Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy

Susanne J van Veluw; Geert Jan Biessels; Catharina J M Klijn; Annemieke J M Rozemuller

doi:10.1212/WNL.0000000000002419

Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy

Susanne J van Veluw, Geert Jan Biessels, Catharina J M Klijn, Annemieke J M Rozemuller

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology.

METHODS: Five decedents (mean age at death 79.6 ± 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury.

RESULTS: On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury.

CONCLUSIONS: This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease.

Original language	English
Pages (from-to)	867-871
Number of pages	5
Journal	Neurology
Volume	86
Issue number	9
DOIs	https://doi.org/10.1212/WNL.0000000000002419
Publication status	Published - 2016

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title = "Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy",

abstract = "OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology.METHODS: Five decedents (mean age at death 79.6 ± 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury.RESULTS: On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury.CONCLUSIONS: This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease.",

author = "{van Veluw}, {Susanne J} and Biessels, {Geert Jan} and Klijn, {Catharina J M} and Rozemuller, {Annemieke J M}",

note = "{\textcopyright} 2016 American Academy of Neurology.",

year = "2016",

doi = "10.1212/WNL.0000000000002419",

language = "English",

volume = "86",

pages = "867--871",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

number = "9",

}

TY - JOUR

T1 - Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy

AU - van Veluw, Susanne J

AU - Biessels, Geert Jan

AU - Klijn, Catharina J M

AU - Rozemuller, Annemieke J M

PY - 2016

Y1 - 2016

N2 - OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology.METHODS: Five decedents (mean age at death 79.6 ± 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury.RESULTS: On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury.CONCLUSIONS: This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease.

AB - OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology.METHODS: Five decedents (mean age at death 79.6 ± 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury.RESULTS: On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury.CONCLUSIONS: This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease.

U2 - 10.1212/WNL.0000000000002419

DO - 10.1212/WNL.0000000000002419

M3 - Article

C2 - 26843561

SN - 0028-3878

VL - 86

SP - 867

EP - 871

JO - Neurology

JF - Neurology

IS - 9

ER -

Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy

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