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.

Interventions

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 Outcomes and Measures

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.

<DIAS3 calculator>

Key Points

Question  What is the individual risk of developing epilepsy after cerebral venous thrombosis (CVT)?

Findings  In this cohort study, the DIAS3 score was developed and externally validated to predict the individual risk of post-CVT epilepsy using 6 readily available variables. The score showed adequate calibration and discrimination in predicting post-CVT epilepsy in 2 independent cohorts.

Meaning  These results demonstrated that the DIAS3 score is a simple tool that can be used to predict post-CVT epilepsy.

요약

소개 : 10명의 환자 중 1명이 뇌 정맥 혈전증(CVT) 진단 후 후기 단계에서 뇌전증이 발생하지만 환자 개개인의 뇌전증 발생 위험도를 예측하는 것은 어렵다. 따라서, 본 연구는 CVT 이후 발작 발생 위험을 추정하기 위한 예후 점수를 개발하는 것을 목적으로 한다.

방법 : 1994년부터 2022년까지 등록된 환자들을 대상으로 하는 후향적 및 전향적 관찰적 코호트 연구이다. DIAS3 score의 변수로는 1) 감압 두개골 절제술 여부 (Decompressive hemicraniectomy) 2) 뇌내 출혈 여부 (intracerebral hemorrhage at presentation) 3) 나이 4) 급성기 발작 여부 (seizure in acute phase) 5) 급성기 뇌전증 지속상태 여부 (status epilepticus in acute phase) 6) 경막밑혈종 여부 (subdural hematoma)가 사용된다.

결과 : 내부 및 외부 검증 결과, DIAS3점수는 예측인자 개발을 위한 파생 코호트(derivation cohort)과 두 개의 독립적 검증 코호트(validation cohort)에서 모두 적절한 구별 능력을 보였다. 또한, 예측된 위험과 관찰된 위험 간의 일치도 적절했다.

결론 및 의의 : 뇌 정맥 혈전증(CVT) 이후 뇌전증 발생에 대한 각 환자의 개별적인 위험도는 DIAS3 점수를 통해 평가할 수 있다. 이 점수는 CVT 이후 뇌전증 발생 가능성을 예측하는 데 좋은 정확성과 변별력을 갖는다. 따라서 DIAS3 점수는 임상에서 환자의 뇌 정맥 혈전증 이후 뇌전증(post-CVT epilepsy)의 위험도를 더 정확하게 평가하고 개인 맞춤형 치료 결정을 내리는 데 도움을 줄 수 있으며, 나아가 항간질 약물의 결정, 환자 상담, 그리고 CVT에서의 간질 발생 연구 촉진에 기여할 수 있다.