International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke

Mishra, Nishant K.; Engel, Jerome; Liebeskind, David S; Sharma, Vijay Kumar; Hirsch, Lawrence J.; Kasner, Scott E.; French, Jacqueline; Devinsky, Orrin; Friedman, Alon; Dawson, Jesse; Quinn, Terence J; Selim, Magdy; Havenon, Adam de; Yasuda, Clarissa Lin; Cendes, Fernando; Benninger, Felix; Zaveri, Hitten P.; Burneo, Jorge G.; Srivastava, M V Padma; Singh, Mamta Bhushan; Bhatia, Rohit; Vishnu, Venugopalan Y; Bentes, Carla; Ferro, José M.; Weiss, Shennan A.; Sivaraju, Adithya; Kim, Jennifer A; Galovic, Marian; Gilmore, Emily J.; Pitkänen, Asla; Davis, Kathryn; Sansing, Lauren H; Sheth, Kevin N; Paz, Jeanne T.; Singh, Anuradha; Sheth, Sunil A; Worrall, Bradford B.; Grotta, James C.; Casillas-Espinos, Pablo M.; Chen, Zhibin; Nicolo, John‐Paul; Yan, Bernard; Kwan, Patrick

doi:10.1016/j.yebeh.2021.108502

Cited by 12 publications

(10 citation statements)

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“…In summary, there is a critical need for a larger collaborative effort to recruit a diverse patient population and investigate the mechanisms by which genetic factors drive epileptogenesis after brain insults such as TBI or stroke. The International Post Stroke Epilepsy Research Consortium (IPSERC) [46] is one such effort, convened to build a community of researchers with variable (and complimentary) expertise across the globe to conduct adequately powered studies to understand and prevent PSE. Similar efforts in other patients with cerebral pathologies and risk of epilepsy are warranted.…”

Section: Discussionmentioning

confidence: 99%

Impact of genetic polymorphisms on the risk of epilepsy amongst patients with acute brain injury: A systematic review

Misra

Quinn

Falcone

et al. 2023

Euro J of Neurology

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Background and purpose:The genetics of late seizure or epilepsy secondary to traumatic brain injury (TBI) or stroke are poorly understood. We undertook a systematic review to test the association of single-nucleotide polymorphisms (SNPs) with the risk of posttraumatic epilepsy (PTE) and post-stroke epilepsy (PSE). Methods:We followed methods from our prespecified protocol on PROSPERO to identify indexed articles for this systematic review. We collated the association statistics from the included articles to assess the association of SNPs with the risk of epilepsy amongst TBI or stroke patients. We assessed study quality using the Q-Genie tool. We report odds ratios (OR) and hazard ratios with 95% confidence intervals (CIs). Results:The literature search yielded 420 articles. We included 16 studies in our systematic review, of which seven were of poor quality. We examined published data on 127 SNPs from 32 genes identified in PTE and PSE patients. Eleven SNPs were associated with a significantly increased risk of PTE. Three SNPs, TRMP6 rs2274924, ALDH2 rs671, and CD40 -1C/T, were significantly associated with an increased risk of PSE, while two, AT1R rs12721273 and rs55707609, were significantly associated with reduced risk. The meta-analysis for the association of the APOE ɛ4 with PTE was nonsignificant (OR 1.8, CI 0.6-5.6). Conclusions:The current evidence on the association of genetic polymorphisms in epilepsy secondary to TBI or stroke is of low quality and lacks validation. A collaborative effort to pool genetic data linked to epileptogenesis in stroke and TBI patients is warranted.

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Section: Discussionmentioning

confidence: 99%

Impact of genetic polymorphisms on the risk of epilepsy amongst patients with acute brain injury: A systematic review

Misra

Quinn

Falcone

et al. 2023

Euro J of Neurology

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“…Also, efforts to reduce the mortality associated with early seizures involve efforts to prevent or correct acute metabolic defects than efforts to prevent seizures, which are just a symptom of the problem. Collaborative efforts to predict and prevent the structural and associated biological changes that lead to late seizures (ie, poststroke epileptogenesis and ictogenesis) can address the disability and mortality of these events …”

Section: Discussionmentioning

confidence: 99%

“…We also observed a significant variation in reporting standards in the published literature and propose future directions for PSS research. Collaborative scientific efforts should be directed toward addressing these challenges . The role of stroke severity and lesion location or volume also requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Outcomes in Patients With Poststroke Seizures

Misra,

Kasner,

Dawson

et al. 2023

JAMA Neurol

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ImportancePublished data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the authors’ knowledge.ObjectiveTo investigate outcomes in people with PSS compared with people without PSS.Data SourcesMEDLINE, Embase, PsycInfo, Cochrane, LILACS, LIPECS, and Web of Science, with years searched from 1951 to January 30, 2023.Study SelectionObservational studies that reported PSS outcomes.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used for abstracting data, and the Joanna Briggs Institute tool was used for risk-of-bias assessment. Data were reported as odds ratio (OR) and standardized mean difference (SMD) with a 95% CI using a random-effects meta-analysis. Publication bias was assessed using funnel plots and the Egger test. Outlier and meta-regression analyses were performed to explore the source of heterogeneity. Data were analyzed from November 2022 to January 2023.Main Outcomes and MeasuresMeasured outcomes were mortality, poor functional outcome (modified Rankin scale [mRS] score 3-6), disability (mean mRS score), recurrent stroke, and dementia at patient follow-up.ResultsThe search yielded 71 eligible articles, including 20 110 patients with PSS and 1 166 085 patients without PSS. Of the participants with PSS, 1967 (9.8%) had early seizures, and 10 605 (52.7%) had late seizures. The risk of bias was high in 5 studies (7.0%), moderate in 35 (49.3%), and low in 31 (43.7%). PSSs were associated with mortality risk (OR, 2.1; 95% CI, 1.8-2.4), poor functional outcome (OR, 2.2; 95% CI, 1.8-2.8), greater disability (SMD, 0.6; 95% CI, 0.4-0.7), and increased dementia risk (OR, 3.1; 95% CI, 1.3-7.7) compared with patients without PSS. In subgroup analyses, early seizures but not late seizures were associated with mortality (OR, 2.4; 95% CI, 1.9-2.9 vs OR, 1.2; 95% CI, 0.8-2.0) and both ischemic and hemorrhagic stroke subtypes were associated with mortality (OR, 2.2; 95% CI, 1.8-2.7 vs OR, 1.4; 95% CI, 1.0-1.8). In addition, early and late seizures (OR, 2.4; 95% CI, 1.6-3.4 vs OR, 2.7; 95% CI, 1.8-4.1) and stroke subtypes were associated with poor outcomes (OR, 2.6; 95% CI, 1.9-3.7 vs OR, 1.9; 95% CI, 1.0-3.6).Conclusions and RelevanceResults of this systematic review and meta-analysis suggest that PSSs were associated with significantly increased mortality and severe disability in patients with history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.

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“…Biomarker discovery requires a robust longitudinal design and methods acceptable to regulatory bodies such as the US FDA. A collaborative effort 49 toward biomarker discovery is therefore warranted. [50][51][52]…”

Section: Discussionmentioning

confidence: 99%

Common Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury

Misra,

Khan,

Lam

et al. 2023

Neurology

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Background and Objective:Epilepsy may result from various brain injuries, including stroke (ischemic and hemorrhagic), traumatic brain injury, and infections. Identifying shared common biological pathways and biomarkers of the epileptogenic process initiated by the different injuries may lead to novel targets for preventing the development of epilepsy. We systematically reviewed biofluid biomarkers to test their association with the risk of post-brain injury epilepsy.Methods:We searched articles until January 25, 2022, in MEDLINE, Embase, PsycINFO, Web of Science, and Cochrane. The primary outcome was the difference in mean biomarker levels in patients with and without post-brain injury epilepsy. We used the modified quality score on prognostic studies for risk of bias assessment. We calculated each biomarker’s pooled standardized mean difference (SMD) and 95% confidence intervals (CI). Molecular interaction network and enrichment analyses were conducted in Cytoscape. (PROSPERO CRD42021297110)Results:We included 22 studies with 1499 cases with post-brain injury epilepsy and 7929 controls without post-brain injury epilepsy. Forty-five biomarkers in blood or cerebrospinal fluid (CSF) were investigated with samples collected at disparate time points. Of 22 studies, 21 had a moderate-to-high risk of bias. Most biomarkers (28/45) were investigated in single studies; only nine provided validation data, and studies used variable definitions for early and late-onset seizures. A meta-analysis was possible for 19 biomarkers. Blood glucose levels in four studies were significantly higher in patients with post-stroke epilepsy (PSE) than without PSE (SMD 0.44; CI 0.19 to 0.69). From individual studies, 15 biomarkers in blood and seven in CSF were significantly associated with post-brain injury epilepsy. Enrichment analysis identified that the significant biomarkers (IL6, IL1β) were predominantly inflammation related.Discussion:We cannot yet recommend using the reported biomarkers for designing anti-epileptogenesis trials or use in the clinical setting because of methodological heterogeneity, bias in the included studies, and insufficient validation studies. Even though our analyses indicate the plausible role of inflammation in epileptogenesis, this is likely not the only mechanism. For example, an individual’s genetic susceptibilities might contribute to his risk of epileptogenesis after brain injury. Rigorously designed biomarker studies with methods acceptable to the regulatory bodies should be conducted.

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International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke

Cited by 12 publications

References 50 publications

Impact of genetic polymorphisms on the risk of epilepsy amongst patients with acute brain injury: A systematic review

Impact of genetic polymorphisms on the risk of epilepsy amongst patients with acute brain injury: A systematic review

Outcomes in Patients With Poststroke Seizures

Common Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury

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