Recurrent Seizures Research Articles

Expanding the Imaging Spectrum of Polymorphous Low-Grade Neuroepithelial Tumor of the Young in Children.

Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) are rare brain tumors first described in 2017 and recently included in the 2021 5th World Health Organization Classification of Tumors of the Central Nervous System. They typically affect children and young adults. Few pediatric cases have been reported in the literature. The most common imaging features described, include location within the temporal lobe, involvement of the cortical/subcortical region, coarse calcifications, and well-defined margins with solid and cystic morphology, with slight-or-no enhancement. However, there is limited information on imaging features in children. We present the imaging spectrum of neuroimaging features in a series of pediatric patients with a histologically and molecularly proved PLNTY diagnosis. Coarse calcifications are uncommon in children compared with the adult literature, and they may develop with time. The transmantle-like sign can be observed, and adjacent cortical dysplasia may be seen. Seizure recurrence may occur despite gross total resection of the tumor.

PTZ-kindled rat model; evaluation of seizure, hippocampal EGR-1, and Rev-erbα gene regulation, behavioral analysis, and antioxidant capacity of Gum Arabic.

Epilepsy is a neurological disease characterized by recurrent seizures, hyperexcitable neurons and various behavioral comorbidities. The electrical charge during seizures depletes the antioxidant defense mechanism in the epileptic brain and increases the oxidative burden. Natural antioxidant compounds are potential therapeutics in the treatment of two major pathologies of epilepsy with their anticonvulsant and anxiolytic effects and can modulate these targets. Gum Arabic is one of the natural plant polysaccharides that is non-toxic and biodegradable. A total of 30 Wistar albino male rats (8-12weeks, 350-500g), were randomly divided into 5 groups with 6 animals in each group: 1-Control, 2-Sham (Phosphate buffer saline (PBS)), 3-PTZ, 4-Gum Arabic, 5-PTZ + Gum Arabic. PTZ was administered i.p at 35mg/kg/day for 11days. After 48h, the injection was completed with 75mg/kg PTZ. Locomotor activity, immobilization, rearing, grooming, eating, and drinking behaviors were recorded with the LABORAS behavior system for 30min after kindling. Animals were treated with Gum Arabic (2mg/kg/day, oral gavage) for 10days. At the end of the period, animal behavior was recorded again. Then the hippocampus tissues were removed. Oxidative parameters (TAS and TOS), early growth response 1 (EGR1) and nuclear receptor subfamily 1 group D member 1 (Rev-erbα) gene expressions and behaviors were analyzed. Gum Arabic increased TAS levels (P = 0.000), decreased TOS levels (P = 0.000), and thus exhibited antioxidant properties by reducing oxidative stress burden. EGR1, which was upregulated in the seizure group, was downregulated after treatment (P = 0.000), and Rev-erbα was downregulated in seizure and upregulated after treatment (P = 0.000). Gum arabic may be an antiepileptic and anxiolytic therapeutic in improving epileptic seizures by reducing oxidative stress burden through EGR1 and Rev-erbα.0.

Cognitive and psychological dysfunction is present after a first seizure, prior to epilepsy diagnosis and treatment at a First Seizure Clinic.

Neuropsychological comorbidities found in chronic epilepsy have also been reported earlier in the disease course. However, recurrent seizures, antiseizure medication (ASM), and adjustment to a chronic diagnosis remain potential confounds of this literature. It thus remains unclear whether these comorbidities are primary or secondary attributes of epilepsy. To capture individuals as close to disease onset as possible, we studied the cognitive and psychological functioning in adults after their first seizure, yet prior to epilepsy diagnosis and treatment. Using a telehealth-based prospective design, we screened cognition, mood, and anxiety symptoms in adult patients referred to a First Seizure Clinic (FSC), who were over 18 years, English-speaking and not taking ASM. We screened cognition via telephone, and psychological symptoms via online questionnaires, all prior to the patients' diagnostic evaluation. Data were collected on 32 individuals subsequently diagnosed with epilepsy at the FSC, and 30 healthy controls from the community, who were matched to the epilepsy group for age, gender, and education. A multivariate analysis of variance revealed that the groups differed significantly on combined cognitive measures with a large effect size (F[1,56] = 5.75, p < 0.001, η2 = 0.45). Post-hoc analyses showed that performances on measures of verbal memory, working memory, and executive functions were significantly worse for the newly diagnosed epilepsy group than controls. The epilepsy group also exhibited higher rates of clinically significant depressive and anxiety symptoms. Cognitive and psychological dysfunction is prevalent in people with epilepsy as early as the first seizure event, before the influence of diagnosis, ASM and recurrent seizures. Their neuropsychological profile parallels that seen in chronic epilepsy, showing that this dysfunction is already present at the very onset of the disease. The current study demonstrates the viability of telehealth neuropsychological screening for all new epilepsy cases. The results of this study show, using telephone-based cognitive assessment and online questionnaires, that people with newly diagnosed epilepsy can experience problems with their thinking and memory skills, and low mood and anxiety, as early as after their first seizure. These issues are apparent at the very beginning of the disease, before an epilepsy diagnosis is made and before antiseizure medication is commenced, which suggests that they are due to the underlying brain disturbance, rather than the secondary effects of seizures, treatment, or lifestyle changes. Telehealth-screening of thinking skills and mental health for all new epilepsy cases is recommended to promote early management of such problems.

Clinical Implications of Various Electroencephalographic Patterns in Post-Stroke Seizures. The Utility of Routine Electroencephalogram.

Objective: Post-stroke seizures (PSS) are one of the major stroke-related complications. Early therapeutic interventions are critical therefore using electroencephalography (EEG) as a predictive tool for future recurrence may be helpful. We aimed to assess frequencies of different EEG patterns in patients with PSS and their association with seizure recurrence and functional outcomes. Methods: All patients admitted with PSS were included and underwent interictal EEG recording during their admission and monitored for seizure recurrence for 24 months. Results: PSS was reported in 106 patients. Generalized slow wave activity (GSWA) was the most frequent EEG pattern observed (n = 62, 58.5%), followed by Focal sharp wave discharges (FSWDs) (n = 57, 55.8%), focal slow wave activity (FSWA) (n = 56, 52.8%), periodic discharges (PDs) (n = 13, 12.3%), and ictal epileptiform abnormalities (n = 6, 5.7%). FSWA and ictal EAs were positively associated with seizure recurrence (p < .001 and p = .015 respectively) and it remained significant even after adjusting for age, sex, stroke severity, stroke subtype, or use of anti-seizure medications (ASMs). Other positive associations were status epilepticus (SE) (p = .015), and use of older ASM (p < .001). FSWA and GSWA in EEG were positively associated with severe functional disability (p = .055, p = .015 respectively). Other associations were; Diabetes Mellitus (p = .034), Chronic Kidney Disease (p = .002), use of older ASMs (p = .037), presence of late PSS (p = .021), and those with Ischemic stroke (p = .010). Conclusions: Recognition and documentation of PSS-related EEG characteristics are important, as certain EEG patterns may help to identify the patients who are at risk of developing recurrence or worse functional outcomes.

Oleaginous Microbial Lipids' Potential in the Prevention and Treatment of Neurological Disorders.

The products of oleaginous microbes, primarily lipids, have gained tremendous attention for their health benefits in food-based applications as supplements. However, this emerging biotechnology also offers a neuroprotective treatment/management potential for various diseases that are seldom discussed. Essential fatty acids, such as DHA, are known to make up the majority of brain phospholipid membranes and are integral to cognitive function, which forms an important defense against Alzheimer's disease. Omega-3 polyunsaturated fatty acids have also been shown to reduce recurrent epilepsy seizures and have been used in brain cancer therapies. The ratio of omega-3 to omega-6 PUFAs is essential in maintaining physiological function. Furthermore, lipids have also been employed as an effective vehicle to deliver drugs for the treatment of diseases. Lipid nanoparticle technology, used in pharmaceuticals and cosmeceuticals, has recently emerged as a biocompatible, biodegradable, low-toxicity, and high-stability means for drug delivery to address the drawbacks associated with traditional medicine delivery methods. This review aims to highlight the dual benefit that lipids offer in maintaining good health for disease prevention and in the treatment of neurological diseases.

Epileptiform electroencephalogram discharges increase seizure recurrence risk in patients with acute symptomatic seizure due to a structural brain lesion

ObjectiveThe risk factors for seizure recurrence after acute symptomatic seizure due to a structural brain lesion are not well established. The aim of this study was to analyze possible associations between demographic, clinical, and electroencephalographic variables and epilepsy development in patients with acute symptomatic seizure due to an acute structural brain lesion. MethodsWe designed an observational prospective study of patients with acute symptomatic seizure due to an acute structural brain lesion (hemorrhagic stroke, ischemic stroke, traumatic brain injury, or meningoencephalitis) who underwent EEG during their initial admission between January 2015 and January 2020. We analyzed prospectively recorded demographic, clinical, electroencephalographic (EEG), and treatment-related variables. All variables were compared between patients with and without seizure recurrence during 2 years of follow up. ResultsWe included 194 patients (41.2 % women; mean [SD] age, 57.3 [15.8] years) with acute symptomatic seizure due to an acute structural brain lesion. They all underwent EEG during admission and were followed for at least 2 years. The identifiable causes were hemorrhagic stroke (44.8 %), ischemic stroke (19.5 %), traumatic brain injury (18.5 %), and meningoencephalitis (17 %). Fifty-six patients (29 %) experienced a second seizure during follow-up. Seizure recurrence was associated with epileptiform discharges on EEG (52% vs 32 %; OR 2.3 [95 % CI, 1.2–4.3], p = 0.008) and onset with status epilepticus (17% vs 0.05 %, OR 4.03 [95 % CI 1.45–11.2], p = 0.009). ConclusionsEpileptiform discharges on EEG and status epilepticus in patients with acute symptomatic seizure due to an acute structural brain lesion are associated with a higher risk of epilepsy development.

Morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative patients with first unprovoked seizure.

The aim of the study was to evaluate the benefits of morphometric magnetic resonance imaging (MRI) postprocessing in patients presenting with a first seizure and negative MRI results and to investigate these findings in the context of the clinical and electroencephalographic data, seizure recurrence rates, and epilepsy diagnosis in these patients. We retrospectively reviewed 97 MRI scans of patients with first unprovoked epileptic seizure and no evidence of epileptogenic lesion on clinical routine MRI. Morphometric Analysis Program (MAP; v2018), automated postprocessing software, was used to identify subtle, potentially epileptogenic lesions in the three-dimensional T1-weighted MRI data. The resulting probability maps were examined together with the conventional MRI images by a reviewer who remained blinded to the patients' clinical and electroencephalographical data. Clinical data were prospectively collected between February 2018 and May 2023. Among the apparently MRI-negative patients, a total of 18 of 97 (18.6%) showed cortical changes suggestive of focal cortical dysplasia. Within the population with positive MAP findings (MAP+), seizure recurrence rates were 61.1% and 66.7% at 1 and 2 years after the first unprovoked seizure, respectively. Conversely, patients with negative MAP findings (MAP-) had lower seizure recurrence rates of 27.8% and 34.2% at 1 and 2 years after the first unprovoked seizure, respectively. Patients with MAP+ findings were significantly more likely to be diagnosed with epilepsy than those patients with MAP- findings (χ2 [1, n = 97] = 14.820, p < .001, odds ratio = 21.371, 95% CI = 2.710-168.531) during a mean follow-up time of 22.51 months (SD = 16.7 months, range = 1-61 months). MRI postprocessing can be a valuable tool for detecting subtle epileptogenic lesions in patients with a first seizure and negative MRI results. Patients with first seizure and MAP+ findings had high seizure recurrence rates, meeting the criteria for beginning epilepsy.

Postoperative interictal epileptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site

ObjectiveThe study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes...

Adrenergic receptor system as a pharmacological target in the treatment of epilepsy (Review).

Epilepsy is a complex and common neurological disorder characterized by spontaneous and recurrent seizures, affecting ~75 million individuals worldwide. Numerous studies have been conducted to develop new pharmacological drugs for the effective treatment of epilepsy. In recent years, numerous experimental and clinical studies have focused on the role of the adrenergic receptor (AR) system in the regulation of epileptogenesis, seizure susceptibility and convulsions. α1-ARs (α1A, α1B and α1D), α2-ARs (α2A, α2B and α2C) and β-ARs (β1, β2 and β3), known to have convulsant or anticonvulsant effects, have been isolated. Norepinephrine (NE), the key endogenous agonist of ARs, is considered to play a crucial role in the pathophysiology of epileptic seizures. However, the effects of NE on different ARs have not been fully elucidated. Although the activation of some AR subtypes produces conflicting results, the activation of α1, α2 and β receptor subtypes, in particular, produces anticonvulsant effects. The present review focuses on NE and ARs involved in epileptic seizure formation and discusses therapeutic approaches.

Febrile Seizures: An Updated Narrative Review for Pediatric Ambulatory Care Providers.

While generally self-limited, febrile seizures result in significant familial distress. Ambulatory pediatric care providers must be prepared to counsel families on the causes, risk factors, management principles, and prognosis of children with febrile seizures. To provide an updated, evidence-based review of febrile seizures focused on the needs of an ambulatory pediatric care provider. A narrative review of the literature prioritizing landmark articles, metanalyses, longitudinal population longitudinal cohort studies and national level guidelines. Febrile seizures are aberrant physiological responses to fever in children caused by complex interactions of cytokine mediated neuroinflammation, environmental triggers, and genetic predisposition. Other than investigations to determine fever etiology, routine bloodwork, lumbar punctures, neuroimaging and electroencephalograms are low yield. The general prognosis is excellent, however, clinicians should be aware of long-term outcomes including: cognitive impairment with non-simple febrile seizures; neuropsychiatric associations; recurrent febrile seizure and epilepsy risk factors; and the association between complex febrile seizures and sudden unexpected death. Children with a high risk of recurrence, complex febrile seizures, limited access to care, or extreme parental anxiety may benefit from intermittent oral diazepam prophylaxis. Clinicians should consider four management priorities: 1) terminating the seizure; 2) excluding critical differential diagnoses; 3) investigating fever etiology; and 4) providing adequate counselling to families. The clinical approach and prognosis of febrile seizure can be based on subtype. Children with non-simple (i.e. complex or febrile status epilepticus) febrile seizures require closer care than the vast majority of children with simple febrile seizures, who have excellent outcomes.

Ketogenic diet in pharmacoresistant epilepsies: a clinical nutritional assessment.

Epilepsies are among the most prevalent chronic neurological diseases, usually beginning in childhood. About 30% of children with epilepsies develop seizures that are difficult to control with medication. Recurrent epileptic seizures hinder diet intake, impairing the nutritional status. Although non-pharmacological interventions (e.g., ketogenic diet therapy) can improve epileptic seizure frequency, few studies analyzed their impact on the nutritional status of children and adolescents with epilepsies. The aim was to evaluate the effects of a ketogenic diet on the nutritional status and clinical course of patients with pharmacoresistant epilepsies. This cross-sectional study included patients under 18 years of age followed up at the Ketogenic Diet Ambulatory Clinic of the Instituto de Medicina Integral Prof. Fernando Figueira between December 2015 and December 2021. Socioeconomic, clinical, nutritional, and laboratory data were collected from medical records at different time points during the ketogenic diet. The sample comprised 49 patients aged between 5 months and 17 years (median = 4.4 years), mostly male (62.1%), and from Recife and the metropolitan region (51%). Underweight patients (BMI-for-age) improved their nutritional status in six months. However, patients who were normal weight and overweight maintained their nutritional status. Dyslipidemia was a common and short-term adverse effect. Moreover, the treatment decreased epileptic seizure frequency and antiseizure medication intake. The ketogenic diet prevented malnutrition from worsening and reduced epileptic seizures and antiseizure medication intake.

Intra-adrenal Paraganglioma and Paraaortic Paraganglioma in 15 Years Old Boys

Intra-adrenal paraganglioma (also called pheochromocytoma) is a chromaffin cell tumor that arises in the adrenal medulla and produces excess catecholamines. Paraganglioma can also be located in the extra-adrenal area. The incidence rate of intra-adrenal and extra-adrenal paraganglioma is about 1 case per 2.500-6.500 population, highest incidence at 40-50 years old, and distribution is the same in males and females. Intra-adrenal paraganglioma in pediatrics is more familial, bilateral, multifocal, and malignant. In children, the incidence rate of these tumors was 8.86%, the ratio of boys to girls was 2:1, and the average age of 11. This article reports a case, of a 15 years old boy with severe headaches, recurrent seizures, and a hypertension crisis (143/103-220/110 mmHg). MSCT scan of abdominal showed solid mass heterogeneous with central necrotic multiple in the supero-anterior of the left and right kidneys and on the right anterolateral aorta as high as CV L2, impressive adrenal gland mass and extra-adrenal, suspect pheochromocytoma. Performed surgery, routine histopathological examination, and Immunohistochemistry. Macroscopic examination showed an oval round shape mass of left and right adrenal tumors as well as the paraaortic, a smooth outer surface of the capsular, with yellowish brown color mass tumor at cut surface, supple consistency. Microscopic examination showing adrenal gland and paraaortic tissue with fibrous capsule contains proliferation of neoplastic cells forming a nested alveolar (Zellballen) pattern with a round oval to polygonal cells, granular eosinophilic cytoplasm, round oval nuclei, surrounded by sustentacular cells. Chromogranin A and S-100 are positive. The case was concluded by clinical findings, histopathological, and immunohistochemistry as intra-adrenal paraganglioma and paraganglioma of paraaortic.

The Influence of Health Education Using Animattion Video Media on the Level of Knowledge of Mothers About the Management of February Seizures in Toddlers

Improper handling of children with febrile seizures has an impact on the occurrence of recurrent febrile seizures or complications can occur. Several factors influence a person's knowledge, namely the provision of health education. Supporting media is important in delivering health education. The purpose of this study was to analyze the effect of health education on the level of mother's knowledge about the cruel treatment of fever in toddlers. The research design was (one-group pre-post test design). The number of samples in this study were 54 mothers who came to Posyandu Dahlia, Kerjen Village. This research was conducted on May 10, 2023. The research instrument used SAP, animated videos and pre-test questionnaires. The results of this study show that based on the results of the Wilcoxon Signed Rank Test statistical test at the pretest and post-test a p-value of 0.000 or &lt;0.05, then Ho was rejected and Ha was accepted, which means that there is an influence in providing health education using animated videos on the level of mother's knowledge about handling febrile seizures in toddlers. It is hoped that the results of this study can be used as material for evaluation and information in supporting Pediatric Nursing regarding the management of damam seizures in toddlers.Keywords: Knowledge, media, febrile seizure

The Influence of Health Education Using Animattion Video Media on the Level of Knowledge of Mothers About the Management of February Seizures in Toddlers

Improper handling of children with febrile seizures has an impact on the occurrence of recurrent febrile seizures or complications can occur. Several factors influence a person's knowledge, namely the provision of health education. Supporting media is important in delivering health education. The purpose of this study was to analyze the effect of health education on the level of mother's knowledge about the cruel treatment of fever in toddlers. The research design was (one-group pre-post test design). The number of samples in this study were 54 mothers who came to Posyandu Dahlia, Kerjen Village. This research was conducted on May 10, 2023. The research instrument used SAP, animated videos and pre-test questionnaires. The results of this study show that based on the results of the Wilcoxon Signed Rank Test statistical test at the pretest and post-test a p-value of 0.000 or &lt;0.05, then Ho was rejected and Ha was accepted, which means that there is an influence in providing health education using animated videos on the level of mother's knowledge about handling febrile seizures in toddlers. It is hoped that the results of this study can be used as material for evaluation and information in supporting Pediatric Nursing regarding the management of damam seizures in toddlers.Keywords: Knowledge, media, febrile seizure

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderateand severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Interleukins in Epilepsy: Friend or Foe.

Epilepsy is a chronic neurological disorder with recurrent unprovoked seizures, affecting ~ 65million worldwide. Evidence in patients with epilepsy and animal models suggests a contribution of neuroinflammation to epileptogenesis and the development of epilepsy. Interleukins (ILs), as one of the major contributors to neuroinflammation, are intensively studied for their association and modulatory effects on ictogenesis and epileptogenesis. ILs are commonly divided into pro- and anti-inflammatory cytokines and therefore are expected to be pathogenic or neuroprotective in epilepsy. However, both protective and destructive effects have been reported for many ILs. This may be due to the complex nature of ILs, and also possibly due to the different disease courses that those ILs are involved in. In this review, we summarize the contributions of different ILs in those processes and provide a current overview of recent research advances, as well as preclinical and clinical studies targeting ILs in the treatment of epilepsy.

Tuning Microelectrodes' Impedance to Improve Fast Ripples Recording.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from abnormal neuronal hyperexcitability. In the case of pharmacoresistant epilepsy requiring resection surgery, the identification of the Epileptogenic Zone (EZ) is critical. Fast Ripples (FRs; 200-600 Hz) are one of the promising biomarkers that can aid in EZ delineation. However, recording FRs requires physically small electrodes. These microelectrodes suffer from high impedance, which significantly impacts FRs' observability and detection. In this study, we investigated the potential of a conductive polymer coating to enhance FR observability. We employed biophysical modeling to compare two types of microelectrodes: Gold (Au) and Au coated with the conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (Au/PEDOT:PSS). These electrodes were then implanted into the CA1 hippocampal neural network of epileptic mice to record FRs during epileptogenesis. The results showed that the polymer-coated electrodes had a two-order lower impedance as well as a higher transfer function amplitude and cut-off frequency. Consequently, FRs recorded with the PEDOT:PSS-coated microelectrode yielded significantly higher signal energy compared to the uncoated one. The PEDOT:PSS coating improved the observability of the recorded FRs and thus their detection. This work paves the way for the development of signal-specific microelectrode designs that allow for better targeting of pathological biomarkers.

Adenosine kinase gene modified mesenchymal stem cell transplantation retards seizure severity and associated cognitive impairment in a temporal lobe epilepsy rat model

PurposeTemporal lobe epilepsy (TLE) has a high risk of developing drug resistant and cognitive comorbidities. Adenosine has potential anticonvulsant effects as an inhibitory neurotransmitter, but drugs targeting its receptors and metabolic enzyme has inevitable side effects. Therefore, we investigated adenosine augmentation therapy for seizure control and cognitive comorbidities in TLE animals. MethodsUsing lentiviral vectors coexpressing miRNA inhibiting the expression of adenosine kinase (ADK), we produced ADK--rMSC (ADK knockdown rat mesenchymal stem cell). ADK--rMSC and LV-con-rMSC (rMSC transduced by randomized scrambled control sequence) were transplanted into the hippocampus of TLE rat respectively. ADK-+DPCPX group was transplanted with ADK--rMSC and intraperitoneally injected with DPCPX (adenosine A1 receptor antagonist). Seizure behavior, EEG, CA1 pyramidal neuron apoptosis, and behavior in Morris water maze and novel object recognition test were studied ResultsAdenosine concentration in the supernatants of 105 ADK--rMSCs was 13.8 ng/ml but not detectable in LV-con-rMSCs. ADK--rMSC (n = 11) transplantation decreased spontaneous recurrent seizure (SRS) duration compared to LV-con-rMSC (n = 11, P < 0.05). CA1 neuron apoptosis was decreased in ADK--rMSC (n = 3, P < 0.05). ADK--rMSC (n = 11) improved the Morris water maze performance of TLE rats compared to LV-con-rMSC (n = 11, escape latency, P < 0.01; entries in target quadrant, P < 0.05). The effect of ADK--rMSC on neuron apoptosis and spatial memory were counteracted by DPCPX. However, ADK--rMSC didn’t improve the performance in novel object recognition test. ConclusionAdenosine augmentation-based ADK--rMSC transplantation is a promising therapeutic candidate for TLE and related cognitive comorbidities.

Indirect structural changes and reduced controllability after temporal lobe epilepsy resection.

To understand the potential behavioral and cognitive effects of mesial temporal resection for temporal lobe epilepsy (TLE) a method is required to characterize network-wide functional alterations caused by a discrete structural disconnection. The objective of this study was to investigate network-wide alterations in brain dynamics of patients with TLE before and after surgical resection of the seizure focus using average regional controllability (ARC), a measure of the ability of a node to influence network dynamics. Diffusion-weighted imaging (DWI) data were acquired in 27 patients with drug-resistant unilateral mesial TLE who underwent selective amygdalohippocampectomy. Imaging data were acquired before and after surgery and a presurgical and postsurgical structural connectome was generated from whole-brain tractography. Edge-wise strength, node strength, and node ARC were compared before and after surgery. Direct and indirect edge-wise strength changes were identified using patient-specific simulated resections. Direct edges were defined as primary edges disconnected by the resection zone itself. Indirect edges were secondary measured edge strength changes. Changes in node strength and ARC were then related to both direct and indirect edge changes. We found nodes with significant postsurgical changes in both node strength and ARC surrounding the resection zone (paired t tests, p < .05, Bonferroni corrected). ARC identified additional postsurgical changes in nodes outside of the resection zone within the ipsilateral occipital lobe, which were associated with indirect edge-wise strength changes of the postsurgical network (Fisher's exact test, p < .001). These indirect edge-wise changes were facilitated through the "hub" nodes including the thalamus, putamen, insula, and precuneus. Discrete network disconnection from TLE resection results in widespread structural and functional changes not predicted by disconnection alone. These can be well characterized by dynamic controllability measures such as ARC and may be useful for investigating changes in brain function that may contribute to seizure recurrence and behavioral or cognitive changes after surgery.

Guidelines and epilepsy practice: Antiseizure medication initiation following an unprovoked first seizure in adults

ObjectivesAdherence rate to evidence-based clinical practice guidelines is relatively low and the impact of guidelines on clinical practice in epilepsy is variable. The 2015 practice guideline on the management of an unprovoked first seizure in adults specifies clinical variables associated with increased risk of seizure recurrence and the impact of immediate antiseizure medication (ASM) treatment on seizure outcome.We aimed to evaluate the impact of the evidence-based guideline for the management of an unprovoked first seizure in adults on clinical practice in our adult neurology department. MethodsWe retrospectively reviewed the computerized database of 169 adult patients admitted to the adult neurology department at Shamir-Assaf Harofeh Medical Center following a first unprovoked seizure between October 2011 and October 2018. ResultsASMs were initiated in 86% of patients with a first unprovoked seizure pre- and in all patients admitted post- guideline publication. Monotherapy and use of old generation ASMs were more common in both groups and a combination of old- and new generation ASMs - among the pre-guideline group. The pre-guideline decision to initiate ASM treatment was significantly influenced only by epileptiform discharges in the electroencephalogram (EEG). DiscussionThis is the first study to evaluate the impact of the 2015 practice guideline on the initiation of ASM treatment after a first unprovoked seizure in adults. Further studies are needed to assess the global contribution of the guideline to clinical practice and its impact on patient outcomes.