Characterizing mixed location hemorrhages/microbleeds with CSF markers

Ulf Jensen-Kondering; Nils G. Margraf; Caroline Weiler; Walter Maetzler; Justina Dargvainiene; Kim Falk; Sarah Philippen; Thorsten Bartsch; Charlotte Flüh; Christoph Röcken; Bettina Möller; Georg Royl; Alexander Neumann; Norbert Brüggemann; Benjamin Roeben; Claudia Schulte; Benjamin Bender; Daniela Berg; Gregor Kuhlenbäumer

doi:10.1177/17474930231152124

Characterizing mixed location hemorrhages/microbleeds with CSF markers

Ulf Jensen-Kondering, Nils G. Margraf^*, Caroline Weiler, Walter Maetzler, Justina Dargvainiene, Kim Falk, Sarah Philippen, Thorsten Bartsch, Charlotte Flüh, Christoph Röcken, Bettina Möller, Georg Royl, Alexander Neumann, Norbert Brüggemann, Benjamin Roeben, Claudia Schulte, Benjamin Bender, Daniela Berg, Gregor Kuhlenbäumer

^*Corresponding author for this work

1 Citation (Scopus)

Abstract

Objective: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer’s disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum.

Patients and Methods: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. Results: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without.

Conclusion: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

Original language	English
Journal	International Journal of Stroke
Volume	18
Issue number	6
Pages (from-to)	728-735
Number of pages	8
ISSN	1747-4930
DOIs	https://doi.org/10.1177/17474930231152124
Publication status	Published - 07.2023

Research Areas and Centers

Academic Focus: Biomedical Engineering

DFG Research Classification Scheme

205-32 Medical Physics, Biomedical Engineering
206-05 Experimental Models for Investigating Diseases of the Nervous System

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1177/17474930231152124

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Jensen-Kondering, U., Margraf, N. G., Weiler, C., Maetzler, W., Dargvainiene, J., Falk, K., Philippen, S., Bartsch, T., Flüh, C., Röcken, C., Möller, B., Royl, G., Neumann, A., Brüggemann, N., Roeben, B., Schulte, C., Bender, B., Berg, D., & Kuhlenbäumer, G. (2023). Characterizing mixed location hemorrhages/microbleeds with CSF markers. International Journal of Stroke, 18(6), 728-735. https://doi.org/10.1177/17474930231152124

@article{116dc146f6fe4d328acc5a80f99f36a5,

title = "Characterizing mixed location hemorrhages/microbleeds with CSF markers",

abstract = "Objective: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer{\textquoteright}s disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. Patients and Methods: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (A{\ss}42, A{\ss}40, t-tau, and p-tau), and histopathological data in patients each group. Results: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). A{\ss}42 levels and the A{\ss}42/A{\ss}40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forA{\ss}40. A{\ss}40 and A{\ss}42 levels as well as the A{\ss}42/A{\ss}40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. A{\ss}40 and A{\ss}42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. Conclusion: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.",

author = "Ulf Jensen-Kondering and Margraf, {Nils G.} and Caroline Weiler and Walter Maetzler and Justina Dargvainiene and Kim Falk and Sarah Philippen and Thorsten Bartsch and Charlotte Fl{\"u}h and Christoph R{\"o}cken and Bettina M{\"o}ller and Georg Royl and Alexander Neumann and Norbert Br{\"u}ggemann and Benjamin Roeben and Claudia Schulte and Benjamin Bender and Daniela Berg and Gregor Kuhlenb{\"a}umer",

note = "Publisher Copyright: {\textcopyright} 2023 World Stroke Organization.",

year = "2023",

month = jul,

doi = "10.1177/17474930231152124",

language = "English",

volume = "18",

pages = "728--735",

journal = "International Journal of Stroke",

issn = "1747-4930",

number = "6",

}

Jensen-Kondering, U, Margraf, NG, Weiler, C, Maetzler, W, Dargvainiene, J, Falk, K, Philippen, S, Bartsch, T, Flüh, C, Röcken, C, Möller, B, Royl, G , Neumann, A , Brüggemann, N, Roeben, B, Schulte, C, Bender, B, Berg, D & Kuhlenbäumer, G 2023, 'Characterizing mixed location hemorrhages/microbleeds with CSF markers', International Journal of Stroke, vol. 18, no. 6, pp. 728-735. https://doi.org/10.1177/17474930231152124

TY - JOUR

T1 - Characterizing mixed location hemorrhages/microbleeds with CSF markers

AU - Jensen-Kondering, Ulf

AU - Margraf, Nils G.

AU - Weiler, Caroline

AU - Maetzler, Walter

AU - Dargvainiene, Justina

AU - Falk, Kim

AU - Philippen, Sarah

AU - Bartsch, Thorsten

AU - Flüh, Charlotte

AU - Röcken, Christoph

AU - Möller, Bettina

AU - Royl, Georg

AU - Neumann, Alexander

AU - Brüggemann, Norbert

AU - Roeben, Benjamin

AU - Schulte, Claudia

AU - Bender, Benjamin

AU - Berg, Daniela

AU - Kuhlenbäumer, Gregor

PY - 2023/7

Y1 - 2023/7

N2 - Objective: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer’s disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. Patients and Methods: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. Results: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. Conclusion: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

AB - Objective: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer’s disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. Patients and Methods: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. Results: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. Conclusion: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

UR - http://www.scopus.com/inward/record.url?scp=85147418178&partnerID=8YFLogxK

U2 - 10.1177/17474930231152124

DO - 10.1177/17474930231152124

M3 - Journal articles

C2 - 36622021

AN - SCOPUS:85147418178

SN - 1747-4930

VL - 18

SP - 728

EP - 735

JO - International Journal of Stroke

JF - International Journal of Stroke

IS - 6

ER -

Characterizing mixed location hemorrhages/microbleeds with CSF markers

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