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Background: 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 ≥ 50 years of age are limited. This study aimed to assess the efficacy and safety of surgery in this age group compared to younger patients. Methods: 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 ≥ 50 years and compared the surgical safety and efficacy variables between this group and a control group of patients aged < 50 years through a case–control study. Results: Among the 450 MTLE/HS patients who underwent surgery during the inclusion period, 61 (13.6%) were aged ≥ 50 years and matched with 183 younger patients, totaling 244 study participants. The two groups had similar characteristics. At the last follow-up (median 5.7 years), 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). Conclusions: This study provides grade 3 evidence that resective surgery for MTLE/HS patients aged ≥ 50 years 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. [ABSTRACT FROM AUTHOR]

Two-thirds of published patients with anti-leucine rich, glioma inactivated 1 (LGI1) encephalitis develop hippocampal sclerosis (HS). It is likely that this contributes to residual cognitive long-term deficits and the risk of epilepsy. Almost all patients harbor anti-LGI1-immunoglobulin G-(IgG-) subclass 4, which is considered a "benign", non-destructive subclass. In contrast, neuropathological case studies have suggested that the classical complement cascade may contribute to mediotemporal cell death in patients with LGI1 antibodies. IgG subclasses 1, 2, or 3 are required to initiate this cascade. We hypothesized that patients with these anti-LGI1-IgG1/2/3 in addition to IgG4 have a higher risk of developing HS than patients with anti-LGI1-IgG4 alone. We retrospectively assessed all anti-LGI1 encephalitis patients from this center with anti-LGI1-IgG-subclass information and follow-up MRI available. Nine out of 20 patients had developed HS (45%). Volumetric FreeSurfer analysis confirmed the visual HS diagnoses. HS and a lower hippocampal volume were associated with anti-LGI1-IgG1/2/3. All six patients with this IgG subclass status developed HS. There was no association with older or younger age at onset, female sex, longer latency from disease onset to start of immunotherapy, less intense immunotherapy, higher serum titers of LGI1 antibodies, LGI1 antibodies in CSF or higher LGI1-specific antibody indices. There was no association between anti-LGI1-IgG1/2/3 status and neuropsychological performance, epilepsy, or general neurological performance. This confirms our hypothesis that anti-LGI1-IgG1/2/3 in serum puts patients at risk of developing HS. If these findings can be confirmed and clinically corroborated, patients with anti-LGI1-IgG1/2/3 might become candidates for anti-complement-directed immunological treatments. [ABSTRACT FROM AUTHOR]

Background Dementia results from multiple neuropathologies causing cognitive impairment sufficiently severe to affect functional status. However, these pathologies and functional impairment are common in persons without dementia. We examined the association of Alzheimer's disease (AD) and multiple other neuropathologies with instrumental and basic activities of daily living in persons with and without dementia. Methods Participants were 1 509 deceased from the Religious Orders Study or Rush Memory and Aging Project. Pathologic AD and 3 other AD indices were examined, in addition to 4 non-AD neurodegenerative pathologies: cerebral amyloid angiopathy (CAA), hippocampal sclerosis, TDP-43, and Lewy bodies, and 4 cerebrovascular pathologies: gross- and microinfarctions, athero- and arteriolosclerosis. Functional assessment included Lawton and Katz Index Instrumental and Basic Activities of Daily Living (IADL and BADL). Ordinal regression models adjusted for age, sex, and education were used to examine the association of neuropathologies with IADL and BADL. Results Alzheimer's disease and the other neuropathologies were associated with impaired IADL (all p s < .001) and with impaired BADL (p s < .01), except for atherosclerosis and CAA, which were not associated with BADL. The effects of most neuropathologies were largely affected by dementia. However, small effects on IADL remained for PHF-tau tangles after adjusting models for dementia. Direct effects of gross infarcts on IADL and BADL and of microinfarcts on BADL remained unchanged after adjusting the models for dementia. Conclusions Alzheimer's disease and all other neuropathologies are strongly associated with functional disability. The association of most neuropathologies with disability was eliminated or attenuated by dementia, except for gross infarcts and microinfarcts. [ABSTRACT FROM AUTHOR]

The ability of the Auditory Verbal Learning Test (AVLT) to lateralize hippocampal sclerosis (HS) in mesial temporal lobe epilepsy (MTLE) was explored in a sample of 50 patients with MTLE-HS (23 right and 27 left). Patients' AVLT scores were adjusted to the demographic characteristics of each individual in accordance with the Portuguese normative data. The laterality of the HS was determined by consensus by two neuroradiologists. ROC curves were used to identify the best AVLT cutoff scores to differentiate right vs. left HS. Diagnostic statistics were applied to different AVLT measures. The study results revealed that four AVLT scores can correctly classify the laterality of HS in the total sample and a sub-group of 39 right-handed patients (Edinburgh Laterality Inventory +100): delayed recall trial (76 and 80%, respectively), delayed recognition trial (64 and 67%, respectively), learning over trials index (64 and 74%, respectively), and long-term percent retention index (68 and 72%, respectively). In right-handed patients, the diagnostic capability of the delayed recall trial was improved by pairing it with the learning over trials index (accuracy of 85%). In sum, AVLT measures of verbal memory differentiate left from right HS in MTLE. The delayed recall trial demonstrated good diagnostic capacity. [ABSTRACT FROM AUTHOR]

Background: There is a lack of further exploration of the epileptogenic network of specific types of epilepsy, such as unilateral hippocampal sclerosis (HS), and there is an urgent need to find exact evidence to confirm the consistency of its brain network changes. Methods: We enrolled 22 mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) patients to compare the differences in brain activity between 22 healthy controls (HCs) and them. Resting-state electroencephalography (EEG) was also measured. Then, we calculated the power spectral density and phase locking values in and between these electrodes. Results: The results showed the increased theta power was related to the high severity of epilepsy in the temporal, parietal, and central regions in mTLE-HS patients, and there were positive correlations between theta power in the contralateral temporal region and seizure frequency. Theta power in the ipsilateral parietal lobe is positively correlated with the number of anti-seizure medications (ASMs), but not with the usage of third-generation ASMs. Meanwhile, the temporal lobe of mTLE-HS patients had more connectivity with parietal lobe and central region. Conclusions: Theta power is an important EEG indicator of mTLE-HS, positively correlates with epilepsy severity and seizure frequency, and has network properties that can be observed outside the lesion. Moreover, the usage of third-generation ASMs did not affect the risk of increased theta power. Lastly, the temporoparietal and temporal-central networks are likely to be causative pathways in epilepsy patients with cognitive impairment. This study provides a potential guideline for the treatment of mTLE-HS in clinical practice. [ABSTRACT FROM AUTHOR]

Abnormal brain aging is suggested in epilepsy. Given the brain network dysfunction in epilepsy, the white matter tracts, which primarily interconnect brain regions, could be of special importance. We focused on white matter brain aging in diverse forms of epilepsy and comorbid psychosis. We obtained brain diffusion tensor imaging (DTI) data at 3 T-MRI in 257 patients with epilepsy and 429 healthy subjects. The tract-based fractional anisotropy values of the healthy subjects were used to build a brain-age prediction model, and we calculated the brain-predicted age difference (brain-PAD: predicted age—chronological age) of all subjects. As a result, almost all epilepsy categories showed significantly increased brain-PAD (p < 0.001), including temporal lobe epilepsy (TLE) with no MRI-lesion (+ 4.2 yr), TLE with hippocampal sclerosis (+ 9.1 yr), extratemporal focal epilepsy (+ 5.1 yr), epileptic encephalopathy or progressive myoclonus epilepsy (+ 18.4 yr), except for idiopathic generalized epilepsy (IGE). Patients with psychogenic non-epileptic seizures also presented increased brain-PAD. In TLE, interictal psychosis significantly raised brain-PAD by 8.7 years. In conclusion, we observed increased brain aging in most types of epilepsy, which was generally consistent with brain morphological aging results in previous studies. Psychosis may accelerate brain aging in TLE. These findings may suggest abnormal aging mechanisms in epilepsy and comorbid psychotic symptoms. [ABSTRACT FROM AUTHOR]

Epilepsy, affecting 0.5%‐1% of the global population, presents a significant challenge with 30% of patients resistant to medical treatment. Temporal lobe epilepsy, a common cause of medically refractory epilepsy, is often caused by hippocampal sclerosis (HS). HS can be divided further by subtype, as defined by the International League Against Epilepsy (ILAE). Type 1 HS, the most prevalent form (60%‐80% of all cases), is characterized by cell loss and gliosis predominantly in the subfields cornu ammonis (CA1) and CA4. Type 2 HS features cell loss and gliosis primarily in the CA1 sector, and type 3 HS features cell loss and gliosis predominantly in the CA4 subfield. This literature review evaluates studies on hippocampal subfields, exploring whether observable atrophy patterns from in vivo and ex vivo magnetic resonance imaging (MRI) scans correlate with histopathological examinations with manual or automated segmentation techniques. Our findings suggest only ex vivo 1.5 Tesla (T) or 3T MRI with manual segmentation or in vivo 7T MRI with manual or automated segmentations can consistently correlate subfield patterns with histopathologically derived ILAE‐HS subtypes. In conclusion, manual and automated segmentation methods offer advantages and limitations in diagnosing ILAE‐HS subtypes, with ongoing research crucial for refining hippocampal subfield segmentation techniques and enhancing clinical applicability. [ABSTRACT FROM AUTHOR]

Objective: As programs expand globally, epilepsy surgery is becoming increasingly available as an effective treatment for some people with medically intractable seizures. Prospective candidates require careful neuropsychological evaluation and follow-up. The aim of this study was to examine the sex differences in neuropsychological function in presurgical presentation and postoperative outcomes in people with temporal lobe epilepsy referred for epilepsy surgery. Methods: Three hundred and seventy-two patients (202 Female; 170 Male) with a homogenous underlying pathology (hippocampal sclerosis) underwent a preoperative assessment on tests of intellectual, language, and memory function and were followed up one year after undergoing a unilateral temporal lobe resection; n = 169 Right (RTL), n = 203 Left (LTL). Results: There was no impact of sex or laterality of surgery on seizure outcome; 84% of males and 80% of females were seizure free at follow-up. Before surgery, sex effects were evident on tests of verbal memory with females performing better than males. Declines in verbal memory function following surgery were greater in females than males. Being female had a stronger association with postoperative decline on immediate prose recall (partial eta squared η2 = 0.029), than side of surgery (η2 = 0.018) albeit with a small effect size. Conclusions: There are subtle but significant sex differences in the neuropsychological profiles of people with temporal lobe epilepsy, before and following surgery. Whilst females generally perform better than males on tests of verbal memory function before surgery they demonstrate greater post-operative declines on these measures following surgery. [ABSTRACT FROM AUTHOR]

Background and purpose: Glucose transporter‐1 (GLUT1) deficiency syndrome (GLUT1‐DS) is a metabolic disorder due to reduced expression of GLUT1, a glucose transporter of the central nervous system. GLUT1‐DS is caused by heterozygous SLC2A1 variants that mostly arise de novo. Here, we report a large family with heterogeneous phenotypes related to a novel SLC2A1 variant. Methods: We present clinical and genetic features of a five‐generation family with GLUT1‐DS. Results: The 14 (nine living) affected members had heterogeneous phenotypes, including seizures (11/14), behavioral disturbances (5/14), mild intellectual disability (3/14), and/or gait disabilities (2/14). Brain magnetic resonance imaging revealed hippocampal sclerosis in the 8‐year‐old proband, who also had drug‐responsive absences associated with attention‐deficit/hyperactivity disorder. His 52‐year‐old father, who had focal epilepsy since childhood, developed paraparesis related to a reversible myelitis associated with hypoglycorrhachia. Molecular study detected a novel heterozygous missense variant (c.446C>T) in exon 4 of SLC2A1 (NM: 006516.2) that cosegregated with the illness. This variant causes an amino acid replacement (p.Pro149Leu) at the fourth transmembrane segment of GLUT1, an important domain located at its catalytic core. Conclusions: Our study illustrates the extremely heterogenous phenotypes in familial GLUT1‐DS, ranging from milder classic phenotypes to more subtle neurological disorder including paraparesis. This novel SLC2A1 variant (c.446C>T) provides new insight into the pathophysiology of GLUT1‐DS. [ABSTRACT FROM AUTHOR]

Objective: Efforts to understand the global variability in cognitive profiles in patients with epilepsy have been stymied by the lack of a standardized diagnostic system. This study examined the cross‐cultural applicability of the International Classification of Cognitive Disorders in Epilepsy (IC‐CoDE) in a cohort of patients with temporal lobe epilepsy (TLE) in India that was diverse in language, education, and cultural background. Methods: A cohort of 548 adults with TLE from Mumbai completed a presurgical comprehensive neuropsychological evaluation. The IC‐CoDE taxonomy was applied to derive cognitive phenotypes in the sample. Analyses of variance were conducted to examine differences in demographic and clinical characteristics across the phenotypes, and chi‐squared tests were used to determine whether the phenotype distribution differed between the Mumbai sample and published data from a multicenter US sample. Results: Using the IC‐CoDE criteria, 47% of our cohort showed an intact cognitive profile, 31% a single‐domain impairment, 16% a bidomain impairment, and 6% a generalized impairment profile. The distribution of cognitive phenotypes was similar between the Indian and US cohorts for the intact and bidomain phenotypes, but differed for the single and generalized domains. There was a larger proportion of patients with single‐domain impairment in the Indian cohort and a larger proportion with generalized impairment in the US cohort. Among patients with single‐domain impairment, a greater proportion exhibited memory impairment in the Indian cohort, whereas a greater proportion showed language impairment in the US sample, likely reflecting differences in language administration procedures and sample characteristics including a higher rate of mesial temporal sclerosis in the Indian sample. Significance: Our results demonstrate the applicability of IC‐CoDE in a group of culturally and linguistically diverse patients from India. This approach enhances our understanding of cognitive variability across cultures and enables harmonized and inclusive research into the neuropsychological aspects of epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Radiofrequency thermocoagulation (RFTC) has emerged as an effective and safe treatment method for patients with refractory focal epilepsy, when stereo‐electroencephalography (SEEG) is implanted. Although real‐world research results are still limited, a considerable number of patients have shown favorable outcomes with this less invasive method. This study aims to describe the outcomes and predictive factors of SEEG‐RFTC in real‐world research. Methods: A retrospective observational study was conducted on patients in the authors' epilepsy center. In total, 121 patients who underwent RFTC were included in the study. Post‐RFTC outcomes were evaluated using the seizure‐free rate and response rate (seizure frequency reduction more than 50%). Predictive factors influencing post‐RFTC outcome were considered by comparing different variables. Results: The mean follow‐up period was 18.3 months. Eighty‐two patients (67.8%) were responders and 54 (44.6%) were seizure free. In 36 patients with malformation of cortical development, the seizure‐free rate and the response rate were 69.44% and 83.33%, respectively. In 20 patients with hippocampal sclerosis, 19 patients were responders and 14 (70%) patients were seizure free at the last follow‐up. The MRI feature and etiology of epilepsy are correlated with the outcome. MR‐positive is a predictive factor for seizure freedom (p < 0.01) and responders (p < 0.01). Other factors have no predictive value for post‐RFTC outcome. Interpretation: SEEG‐RFTC is a safe procedure and yields favorable outcomes in numerous cases of focal DRE. The MRI feature and etiology of epilepsy are correlated with the seizure‐free rate and response rate. And MRI positivity is the predictor for good RFTC outcome. [ABSTRACT FROM AUTHOR]

Objective: Perineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer's disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age‐dependent shift was experimentally associated also with hippocampal engram formation during brain maturation. Our aim was to histopathologically assess PNN in the hippocampus of adult and pediatric patients with temporal lobe epilepsy (TLE) compared to age‐matched post‐mortem control subjects and to compare PNN‐related changes with memory impairment observed in our patient cohort. Methods: Sixty‐six formalin‐fixed and paraffin‐embedded tissue specimens of the human hippocampus were retrieved from the European Epilepsy Brain Bank. Twenty‐nine patients had histopathologically confirmed hippocampal sclerosis (HS), and eleven patients suffered from TLE without HS. PNN were immunohistochemically visualized using an antibody directed against aggrecan and manually counted from hippocampus subfields and the subiculum. Results: PNN density increased with age in both human controls and TLE patients. However, their density was significantly higher in all HS patients compared to age‐matched controls. Intriguingly, TLE patients presented presurgically with better memory when their hippocampal PNN density was higher (p < 0.05). Significance: Our results were compatible with age‐dependent ECM specialization in the human hippocampus and its precocious aging in the epileptic condition. These observations confirm recent experimental animal models and also support the notion that PNN play a role in memory formation in the human brain. Plain Language Summary: "Perineuronal nets" (PNN) are a specialized compartment of the extracellular matrix (ECM), especially surrounding highly active neurons of the mammalian brain. There is evidence that PNN play a role in memory formation, brain maturation, and in some pathologies like Alzheimer's disease, schizophrenia or epilepsy. In this study, we investigated the role of PNN in patients suffering from drug‐resistant focal epilepsy compared to controls. We found that with increasing age, more neurons are surrounded by PNN. Similarly, all epilepsy patients but especially patients with better memory performance also had more PNN. This study raises further interest in studying ECM molecules in the human brain under physiological and pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Agyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I–IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I–IV and no or minimal Aβ deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per × 400 visual field in the amygdala (OR 10.02, 95% CI 1.12–89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70–87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03–65.13) affected dementia independent of age, moderate Braak stages (III–IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage. [ABSTRACT FROM AUTHOR]

Background: Micronutrient levels play a critical role in epilepsy. This study investigates the impact of micronutrient levels on epilepsy via Mendelian randomization (MR). Methods: A two-sample MR framework evaluated the genetic association between 15 serum micronutrients and epilepsy phenotypes. The analysis included calcium, iron, zinc, selenium, copper, magnesium, potassium, folate, vitamins B6, B12, C, D, E, retinol, and carotene against all epilepsy, generalized epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic-clonic seizures alone and with spike-wave electroencephalography (GTCS), and various focal epilepsy phenotypes [with hippocampal sclerosis (HS), lesions other than HS, lesionnegative]. The random-effects inverse-variance weighted (IVW) model was the primary method used, supported by heterogeneity and pleiotropy assessments. Multivariable Mendelian randomization analyses (MVMR) were used to identify micronutrients that are significantly causally associated with different epilepsy subtypes and to confirm the most potential causal risk factors for these subtypes. Results: Zinc conferred an increased risk of focal epilepsy with HS (OR = 1.01; p = 0.045). Carotene was similarly linked to higher risks of lesion-negative cases (OR = 1.129; p = 0.037). Conversely, vitamin B6 was associated with reduced risks of focal epilepsy with HS (OR = 0.949; p = 0.020), and vitamin D was linked to decreased risks of both CAE (OR = 0.976, 95% CI: 0.959-0.993, p = 0.006) and JAE (OR = 0.986, 95% CI: 0.973-0.999, p = 0.032). These associations were robust, showing minimal heterogeneity and no evidence of pleiotropy across various sensitivity analyses. After adjustment using MVMR, significant causal relationships between vitamin D and both CAE and JAE remained. Furthermore, the causal relationship between zinc and vitamin B6 on focal epilepsy with HS became non-significant, while carotene shifted from a risk factor to a protective factor for focal epilepsy lesion-negative after adjusting for vitamin D. Conclusion: MR estimates provide robust evidence for the causal effects of vitamin D on reducing the risk of CAE, and JAE, which might provide alternative treatment strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] • First critical review focusing on the role of circRNA in pathogenesis of epilepsy. • Pathogenesis of epilepsy is closely related to circRNA. • circRNA has the potential to serve as a biomarker for epilepsy. Recent studies evidenced the involvement of circular RNA (circRNA) in neuroinflammation, apoptosis, and synaptic remodeling suggesting an important role for circRNA in the occurrence and development of epilepsy. This review provides an overview of circRNAs considered to be playing regulatory roles in the process of epilepsy and to be involved in multiple biological epilepsy-related processes, such as hippocampal sclerosis, inflammatory response, cell apoptosis, synaptic remodeling, and cell proliferation and differentiation. This review covers the current research status of differential expression of circRNA-mediated seizures, m6A methylation, demethylation-mediated seizures in post transcriptional circRNA modification, as well as the mechanisms of m5C- and m7G-modified circRNA. In summary, this article reviews the research progress on the relationship between circRNA in non-coding RNA and epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacoresistant epilepsy is a multicomponent disease that can be successfully treated surgically if the surgical tactics are properly defined. We present the first case of stimulation of anterior thalamic nuclei in pharmacoresistant epilepsy in Kazakhstan. This will be a new opportunity for Kazakhstanis diagnosed with epilepsy to achieve stable epilepsy remission. Materials: The patient was born in 2000. The first episode of tonic clonic seizures with loss of consciousness occurred in 2014. Repeatedly underwent therapeutic and diagnostic measures in the neurological department. The frequency of seizures increased in dynamics. The results of instrumental examination revealed the following morphological changes: Morphological changes: Focal cortical dysplasia (FCD) in the left cingulate gyrus, hypometabolism in the left thalamus and forehead, signs of hippocampal sclerosis on both sides. Electroencephalogram (EEG) shows activity in frontal areas on both sides, more on the right. Based on clinical and instrumental data according to the 2017 ILAE classification, the diagnosis was Structural focal frontal lobe epilepsy with bilateral tonic-clonic seizures. FCD of the left cingulate gyrus. Resistance to antiepileptic therapy. Methods: The patient was hospitalized in the department of neurosurgery. In light of the evidence indicating structural changes in the brain substance and ambiguous EEG findings, the indications for deep brain stimulation (DBS) of the anterior nucleus (ANT) were made. Electrode implantation was performed under general anesthesia, and preoperative computer tomography (CT) scans were performed using the CRWR stereotactic system in combination with magnetic resonance imaging (MRI) scans using Brainlab Neuronavigation with 3D Atlas to identify the anterior thalamic nuclei. Conclusion: The observed structural changes in the brain substance and the ambiguous EEG results call into question the efficacy of surgical procedures aimed at removing existing foci or destroying them. Based on the above, as well as the experience of foreign colleagues, the choice of neurosurgeons was DBS ANT. Although the selection of ideal candidates for thalamic stimulation is still controversial, in the described case we were able to achieve control of seizure activity. The patient was seizure free for 2 months after surgery. The patient was discharged on postoperative day 7. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest a link between diet-derived circulating antioxidants and epilepsy, but the causal relationship is unclear. This study aims to investigate the causal effect of these antioxidants on epilepsy. Methods: To assess the causal link between dietary antioxidants and epilepsy risk, we conducted a two-sample Mendelian randomization (MR) analysis. This involved examining antioxidants such as zinc, selenium, α- and β-tocopherol, vitamin A (retinol), vitamin C (ascorbate), and vitamin E (α-tocopherol). We utilized instrumental variables (IVs) which were genetic variations highly associated with these commonly used antioxidants. Exposure data were sourced from a comprehensive genome-wide association study (GWAS). We aggregated data from the International League Against Epilepsy (ILAE) Consortium sample, which included various types of epilepsy, as an outcome variable. Finally, we applied the inverse variance weighting method and conducted sensitivity analyses for further validation. Results: Based on the primary MR estimates and subsequent sensitivity analyses, the inverse variance weighting (IVW) method revealed that a genetically predicted increase in zinc per standard deviation was positively associated with three types of epilepsy. This includes all types of epilepsy (OR = 1.06, 95% CI: 1.02-1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01-1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00-1.02, p = 0.025). However, there is no evidence indicating that other antioxidants obtained from the diet affect the increase of epilepsy either positively or negatively. Conclusion: Our research indicates that the risk of developing epilepsy may be directly linked to the genetic prediction of zinc, whereas no such association was found for other antioxidants. [ABSTRACT FROM AUTHOR]

For >30 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided a forum for the discussion of advances in the development of new therapies for seizures and epilepsy. The EILAT XVII conference took place in Madrid, Spain, on May 5–8, 2024. Participants included basic scientists and clinical investigators from industry and academia, other health care professionals, and representatives from lay organizations. We summarize in this article information on treatments in preclinical and in early clinical development discussed at the conference. These include AMT‐260, a gene therapy designed to downregulate the expression of Glu2K subunits of kainate receptors, in development for the treatment of drug‐resistant seizures associated with mesial temporal sclerosis; BHV‐7000, a selective activator of heteromeric Kv7.2/7.3 potassium channels, in development for the treatment of focal epilepsy; ETX101, a recombinant adeno‐associated virus serotype 9 designed to increase NaV1.1 channel density in inhibitory γ‐aminobutyric acidergic (GABAergic) neurons, in development for the treatment of SCN1A‐positive Dravet syndrome; GAO‐3‐02, a compound structurally related to synaptamide, which exerts antiseizure activity at least in part through an action on cannabinoid type 2 receptors; LRP‐661, a structural analogue of cannabidiol, in development for the treatment of seizures associated with Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex; OV329, a selective inactivator of GABA aminotransferase, in development for the treatment of drug‐resistant seizures; PRAX‐628, a functionally selective potent sodium channel modulator with preference for the hyperexcitable state of sodium channels, in development for the treatment of focal seizures; RAP‐219, a selective negative allosteric modulator of transmembrane α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor regulatory protein γ‐8, in development for the treatment of focal seizures; and rozanolixizumab, a humanized anti‐neonatal Fc receptor monoclonal antibody, in development for the treatment of LGI1 autoimmune encephalitis. Treatments in more advanced development are summarized in Part II of this report. [ABSTRACT FROM AUTHOR]

Objective: Several clinical studies have explored the feasibility and efficacy of radiosurgical treatment for mesial temporal lobe epilepsy, but the long-term safety of this treatment has not been fully characterized. This study aims to report and describe radiation-induced cavernous malformation as a delayed complication of radiosurgery in epilepsy patients. Methods: The series includes 20 patients with mesial temporal lobe epilepsy who underwent Gamma Knife radiosurgery (GKRS). The majority received a prescribed isodose of 24 Gy as an adjuvant treatment after anterior temporal lobectomy. Results: In this series, we identified radiation-induced cavernous malformation in three patients, resulting in a cumulative incidence of 18.4% (95% confidence interval, 6.3% to 47.0%) at an 8-year follow-up. These late sequelae of vascular malformation occurred between 6.9 and 7.6 years after GKRS, manifesting later than other delayed radiation-induced changes, such as radiation necrosis. Neurological symptoms attributed to intracranial hypertension were present in those three cases involving cavernous malformation. Of these, two cases, which initially exhibited an insufficient response to radiosurgery, ultimately demonstrated seizure remission following the successful microsurgical resection of the cavernous malformation. Conclusion: All things considered, the development of radiation-induced cavernous malformation is not uncommon in this population and should be acknowledged as a potential long-term complication. Microsurgical resection of cavernous malformation can be preferentially considered in cases where the initial seizure outcome after GKRS is unsatisfactory. [ABSTRACT FROM AUTHOR]

Objective: Focal cooling is emerging as a relevant therapy for drug‐resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep‐seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures. Methods: A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non‐human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography) lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two Macaca fascicularis monkeys at three temperatures. Results: Hippocampal seizures were observed 40–120 min post‐injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures. Significance: In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. Methods: Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. Results: At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex—with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials—with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = − 2.341, p = 0.019). Conclusions: SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of clinical assessment scales for MRI and 18F-FDG-PET as potential in vivo predictive diagnostic tools for TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy in cases with low–intermediate Alzheimer's disease neuropathologic changes (ADNC) and primary age-related tauopathy (PART). Methods: We conducted a cross-sectional analysis on patients with antemortem MRI and 18F-FDG-PET scans and postmortem diagnosis of low–intermediate ADNC or PART (Braak stage ≤ III; Thal β-amyloid phase 0–5). We employed visual imaging scales to grade structural changes on MRI and metabolic changes on 18F-FDG-PET and statistically compared demographic and clinicopathological characteristics between TDP-43 positive and negative cases. Independent regression analyses were performed to assess further influences of pathological characteristics on imaging outcomes. Within-reader repeatability and inter-reader reliability were calculated (CI = 0.95). Additional quantitative region-of-interest analyses of MRI gray matter volumes and PET ligand uptake were performed. Results: Of the 64 cases in the study, 20 (31%) were TDP-43 (+), of which 12 (60%) were female. TDP-43 (+) cases were more likely to have hippocampal sclerosis (HS) (p = 0.014) and moderate–severe medial temporal lobe atrophy on MRI (p = 0.048). TDP-43(+) cases also showed a trend for less parietal atrophy on MRI (p = 0.086) and more medial temporal lobe hypometabolism on 18F-FDG-PET (p = 0.087) than TDP-43(–) cases. Regression analysis showed an association between medial temporal hypometabolism and HS (p = 0.0113). ICC values for MRI and PET within one reader were 0.75 and 0.91; across two readers were 0.79 and 0.82. The region-of-interest-based analysis confirmed a significant difference between TDP-43(+) and TDP-43(–) cases for medial temporal lobe gray matter volume on MRI (p = 0.014) and medial temporal metabolism on PET (p = 0.011). Conclusion: Visual inspection of the medial temporal lobe on MRI and FDG-PET may help to predict TDP-43 status in the context of low–intermediate ADNC and PART. [ABSTRACT FROM AUTHOR]

Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusual nocturnal episodes and a history of microcytic anemia, as well as a review of the existing literature on NPRL3-related epilepsy, with an emphasis on individuals with deletions who also present with α-thalassemia trait. The proband's episodes were mistaken for gastroesophageal reflux disease for several years. He had molecular testing for his α-thalassemia trait and was noted to carry a deletion encompassing the regulatory region of the α-thalassemia gene cluster. Following the onset of overt focal motor seizures, genetic testing revealed a heterozygous loss of NPRL3, within a 106 kb microdeletion on chromosome 16p13.3, inherited from his mother. This deletion encompassed the entire NPRL3 gene, which overlaps the regulatory region of the α-globin gene cluster, giving him the dual diagnosis of NPRL3-related epilepsy and α-thalassemia trait. Brain imaging postprocessing showed left hippocampal sclerosis and mid-posterior para-hippocampal focal cortical dysplasia, leading to the consideration of epilepsy surgery. Conclusions: This case underscores the necessity of early and comprehensive genetic assessments in children with epilepsy accompanied by systemic features, even in the absence of a family history of epilepsy or a developmental delay. Recognizing phenotypic overlaps is crucial to avoid diagnostic delays. Our findings also highlight the impact of disruptions in regulatory regions in genetic disorders: any individual with full gene deletion of NPRL3 would have, at a minimum, α-thalassemia trait, due to the presence of the major regulatory element of α-globin genes overlapping the gene's introns. [ABSTRACT FROM AUTHOR]

Background: Mesial temporal lobe epilepsy (MTLE) with dystonia is a rare case. Seizures and movement disorders have almost the same phenomenology, so it is often difficult to distinguish them. In this study, we report a unique case of MTLE and co-occurring dystonia. Case: A 21 years old male with complaints of seizures since 4 years ago. Seizures of one body jerking and drooling with a duration of less than 5 minutes. Prior to the seizure the patient was nauseous then vomited and followed by an empty mind, after the seizure the patient was confused. The patient also complained of unconscious movements in his right hand since 8 years ago. The movements disappeared when the patient slept. Physical examination revealed dystonic movement with a sensory trick on the right hand. Magnetic resonance imaging (MRI) of the brain with contrast showed bilateral hippocampal atrophy accompanied by left hippocampal sclerosis. Blood laboratory results, electroencephalography, and neurobehavior examination were within normal limits.. Discussion: MTLE can be caused by mutations in SCN1A, VPS13A, C90RF72, or TDP 43. Dystonia can be caused by mutations in SCN1A, TUBB4A, TOR1A, THAP1, or GNAL. SCN1A causes an increase in sodium influx, causing depolarization which causes clinical manifestations in the form of seizures and dystonia. For some disorders, although genetic causes have been identified, the molecular pathophysiology remains largely unknown, requiring further research. Conclusion: For some disorders, although genetic causes have been identified, the molecular pathophysiology remains largely unknown, requiring further research. [ABSTRACT FROM AUTHOR]

As one of the most common neurological diseases, epilepsy is often accompanied by psychiatric disorders. Depression is the most universal comorbidity of epilepsy, especially in temporal lobe epilepsy (TLE). Therefore, it is urgently needed to figure out potential mechanisms and the optimization of therapeutic strategies. Microglia play a pivotal role in the coexistent relationship between epilepsy and depression. Activated microglia released cytokines like IL-6 and IL-1β, orchestrating neuroinflammation especially in the hippocampus, worsening both depression and epilepsy. The decrease of intracellular K+ is a common part in various molecular changes. The P2X7–NLRP3–IL-1β is a major inflammatory pathway that disrupts brain network. Extra ATP and CX3CL1 also lead to neuronal excitotoxicity and blood-brain barrier (BBB) disruption. Regulating neuroinflammation aiming at microglia-related molecules is capable of suspending the vicious mutual aggravating circle of epilepsy and depression. Other overlaps between epilepsy and depression lie in transcriptomic, neuroimaging, diagnosis and treatment. Hippocampal sclerosis (HS) and amygdala enlargement (AE) may be the underlying macroscopic pathological changes according to current studies. Extant evidence shows that cognitive behavioral therapy (CBT) and antidepressants like selective serotonin-reuptake inhibitors (SSRIs) are safe, but the effect is limited. Improvement in depression is likely to reduce the frequency of seizure. More comprehensive experiments are warranted to better understand the relationship between them. [ABSTRACT FROM AUTHOR]

Introduction. Temporal lobe epilepsy (TLE) is the most common cause of focal onset seizures, affecting 40% of adolescents and adults with epilepsy. TLE is also one of the most common drug resistant forms of epilepsy. Surgical resection remains the treatment of choice for TLE, but not all patients with TLE are suitable candidates for resective neurosurgery. For such patients, deep brain stimulation (DBS) of the hippocampus remains a reversible and efficient treatment alternative. State of the art. We undertook a systematic review of the literature on hippocampal DBS efficacy and safety in the management of patients with TLE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL), was conducted. Clinical implications. We found 14 articles related to hippocampal DBS for the treatment of TLE. The responder rate (defined as at least 50% reduction in seizure frequency) for all patients was 83.4%, Of 99 patients treated by hippocampal DBS, 82 were regarded as responders, and 17 as non-responders. Future directions. Hippocampal DBS appears to be a safe and efficacious treatment alternative for patients who are not candidates for temporal lobectomy or selective amygdalohippocampectomy due to serious postoperative cognitive deficits. In selected patients with TLE, this neuromodulatory therapy may be very safe and efficacious. [ABSTRACT FROM AUTHOR]

IntroductionThe extent to which the Big Five personality traits and subjective well-being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia-related neuropathology is unclear.MethodsUsing data from eight independent studies (Ntotal = 44,531; Ndementia = 1703; baseline Mage = 49 to 81 years, 26 to 61% female; Mfollow-up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia.ResultsSynthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long-term dementia diagnosis. There were no consistent associations with neuropathology.DiscussionThis multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy.HighlightsN(+), C(-), E(-), PA(-), and NA(+) were associated with incident diagnosis. Results were consistent despite self-report versus clinical diagnosis of dementia. Psychological factors were not associated with neuropathology at autopsy. Individuals with higher conscientiousness and no diagnosis had less neuropathology. High C individuals may withstand neuropathology for longer before death.

Abstract Objective Perineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer's disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age‐dependent shift was experimentally associated also with hippocampal engram formation during brain maturation. Our aim was to histopathologically assess PNN in the hippocampus of adult and pediatric patients with temporal lobe epilepsy (TLE) compared to age‐matched post‐mortem control subjects and to compare PNN‐related changes with memory impairment observed in our patient cohort. Methods Sixty‐six formalin‐fixed and paraffin‐embedded tissue specimens of the human hippocampus were retrieved from the European Epilepsy Brain Bank. Twenty‐nine patients had histopathologically confirmed hippocampal sclerosis (HS), and eleven patients suffered from TLE without HS. PNN were immunohistochemically visualized using an antibody directed against aggrecan and manually counted from hippocampus subfields and the subiculum. Results PNN density increased with age in both human controls and TLE patients. However, their density was significantly higher in all HS patients compared to age‐matched controls. Intriguingly, TLE patients presented presurgically with better memory when their hippocampal PNN density was higher (p

Abstract Agyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I–IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I–IV and no or minimal Aβ deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per × 400 visual field in the amygdala (OR 10.02, 95% CI 1.12–89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70–87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03–65.13) affected dementia independent of age, moderate Braak stages (III–IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage.

Hippocampal sclerosis of aging (HS-A) is a common age-related neuropathological lesion characterized by neuronal loss and astrogliosis in subiculum and CA1 subfield of hippocampus. HS-A is associated with cognitive decline that mimics Alzheimer's disease. Pathological diagnosis of HS-A is traditionally binary based on presence/absence of the lesion. We compared this traditional measure against our novel quantitative measure for studying the relationship between HS-A and other neuropathologies and cognitive impairment. We included 409 participants from The 90+ study with neuropathological examination and longitudinal neuropsychological assessments. In those with HS-A, we examined digitized H&E and LFB stained hippocampal slides. The length of HS-A in each subfield of hippocampus and subiculum, each further divided into three subregions, was measured using Aperio eSlide Manager. For each subregion, the proportion affected by HS-A was calculated. Using regression models, both traditional/binary and quantitative measures were used to study the relationship between HS-A and other neuropathological changes and cognitive outcomes. HS-A was present in 48 (12%) of participants and was always focal, primarily affecting CA1 (73%), followed by subiculum (9%); overlapping pathology (subiculum and CA1) affected 18% of individuals. HS-A was more common in the left (82%) than the right (25%) hemisphere and was bilateral in 7% of participants. HS-A traditional/binary assessment was associated with limbic-predominant age-related TDP-43 encephalopathy (LATE-NC; OR = 3.45, p

Abstract Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein–protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Abstract Objective Stereo‐electroencephalography‐guided three‐dimensional radiofrequency thermocoagulation (SEEG‐3D RFTC) is a minimally invasive treatment for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS). This study aimed to investigate the long‐term prognosis after SEEG‐3D RFTC treatment in patients with MTLE‐HS. Methods This single‐center retrospective study included 28 patients with MTLE‐HS treated with SEEG‐3D RFTC from January 2016 to May 2018. Postoperative curative effects were evaluated using the Engel classification, and the patients were followed up for 5 years. Results The proportions of patients categorized as Engel I between 1 and 5 years after surgery were 72.41% (12 months after surgery), 67.86% (18 months after surgery), 62.07% (24 months after surgery), 50.00% (36 months after surgery), 42.86% (48 months after surgery), and 42.86% (60 months after surgery), respectively. Regarding long‐term efficacy, based on the Engel classification, SEEG‐3D RFTC showed room for improvement. Significance This was the first study to evaluate the efficacy of SEEG‐3D RFTC for MTLE‐HS with long‐term follow‐up. SEEG‐3D RFTC is a promising alternative for patients with MTLE‐HS. Plain Language Summary This study explored the potential of stereoelectroencephalography‐guided three‐dimensional radiofrequency thermocoagulation, a minimally invasive approach, for treating medial temporal lobe epilepsy with hippocampal sclerosis. Involving 28 patients, the research tracked the treatment’s success over five years using the Engel classification. Initial results were promising, with 72.41% of patients achieving the most favorable outcome (Engel I) at one year. While there was a gradual decrease in this proportion over time, 42.86% of patients maintained this positive outcome at five years, highlighting the treatment's potential for long‐term efficacy.

Objective Methods Results Significance This study was undertaken to analyze whether the rate of breakthrough seizures in patients taking antiseizure medication (ASM) who have been seizure‐free for at least 12 months varies among different types and etiologies of epilepsy. Given the relative ease of achieving seizure freedom with ASM in patients with post‐ischemic stroke epilepsy, we hypothesized that this etiology is associated with a reduced risk of breakthrough seizures.We defined a breakthrough seizure as an unprovoked seizure occurring while the patient was taking ASM after a period of at least 12 months without seizures. Data were analyzed retrospectively from a tertiary epilepsy outpatient clinic. Patients were eligible for inclusion if they either had a breakthrough seizure at any time or a seizure‐free interval of at least 2 years. Our primary endpoint was rate of breakthrough seizures. We conducted univariable and multivariable analyses to identify variables associated with breakthrough seizures.Of 521 patients (53% females, median age = 49 years) included, 29% had a breakthrough seizure, which occurred after a median seizure‐free interval of 34 months (quartiles = 22, 62). When controlling for clinically relevant covariates, breakthrough seizures were associated with post‐ischemic stroke epilepsy (odds ratio [OR] = .267, 95% confidence interval [CI] = .075–.946), genetic generalized epilepsy (OR = .559; 95% CI = .319–.978), intellectual disability (OR = 2.768, 95% CI = 1.271–6.031), and the number of ASMs previously and currently tried (OR = 1.203, 95% CI = 1.056–1.371). Of the 151 patients with breakthrough seizures, 34.3% did not reachieve terminal 12‐month seizure freedom at the last visit.This is the first study to show an association between type and etiology of epilepsy and risk of breakthrough seizures. Our data suggest that epilepsies in which seizure freedom can be obtained more easily also exhibit a lower risk of breakthrough seizures. These findings may help to better counsel seizure‐free patients on their further seizure prognosis. [ABSTRACT FROM AUTHOR]

Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein–protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. Methods: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow‐up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. Results: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow‐up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10‐year follow‐up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal‐appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty‐four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten‐year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. Significance: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status. [ABSTRACT FROM AUTHOR]

The postictal state, an abnormal cerebral condition following a seizure until the return to the interictal baseline, is frequently overlooked, despite often exceeding ictal duration and significantly impacting patients' lives. This study analyzes stereo‐EEG (SEEG) signal dynamics using permutation entropy to quantify recovery time (postictal alteration time – PAT) in focal epilepsy and its clinical correlations. The average PAT was 4.5 min, extending up to an hour and was highest in temporal epilepsy and hippocampal sclerosis. Correlating with age at seizure onset and at SEEG, PAT provides a solution for operationally defining the postictal state and guiding interventions. [ABSTRACT FROM AUTHOR]

Background: Although a growing body of research has indicated a strong link between oxidative stress and epilepsy, the exact nature of their interaction remains elusive. To elucidate this intricate relationship, we conducted a bidirectional Mendelian randomization (MR) analysis employing two independent datasets. Methods: A two‐sample MR analysis was performed using instrumental variables derived from genome‐wide association study summary statistics of oxidative stress injury biomarkers (OSIB) and epilepsy. The OSIBs were selected from eight primary metabolic pathways associated with oxidative stress. Additionally, seven distinct epilepsy phenotypes were considered, which encompassed all epilepsy, generalized epilepsy, generalized tonic‐clonic seizures, focal epilepsy, focal epilepsy with hippocampal sclerosis (focal HS), focal epilepsy with lesions other than HS (focal NHS), and lesion‐negative focal epilepsy. Causal estimates were computed using the inverse‐variance weighted method or the Wald ratio method, and the robustness of causality was assessed through sensitivity analyses. Results: For OSIB and epilepsy, 520 and 23 genetic variants, respectively, were selectively extracted as instrumental variants. Genetically predicted higher kynurenine level was associated with a decreased risk of focal epilepsy (odds ratio [OR] 1.950, 95% CI 1.373–2.528, p =.023) and focal NHS (OR 1.276, 95% CI 1.100–1.453, p =.006). For reverse analysis, there was a suggestive effect of focal NHS on urate (OR 1.19 × 1015, 95% CI 11.19 × 1015 to 1.19 × 1015, p =.0000746) and total bilirubin (Tb) (OR 4.98, 95% CI 3.423–6.543, p =.044). In addition, genetic predisposition to focal HS was associated with higher Tb levels (OR 9.83, 95% CI 7.77–11.888, p =.034). Conclusion: This MR study provides compelling evidence of a robust association between oxidative stress and epilepsy, with a notable emphasis on a causal relationship between oxidative stress and focal epilepsy. Additional research is warranted to confirm the connection between oxidative stress and the risk of epilepsy and to unravel the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: The goal of our study was to determine the incidence of cerebellar atrophy, assess the imaging findings in the posterior fossa and determine the incidence of hippocampal sclerosis in a cohort of pediatric patients with confirmed tuberous sclerosis complex (TSC). Material and methods: MRI studies of 98 TSC pediatric patients (mean age 7.67 years) were evaluated for cerebellar atrophy, cerebral/cerebellar tubers, white matter lesions, subependymal nodules, subependymal giant cell astrocytomas, ventriculomegaly, and hippocampal sclerosis. Clinical charts were revisited for clinical symptoms suggesting cerebellar involvement, for seizures and treatment for seizures, behavioral disorders and autism. Results: Cerebral tubers were present in 97/98 cases. In total, 97/98 had subependymal nodules, 15/98 had SEGA, 8/98 had ventriculomegaly and 4/98 had hippocampal sclerosis. Cerebellar tubers were found in 8/98 patients (8.2%), whereas cerebellar atrophy was described in 38/98 cases (38.8%). In 37/38 patients, cerebellar volume loss was mild and diffuse, and only one case presented with left hemi-atrophy. Briefly, 32/38 presented with seizures and were treated with anti-seizure drugs. In total, 8/38 (21%) presented with behavioral disorders, 10/38 had autism and 2/38 presented with seizures and behavioral disorders and autism. Conclusions: Several studies have demonstrated cerebellar involvement in patients with TSC. Cerebellar tubers differ in shape compared with cerebral tubers and are associated with cerebellar volume loss. Cerebellar atrophy may be focal and diffuse and one of the primary cerebellar manifestations of TSC, especially if a TSC2 mutation is present. Cerebellar degeneration may, however, also be secondary/acquired due to cellular damage resulting from seizure activity, the effects of anti-seizure drugs and anoxic–ischemic injury from severe seizure activity/status epilepticus. Further, prospective studies are required to identify and establish the pathogenic mechanism of cerebellar atrophy in patients with TSC. [ABSTRACT FROM AUTHOR]

Objective: Stereo‐electroencephalography‐guided three‐dimensional radiofrequency thermocoagulation (SEEG‐3D RFTC) is a minimally invasive treatment for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS). This study aimed to investigate the long‐term prognosis after SEEG‐3D RFTC treatment in patients with MTLE‐HS. Methods: This single‐center retrospective study included 28 patients with MTLE‐HS treated with SEEG‐3D RFTC from January 2016 to May 2018. Postoperative curative effects were evaluated using the Engel classification, and the patients were followed up for 5 years. Results: The proportions of patients categorized as Engel I between 1 and 5 years after surgery were 72.41% (12 months after surgery), 67.86% (18 months after surgery), 62.07% (24 months after surgery), 50.00% (36 months after surgery), 42.86% (48 months after surgery), and 42.86% (60 months after surgery), respectively. Regarding long‐term efficacy, based on the Engel classification, SEEG‐3D RFTC showed room for improvement. Significance: This was the first study to evaluate the efficacy of SEEG‐3D RFTC for MTLE‐HS with long‐term follow‐up. SEEG‐3D RFTC is a promising alternative for patients with MTLE‐HS. Plain Language Summary: This study explored the potential of stereoelectroencephalography‐guided three‐dimensional radiofrequency thermocoagulation, a minimally invasive approach, for treating medial temporal lobe epilepsy with hippocampal sclerosis. Involving 28 patients, the research tracked the treatment's success over five years using the Engel classification. Initial results were promising, with 72.41% of patients achieving the most favorable outcome (Engel I) at one year. While there was a gradual decrease in this proportion over time, 42.86% of patients maintained this positive outcome at five years, highlighting the treatment's potential for long‐term efficacy. [ABSTRACT FROM AUTHOR]

Objective: Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level. Methods: This study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy. Results: We found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome. Significance: Our research highlights the role of hippo-thalamic-basalcortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy. [ABSTRACT FROM AUTHOR]

Background: Epilepsy has many neurobiological consequences. This study aimed to identify the profile of adult patients with new onset epilepsy in our university hospitals as regarding clinical picture, etiology, cerebral imaging and electroencephalogram (EEG) correlation, comorbidities, management, drug therapy and seizure severity and quality of life. We recruited one hundred patients with adult onset epilepsy, and we assessed them clinically, radiologically, and electrophysiologically. We performed Liverpool Seizure Severity Scale (LSSS) to assess seizure severity and the Quality of Life In Epilepsy-10 Questionnaire (QOLIE-10) to assess quality of life of adult patients with new onset epilepsy. Results: Fifty-seven percent of the studied patients were males, and 43.0% were females with mean (± SD) of age was 52.83 (± 17.33), 13.0% of the studied patients had positive family history of epilepsy. 32.0% had focal epilepsy, and 68.0% had generalized epilepsy, 53% of patients had uncontrolled seizures, 49% of patients were on monotherapy, and 51.0% were on polytherapy. The mean (± SD) seizure frequency per month in the studied patients was 4.0 (± 3.15). Imaging abnormalities were found in 88% of studied patients. 43% of the studied patients had abnormal EEG. Post-traumatic epilepsy, focal cortical dysplasia and mesial temporal sclerosis were statistically significant higher in male patients than female patients. Arteriovenous malformations were significantly higher in females. Middle-aged adults' group had hypertension more than other age groups, older adult age group had atrial fibrillation, coronary heart disease, diabetes mellitus and dyslipidemia more than other age groups. Young adults had migraine more than other age groups. Post-stroke epilepsy was higher in older adult and middle-aged adult groups more than young adult age group. Intracranial neoplasms were higher in older adult age group than other age groups. Patients with moderate, severe, and very severe LSSS score had significantly more frequent uncontrolled seizures, abnormal EEG and higher rate of polytherapy as compared to those with mild LSSS score. Patients with impaired quality of life had more seizure frequency, less seizure control, higher seizure severity, more EEG abnormalities and were mostly treated by AEDs polytherapy than those with average life quality. Conclusions: Levetiracetam was the most preferred drug for treating patients with adult-onset epilepsy (40%), whether used as monotherapy or in combination with other drugs. Seizure severity, and seizure frequency per month strongly impaired patients' quality of life. [ABSTRACT FROM AUTHOR]