Incidence Of Early Seizures Research Articles

Effectiveness of Levetiracetam versus phenytoin in preventing seizure in traumatic brain injury patients: A systematic review and meta-analysis

ObjectiveTraumatic brain injury (TBI) and the subsequent Post-traumatic seizure (PTS) is a growing public health concern. Generally, anti-seizure drugs (ASDs) are recommended for PTS prophylaxis and treatment. This meta-analysis aimed to review the current state of knowledge and the evidence for the efficacy and safety of Levetiracetam (LEV) on the incidence of seizure in TBI patients compared to Phenytoin (PHT). MethodsA search was carried out based on PubMed, MEDLINE, Europe PMC database, and Cochrane Library up to November 2023. A total of 16 studies (3 randomized clinical trials, 10 retrospective cohort studies, and 3 prospective cohort studies) including 5821 TBI patients included in our meta-analysis. We included studies comparing LEV and PHT after brain injury in both adults and children. Risk of bias assessment was done for randomized controlled trials (RCTs) with a risk-of-bias tool (RoB-2) and the Newcastle–Ottawa Scale (NOS) was used to assess the quality of cohort studies. Two RCTs in our meta-analysis had a high risk of bias, therefore we applied sensitivity analysis to evaluate the robustness of our results. ResultsThe most commonly reported dosage for LEV was 500 mg twice daily and for PHT it was 5 mg/kg. There was no significant difference between LEV and PHT groups in reducing the early seizure incidence (OR = 0.85; 95% CI = [0.60, 1.21]; p = 0.375, fixed-effect, I2 = 21.75%). The result of sensitivity analysis for late seizure showed no significant difference between LEV and PHT in reducing the late seizure occurrence after TBI (OR = 0.87; 95% CI = [0.21, 3.67]; p = 0.853, fixed-effect, I2 = 0%). The mortality in TBI patients treated with LEV was not statistically significant compared to the PHT group (OR = 1.11; 95% CI = [0.92, 1.34], p = 0.266). The length of stay in the hospital was not significantly different between the LEV and PHT groups (MD = –1.33; 95% CI = [–4.55, 1.90]; p = 0.421). However, in comparison to PHT, LEV shortened the length of ICU stay (MD = –2.25; 95% CI = [–3.58, –0.91]; p =0.001). In terms of adverse effects, more patients in the PHT group have experienced adverse events compared to LEV but the difference was not significant (OR = 0.69; 95% CI = [0.44, 1.08]; p = 0. 11). ConclusionThe results of our meta-analysis showed LEV and PHT have similar effects on the occurrence of early and late seizures in TBI patients. Therefore, none of the drugs is superior to the other in reducing PTS. However, treating TBI patients with LEV did not shorten the length of hospital stay in comparison to PHT but reduced the length of ICU stay significantly. The analysis showed that patients in the LEV experienced fewer side effects than in the PHT group, while it was not sufficiently clear whether all reported side effects were related to the drug alone or other factors. The mortality was similar between the LEV and PHT groups. Finally, we recommend more high-quality randomized controlled trials to confirm the current findings before making any recommendations in practice.

Predictors of early seizures after first acute stroke

Background and objective:
 There is a lack of local data regarding the frequency and predictors of early seizures after stroke. The objective of this study was to determine the frequency of early seizures after stroke and identify the predictors which lead to them after first acute stroke.
 Methods:
 This cross-sectional observational study was conducted in the Department of Neurology, Pakistan Institute of Medical Sciences, Islamabad from October 2021 to June 2022. A total of 310 consecutive eligible patients of acute stroke were recruited. Key inclusion criteria included any patient of >20 years of age with confirmed diagnosis of stroke on imaging, non-traumatic, with no history of seizures in past. Data was analyzed by SPSS version 23.0.
 Results: 
 The mean age of patients in the seizures group was 48.40 ± 20.9 years. Hypertension was the most common co-morbid present in 225 (76.5%) patients. Early seizures were found in 52 (16.8%) patients with 42 (80.76%) having seizures in first 24 hours of stroke (p value 0.001). On National Institute of Health Sciences Scale (NIHSS) score most patients 125 (40.3%) had moderate severity score i.e. score in between 7 to 25 (p value 0.05). Ischemic stroke was identified as the stroke variety with most of the early seizures i.e. 16 (30.76%) (p value 0.003).
 Conclusion: 
 Early seizures were not infrequent after acute stroke (16.77%) in our study. Early seizures were associated with younger age, cortical region lesion, ischemic stroke, followed by cerebral venous thrombosis. Higher NIHSS score and greater disability was associated with increased incidence of early seizures.

Overview of systematic reviews: Management of common Traumatic Brain Injury-related complications.

Many clinical interventions are trialled to manage medical complications following Traumatic Brain Injury (TBI). However, published evidence for the effects of those clinical interventions is limited. This article is an overview of common complications and their management from published systematic reviews in TBI. A health science electronic database search for published systematic reviews for management of common complications in TBI was conducted in the last decade till 31st January 2021. Methodological quality and evidence were critically appraised using the Grading of Recommendations, Assessment, Development and Evaluations and Revised-Assessment of Multiple Systematic review tools. Overall, only six systematic reviews complied with search criteria, these evaluated fatigue, spasticity and post traumatic seizures (29 RCTs, 13 cohort studies, n = 5639 participants). No systematic reviews for other common TBI-related complications met criteria for this review. The included reviews varied from 'moderate to high' in methodological quality. The findings suggest beneficial treatment effect of anti-epileptic drugs (phenytoin/levetiracetam) compared with placebo in reducing early seizure incidence, but no significant benefit of phenytoin over levetiracetam, valproate, or neuroprotective agent for early or late posttraumatic seizures. There was 'limited' evidence for spasticity-related interventions, and 'insufficient' evidence of cardiorespiratory training on fatigue levels. Despite the high prevalence and associated functional impact of TBI-related complications, there is limited evidence to guide treating clinicians for management of common TBI complications. More robust studies are needed to build evidence in this population.

Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial

The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage. The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding. Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group. Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage. French Ministry of Health.

Effect of Reperfusion Therapies on Incidence of Early Post-Stroke Seizures.

Objective: This study aimed to determine the effect of reperfusion therapies on the occurrence of early post-stroke seizures (PSS) in patients with acute ischemic stroke (AIS).Background: Reperfusion therapies are paramount to the treatment of stroke in the acute phase. However, their effect on the incidence of early seizures after an AIS remains unclear.Design and Methods: The stroke database at Hamad Medical Corporation was used to identify all patients who received reperfusion therapies for AIS from 2016 to 2019. They were matched with patients of similar diagnosis, gender, age, and stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS) who did not receive such treatment. The rates of early PSS were calculated for each group.Results: The results showed that 508 patients received reperfusion therapies (342 had IV thrombolysis only, 70 had thrombectomies only, and 96 had received both), compared with 501 matched patients receiving standard stroke unit care. Patients who received reperfusion therapies were similar to their matched controls for mean admission NIHSS score (9.87 vs. 9.79; p = 0.831), mean age (53.3 vs. 53.2 years; p = 0.849), and gender distribution (85 vs. 86% men; p = 0.655). The group receiving reperfusion therapies was found to have increased stroke cortical involvement (62 vs. 49.3%, p < 0.001) and hemorrhagic transformation rates (33.5 vs. 18.6%, p < 0.001) compared with the control group. The rate of early PSS was significantly lower in patients who received reperfusion therapies compared with those who did not (3.1 vs. 5.8%, respectively; p = 0.042). When we excluded seizures occurring at stroke onset prior to any potential treatment implementation, the difference in early PSS rates between the two groups was no longer significant (2.6 vs. 3.9%, respectively; p = 0.251). There was no significant difference in early PSS rate based on the type of reperfusion therapy either (3.2% with thrombolysis, 2.9% with thrombectomy, and 3.1% for the combined treatment, p = 0.309).Conclusions: Treatment of AIS with either thrombectomy, thrombolysis, or both does not increase the risk of early PSS.

The Incidence of Early Seizures in Non-Severe Traumatic Brain Injury Patients and the Efficacy of Prophylactic Antiepileptic Drugs

The Incidence of Early Seizures in Non-Severe Traumatic Brain Injury Patients and the Efficacy of Prophylactic Antiepileptic Drugs

Management of Post-traumatic Seizures and Epilepsy

Post-traumatic seizures and epilepsy are major complication of traumatic brain injury. Early and late and seizures have different implications for prognosis and management. Early seizures, which occur within one week of the trauma, are acute symptomatic events. On the other hand, presence of late seizures indicate epilepsy. Patients with early seizures are treated with anti-epileptic drugs(AEDs)within weeks to avoid status epilepticus, which may increase cerebral blood flow and increase intracranial pressure. Because prophylactic administration of AEDs reduces the incidence of early seizures but not late seizures, it is recommended to limit it to one week. A long-term AED administration is recommended for patients with late seizures, because late seizures represent epilepsy. AED should be selected according to the considerations of age and comorbidity that apply to other individuals with new-onset epilepsy. Since epileptic seizures often cause serious accidents, such as traffic accidents, drowning, burns, falls and others, lifestyle guidance for patients and their families is important.

Statin treatment can reduce incidence of early seizure in acute ischemic stroke: A propensity score analysis

A previous study showed early statin administration in patients with acute ischemic stroke (AIS) was associated with a lower risk of early-onset seizure (ES), which is a high risk of epilepsy, but this retrospective study design may not have eliminated confounding factor effects. We aimed to verify the determinants and prognostic significance of ES and clarify the effects of statin administration. Consecutive AIS patients without a history of epilepsy were enrolled. The relationship between ES (within 7 days of index-stroke) and statin treatment was assessed using multivariate and propensity scores (PS). Of 2,969 patients with AIS, 1,623 (54.6%) were treated with statin, and 66 (2.2%) developed ES. In logistic regression models, cortical stroke lesion [odds ratio (OR), 2.82; 95% confidence interval (CI), 1.29–7.28) and pre-morbid modified Rankin Scale (per 1 point) (OR, 1.39; 95% CI, 1.18–1.65) were higher risks for ES, while statin significantly reduced the risk of ES (OR, 0.44; 95% CI, 0.24–0.79). In accordance with PS-matching, statin treatment produced consistent results for ES after adjusting by inverse probability of treatment-weighting PS (OR, 0.41; 95% CI, 0.22–0.75). In conclusion, as previously, statin treatment was independently associated with a lower risk of ES in AIS.

Serum osmolarity and blood viscosity in neuroleptic malignant syndrome

Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE.We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury.Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p < 0.001), worse functional recovery (p = 0.003), and greater temporal lobe atrophy (p = 0.029).Our results indicate that in a cohort of patients with a moderate-severe TBI, 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of PTE, 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.

Epilepsy in the Elderly: Treatment and Consideration of Comorbid Diseases.

Epilepsy is the third most common neurological disorder affecting older adults after stroke and dementia, and the incidence of epilepsy is increasing rapidly in this population. A further increase in the incidence and prevalence of epilepsy is expected in aging societies. The establishment of a correct differential diagnosis between epilepsy and other seizure disorders that are common in the elderly is crucial. The symptoms of seizures in the elderly may be different from those in younger populations. The diagnosis is difficult, probably because of nonspecific characteristics, short-term symptoms, and absence of witnesses. There are three important issues in the treatment of epilepsy in the elderly: changes in pharmacokinetic parameters, polytherapy (including non-antiepileptic and antiepileptic drugs), and susceptibility to adverse drug effects. Antiepileptic drugs (AEDs) with fewer adverse effects, including cognitive effects, and AEDs without significant pharmacokinetic drug interactions are needed. Several studies found that stroke was strongly associated with a high incidence of early seizures and epilepsy. Stroke is also one of the major causes of status epilepticus. Cortical involvement and large lesions are strongly associated with the development of seizures and epilepsy. The severity of the initial neurological deficit is a strong clinical predictor of seizures after ischemic stroke. The optimal quality of life of dementia patients cannot be achieved without a proper diagnosis of coexisting epilepsy.

Epidemiology of traumatic brain injury-associated epilepsy and early use of anti-epilepsy drugs: An analysis of insurance claims data, 2004–2014

BackgroundAbout 2.8 million TBI-related emergency department visits, hospitalizations and deaths occurred in 2013 in the United States. Post-traumatic epilepsy (PTE) can be a disabling, life-long outcome of TBI. ObjectivesThe purpose of this study is to address the probability of developing PTE within 9 years after TBI, the risk factors associated with PTE, the prevalence of anti-epileptic drug (AEDs) use, and the effectiveness of using AEDs prophylactically after TBI to prevent the development of PTE. MethodsUsing MarketScan® databases covering commercial, Medicare Supplemental, and multi-state Medicaid enrollees from 2004 to 2014, we examined the incidence of early seizures (within seven days after TBI) and cumulative incidence of PTE, the hazard ratios (HR) of PTE by age, gender, TBI severity, early seizure and AED use (carbamazepine, clonazepam, divalproex sodium, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, pregabalin, topiramate, acetazolamide). We used backward selection to build the final Cox proportional hazard model and conducted multivariable survival analysis to obtain estimates of crude and adjusted HR (cHRs, aHRs) of PTE and 95% confidence intervals (CI). ResultsThe incidence of early seizure among TBI patients in our study was 0.5%. The cumulative incidence of PTE increased from 1.0% in one year to 4.0% in nine years. Most patients with TBI (93%) were not prescribed any AED. Gender was not associated with PTE. The risk of PTE was higher for individuals with older age, early seizures, and more severe TBI. Only individuals using prophylactic acetazolamide had significantly lower risk of PTE (aHR = 0.6, CI 0.4-0.9) compared to those not using any AED. ConclusionThe probability of developing PTE increased within the study period. The risk of developing PTE significantly increased with age, early seizure and TBI severity. Most of the individuals did not receive AED after TBI. There was no evidence suggesting AEDs helped to prevent PTE with the possible exception of acetazolamide. However, further studies may be needed to test the efficacy of acetazolamide in preventing PTE.

Early post-stroke seizures in a sample of Egyptian patients with first-ever stroke.

Cerebrovascular stroke is considered as the most common cause of symptomatic seizures. Post-stroke seizures herald a poor functional outcome, a high mortality rate, and a long in-hospital duration of stay. To assess the incidence and risk factors responsible for early seizures after the first-ever cerebral stroke, and its relation to the functional outcome and the in-hospital mortality following stroke as well as the duration of stay. 150 patients with first-ever stroke, who were admitted in an intensive care and stroke unit of the Neurology Department of Zagazig University Hospitals, Egypt, within the first 24 hours of stroke onset were included in the study. Early seizures (within 7 days of stroke onset), stroke severity (National Institutes of Health stroke scale; NIHSS), radiological data, functional outcome (Barthel index), in-hospital mortality and duration of stay were collected and analyzed. The incidence of early seizures associated with first-ever stroke was 9.3%. Risk factors for early seizures were intracerebral hemorrhage (ICH) [odds ratio (OR) = 3.2, P = <0.001), cortical lesions (OR = 2.8, P = <0.05), and a large lesion size (OR = 2, P= <0.05). Patients with early seizures had lower scores on the Barthel index than those without seizures (7.5 ± 4.1 versus 10.5 ± 3.5), had higher discharge National Institutes of Health Stroke scale (NIHSS) scores, had a higher in-hospital mortality rate (35.7% versus 6.6% in patients without seizures) and duration of stay (19.4 ± 6.5 versus 10.7 ± 4.2 days respectively). The incidence of early post-stroke seizures was high in our study and was positively associated with a poor functional outcome, a higher in-hospital mortality rate and a longer duration of in-hospital stay. The most important risk factors were ICH, the cortical site of involvement and a large size of the lesion.

Early and Late Posttraumatic Epilepsy in the Setting of Traumatic Brain Injury: A Meta-analysis and Review of Antiepileptic Management.

Moderate to severe traumatic brain injury confers increased risk of posttraumatic seizures (PTSs). Early PTSs are diagnosed when seizures develop within 7 days after injury, whereas seizures diagnosed as late PTSs occur later. Patients have been treated with phenytoin (PHT) to prevent early PTSs and more recently with levetiracetam (LEV). Various regimens have been tried in patients to prevent late PTSs with variable success. We assessed and compared effectiveness of these drugs on early and late PTS prevention. A literature search revealed 120 articles. Data were included if the same factors were compared across studies with identical treatment arms. Random effects models were used for meta-analysis to combine data into an overriding odds ratio (OR) comparing PTS incidence. For early PTSs, PHT was compared with placebo and LEV with PHT. For late PTSs, each drug was compared with placebo. Sixteen studies were included. PHT was associated with decreased odds of early seizures relative to placebo (OR= 0.34, 95% confidence interval [CI] 0.19-0.62). There was no difference in early seizure incidence between LEV and PHT (OR= 0.83, 95% CI 0.33-2.1). Neither LEV (OR=0.69, 95% CI 0.24-1.96) nor PHT (OR= 0.4, 95% CI 0.1-1.6) was associated with fewer late PTSs than placebo. New literature is consistent with current guidelines supporting antiepileptic drug administration for prevention of early, but not late, PTSs. With regard to early PTS prevention, LEV and PHT are similarly efficacious, which is consistent with current guidelines. Side-effect profiles favor LEV administration over PHT.

Early Seizure Prophylaxis in Traumatic Brain Injuries Revisited: A Prospective Observational Study.

Pharmacological prophylaxis for early seizures following traumatic brain injury (TBI) is a recommendation in the Brain Trauma Foundation Guidelines. However, several studies have challenged the efficacy and safety of this practice, resulting in varied practice across centers around the world. The purpose of the present study was to compare the incidence of early clinical seizures following TBI, between two large centers, a US Center that practises routine seizure prophylaxis and a Chinese Center that does not use seizure prophylaxis following TBI. This was a prospective observational study including an urban level I trauma center in the USA and a large hospital in Shenzhen, China. At the US Center, all patients received seizure prophylaxis with levetiracetam. At the Chinese Center, no seizure prophylaxis was given. All patients with blunt TBI and positive computed tomography findings for epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intracerebral hemorrhage or diffuse axonal injury were included. Patients who died within 24h of admission were excluded. The study population was monitored daily for clinical seizures for the first 7 post-injury days. Data collected included demographics, mechanism of injury, vital signs upon arrival, injury severity and emergency interventions. Primary outcome was the incidence of early seizures, defined as those occurring within 7days of injury. A total of 522 patients were included in the analysis: 272 patients at the US Center who received seizure prophylaxis and 250 patients at the Chinese Center who did not receive prophylaxis. Overall, 3.7% of patients who received seizure prophylaxis developed early seizures, compared to 2.8% of patients who did not receive any prophylaxis (p=0.573). Decompressive craniectomy was associated with the highest incidence of early seizure (9.2%). In this subgroup, the seizure rate was 10.4% in the prophylaxis group and 7.1% in the no-prophylaxis group (p=0.738). Patients with admission GCS<9 had an overall early seizure incidence of 7.0%: 4.3% in the prophylaxis group and 14.3% in the no-prophylaxis group (p=0.062). Analysis of the subgroup with isolated blunt TBI showed an incidence of early seizures of 3.4% in the prophylaxis group versus 2.4% in the no-prophylaxis group (p=0.593). Further analyses of outcomes according to head AIS 3, 4 and 5 showed no significant difference in the seizure rate between the two groups: head AIS 3: 6.1% in the prophylaxis group versus 2.6% in the no-prophylaxis group, p=0.329; head AIS 4: 0 versus 2.7%, p=0.302; head AIS 5: 8.7 versus 4.0%, p=0.601. The present study failed to show any benefit of routine early seizure prophylaxis following blunt TBI. This practice should be reexamined in a large randomized clinical study.

Incidence of seizure in stroke patients treated with recombinant tissue plasminogen activator: A systematic review and meta-analysis.

Background Recombinant tissue plasminogen activator is the only FDA-approved thrombolytic agent for acute stroke treatment. However, there are concerns that recombinant tissue plasminogen activator may increase the risk of seizures (including early and late seizures). Aims We performed a systematic review to assess the incidence of seizures and the association of recombinant tissue plasminogen activator with seizure occurrence. Summary of review We searched major databases for articles published between 1995 and February 2016. The pooled incidence of post-stroke seizure, early seizure, late seizure, and seizures sub-types was estimated overall and by status for recombinant tissue plasminogen activator treatment, and unadjusted odds ratio used to quantify the effects of recombinant tissue plasminogen activator on post-stroke seizure occurrence. In all, 4362 stroke participants were included with 49-63% being male and median age ranging from 68 to 71 years. A total of 792 received recombinant tissue plasminogen activator. The incidence of post-stroke seizure per 1000 participants (95% CI) was 95 (31-196) overall, 113 (49-202) in recombinant tissue plasminogen activator and 169 (6-326) in non-recombinant tissue plasminogen activator-treated (all heterogeneity- p<0.0001). Incidence of early seizure per 1000 (95% CI) was 35 (27-45) overall; 34 (22-50) among recombinant tissue plasminogen activator-treated patients, and 36 (25-48) among recombinant tissue plasminogen activator naïve participants (all heterogeneity- p > 0.826). The pool incidence rate per 1000 (95% CI) of late seizure was 84 (4-263), 46 (2-145), and 212 (184-241), respectively, in the overall, the recombinant tissue plasminogen activator-treated group and non-recombinant tissue plasminogen activator-treated group (heterogeneity for overall and recombinant tissue plasminogen activator-treated group < 0.0001, non-recombinant tissue plasminogen activator naïve = 0.999). The pooled odds ratio for post-stroke seizure (recombinant tissue plasminogen activator vs. no recombinant tissue plasminogen activator) was 0.94 (95% CI: 0. 17-5.26, heterogeneity- p < 0.0001). The pooled incidence per 1000 participants (95% CI) was 30 (0-144), 17 (2-49), 16 (2-44), and 9 (0-50), respectively, for focal seizure without impairment of consciousness, focal seizure with impairment of consciousness, generalized convulsive seizure, and status epilepticus; all heterogeneity- p < 0.0003. Accompanying pooled odds ratio (recombinant tissue plasminogen activator vs. no recombinant tissue plasminogen activator) based on one study was always in favor of non-significantly lower risk in recombinant tissue plasminogen activator-treated patients (all heterogeneity- p = 1). There were insufficient data to compute pooled odds ratio for early and late seizure. Conclusions Seizures affect nearly 1 out of every 10 stroke patients with inconclusive suggestion that rates are similar in recombinant tissue plasminogen activator-treated and recombinant tissue plasminogen activator naïve patients. Large prospective studies are needed to better understand the relationship between recombinant tissue plasminogen activator and post-stroke seizure occurrence.

The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats

An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration. The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults. We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes. Effects of an acute post-insult administration of the endocannabinoid receptor agonist WIN55,212-2 on early seizure occurrence, animal mortality and hippocampal cell loss were studied in the lithium–pilocarpine status model. A single dose of WIN55,212-2 (5mg/kg) administered four hours after the end of status epilepticus (SE) reduced the incidence of early seizures during the first two post-SE days though did not change their duration and latency. Brief 4–6-Hz spike–wave discharges appeared de novo in the latent post-SE period and the acute administration of WIN55,212-2 also reduced the incidence of the epileptiform events. A single dose of WIN55,212-2 administered soon after SE improved survival of animals and reduced cell loss in the dentate hilus but did not prevent appearance of spontaneous recurrent seizures in the chronic period. Thus, a brief pharmacological stimulation of the endocannabinoid system soon after a brain insult exerts beneficial effects on its pathological outcome though does not prevent epileptogenesis.

Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Seizure following traumatic brain injury (TBI) constitutes a common complication that requires effective prevention to improve the outcome of TBI. Phenytoin has been the only recommended antiepileptic drug (AED) for seizure prophylaxis; however, several shortcomings have affected its use. Intravenous levetiracetam has been available since 2006 and has been increasingly accepted as a seizure prophylaxis for brain injury, mainly due to its favorable pharmacokinetic features and minimal adverse events profile. However, the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI are not well clarified. The aim of this study was to assess the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI. We conducted a search of the MEDLINE, EMBASE, and Cochrane library databases to March 2016, and screened original research that included patients with TBI who received levetiracetam. We included randomized controlled trials (RCTs) or controlled observational cohort studies that compared levetiracetam and phenytoin, as well as uncontrolled case series regarding prophylactic levetiracetam following TBI. The outcomes included early or late seizure prophylaxis and safety. The estimates of seizure prophylaxis were pooled using a meta-analysis, and the estimates for the case series were pooled using descriptive statistics. A total of 1614 patients from 11 studies were included in this review, of whom 1285 patients from eight controlled studies (one RCT and seven cohort studies) were included in the meta-analysis. Levetiracetam was not superior to phenytoin with regard to early seizure prophylaxis (risk ratio [RR] 1.10, 95% confidence interval [CI] 0.64-1.88); the estimate of early seizure incidence was 0.05 (95% CI 0.02-0.08). Three studies that assessed late seizure did not indicate the superiority of levetiracetam to phenytoin. There were no differences in mortality during hospitalization or after 6months, or in the number of patients with adverse reactions between levetiracetam and phenytoin. Levetiracetam does not appear to be superior to phenytoin in efficacy or safety with regard to early or late seizure prophylaxis following TBI; however, no class I evidence was identified. Additional evidence from high-quality studies is required.

Seizures in the acute stroke setting

Stroke is one of the leading causes of long-term disability. One in six people in the world will suffer a stroke in their lifetime, with the annual incidence about 117 per 100 000 person-years in developing countries. It has also been shown to be the cause of 10–15% of epilepsies, more prevalent in patients above 60 years of age. The incidence of early seizures in acute stroke ranges 3–33%, with 50–78% of the seizures occurring within the first 24 hours. Occurrence of seizures within 24 hours of stroke is associated with higher 30-day mortality, which may be a reflection of severe neuronal damage. Alteration in intracellular ion concentrations and hyper-excitability are thought to be etiologies for early seizures in acute stroke, and the increased stress on already vulnerable tissues may result in worsening of stroke symptoms. Early detection of seizures and subsequent effective treatment can prevent additional metabolic burden and damage to the blood–brain barrier, which may improve recovery and overall outcome. Clinical seizures can be recognized readily at bedside and lead to prompt medical intervention. In contrast, electrographic seizures with subtle or no clinical sign and non-convulsive status epilepticus (NCSE) may escape clinical observation and be left untreated. With the use of continuous electroencephalogram monitoring (cEEG), patients with electrographic seizures can be better identified and medically treated more quickly. In addition to electrographic seizures, the presence of isolated and periodic epileptiform patterns on electroencephalogram (EEG) suggests the need for medical treatment since up to 75% of these patients have been found to develop early post-stroke seizures. Newer anti-epileptic medications with intravenous formulation, together with traditional regimen and barbiturate, have shown promise in controlling early post-stroke seizures and possibly improving outcome.

Stroke : Highlights of Selected Articles

HomeStrokeVol. 44, No. 6Stroke: Highlights of Selected Articles Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBStroke: Highlights of Selected Articles Scott B. Silverman, MD Scott B. SilvermanScott B. Silverman Search for more papers by this author Originally published1 Jun 2013https://doi.org/10.1161/STROKEAHA.113.002000Stroke. 2013;44:1499Paroxysmal Supraventricular Tachycardia and the Risk of Ischemic StrokeAtrial fibrillation and atrial flutter are currently the only cardiac arrhythmias known to be risk factors for ischemic stroke. Patients with cardioembolic-appearing stroke have supraventricular arrhythmias more often than patients with other types of stroke. Multiple studies have also shown a link between frequent supraventricular ectopy and stroke in the absence of atrial fibrillation. Paroxysmal supraventricular tachycardia (PSVT) affects mostly older patients who have a high burden of cardiovascular disease. Atrial fibrillation is associated with PSVT. The current retrospective study by Kamel et al sought to demonstrate a possible association between PSVT and stroke. They reviewed ≈4.8 million patients from emergency room visits and hospitalizations at California’s nonfederal acute care hospitals in 2009. Of these patients, >14 000 (0.29%) were diagnosed with PSVT, and >14 000 (0.30%) had a diagnosis of ischemic stroke. Patients with PSVT were older and had significantly more cardiovascular risk factors than patients without PSVT. The cumulative stroke rate after the diagnosis of PSVT (0.94%) significantly exceeded the rate among patients without PSVT (0.21%; P<0.001). Stroke occurred a median of 70 days after index visit. PSVT was independently associated with a higher risk of subsequent stroke (hazard ratio, 2.10). An age cutoff existed such that PSVT was associated with a higher risk of stroke in patients ≥65 years old. This is an important work, for PSVT may be an independent risk factor for ischemic stroke and thus accounts for a proportion of stroke currently classified as cryptogenic. Further prospective studies are needed. See p 1550.Incidence and Predictors of Late Seizures in Intracerebral HemorrhagesThe Prognosis of InTra-Cerebral Hemorrhage cohort is an observational cohort at the Lille University Hospital in France. Early seizures were classified as ≤7 days and late seizures (LSs) as >7 days after stroke onset. The authors previously reported an early seizure incidence of 14%. Early seizures in this cohort were associated with cortical intracerebral hemorrhage and did not influence in-hospital mortality or 6-month outcome. The current study population consisted of 324 patients. During 778 person-years of follow-up, 31 patients developed ≥1 LS, resulting in an incidence rate of 4 new cases/100 person-years. Nine months were the median delay between intracerebral hemorrhage and LS. Cortical involvement of the intracerebral hemorrhage was the only factor independently associated with LS. Lobar microbleeds were predictors of LS as well. Early seizures were not predictive of LSs. Interestingly, LSs were associated with a worse functional outcome after 3 years of follow-up. Further prospective studies are needed to confirm these findings. It would be interesting to know as well whether location of the cortical hemorrhage and microbleed differed significantly with the risk of LS. See p 1723. Previous Back to top Next FiguresReferencesRelatedDetails June 2013Vol 44, Issue 6 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.113.002000 Originally publishedJune 1, 2013 PDF download Advertisement

A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors

Seizures are a potentially devastating complication of resection of brain tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas. Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned. The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of 0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients. The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%-18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.