of epilepsy-15.53 ± 10.14 years). All subjects underwent EEG-based auditory and visual oddball tasks and cognitive assessment. The P300 latencies (in milliseconds) as well as amplitudes (in microvolts) were predicted in EEG and were correlated with cognitive scores. Source localization of P300 was performed with the CLARA algorithm. ResultsThe auditory P300 latencies in controls, right HS, and left HS were 323.93 ± 40.28, 351.06 ± 47.23, and 328.80 ± 36.03, respectively (p = 0.18) and its amplitudes were 2.3040 ± 1.46, 2.77 ± 1.19, and 2.68 ± 1.78, respectively (p = 0.48). Visual P300 latencies in controls, right HS, and left HS were 365.87 ± 47.37, 359.67 ± 64.45, and 376.00 ± 60.06, respectively (p = 0.51) and its amplitudes were 3.93 ± 2.28, 2.09 ± 1.45, and 3.56 ± 1.74, respectively (p = 0.014). Further, when compared to the control group the cognitive scores were lower in the patient group (p < 0.05). SignificanceIn comparison to the controls, patients with right HS recorded lesser amplitude on visual P300 and lower scores on cognitive tests. P300 and cognitive parameters exhibited varied relationship. P300 could be a complementary objective tool to assess cognition in patients with TLE.

Bilateral epileptogenesis in temporal lobe epilepsy due to unilateral hippocampal sclerosis: A case series

IntroductionBitemporal epilepsy (biTLE), a potential cause of failure in TLE surgery, is rarely associated with unilateral HS and could be suggested by not lateralizing ictal scalp EEG/interictal PET-FDG findings. We evaluated the proportion of biTLE in a population of drug-resistant TLE-HS subjects who underwent intracranial investigation for lateralizing purpose. Methods. We retrospectively included all consecutive refractory TLE-HS patients and not lateralizing ictal scalp EEG/interictal PET-FDG findings, investigated by intracranial bilateral longitudinal hippocampal electrodes. Demographic characteristics, electroclinical findings and seizure outcome were evaluated. Results. We identified 14 subjects (7 males; mean age 39.5 years; mean age at disease onset 14.4 years), 7 of them had biTLE diagnosed after intracranial investigations. In the remaining 7 with unilateral epileptogenesis (uniTLE) anterior temporal lobectomy was performed (6/7 were in Engel class I). Preoperative neuropsychological assessment differentiated biTLE from uniTLE, as it was normal in six uniTLE patients but only in one with biTLE (p < 0.05). Conclusions. Not lateralizing ictal scalp EEG and functional imaging findings in TLEHS should alert about the possibility of a true biTLE also in presence of unilateral findings at MRI. Intracranial investigations with bilateral longitudinal hippocampal electrodes can localize the EZ with a good risk-benefit profile. Consistently with the warning on memory functions in TLE patients explored by using longitudinal hippocampal electrodes, further studies are needed to better define the optimal investigation strategy.

Regional Ictal Hyperperfusion in the Contralateral Occipital Area May Be a Poor Prognostic Marker of Anterior Temporal Lobectomy: A SISCOM Analysis of MTLE Cases.

Background and ObjectiveSubtraction of ictal SPECT coregistered to MRI (SISCOM) provides complementary information for detecting the ictal onset zone, especially in patients with MRI-negative focal epilepsy, and provides additional useful information for predicting long-term postresection outcomes. This study sought to investigate the relationship between surgical failure and increased cerebral blood flow (CBF) pattern using SPECT in patients with mesial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE-HS).MethodsAmong 42 subjects who underwent anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) for MTLE-HS, 29 (69.0%) were seizure-free (SF group). Hyperperfusion was compared in 14 ipsilateral and contralateral brain regions in SISCOM images between the two groups.ResultsThe pattern of ictal hyperperfusion in temporal regions did not vary significantly between the SF and non-seizure-free (NSF) groups. However, CBF increases in the contralateral occipital area was more frequent in the NSF group than in the SF group. Furthermore, ictal hyperperfusion of the ipsilateral occipital and contralateral parietal areas tended to be more frequent in the NSF group.ConclusionThe results indicate that poor ATL-AH surgical outcome is associated with a tendency of ictal hyperperfusion of the contralateral occipital cortex based on SISCOM analysis. The pattern of early ictal CBF changes implicating the propagation from temporal to occipital cortices can be considered a marker of poor surgical outcomes of ATL-AH in MTLE-HS patients.

Effects of seizure burden on structural global brain networks in patients with unilateral hippocampal sclerosis.

Background and purposeTemporal lobe epilepsy secondary to hippocampal sclerosis is related to epileptogenic networks rather than a focal epileptogenic source. Graph‐theoretical gray and white matter networks may help to identify alterations within these epileptogenic networks.MethodsTwenty‐seven patients with hippocampal sclerosis and 14 controls underwent magnetic resonance imaging, including 3D‐T1, fluid‐attenuated inversion recovery, and diffusion tensor imaging. Subject‐specific structural gray and white matter network properties (normalized path length, clustering, and small‐worldness) were reconstructed. Group differences and differences between those with higher and lower seizure burden (<4 vs. ≥4 average monthly seizures in the last year) in network parameters were evaluated. Additionally, correlations between network properties and disease‐related variables were calculated.ResultsAll patients with hippocampal sclerosis as one group did not have altered gray or white matter network properties (all p > .05). Patients with lower seizure burden had significantly lower gray matter small‐worldness and normalized clustering compared to controls and those with higher seizure burden (all p < .04). A higher number of monthly seizures was significantly associated with increased gray and white matter small‐worldness, indicating a more rigid network.ConclusionOverall, there were no differences in network properties in this group of patients with hippocampal sclerosis. However, patients with lower seizure burden had significantly lower gray matter network indices, indicating a more random organization. The correlation between higher monthly seizures and a more rigid network is driven by those with higher seizure burden, who presented a more rigid network compared to those with a lower seizure burden.