Objective <p>To evaluate predictors of ischemic stroke in patients with primary angiitis of the central nervous system after initiation of immunosuppressive therapy.</p> Materials and methods <p>This retrospective study included 204 MRI examinations of 23 patients with primary angiitis of the central nervous system, treated with immunosuppressive therapy between 2015 and 2020 at the University Hospital Bern and the Cantonal Hospital St. Gallen, Switzerland. Two senior neuroradiologists evaluated the MRI exams with regard to the occurrence and location of ischemic stroke and hemorrhage, as well as the following characteristics of inflamed vessels on 3D time-of-flight angiography and T1 dark-blood post contrast: signal intensity of vessel walls, length of enhancement, circular extent of enhancement, and stenosis. After matching ischemic strokes to their corresponding vessel, the temporal relationship of vessel alterations in accordance with therapy initiation and stroke onset was calculated.</p> Results <p>The majority (77.6%) of observed strokes were in the vascular territory of an inflamed vessel. A significant, non-linear temporal relationship between the timing of MRI and the initiation of immunosuppression was found. The highest predicted probability of ischemic stroke was observed between 10 and 20 days after the initiation of immunosuppressant therapy, reaching approximately 12%. Out of all evaluated vessel characteristics, a higher degree of stenosis (Estimate: 0.93, <i>p</i> = 0.006) and a higher circularity of enhancement (Estimate: 0.76, <i>p</i> = 0.01) were significantly associated with a higher likelihood of stroke.</p> Conclusions <p>A better understanding of unfavorable constellations (critical timeframe, characteristic vessel wall changes) in patients treated for primary angiitis of the central nervous system may help to prevent secondary ischemic strokes.</p> Critical relevance statement <p>A better understanding of ischemic stroke predictors in patients treated for primary angiitis of the central nervous system may prompt closer monitoring or therapy adjustment.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>To evaluate risk factors for ischemic stroke in patients treated for primary angiitis of the central nervous system.</p> </ItemContent> <ItemContent> <p>Higher degree of stenosis and circular enhancement are associated with a higher likelihood of ischemic strokes, which typically occur between 10 and 20 days after therapy onset.</p> </ItemContent> <ItemContent> <p>Data obtained from this may prompt closer monitoring or therapy adjustment.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>