CADMUS
Martina Goeldlin, Madlaine Mueller, Bernhard Siepen, Wenpeng Zhang, Hatice Özkan, Martina Locatelli, Yang Du, Waldo Valenzuela, Piotr Radojewski, Arsany Hakim, Johannes Kaesmacher, Thomas R. Meinel, Leander Clénin, Mattia Branca, Davide Strambo, Tim Fischer, Friedrich Medlin, Nils Peters, Emmanuel Carrera, Karl‐Olof Lövblad, Grzegorz Marek Karwacki, Carlo W. Cereda, Julien Niederhäuser, Marie‐Luise Mono, Achim Mueller, Susanne Wegener, Sabine Sartoretti, Alexandros A. Polymeris, Valerian Altersberger, Mira Katan, Marios Psychogios, Rolf Sturzenegger, Claude Nauer, Michael Schaerer, Carlos Buitrago Tellez, Susanne Renaud, Katharina Minkner Klahre, Werner J. Z’Graggen, David Bervini, Leo H. Bonati, Roland Wiest, Marcel Arnold, Robert Simister, Duncan Wilson, Hans Rolf Jäger, Urs Fischer, David J. Werring, David Seiffge, for Swiss Stroke Registry Investigators and SIGNAL Investigators
Abstract
BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. METHODS: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. RESULTS: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. DISCUSSION: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.