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CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small
Martina B Goeldlin1, Madlaine Mueller1, Bernhard M Siepen1
1From the Departments of Neurology (M.B.G., M.M., B.M.S., T.R.M., L.C., M.A., U.F., D.J.S., W.J.Z.G.) and Neurosurgery (D.B., W.J.Z.G.), and the University Institute for Diagnostic and Interventional Neuroradiology (W.V., P.R., A.H., J.K., R.W.), Inselspital Bern University Hospital and University of Bern; Graduate School for Health Sciences (M.B.G., B.M.S.) and CTU Bern (M.B.), University of Bern, Switzerland; Stroke Research Centre (M.B.G., W.Z., H.O., M.L., Y.D., D.J.W.), University College London Queen Square Institute of Neurology, United Kingdom; Service of Neurology (D.S.), Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne; Department of Radiology (T.F.), Cantonal Hospital St. Gallen; Department of Internal Medicine (F.M.), Stroke Unit and Division of Neurology, HFR Fribourg-Cantonal Hospital; Stroke Center Hirslanden (N.P.), Klinik Hirslanden Zurich; Stroke Research Group (E.C.), Department of Clinical Neurosciences, University Hospital and Faculty of Medicine, Geneva; Department of Radiology and Medical Informatics (K.-O.L.), University of Geneva; Department of Radiology and Nuclear Medicine (G.M.K.), Luzerner Kantonsspital; Stroke Center EOC (C.W.C.), Neurocenter of Southern Switzerland; Stroke Unit (J.N.), GHOL, Hôpital de zone de Nyon; Stadtspitäler Triemli und Waid (M.-L.M.), Zurich; Department of Neurology (A.M., S.W.), University Hospital and University of Zurich; Department of Radiology and Nuclear Medicine (S.S.), Kantonsspital Winterthur; Department of Neurology and Stroke Center (A.A.P., V.A., M.K., U.F., L.H.B.) and Center for Rehabilitation Rheinfelden (L.H.B.), University Hospital Basel and University of Basel; Diagnostic and Interventional Neuroradiology (M.P.), Department of Radiology and Nuclear Medicine, University Hospital Basel; Department of Neurology (R.S.), Kantonsspital Graubünden, Chur; Department of Radiology/Neuroradiology (C.N.), Kantonsspital Graubünden, Chur; Department of Neurology (M.S.), and Department of Radiology (C.B.T.), Buergerspital Solothurn; Division of Neurology (S.R.), Pourtalès Hospital, Neuchâtel; Department of Radiology (K.M.K.), Réseau Hospitalier Neuchâtelois, Switzerland; Comprehensive Stroke Service (R.J.S., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair & Rehabilitation, University College London Hospital, United Kingdom; and New Zealand Brain Research Institute (D.W.), Christchurch.
Insights
A new MRI classification, CADMUS, aids in categorizing small vessel disease-related intracerebral hemorrhage (ICH) subtypes. This reproducible method shows promise for improving clinical practice and research in ICH diagnosis.
Area of Science:
- Neurology
- Radiology
- Stroke Medicine
Background:
- Cerebral small vessel disease (SVD) is a primary cause of intracerebral hemorrhage (ICH).
- Existing MRI classifications for SVD-related ICH lack comprehensiveness and ease of application.
- A standardized classification is needed for improved clinical management and research.
Purpose of the Study:
- To develop and validate a novel MRI-based classification system for SVD-related ICH subtypes.
- To assess the feasibility, reproducibility, and potential clinical utility of the new classification.
Main Methods:
- Retrospective analysis of prospectively collected data from the Swiss Stroke Registry (SSR) and SIGNAL cohort.
- Development of the Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD (CADMUS) classification using MRI markers.
- Evaluation of inter-rater reliability (Gwet's AC1) and analysis of recurrent stroke events.
Main Results:
- The CADMUS classification was applied to 1,180 patients in the SSR cohort and 313 in the SIGNAL cohort.
- The most frequent phenotype was Mixed CAA-DPA (63.6%), followed by Undetermined SVD (17.2%), CAA (13.1%), and DPA (6.3%).
- Good inter-rater reliability was achieved (Gwet's AC1 for SSR/SIGNAL 0.69/0.74), with comparable 3-month event rates across phenotypes.
Conclusions:
- The CADMUS classification is a feasible and reproducible MRI-based tool for categorizing SVD-associated ICH.
- This novel classification has the potential to enhance the accuracy of ICH subtyping in both clinical practice and research settings.
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.
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