Development Of Epileptic Seizures Research Articles

A Comparison of Post-Stroke Seizure Rates in Patients Receiving IV Thrombolytic, Mechanical Thrombectomy, and Conventional Treatment Following Acute Ischemic Stroke

Objective: The incidence of epileptic seizures after a stroke falls within a range of 2.3-43%. Varying opinions exist in the literature concerning the association between thrombolytic therapy, endovascular interventions, and the development of epileptic seizures post-stroke. Material and Methods: Seizure rates were compared based on the treatment method (thrombolytic therapy, endovascular intervention, or conventional therapy) in patients experiencing acute ischemic stroke within a two-year period in the neurology and neurology intensive care unit. Patients were categorized into three groups: the first group received IV thrombolytic therapy, the second group underwent mechanical thrombectomy, and the third group received conventional therapy. The occurrence of epileptic seizures from hospitalization to discharge was compared. Results: IV thrombolytics were administered to 1.5% of patients, mechanical thrombectomy to 3.6%, and 94.9% received medical treatment. Epileptic seizures were observed in 0.9% of patients. No statistically significant relationship was found between the development of epileptic seizures and the treatment method for ischemic stroke. Furthermore, no statistically significant correlation was identified between the development of epileptic seizures and the modified Rankin score at discharge. Conclusion: Our findings align with existing studies. In conclusion, this retrospective study aimed to assess how the treatment method applied in acute ischemic stroke might influence the background of epileptic seizures.

A Pediatric Rat Model of Organophosphate-Induced Refractory Status Epilepticus: Characterization of Long-Term Epileptic Seizure Activity, Neurologic Dysfunction and Neurodegeneration.

Children are highly vulnerable to the neurotoxic effects of organophosphates (OPs), which can cause neuronal developmental defects, including intellectual disability, autism, epilepsy, and related comorbidities. Unfortunately, no specific pediatric OP neurotoxicity model currently exists. In this study, we developed and characterized a pediatric rat model of status epilepticus (SE) induced by the OP diisopropylfluorophosphate (DFP) and examined its impact on long-term neurological outcomes. Postnatal day 21 rats were exposed to a DFP regimen with standard antidotes. Progressive behavioral deteriorations were assessed over a three-month period. Development of epileptic seizures, ictal discharges, high-frequency oscillations (HFOs), and interictal spikes were monitored by video-electroencephalography recordings. Histology-stereology analysis was performed to assess neurodegeneration, neuroinflammation, and morphologic abnormalities. DFP-exposed, post-SE animals exhibited significantly elevated levels of anxiety and depression than age-matched controls at 1, 2, and 3 months post-exposure. DFP-exposed animals displayed aggressive behavior and a marked decline in object recognition memory, as well as prominent impairment in spatial learning and memory. DFP-exposed animals had striking electrographic abnormalities with the occurrence of displayed epileptic seizures, ictal discharges, HFOs, and interictal spikes, suggesting chronic epilepsy. Neuropathological analysis showed substantially fewer principal neurons and inhibitory interneurons with a marked increase in reactive microglia and neuroinflammation in the hippocampus and other brain regions. DFP-exposed animals also exhibited mossy fiber sprouting indicating impaired network formations. Long-term epileptic seizures and neuropsychiatric functional deficits induced by DFP were consistent with neuropathological defects. Collectively, this pediatric model displays many hallmarks of chronic sequelae reminiscent of children exposed to OPs, suggesting that it will be a valuable tool for investigating pathologic mechanisms and potential treatment strategies to attenuate long-term OP neurotoxicity. SIGNIFICANCE STATEMENT: Millions of children are exposed to organophosphates (OPs) used in agriculture or chemical incidents. This study investigated the long-term impact of neonatal exposure to the OP chemical diisopropylfluorophosphate (DFP) on neurobehavioral and neurodevelopmental outcomes in adulthood. DFP exposure caused long-lasting behavioral abnormalities, epileptic seizures, and bilateral brain defects with an array of neurological sequelae seen in children's OP neurotoxicity. Thus, this model provides a novel tool to explore therapeutic interventions that mitigate long-term neurotoxic effects of children exposed to OP-induced seizures and status epilepticus.

Modern treatment of epileptic encephalopathies in young children: improvement of precision medicine

Background. Treatment of epileptic seizures in young children, especially with epileptic encephalopathies (EE), is a difficult task, which is impossible in modern conditions without the use of a personified (precision) therapy. The diagnostic algorithm for EE must include genetic examination by the next-generation sequencing, which makes it possible to prescribe targeted therapy depending on the genetic etiology of the disorder. The article presents the results of own research on the effectiveness and approaches to targeted therapy of genetic epileptic encephalopathies in young children. Materials and methods. Fifty-eight children aged 0–3 years with clinical manifestations of epileptic encephalopathies, onset of seizures in the first year of life and diagnosed genetic etiology were included in the study. Pathogenic variants in genes associated with the development of epileptic seizures were identified in all children using the next-generation sequencing. The study included assessment of neurological status, history collection, evaluation of semiology and seizure type, development and screening for autism spectrum disorders at the age of 18 and 24 months, video-electroencephalography during night sleep, magnetic resonance imaging of the brain, assessment of antiepileptic treatment received by the child. Results. Of 58 children with EE who were prescribed antie­pileptic drugs, 10 (17.2 %) received monotherapy, 40 patients (69 %) received combined therapy with two anticonvulsants, and 8 children (13.8 %) — combined therapy with three or more anticonvulsants. Levetiracetam (31 patients), valproic acid salt preparations (20 cases), topiramate (11 children) and vigabatrin (10 cases) were most used antiepileptic drugs. In all examined patients with EE, we used schemes of targeted (persona­lized) antiepileptic therapy focused on the genetic etiology of the disorder. In children with tuberous sclerosis caused by mutations in the TSC1 and TSC2 genes, vigabatrin (50–150 mg/kg per day) was included in the antiepileptic therapy and showed efficacy in 75.0 % (9/12) of children with infantile spasms. Corticosteroids (adrenocorticotropic hormone or prednisone) were additionally included in the treatment regimen and showed effectiveness in 66.7 % of cases (4/6). In children with mutations in SCN1A gene, combined therapy including valproic acid, topiramate and clobazam, or valproic acid with levetiracetam and corticosteroids was used, which showed effectiveness in reducing the frequency of seizures in 100 % of cases. Conclusions. Epileptic encephalopathies are a heterogeneous group of genetic disorders in young children that are difficult to treat and often have a malignant course. Since standard antiepileptic drugs are often insufficiently effective in epileptic encephalopathies, the use of targeted therapy drugs and alternative treatments such as hormone therapy are extremely important. The goal of treatment for epileptic encephalopathies is not only to control seizures, but also to prevent the development of neurological and cognitive deficits and restore lost functions.

COMORBIDITY OF MULTIPLE SCLEROSIS AND EPILEPSY: MORE QUESTIONS OR ANSWERS?

The literature data of the last three decades on the problem of comorbidity of multiple sclerosis (MS) and epilepsy have been analyzed, such as issues of pathogenesis, clinical course, prognosis, and treatment of this dual pathology. Epileptic seizures occur in 2–3% to 5.9% of patients with MS, which is 3–6 times more common than in the general population. The incidence of epilepsy raises with increasing duration and severity of MS, with its progressive course, and also depends on the effect of drugs for the treatment of MS. There is no unanimity in the literature on the age and gender characteristics of the occurrence of epileptic seizures in MS. Probable mechanisms of MS comorbidity and epilepsy are analyzed. Data on certain common pathophysiology of MS and epilepsy and the concept according to which the model of epilepsy in MS is considered as a network disease are presented. Data on clinical manifestations and diagnosis of comorbid MS with epilepsy are presented. Epileptic seizures can occur at any stage of MS: before the clinical manifestations, at the onset of the disease, in the late stages, or can indicate exacerbation of MS. Types of epileptic seizures with a dual diagnosis (MS + epilepsy) are diverse. The majority of patients (up to 87.5%) have focal seizures (aware or unaware) or focal seizures to bilateral tonic-clonic, and a small share of patients have seizures of unknown origin. Most researchers believe that patients with MS and epilepsy have a more severe MS course and a worse long-term prognosis. The main directions of MS treatment and the impact of such treatment on the development of epileptic seizures are highlighted. Data on the effect of some disease-modifying drugs for the treatment of MS on the course of epilepsy and, on the other hand, on the impact of some antiseizure medications on the course of MS are presented. It is concluded that patients with MS have individual profiles and inter-individual variability of epileptogenicity. The principles of treatment of epileptic seizures/epilepsy in patients with MS are proposed.

The Protection by Vitamin E Against Tramadol-Induced Proconvulsant Effects and Brain Damage in Pentylenetetrazole-Induced Status Epilepticus in Rats

We investigated the effect of the opioid analgesic tramadol on the development of epileptic seizures and neuronal injury and the possible modulatory effect of vitamin E (Vit E) in rats with pentylenetetrazole (PTZ)-induced status epilepticus. Rats received repeated intraperitoneal (i.p.) injections of PTZ till the development of status epilepticus and were pretreated once with tramadol (30, 60 or 90 mg/kg), vitamin E (Vit E, 70 mg/kg) or both tramadol (90 mg/kg) and Vit E (70 mg/kg) prior to starting PTZ injections. Seizure scores, the latency time and the PTZ dose for each group required to reach status epilepticus were determined and histopathological examination of the brain tissue was done. Results indicated that tramadol produced both anticonvulsant and proconvulsant effects. The anticonvulsant effects of tramadol were observed for facial twitching (stage 1), convulsive body waves (stage 2), and myoclonic jerks and rearing (stage 3) and turn over onto one side position (stage 4) that were significantly inhibited by tramadol. In contrast, tonic-clonic convulsions (stage 5) were significantly increased by 60 or 90 mg/kg of tramadol as compared to PTZ control group. The mean latency and PTZ threshold dose for status epilepticus were markedly decreased after tramadol. The administration of Vit E exerted beneficial effects in decreasing epilepsy scores and increasing both the latency time and threshold dose of PTZ for reaching status epilepticus. Meanwhile, rats treated with both tramadol and Vit E exhibited significant increase in tonic-clonic convulsions and markedly shortened latency time to reach status epilepticus compared to those treated with only Vit E. In cerebral cortex and hippocampus, PTZ resulted in apoptotic cells, darkly stained degenerated and vacuolated neurons and gliosis. These pathological changes increased after tramadol but were markedly reduced by Vit E treatment. Collectively, these results suggest that: (i) tramadol exerts both anticonvulsant and proconvulsant effects; (ii) tramadol shortened the latency time and decreased the threshold dose of PTZ for evoking status epilepticus; (iii) PTZ-induced seizures and brain damage can be inhibited by Vit E; (iv) tramadol at high doses interferes with the effect of Vit E in inhibiting tonic-clonic convulsions and in reducing brain damage.

Application of Machine Learning Methods for Epilepsy Risk Ranking in Patients with Hematopoietic Malignancies Using.

Machine learning methods to predict the risk of epilepsy, including vascular epilepsy, in oncohematological patients are currently considered promising. These methods are used in research to predict pharmacoresistant epilepsy and surgical treatment outcomes in order to determine the epileptogenic zone and functional neural systems in patients with epilepsy, as well as to develop new approaches to classification and perform other tasks. This paper presents the results of applying machine learning to analyzing data and developing diagnostic models of epilepsy in oncohematological and cardiovascular patients. This study contributes to solving the problem of often unjustified diagnosis of primary epilepsy in patients with oncohematological or cardiovascular pathology, prescribing antiseizure drugs to patients with single seizure syndromes without finding a disease associated with these cases. We analyzed the hospital database of the V.A. Almazov Scientific Research Center of the Ministry of Health of Russia. The study included 66,723 treatment episodes of patients with vascular diseases (I10–I15, I61–I69, I20–I25) and 16,383 episodes with malignant neoplasms of lymphoid, hematopoietic, and related tissues (C81–C96 according to ICD-10) for the period from 2010 to 2020. Data analysis and model calculations indicate that the best result was shown by gradient boosting with mean accuracy cross-validation score = 0.96. f1-score = 98, weighted avg precision = 93, recall = 96, f1-score = 94. The highest correlation coefficient for G40 and different clinical conditions was achieved with fibrillation, hypertension, stenosis or occlusion of the precerebral arteries (0.16), cerebral sinus thrombosis (0.089), arterial hypertension (0.17), age (0.03), non-traumatic intracranial hemorrhage (0.07), atrial fibrillation (0.05), delta absolute neutrophil count (0.05), platelet count at discharge (0.04), transfusion volume for stem cell transplantation (0.023). From the clinical point of view, the identified differences in the importance of predictors in a broader patient model are consistent with a practical algorithm for organic brain damage. Atrial fibrillation is one of the leading factors in the development of both ischemic and hemorrhagic strokes. At the same time, brain infarction can be accompanied both by the development of epileptic seizures in the acute period and by unprovoked epileptic seizures and development of epilepsy in the early recovery and in a longer period. In addition, a microembolism of the left heart chambers can lead to multiple microfocal lesions of the brain, which is one of the pathogenetic aspects of epilepsy in elderly patients. The presence of precordial fibrillation requires anticoagulant therapy, the use of which increases the risk of both spontaneous and traumatic intracranial hemorrhage.

Neurophysiological and morphological features of the formation of the pathological hippocampal system in structural epilepsy (Literature review)

Modern scientific research shows that often violations of the structure and function of the hippocampus can lead to the onset of epilepsy. The hippocampal formation and the amygdala are important anatomical structures involved in the development of local discharges of epileptiform activity and temporal lobe epilepsy. It accounts for up to 25 % of all epileptic syndromes, and among locally caused symptomatic epilepsy — up to 60–70 %. At the same time, temporal lobe epilepsy is considered as a pathology with an initial imbalance of excitatory and inhibitory mechanisms of the neocortex, which occurs under the influence of various endoand exogenous factors during early embryogenesis. The scientific literature presents various pathophysiological theories of exactly how the hippocampus is involved in the development of epileptic seizures. Anatomically, the hippocampus has a relatively poor blood supply, and inhibitory interneurons are deep intraparenchymal structures, making them more susceptible to factors such as hypoxia, ischemia, and oxidative stress. This article addresses issues related not only to changes in the structure and function of the hippocampus, but also aspects of neu rophysiological diagnosis and prognosis. In addition, an evidence base is provided on the possibility of achieving remission of seizures after the use of neurosurgical methods of treatment.

The state of the lumen of the major cerebral vessels and systems of regulation of cerebral circulation in patients with cerebral ischemia with the development of epileptic seizures

Introduction. Cerebrovascular diseases are often associated with the development of epileptic seizures. It was suggested that in the implementation of epileptogenesis in patients with ischemic brain damage, a hemodynamic factor, namely the state of the perfusion reserve, may be important.Objective. The examination of the state of cerebrovascular reactivity of different cerebral vascular basins in patients with the development of epileptic seizures affected by cerebral ischemia.Materials and methods. 772 patients with acute and chronic cerebral ischemia (265 stroke patients with epileptic seizures and 174 patients with seizures on the background of chronic cerebral ischemia and 203 patients with stroke and 130 patients with chronic cerebral ischemia without seizures) was comprehensively examined.Results. In patients with cerebral ischemia, focal seizures prevail. Cortical localization of ischemic foci prevailed in patients with both acute and chronic cerebral ischemia. Stenosis of the main arteries were more often detected as in patients with ischemic stroke with the development of epileptic seizures – 218 (82.3%) compared with patients with stroke in the comparison group – 151 (74.4%) patients, р < 0.05), and in patients with CBI (chronic brain ischemia) with the development of epileptic seizures – 121 (69.5%) people, p < 0.05) compared with patients in the comparison group – 74 (56.9%) patients. The prevalence of stenosisof the main cerebral arteries was revealed in more than 70% in patients with pre-stroke epileptic seizures – 77 (33.5%) compared with patients without precursor seizures, who have been diagnosed with stenosis of more than 70% were found in only 4 (11.5%) patients (χ2 = 10.1; p = 0.03). In the comparison group of patients, there was no significant difference in CVR (cerebrovascular reactivity) changes in the carotid system and in the VBS (vertebrobasilar system) – 30 (36.6%) and 42 (47.7%) examined, respectively.Conclusion. The revealed decrease in cerebrovascular reactivity in the vertebrobasilar basin can be considered as one of the risk factors for the development of epilepsy in conditions of brain ischemia.

Структурно-морфометрические и клинико-энцефалографические особенности эпилепсии у больных в позднем восстановительном периоде ишемического инсульта (обзор литературы)

Актуальность. В последние годы во всех странах отмечается существенный рост заболеваемости эпилепсией у лиц старших возрастных групп. Одним из наиболее частых факторов риска развития эпилептических припадков являются цереброваскулярные заболевания. Считается, что 10–30 % впервые диагностированных эпилептических припадков у пациентов старше 60 лет возникают после инсульта, что в дальнейшем значительно усложняет клиническую картину заболевания и служит причиной ухудшения качества жизни больных, замедляет восстановление потерянных вследствие инсульта функций, усиливает когнитивные и мнестические расстройства, увеличивает риск внезапной смерти, что, в свою очередь, требует пересмотра проводимой терапии с учетом фармакологического взаимодействия препаратов. Кроме того, достоверно установлено, что эпилептический приступ, который дебютировал в возрасте старше 60 лет, значительно увеличивает риск первичного и повторного инсульта. Несмотря на длительный период изучения данной проблемы, диагностика постинсультной эпилепсии (ПИЭ) затруднена до настоящего времени в связи с отсутствием единой позиции относительно понимания патогенеза, разной дефиницией диагноза, необъективной интерпретацией межприступной (интериктальной) электроэнцефалографии. Цель: провести анализ литературных данных относительно структурно-морфометрических и клинико-энцефалографических особенностей эпилепсии у больных в разные периоды ишемического инсульта. Проанализировать вероятность риска дебюта ПИЭ. Материалы и методы. Про-анализированы имеющиеся публикации, касающиеся вопросов ПИЭ, с помощью поиска, проведенного по таким базам данных, как Кокрановская база систематических обзоров (CDSR), центральный реестр контролируемых исследований Кокрана (CENTRAL), база данных SCOPUS и MEDLINE. Были отобраны соответствующие рандомизированные контролируемые исследования, однако из-за нехватки обзорных исследований и метаанализа в работу включены, в частности, наблюдательные и эпидемиологические исследования. Результаты. В большинстве проанализированных исследований авторы показали большую вариабельность частоты развития ПИЭ. Высокая вариабельность объясняется особенностями течения инсульта в разных популяциях, разной дефиницией диагноза ПИЭ, различным дизайном проведенных исследований. Однако в большинстве исследований было установлено, что риск развития ПИЭ удваивается от первого до пятого года после перенесенного инсульта и составляет около 4,2–5 %. Выводы. Таким образом, изучение нейрофункциональных и структурно-морфометрических изменений у больных эпилепсией в позднем восстановительном периоде ишемического инсульта является важной проблемой клинической неврологии, многие аспекты которой имеют в настоящее время неоднозначные, нередко противоречивые толкования. Поэтому изучение данной взаимосвязи позволит лучше понять патогенез ПИЭ, расширит возможности ее терапии и диагностики.

Analysis of the role of viral encephalitis in the development of epileptic seizures and epilepsy

The aim – to determine the role of viral lesions of the central nervous system (CNS) in the development of epileptic seizures and epilepsy.Materials and methods: analysis of scientific literature data. The review discusses the role of non-epidemic viral encephalitis and human immunodeficiency virus in the development of acute epileptic seizures and epilepsy; epidemiological data and risk factors.Results. Viral infections are often complicated by acute (early) epileptic seizures and causes the risk of further epilepsy. The mechanisms of development of early and late seizures differ. Except herpetic encephalitis, in which risk of epilepsy in early seizures is up to 60 %, the risk of late seizures in other viral encephalitis hasn't been determined. Timely treatment of viral infections and early seizures reduces the risk of epilepsy. Treatment of epilepsy with infectious lesions of the central nervous system and other types of symptomatic epilepsy is similar, and the antiepileptic drug is determined by the semiology of seizures. The interaction between it and anti-infective drugs can change the concentration in the blood of each of them, which will lead to reduced effectiveness or toxicity. This is especially important for individuals with human immunodeficiency virus infection in whom antiretroviral drugs have significant interactions with antiepileptic drugs. Since epileptic activity of the brain is associated with the severity and complications of the underlying infection, early aggressive therapy prevents the development of late seizures and epilepsy.Conclusions. CNS infections account for 15 % of all newly diagnosed symptomatic epileptic seizures. The 20-year risk of unprovoked seizures and epilepsy after CNS infections ranges from 2.4 % to 22 %. The risk depends on the etiology, location of the lesion and the severity; it is high in herpes-associated encephalitis

ANALYSIS OF PECULIARITIES OF EPILEPTIC SEIZURES AND STRUCTURAL DAMAGES OF BRAIN IN PATIENTS WITH ISCHEMIC STROKE

The aim of the research: epilepsy on the background of ischemic stroke. Studied problem: improve of diagnosis of epilepsy on the background of ischemic stroke by establishing the clinical features of epileptic seizures and by detection of brain structural damages The main scientific results: a cross-sectional randomized cohort comparative study with retrospective and prospective stages was performed in 60 patients (men and women) with ischemic stroke aged 65 [57.0; 74.0] years, in 30 of which epileptic seizures were detected. The predominance of generalized single (66.7±38.5 %) variants was found in the structure of epileptic seizures in patients with acute cerebrovascular pathology. A higher frequency of generalized variants of seizures in patients over 60 years of age (maximum at 61–70 years, at descending – 71–80 years, over 80 years) has been revealed. The descending distribution of localization frequency of brain lesions (detected with MRI, CT) in patients with epileptic seizures after ischemic stroke is as follows: dilation of the subarachnoid space (93.3±24.1 %), dilation of the brain ventricles (83.3±34.0 %), subcortical ganglia (76.7±37.0 %), right hemisphere or temporal lobe (60.0±37.9 %), subcortex (56.7±37.3 %), frontal lobe (50.0±35.4 %), left hemisphere or diffuse-atrophic changes in the cortical region (43.3±32.6 %), temporal lobe (20.0±17.9 %), occipital lobe (16.7±15.2 %). The area of practical use of the research results: clinical medicine, especially neurology. Innovative technological product: methodology of diagnosis of epilepsy on the background of ischemic stroke. Scope of the innovative technological product: the evaluation of seizures and brain’s structural damages in patients with ischemic stroke with the development of epileptic seizures may be a means of improving the diagnosis of epilepsy on the background of cerebrovascular disease.

Platelets promote epileptic seizures by modulating brain serotonin level, enhancing neuronal electric activity, and contributing to neuroinflammation and oxidative stress.

The drugs currently available for treating epilepsy are only partially effective in managing this condition. Therefore, it is crucial to investigate new pathways that induce and promote epilepsy development. Previously, we found that platelets interact with neuronal glycolipids and actively secrete pro-inflammatory mediators during central nervous system (CNS) pathological conditions such as neuroinflammation and traumatic brain injury (TBI). These factors increase the permeability of the blood-brain barrier (BBB), which may create a predisposition to epileptic seizures. In this study, we demonstrated that platelets substantially enhanced epileptic seizures in a mouse model of pentylenetetrazole (PTZ) -induced seizures. We found that platelets actively secreted serotonin, contributed to increased BBB permeability, and were present in the CNS parenchyma during epileptic seizures. Furthermore, platelets directly stimulated neuronal electric activity and induced the expression of specific genes related to early neuronal response, neuroinflammation, and oxidative phosphorylation, leading to oxidative stress in neurons. The intracranial injection of physiological numbers of platelets that mimicked TBI-associated bleeding was sufficient to induce severe seizures, which resembled conventional PTZ-induced epileptic activity. These findings highlight a conceptually new role of platelets in the development of epileptic seizures, and indicate a potential new therapeutic approach targeting platelets to prevent and treat epilepsy.

Capsaicin Exerts Anti-convulsant and Neuroprotective Effects in Pentylenetetrazole-Induced Seizures.

The transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the development of epileptic seizures. We examined the effect of the TRPV1 agonist capsaicin on epileptic seizures, neuronal injury and oxidative stress in a model of status epilepticus induced in the rat by intraperitoneal (i.p.) injections of pentylenetetrazole (PTZ). Capsaicin was i.p. given at 1 or 2 mg/kg, 30 min before the first PTZ injection. Other groups were i.p. treated with the vehicle or the anti-epileptic drug phenytoin (30 mg/kg) alone or co-administered with capsaicin at 2 mg/kg. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1) activity, seizure scores, latency time and PTZ dose required to reach status epilepticus were determined. Histopathological assessment of neuronal damage was done. Results showed that brain MDA decreased by treatment with capsaicin, phenytoin or capsaicin/phenytoin. Nitric oxide decreased by capsaicin or capsaicin/phenytoin. GSH and PON-1 activity increased after capsaicin, phenytoin or capsaicin/phenytoin. Mean total seizure score decreased by 48.8% and 66.3% by capsaicin compared with 78.7% for phenytoin and 69.8% for capsaicin/phenytoin treatment. Only phenytoin increased the latency (115.7%) and threshold dose of PTZ (78.3%). Capsaicin did not decrease the anti-convulsive effect of phenytoin but prevented the phenytoin-induced increase in latency time and threshold dose. Neuronal damage decreased by phenytoin or capsaicin at 2 mg/kg but almost completely prevented by capsaicin/phenytoin. Thus in this model of status epilepticus, capsaicin decreased brain oxidative stress, the severity of seizures and neuronal injury and its co-administration with phenytoin afforded neuronal protection.

Abstract TP319: Risk Factors of Post-stroke Epilepsy

Purpose: The aim of the study was to identify the risk factors for seizures in patients with ischemic stroke using clinical, functional, neuroimaging research methods. Materials and methods: The results of the complex survey of 468 patients suffering from ischemic stroke (256 patients experienced epileptic seizures and 203 experienced no epileptic seizures) are presented. The diagnostic procedures included clinical evaluation, magnetic resonance imaging, electroencephalography, extracranial and transcranial Doppler sonography. In addition the assessment of the rate of sodium lithium countertransport (the marker of genetically determined on transport mechanisms of cell membranes) in patients with c ischemic stroke with the development of epileptic seizures and no seizures was carried out. Results: The focal seizures are the most common (92,5%). Cortical ischemic brain lesions prevailed in patients with seizures (81,1%), whereas in the control group cortex was affected in 38,9% patients (χ2=89.2, <0,001). Stenosis of cerebral arteries was more common in patients with epilepsy (82.3%) compared to patients without seizures (74.4%, <0.05). Reduced cerebrovascular reactivity (CVR) in vertebro-basilar basin was more frequently detected in patients with seizures (85.9%, p<0.001) compared to controls (71.6%). CVR < 10% was registered in 33.8% patients with seizures versus 13.4% controls (p<0.001). Patients with epileptic seizures showed cerebral perfusion reduction mostly in vertebro-basilar basin (85.9%) rather than in carotid basin (61.2%, p<0.001). Patients experienced epileptic seizures had high rates of sodium-lithium antitransport (> 346 μmol/liter cells x hour) more often than patients without epileptic seizures (52,6% and 35,5%, respectively, <0,05). Patients experienced epileptic seizures with high rates of sodium-lithium antitransport had a higher seizure frequency than patients with low rates of sodium-lithium antitransport. Conclusion: Thus, cortical ischemic brain lesions, significant stenosis of cerebral arteries, predominant perfusion reserve reduction in the posterior cerebral circulation, as well as a high rate of sodium lithium countertransport may be considered as risk factors for post-stroke epilepsy.

D-Serine Contributes to Seizure Development via ERK Signaling.

A seizure is one of the leading neurological disorders. NMDA receptor-mediated neuronal excitation has been thought to be essential for epileptogenesis. As an endogenous co-agonist of the NMDA receptor, D-serine has been suggested to play a role in epileptogenesis. However, the underlying mechanisms remain unclear. In the current study, we investigated the effects of antagonizing two key enzymes in D-serine metabolism on the development of seizures and the downstream signaling. Our results showed that serine racemase (SR), a key enzyme in regulating the L-to-D-serine conversion, was significantly up-regulated in hippocampal astrocytes in rats and patients who experienced seizure, in comparison with control rats and patients. L-aspartic acid β-hydroxamate (LaaβH), an inhibitor of SR, significantly prolonged the latencies of seizures, shortened the durations of seizures, and decreased the total EEG power in rats. In contrast, D-amino acid oxidase inhibitor 5-chlorobenzo[d]isoxazol-3-ol (CBIO), which can increase D-serine levels, showed the opposite effects. Furthermore, our data showed that LaaβH and CBIO significantly affected the phosphorylation of Extracellular Signal-regulated Kinase (ERK). Antagonizing or activating ERK could significantly block the effects of LaaβH/CBIO on the occurrence of seizures. In summary, our study revealed that D-serine is involved in the development of epileptic seizures, partially through ERK signaling, indicating that the metabolism of D-serine may be targeted for the treatment of epilepsy.

Clinical, neuroimaging and eeg correlations in epileptic syndrome in patients with a brain tumor

The results of the survey of 193 neuro-oncological patients with epileptic seizures are showed. The control group consisted of 97 patients with brain tumors without the development of epileptic seizures. It is found that in patients with the development of epileptic seizures as a first symptom of cerebral tumors predominated simple partial seizures. Early seizures occurred more frequently in lesions of the left hemisphere of the brain with the formation of focal abnormal EEG activity in the same hemisphere of the brain. Convulsive disorder prevailed in the localization of intracerebral tumors with caudal direction of its growth.

Serum magnesium in adult patients with idiopathic and symptomatic epilepsy in Maiduguri, Northeast Nigeria.

Alteration in the homeostasis of trace elements such as magnesium may play a role in the development of epileptic seizures. This study aims to investigate the levels of serum magnesium in people with idiopathic generalized epileptic (IGE) seizures and symptomatic seizures in Northeast Nigeria. Serum magnesium level was measured using atomic absorption spectrometry among 40 adults with IGE, 20 adults with symptomatic epileptic seizures, and 30 healthy controls. Serum calcium, potassium, phosphate, and albumin were also measured. The mean serum magnesium level was significantly lower among people with epilepsy compared with the controls [0.79 ± 0.18 mmol/L vs 0.90 mmol/L ± 0.17, P = 0.007, 95% confidence interval (CI): (-0.189 to -0.031)]. People with IGE had significantly lower levels of magnesium compared with those with symptomatic seizures [0.74 ± 0.17 mmol/L vs 0.9 ± 0.16 mmol/L, P < 0.001 95% CI: (-0.251 to -0.069)]. The mean magnesium level for all groups was in the reference range, but the lowest levels were observed in those with IGE. There is no significant correlation between the level of serum magnesium and the severity of seizure attacks. There was significantly lower level of calcium in people with IGE compared with those with symptomatic seizures [2.3 ± 0.13 mmol/L vs 2.4 ± 0.16 mmol/L, P = 0.012, 95% CI: (-0.177 to 0.023)] or controls [2.3 ± 0.13 mmol/L vs 2.4 ± 0.12 mmol/L, P < 0.01, 95% CI: (-0.156 to -0.044)]. No significant differences were observed in the levels of potassium, phosphate, and albumin. This study suggests that low serum magnesium and calcium may play a role in IGE, and supplementation may be useful in reducing seizures in Black patients with epilepsy.

Inhibition of Inwardly Rectifying Potassium (Kir) 4.1 Channels Facilitates Brain-Derived Neurotrophic Factor (BDNF) Expression in Astrocytes.

Inwardly rectifying potassium (Kir) 4.1 channels in astrocytes regulate neuronal excitability by mediating spatial potassium buffering. Although dysfunction of astrocytic Kir4.1 channels is implicated in the development of epileptic seizures, the functional mechanisms of Kir4.1 channels in modulating epileptogenesis remain unknown. We herein evaluated the effects of Kir4.1 inhibition (blockade and knockdown) on expression of brain-derived neurotrophic factor (BDNF), a key modulator of epileptogenesis, in the primary cultures of mouse astrocytes. For blockade of Kir4.1 channels, we tested several antidepressant agents which reportedly bound to and blocked Kir4.1 channels in a subunit-specific manner. Treatment of astrocytes with fluoxetine enhanced BDNF mRNA expression in a concentration-dependent manner and increased the BDNF protein level. Other antidepressants (e.g., sertraline and imipramine) also increased the expression of BDNF mRNA with relative potencies similar to those for inhibition of Kir4.1 channels. In addition, suppression of Kir4.1 expression by the transfection of small interfering RNA (siRNA) targeting Kir4.1 significantly increased the mRNA and protein levels of BDNF. The BDNF induction by Kir4.1 siRNA transfection was suppressed by the MEK1/2 inhibitor U0126, but not by the p38 MAPK inhibitor SB202190 or the JNK inhibitor SP600125. The present results demonstrated that inhibition of Kir4.1 channels facilitates BDNF expression in astrocytes primarily by activating the Ras/Raf/MEK/ERK pathway, which may be linked to the development of epilepsy and other neuropsychiatric disorders.

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy.

The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice.

The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amygdala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV). During amygdala kindling, behavioral changes (from stage 0 to stage 5) of mice were accompanied by after-discharges (ADs) of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. During seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with seizure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchronization were different.