Stroke Seizures Research Articles

Abstract 41: Acute Seizures and Neurologic Deficits Predict Epilepsy After Pediatric Stroke

Background: Epilepsy may be frequent after pediatric stroke. However, current incidence estimates are from tertiary referral centers and vary widely, and little is known about its risk factors. Methods: We performed a population-based study of epilepsy within a cohort of children with stroke (birth-20 years) enrolled in a Northern California integrated health care system, from January 1993 through December 2007, to determine epilepsy incidence rates and predictors. Children with symptomatic ischemic and hemorrhagic stroke surviving to hospital discharge were included in the analysis. Seizures were identified using clinical databases, and epilepsy diagnoses were confirmed by independent record review by two neurologists with arbitration by a third. Based on International League Against Epilepsy proposed guidelines, epilepsy was defined as a confirmed unprovoked seizure > 30 days after stroke. Survival analysis was used to determine rates and predictors of epilepsy after stroke. Using multivariable analysis, hazard ratios (HR) were adjusted for gender, age (neonatal versus later childhood), stroke subtype (ischemic versus hemorrhagic), outcome at hospital discharge, and acute seizures at the time of stroke. Results: From an initial study population of 2.4 million children, 371 children with stroke were included. Of these, 110 cases were neonatal and 261 were later childhood; 226 were ischemic and 145 were hemorrhagic. At stroke ictus, 36% had an acute seizure, and 66% had a neurologic deficit at hospital discharge. Median length of follow-up was 4.5 years (IQR 1.9-8.6). Post-stroke epilepsy occurred in 89 subjects. The average annual incidence rate of epilepsy was 6.4% (95% CI 5.2%, 8%), with a 5-year cumulative risk of 25% (95% CI 20%, 30%) and 10 year cumulative risk of 40% (95% CI 32%, 51%) ( Figure ). Predictors of epilepsy included neurologic deficit at hospital discharge (HR 1.8, 95% CI 1.07-3) and seizure at stroke ictus (HR 4.1, 95% CI 2.6-6.5) ( Figure ), but not gender, age or stroke subtype. Conclusions: Epilepsy is common after stroke in children. Those with seizures at onset of stroke are at particularly high risk, in keeping with animal models of epileptogenesis and recent studies of human neonatal hypoxic ischemic brain injury. Future studies are needed to further identify children at greatest risk for post-stroke epilepsy. Figure. Kaplan Meier curves of (A) seizure free survival after pediatric stroke, (B) among children with or without neurologic deficit, and (C) among children with our without seizure at the time of stroke.

Seizures in Acute Childhood Stroke

To describe the risk of seizures in children with acute stroke and identify factors predicting their later risk of epilepsy. Data for patients >3.5 years of age at a tertiary care children's hospital with acute stroke were collected and reviewed. Seventy-seven patients were identified (mean age, 8.4 years); 21% had clinical seizures. An additional 10% of patients had a clinical seizure during the acute hospitalization. Status epilepticus was common in infants and patients with cortical strokes. Non-convulsive status epilepticus was captured only in patients with prolonged electroencephalograms and always within 24 hours of monitoring. Six months after their stroke, 24% of our patients had epilepsy, all of whom experienced seizures at initial presentation with stroke. In our series of pediatric patients with stroke, most of the clinical seizures occurred within the first 24 hours of presentation and did not vary in stroke subtype. Status epilepticus was common, especially in infants. Epilepsy had a high likelihood of developing in the next 6 months in children with seizures in the first 24 hours of stroke onset. Prolonged electroencephalogram monitoring was useful in detecting non-convulsive status epilepticus, but not in predicting the risk of epilepsy at 6 months.

Maladie de Fabry : une maladie du métabolisme par déficit d’une enzyme lysosomale (alpha-galactosidase), de transmission héréditaire liée au chromosome X accessible au traitement enzymatique de substitution

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result is intralysosomal accumulation of glycosphingolipids. In males who carry the mutation, severe multisystem disease develops in childhood or adolescence. Attacks of acute pain lasting a few minutes to a few days occur in the hands and feet, joints, muscles, and abdomen, sometimes with a fever and an acute phase reaction. Highly suggestive skin lesions called angiokeratomas develop, as well as cornea verticillata characterized by corneal deposits without visual impairment. Stroke seizures, heart disorders (conduction disturbances, valve disease, and left heart failure) and kidney disorders (proteinuria and chronic renal failure) develop in the third or fourth decade of life. Women who are heterozygous for the Gal gene can transmit the disease to their sons but are usually free of symptoms although many have cornea verticillata. However, they may have moderate or severe disease related to uneven chromosome X inactivation. Late-onset variants with predominant neurological, cardiac, or renal manifestations have been described, and also a few cases of osteoporosis or aseptic osteonecrosis. The diagnosis is difficult when the family history is negative for Fabry disease. Tests on plasma and leukocytes show very low levels or absence of alpha GalA activity in affected men, confirming the diagnosis. The Gal gene mutation should be looked for to detect heterozygous women. Symptomatic treatments include analgesics, antihypertensives, antiplatelet agents or anticoagulants to treat ischemic events, and hemodialysis or kidney transplantation to treat chronic renal failure. The prescription of enzyme replacement therapy with agalsidase alpha or beta is a major breakthrough in the treatment of patients suffering from Fabry disease. Enzyme replacement therapy relieves the pain and decreases the risk of the complications. Other lysosomal metabolic diseases as Farber disease or Niemann-Pick disease are due to a specific enzyme deficit, but without enzyme replacement therapy.

Clinical spectrum of post-stroke seizures.

To determine the characteristics of post-stroke seizures and compare these in early vs. late post-stroke seizures. Observational study. Department of Neurology, Liaquat National Hospital, Karachi, from March to September 2007. All admitted patients aged over 25 years, with diagnosis of post-stroke seizures were included. Those with known epilepsy, sepsis and electrolyte imbalance were excluded. Age, co-morbid condition, details of seizures and radiological findings regarding type and location of stroke were collected and entered in a pre-formed proforma. Results were described as frequency and mean. Association of variables was determined through chi-square test with significance at p < 0.05. Out of the 50 patients, there were 28 (56%) males and 22 (44%) females with the mean age of 56.86 ± 15.26 years. Thirty-one (62%) patients had history of hypertension. Early seizures i.e. within 2 weeks were seen in 29 (58%) patients. Generalized seizures were seen more frequently i.e. in 37 (74%) patients. Thirty-one (62%) subjects experienced more than 2 seizures. Forty (80%) had an ischemic stroke including 36 (72%) arterial infarct and 3 (6%) venous infarcts. Intracerebral hematoma was seen in 10 (20%) of subjects. Comparison between early and late onset seizures revealed significant association between ischemic heart disease (IHD), old stroke, hypertension and late onset seizures (p < 0.05). Post-stroke seizures were more frequent in males, with history of hypertension, and with cortical ischemic strokes. Early seizures, multiple episodes and generalized seizure type were more common. Venous infarcts were chiefly associated with seizures at presentation. History of old stroke, ischemic heart disease, hypertension and hypercholesterolemia showed a strong relationship with the occurrence of late onset seizures.

EEG Patterns and Epileptic Seizures in Acute Phase Stroke

Background: The rate of early post-stroke epileptic seizures ranges from 2 to 33%. This wide range is likely due to differences in study design, patient selection and type of neurophysiological monitoring. Electroencephalography (EEG), which is not used in the routine work-up of acute stroke, is the best neurodiagnostic technique for detecting epileptic activity, especially in patients with non-convulsive post-stroke epileptic activity. The aim of this study was to analyze patterns on EEGs performed within 24 h of stroke onset, and to investigate correlations between these patterns and the occurrence of early epileptic seizures and status epilepticus (SE), vascular risk factors, stroke subtypes and short-term outcome. Methods: We prospectively studied 232 patients (mean age 71 ± 12 years; 177 ischemic strokes and 55 hemorrhagic). EEG recording was performed within 24 h from hospitalization. The follow-up lasted 1 week. Results: Fifteen patients (6.5%) had early seizures within 24 h; 10 of these patients had focal SE with or without secondary generalization. EEG revealed sporadic epileptiform focal abnormalities in 10% and periodic lateralized epileptiform discharges (PLEDs) in 6%. SE was recorded in 71.4% of patients with PLEDs. At the multivariate analysis, only early epileptic manifestations (p < 0.001) were independently associated with PLEDs. Conclusions: Our study confirms that seizures are not frequent in the early phase of acute stroke and occur prevalently as focal SE at onset. EEG may help to detect specific patterns, such as PLEDs, that are closely related to early seizures. EEG monitoring should be performed in order to detect purely electrographic seizures.

Halogenated aromatic amino acid 3,5-dibromo-d-tyrosine produces beneficial effects in experimental stroke and seizures

The effects of the halogenated aromatic amino acid 3,5-dibromo-D: -tyrosine (3,5-DBr-D: -Tyr) were studied in rat models of stroke and epileptic seizures caused by middle cerebral artery occlusion (MCAo) through respective intracerebral injection of endothelin-1 (ET-1) and intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ). 3,5-DBr-D: -Tyr was administered as three bolus injections (30 or 90 mg/kg, i.p.) starting at 30, 90, and 180 min after ET-1 administration or as a single bolus (30 mg/kg, i.p.) 15 min prior to PTZ administration. Neurological deficits and infarct volume were estimated 3 days after ET-1 administration and seizure score was assessed during the first 20 min after PTZ administration. The safety of 3,5-DBr-D: -Tyr was evaluated in control animals using telemetry to measure cardiovascular parameters and immunostaining to assess the level of activated caspase-3. 3,5-DBr-D: -Tyr significantly improved neurological function and reduced infarct volume in the brain even when the treatment was initiated 3 h after the onset of MCAo. 3,5-DBr-D: -Tyr significantly depressed PTZ-induced seizures. 3,5-DBr-D: -Tyr did not cause significant changes in arterial blood pressure, heart rate and spontaneous locomotor activity, nor did it increase the number of activated caspase-3 positive cells in the brain. We conclude that 3,5-DBr-D: -Tyr, by alleviating the deleterious effects of MCAo and PTZ in rats with no obvious intrinsic effects on cardiovascular parameters and neurodegeneration, exhibits promising potential as a novel therapeutic direction for stroke and seizures.

Acute symptomatic seizures—Should we retain the term?

Acute symptomatic seizures—Should we retain the term?

Seizures in Childhood Ischemic Stroke

Clinical and radiographic findings in children (age range, 1 month to 18 years) with seizures after ischemic stroke between 1996 and 2006 were analyzed retrospectively at Chang Gung Children’s Hospital and University College of Medicine, Taoyuan, Taiwan.

Frequency and characteristics of early seizures in Chinese acute stroke.

We retrospectively studied 1200 hospitalized acute strokes of all etiologies between July 1990 and August 1992. Ninety-six % of all strokes underwent computed tomography of the head. Fifty-eight percent of the 1200 strokes were brain infarction, 32% brain hemorrhage, 6% subarachnoid hemorrhage and 4% were other stroke subtypes. Thirty (2.5%) of all strokes suffered from early seizures. The incidences of early seizures were 2.8% in brain hemorrhage, 2.3% in brain infarction, 2.7% in subarachnoid hemorrhage and 2% in other stroke subtypes. Early seizures were documented in 6% of the patients with carotid territory cortical infarctions and 12% of the patients with lobar hemorrhage, whereas only 0.6% of the patients without carotid territory cortical infarctions and 0.6% of the patients without lobar hemorrhage were affected. Sixty-six percent of 30 early seizures were partial seizures, 24% generalized and status epilepticus were seen only in 10%. In conclusion, we found the early seizure incidence was 2.5% in Chinese patients hospitalized with acute strokes. There was no correlation between seizure occurrence and stroke subtypes. Early seizure developed significantly higher in acute stroke patients with lesions of the cortex than those patients without cortical involvement. The partial seizures were the most frequent type occurring in 66% of all acute stroke patients with early seizures.

Induction of Akt by endogenous neurosteroids and calcium sequestration in P19 derived neurons

Neuronal cell death caused by pathophysiological over-activation of glutamate receptors and the subsequent CaII overloading, has been implicated in neurodegeneration after stroke, cerebral trauma and epileptic seizures. Recent findings suggest that certain progesterone metabolites (neurosteroids) such as allopregnanolone and dehydroepiandrosterone can protect neuronal cells from such insults. In the present study, murine P19 cells were induced to differentiate into postmitotic neurons expressing specific neuronal markers, including GABA(A) and NMDA receptors. Activation of NMDA receptors in P19-N neurons resulted in excitotoxic cell death, which involved suppression of the phosphorylation of the survival kinase PKB/Akt. Allopregnanolone and DHEA induced a rapid and prolonged phosphorylation of the Akt kinase and they were able to reverse the NMDA-induced suppression of the PI3-K/Akt pathway. The specificity of the neuroprotective effects of these neurosteroids was confirmed by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin, as well as by the GABA(A) receptor antagonist, bicuculline. The neurotoxic effect of NMDA on P19-N neurons was directly correlated with increased CaII entry, since the addition of EGTA or BAPTA-AM, significantly suppressed the NMDA-induced decrease of phospho-Akt and subsequent neuronal death. These results suggest that neurosteroids are able to act as survival factors on P19-N neurons, promoting the activation of the PI3-K/Akt pathway through a calcium-entry dependent mechanism.

Seizures in childhood ischemic stroke in Taiwan

In this retrospective study, we collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of seizure after ischemic stroke for the period of January 1996 to July 2006. Thirty-nine out of 94 children with ischemic stroke had poststroke seizures. Thirty-three out of 39 children with poststroke seizures had new onset seizures but only data of 28 were available. Infection was the most common etiology in the early poststroke seizure group (52.4%) but not in the late poststroke seizure group (0%). Infarction involving arterial ischemic stroke of anterior circulation were the most common in both the early poststroke seizure (61.9%) and the late poststroke seizure group (57.1%). Epilepsy was the most common sequelae in both the early poststroke seizure (38.1%) and late poststroke seizure group (100%). Children who had initial focal neurological sign (100% vs. 38.1%; P = 0.007) or the focal cortical dysfunction on EEG (85.7% vs. 33.3%; P = 0.029) were prone to develop late poststroke seizures. Late poststroke seizures had a high risk of developing poststroke epilepsy (100% vs. 38.1%; P = 0.007). We conclude that seizures commonly occur in childhood ischemic stroke. Most poststroke seizures developed at an early stage. Infection was the most common etiology that caused early poststroke seizures in childhood ischemic stroke. Initial focal neurological signs and focal cortical dysfunction on EEG are risk factors for developing epilepsy. Poststroke seizures did not affect mortality, but there was a significant difference in normal outcome and epilepsy between those with or without poststroke seizures.

Effects of Ascorbic and Dehydroascorbic Acids on Apoptotic Cell Death in Hippocampal Slice Culture

Ascorbic acid (AA) and dehydroascorbic acid (DHA) are known to have protective effects in experimental central nerve system disorder models such as stroke, ischemia, and epileptic seizures. The present study was conducted to examine the protective effect of AA and DHA on kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures (OHSC). Protective effects of AA and DHA on KA-induced cell death were evaluated by analyzing caspase-3. In addition, to determine if the prooxidant effect of AA is related to iron, the effect of AA on cell death was examined using desferrioxamine (DFO), an iron chelator. After 12h-KA treatment, significant delayed neuronal death was detected in CA3 region, but not in CA1. The AA (500 μM) and DHA (100 and 500μM) pretreatments significantly prevented cell death by inhibiting caspase-3 activation in CA3 region. In the concentration of 1,000μM, however, AA pretreatment might have prooxidant effect, but AA-induced oxidative reaction is mainly not related to transition metal ions. These data showed that the pretreatments of intermediate-dose AA and DHA protected KA-induced neuronal damage in OHSCs and co-pretreatment of AA and DFO did not affect cell death except for a few cases. These data suggest that both AA and DHA pretreatment have antioxidant or prooxidant effect depending on doses treated on KA-induced neuronal injury and the possible prooxidant effect of AA may not depend on the Fenton reaction.

Management of arterial hypertension in patients with acute stroke

Management of arterial hypertension in the hyperacute period immediately after stroke ictus remains controversial. Extremes of blood pressure (BP) are associated with poor outcomes in all stroke subtypes. Severely hypertensive patients likely benefit from modest BP reductions, but aggressive BP reduction may worsen outcome. Although little evidence is currently available to definitively establish guideline recommendations for optimal BP goals at stroke presentation, recently published research is shedding some light on how to approach management of BP after stroke. Antihypertensive treatment should probably be deferred in ischemic stroke patients except in cases of severe hypertension or when thrombolytic therapy is warranted and the patient's BP is above acceptable levels. Hypertensive hemorrhagic stroke patients may benefit from modest BP reductions. Relative hypotension causing regional hypoperfusion is an increasingly understood concept immediately following ischemic or hemorrhagic stroke, emphasizing the need for careful titration of appropriate medications to minimize fluctuations in BP for treated patients. Ongoing trials will improve our current knowledge regarding BP management after ischemic and hemorrhagic stroke.

Seizures and epilepsy after ischemic stroke.

Although a long-recognized clinical phenomenon, there remain many questions regarding the epidemiology of seizures and epilepsy after ischemic stroke, their effect on outcome, and their treatment. Interpretation of the various studies that have been conducted of postischemic stroke seizures and epilepsy are complicated by their heterogeneous designs, inconsistent uses of terminology, small sample sizes, different periods of follow-up, and ambiguities in seizure identification and classification. Estimates of the rate of early postischemic stroke seizures range from 2% to 33%. The rates of late seizures vary from 3% to 67%. The rate of postischemic stroke epilepsy is approximately 2% to 4% and is higher in those who have a late seizure. Data reflecting seizure subtypes are limited. Aside from cortical location and, possibly, stroke severity, no other risk factors for postischemic stroke seizures have been consistently demonstrated. Much additional work is needed to better understand the epidemiology and social impact of postischemic stroke seizures and epilepsy, their prevention, and optimal management.

Prodromal and early epileptic seizures in acute stroke: does higher serum cholesterol protect?

In a case-control study, patients (n = 43/3,628) presenting seizures <1 week before (n = 6), < or =3 hours after (n = 26), and 3 to 24 hours after (n = 11) a first-ever stroke were studied. On multivariate analysis, they were characterized by lower levels of serum cholesterol (5.86 +/- 0.51 vs 6.34 +/- 0.58; p < 0.0001). Mortality and functional outcome at discharge were not influenced. Early poststroke seizures occur mainly during the critical 3-hour window for thrombolysis. Hypercholesterolemia appears to protect against seizures and cerebral ischemia.

Abstracts of Literature

Abstracts of Literature

Epileptic seizures after a first stroke: the Oxfordshire community stroke project

Objective: To describe the immediate and long term risk of epileptic seizures after a first ever stroke.Design: Cohort study following up stroke survivors for 2 to 6.5 years; comparison with...

Seizures in acute stroke: predictors and prognostic significance. The Copenhagen Stroke Study.

Despite the common occurrence of seizures during the early phase of stroke (ES), the effect of ES on prognosis is not known. We determined the relationships between ES and stroke outcome and identified predictors of ES. In this community-based study, we prospectively and consecutively studied 1197 patients with acute stroke. We determined the number and type of seizures, initial stroke severity, infarct size, mortality, and outcome in survivors. Stroke severity was measured on admission, weekly, and at discharge using the Scandinavian Stroke Scale (SSS). Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors, including age, gender, stroke severity on admission, atrial fibrillation, ischemic heart disease, diabetes, blood glucose level on admission, claudication, and hypertension. Fifty patients (4.2%) had seizures within 14 days of the stroke. In the multivariate analyses, only initial stroke severity was related to ES; stroke type and lesion localization were not related. For each 10-point increase in stroke severity (SSS score), the relative risk of ES increased by a factor of 1.65 (95% confidence interval, 1.4 to 1.9) (P < .0001). ES did not influence the risk of death during hospital stay (P = .56). In survivors, ES was related to a better outcome, equivalent to an increased SSS score of 5.7 points (SE [b] = 1.8; P = .002). The decisive factor of ES was initial stroke severity. ES per se was not related to mortality. Surprisingly, in survivors, ES predicted a better outcome. We explain this finding by a relatively larger ischemic penumbra in patients who have an ES after a stroke.

Poststroke Seizures in the Elderly

Strokes are the most common cause of epilepsy in the elderly. Seizures after an acute stroke have been estimated to occur in 5% to 10% of cases. A distinction between early and late seizures should be made. Early seizures are more common, occur very early in the evolution of the stroke, and tend to be focal motor, brief, and isolated. They are likely to be the result of an acute local brain metabolic alteration induced by the cerebrovascular event, and once these derangements are reversed, seizures disappear. Epilepsy usually does not follow early seizures, but the risk is probably increased. Late seizures occur months to years after the stroke and are probably due to structural brain abnormalities leading to the development of an epileptic focus. The majority of these cases develop epilepsy. The risk of seizures is markedly increased when the cerebrovascular event involves the cerebral cortex. Deep-seated hemispheric or infratentorial lesions rarely produce seizures or epilepsy. It is possible that hemorrhagic stroke carries a higher incidence of seizures, but the issue remains controversial. It has also been suggested that embolic infarction has a higher incidence of seizures that does thrombotic infarction, but definitive evidence is lacking. The presence of seizures in an acute stroke does not seem to correlate with the size of the lesion, functional outcome, or mortality. Prophylactic treatment with antiepileptic drugs is probably not indicated in most types of strokes, except for subarachnoid hemorrhage after a ruptured intracranial aneurysm. When early seizures develop, treatment is indicated but may not be necessary for a prolonged period of time. If late seizures develop, chronic anticonvulsant therapy is recommended.

Epileptic seizures in thrombotic stroke

Epileptic seizures due to thrombotic cerebral infarction were studied in 118 patients. The occurrence of seizures had a bimodal distribution with one peak period within 2 weeks and another peak period from 6 to 12 months after stroke. Four patients had seizures preceding stroke, while 23 patients without a history of previous stroke had "silent infarct" on the CT scan. Fifteen patients (13%) had status epilepticus. Simple partial seizures occurred in 56% of patients, complex partial seizures in 24% and generalized tonic-clonic seizures in 4%. Epilepsy developed in 35% of patients with early seizures and in 90% of patients with late seizures.