Remote Diffusion-Weighted Imaging Lesions and Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis

Abstract

BACKGROUND: Remote diffusion-weighted imaging lesions (RDWILs) in the context of spontaneous intracerebral hemorrhage (ICH) are associated with an increased risk of recurrent stroke, worse functional outcome, and death. To update current knowledge on RDWILs, we conducted a systematic review and meta-analysis of the prevalence, associated factors and presumed causes of RDWILs. METHODS: We searched Pubmed, Embase, and Cochrane up to June 2022 for studies reporting RDWILs in adults with symptomatic ICH of no-identified-cause, assessed by magnetic resonance imaging, and analyzed associations between baseline variables and RDWILs in random-effects meta-analyses. RESULTS: Eighteen observational studies (7 prospective), reporting 5211 patients were included, of whom 1386 had ≥1 RDWIL (pooled prevalence: 23.5% [19.0–28.6]). RDWIL presence was associated with neuroimaging features of microangiopathy, atrial fibrillation (odds ratio, 3.67 [1.80–7.49]), clinical severity (mean difference in National Institutes of Health Stroke Scale score, 1.58 points [0.50–2.66]), elevated blood pressure (mean difference, 14.02 mmHg [9.44–18.60]), ICH volume (mean difference, 2.78 mL [0.97–4.60]), and subarachnoid (odds ratio, 1.80 [1.00–3.24]) or intraventricular (odds ratio, 1.53 [1.28–1.83]) hemorrhage. RDWIL presence was associated with poor 3-month functional outcome (odds ratio, 1.95 [1.48–2.57]). CONCLUSIONS: RDWILs are detected in approximately 1-in-4 patients with acute ICH. Our results suggest that most RDWILs result from disruption of cerebral small vessel disease by ICH-related precipitating factors such as elevated intracranial pressure and cerebral autoregulation impairment. Their presence is associated with worse initial presentation and outcome. However, given the mostly cross-sectional designs and heterogeneity in study quality, further studies are needed to investigate whether specific ICH treatment strategies may reduce the incidence of RDWILs and in turn improve outcome and reduce stroke recurrence.

Interaction between cerebral small vessel disease, blood pressure, and remote ischemic lesions in acute spontaneous intracerebral hemorrhage

“…RDWILs were proposed to be surrogate markers of ischemic processes in microangiopathy due to their close associations with the severity of cSVD. 6,15 Nevertheless, the causes of RDWILs could be heterogenous, with several other factors also contributing to the insults. These factors include hemodynamic instability, large-artery atherosclerosis, embolic events, and venous drainage disorders.…”

“…2,3 In addition, a larger acute BP reduction has been associated with the occurrence of small acute ischemic insults that can be detected by diffusion-weighted imaging (DWI) and that are spatially remote to the hematoma; thus, these lesions have been named remote DWI lesions (RDWILs). [4][5][6] RDWILs are found in around 11%-41% of patients with acute spontaneous ICH. [4][5][6] Although they are usually small and asymptomatic, RDWILs are associated with a higher risk of recurrent cerebrovascular events, higher rate of vascular death, and worse functional outcomes at 3 months.…”

“…5,7,8 The underlying mechanisms are heterogenous and cSVD pathology plays a major role in the formation of RDWILs. [4][5][6] Emerging research has highlighted that radiological markers of cSVD, including the burden of cerebral microbleeds (CMBs), extension of cortical superficial siderosis (cSS), white matter hyperintensity (WMH) volume, the degree of enlarged perivascular space (EPVS), lacunes count, and total cSVD score are associated with the risk of RDWILs. 5,7 Intensive BP reduction has been proposed to lead to cerebral hypoperfusion and consequent ischemic changes at vulnerable areas due to impaired cerebral autoregulation resulting from cSVD.…”

“…2,3 In addition, a larger acute BP reduction has been associated with the occurrence of small acute ischemic insults that can be detected by diffusion-weighted imaging (DWI) and that are spatially remote to the hematoma; thus, these lesions have been named remote DWI lesions (RDWILs). 4–6…”

“…[4][5][6] RDWILs are found in around 11%-41% of patients with acute spontaneous ICH. [4][5][6] Although they are usually small and asymptomatic, RDWILs are associated with a higher risk of recurrent cerebrovascular events, higher rate of vascular death, and worse functional outcomes at 3 months. 5,7,8 The underlying mechanisms are heterogenous and cSVD pathology plays a major role in the formation of RDWILs.…”