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Observational Study
. 2024 Dec 1;81(12):1274-1283.
doi: 10.1001/jamaneurol.2024.3481.

Development and Validation of a Clinical Score to Predict Epilepsy After Cerebral Venous Thrombosis

Erik Lindgren  1 , Liqi Shu  2 , Naaem Simaan  3 , Katarzyna Krzywicka  4 , Maria A de Winter  5 , Mayte Sánchez van Kammen  4 , Jeremy Molad  6 , Piers Klein  7 , Hen Hallevi  6   8 , Rani Barnea  9 , Mirjam R Heldner  10 , Sini Hiltunen  11 , Diana Aguiar de Sousa  12   13 , José M Ferro  14 , Antonio Arauz  15 , Jukka Putaala  11 , Marcel Arnold  10 , Thanh N Nguyen  7 , Christoph Stretz  2 , Turgut Tatlisumak  1   11 , Katarina Jood  1 , Shadi Yaghi  2 , Ronen R Leker  16 , Jonathan M Coutinho  4 ; DIAS research collaboration; Maryam Mansour  15 , Patrícia Canhão  14 , Esme Ekizoglu  16 , Miguel Rodrigues  17 , Elisa M Silva  17 , Carlos Garcia-Esperon  18 , Valentina Arnao  19 , Shorooq Aladin  20 , Rom Mendel  21 , Paolo Aridon  19 , Mine Sezgin  16 , Andrey Alasheev  22 , Andrey Smolkin  22 , Daniel Guisado-Alonso  23 , Nilufer Yesilot  16 , Miguel A Barboza  24 , Masoud Ghiasian  15 , Suzanne M Silvis  4   25 , Ton Fang  26 , James E Siegler  27 , Teddy Wu  28 , Duncan Wilson  28 , Syed Daniyal Asad  29 , Sami Al Kasab  30 , Eyad Almallouhi  30 , Jennifer Frontera  31 , Aaron Rothstein  32 , Ekaterina Bakradze  33 , Setareh Salehi Omran  34 , Nils Henninger  26   35 , Lindsey Kuohn  31 , Adeel Zubair  36 , Richa Sharma  36 , Deborah Kerrigan  37 , Yasmin Aziz  38 , Eva Mistry  38 , Susanna M Zuurbier  4
Affiliations
Observational Study

Development and Validation of a Clinical Score to Predict Epilepsy After Cerebral Venous Thrombosis

Erik Lindgren et al. JAMA Neurol. .

Abstract

Importance: One of 10 patients develop epilepsy in the late phase after cerebral venous thrombosis (CVT) diagnosis but predicting the individual risk is difficult.

Objective: To develop and externally validate a prognostic score to estimate the individual risk of post-CVT epilepsy.

Design, setting, and participants: This observational cohort study included both retrospective and prospective patients enrolled from 1994 through 2022. For development of the DIAS3 score, data from the International CVT Consortium (n = 1128), a large international hospital-based multicenter CVT cohort, were used. For validation, data from 2 independent multicenter cohorts, the ACTION-CVT (n = 543) and the Israel CVT study (n = 556), were used. Of 2937 eligible, consecutively enrolled adult patients with radiologically verified CVT, 710 patients with a history of epilepsy prior to CVT, follow-up less than 8 days, and missing late seizure status were excluded.

Exposure: The prediction score (DIAS3) was developed based on available literature and clinical plausibility and consisted of 6 readily available clinical variables collected during the acute phase: decompressive hemicraniectomy, intracerebral hemorrhage at presentation, age, seizure(s) in the acute phase (excluding status epilepticus), status epilepticus in the acute phase, and subdural hematoma at presentation.

Main outcome and measure: Time to a first late seizure, defined as occurring more than 7 days after diagnosis of CVT.

Results: Of 1128 patients included in the derivation cohort (median age, 41 [IQR, 30-53] years; 805 women [71%]), 128 (11%) developed post-CVT epilepsy during a median follow-up of 12 (IQR, 3-26) months. According to the DIAS3 score, the predicted 1-year and 3-year risk of epilepsy in individual patients ranged from 7% to 68% and 10% to 83%, respectively. Internal and external validation showed adequate discrimination in the derivation cohort (1 year and 3 years: C statistic, 0.74; 95% CI, 0.70-0.79) and the 2 independent validation cohorts, (ACTION-CVT) 1 year: C statistic, 0.76; 95% CI, 0.67-0.84; 3 years: C statistic, 0.77; 95% CI, 0.66-0.84; and Israel CVT study 1 year: C statistic, 0.80; 95% CI, 0.75-0.86. Calibration plots indicated adequate agreement between predicted and observed risks.

Conclusions and relevance: The DIAS3 score (freely available online) is a simple tool that can help predict the risk of post-CVT epilepsy in individual patients. The model can improve opportunities for personalized medicine and may aid in decision-making regarding antiseizure medication, patient counseling, and facilitation of research on epileptogenesis in CVT.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lindgren reported grants from the Swedish Neurological Society, Elsa and Gustav Lindh’s Foundation, Per Olof Ahl’s Foundation, the Ulla Amlöv Foundation, and the Wennerstöm Foundation during the conduct of the study. Dr Heldner reported grants from the Swiss National Science Foundation, SITEM research funds, and the Swiss Heart Foundation outside the submitted work. Dr Aguiar de Sousa reported personal fees from AstraZeneca, Daiichi-Sankyo, Bial, Johnson & Johnson, and Organon and grants from MSD outside the submitted work. Dr Rodrigues reported grants from CUF outside the submitted work. Dr Garcia-Esperon reported personal fees from the American Academy of Neurology, nonfinancial support for travel from Boehringer Ingelheim and Bayer, and personal fees from AstraZeneca outside the submitted work. Dr Siegler reported grants from Viz.Ai, Medtronic, and Philips and consultant fees from AstraZeneca outside the submitted work. Dr Frontera reported grants from the National Institutes of Health and personal fees from AstraZeneca, Physician Education Resource, and Lumosa outside the submitted work. Dr Rothstein reported grants from the American Heart Association Career Development Award during the conduct of the study. Dr Sharma reported a patent pending (63/505,006) for Yale-New Haven Hospital for methods of training an algorithm to predict ischemic stroke etiology. Dr Mistry reported grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Patient-Centered Outcomes Research Institute, RAPID AI, SilverCreek Pharmaceuticals, and AbbVie and compensation for editorial activities from the American Heart Association outside the submitted work. Dr Putaala reported personal fees and grants from Bayer, grants from Amgen, personal fees from Novo Nordisk, Herantis Pharma, BMS-Pfizer, and Abbott, research collaboration from Bittium and Medixine, and research collaboration and stock ownership from Vital Signum and reported being a Visiting Editor for Terve Media. Dr Arnold reported grants from the Swiss National Science Foundation, personal fees from Bayer, Novartis, Sanofi, Amgen, Boehringer Ingelheim, Daiichi Sankyo, Novartis, and Novonordisk outside the submitted work. Dr Nguyen reported personal fees from Aruna Bio, Brainomix, and the American Stroke Association outside the submitted work. Dr Tatlisumak reported grants from Sahlgrenska University Hospital, University of Gothenburg, the Wennerströn Foundation, and the Sigrid Juselius Foundation during the conduct of the study, personal fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma outside the submitted work. Dr Jood reported grants from the Swedish State under the ALF agreement during the conduct of the study. Dr Leker reported personal fees from IschemiaView, Population Health Research Institute, and Bayer outside the submitted work. Dr Coutinho reported grants to their employer from Boehringer Ingelheim, Bayer All, and AstraZeneca outside the submitted work; and Dr Coutinho is co-founder and shareholder of TrianecT B.V. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Selection of Patients With Cerebral Venous Thrombosis (CVT) Included in the Model Development Analysis
Figure 2.
Figure 2.. Calibration Plots for Predicting Epilepsy 1 Year and 3 Years After Cerebral Venous Thrombosis (CVT) in the Derivation and Validation Cohorts
Vertical bars show 95% CIs. The 45° diagonal reference line indicates perfect calibration, where relevant deviations above or below the line are indicative of underestimation and overestimation of the predicted risk.
See this image and copyright information in PMC

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