Development and Validation of a Clinical Score to Predict Epilepsy After Cerebral Venous Thrombosis
Authors: Erik Lindgren, Liqi Shu, Naaem Simaan, Katarzyna Krzywicka, Maria A. de Winter, Mayte Sánchez van Kammen, Jeremy Molad, Piers Klein, Hen Hallevi, Rani Barnea, Mirjam R. Heldner, Sini Hiltunen, Diana Aguiar de Sousa, José M. Ferro, Antonio Arauz, Jukka Putaala, Marcel Arnold, Thanh N. Nguyen, Christoph Stretz, Turgut Tatlisumak, Katarina Jood, Shadi Yaghi, Ronen R. Leker, Jonathan M. Coutinho, Maryam Mansour, Patrícia Canhão, Esme Ekizoglu, Miguel Rodrigues, Elisa M. Silva, Carlos Garcia-Esperon, Valentina Arnao, Shorooq Aladin, Rom Mendel, Paolo Aridon, Mine Sezgin, Andrey Alasheev, Andrey Smolkin, Daniel Guisado-Alonso, Nilufer Yesilot, Miguel A. Barboza, Masoud Ghiasian, Suzanne M. Silvis, Ton Fang, James E. Siegler, Teddy Wu, Duncan Wilson, Syed Daniyal Asad, Sami Al Kasab, Eyad Almallouhi, Jennifer Frontera, Aaron Rothstein, Ekaterina Bakradze, Setareh Salehi Omran, Nils Henninger, Lindsey Kuohn, Adeel Zubair, Richa Sharma, Deborah Kerrigan, Yasmin Aziz, Eva Mistry, Susanna M. Zuurbier
Journal: JAMA Neurology (2024)

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 DIAS 3 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 (DIAS 3 ) 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 DIAS 3 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 DIAS 3 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.