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|NI FEATURE: THE EDITORIAL DEBATE II-- PROS AND CONS
|Year : 2018 | Volume
| Issue : 4 | Page : 952-954
Not to forget: Seizures in acute stroke
Achal Kumar Srivastava, Anand R Warrier
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||18-Jul-2018|
Dr. Achal Kumar Srivastava
Room No. 60, Ground Floor, Neurosciences Center, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Srivastava AK, Warrier AR. Not to forget: Seizures in acute stroke. Neurol India 2018;66:952-4
Stroke is the major cause of epilepsy in middle-aged adults. Concern regarding post stroke seizure has grown over the past few years with the advent of newer revascularisation strategies paralleled with raised outcome expectations with secondary prophylaxis and newer rehabilitation techniques. The vexing question concerning the therapy in post stroke epilepsy (PSE) has resulted in the stratification of post stroke seizures into 'early' and 'late' PSE , (defined by the International League Against Epilepsy [ILAE] as seizures developing within 7 days, or more than 7 days after the ictus, respectively) as pathogenesis, and consequently, management and prognosis differs in both the entities. The accepted terminology for epilepsy has now changed following the publication of the recent ILAE classification. Even if one unprovoked seizure in a patient with an enduring predisposition of the brain to generate further seizures, and the probability of further seizures is similar to the general recurrence risk after two unprovoked seizures (at least 60%), then the person should be considered to be suffering from epilepsy. This definition of 'post stroke epilepsy' has far reaching consequences with regard to the initiation and continuation of anti-epileptic (AED) therapy and the stigma associated with the terminology of 'epilepsy'. The incidence of early seizures was 3.3%, and that of late seizures or epilepsy 18 per 1,000 person-years in a recent metaanalysis of early and late post stroke seizures. Most of the seizures after stroke develop early within a few days of stroke onset. Almost 43% patients in a seizures-after-stroke study had seizures within 24 hours of stroke onset. The pathways of epileptogenesis clearly differ in early and late seizures, as early seizures are said to be due to ionic shifts and excitotoxic neuronal injury, whereas late epileptogenesis may be the result of cerebromeningeal cicatrix formation., PSE risk is higher after late onset seizures than early onset seizures., In ischemic or hemorrhagic strokes, epilepsy developed in approximately 30% of patients with early onset seizures and in 90% of patients with late onset seizures. The risk of future epilepsy is higher in those stroke patients with an early onset seizure (30%) than in those without a seizure (5%–20%).
The long-term cumulative risk of PSE after a cerebrovascular event varies between 2% and 15%., This variability is attributed to the great heterogeneity in studies in terms of types of stroke included, variability in follow up time, definition of early seizure, outcome measures, patient drop-outs, and whether or not patient survival correction was applied. The risks of PSE depends on the type of stroke (intracerebral hemorrhage, anterior circulation infarcts having a higher incidence), volume of infarcts (larger strokes having a greater predisposition to developing PSE), the severity of stroke [those with a higher National Institutes of Health Stroke Scale (NIHSS) having a greater incidence], the location of infarcts in ischemic stroke (cortical infarcts having a higher PSE risk), age of stroke onset (younger age predisposing to greater PSE risk, which actually reflects survival rather than increased susceptibility to epileptogenesis), and cortical symptoms like dysphasia.,, In the largest study to date that was performed in the United Kingdom and followed 3310 patients with newly diagnosed stroke for an average of 3.8 years, 213 subjects (6.4%) developed of PSE and the 10-year cumulative risk was estimated to be 12.4%. Early seizures were associated with an increased risk of PSE in the Copenhagen stroke study but their definition of early PSE was a seizure occurring within 2 weeks, unlike the new ILAE definition of 7 days. Other than surgical intervention in intracranial haemorrhage, none of the clinical risk factors identified to date indicate a seizure risk high enough to warrant prophylactic antiepileptic treatment in early seizures though the actual practice varies. Regarding stroke severity, the incidence of seizures among 306 patients admitted to a rehabilitation facility because of the development of a stroke sequelae was 15%, with a recurrence of seizures observed in 90% of them within a year, in spite of the institution of AED treatment.
Antiepileptics, as we already know, act through neuronal signal modulation, and their use in a single post stroke seizure, especially early seizures, may hamper post stroke rehabilitation measures and poses an ethical dilemma. It is, therefore, logical and justifiable to administer AEDs based on risk stratification in post stroke patients. The use of AEDs, however, in the presence of early seizures (where epileptogenesis and permanent changes in neuronal modulation may not have set in) is controversial, though as previously mentioned, the presence of early onset seizures after an acute stroke leads to an increasing propensity to having a higher incidence of PSE than is seen in a post stroke patient without early onset seizures. Attempts have been made to prevent PSE in high-risk populations like those patients presenting with an intracerebral haemorrhage, where valproic acid was given as primary prophylaxis for 1 month, which reduced the number of early seizures but had no impact on the development of epilepsy (however, the study was underpowered). Similar randomized control trials involving levetiracetam (LEV) and diazepam did not show any benefit in PSE. LEV, lamotrigine (LTG), and sometimes gabapentin (GBP), have been utilized as reasonable first choices in PSE. In cases of severe or frequent seizures, GBP would probably not be a first choice, given the results of the SANAD study regarding the first-choice drug for newly diagnosed epilepsy. But no randomized control trials exist with regard to secondary prophylaxis. The European Stroke Organisation guidelines for post stroke seizures 2017 state that the level of evidence of AEDs for primary prophylaxis for acute symptomatic seizures in post stroke patients is very weak, considering the fact that the incidence of post stroke seizures is very less and that of early recurrence is even lesser. The European Stroke Organisation (ESO) guidelines advocate AED secondary prophylaxis in many centres to reduce the risk of clinical worsening in the acute setting, the underlying concept of this approach being pathophysiological considerations such as increased neuronal excitotoxicity, peri-infarct depolarisations and inflammatory response. There are no trials on the effect of continued long term post-stroke AED treatment vs placebo on the functional outcome. All other available studies focus on the question on whether or not acute symptomatic seizure/unprovoked seizures are independant risk factors for an unfavourable functional outcome, but the results are ambiguous., Patients with intracerebral haemorrhage and cortical involvement, a younger age, with more than 10 ml intracerebral hemorrhage and acute symptomatic epilepsy (a high CAVE score) had an unprovoked seizure risk of 46.2%, and hence, AED primary prophylaxis may be justified. Randomized studies comparing newer AEDs like levetiracetam (the EPiC study) with carbamazepine showed comparable seizure outcomes in both the arms, and hence, the former maybe used as an alternative drug for post-stroke AED treatment. Also with regard to mortality, PSE seems to have mixed results, and future larger studies are needed to confirm the results.,,,, In a multivariate analysis, PSE was independently associated with a poor outcome after cerebral infarction, as assessed by the mRs (modified Rankin scale) [The FUTURE study  with a 10-year follow up, in 2013 showed that epilepsy was an independent predictor of a poor functional outcome after stroke or transient ischemic attack].
The study by Shehta et al., is yet another emphatic contribution to the existing knowledge of a bit complex relation of seizure with acute stoke. In this, the study population is clearly defined as having early post stroke seizures (seizures within 7 days of onset of stroke). Most of the baseline parameters are comparable. This study showed similar results as that of previous data, with a large volume infarct, the cortical location of the infarct, and the presence of intracerebral haemorrhage, predicting an increased risk of post stroke early seizures with an odds ratio of 2.8, 2 and 3.2, respectively. But the severity of stroke in both the arms (those with early seizures and those without) were not balanced at the baseline. Those with seizures had a poorer NIHSS score at presentation (14.3 ± 7.8 in the early seizure group and 9.6 ± 6.8 in those without an early seizure). Though one can argue that seizures before the presentation might be the reason for a higher NIHSS at admission and consequently, poorer functional outcome and higher mortality, the fact whether or not early seizures independantly predicted the outcome still remains an enigma as the data regarding the NIHSS score prior to the seizure onset is unavailable. Also, the distribution of early seizures in various etiological types of stroke is unclear as anterior circulation strokes and embolic strokes are more predisposed to early seizures. The higher incidence of early seizures (9.2%) as compared to data from larger cohorts may be due to the smaller sample size and selection bias. The sample size being small, and confidence intervals of the results not being mentioned by the authors, the predictive value of the relationship of ICH, cortical infarcts and large volume infarcts to post stroke epilepsy seems dubious in this study. Nevertheless, this study again emphasizes the relationship of seizures with acute stroke and the necessity of early risk stratification so as to deliver targeted AED therapy.
Nevertheless, this study again emphasizes the relationship of seizures with acute stroke and the need for identifying at-risk patients so that appropriate therapeutic options may be provided in the current scenario.
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