Microbleeds on MRI are associated with microinfarcts on autopsy in cerebral amyloid angiopathy.
OBJECTIVE
To identify in vivo MRI markers that might correlate with cerebral microinfarcts (CMIs) on autopsy in patients with cerebral amyloid angiopathy (CAA).


METHODS
We included patients with neuropathologic evidence of CAA on autopsy and available antemortem brain MRI. Clinical characteristics and in vivo MRI markers of CAA-related small vessel disease were recorded, including white matter hyperintensities, cerebral microbleeds, cortical superficial siderosis, and centrum semiovale perivascular spaces. In addition, the presence of intracerebral hemorrhage on MRI was assessed. Evaluation of the presence and number of CMIs was performed in 9 standard histology sections.


RESULTS
Of 49 analyzed patients with CAA, CMIs were present in 36.7%. The presence of ≥1 CMIs on autopsy was associated with higher numbers of microbleeds on antemortem MRI (median 8 [interquartile range 2.5-33.0] vs 1 [interquartile range 0-3], p = 0.003) and with the presence of intracerebral hemorrhage (44.4% vs 16.1%, p = 0.03). No associations between CMIs and other in vivo MRI markers of CAA were found. In a multivariable model adjusted for severe CAA pathology, higher numbers of microbleeds were independent predictors of the presence of CMIs on pathology.


CONCLUSIONS
CMIs are a common finding at autopsy in patients with CAA. The strong association between MRI-observed microbleeds and CMIs at autopsy may suggest a shared underlying pathophysiologic mechanism between these lesions.
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston. arne.lauer@gmx.de.
Arne
A
Lauer
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Susanne J
SJ
van Veluw
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Christopher M
CM
William
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Andreas
A
Charidimou
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Duangnapa
D
Roongpiboonsopit
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Anastasia
A
Vashkevich
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Alison
A
Ayres
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Sergi
S
Martinez-Ramirez
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Edip M
EM
Gurol
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Geert Jan
GJ
Biessels
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Matthew
M
Frosch
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Steven M
SM
Greenberg
From the Hemorrhagic Stroke Research Program (A.L., S.J.v.V., A.C., D.R., A.V., A.A., S.M.-R., E.M.G., S.M.G., A.V.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurology (S.J.v.V., G.J.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Pathology (C.M.W.), New York University Langone Medical Center, New York University School of Medicine; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and C.S. Kubik Laboratory for Neuropathology (M.F.), Massachusetts General Hospital, Harvard Medical School, Boston.
Anand
A
Viswanathan
D000367:Age Factors; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D020520:Brain Infarction / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis