Early Predictors of the Increase in Perihematomal Edema Volume After Intracerebral Hemorrhage: A Retrospective Analysis From the Risa-MIS-ICH Study

Abstract

Background and Purpose: Perihematomal edema (PHE) is associated with poor functional outcomes after intracerebral hemorrhage (ICH). Early identification of risk factors associated with PHE growth may allow for targeted therapeutic interventions.Methods: We used data contained in the risk stratification and minimally invasive surgery in acute intracerebral hemorrhage (Risa-MIS-ICH) patients: a prospective multicenter cohort study. Patients' clinical, laboratory, and radiological data within 24 h of admission were obtained from their medical records. The absolute increase in PHE volume from baseline to day 3 was defined as iPHE volume. Poor outcome was defined as modified Rankin Scale (mRS) of 4 to 6 at 90 days. Binary logistic regression was used to assess the relationship between iPHE volume and poor outcome. The receiver operating characteristic curve was used to find the best cutoff. Linear regression was used to identify variables associated with iPHE volume (ClinicalTrials.gov Identifier: NCT03862729).Results: One hundred ninety-seven patients were included in this study. iPHE volume was significantly associated with poor outcome [P = 0.003, odds ratio (OR) 1.049, 95% confidence interval (CI) 1.016–1.082] after adjustment for hematoma volume. The best cutoff point of iPHE volume was 7.98 mL with a specificity of 71.4% and a sensitivity of 47.5%. Diabetes mellitus (P = 0.043, β = 7.66 95% CI 0.26–15.07), black hole sign (P = 0.002, β = 18.93 95% CI 6.84–31.02), and initial ICH volume (P = 0.018, β = 0.20 95% CI 0.03–0.37) were significantly associated with iPHE volume. After adjusting for hematoma expansion, the black hole sign could still independently predict the increase of PHE (P < 0.001, β = 21.62 95% CI 10.10–33.15).Conclusions: An increase of PHE volume >7.98 mL from baseline to day 3 may lead to poor outcome. Patients with diabetes mellitus, black hole sign, and large initial hematoma volume result in more PHE growth, which should garner attention in the treatment.

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

“…Meanwhile, data from the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) indicated that a history of hypertension, baseline hematoma volume, body temperature, and time from the onset of symptoms to CT scan were independently associated with a relative increase in PHE in 207 patients with acute ICH [ 138 ]. In particular, many studies implied that a large volume of ICH was correlated with the severity and progression of PHE [ 115 , 116 , 138 , 139 ]. Probably due to the ambiguous effects of fever on ICH outcomes, the effects of therapeutic hypothermia on brain edema are currently heterogeneous in patients with ICH [ 123 , 140 , 141 ].…”

“…The growth of PHE measured by PHE expansion and EED was also used to evaluate the severity of brain edema after ICH in patients. Two clinical studies have found that an increase in absolute PHE volume from baseline to day 3 was correlated with a poor outcome 3 months after ICH [ 116 , 179 ]. A study with 115 patients also found that the PHE expansion rate from baseline to 72 hours was associated with poor functional outcomes after deep ICH [ 180 ].…”

“…Relative PHE (rPHE) refers to the ratio of the absolute PHE volume to the initial hematoma volume (rPHE = absolute PHE/ initial hematoma volume) [109][110][111]. Studies on absolute PHE have indicated that more extensive hemorrhages lead to a larger volume of PHE [21,116]. However, rPHE showed an inverse correlation with the initial volume of ICH, where a small ICH produced a volume of edema relatively more prominent than a large ICH [111].…”

“…It will be necessary to explore further the mechanisms underlying the association between these genotype variations and the evolution of PHE after ICH. Regarding other demographic or clinical variables, EED studies revealed that PHE tended to be more severe inpatients of males, older age, a higher score on the National Institutes of Health Stroke Scale (NIHSS), a lower Glasgow Coma Scale score, a larger volume of ICH, larger initial EED, irregularly shaped hematoma, black hole sign, or higher glucose concentration [111,115,116,136,137]. Meanwhile, data from the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) indicated that a history of hypertension, baseline hematoma volume, body temperature, and time from the onset of symptoms to CT scan were independently associated with a relative increase in PHE in 207 patients with acute ICH [138].…”

“…Higher glucose [115] Larger initial ICH volume [116,138] Higher admission hematocrit [21] History of hypertension [138] Irregular hematoma or black hole sign [115,116] Higher admission time for partial thromboplastin time [21] Higher admission SBP [144,145] Larger initial EED [115] Absence in warfarin preuse [99,149] Impaired blood pressure regulation [139] Time from symptom onset [138] Higher serum levels of IL-6 and soluble CD163 [150,153] Higher body temperature [123,124,138,140,141] Absence in sulfonylurea drug pretreatment [142,143] Higher serum MMP-3 or MMP-8 levels [151,152] Abbreviations: PHE: perihematomal edema; APOE4: apolipoprotein E; AQP4: aquaporin 4; TIMP-2: tissue inhibitor of metalloproteinases 2; Hp: haptoglobin; SBP: systolic blood pressure; ICH: intracerebral hemorrhage; EED: edema extension distance; MMP: matrix metallopeptidase; AIVF: absent in ipsilateral venous filling; JVR: jugular vein reflex; CVFV: cerebral venous outflow volume. Oxidative Medicine and Cellular Longevity rPHE in patients with ICH [139].…”