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MRI-Based Prediction of Macrovascular Causes of Intracerebral Hemorrhage: The MACRO Score
Simon Fandler-Höfler1, Gareth Ambler1, Martina B Goeldlin1
1From the Department of Neurology (S.F.-H., L.O., M.K., C.E., T.G.), Medical University of Graz, Austria; Department of Statistical Science (G.A.), University College London, United Kingdom; Department of Neurology (M.B.G., D.J.S.), University Hospital Bern, Inselspital, University of Bern, Switzerland; Institute for Medical Informatics, Statistics and Documentation (G.W.), Medical University of Graz, Austria; Stroke Research Centre (S.F.-H., W.Z., Y.D., M.L., H.O., P.S.N., L.P., R.M., K.T., R.J.S., D.J.W.), Department of Brain Repair & Rehabilitation, UCL Queen Square Institute of Neurology, United Kingdom; Division of Neuroradiology, Vascular and Interventional Radiology (O.N.), Department of Radiology, Medical University of Graz, Austria; and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair & Rehabilitation, UCL Queen Square Institute of Neurology, United Kingdom.
Insights
The new MRI-based MACRO score accurately predicts macrovascular causes of intracerebral hemorrhage (ICH), aiding diagnosis. This tool helps identify patients needing further investigation for conditions like aneurysms or AVMs.
Area of Science:
- Neurology
- Radiology
- Vascular Medicine
Background:
- Most spontaneous intracerebral hemorrhages (ICH) stem from small vessel diseases (SVDs), but 7-10% arise from macrovascular causes.
- Accurate diagnosis of macrovascular ICH is crucial for timely treatment and improved patient outcomes.
- Existing diagnostic tools may be invasive (e.g., digital subtraction angiography) or lack sensitivity for SVD markers on MRI.
Purpose of the Study:
- To develop and validate a novel risk stratification score, the MRI Assessment of the Causes of intRacerebral haemOrrhage (MACRO) score.
- To integrate MRI findings of SVD into a score to predict the probability of macrovascular causes of ICH.
- To guide further diagnostic investigations for patients with spontaneous ICH.
Main Methods:
- Pooled data from two large observational cohorts (UK and Austria) of consecutive ICH patients with brain MRI and angiography within 90 days.
- Developed the MACRO score using lasso logistic regression, incorporating age, ICH location, and SVD markers (microbleeds, lacunes, superficial siderosis, white matter hyperintensities).
- Validated the score internally using bootstrapping and externally in an independent Swiss cohort.
Main Results:
- The study included 1,043 ICH patients (7.5% with macrovascular causes).
- The MACRO score demonstrated high predictive performance with an optimism-adjusted c-statistic of 0.90 (internal) and 0.87 (external validation).
- High MACRO scores (≥6) identified patients with a very low risk (0.2%) of macrovascular causes, while low scores (≤2) indicated a high risk (48.9%).
Conclusions:
- The MRI-based MACRO score is a highly effective tool for predicting the likelihood of macrovascular etiologies in spontaneous ICH.
- The MACRO score can reliably guide the necessity and type of further diagnostic investigations, potentially reducing invasive procedures.
- Limitations include the observational design and the fact that digital subtraction angiography was performed in only a minority of patients.
Background And Objectives:
Although most spontaneous intracerebral hemorrhages (ICHs) are due to cerebral small vessel diseases (SVDs), between 1 in 7 and 1 in 10 are due to a macrovascular cause. Rapid diagnosis has important therapeutic and prognostic implications but sometimes requires digital subtraction angiography (DSA), an invasive procedure which cannot be performed in all patients. MRI provides optimal sensitivity for markers of SVD but was not included in previous risk stratification scores. We aimed to create and validate a risk stratification score for macrovascular causes of ICH including MRI findings to guide diagnosis and further investigations.
Methods:
We pooled data from 2 large observational study cohorts (London/United Kingdom and Graz/Austria) of consecutive patients with ICH who had brain MRI and at least 1 angiographic modality within 90 days of symptom onset. The primary outcome was a macrovascular cause of ICH (arteriovenous malformation/dural arteriovenous fistula, aneurysm, cavernoma, or cerebral venous thrombosis), with the diagnosis based on neurovascular multidisciplinary meetings. Using lasso logistic regression, we built the MRI Assessment of the Causes of intRacerebral haemOrrhage (MACRO) score to assess the probability of a macrovascular cause. We performed internal validation using bootstrapping and external validation in an independent cohort (Bern/Switzerland).
Results:
We included 1,043 patients with ICH (mean age 66 years, 42% female), 78 of whom had a macrovascular cause (7.5%). The final score includes age (0-39, 40-69, or ≥70), location of ICH (lobar, deep, or infratentorial), and SVD markers on MRI (≥1 microbleed, ≥1 lacune, presence of cortical superficial siderosis, or white matter hyperintensities using the Fazekas scale). The MACRO score showed an optimism-adjusted c-statistic of 0.90 (95% CI 0.88-0.93), superior to existing CT-based scores (p < 0.001). In external validation, the c-statistic was 0.87 (95% CI 0.80-0.94). MACRO scores ≥6 (59.5% of patients) indicated a very low risk of a macrovascular cause (0.2%), while scores ≤2 (9% of patients) indicated a high risk (48.9%).
Discussion:
The MRI-based MACRO score shows excellent performance in predicting the likelihood of macrovascular causes of spontaneous intracerebral hemorrhage, making it useful in guiding further investigations. Important limitations include the observational study design and the performance of DSA in a minority of patients.
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