Temporal Dynamics of Cortical Microinfarcts in Cerebral Small Vessel Disease

IMPORTANCE: Neuropathology studies show a high prevalence of cortical microinfarcts (CMIs) in aging individuals, especially in patients with cerebrovascular disease and dementia. However, most, are invisible on T1- and T2-weighted magnetic resonance imaging (MRI), raising the question of how to expl...

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Veröffentlicht in:Archives of neurology (Chicago) 2020-05, Vol.77 (5), p.643-647
Hauptverfasser: ter Telgte, Annemieke, Wiegertjes, Kim, Gesierich, Benno, Baskaran, Brendon Sri, Marques, José P, Kuijf, Hugo J, Norris, David G, Tuladhar, Anil M, Duering, Marco, de Leeuw, Frank-Erik
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container_issue 5
container_start_page 643
container_title Archives of neurology (Chicago)
container_volume 77
creator ter Telgte, Annemieke
Wiegertjes, Kim
Gesierich, Benno
Baskaran, Brendon Sri
Marques, José P
Kuijf, Hugo J
Norris, David G
Tuladhar, Anil M
Duering, Marco
de Leeuw, Frank-Erik
description IMPORTANCE: Neuropathology studies show a high prevalence of cortical microinfarcts (CMIs) in aging individuals, especially in patients with cerebrovascular disease and dementia. However, most, are invisible on T1- and T2-weighted magnetic resonance imaging (MRI), raising the question of how to explain this mismatch. Studies on small acute infarcts, detected on diffusion-weighted imaging (DWI), suggest that infarcts are largest in their acute phase and reduce in size thereafter. Therefore, we hypothesized that a subset of the CMI that are invisible on MRI can be detected on MRI in their acute phase. However, to our knowledge, a serial imaging study investigating the temporal dynamics of acute CMI (A-CMI) is lacking. OBJECTIVE: To determine the prevalence of chronic CMI (C-CMI) and the cumulative incidence and temporal dynamics of A-CMI in individuals with cerebral small vessel disease (SVD). DESIGN, SETTING, PARTICIPANTS AND EXPOSURES: The RUN DMC—Intense study is a single-center hospital-based prospective cohort study on SVD performed between March 2016 and November 2017 and comprising 10 monthly 3-T MRI scans, including high-resolution DWI, 3-dimensional T1, 3-dimensional fluid-attenuated inversion recovery, and T2. One hundred six individuals from the previous longitudinal RUN DMC study were recruited based on the presence of progression of white matter hyperintensities on MRI between 2006 and 2015 and exclusion of causes of cerebral ischemia other than SVD. Fifty-four individuals (50.9%) participated. The median total follow-up duration was 39.5 weeks (interquartile range, 37.8-40.3). Statistical data analysis was performed between May and October 2019. MAIN OUTCOMES AND MEASURES: We determined the prevalence of C-CMI using the baseline T1, fluid-attenuated inversion recovery, and T2 scans. Monthly high-resolution DWI scans (n = 472) were screened to determine the cumulative incidence of A-CMI. The temporal dynamics of A-CMI were determined based on the MRI scans collected during the first follow-up visit after A-CMI onset and the last available follow-up visit. RESULTS: The median age of the cohort at baseline MRI was 69 years (interquartile range, 66-74 years) and 34 participants (63%) were men. The prevalence of C-CMI was 35% (95% CI, 0.24-0.49). Monthly DWI detected 21 A-CMI in 7 of 54 participants, resulting in a cumulative incidence of 13% (95% CI, 0.06-0.24). All A-CMI disappeared on follow-up MRI. CONCLUSIONS AND RELEVANCE: Acute CMI never evol
doi_str_mv 10.1001/jamaneurol.2019.5106
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However, most, are invisible on T1- and T2-weighted magnetic resonance imaging (MRI), raising the question of how to explain this mismatch. Studies on small acute infarcts, detected on diffusion-weighted imaging (DWI), suggest that infarcts are largest in their acute phase and reduce in size thereafter. Therefore, we hypothesized that a subset of the CMI that are invisible on MRI can be detected on MRI in their acute phase. However, to our knowledge, a serial imaging study investigating the temporal dynamics of acute CMI (A-CMI) is lacking. OBJECTIVE: To determine the prevalence of chronic CMI (C-CMI) and the cumulative incidence and temporal dynamics of A-CMI in individuals with cerebral small vessel disease (SVD). DESIGN, SETTING, PARTICIPANTS AND EXPOSURES: The RUN DMC—Intense study is a single-center hospital-based prospective cohort study on SVD performed between March 2016 and November 2017 and comprising 10 monthly 3-T MRI scans, including high-resolution DWI, 3-dimensional T1, 3-dimensional fluid-attenuated inversion recovery, and T2. One hundred six individuals from the previous longitudinal RUN DMC study were recruited based on the presence of progression of white matter hyperintensities on MRI between 2006 and 2015 and exclusion of causes of cerebral ischemia other than SVD. Fifty-four individuals (50.9%) participated. The median total follow-up duration was 39.5 weeks (interquartile range, 37.8-40.3). Statistical data analysis was performed between May and October 2019. MAIN OUTCOMES AND MEASURES: We determined the prevalence of C-CMI using the baseline T1, fluid-attenuated inversion recovery, and T2 scans. Monthly high-resolution DWI scans (n = 472) were screened to determine the cumulative incidence of A-CMI. The temporal dynamics of A-CMI were determined based on the MRI scans collected during the first follow-up visit after A-CMI onset and the last available follow-up visit. RESULTS: The median age of the cohort at baseline MRI was 69 years (interquartile range, 66-74 years) and 34 participants (63%) were men. The prevalence of C-CMI was 35% (95% CI, 0.24-0.49). Monthly DWI detected 21 A-CMI in 7 of 54 participants, resulting in a cumulative incidence of 13% (95% CI, 0.06-0.24). All A-CMI disappeared on follow-up MRI. CONCLUSIONS AND RELEVANCE: Acute CMI never evolved into chronically MRI-detectable lesions. We suggest that these A-CMI underlie part of the submillimeter C-CMI encountered on neuropathological examination and thereby provide a source for the high CMI burden on neuropathology.</description><identifier>ISSN: 2168-6149</identifier><identifier>EISSN: 2168-6157</identifier><identifier>DOI: 10.1001/jamaneurol.2019.5106</identifier><identifier>PMID: 32065609</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Aged ; Aging ; Blood vessels ; Brief Report ; Cerebral Infarction - diagnostic imaging ; Cerebral Infarction - epidemiology ; Cerebral Infarction - etiology ; Cerebral Small Vessel Diseases - complications ; Cerebral Small Vessel Diseases - pathology ; Cerebrovascular diseases ; Cohort Studies ; Comments ; Data analysis ; Dementia disorders ; Diffusion Magnetic Resonance Imaging - methods ; Dynamics ; Female ; High resolution ; Humans ; Incidence ; Inversion ; Ischemia ; Magnetic resonance imaging ; Male ; Median (statistics) ; Medical imaging ; Neuropathology ; Online First ; Recovery ; Substantia alba ; Time Factors ; Vascular diseases</subject><ispartof>Archives of neurology (Chicago), 2020-05, Vol.77 (5), p.643-647</ispartof><rights>Copyright American Medical Association May 2020</rights><rights>Copyright 2020 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a521t-e90ef88e29ced66899a08c8ac505e499e5b0462848501a4ea532aa314336e0733</citedby><cites>FETCH-LOGICAL-a521t-e90ef88e29ced66899a08c8ac505e499e5b0462848501a4ea532aa314336e0733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamaneurology/articlepdf/10.1001/jamaneurol.2019.5106$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2019.5106$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,780,784,885,3340,27924,27925,76489,76492</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32065609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ter Telgte, Annemieke</creatorcontrib><creatorcontrib>Wiegertjes, Kim</creatorcontrib><creatorcontrib>Gesierich, Benno</creatorcontrib><creatorcontrib>Baskaran, Brendon Sri</creatorcontrib><creatorcontrib>Marques, José P</creatorcontrib><creatorcontrib>Kuijf, Hugo J</creatorcontrib><creatorcontrib>Norris, David G</creatorcontrib><creatorcontrib>Tuladhar, Anil M</creatorcontrib><creatorcontrib>Duering, Marco</creatorcontrib><creatorcontrib>de Leeuw, Frank-Erik</creatorcontrib><title>Temporal Dynamics of Cortical Microinfarcts in Cerebral Small Vessel Disease</title><title>Archives of neurology (Chicago)</title><addtitle>JAMA Neurol</addtitle><description>IMPORTANCE: Neuropathology studies show a high prevalence of cortical microinfarcts (CMIs) in aging individuals, especially in patients with cerebrovascular disease and dementia. However, most, are invisible on T1- and T2-weighted magnetic resonance imaging (MRI), raising the question of how to explain this mismatch. Studies on small acute infarcts, detected on diffusion-weighted imaging (DWI), suggest that infarcts are largest in their acute phase and reduce in size thereafter. Therefore, we hypothesized that a subset of the CMI that are invisible on MRI can be detected on MRI in their acute phase. However, to our knowledge, a serial imaging study investigating the temporal dynamics of acute CMI (A-CMI) is lacking. OBJECTIVE: To determine the prevalence of chronic CMI (C-CMI) and the cumulative incidence and temporal dynamics of A-CMI in individuals with cerebral small vessel disease (SVD). DESIGN, SETTING, PARTICIPANTS AND EXPOSURES: The RUN DMC—Intense study is a single-center hospital-based prospective cohort study on SVD performed between March 2016 and November 2017 and comprising 10 monthly 3-T MRI scans, including high-resolution DWI, 3-dimensional T1, 3-dimensional fluid-attenuated inversion recovery, and T2. One hundred six individuals from the previous longitudinal RUN DMC study were recruited based on the presence of progression of white matter hyperintensities on MRI between 2006 and 2015 and exclusion of causes of cerebral ischemia other than SVD. Fifty-four individuals (50.9%) participated. The median total follow-up duration was 39.5 weeks (interquartile range, 37.8-40.3). Statistical data analysis was performed between May and October 2019. MAIN OUTCOMES AND MEASURES: We determined the prevalence of C-CMI using the baseline T1, fluid-attenuated inversion recovery, and T2 scans. Monthly high-resolution DWI scans (n = 472) were screened to determine the cumulative incidence of A-CMI. The temporal dynamics of A-CMI were determined based on the MRI scans collected during the first follow-up visit after A-CMI onset and the last available follow-up visit. RESULTS: The median age of the cohort at baseline MRI was 69 years (interquartile range, 66-74 years) and 34 participants (63%) were men. The prevalence of C-CMI was 35% (95% CI, 0.24-0.49). Monthly DWI detected 21 A-CMI in 7 of 54 participants, resulting in a cumulative incidence of 13% (95% CI, 0.06-0.24). All A-CMI disappeared on follow-up MRI. CONCLUSIONS AND RELEVANCE: Acute CMI never evolved into chronically MRI-detectable lesions. We suggest that these A-CMI underlie part of the submillimeter C-CMI encountered on neuropathological examination and thereby provide a source for the high CMI burden on neuropathology.</description><subject>Aged</subject><subject>Aging</subject><subject>Blood vessels</subject><subject>Brief Report</subject><subject>Cerebral Infarction - diagnostic imaging</subject><subject>Cerebral Infarction - epidemiology</subject><subject>Cerebral Infarction - etiology</subject><subject>Cerebral Small Vessel Diseases - complications</subject><subject>Cerebral Small Vessel Diseases - pathology</subject><subject>Cerebrovascular diseases</subject><subject>Cohort Studies</subject><subject>Comments</subject><subject>Data analysis</subject><subject>Dementia disorders</subject><subject>Diffusion Magnetic Resonance Imaging - methods</subject><subject>Dynamics</subject><subject>Female</subject><subject>High resolution</subject><subject>Humans</subject><subject>Incidence</subject><subject>Inversion</subject><subject>Ischemia</subject><subject>Magnetic resonance imaging</subject><subject>Male</subject><subject>Median (statistics)</subject><subject>Medical imaging</subject><subject>Neuropathology</subject><subject>Online First</subject><subject>Recovery</subject><subject>Substantia alba</subject><subject>Time Factors</subject><subject>Vascular diseases</subject><issn>2168-6149</issn><issn>2168-6157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU2LFDEQhoMo7rLuHxCRBi9eZqx8dnIRZHRXYcSDq9dQk63WDN2dMekW9t-bZtbxIxBSpJ63qKqXsWcc1hyAv9rjgCPNOfVrAdytNQfzgJ0LbuzKcN0-PMXKnbHLUvZQjwVQUj1mZ1KA0QbcOdve0HBIGfvm7d2IQwylSV2zSXmKoX5-jCGnOHaYw1SaODYbyrRb8M8D9n3zlUqhqo2FsNAT9qjDvtDl_XvBvly9u9m8X20_XX_YvNmuUAs-rcgBddaScIFujbHOIdhgMWjQpJwjvQNlhFVWA0dFqKVAlFxJaQhaKS_Y62Pdw7wb6DbQONWW_CHHAfOdTxj9v5kxfvff0k_fghJWqlrg5X2BnH7MVCY_xBKo7-tS01y8kNpo60At6Iv_0H2a81jH80KB0NA6wSuljlRdVymZulMzHPzimP_jmF8c84tjVfb870FOot_-VODpEajqU1a0htcrfwEmb5xP</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>ter Telgte, Annemieke</creator><creator>Wiegertjes, Kim</creator><creator>Gesierich, Benno</creator><creator>Baskaran, Brendon Sri</creator><creator>Marques, José P</creator><creator>Kuijf, Hugo J</creator><creator>Norris, David G</creator><creator>Tuladhar, Anil M</creator><creator>Duering, Marco</creator><creator>de Leeuw, Frank-Erik</creator><general>American Medical Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200501</creationdate><title>Temporal Dynamics of Cortical Microinfarcts in Cerebral Small Vessel Disease</title><author>ter Telgte, Annemieke ; 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Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of neurology (Chicago)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ter Telgte, Annemieke</au><au>Wiegertjes, Kim</au><au>Gesierich, Benno</au><au>Baskaran, Brendon Sri</au><au>Marques, José P</au><au>Kuijf, Hugo J</au><au>Norris, David G</au><au>Tuladhar, Anil M</au><au>Duering, Marco</au><au>de Leeuw, Frank-Erik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Temporal Dynamics of Cortical Microinfarcts in Cerebral Small Vessel Disease</atitle><jtitle>Archives of neurology (Chicago)</jtitle><addtitle>JAMA Neurol</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>77</volume><issue>5</issue><spage>643</spage><epage>647</epage><pages>643-647</pages><issn>2168-6149</issn><eissn>2168-6157</eissn><abstract>IMPORTANCE: Neuropathology studies show a high prevalence of cortical microinfarcts (CMIs) in aging individuals, especially in patients with cerebrovascular disease and dementia. However, most, are invisible on T1- and T2-weighted magnetic resonance imaging (MRI), raising the question of how to explain this mismatch. Studies on small acute infarcts, detected on diffusion-weighted imaging (DWI), suggest that infarcts are largest in their acute phase and reduce in size thereafter. Therefore, we hypothesized that a subset of the CMI that are invisible on MRI can be detected on MRI in their acute phase. However, to our knowledge, a serial imaging study investigating the temporal dynamics of acute CMI (A-CMI) is lacking. OBJECTIVE: To determine the prevalence of chronic CMI (C-CMI) and the cumulative incidence and temporal dynamics of A-CMI in individuals with cerebral small vessel disease (SVD). DESIGN, SETTING, PARTICIPANTS AND EXPOSURES: The RUN DMC—Intense study is a single-center hospital-based prospective cohort study on SVD performed between March 2016 and November 2017 and comprising 10 monthly 3-T MRI scans, including high-resolution DWI, 3-dimensional T1, 3-dimensional fluid-attenuated inversion recovery, and T2. One hundred six individuals from the previous longitudinal RUN DMC study were recruited based on the presence of progression of white matter hyperintensities on MRI between 2006 and 2015 and exclusion of causes of cerebral ischemia other than SVD. Fifty-four individuals (50.9%) participated. The median total follow-up duration was 39.5 weeks (interquartile range, 37.8-40.3). Statistical data analysis was performed between May and October 2019. MAIN OUTCOMES AND MEASURES: We determined the prevalence of C-CMI using the baseline T1, fluid-attenuated inversion recovery, and T2 scans. Monthly high-resolution DWI scans (n = 472) were screened to determine the cumulative incidence of A-CMI. The temporal dynamics of A-CMI were determined based on the MRI scans collected during the first follow-up visit after A-CMI onset and the last available follow-up visit. RESULTS: The median age of the cohort at baseline MRI was 69 years (interquartile range, 66-74 years) and 34 participants (63%) were men. The prevalence of C-CMI was 35% (95% CI, 0.24-0.49). Monthly DWI detected 21 A-CMI in 7 of 54 participants, resulting in a cumulative incidence of 13% (95% CI, 0.06-0.24). All A-CMI disappeared on follow-up MRI. CONCLUSIONS AND RELEVANCE: Acute CMI never evolved into chronically MRI-detectable lesions. We suggest that these A-CMI underlie part of the submillimeter C-CMI encountered on neuropathological examination and thereby provide a source for the high CMI burden on neuropathology.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>32065609</pmid><doi>10.1001/jamaneurol.2019.5106</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Aging
Blood vessels
Brief Report
Cerebral Infarction - diagnostic imaging
Cerebral Infarction - epidemiology
Cerebral Infarction - etiology
Cerebral Small Vessel Diseases - complications
Cerebral Small Vessel Diseases - pathology
Cerebrovascular diseases
Cohort Studies
Comments
Data analysis
Dementia disorders
Diffusion Magnetic Resonance Imaging - methods
Dynamics
Female
High resolution
Humans
Incidence
Inversion
Ischemia
Magnetic resonance imaging
Male
Median (statistics)
Medical imaging
Neuropathology
Online First
Recovery
Substantia alba
Time Factors
Vascular diseases
title Temporal Dynamics of Cortical Microinfarcts in Cerebral Small Vessel Disease
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