Seizures Research Articles

Distinct Ventral Hippocampus Network Properties inDissociated Cultures.

Extensive research has been focused in the past century on structural, physiological, and molecular attributes of the hippocampus. This interest was created by the unique involvement of the hippocampus in cognitive and affective functions of the brain. Functional analysis revealed that the hippocampus has divergent properties along its axial dimension to the extent that the dorsal sector (dorsal hippocampus, DH) has different connections with the rest of the brain than those of the ventral sector (VH). Still, longitudinal pathways connect the DH with the VH and dampen the functional differences between the sectors. To be able to identify the intrinsic functional difference between the DH and VH, we produced dissociated monolayer cultures from prenatal DH and VH and examined their properties at 10-20 days after plating by imaging the spontaneous activity of the network using Fluo-2 AM, a calcium indicator. Surprisingly, while DH and VH sectors produced dissociated cultures with similar morphological attributes, VH cultures were more active spontaneously than DH cultures. Furthermore, when stimulated to produce action potentials, VH neurons triggered network bursts in postsynaptic neurons more often than DH cultures. Finally, in both DH and VH cultures, electrical stimulation of single cells produced network bursts in response to a burst of action potentials rather than to single spikes. These experiments indicate that even in dissociated cultures, neurons of the VH are more excitable and sensitive to electrical stimulation than DH; hence, they are more likely to generate network bursts and epileptic seizures, as suggested for invivo brains.

Multi-target Phenylpropanoids Against Epilepsy.

Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.

Evaluation of simplified wireless EEG recordings in the neurological emergency room.

In the neurological emergency room (nER), timely electroencephalography (EEG) diagnostic is often crucial in patients with altered state of consciousness as well as in patients presenting with a first seizure. Yet, routine-EEG (rEEG) is often not available, especially during off-hours. We analyzed the value of a commercially available, simplified wireless eight-channel EEG recording (swEEG, CerebAir® EEG headset, Nihon Kohden), applied by non-EEG-specialized medical students, in patients presenting in our nER with (suspicion of) epileptic seizures and/or loss of or altered state of consciousness between 08/2019 and 08/2022. We evaluated the feasibility and validity compared to a standard rEEG (21 electrodes according to the international 10/20 system) and also included the clinical follow-up of the patients. 100 patients were included in our analysis (mean age 57.6 ± 20.4 years; 61 male). Median time of electrode application was 7 minutes (range 4-20 minutes), with significantly longer duration in patients with altered level of consciousness (median 8 minutes, p = 0.035). Electrode impedances also differed according to state of consciousness (p = 0.032), and were higher in females (p<0.001). 55 patients received additional rEEG, either during their acute nER stay (25) and/or during the next days (38). Considering normal EEG findings vs. pathological slowing vs. epileptiform activity, swEEG matched first rEEG results in 48/55 cases (87.3%). Overall, swEEG detected the same or additional pathological EEG patterns in 52/55 cases (94.5%). In 7/75 patients (9.3%) who did not receive rEEG, or had their rEEG scheduled to a later time point during their hospital stay, swEEG revealed important additional pathological findings (e.g. status epilepticus, interictal epileptiform discharges), which would have triggered acute therapeutic consequences or led to further diagnostics and investigations. The introduced swEEG represents a practicable, valuable technique to be quickly applied by non-EEG-specialized ER staff to initiate timely diagnostic and guide further investigations and treatment in the nER. Moreover, it may help to avoid under-diagnostic with potentially harmful consequences caused by skipped or postponed regular 10/20 EEG examinations, and ultimately improve the outcome of patients.

Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice

Clinical studies have shown that epileptic seizures worsen Alzheimer’s disease (AD) pathology and related cognitive deficits; however, the underlying mechanism is unclear. To assess the effects of seizures on the progression of AD, chronic temporal lobe epilepsy was induced in five familial AD mutation (5×FAD) mice by kindling with the chemoconvulsant pentylenetetrazole (PTZ) at 3–3.5 months of age. The amyloidogenic pathway, tauopathy, synaptic damage, neuronal death, neurological inflammatory response and associated kinase signaling pathway dysregulation were examined at 9 months of age. We found that APP, p-APP, BACE1, Aβ and kinase-associated p-tau levels were elevated after PTZ kindling in 5×FAD mice. In addition, PTZ kindling exacerbated hippocampal synaptic damage and neuronal cell death, as determined by scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, respectively. Finally, the levels of the neuroinflammation markers GFAP and Iba1, as well as the inflammatory cytokine IL-1β, were increased after PTZ insult. PTZ kindling profoundly exacerbated extracellular regulated kinase (ERK)-death-associated protein kinase (DAPK) signaling pathway overactivation, and acute ERK inhibitor treatment downregulated Aβ production and p-APP and p-tau levels in epileptic 5×FAD mice. In addition, long-term use of the antiseizure drug carbamazepine (CBZ) alleviated seizure-induced accelerated amyloid and tau pathology and ERK-DAPK overactivation in 5×FAD mice. Collectively, these results demonstrate that seizure-induced increases in AD-like neuropathology in 5×FAD mice are partially regulated by the ERK-DAPK pathway, suggesting that the ERK-DAPK axis could be a new therapeutic target for the treatment of AD patients with comorbid seizures.

Distinguishing clinical and imaging characteristics of primary central nervous system lymphoma from high-grade glioma and metastatic brain tumors.

The purpose of this retrospective analysis was to evaluate the clinical presentations, radiological characteristics, patient outcomes, and therapeutic approaches among individuals diagnosed with primary central nervous system lymphoma (PCNSL), high-grade glioma (HGG), and metastatic brain tumors (METS). We assembled a cohort of brain tumor patients from two medical centers, with two oncologists independently reviewing their clinical profiles. A retrospective examination of 87 PCNSL, 87 HGG, and 71 METS cases was performed to assess the aforementioned parameters. Notable variations were identified in the incidence of epileptic seizures and cognitive impairments between PCNSL and METS patients. Cerebral hemisphere involvement was predominantly observed in HGG and METS cases. PCNSL cases exhibited a higher likelihood of multiple lesions, whereas HGG showed a greater tendency for recurrence. The median survival times were established at 24.3months for PCNSL, 44.5months for HGG, and 27.1months for METS patients. In PCNSL cases, the number of lesions was identified as a significant predictor of mortality (P = 0.008). Our findings highlight the importance of clinical and imaging features in diagnosing PCNSL, which may present distinct features compared to HGG and METS.

Comparison Between Methods of Choosing EEG Training Data in Epileptic Seizures Prediction Systems

Considering the large number of people that suffer with epilepsy, there is great interest in developing a system capable of predicting the occurrence of the seizures. Warning patients about the proximity of a seizure can help them to avoid dangerous situations. Many efforts in the development of this system have been placed using, basically, machine learning techniques. In most of these works, regardless of the technique employed, it is assumed that the system is able to learn when the patient’s brain signals, obtained from electroencephalogram (EEG), change from interictal to pre-ictal state. Some published works do not explicitly clarify the method of choosing training and test data. This means that good results may be due to the use of an inadequate method. That is, the EEG segments may have been temporarily mixed up during training, which would help the network correctly predict the seizure. However, this would not work from a real point of view. The objective of this work is to investigate, through experiments, the effect of the way of choosing the training and test data on the accuracy of a seizure prediction system. Experimental results showed that the accuracy of the systems increases when training is performed with windows close to the seizure used for testing.

Multi-branch fusion graph neural network based on multi-head attention for childhood seizure detection

The most common manifestation of neurological disorders in children is the occurrence of epileptic seizures. In this study, we propose a multi-branch graph convolutional network (MGCNA) framework with a multi-head attention mechanism for detecting seizures in children. The MGCNA framework extracts effective and reliable features from high-dimensional data, particularly by exploring the relationships between EEG features and electrodes and considering the spatial and temporal dependencies in epileptic brains. This method incorporates three graph learning approaches to systematically assess the connectivity and synchronization of multi-channel EEG signals. The multi-branch graph convolutional network is employed to dynamically learn temporal correlations and spatial topological structures. Utilizing the multi-head attention mechanism to process multi-branch graph features further enhances the capability to handle local features. Experimental results demonstrate that the MGCNA exhibits superior performance on patient-specific and patient-independent experiments. Our end-to-end model for automatic detection of epileptic seizures could be employed to assist in clinical decision-making.

Impact of age on surgical outcomes for world federation of neurosurgical societies grade I and II aneurysmal subarachnoid haemorrhage: a novel prognostic model using recursive partitioning analysis

This study aimed to evaluate age as a prognostic factor and develop a comprehensive prognostic model for patients undergoing clipping surgery for World Federation of Neurosurgical Societies (WFNS) grade I/II aneurysmal subarachnoid haemorrhage (SAH). We retrospectively investigated 188 patients with WFNS grade I/II SAH who underwent microsurgical clipping at our institute between December 2010 and January 2020. The data of 176 patients (75 with grade I and 101 with grade II) were analysed. Data on patient demographics, aneurysm characteristics, SAH factors, surgical details, and clinical outcomes were collected. Prognostic factors were assessed using bivariate and multivariable logistic regression analyses, and recursive partitioning analysis. Favourable outcomes (mRS 0–2) were observed in 76% of patients. Age, a significant negative prognostic factor in multivariable analysis (odds ratio 0.55, 95% confidence interval 0.40–0.76, p < 0.001), was cutoff at 70 years by the receiver operating characteristic curve. Patients aged ≤ 70 years had significantly better outcomes than those aged > 70 years (84% vs. 46%, respectively; p < 0.001). Epileptic seizures were significantly associated with poor outcomes in older adults (p < 0.001). A prognostic model (favourable, intermediate, and poor) based on age and postoperative adverse events showed significantly different outcomes between age groups (p < 0.001). Age was a stronger prognostic factor than WFNS grading for patients with grade I/II SAH undergoing microsurgical clipping. For patients aged ≤ 70 years, precise microsurgeries with fewer complications were associated with favourable outcomes beyond WFNS grade. For older patients, postoperative intensive seizure management may prevent poor outcomes.

Clinical characteristics and prognosis analysis of acute symptomatic seizures secondary to autoimmune encephalitis

ObjectiveThis study aimed to analyze the clinical characteristics and prognosis of patients with autoimmune encephalitis (PWAE) who experienced seizures during the acute phase.MethodsClinical data were collected from 84 patients diagnosed with AE at the General Hospital of Ningxia Medical University between January 2015 and January 2023. Patients were divided into seizure and non-seizure groups. Clinical characteristics of both groups were compared, including differences between anti-NMDAR and anti-LGI1 encephalitis within the seizure group. Due to the limited sample size and to avoid overfitting, we focused on univariate logistic regression analysis to identify individual prognostic factors.ResultsA total of 84 patients were enrolled, with 76.19% (64/84) in the seizure group and 23.81% (20/84) in the non-seizure group. The seizure group had a longer hospital stay (p = 0.013), higher rates of impaired consciousness (p = 0.001), and more frequent intensive care unit (ICU) admission (p = 0.011). They also had higher peripheral blood neutrophil-to-lymphocyte ratio (NLR), leukocyte count, and uric acid levels (p = 0.038, p = 0.006, p = 0.020), and were more likely to show slow-wave rhythms on electroencephalography (EEG) (p = 0.031). At 2-year follow-up, there was no significant difference in prognosis between the seizure and non-seizure groups (p = 0.653), with 35.94% (23/64) of the seizure group having a poor prognosis. Status epilepticus (SE), complications, endotracheal intubation, mRS score at discharge, APE2, and RITE2 scores increased the risk of poor prognosis (OR &amp;gt; 1), while intensive care and albumin reduced the risk (OR &amp;lt; 1).ConclusionSeizures are common in the early stages of AE, with faciobrachial dystonic seizures (FBDS) characteristic of anti-LGI1 encephalitis and SE and super-refractory status epilepticus (Sup-RSE) frequently observed in anti-NMDAR encephalitis. Seizure semiology across AE subtypes lacks specificity, and no symptoms clearly distinguish immune-mediated from non-immune causes. While seizures are linked to AE severity, particularly in anti-NMDAR encephalitis, they do not appear to impact overall prognosis. SE, complications, endotracheal intubation, modified Rankin Scale (mRS) score at discharge, Antibody-Prevalence in Epilepsy and Encephalopathy (APE2) score, Response to Immunotherapy in Epilepsy and Encephalopathy (RITE2) score, intensive care, and albumin were identified as significant prognostic factors.

Posterior Basolateral Amygdala is a Critical Amygdaloid Area for Temporal Lobe Epilepsy.

The amygdaloid complex consists of multiple nuclei and is a key node in controlling temporal lobe epilepsy (TLE) in both human and animal model studies. However, the specific nucleus in the amygdaloid complex and the neural circuitry governing seizures remain unknown. Here, it is discovered that activation of glutamatergic neurons in the posterior basolateral amygdala (pBLA) induces severe seizures and even mortality. The pBLA glutamatergic neurons project collateral connections to multiple brain regions, including the insular cortex (IC), bed nucleus of the stria terminalis (BNST), and central amygdala (CeA). Stimulation of pBLA-targeted IC neurons triggers seizures, whereas ablation of IC neurons suppresses seizures induced by activating pBLA glutamatergic neurons. GABAergic neurons in the BNST and CeA establish feedback inhibition on pBLA glutamatergic neurons. Deleting GABAergic neurons in the BNST or CeA leads to sporadic seizures, highlighting their role in balancing pBLA activity. Furthermore, pBLA neurons receive glutamatergic inputs from the ventral hippocampal CA1 (vCA1). Ablation of pBLA glutamatergic neurons mitigates both acute and chronic seizures in the intrahippocampal kainic acid-induced mouse model of TLE. Together, these findings identify the pBLA as a pivotal nucleus in the amygdaloid complex for regulating epileptic seizures in TLE.

Somatostatin-expressing inhibitory neurons with mTORC1 activation in cortical layers 4/5 are involved in the epileptogenesis of mice

Aim: Patients with tuberous sclerosis complex (TSC) which is caused by hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) often show giant cells in the brain. These giant cells are thought to be involved in epileptogenesis, but the underlying mechanisms are unknown. In this study, we focused on mTORC1 activation and γ-amino butyric acid (GABA)ergic signaling in somatostatin-expressing inhibitory neurons (SST-INs) using TSC-related epilepsy model mice. Methods: We analyzed the 8-week-old Tsc2 conditional knockout (Tsc2 cKO) mice, which have epileptic seizures that are cured by sirolimus, an mTORC1 inhibitor. After the occurrence of epileptic seizures was confirmed, Tsc2 cKO mice were treated with vehicle or sirolimus. Then, their brains were investigated by hematoxylin and eosin staining, immunohistochemical staining and immunoblotting assay. Results: As in TSC patients, giant cells with hyperactivation of mTORC1 were found in the cerebral cortex of Tsc2 cKO mice. These giant cells were mainly SST-INs in the cortical layers 4/5. Giant cells showed decreased expression of GABA type A receptor subunit α1 (GABAAR-α1) compared with normal size cells in control mice and Tsc2 cKO mice. In addition, decreased GABAAR-α1 expression was also confirmed by immunoblotting assay of the whole cerebral cortex. In the cerebral cortex of sirolimus-treated Tsc2 cKO mice, whose epileptic seizures were cured, decreased GABAAR-α1 expression was recovered to the same level as in control mice. Conclusions: These results suggest that the epileptic seizures in Tsc2 cKO mice are caused by the deregulation of GABAergic signaling through mTORC1 activation of SST-INs localized in cortical layers 4/5.

Investigating the role of electroencephalogram based rhythmic bands: applications in imagined speech classification and epileptic seizure severity detection

Investigating the role of electroencephalogram based rhythmic bands: applications in imagined speech classification and epileptic seizure severity detection

Anchoring temporal convolutional networks for epileptic seizure prediction.

Accurate and timely prediction of epileptic seizures is crucial for empowering patients to mitigate their impact or prevent them altogether. Current studies predominantly focus on short-term seizure predictions, which causes the prediction time to be shorter than the onset of antiepileptic, thus failing to prevent seizures. However, longer epilepsy prediction faces the problem that as the preictal period lengthens, it increasingly resembles the interictal period, complicating differentiation. To address these issues, we employ the sample entropy method for feature extraction from electroencephalography (EEG) signals. Subsequently, we introduce the Anchoring Temporal Convolutional Networks (ATCN) model for longer-term, patient-specific epilepsy prediction. ATCN utilizes dilated causal convolutional networks to learn time-dependent features from previous data, capturing temporal causal correlations within and between samples. Additionally, the model also incorporates anchoring data to enhance the performance of epilepsy prediction further. Finally, we proposed a multilayer sliding window prediction algorithm for seizure alarms. Evaluation on the Freiburg intracranial EEG dataset shows our approach achieves 100% sensitivity, a false prediction rate (FPR) of 0.08 per hour and an average prediction time (APT) of 99.98 minutes. Using the CHB-MIT scalp EEG dataset, we a achieve 97.44% sensitivity, an FPR of 0.11 per hour, and an APT of 92.99 minutes. These results demonstrate that our approach is adequate for seizure prediction over a more extended prediction range on intracranial and scalp EEG datasets. The average prediction time of our approach exceeds the typical onset time of antiepileptic. This approach is particularly beneficial for patients who need to take medication at regular intervals, as they may only need to take their medication when our method issues an alarm. This capability has the potential to prevent seizures, which will greatly improving patients' quality of life.

Carbon monoxide poisoning is associated with an increased risk of epilepsy and status epilepticus: a nationwide population-based cohort study conducted in the Republic of Korea between 2002–2021

Introduction Carbon monoxide poisoning may result in various neurological injuries, including acute symptomatic seizures. We aimed to investigate the long-term risk of epilepsy and status epilepticus in patients with previous carbon monoxide poisoning. Methods The study population was derived from the National Health Insurance Service database of the Republic of Korea between 1 January 2002 and 31 December 2021. We included adults with at least one documented visit to medical facilities because of carbon monoxide poisoning (International Classification of Diseases, Tenth Revision, code T58). Patients were matched, on the same index date, with controls, without a T58 code, for age, sex, insurance type, income level, and residence location in a 1:1 ratio. Follow-up continued until death, migration, or the end of the observation period (31 December 2021). The primary outcome was the incidence of epilepsy (codes G40 or R56) and status epilepticus (code G41). Results This study included 53,380 patients with carbon monoxide poisoning and 53,380 controls, with 44.2% women and a mean age of 45.7 years. The mean (±SD) follow-up period was 5.7 ± 4.3 years in the carbon monoxide poisoned group and 6.4 ± 4.4 years in controls. The overall risk of epilepsy (adjusted hazard ratio 2.60; 95% CI: 2.43–2.78; P < 0.001) and status epilepticus (adjusted hazard ratio 4.10; 95% CI: 2.84–5.92; P < 0.001) was significantly increased in the carbon monoxide poisoned group compared to controls. The risk of epilepsy and status epilepticus was increased in patients with previous carbon monoxide poisoning, regardless of sex, age or a history of stroke, neurodegenerative diseases, or central nervous system tumour or infection. However, in the subgroup analysis according to age, the highest risk of epilepsy and status epilepticus was observed in patients less than 40 years of age. Discussion In this population-based cohort study, previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus. The risk was more noticeable in patients aged less than 40 years. Further studies are needed to confirm such an association in other populations. Conclusions Previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus, particularly in the younger population. The long-term management of survivors of carbon monoxide poisoning should include monitoring for epilepsy and status epilepticus.

Surgical Considerations in Treating Central Nervous System Lymphomas: A Case Series of 11 Patients

In this retrospective unicentric study, we analyzed the medical records of 11 patients who were surgically treated for CNS lymphoma, both primary and secondary, between 2009 and 2024. Given the rarity of CNS lymphomas and their diverse signs and symptoms based on tumoral location, our aim was to describe key aspects, such as clinical presentations and surgical management. A possible relationship between obesity and CNS lymphoma progression was investigated through an analysis of previous study findings. The literature suggests a wide spectrum of manifestations, from nausea and headaches to loss of equilibrium and speech impairment. A predominance of unsystematized balance disorders and epileptic seizures were affirmed. Notably, as emerged from our study, aphasia was a particularly interesting neurological symptom due to its rarity in the clinical features of CNSL. Other significant factors, such as tumor localization and perioperative phases, were thoroughly investigated, with the latter highlighted by an illustrative case report. Additionally, a literature review was included, comprising nine recent retrospective studies on the efficacy of surgical resection for patients diagnosed with PCNSL.

Pattern of Injuries in Children with Epilepsy: A Hospital-Based Case-Control Study

Abstract Objective The aim of this study is to examine the profile and pattern of injuries in children with epilepsy (CWE) as compared with healthy controls. Methods This prospective, cross-sectional study conducted over 1 year in a tertiary care pediatric center included consecutive CWE aged 4 to 16 years who had active seizures during the preceding 1 year. A similar number of age- and sex-matched healthy controls were enrolled. Children with acute symptomatic seizures or degenerative neurologic disorders were excluded. Standardized scales were used to assess intelligent quotient, psychopathology, seizure severity, and restriction of daily activities. Results Two hundred and eight CWE (mean age: 107 ± 37months; range: 3.5–16 years) and an equal number of healthy controls (mean age: 108 ± 43 months; range: 3.5–16 years; p = 0.07) were evaluated. The majority of CWE had generalized epilepsy (n = 117, 59.6%) followed by focal epilepsy (n = 84, 40.3%). The mean duration of epilepsy was 47.4 ± 36.3 months. The prevalence of injury was significantly greater in CWE (n = 118/208, 56.7%) compared with controls (n = 56/208, 26.9%; p &lt; 0.001). CWE suffered significantly greater number of 293 injuries in the past 1 year in contrast to 83 injuries in controls (p &lt; 0.001). In CWE, the majority of injuries were unrelated to seizures (n = 85/118, 72%, 211 injuries), while only one-third (n = 33/118, 27.9%, 82 injuries) suffered seizure-related injuries. The incidence of injures unrelated to seizures and that of seizure-related injuries were similar (2.48 seizure-related injuries per person per year). Among CWE, a comparison of the injury versus noninjury group showed a significantly longer duration of epilepsy (53 ± 34 vs. 40 ± 38 months, p &lt; 0.007), higher prevalence of underlying structural etiology in generalized epilepsy (34.7 vs. 13.3%, p &lt; 0.001), higher mean seizure severity and restriction of daily activity scores, and higher prevalence of hyperactivity (36.4 vs. 18.9%, p = 0.006) and intellectual disability (35.6 vs. 10%, p &lt; 0.001) in the injury group. Injuries on the head, face, and upper limb were significantly more in CWE as compared with controls, and tongue injuries were found only in CWE (p =&lt; 0.05), and were seen significantly more as seizure-related injury (n = 7 vs. 1, p &lt; 0.001) compared with non-seizure-related injuries. The majority of injuries in children with CWE and controls were mild in nature (n = 112, 53.8% vs. n = 54, 26%; p &lt; 0.001). Conclusions The prevalence of injuries among CWE aged between 4 and 16 years is high and is significantly greater than in healthy controls, although the majority of injuries are mild in severity in both and are non-seizure-related injuries. Longer duration of epilepsy, higher seizure severity, and restriction of daily activities, and higher prevalence of underlying structural etiology, hyperactivity, and intellectual disability are associated with injuries in CWE.

Element Changes Occurring in Brain Point at the White Matter Abnormalities in Rats Exposed to the Ketogenic Diet During Prenatal Life.

A large number of clinical studies demonstrate that the ketogenic diet (KD) may be an effective approach to the reduction of epileptic seizures in children and adults. Such dietary therapy could also help pregnant women with epilepsy, especially since most antiseizure drugs have teratogenic action. However, there is a lack of medical data, considering the safety of using KD during gestation for the progeny. Therefore, we examined the influence of KD used prenatally in rats on the elemental composition of the selected brain regions in their offspring. For this purpose, synchrotron radiation-induced X-ray fluorescence (SR-XRF) microscopy was utilized, and elements such as P, S, K, Ca, Fe, and Zn were determined. Moreover, to verify whether the possible effects of KD are temporary or long-term, different stages of animal postnatal development were taken into account in our experiment. The obtained results confirmed the great applicability of SR-XRF microscopy to track the element changes occurring in the brain during postnatal development as well as those induced by prenatal exposure to the high-fat diet. The topographic analysis of the brains taken from offspring of mothers fed with KD during pregnancy and appropriate control individuals showed a potential influence of such dietary treatment on the brain levels of elements such as P and S. In the oldest progeny, a significant reduction of the surface of brain areas characterized by an increased P and S content, which histologically/morphologically correspond to white matter structures, was noticed. In turn, quantitative elemental analysis showed significantly decreased levels of Fe in the striatum and white matter of 30-day-old rats exposed prenatally to KD. This effect was temporary and was not noticed in adult animals. The observed abnormalities may be related to the changes in the accumulation of sphingomyelin and sulfatides and may testify about disturbances in the structure and integrity of the myelin, present in the white matter.

Gentiopicroside Attenuates Lithium/Pilocarpine-Induced Epilepsy Seizures by Down-Regulating NR2B/CaMKII/CREB and TLR4/NF-κB Signaling Pathways in the Hippocampus of Mice

Background: Epilepsy is a prevalent and disabling neurological condition characterized by recurrent seizures. Approximately 50% of adults with active epilepsy have at least one comorbidity and they are at a greater risk of premature death than the general population. Gentiopicroside (Gent) is a primary component of Gentiana macrophylla Pall. that has been shown to have diverse pharmacological properties. However, its role in epileptic seizures in adult mice and its underlying mechanism of action remain obscure. We aimed to explore the anti-epileptic effect and mechanism of Gent on lithium/pilocarpine (Pilo)-induced epilepsy seizures in mice. Methods: In this study, we established a lithium/Pilo-induced epilepsy model, and Gent was first given to mice 30 min before Pilo administration. Then, we detected behavioral and histopathological changes through electrocorticographic (ECoG) measurements, Nissl staining, Fluoro-Jade B (FJB) staining, and immunohistochemical staining. We then used molecular biology techniques, such as Western blotting, quantitative polymerase chain reaction (qPCR) analysis, and the enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms of Gent in lithium/Pilo-induced epileptic seizures in mice and lipopolysaccharide (LPS)-induced inflammatory astrocytes. Results: We confirmed that Gent could prevent abnormal ECoG activity, behavioral changes, and neurodegeneration. Subsequently, we found Gent could downregulate the factors that could promote apoptosis (i.e., the NR2B/CaMKII/CREB signaling cascade) and neuroinflammatory-related factors (i.e., the TLR4/NF-κB signaling cascade). Conclusions: Gent could be a potential therapeutic agent for epilepsy, offering possibilities for both prevention and treatment. Our research establishes a preliminary experimental framework for ongoing studies into Gent’s efficacy as a treatment for epilepsy.

Paroxysmal sympathetic hyperactivity syndrome after recurrent stroke: A case report

Paroxysmal sympathetic hyperactivity (PSH) is a state of autonomic dysfunction characterized by symptoms such as tachypnea, tachycardia, hypertension, hyperthermia, sweating, and dystonia. It can occur after traumatic brain injury, hypoxic-ischemic encephalopathy, and diseases such as stroke. Hypoxia, extensive axonal damage, and young age are believed to predispose to the development of PSH. These patients may be diagnosed with pulmonary embolism, septicemia, or epileptic seizures. Delays in diagnosis prolong hospital stay. Here, we present an 81-year-old man who developed PSH after a recurrent stroke and our management.

TRANscranial direct current stimulation for FOcal Refractory epilepsy in mitochondrial disease (TRANSFORM): delayed-start, randomised, double-blinded, placebo-controlled study

BackgroundFocal epilepsy is common in children and adults with mitochondrial disease. Seizures are often refractory to pharmacological treatment and, in this patient group, frequently evolve to refractory focal status epilepticus (also known as epilepsia partialis continua). Where this occurs, the long-term prognosis is poor. Transcranial DC stimulation (tDCS) is a promising, non-invasive, adjunctive treatment alternative to common surgical procedures. Limited recruitment of study participants with this rare disease and the ethical challenges of administering a treatment to one group and not another, while maintaining strict methodological rigour can pose challenges to the design of a clinical study.MethodWe designed the first delayed start, double-blinded, sham-controlled study to evaluate the efficacy of tDCS as an adjunctive treatment for focal epilepsy. We will include participants with a genetically confirmed diagnosis of mitochondrial disease with drug-resistant focal epilepsy aged ≥ 2 years, aiming to collect 30 episodes of focal status epilepticus, each treated for a maximum period of 14 days. The early start intervention arm will receive tDCS from day 1. The delayed start intervention arm will receive sham stimulation until crossover on day 3. Our primary endpoint is a greater than 50% reduction from baseline (on day 0) in seizure frequency assessed by 3x daily reporting, accelerometery, and video monitoring. Changes in the underlying epileptogenic focus within the brain related to the tDCS intervention will be assessed by magnetic resonance imaging (MRI) and/or electroencephalography (EEG).DiscussionStudy results in favour of treatment efficacy would support development of tDCS into a mainstream treatment option for focal epileptic seizures related to mitochondrial disease.Trials registrationISRCTN: 18,241,112; registered on 16/11/2021.