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

ImportanceOne of 10 patients develop epilepsy in the late phase after cerebral venous thrombosis (CVT) diagnosis but predicting the individual risk is difficult.ObjectiveTo develop and externally validate a prognostic score to estimate the individual risk of post-CVT epilepsy.Design, Setting, and ParticipantsThis 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.ExposureThe 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 MeasureTime to a first late seizure, defined as occurring more than 7 days after diagnosis of CVT.ResultsOf 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 RelevanceThe 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.