Associations of Radiographic Cerebral Small Vessel Disease with Acute Intracerebral Hemorrhage Volume, Hematoma Expansion, and Intraventricular Hemorrhage

Abstract

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.

Higher cerebral small vessel disease burden is associated with smaller hematoma volume in mixed‐location intracerebral hemorrhage

“…This remodeling of microvascular wall might protect from secondary ruptures 35 . In addition, higher CMBs 7 and more severe brain atrophy, 10 both are significantly correlated with WMH, 34 have been found to be associated with smaller hematoma volume in ICH patients. Taken together, cerebral white matter might be a possible epicenter for brain protection and could heighten brain health by mechanistic pathways 36 .…”

“…Two studies found no significant difference between WMH and hematoma volume, 7,9 which contradicted one study 8 reporting that severe WMH was independently associated with large hematoma volume in the whole population of primary ICH. More recently, Uniken Venema SM et al 10 found an opposing association of leukoaraiosis on brain CT with hematoma volume in univariable analysis, albeit not meeting statistical significance in multivariable analysis. Because of the controversies about the relationship of white matter lesions with hematoma volume, there is a need to investigate it further.…”

“…However, this relationship remains unclear. Positive, negative, and opposite correlations have been described 7–10 . The specific ICH subtypes reflect different etiology, while none of the prior studies have explored the association between CSVD and hematoma volume in specific ICH subtype (mixed‐location ICH, HA‐ICH, and CAA‐ICH), especially when the distribution of CSVD markers varies by particular small vessel disease 1,11–13 …”

Intracerebral Hemorrhage with Intraventricular Extension Associated with Loss of Consciousness at Symptom Onset

“…Assessment of neuroimaging and determination of hematoma volumes in the ERICH cohort has been described previously [ 20 – 22 ]. Initial and follow-up CT images were used to obtain the following variables: ICH location and ICH and IVH volumes, using semiautomated computerized volumetric analysis (Alice software, Parexel Corporation, Waltham, MA).…”

Commentary on Associations of Radiographic Small Vessel Disease with Acute Intracerebral Hemorrhage Volume, Hematoma Expansion, and Intraventricular Hemorrhage

“…Venema et al [1] performed a study based on Ethnic and Racial Variations in Intracerebral Hemorrhage, a multicenter, racially balanced, prospective study of spontaneous intracerebral hemorrhage (ICH). The authors hypothesize that underlying cerebral small vessel disease (CSVD) and poor outcome from ICH stem from two mechanisms: (1) how CSVD affects ICH severity, and (2) CSVD's influence on brain recovery after ICH; the authors intend to address the former in this study.…”