Occurrence Of Epileptic Seizures Research Articles

The visibility of the periventricular crossroads of pathways in preterm infants as a predictor of neurological outcome and occurrence of neonatal epileptic seizures

AimTo evaluate the relationship between the neurological outcome, neonatal epileptic seizures, and signal-intensity visibility of the frontal and parietal periventricular crossroads of pathways on brain magnetic resonance imaging (MRI) in preterm infants at term-equivalent age.MethodsThe study enrolled 48 preterm infants born between 2012 and 2016. The signal-intensity characteristics of the frontal and parietal periventricular crossroads were evaluated and classified into four grades. A non-favorable outcome was defined as a motor and functional disorder with developmental delay and/or cerebral palsy.ResultsNeonatal seizures, epilepsy, pathological EEG and brain ultrasound finding, and brain MRI abnormalities were mostly found in neonates with non-favorable outcomes. Visible frontal and parietal periventricular crossroads were associated with a normal neurologic outcome (P = 0.0004; P = 0.0009, respectively). Not-visible or slightly visible periventricular crossroads were associated with non-favorable outcomes in the case of frontal crossroads (P = 0.036) and not-visible periventricular crossroads in the case of both frontal and parietal crossroads (P = 0.001, P = 0.015, respectively). The visibility of the frontal and parietal periventricular crossroads was associated with a lack of neonatal epileptic seizures (P = 0.03; P = 0.02, respectively). The frontal crossroads were more frequently slightly visible, while the parietal periventricular crossroads were more frequently visible.ConclusionPoor visibility of the frontal and parietal crossroads of pathways on MRI is associated with neonatal epileptic seizures and poor neurological outcomes in preterm infants at term-equivalent age.

Patients with epilepsy as drivers in Poland.

Drivers suffering from epilepsy are commonly regarded as a threat to road safety. However, inability to use their own means of transport very often implies specific professional effects and lowers the quality of life. The aim of this study was to analyze the driving status of patients with epilepsy in Poland. The prospective study was performed using an independent questionnaire developed by the authors, consisting of 4 parts: 1) socio-demographic information, 2) clinical information, 3) driving information, and 4) opinions about patients with epilepsy as drivers. The study was conducted in November 2018-September 2019. A total of 188 patients completed this study. More than one-quarter of the patients have a driving license. Among them, 35 individuals (accounting for 18.62% of the whole study group) said that they had received their driving license after the diagnosis of epilepsy. In 10 cases (5.32%), seizures occurred while the patients were driving and in 72 cases (38.30%) while they were traveling as passengers. Among all socio-clinical factors, having a driving license was conditioned by the marital status (p = 0.008) and education (p = 0.007). Other factors did not affect having a driving license or the time of obtaining the license (p > 0.05 for all cases). A relationship was observed between the occurrence of side effects of antiepileptic drugs and the occurrence of seizures while traveling as a car passenger (p = 0.001). Other factors did not affect the occurrence of epileptic seizures while traveling by car, either as a driver or a passenger (p > 0.05). A significant proportion of the respondents were of the opinion that patients with epilepsy should not be allowed to obtain a driving license, which is probably related to concerns about the occurrence of epileptic seizures while driving. It is necessary to conduct a nationwide educational and information campaign on epilepsy in various aspects. Med Pr. 2021;72(4):341-50.

Molecular mechanisms of sex differences in epilepsy and seizure susceptibility in chemical, genetic and acquired epileptogenesis

This article provides a succinct overview of sex differences in epilepsy and putative molecular mechanisms underlying sex differences in seizure susceptibility in chemical, genetic, and acquired epileptogenesis. The susceptibility to excitability episodes and occurrence of epileptic seizures are generally higher in men than women. The precise molecular mechanisms remain unclear, but differences in regional morphology and neural circuits in men and women may explain differential vulnerability to seizures and epileptogenic cascades. Changes in seizure sensitivity can be attributed to steroid hormones, including fluctuations in neurosteroids as well as neuroplasticity in their receptor signaling systems. Other potential neurobiological bases for sex differences in epilepsies include differences in brain development, neurogenesis, neuronal chloride homeostasis, and neurotrophic and glial responses. In catamenial epilepsy, a gender-specific neuroendocrine condition, epileptic seizures are most often clustered around a specific menstrual period in adult women. A deeper understanding of the molecular and neural network basis of sex differences in seizures and response to antiepileptic drugs is highly warranted for designing effective, sex-specific therapies for epilepsy, epileptogenesis, and seizure disorders.

Relationship between Delta Rhythm, Seizure Occurrence and Allopregnanolone Hippocampal Levels in Epileptic Rats Exposed to the Rebound Effect.

Abrupt withdrawal from antiepileptic drugs is followed by increased occurrence of epileptic seizures, a phenomenon known as the “rebound effect”. By stopping treatment with levetiracetam (LEV 300 mg/kg/day, n = 15; vs. saline, n = 15), we investigated the rebound effect in adult male Sprague-Dawley rats. LEV was continuously administered using osmotic minipumps, 7 weeks after the intraperitoneal administration of kainic acid (15 mg/kg). The effects of LEV were determined by comparing time intervals, treatments, and interactions between these main factors. Seizures were evaluated by video-electrocorticographic recordings and power band spectrum analysis. Furthermore, we assessed endogenous neurosteroid levels by liquid chromatography-electrospray-tandem mass spectrometry. LEV significantly reduced the percentage of rats experiencing seizures, reduced the seizure duration, and altered cerebral levels of neurosteroids. In the first week of LEV discontinuation, seizures increased abruptly up to 700% (p = 0.002, Tukey’s test). The power of delta band in the seizure postictal component was related to the seizure occurrence after LEV withdrawal (r2 = 0.73, p < 0.001). Notably, allopregnanolone hippocampal levels were positively related to the seizure occurrence (r2 = 0.51, p = 0.02) and to the power of delta band (r2 = 0.67, p = 0.004). These findings suggest a role for the seizure postictal component in the rebound effect, which involves an imbalance of hippocampal neurosteroid levels.

Neuroproteomics in Epilepsy: What Do We Know so Far?

Epilepsies are chronic neurological diseases that affect approximately 2% of the world population. In addition to being one of the most frequent neurological disorders, treatment for patients with epilepsy remains a challenge, because a proportion of patients do not respond to the antiseizure medications that are currently available. This results in a severe economic and social burden for patients, families, and the healthcare system. A characteristic common to all forms of epilepsy is the occurrence of epileptic seizures that are caused by abnormal neuronal discharges, leading to a clinical manifestation that is dependent on the affected brain region. It is generally accepted that an imbalance between neuronal excitation and inhibition generates the synchronic electrical activity leading to seizures. However, it is still unclear how a normal neural circuit becomes susceptible to the generation of seizures or how epileptogenesis is induced. Herein, we review the results of recent proteomic studies applied to investigate the underlying mechanisms leading to epilepsies and how these findings may impact research and treatment for these disorders.

Diagnosis of pediatric anti-NMDAR encephalitis at the onset: A clinical challenge.

To investigate the clinical and instrumental features at the onset addressing to the diagnosis of anti-NMDAR encephalitis. Twenty children (age: 15 months-17 years; 7 males, 13 females) with initial suspected diagnosis of autoimmune encephalitis, observed between January 2008 and March 2018, were included. The final diagnosis was anti-NMDAR encephalitis in 7 children, other/probable autoimmune encephalitis in 7 children, and primary psychosis in the remaining 6 children. At the clinical onset, anxiety disorder was the main symptom that helped in distinguishing the group of psychotic children from children with non-infectious encephalitis (P=0.05 OR=0.001), while epileptic seizures strongly predicted anti-NMDAR encephalitis (P=0.04 OR=28.6). At the onset, anti-NMDAR encephalitis could be distinguished from other/probable autoimmune encephalitis for the presence of sleep/wake rhythm alteration (P=0.05 OR=15). Among the symptoms occurring during the hospitalization, movement disorders (P=0.031 OR=12) were predictive of non-infectious encephalitis rather than primary psychosis. More specifically, the occurrence of language impairment (P=0.03 OR=33), epileptic seizures (P=0.04 OR=28.6) and catatonia (P=0.03, OR=33), were predictive of anti-NMDAR encephalitis. Also at this stage, anxiety disorder (P=0.03 OR=0.033) was predictive of primary psychosis. Our findings suggest that at the clinical onset epileptic seizures and sleep/wake rhythm alteration represent the main features addressing to the diagnosis of anti-NMDAR encephalitis rather than primary psychosis and other/probable autoimmune encephalitis, while anxiety disorder could be a solid predictor of primary psychosis.

Development of a Rat Model for Glioma-Related Epilepsy.

Seizures are common in patients with high-grade gliomas (30–60%) and approximately 15–30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle only (control group) in the right entorhinal cortex. MRI was performed to visualize tumor presence. A subset of seven GB and two control rats were implanted with recording electrodes to determine the occurrence of epileptic seizures with video-EEG recording over multiple days. In a subset of rats, tumor size and expression of tumor markers were investigated with histology or mRNA in situ hybridization. Tumors were visible on MRI six days post-inoculation. Time-dependent changes in tumor morphology and size were visible on MRI. Epileptic seizures were detected in all GB rats monitored with video-EEG. Twenty-one days after inoculation, rats were euthanized based on signs of discomfort and pain. This study describes, for the first time, reproducible tumor growth and spontaneous seizures upon inoculation of F98 cells in the rat entorhinal cortex. The development of this new model of GB-related epilepsy may be valuable to design new therapies against tumor growth and associated epileptic seizures.

Evaluation of recurrent neural networks as epileptic seizure predictor

Abstract The occurrence of epileptic seizures is a problem that makes everyday life difficult for many people who suffer from this disorder, which may causes risks to the subjects and people around them. The possibility of predicting epileptic seizures could create a way to minimize risks associated with these attacks. Through computational analysis of Electroencephalography (EEG) signals, a variation of Recurrent Artificial Neural Network (RNN), of Long Short Term Memory (LSTM) type, was developed in an attempt to classify segments of EEG signals that occur before the onset of epileptic seizures, segments which evince the pre-ictal state. Using an EEG database of pediatric subjects with intractable seizures, groups of patients were created, then redundant EEG channels were selected and reduced by only 25%. Temporal and spectral features were extracted to improve the evaluation of data patterns related to seizures. Besides using the unprocessed data, two techniques were proposed, first using the superposition of inputs, then anticipating targets in the training data. A third technique was also proposed by joining the first two. Finally, two LSTM structures were created. The proposed Neural Network achieved high accuracies above 99%; however, the results showed that it was not possible to classify pre-ictal regions by using this combination of architecture and individuals. Furthermore, it was observed that the Neural Network was able to classify ictal regions with up to 61% sensitivity and 99% specificity, confirming the capacity of RNNs of LSTM type to assimilate temporal patterns in EEG data.

Occurrence and risk factors of unprovoked epileptic seizures in ischaemic stroke patients

Occurrence and risk factors of unprovoked epileptic seizures in ischaemic stroke patients

Seasonal Pattern of Epileptic Seizures: A Single-Center Experience

Purpose: To evaluate the seasonal fluctuation of epileptic seizures during one year. Methods: This was a single centre retrospective observational study. Demographic data, number and type of epileptic seizures were collected and analyzed using a dataset from the outpatient epilepsy clinic of a tertiary hospital, during one year. The statistical tools included descriptive statistics, contingency tables, Chi-square of goodness-of-fit tests, and general linear models. Results: In total, 143 consecutive patients were included in the study. Among the patients, 72 were women and 71 men. In total, 1,351 epileptic seizures were recorded during one year. A significantly higher rate of epileptic seizures during spring and summer was revealed. An association between the type of epileptic seizure and the month of the year was recorded. Specifically, focal seizures with impairment of awareness fluctuate throughout the year, with a sudden peak during June. Significance: Epidemiologic data regarding epilepsy seasonality have so far received only limited attention. In our study, a seasonal pattern was recorded on the occurrence of epileptic seizures. Further research combining different weather conditions and environments is needed to fully characterize the seasonality of epilepsy.

ІНФОРМАЦІЙНА ТЕХНОЛОГІЯ ОЦІНЮВАННЯ ЗМІН ПЕРІОДІВ ЕПІЛЕПТИЧНОГО НАПАДУ

According to the technology developed, decision support during the diagnostic process of determining periods of epileptic seizure by EEG is carried out in three stages: obtaining and processing of data, development of prognostic models and formation of diagnostic conclusions. The information technology of the prediction of the occurrence of epileptic seizure on the basis of an EEG signal which uses the developed software of complexity and variability indices calculation, and also built on the basis of these indices individualized prognostic models, with use of informative leads, enables to identify the periods of functioning of the brain in patients with epilepsy.

Akutni bakterijski meningitisi u Zlatiborskom okrugu

Introduction: Acute bacterial meningitis is present worldwide, with a lethality rate up to 50%. The most common causes are Streptococcus pneumoniae and Neisseria meningitidis. The aim of the research is to analyze acute bacterial meningitis in the Zlatibor district. Material and methods: Patients treated at the General Hospital in Uzice were examined retrogradely. Demographic data, risk factors, hematological and biochemical data from blood and cerebrospinal fluid and the findings of computed tomography scan of the endocranium were analyzed. All patients underwent lumbar puncture. The etiological diagnosis was made by identifying the pathogens from cerebrospinal fluid or blood culture. The clinical course was monitored, and the prognosis was determined according to the Glasgow coma scale. Results: We examined 148 patients with acute bacterial meningitis (92 men, 56 women), mean age 55.8 +/-13.1. Half of the patients had comorbidities. In 42%, the possible focus of infection was sinusitis. Main symptoms were headache (100%), fever (97.2%), neck stiffness (95.9%). CSF analysis showed less than 100 polymorphonuclear leukocytes/mm3 in 65% of patients, and CSF protein elevation in 95.3%. 94.6% of patients had leukocytosis in the blood, and 86.5% had elevated C-reactive protein. The most commonly isolated bacterium was Streptococcus pneumoniae (40.5%). 74.3% of patients had a favorable disease outcome. One third of the patients showed epileptic seizures. In 16.2% of patients, the disease ended lethally. Risk factors for lethal outcome were the presence of comorbidities, Streptococcus pneumoniae as the pathogen, the occurrence of epileptic seizures, age over 50 years and male gender. Conclusion: The most common cause of acute bacterial meningitis in adult population of the Zlatibor district is Streptococcus pneumoniae, which is also the most common cause of adverse disease outcomes. Majority of patients are men over the age of 50 with comorbidities, which are also a risk group for an unfavorable disease outcome.

Neuroinflammation and progressive myoclonus epilepsies: from basic science to therapeutic opportunities.

Progressive myoclonus epilepsies (PMEs) are a group of genetic neurological disorders characterised by the occurrence of epileptic seizures, myoclonus and progressive neurological deterioration including cerebellar involvement and dementia. The primary cause of PMEs is variable and alterations in the corresponding mutated genes determine the progression and severity of the disease. In most cases, they lead to the death of the patient after a period of prolonged disability. PMEs also share poor information on the pathophysiological bases and the lack of a specific treatment. Recent reports suggest that neuroinflammation is a common trait under all these conditions. Here, we review similarities and differences in neuroinflammatory response in several PMEs and discuss the window of opportunity of using anti-inflammatory drugs in the treatment of several of these conditions.

Multiday Cycles of Heart Rate Modulate Seizure Likelihood at Daily, Weekly and Monthly Timescales: An Observational Cohort Study

Background: Circadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology and immunology. In people with epilepsy, epileptic brain activity and seizure occurrence have been found to follow circadian, weekly and monthly rhythms. Understanding the relationship between these cycles of brain excitability and other physiological systems can provide new insight into the causes of multiday cycles. The brain-heart link is highly relevant for epilepsy, with implications for seizure prediction, therapy (i.e. vagal nerve stimulation) and mortality (i.e. sudden unexpected death in epilepsy). Methods: We report the results from a non-interventional, observational cohort study, Tracking Seizure Cycles. This study quantified multiday cycles of heart rate and seizures in human participants (N=26) using wearable smartwatches and mobile seizure diaries over at least two months (M=6.4, SD=4.0). Participants had an epilepsy diagnosis and uncontrolled or partially controlled seizures. Significant cycles in heart rate were detected using a continuous wavelet transform. Significant co-modulation between heart rate cycles and seizure occurrence were measured from the distributions of seizure likelihood with respect to underlying cycle phase (Omnibus test). Weekly trends were also investigated from a retrospective cohort of continuous video-EEG-ECG records of people (N=29) undergoing diagnostic epilepsy monitoring for at least eight days (M=9.7, SD=1.3). Findings: Heart rate cycles were found in all participants, with circadian (100%), about-weekly (88%) and about-monthly (92%) rhythms being the most prevalent. Seizures were significantly locked onto at least one heart rate cycle in 76% of eligible participants. Seizures occurred preferentially during the rising phase of the heart rate cycles. Significant weekly trends were also verified in 52% of the video-EEG-ECG cohort. Interpretation: The existence and prevalence of multiday heart rate cycles may have clinical implications for cardiology. Heart rate cycles showed striking similarities to multiday epileptic rhythms and were co-modulated with seizure likelihood. The relationship between heart rate and seizures is relevant for epilepsy therapy, including seizure forecasting. More broadly, understanding the link between multiday cycles in the heart and brain can shed new light on endogenous physiological rhythms in humans. Funding Statement: This research was funded by an NHMRC Investigator Grant 1178220. This research was supported by the Epilepsy Foundation of America's My Seizure Gauge grant. Declaration of Interests: Dr. Brinkmann reports grants from Epilepsy Foundation of America, My Seizure Gauge, during the conduct of the study; other from Cadence Neurosciences, outside the submitted work. Dr. Freestone reports grants from Epilepsy Foundation USA, personal fees and other from Seer Medical, during the conduct of the study; In addition, Dr. Freestone has a patent Methods and Systems of Seizure Forecasting issued. Dr. Nurse reports grants from Epilepsy Foundation of America, grants from MTPConnect, during the conduct of the study; personal fees from Seer Medical, outside the submitted work. Dr. Cook reports personal fees and other from Seer Medical Australia, personal fees and other from Epi Minder, outside the submitted work; In addition, Dr. Cook has a patent Methods and Systems of Seizure Forecasting issued. Dr. Karoly reports grants from National Health and Medical Research Council (NHMRC), during the conduct of the study; other from Seer Medical (Australia), outside the submitted work; In addition, Dr. Karoly has a patent Methods and Systems of Seizure Forecasting issued. The remaining authors have no competing interests to declare. Ethics Approval Statement: The study was approved by the St Vincent’s Hospital Human Research Ethics Committee (HREC 009.19) and first enrolment was in August 2019. All participants provided written informed consent.

АНАЛИЗ ПРЕДИКТОРОВ ЭПИЛЕПТИЧЕСКИХ ПРИСТУПОВ

The statistical data on epilepsy, etiology and pathogenesis of the disease are given in the article. The main causes that affect the occurrence of epileptic seizures, and possible predictors that are sensitive to these causes (metabolic rate, blood flow velocity, change in electrical activity of the brain) are highlighted. The blood flow dynamics in the common carotid artery, which supplies the brain with oxygen and nutrients is proposed to be considered as one of the possible internal physiological parameters that are believed to be predictors of epileptic seizures.

Sexual and reproductive dysfunction in women with epilepsy in the aspect of current anti-epileptic pharmacotherapy

Based on current literature analysis this review provides information on various issues of a woman’s reproductive system functioning under altered conditions of a pathologically functioning brain during epilepsy, outlines possible pathogenetic mechanisms of hormonal imbalance and its effect on epileptogenesis. There are complex multidirectional interactions between female sex hormones and epileptic pathological process. Any changes in the concentrations of endogenous or exogenous hormones can affect the occurrence of epileptic seizures directly or by pharmacokinetic interactions through the modification of antiepileptic drugs level in plasma. These effects are realized by acting on various links of the hypothalamic-pituitary-ovarian axis. Special catamenial epilepsy when hormonal imbalance determines the epileptic process, mechanisms of its formation and therapeutic approaches to treatment are also considered. The questions of reproductive dysfunctions typical for women with epilepsy are described, such as hyperandrogenism, high luteinizing hormone levels, irregular menstruation, hyperprolactinemia, polycystic ovary syndrome, infertility, premature menopause. The result of these dysfunctions is that 30–60% of patients with epilepsy have a low pregnancy and childbirth rate. Worsening of life quality in women with epilepsy results in approximately five-fold increase in the risk of sexual dysfunction compared with the general population, which is manifested by a decrease of sexual contacts quantity, libido problems, decreased lubrication, dyspareunia, vaginismus, problems with arousal and orgasm dissatisfaction despite a normal attraction. It needs consider the effects of epilepsy pharmacotherapy and drugs interaction with hormonal contraception, that reduces its effectiveness. The possibilities of this problem solution and hormone replacement therapy in menopausal patients with epilepsy are reviewed. Information is presented on the current pharmacotherapy of epilepsy in the aspect of antiepileptic drugs as the causes of sexual and reproductive dysfunctions, primarily valproate and anticonvulsant inducers of cytochrome P450, as well as other drugs of this group.

The concept of disease modification.

Traditionally treatment of epileptic seizures has been symptomatic, namely medication has been targeted at raising the threshold to the occurrence of epileptic seizures. This has had little impact on the rate of drug resistance over time, or impact on comorbidities such as learning and behaviour particularly in the early onset epilepsies. The advent of advanced neuroimaging and genomics has revealed the cause of the epilepsy in a much higher percentage, and advanced our knowledge as to the underlying pathophysiology. This has given us the opportunity to turn to the possibility of interventional treatment, targeting the underlying cause, and consequently the possibility of changing the natural history of disease. Here we review the options open to us, and the evidence to date.

Clinical Profile and Outcomes of Early Seizures in Asian Patients With Acute Intracerebral Hemorrhage.

Seizures are one of the most common complications of stroke. We aimed to establish the incidence and clinical profile of post-stroke early seizure (ES) in patients with intracerebral hemorrhage (ICH). Patients with ICH within 10 days of onset who were admitted to Landseed International Hospital were recruited consecutively between January 1, 2006, and December 31, 2009. The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale were used to access patients initial stroke severity and functional outcome at discharge, respectively. The occurrence of epileptic seizures within 30 days after onset of the index ICH was recorded. Early post-ICH seizure was defined by the occurrence of clinically identifid seizure episodes or non-epileptic seizure within 7 days after the stroke onset. A total of 297 ICH patients were included. The mean age of the participants was 62 ± 16 years, and 72% of them were male. A total of 9 (3%) participants had seizures during acute hospitalization. Patients with seizures had higher median NIHSS scores at baseline (34 vs. 16, p = 0.004). No difference was noted in the cortical involvement of ICH (22% for patients with seizures and 14% for those without, p = 0.156). Patients with seizures had higher in-hospital mortality ( 56% vs. 23%, p = 0.024). The multivariate Cox regression model showed the factors significantly associated with ES were higher initial NIHSS scores on admission (adjusted odds ratio [aOR] = 1.1 per 1 point increased, 95% confidence interval [CI] = 1.0-1.2) and coronary artery disease (aOR = 7.0, 95% CI = 1.3-36.4). The NIHSS scores and coronary heart disease were associated with ES in ICH, whereas cortical involvement was not. These findings may reflect difference in post-stroke seizure and primary ICH between Asian and Western populations.

Factors of epilepsy in children with neurofibromatosis type 1 in Turkey

Objectives: Epilepsy is one of the complications of neurofibromatosis type 1 (NF1). The aim of this study was to investigate the relationship between risk factors and epileptic seizures in NF1 patients. Materials & Methods: We retrospectively studied 105 Turkish children with NF1 in this study. Results: We found 15 (14.3%) patients epilepsy patients in our study. The mean age at onset of seizures was 7.33± 4.33 years (range 1 to 15 years). The most common seizure type was partial onset seizures. In the epilepsy patients, unidentified bright objects (UBOs) were present in seven patients, brain tumors in four patients, mesial temporal sclerosis in one patient, hydrocephalus in one patient, and cortical dysplasia in one patient. One patient had normal neuroimaging findings. There was no correlation between epilepsy and age, sex, consanguinity, family history of NF1, family history of epilepsy, neurologic deficits, presence of UBOs, location of UBOs, and presence of optic pathway glioma. We found that intellectual disability, and brain tumors were a significant risk factors for epilepsy development. Conclusions: The occurrence of epileptic seizures in NF1 patients is related to intellectual disability and brain tumors.

Prophylactic levetiracetam for the prevention of post stroke seizures (PROLEVIS): A randomized, double blind, placebo-controlled trial protocol

Stroke is the most common cause of acquired epilepsy. Currently, there is insufficient evidence to recommend for or against prophylactic antiepileptic therapy for the primary prevention of post-stroke seizures. To determine whether 3 months of prophylactic levetiracetam can prevent seizures in patients with supra-tentorial cortical stroke PROLEVIS is an investigator-initiated, single centre, prospective, stratified, randomized, double blind, placebo controlled superiority trial which will enroll 800 patients (400 ischemic stroke and intracranial haemorrhage each, 1:1 allocation using permuted block randomisation, 200 in active arm and 200 in placebo arm). Eligibility will require a diagnosis of ischemic stroke, or parenchymal intracerebral haemorrhage (spontaneous non-aneurysmal, nontraumatic intracerebral haemorrhage) with a cortical syndrome (either parenchymal involvement documented by imaging or presence of aphasia, apraxia, agnosia or cortical visual disorders). Recruitment should happen within 1 week of onset in arterial stroke or intracranial haemorrhage. Patients will be randomized to either oral levetiracetam or placebo twice a day for 3 months The primary outcome measure will be occurrence of first post stroke seizure. Secondary outcomes include time from stroke to occurrence of seizure, occurrence of early or late epileptic seizure after stroke, seizure severity, functional outcome at 3 months (Glasgow outcome scale, and modified Rankin Scale), occurrence of side effects of the medication and mortality. The trial has recruited 25 patients till now. The trial tests an important clinically relevant research question. The results could have a major influence in the clinical practice regarding prophylactic antiepileptic therapy to stroke patients. (CTRI/2018/02/011926)