Development Of Seizures Research Articles

Levetiracetam Prophylaxis Therapy for Brain Tumor-Related Epilepsy (BTRE) Is Associated With a Higher Psychiatric Burden

Purpose: Brain tumor-related epilepsy (BTRE) is a condition characterized by the development of seizures in the context of an undergoing oncological background. Levetiracetam (LEV) is a third-generation anti-seizure medication (ASM) widely used in BTRE prophylaxis. The study evaluated LEV neuropsychiatric side effects (SEs) in BTRE prophylaxis.Method: Twenty-eight patients with brain tumors were retrospectively selected and divided into two groups. In one group, we evaluated patients with a BTRE diagnosis using LEV (BTRE-group). The other group included patients with brain tumors who never had epilepsy and used a prophylactic ASM regimen with LEV (PROPHYLAXIS-group). Neuropsychiatric SEs of LEV were monitored using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at the baseline visit and the 6- and 12-month follow-up.Results: Eighteen patients of the BTRE-group and 10 patients of the PROPHYLAXIS-group were included. Compared to the BTRE-group, the PROPHYLAXIS-group showed a higher severity of neuropsychiatric symptoms. According to Linear Mixed Models (LMM), a multiplicative effect was observed for the interaction between group treatment and time. For the caregiver distress score (CDS), only a time-effect was observed.Conclusion: Prophylactic ASM with LEV is associated with an increased frequency of neuropsychiatric SE. Accurate epileptological evaluations in patients with brain tumors are mandatory to select who would benefit most from ASM.

Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells.

DL-3-n-butylphthalide promotes hippocampal neurogenesis and reduces mossy fiber sprouting in chronic temporal lobe epilepsy rats

BackgroundA decrease in hippocampal neurogenesis is considered an important cause of cognitive impairment, while changes in mossy fiber sprouting are closely related to development of spontaneous recurrent seizures in chronic temporal lobe epilepsy (TLE). Racemic l-3-n-butylphthalide (DL-NBP) can alleviate cognitive impairment in ischemic stroke and Alzheimer’s disease by promoting neurogenesis. DL-NBP treatment can also improve cognitive function and reduce seizure incidence in chronic epileptic mice. However, the mechanisms of action of DL-NBP remain unclear. The aim of the present study was to examine the effects of DL-NBP on mossy fiber sprouting, hippocampal neurogenesis, spontaneous epileptic seizures, and cognitive functioning in the chronic phase of TLE.MethodsNissl staining was used to evaluate hippocampal injury, while immunofluorescent staining was used to analyze hippocampal neurogenesis. The duration of spontaneous seizures was measured by electroencephalography. The Morris water maze was used to evaluate cognitive function. Timm staining was used to assess mossy fiber sprouting.ResultsTLE animals showed reduced proliferation of newborn neurons, cognitive dysfunction, and spontaneous seizures. Treatment with DL-NBP after TLE increased the proliferation and survival of newborn neurons in the dentate gyrus, reversed the neural loss in the hippocampus, alleviated cognitive impairments, and decreased mossy fiber sprouting and long-term spontaneous seizure activity.ConclusionsWe provided pathophysiological and morphological evidence that DL-NBP might be a useful therapeutic for the treatment of TLE.

MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy

Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium–pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy.

In-silico, Antioxidant and Antiepileptic Effect of N(2,3-methylenedioxy-4benzoyloxy-phenthylamine)-3,4-dimethyl-1, propanoamide Derivatives

Epilepsy is a severe neurological illness that affects millions of people the globally and is characterized by unpredicted and intermittent seizures.This research aimed to investigate the antiepileptic and antioxidant properties of papaverine derivatives using in-silico, in-vitro, and in-vivo methods.Epileptic seizure was induced in Swiss albino mice of either gender by administering PTZ (pentylenetetrazol). The antioxidant potential of test compounds was computed using previously published DPPH assay methods with minor modifications, while In-silico experiments were conducted using Auto-dock Vina (1.5.6) software and post dock analysis was completed using Discovery Studio Visualizer. The results showed that both compounds have strong antioxidant potential, with a noticeable change in color when compared to ascorbic acid as a control, and very low mortality when anti-epileptic potential was observed. The development of seizures was greatly delayed at first, but after 30 minutes of PTZ, they were completely gone. Both synthesized derivatives also comply the andquot;Lipinskiand#39;s rule of 5andquot;, which states that after structural alterations, extensive investigations, and trials, the chemical products would be evaluated for epilepsy management in the future In-silico investigations demonstrated that ligands with sufficient hydrogen bonds, pi-pi bonds, and Vander-Waals forces have a suitable propensity to engage with the binding pocket of selected protein targets. The current investigation of papaverine derivatives and their binding affinities against gamma aminobutyric acid (GABA) protein may have a vital function in epilepsy aetiology, according to the results of the studies. H1 and H2 were further verified in vivo for their anticonvulsant and antioxidant therapeutic potential. This could lead to more research into neurological problems.

Involvement of Glutamine Synthetase in the Development of Hyperbaric Oxygen Seizures

Involvement of Glutamine Synthetase in the Development of Hyperbaric Oxygen Seizures

Role of pericytes in the development of late-onset posttraumatic seizure.

Role of pericytes in the development of late-onset posttraumatic seizure.

Assessment of Integrated Antioxidant Systems and Hormezis Effect of Radon in Experimental Studies

According to our research, the use of radon inhalation in experimental animals, particularly in genetically determined rats with epileptic seizures, altered all parameters of the epileptic seizure development picture, namely the hidden period, the first and second wild jog duration after the audiogenic signal. On the third day, no response to the audiogenic signal was observed at all, and not even a single episode of tonic-clonic seizures. All mentioned suggest that radon inhalation could be used to treat epilepsy. Presented study is the first precedent of attempt R-Ho through inhalation for treatment of epileptic seizures in animal models with further translation to clinical study in humans through pilot phase II study. More profound and scientifically systematized approach is needed to determine uniqueness of Tskhaltubo water springs, great importance investigation of the mechanisms of radon effects on the excitatory and inhibitory functioning of CNS and further clinical studies to establish its effect on humans.

Novel urinary markers: taurine, dopamine and L-fucose levels in predicting neonatal seizures

Introduction and Aim: Neonatal seizure is an age specific neurological emergency. Their unique pathophysiological mechanism has become subject of interest for many research studies. The recurrence risk for seizures is high during neonatal period and currently used treatment strategies have limited efficacy in preventing it. From past decades although the treatment has not changed, there is a gradual progress in various mechanisms that are involved in generation of seizures and their response to anti-epileptics. With the emergence of new biochemical parameters for risk assessment in patients with seizures, there is a strong need for their comparative evaluation in order to evaluate their potential clinical application. So, this study was carried out to compare the urine levels of taurine, dopamine and fucose in assessing their role in mechanism of seizure. Materials and Methods: After obtaining ethical approval and consent from parents total 43 neonates, urine taurine, dopamine and fucose were measured in 24 cases of seizures and 19 apparently healthy normal controls. Dopamine and Taurine were measured using ELISA and L-fucose by Dische and Shettles method. Results: The median level of urine fucose was significantly higher in male neonates, taurine was significantly decreased in cases compared to that of controls. Males had higher preponderance to develop seizures. The median levels of urine dopamine were high in cases compared to controls but has not showed any significance. Conclusion: Amino acid like taurine, carbohydrate moiety like fucose and a neuromodulator like dopamine may have a mechanistic role in development of seizures in neonatal period.

Limbic Encephalitis Associated with COVID-19

Limbic encephalitis (LE) is an inflammatory disease of the brain, in which lesion is anatomically limited in structures of the limbic system. In some cases, LE can start with symptoms of limbic dysfunction with further involvement of other regions of the brain. Classic LE syndrome includes such symptoms as the development of personality disorders, depression, sleep disorders, epileptic seizures, hallucinations and cognitive disorders (short-term and long-term memory impairment). The information of clinical examination, electroencephalogram (EEG), magnetic resonance imaging (MRI) and cerebrospinal fluid studies (CSF) suggest the diagnosis of LE in most patients with Coronavirus Disease 2019 (COVID-19).

Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy.

Post-stroke Epilepsy (PSE) is one of the most common forms of acquired epilepsy, especially in the elderly population. As people get increasingly older, the number of stroke patients is expected to rise and concomitantly the number of people with PSE. Although many patients are affected by post-ischemic epileptogenesis, not much is known about the underlying pathomechanisms resulting in the development of chronic seizures. A common hypothesis is that persistent neuroinflammation and glial scar formation cause aberrant neuronal firing. Here, we summarize the clinical features of PSE and describe in detail the inflammatory changes after an ischemic stroke as well as the chronic changes reported in epilepsy. Moreover, we discuss alterations and disturbances in blood-brain-barrier leakage, astrogliosis, and extracellular matrix changes in both, stroke and epilepsy. In the end, we provide an overview of commonalities of inflammatory reactions and cellular processes in the post-ischemic environment and epileptic brain and discuss how these research questions should be addressed in the future.

Synthesis of novel thiazolidinic-phthalimide derivatives evaluated as new multi-target antiepileptic agents

Epilepsy is a disease that affects millions of people around the globe and has a multifactorial cause. Inflammation is a process that can be involved in the development of seizures. Thus, the present study proposed the design and synthesis of new candidates for antiepileptic drugs that would also control the inflammatory process. Nine new derivatives of the substituted thiazophthalimide hybrid core were obtained with satisfactory purity ≥99% and yields between 27% and 87%. All compounds showed cell viability values greater than 90% in the culture of PBMC cells from healthy volunteers and, therefore, were not considered cytotoxic. These compounds modulated proinflammatory cytokines IFN-y and IL-17A and can mitigate inflammation. Acute toxicity studies of compound 7i in an animal model indicated that the compound has low toxicity and an LD50 greater than 2 g/kg in healthy adult rats. The same compound did not show positive results for anticonvulsant activity through the PTZ test. However, 7i demonstrates the interaction with the target GABA-A receptor in silico, indicating a possible activity as an agonist of that receptor. Thus, further studies are needed to investigate the anticonvulsant activity, in particular, using models in which the inflammatory process triggers epileptic seizures.

Incident epilepsy in the cognitively normal geriatric population, irrespective of seizure control, impairs quality of life

Purpose of the researchThe geriatric population is the fastest-growing population in the United States and the impact of incident epilepsy on the cognitively intact geriatric population is not well-studied. Understanding how epilepsy affects the elderly is important to improve the quality of treatment and care for our aging population. This study sought to address the impact of incident epilepsy on the perceived Quality of Life (QOL) in cognitively intact elderly using the SF-36 questionnaire. MethodsNine hundred and twenty-seven participants were assessed from a community-based cohort. Based on a history of subsequent development of new-onset seizures, participants were divided into two groups, an incident seizure group that developed new-onset seizures after 65 years of age and the control group without incident seizures. Of this, six hundred eleven were analyzed with the SF-36 questionnaire after excluding for cognitive decline and inconsistent medical data. Principal resultsStatistically significant differences were found in 9 items on SF-36, involving perception of increased physical disability (p < 0.01; t-test), frailty (p < 0.04; t-test), emotional health limitations (p < 0.03; t-test), anxiety and sadness (p < 0.04; t-test), problems interfering with social activities (p < 0.0001; t-test). No between-group differences were found for demographic variables including age, education, gender, or minority status. Among the 611 subjects who remained cognitively normal across all longitudinal visits, 12 reported a history of new-onset seizures. Ten of these 12 subjects were seizure free as a result of treatment, with only 2 experiencing recent seizures. The incidence of seizures in our population was 300 per 100,000 person years. Major conclusionsThis study identified the elderly population with incident epilepsy as a subgroup with an unmet health need, and healthcare professionals should address the potential impact of seizures with their geriatric patients to ensure comprehensive care.

How Is the Norepinephrine System Involved in the Antiepileptic Effects of Vagus Nerve Stimulation?

Vagus Nerve Stimulation (VNS) is an adjunctive treatment for patients suffering from inoperable drug-resistant epilepsy. Although a complete understanding of the mediators involved in the antiepileptic effects of VNS and their complex interactions is lacking, VNS is known to trigger the release of neurotransmitters that have seizure-suppressing effects. In particular, norepinephrine (NE) is a neurotransmitter that has been associated with the clinical effects of VNS by preventing seizure development and by inducing long-term plastic changes that could restore a normal function of the brain circuitry. However, the biological requisites to become responder to VNS are still unknown. In this review, we report evidence of the critical involvement of NE in the antiepileptic effects of VNS in rodents and humans. Moreover, we emphasize the hypothesis that the functional integrity of the noradrenergic system could be a determining factor to obtain clinical benefits from the therapy. Finally, encouraging avenues of research involving NE in VNS treatment are discussed. These could lead to the personalization of the stimulation parameters to maximize the antiepileptic effects and potentially improve the response rate to the therapy.

Frequency, Predictors, and Outcome of Seizures in Patients With Myelomeningocele: Single-Center Retrospective Cohort Study.

To determine the frequency, predictors, and outcomes of seizures in patients with myelomeningocele, we retrospectively analyzed the data from patients with myelomeningocele followed longitudinally at a single center from 1975 to 2013. We identified a total of 122 patients (61% female). The mean follow-up duration was 11.1 years (minimum-maximum = 0-34.5 years, SD = 8.8, median = 9.1 years). A total of 108 (88.5%) patients had hydrocephalus, and 98 (90.7%) of those patients required a ventriculoperitoneal shunt procedure. Twenty-four (19.7%) patients manifested with seizures, 23 of whom had hydrocephalus. The average age of seizure onset was 4.8 years (median 2 years of age). Falx dysgenesis (P = .004), lumbar myelomeningocele (P = .007), and cortical atrophy (P = .028) were significantly associated with epileptic seizure development. The average seizure-free period at the last follow-up in patients with a history of myelomeningocele and seizures was 8.1 years. We conclude that myelomeningocele patients with seizures have an overall good prognosis with considerable long-term seizure freedom.

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.

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Intravenous kainic acid induces status epilepticus and late onset seizures in mice

We set out to establish a novel model of temporal lobe epilepsy (TLE) in a mouse. We sought to induce TLE through the injection of kainic acid (KA) into the tail vein with subsequent development of status epilepticus (SE). Using C57BL/6 mice, we implanted hippocampal EEG recording electrodes before or after injection of KA or phosphate buffered saline (PBS). Video and EEG analysis were conducted to evaluate for SE and development of recurrent seizures, the hallmark of TLE. All mice injected with KA developed SE while those who were injected with PBS did not. Of the animals injected with KA monitored for recurrent seizures following SE, 33% developed spontaneous recurrent seizures while those injected with PBS did not. Injection of KA through the tail vein of a mouse reliably and rapidly induces SE which remits spontaneously and leads to the development of TLE in a subset of mice.

Seizure Rates After Stereotactic Radiosurgery for Cerebral AVMs: A Single Center Study

Seizure control after stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is an area of growing interest, with previous studies reporting up to 70% seizure freedom after treatment. The goals of this study were to identify specific patient and AVM characteristics associated with seizure presentation and seizure outcomes after SRS treatment. A retrospective review of consecutive patients undergoing SRS for brain AVMs between 2009 and 2019 at our institution was conducted. Chi-squared and logistic regression analyses were utilized to identify patient and AVM factors associated with preoperative seizure presentation and development of new onset seizures after SRS. Two hundred ten consecutive patients presenting with AVMs treated with SRS were reviewed. Factors associated with seizure presentation included larger AVM size (P= 0.02), superficial venous drainage (P< 0.05), and parietal location (P= 0.04). Of 188 patients with follow-up (90%), 30 patients presented with seizures and 14 (47%) were seizure-free post-SRS. Of 158 patients presenting without seizure, 29 (18%) developed de novo seizures during follow-up. De novo post-SRS seizures were associated with prior craniotomy for resection of AVM (P= 0.04), post-treatment hemorrhage (P= 0.02), parietal location (P= 0.05), adverse effect requiring steroids (P < 0.01), and adverse effect requiring surgery (P < 0.01). Seizures are a common presentation of brain AVMs and can be treated effectively with SRS. However, seizures can also be a complication of SRS and are associated with post-treatment hemorrhage, edema, and need for future open surgery.

Perioperative routine EEG can reliably predict de novo seizures after supratentorial craniotomy.

The contributing risk factors in development of seizure after supratentorial craniotomy, the optimal duration of prophylactic antiepileptic therapy, the high-risk patient to treat, and the drug of choice are subjects of debate as is the gold standard diagnostic tool for patient screening. Combining routine electroencephalography (EEG) with clinical data to identify high-risk patients and determine the ideal time of recording after surgery was the goal of this study. In this prospective cohort, 59 patients were evaluated with three EEG recordings after different intervals of supratentorial craniotomy due to different etiologies and were followed for 9months for development of seizures. Demographic and disease-related variables as well as EEG results were analyzed to determine the contributing risk factors for development of seizures. Neoplastic etiology and abnormal perioperative EEG (performed before surgery or in the first postoperative week) were the only independent variables associated with development of de novo seizure. Routine EEG in the perioperative period and neoplastic etiology are two independent powerful predictors of developing seizure after supratentorial craniotomy and may help deciding whether to continue prophylactic antiepileptic medications for an extended period or not.