Associations of Cerebral Small Vessel Disease and Chronic Kidney Disease in Patients With Acute Intracerebral Hemorrhage: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) may be associated with the pathogenesis and phenotype of cerebral small vessel disease (SVD), which is the commonest cause of intracerebral hemorrhage (ICH). The purpose of this study was to investigate the associations of CKD with ICH neuroimaging phenotype, volume, and location, total burden of small vessel disease, and its individual components. METHODS: In 2 cohorts of consecutive patients with ICH evaluated with MRI, we investigated the frequency and severity of CKD based on established Kidney Disease Improving Global Outcomes criteria, requiring estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.732 ≥ 3 months apart to define CKD. MRI scans were rated for ICH neuroimaging phenotype (arteriolosclerosis, cerebral amyloid angiopathy, mixed location SVD, or cryptogenic ICH) and the presence of markers of SVD (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces, defined according to the STandards for ReportIng Vascular changes on nEuroimaging criteria). We used multinomial, binomial logistic, and ordinal logistic regression models adjusted for age, sex, hypertension, and diabetes to account for possible confounding caused by shared risk factors of CKD and SVD. RESULTS: Of 875 patients (mean age 66 years, 42% female), 146 (16.7%) had CKD. After adjusting for age, sex, and comorbidities, patients with CKD had higher rates of mixed SVD than those with eGFR >60 (relative risk ratio 2.39, 95% CI 1.16-4.94, p = 0.019). Severe WMHs, deep microbleeds, and lacunes were more frequent in patients with CKD, as was a higher overall SVD burden score (odds ratio 1.83 for each point on the ordinal scale, 95% CI 1.31-2.56, p < 0.001). Patients with eGFR ≤30 had more CMBs (median 7 [interquartile range 1-23] vs 2 [0-8] for those with eGFR >30, p = 0.007). DISCUSSION: In patients with ICH, CKD was associated with SVD burden, a mixed SVD phenotype, and markers of arteriolosclerosis. Our findings indicate that CKD might independently contribute to the pathogenesis of arteriolosclerosis and mixed SVD, although we could not definitively account for the severity of shared risk factors. Longitudinal and experimental studies are, therefore, needed to investigate causal associations. Nevertheless, stroke clinicians should be aware of CKD as a potentially independent and modifiable risk factor of SVD.

Temporal and Spatial Clustering of Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy.

OBJECTIVES: Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH. METHODS: We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI. RESULTS: In 682 included patients (median age 68 years, 40.3% female, median follow-up time 4.1 years), 18 (2.6%) had an early recurrent ICH, which was associated with higher age and CAA. In patients with probable CAA, the risk of early recurrent ICH was increased 5-fold within the first 3 months compared with during months 4-12 (hazard ratio 5.41, 95% CI 2.18-13.4) while no significant difference was observed in patients without CAA. In patients with an ICH cluster, we observed spatial clustering (recurrent ICH within close proximity of index ICH in 63.0%) and a tendency for multiple sequential hemorrhages (≥3 ICH foci within 3 months in 44.4%). DISCUSSION: Our data provide evidence of both temporal and spatial clustering of ICH in CAA, suggesting a transient and localized active bleeding-prone process.

Association of the Presence and Pattern of MRI Markers of Cerebral Small Vessel Disease With Recurrent Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiologic subtypes (including cryptogenic ICH) relevant for recurrence risk. METHODS: We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural, or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (nonlobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes), or cryptogenic ICH (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multicenter cohort (CROMIS-2 ICH) were used to confirm core findings. RESULTS: Of 443 patients with ICH (mean age 67 ± 13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic ICH in 16.7%. During a median follow-up period of 5.7 years (interquartile range 2.9-10.0, 2,682 patient-years), recurrent ICH was found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by that in those with mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n = 216), in which also there was no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related to ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6). DISCUSSION: MRI-based etiologic subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis and negligible for cryptogenic ICH.