Dataset Information

Association between Computed Tomographic Biomarkers of Cerebral Small Vessel Diseases and Long-Term Outcome after Spontaneous Intracerebral Hemorrhage.

ABSTRACT:

Objective

A study was undertaken to assess whether cerebral small vessel disease (SVD) computed tomographic (CT) biomarkers are associated with long-term outcome after intracerebral hemorrhage.

Methods

We performed a prospective, community-based cohort study of adults diagnosed with spontaneous intracerebral hemorrhage between June 1, 2010 and May 31, 2013. A neuroradiologist rated the diagnostic brain CT for acute intracerebral hemorrhage features and SVD biomarkers. We used severity of white matter lucencies and cerebral atrophy, and the number of lacunes to calculate the CT SVD score. We assessed the association between CT SVD biomarkers and either death, or death or dependence (modified Rankin Scale scores = 4-6) 1?year after first-ever intracerebral hemorrhage using logistic regression, adjusting for known predictors of outcome.

Results

Within 1?year of intracerebral hemorrhage, 224 (56%) of 402 patients died. In separate models, 1-year death was associated with severe atrophy (adjusted odds ratio [aOR] =?2.54, 95% confidence interval [CI] =?1.44-4.49, p = 0.001) but not lacunes or severe white matter lucencies, and CT SVD sum score ??1 (aOR = 2.50, 95% CI = 1.40-4.45, p = 0.002). Two hundred seventy-seven (73%) of 378 patients with modified Rankin Scale data were dead or dependent at 1?year. In separate models, 1-year death or dependence was associated with severe atrophy (aOR = 3.67, 95% CI = 1.71-7.89, p = 0.001) and severe white matter lucencies (aOR = 2.18, 95% CI = 1.06-4.51, p = 0.035) but not lacunes, and CT SVD sum score ??1 (aOR = 2.81, 95% CI = 1.45-5.46, p = 0.002).

Interpretation

SVD biomarkers on the diagnostic brain CT are associated with 1-year death and dependence after intracerebral hemorrhage, independent of known predictors of outcome. ANN NEUROL 2021;89:266-279.

SUBMITTER: Rodrigues MA

PROVIDER: S-EPMC7894327 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between Computed Tomographic Biomarkers of Cerebral Small Vessel Diseases and Long-Term Outcome after Spontaneous Intracerebral Hemorrhage.

Rodrigues Mark A MA E Samarasekera Neshika N Lerpiniere Christine C Perry Luke A LA Moullaali Tom J TJ J M Loan James J Wardlaw Joanna M JM Al-Shahi Salman Rustam R

Annals of neurology 20201120 2

<h4>Objective</h4>A study was undertaken to assess whether cerebral small vessel disease (SVD) computed tomographic (CT) biomarkers are associated with long-term outcome after intracerebral hemorrhage.<h4>Methods</h4>We performed a prospective, community-based cohort study of adults diagnosed with spontaneous intracerebral hemorrhage between June 1, 2010 and May 31, 2013. A neuroradiologist rated the diagnostic brain CT for acute intracerebral hemorrhage features and SVD biomarkers. We used seve ...[more]

PMID: 33145789

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Project description:BACKGROUND AND PURPOSE:Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. METHODS:We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P<5×10-8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. RESULTS:The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: a genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: ?, 1.84; SE, 0.32; P=4.4×10-8) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: ?, 0.95; SE, 0.17; P=4.3×10-8) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 (P=0.04; meta-analysis P=2.5×10-9; heterogeneity, P=0.16) but not for 22q13 (P=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P=0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P=0.045). CONCLUSIONS:We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association.

Project description:BACKGROUND AND OBJECTIVE:The aim of this study was to evaluate the impact of radiographic cerebral small vessel disease (CSVD) on the severity of acute intracerebral hemorrhage (ICH) as measured by: ICH volume, hematoma expansion, and extension of intraventricular hemorrhage (IVH). METHODS:CSVD was determined on baseline computed tomography (CT) scans of patients from the Ethnic and Racial Variations of Intracerebral Hemorrhage study through the extent of leukoaraiosis and cerebral atrophy using visual rating scales. The associations of leukoaraiosis and atrophy with ICH volume, hematoma expansion, IVH presence, and severity of IVH were tested using multivariable regression models. Secondary analyses were stratified by hemorrhage location. Bonferroni correction was applied to correct for multiple testing. RESULTS:A total of 2579 patients (mean age 61.7 years, 59% male) met inclusion criteria. Median ICH volume was 10.5 (Interquartile range [IQR] 4.0-25.3) mL. IVH was detected in 971 patients (38%). Neither leukoaraiosis nor atrophy was associated with hematoma expansion. Increasing grades of leukoaraiosis were associated with increased risk of IVH in a dose-dependent manner, while cerebral atrophy was inversely associated with IVH (both P for trend?<?0.001). Increasing grades of global atrophy were dose-dependently associated with lower ICH volumes (ß (95% Confidence Interval [CI]) -?0.30[-?0.46, -?0.14], -?0.33[-?0.49, -?0.17], -?0.40[-?0.60, -?0.20], and -?0.54[-?0.76, -?0.32], for grades 1, 2, 3 and 4 compared to 0; all P?<?0.001). The associations of leukoaraiosis with ICH volume were consistent with those of atrophy, albeit not meeting statistical significance. CONCLUSIONS:Leukoaraiosis and cerebral atrophy appear to have opposing associations with ICH severity. Cerebral atrophy correlates with smaller ICH volume and decreased risk and severity of IVH, while leukoaraiosis is associated with increased risk of IVH. Whether these observations reflect overlapping or divergent underlying mechanisms requires further study.

Dataset Information

Association between Computed Tomographic Biomarkers of Cerebral Small Vessel Diseases and Long-Term Outcome after Spontaneous Intracerebral Hemorrhage.

Objective

Methods

Results

Interpretation

Publications

Association between Computed Tomographic Biomarkers of Cerebral Small Vessel Diseases and Long-Term Outcome after Spontaneous Intracerebral Hemorrhage.

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