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Abstract
Background and Objectives Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in patients with mixed ICH with cortical superficial siderosis (cSS), a marker strongly associated with CAA.
Methods Brain MRIs from a prospective database of consecutive patients with nontraumatic ICH admitted to a referral center were reviewed for the presence of CMBs, cSS, and nonhemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces [CSO-EPVS], and multispot white matter hyperintensity [WMH] pattern). The frequencies of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between patients with mixed ICH with cSS (mixed ICH/cSS[+]) and without cSS (mixed ICH/cSS[–]) in univariate and multivariable models.
Results Of 1,791 patients with ICH, 40 had mixed ICH/cSS(+) and 256 had mixed ICH/cSS(−). LVH was less common in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(−) (34% vs 59%, p = 0.01). The frequencies of CAA imaging markers, namely multispot pattern (18% vs 4%, p < 0.01) and severe CSO-EPVS (33% vs 11%, p < 0.01), were higher in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(−). In a logistic regression model, older age (adjusted odds ratio [aOR] 1.04 per year, 95% CI 1.00–1.07, p = 0.04), lack of LVH (aOR 0.41, 95% CI 0.19–0.89, p = 0.02), multispot WMH pattern (aOR 5.25, 95% CI 1.63–16.94, p = 0.01), and severe CSO-EPVS (aOR 4.24, 95% CI 1.78–10.13, p < 0.01) were independently associated with mixed ICH/cSS(+) after further adjustment for hypertension and coronary artery disease. Among ICH survivors, the adjusted hazard ratio of ICH recurrence in patients with mixed ICH/cSS(+) was 4.65 (95% CI 1.38–11.38, p < 0.01) compared with that in patients with mixed ICH/cSS(−).
Discussion The underlying microangiopathy of mixed ICH/cSS(+) likely includes both HTN-cSVD and CAA, whereas mixed ICH/cSS(−) is likely driven by HTN-cSVD. These imaging-based classifications can be important to stratify ICH risk but warrant confirmation in studies incorporating advanced imaging/pathology.
Glossary
- aHR=
- adjusted hazard ratio;
- aOR=
- adjusted odds ratio;
- CAA=
- cerebral amyloid angiopathy;
- CMB=
- cerebral microbleed;
- CSO=
- centrum semiovale;
- cSS=
- cortical superficial siderosis;
- cSVD=
- cerebral small vessel disease;
- EPVS=
- enlarged perivascular space;
- HTN-cSVD=
- hypertensive cSVD;
- ICH=
- intracerebral hemorrhage;
- IQR=
- interquartile range;
- LVH=
- left ventricular hypertrophy;
- WMH=
- white matter hyperintensity
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.
CME Course: NPub.org/cmelist
- Received January 19, 2023.
- Accepted in final form April 17, 2023.
- © 2023 American Academy of Neurology
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