Underlying Small Vessel Disease Associated With Mixed Cerebral Microbleeds

Abstract

Background and Purpose: Whether patients with both lobar and deep cerebral microbleeds (mixed CMB) have advanced cerebral amyloid angiopathy (CAA), hypertensive angiopathy (HA) or both is uncertain. To get insight into the underlying small vessel disease (SVD) associated with mixed CMB, we explored its association with cortical superficial siderosis (cSS), a key marker of CAA and other MRI markers of SVD in patients with intracerebral hemorrhage (ICH).Methods: Of 425 consecutive patients with acute ICH who had received brain MRIs, 260 had ≥1 CMB and were included in the analysis. They were categorized as strictly lobar CMB (suggesting CAA), strictly deep CMB (suggesting HA) or mixed CMB. Clinical and imaging characteristics were compared (1) between the three CMB groups and (2) within mixed CMB patients according to the symptomatic ICH location.Results: Overall, 111 (26%) patients had mixed CMB. Compared to strictly lobar CMB (n = 111) and strictly deep CMB (n = 38), patients with mixed CMB had a more severe burden of lacune, white matter hyperintensities and CMB. cSS was observed in 24.3% of patients with mixed CMB compared to 44.1% in strictly lobar CMB and 10.5% in strictly deep CMB (p < 0.0001). Among patients with mixed CMB, 44 (39.6%) had a lobar symptomatic ICH and 67 (60.4%) had a non-lobar ICH. Patients with non-lobar ICH were more likely to have hypertension, whereas those with lobar ICH were more likely to have cSS and chronic lobar ICH and had higher ratio lobar CMB count/total CMB count.Conclusions: Mixed CMB is frequently encountered in patients with ICH and appears as a heterogeneous group, suggesting that both CAA and HA may be contributing to mixed CMB. Neuroimaging markers including ICH location, cSS, and CMB distribution may indicate the predominant underlying vasculopathy, with potential prognostic implications.

Prevalence of cerebral amyloid angiopathy: A systematic review and meta‐analysis

“…48 Similarly, we found a relatively high prevalence of mixed cerebral microbleeds in patients with ICH irrespective of location, which may reflect the presence of etiologies other than or in addition to CAA. 49,50 Our observation that the prevalence of cortical superficial siderosis was much higher in patients with ICH or lobar ICH compared to the general population, cognitively normal individuals, and patients with AD, indicates that cortical superficial siderosis is not a marker for CAA in general, but may be confined to specific clinical phenotypes 37 and related with the development of lobar ICH. 51…”

Clinical and radiological differences between patients with probable cerebral amyloid angiopathy and mixed cerebral microbleeds

“…Third, the number of patients is considerably smaller compared to the above mentioned studies maybe mitigating a possible difference between the groups. Studies on patients with CAA and mixed CMB and macrohaemorrhages in European [ 20 ] and Asian [ 21 ] populations found that CMB is mainly driven by hypertensive vasculopathy although a subgroup of these patients might have coexisting or dominant CAA. Further studies on the natural history of mixed CMB should shed more light on the early stages of the disease.…”

Cerebral microbleeds: from depiction to interpretation

“…115 The association between CMB presence (≥1) and symptomatic ICH failed to reach statistical significance (adjusted OR (aOR) =1. 42 115 Interestingly, a recent study using a multistep algorithm populated with data from clinical studies to estimate 3-month clinical and imaging outcomes in patients with acute IS with high CMB burden (>10 CMBs) treated with IVT reported the following findings: (A) the beneficial treatment effect of IVT on 3-month functional outcome was attenuated in patients with >10 CMBs compared with patients with ≤10 CMBs on pretreatment brain MRI; (B) IVT was related to an increased risk of mortality in patients with >10 CMBs; (C) IVT might be related to net harm in subgroups of patients with >10 CMBs defined by age, stroke symptom severity and treatment delay; nevertheless, (d) Routine pretreatment MRI to quantify CMB burden before IVT cannot generally be recommended, as long as it causes even a small additional treatment delay given the low general pretest probability of >10 CMBs (0.6%-2.7%). 116 However, these inferences derived from observational data need to be treated cautiously.…”