Hippocampal Sclerosis Research Articles

Surgical treatment of long-term epilepsy-associated tumors guided by stereoelectroencephalography

PurposeAccurate detection and resection of the epileptogenic zone (EZ) in patients with long-term epilepsy-associated tumors (LEATs) are significantly correlated with favorable seizure prognosis. However, the relationship between tumors and the EZ remains unknown. This study aimed to evaluate the spatial relationship between LEATs and the EZ, as well as the electrophysiological features of LEATs.MethodsWe retrospectively studied five patients with LEATs who underwent deep electrode implantation and EZ resection in the hospital. The clinical characteristics, surgical outcomes, localizing features and intracranial SEEG results were reviewed.ResultsOne female and four males (mean age: 25.2 years; median age: 24 years; range: 13–45 years) were included in the study. Five-to-eleven electrodes (mean: 8.4) were implanted per patient. The EZ was located in the tumor and nearby cortex in three cases and in the tumor and distant areas in two cases. Pathological examination revealed ganglioglioma in four cases, two of which were associated with hippocampal sclerosis, and the other case showed a multinodular and vacuolating neuronal tumor with gliosis. All patients were seizure-free for at least 24 months postoperatively.ConclusionsSEEG provides valuable insights into the electrophysiological mechanisms of LEATs. The EZ often contains brain tissue around the tumor. However, only a few cases, particularly those with temporoparietal occipital (TPO) area involvement, a long history of epilepsy and other abnormalities on MRI, such as hippocampal sclerosis and focal cortical dysplasia, may include distant areas.

Detection of seizure clustering using ultralong-term subcutaneous EEG monitoring

AbstractEpileptic seizures usually occur unpredictably yet not necessarily at random times. Cyclical patterns of seizure recurrence have been broadly described. Long-term seizure documentation may reveal individual cyclical seizure patterns; however, seizure reporting by patients or their caregivers is often inaccurate. Modern technologies for at-home monitoring of epileptic seizures enable continuous EEG recording for objective seizure counts over long-term timescales. Here, we present the clinical case of a patient with temporal lobe epilepsy due to hippocampal sclerosis who underwent ultralong-term subcutaneous EEG recording over a 1-year period, which revealed the occurrence of seizure clusters at three- to four-weekly intervals. The case demonstrates the possibility of detection of subject-specific seizure timing using a minimally invasive subcutaneous EEG recorder for ultralong-term at-home seizure monitoring. Information about individual seizure timing may contribute to a more personalized chronotherapeutic treatment approach in which antiseizure medication can be maintained at low doses during the low-risk periods and increased briefly before the anticipated seizures.

A Mouse Model of Temporal Lobe Contusion.

Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, "computed tomography-positive," that is, hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. TlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety, and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus, and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days and nonconvulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.

The association between structural connectivity and anti-seizure medication response in patients with temporal lobe epilepsy.

This study aimed to investigate the differences in structural connectivity and glymphatic system function between patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and healthy controls. Additionally, we analyzed the association between structural connectivity, glymphatic system function, and antiseizure medication (ASM) response. We retrospectively enrolled patients with TLE and HS and healthy controls who underwent diffusion tensor imaging at our hospital. We assessed structural connectivity in patients with TLE and HS and healthy controls by calculating network measures using graph theory and evaluated glymphatic system function using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Patients with TLE and HS were categorized into two groups: ASM poor and good responders. We enrolled 55 patients with TLE and HS and 53 healthy controls. Of the 55 patients with TLE and HS, 39 were ASM poor responders, and 16 were ASM good responders. The assortativity coefficient in patients with TLE and HS was higher than that in healthy controls (0.004 vs. -0.007, p = 0.004), and the assortativity coefficient in ASM poor responders was lower than that in ASM good responders (-0.001 vs. -0.197, p = 0.003). The DTI-ALPS index in patients with TLE and HS was lower than that in healthy controls (1.403 vs. 1.709, p < 0.001); however, the DTI-ALPS index did not differ between ASM poor and good responders (1.411 vs. 1.385, p = 0.628). The DTI-ALPS index had a significant negative correlation with age in patients with TLE and HS (r = -0.267, p = 0.049). We confirmed increased assortativity coefficient in structural connectivity and decreased DTI-ALPS index in patients with TLE and HS compared with healthy controls. Additionally, we demonstrated an association between decreased assortativity coefficient in structural connectivity and ASM poor response in patients with TLE patients and HS. This study investigates the relationship between brain connectivity changes and glymphatic system function with antiseizure medication response in patients with temporal lobe epilepsy and hippocampal sclerosis. The research reveals that these patients show altered brain connectivity and glymphatic function compared to healthy individuals. A key finding is the strong link between a specific connectivity measure (assortativity coefficient) and antiseizure medication response, providing valuable insights that could influence epilepsy treatment and future research directions.

Microangiopathy in temporal lobe epilepsy with diffusion MRI alterations and cognitive decline

White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05–0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorβ and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE.

Clinical case of an atypical variant of Labbe's vein structure in a patient with pharmacoresistant temporal epilepsy

Among the commonly recognised structural lesions that cause drug-resistant temporal lobe epilepsy, such as mesial temporal sclerosis, focal cortical dysplasia, benign intracerebral tumors, arteriovenous malformations and cavernous angiomas, researchers have recently noted other pathologies, such as, encephalocele. There are a number of publications on the connection between epilepsy and cerebral venous angiomas. However, there are no published cases of the influence of the abnormal structure and location of normal cerebral vessels on the development of epilepsy. This article presents a case of an atypically large and unusually located vein of Labbe that may have been involved in epileptogenesis and also complicated an anteromedial temporal lobectomy. Forced coagulation and excision of the Labbe vein during surgery did not lead to venous infarction and neurological deficit.

Hippocampal dentate granule cells in temporal lobe epilepsy: A morphometry and transcriptomic study.

The dentate gyrus (DG) plays a critical role in hippocampal circuitry, providing a "gate-like" function to the downstream cornu ammonis (CA) sectors. Despite this critical role, pathologies in DG are less commonly described than those in the CA sectors in the diagnosis of mesial temporal lobe epilepsy (mTLE). To elucidate the role of the DG in mTLE, we analysed hippocampal sclerosis (HS), no-HS, non-TLE epilepsy control, and non-epilepsy control cohorts using morphometry and gene expression profiling techniques. Morphometry techniques analysed DG cell spacing, nucleus size, and nucleus circularity. Our data show distinct DG morphometry and RNA expression profiles between HS and No-HS. Dentate granule cells are more dispersed in patients with HS, and the DG shows an elevated expression of the complement system, apoptosis, and extracellular matrix remodelling-related RNA. We also observe an overall decrease in neurogenesis-related RNA in HS DG. Interestingly, regardless of the pathological diagnosis, the DG morphometry correlates with post-operative outcomes. Increased cell spacing is observed in the DG of mTLE cases that achieve seizure freedom post-operatively. This study reveals the possible prognostic value of DG morphometry, as well as supporting the notion that HS and no-HS TLE may be distinct disease entities with differing contributing mechanisms.

Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.

Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors' clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.

Tropisetron, an Antiemetic Drug, Exerts an Anti-Epileptic Effect Through the Activation of α7nAChRs in a Rat Model of Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE), a prevalent chronic neurological disorder, affects millions of individuals and is often resistant to anti-epileptic drugs. Increasing evidence has shown that acetylcholine (ACh) and cholinergic neurotransmission play a role in the pathophysiology of epilepsy. Tropisetron, an antiemetic drug used for chemotherapy in clinic, has displayed potential in the treatment of Alzheimer's disease, depression, and schizophrenia in animal models. However, as a partial agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), whether tropisetron possesses the therapeutic potential for TLE has not yet been determined. In this study, tropisetron was intraperitoneally injected into pilocarpine-induced epileptic rats for 3 weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was applied to investigate the mechanism of tropisetron. Rats were assessed for spontaneous recurrent seizures (SRS) and cognitive function using video surveillance and Morris's water maze testing. Hippocampal impairment and synaptic structure were evaluated by Nissl staining, immunohistochemistry, and Golgi staining. Additionally, the levels of glutamate, γ-aminobutyric acid (GABA), ACh, α7nAChRs, neuroinflammatory cytokines, glucocorticoids and their receptors, as well as synapse-associated protein (F-actin, cofilin-1) were quantified. The results showed that tropisetron significantly reduced SRS, improved cognitive function, alleviated hippocampal sclerosis, and concurrently suppressed synaptic remodeling and the m6A modification of cofilin-1 in TLE rats. Furthermore, tropisetron lowered glutamate levels without affecting GABA levels, reduced neuroinflammation, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. The effects of tropisetron treatment were counteracted by α-bgt. In summary, these findings indicate that tropisetron exhibits an anti-epileptic effect and provides neuroprotection in TLE rats through the activation of α7nAChRs. The potential mechanism may involve the reduction of glutamate levels, enhancement of cholinergic transmission, and suppression of synaptic remodeling. Consequently, the present study not only highlights the potential of tropisetron as an anti-epileptic drug but also identifies α7nAChRs as a promising therapeutic target for the treatment of TLE.

Evaluating the updated LATE-NC staging criteria using data from NACC.

Limbic-predominant age-related TAR DNA-binding protein of 43kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data. We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models. Of 1352 participants, 502 (37%) had LATE-NC (23% stage 1a, 6% stage 1b, 58% stage 2, 13% stage 3). LATE-NC stages were associated with cognition, hippocampal sclerosis of aging (HS-A), Alzheimer's disease NC (ADNC), Lewy bodies (LBs), and hippocampal atrophy. While stage 1b was associated with cognition and HS-A consistent with other stages, it was not associated with ADNC or LBs. All LATE-NC stages remained significantly associated with worse cognition when accounting for other NCs. The updated LATE-NC staging criteria capture variations in early TDP-43 pathology spread which are consequential for cognition and associations with other NCs. We applied the updated limbic-predominant age-related TAR DNA-binding protein of 43kDa encephalopathy neuropathologic change (LATE-NC) staging criteria to data from the National Alzheimer's Coordinating Center. LATE-NC stage 1b was identified in 22% of participants with stage 1. In contrast to other LATE-NC stages, stage 1b was not associated with Alzheimer's disease neuropathologic change (ADNC) or Lewy bodies. Stages 1a and 1b were significantly associated with dementia and memory impairment. Stages 1b+ were more strongly tied to dementia than all other neuropathologic changes except high likelihood ADNC.

Excitatory neurons and oligodendrocyte precursor cells are vulnerable to focal cortical dysplasia type IIIa as suggested by single-nucleus multiomics.

Focal cortical dysplasia (FCD) is a heterogeneous group of cortical developmental malformations that constitute a common cause of medically intractable epilepsy. FCD type IIIa (FCD IIIa) refers to temporal neocortex alterations in architectural organisation or cytoarchitectural composition in the immediate vicinity of hippocampal sclerosis. Slight alterations in the temporal neocortex of FCD IIIa patients pose a challenge for the preoperative diagnosis and definition of the resection range. We have performed multimodal integration of single-nucleus RNA sequencing and single-nucleus assay for transposase-accessible chromatin sequencing in the epileptogenic cortex of four patients with FCD IIIa, and three relatively normal temporal neocortex were chosen as controls. Our study revealed that the most significant dysregulation occurred in excitatory neurons (ENs) and oligodendrocyte precursor cells (OPCs) in the epileptogenic cortex of FCD IIIa patients. In ENs, we constructed a transcription factor (TF)-hub gene regulatory network and found DAB1high ENs subpopulation mediates neuronal immunity characteristically in FCD IIIa. Western blotting and immunofluorescence were used to validate the changes in protein expression levels caused by some of the key genes. The OPCs were activated and exhibited aberrant phenotypes in FCD IIIa, and TFs regulating reconstructed pseudotime trajectory were identified. Finally, our results revealed aberrant intercellular communication between ENs and OPCs in FCD IIIa patients. Our study revealed significant and intricate alterations in the transcriptomes and epigenomes in ENs and OPCs of FCD IIIa patients, shedding light on their cell type-specific regulation and potential pathogenic involvement in this disorder. This work will help evaluate the pathogenesis of cortical dysplasia and epilepsy and explore potential therapeutic targets. Paired snRNA-seq and snATAC-seq data were intergrated and analysed to identify crucial subpopulations of ENs and OPCs in the epileptogenic cortex of FCD IIIa patients and explore their possible pathogenic role in the disease. A TF-hub gene regulatory network was constructed in ENs, and the DAB1high Ex-1 mediated neuronal immunity was characterstically in FCD IIIa patients. The OPCs were activated and exhibited aberrant phenotypes in FCD IIIa patients, and TFs regulating reconstructed pseudotime traectory were identified. Aberrant intercelluar communications between ENs and OPCs in FCD IIIa patients were identified.

Brain imaging traits and epilepsy: Unraveling causal links via mendelian randomization.

Epilepsy, a complex neurological disorder, is closely linked with structural and functional irregularities in the brain. However, the causal relationship between brain imaging-derived phenotypes (IDPs) and epilepsy remains unclear. This study aimed to investigate this relationship by employing a two-sample bidirectional Mendelian randomization (MR) approach. The analysis involved 3935 cerebral IDPs from the UK Biobank and all documented cases of epilepsy (all epilepsies) cohorts from the International League Against Epilepsy, with further validation through replication and meta-analyses using epilepsy Genome-Wide Association Studies datasets from the FinnGen database. Additionally, a multivariate MR analysis framework was utilized to assess the direct impact of IDPs on all epilepsies. Furthermore, we performed a bidirectional MR analysis to investigate the relationship between the IDPs identified in all epilepsies and the 15 specific subtypes of epilepsy. The study identified significant causal links between four IDPs and epilepsy risk. Decreased fractional anisotropy in the left inferior longitudinal fasciculus was associated with a higher risk of epilepsy (odds ratio [OR]: 0.89, p=3.31×10-5). Conversely, increased mean L1 in the left posterior thalamic radiation (PTR) was independently associated with a heightened epilepsy risk (OR: 1.14, p=4.72×10-5). Elevated L3 in the left cingulate gyrus was also linked to an increased risk (OR: 1.09, p=.03), while decreased intracellular volume fraction in the corpus callosum was correlated with higher epilepsy risk (OR: 0.94, p=1.15×10-4). Subtype analysis revealed that three of these IDPs are primarily associated with focal epilepsy (FE). Notably, increased L1 in the left PTR was linked to an elevated risk of hippocampal sclerosis (HS) and lesion-negative FE, whereas elevated L3 in the left cingulate gyrus was associated with HS-related FE. Our research offers genetic evidence for a causal link between brain IDPs and epilepsy. These results enhance our understanding of the structural brain changes associated with the onset and progression of epilepsy.

Estimated Disease Progression Trajectory of White Matter Disruption in Unilateral Temporal Lobe Epilepsy: A Data-Driven Machine Learning Approach.

Although the involvement of progressive brain alterations in epilepsy was recently suggested, individual patients' trajectories of white matter (WM) disruption are not known. We investigated the disease progression patterns of WM damage and its associations with clinical metrics. We examined the cross-sectional diffusion tensor imaging (DTI) data of 155 patients with unilateral temporal lobe epilepsy (TLE) and 270 age/gender-matched healthy controls, and we then calculated the average fractional anisotropy (FA) values within 20 WM tracts of the whole brain. We used the Subtype and Stage Inference (SuStaIn) program to detect the progression trajectory of FA changes and investigated its association with clinical parameters including onset age, disease duration, drug-responsiveness, and the number of anti-seizure medications (ASMs). The SuStaIn algorithm identified a single subtype model in which the initial damage occurs in the ipsilateral uncinate fasciculus (UF), followed by damage in the forceps, superior longitudinal fasciculus (SLF), and anterior thalamic radiation (ATR). This pattern was replicated when analyzing TLE with hippocampal sclerosis (n = 50) and TLE with no lesions (n = 105) separately. Further-progressed stages were associated with longer disease duration (p < 0.001) and a greater number of ASMs (p = 0.001). the disease progression model based on WM tracts may be useful as a novel individual-level biomarker.

Temporopolar blurring signifies abnormalities of white matter in mesial temporal lobe epilepsy.

The single-center retrospective cohort study investigated underlying pathogenic mechanisms and clinical significance of patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS), in the presence/absence of gray-white matter abnormalities (usually called "blurring"; GMB) in ipsilateral temporopolar region (TPR) on MRI. The study involved 105 patients with unilateral TLE-HS (60 GMB+ and 45 GMB-) who underwent standard anterior temporal lobectomy, along with 61 healthy controls. Resected specimens were examined under light microscope. With combined T1-weighted and DTI data, we quantitatively compared large-scale morphometric features and exacted diffusion parameters of ipsilateral TPR-related superficial and deep white matter (WM) by atlas-based segmentation. Along-tract analysis was added to detect heterogeneous microstructural alterations at various points along deep WM tracts, which were categorized into inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and temporal cingulum. Comparable seizure semiology and postoperative seizure outcome were found, while the GMB+ group had significantly higher rate of HS Type 1 and history of febrile seizures, contrasting with significantly lower proportion of interictal contralateral epileptiform discharges, HS Type 2, and increased wasteosomes in hippocampal specimens. Similar morphometric features but greater WM atrophy with more diffusion abnormalities of superficial WM was observed adjacent to ipsilateral TPR in the GMB+ group. Moreover, microstructural alterations resulting from temporopolar GMB were more localized in temporal cingulum while evenly and widely distributed along ILF and UF. Temporopolar GMB could signify more severe and widespread microstructural damage of white matter rather than a focal cortical lesion in TLE-HS, affecting selection of surgical procedures.

Hippocampal sclerosis in women with temporal lobe epilepsy: seizure and pregnancy outcomes

BackgroundTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is typically resistant to pharmacological interventions; however, achieving seizure freedom is possible through surgery. Our objective was to focus on the pregnancy and seizure outcomes during pregnancy of women with TLE-HS, and aim to identify predictors of seizure control.MethodsThe West China Registry of Pregnancy of Women with Epilepsy (WCPR_EPi) was a monocentric prospective cohort study of women with epilepsy (WWE). We screened women with TLE-HS in this database. Their clinical profile, anti-seizure medication (ASM) use, and pregnancy outcomes were extracted from the records of the registry (2010–2023).ResultsOut of 2320 WWE followed up, 47 pregnancies in women with TLE-HS were identified and analyzed. Seizure exacerbation occurred in 40.4% of pregnancies, and seizure freedom was present in 34.0% of these during pregnancy. Factors associated with seizure exacerbation during pregnancy was ASM non-adherence (odds ratio [OR] =7.00, 95% confidence interval [CI] 1.43–34.07, P=0.016). The surgery group showed a significantly higher seizure freedom rate (OR = 6.87, 95% CI 1.02–46.23, P=0.016) and lower rate of induced labor (0.0% vs 26.5%, P=0.047) compared to the medically-treated group alone. Caesarean section was chosen in 77.1% of cases due to seizure concerns, with comparable in epilepsy-related (n=20) and obstetric causes (n=24). No major congenital malformations were reported.ConclusionsSurgical treatment before pregnancy appears to offer a higher chance of seizure freedom compared to medication alone. Most of women with TLE-HS can deliver healthy offspring regardless of suboptimal seizure control and unwarranted concerns.

Laser Ablation of Periventricular Nodular Heterotopia for Medically Refractory Epilepsy

ObjectivePeriventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco‐resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo‐electroencephalography (SEEG) ‐informed magnetic resonance‐guided laser interstitial thermal therapy (MRgLITT).MethodsA retrospective review of consecutive cases from a single high‐volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes.ResultsThirty‐nine patients underwent SEEG‐guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow‐up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (p &lt; 0.001).InterpretationPVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH‐associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further. ANN NEUROL 2024

Temporal PLGG and epilepsy.

Temporal lobe epilepsy in children is often secondary to various low-grade glial and glioneural tumors and rarely secondary to mesial temporal sclerosis. Despite the benign nature, tumor-associated TLE in children often becomes refractory over time. Abundant literature has shown the significant advantage of tumor resection compared to conservative treatment, in achieving seizure control, as well as the rates of antiseizure medication reduction. Despite these advantages, several considerations are to be related to when considering surgery. These include the impact of surgery on linguistic and neurocognitive development, especially at the younger age; the extent of resection and the role of ECoG; and the need for mesial temporal resection. Over recent years, traditional resection has been complemented with newer treatment options such as laser ablation and biological treatment, and these should be taken into account depending on the exact location and the ability to perform extensive resection in eloquent regions. In this overview manuscript, we discuss the various considerations treating tumor-associated pediatric temporal epilepsy.

Single-cell, single-nucleus and xenium-based spatial transcriptomics analyses reveal inflammatory activation and altered cell interactions in the hippocampus in mice with temporal lobe epilepsy

BackgroundTemporal lobe epilepsy (TLE) is among the most common types of epilepsy and often leads to cognitive, emotional, and psychiatric issues due to the frequent seizures. A notable pathological change related to TLE is hippocampal sclerosis (HS), which is characterized by neuronal loss, gliosis, and an increased neuron fibre density. The mechanisms underlying TLE-HS development remain unclear, but the reactive transcriptomic changes in glial cells and neurons of the hippocampus post-epileptogenesis may provide insights.MethodsTo induce TLE, 200 nl of kainic acid (KA) was stereotactically injected into the hippocampal CA1 region of mice, followed by a 7-day postinjection period. Single-cell RNA sequencing (ScRNA-seq), single-nucleus RNA sequencing (SnRNA-seq), and Xenium-based spatial transcriptomics analyses were employed to evaluate the changes in mRNA expression in glial cells and neurons.ResultsFrom the ScRNA-seq and SnRNA-seq data, 31,390 glial cells and 48,221 neuronal nuclei were identified. Analysis of the differentially expressed genes (DEGs) revealed significant transcriptomic alterations in the hippocampal cells of mice with TLE, affecting hundreds to thousands of mRNAs and their signalling pathways. Enrichment analysis indicated notable activation of stress and inflammatory pathways in the TLE hippocampus, while pathways related to axonal development and neural support were suppressed. Xenium analysis demonstrated the expression of all 247 genes across mouse brain sections, revealing the spatial distributions of their expression in 27 cell types. Integrated analysis of the DEGs identified via the three sequencing techniques revealed that Spp1, Trem2, and Cd68 were upregulated in all glial cell types and in the Xenium data; Penk, Sorcs3, and Plekha2 were upregulated in all neuronal cell types and in the Xenium data; and Tle4 and Sipa1l3 were downregulated in all glial cell types and in the Xenium data.ConclusionIn this study, a high-resolution single-cell transcriptomic atlas of the hippocampus in mice with TLE was established, revealing potential intrinsic mechanisms driving TLE-associated inflammatory activation and altered cell interactions. These findings provide valuable insights for further exploration of HS development and epileptogenesis.

Chinese Verbal Fluency Deficiency in Temporal Lobe Epilepsy with and without Hippocampal Sclerosis: A Multiscale Study.

To test a Chinese character version of the phonemic verbal fluency task in patients with temporal lobe epilepsy (TLE) and assess the verbal fluency deficiency pattern in TLE with and without hippocampal sclerosis, a cross-sectional study was conducted including 30 patients with TLE and hippocampal sclerosis (TLE-HS), 28 patients with TLE and without hippocampal sclerosis (TLE-NHS), and 29 demographically matched healthy controls (HC). Both sexes were enrolled. Participants finished a Chinese character verbal fluency (VFC) task during functional MRI. The activation/deactivation maps, functional connectivity, degree centrality, and community features of the left frontal and temporal regions were compared. A neural network classification model was applied to differentiate TLE-HS and TLE-NHS using functional statistics. The VFC scores were correlated with semantic fluency in HC while correlated with phonemic fluency in TLE-NHS. Activation and deactivation deficiency was observed in TLE-HS and TLE-NHS (p < 0.001, k ≥ 10). Functional connectivity, degree centrality, and community features of anterior inferior temporal gyri were impaired in TLE-HS and retained or even enhanced in TLE-NHS (p < 0.05, FDR-corrected). The functional connectivity was correlated with phonemic fluency (p < 0.05, FDR-corrected). The neural network classification reached an area under the curve of 0.90 in diagnosing hippocampal sclerosis. The VFC task is a Chinese phonemic verbal fluency task suitable for clinical application in TLE. During the VFC task, functional connectivity of phonemic circuits was impaired in TLE-HS and was enhanced in TLE-NHS, representing a compensative phonemic searching strategy applied by patients with TLE-NHS.

Resective surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis in patients over 50 years: a case-control study.

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS) is the most common cause of drug-resistant focal seizures and surgical resection is the primary treatment option, with seizure-free rates ranging from 60 to 80%. However, data on postsurgical seizure outcomes in patients ≥ 50years of age are limited. This study aimed to assess the efficacy and safety of surgery in this age group compared to younger patients. We performed a retrospective analysis of data from resective surgeries conducted in patients with MTLE/HS between 1990 and 2022. We focused on patients aged ≥ 50years and compared the surgical safety and efficacy variables between this group and a control group of patients aged < 50years through a case-control study. Among the 450 MTLE/HS patients who underwent surgery during the inclusion period, 61 (13.6%) were aged ≥ 50years and matched with 183 younger patients, totaling 244 study participants. The two groups had similar characteristics. At the last follow-up (median 5.7years), Engel I outcomes were achieved in 80.3% of the older patients and 81.4% of the younger patients, with no significant difference (p = 0.85). Postoperative cognitive and psychiatric outcomes did not differ between the groups. Major complication rates were also comparable, at 3.3% in the older group and 2.7% in the younger group (p = 0.83). The extratemporal ictal abnormalities observed on video-EEG were the only variable that demonstrated a significant association with an unfavorable seizure outcome in the older group (OR 9.3, 95% CI [1.8-47.6], p = 0.005). This study provides grade 3 evidence that resective surgery for MTLE/HS patients aged ≥ 50years is as effective and safe as it is for younger patients, and thus should be considered as the primary treatment option for drug-resistant cases.