Association of 72-hour spleen volume change with 45-day mortality in patients with spontaneous intracerebral hemorrhage
Year: 2026
Type: article
Abstract: Introduction: Spontaneous intracerebral hemorrhage (ICH) is a major neurological emergency with a high risk of early mortality and permanent disability. Prognostic tools such as the Intracerebral Hemorrhage Score (ICH Score) assess clinical and radiological disease severity at presentation but do not reflect the dynamic systemic responses that develop in the days after the hemorrhage. The spleen is an extracerebral organ that may take part in brain–periphery immune interaction through autonomic activation, redistribution of immune cells, and the systemic inflammatory response. The primary aim of this study was to determine the association of spleen volume change over the first 72 hours (ΔSpleen) with 45-day mortality. We also aimed to compare the prognostic performance of ΔSpleen with that of hematoma volume change and to assess whether adding it to the ICH Score improves the discrimination of mortality.Methods: In this prospective, single-center observational cohort study, patients over 18 years of age whose diagnosis of spontaneous ICH had been confirmed by brain computed tomography (CT) in the emergency department were evaluated consecutively. Of the 117 patients screened for eligibility, 75 who completed baseline and 72-hour brain CT and spleen ultrasonography and whose 45-day clinical outcome could be determined were included. Patients who died before the 72-hour measurement, who had sepsis or active infection, hematological disease, active malignancy, a recent history of chemotherapy, or any condition that could cause splenomegaly, or whose serial imaging could not be completed were excluded. To compare baseline spleen volume, 75 healthy controls without acute neurological disease were evaluated. Demographic characteristics, comorbidities, antithrombotic medication use, routine laboratory findings, the Glasgow Coma Scale, the ICH Score, and radiological features were recorded at presentation. Hematoma volume was calculated with the ABC/2 method at baseline and at 72 hours. ΔHematoma was obtained by subtracting the baseline volume from the 72-hour volume. Spleen ultrasonography was performed with a Butterfly iQ+ handheld ultrasound device according to a standardized abdominal imaging protocol. Spleen length, width, and depth were measured in standard orthogonal planes. To reduce temporal variability, baseline ultrasonography was performed within the first two hours after the diagnostic brain CT and was repeated 72 hours later. Spleen volume was calculated with the formula length × width × depth × 0.523. ΔSpleen was obtained by subtracting the baseline volume from the 72-hour volume; positive values indicated an increase and negative values a decrease. The primary outcome was 45-day all-cause mortality. The associations of ΔSpleen, ΔHematoma, and the ICH Score with mortality were evaluated with logistic regression. To limit the risk of overfitting and to directly examine whether ΔSpleen provided information beyond the ICH Score, the prespecified multivariable model included only the ICH Score and ΔSpleen per 10 mL increase. Discriminative performance was assessed with the area under the receiver operating characteristic curve (AUC), and the optimal threshold was determined with the Youden index. The AUCs of the ICH Score model and the ICH Score + ΔSpleen model were compared with the DeLong method. The combined model was internally validated with 1,000 bootstrap resamples. Interrater reliability of measurements between two independent operators was examined in 30 patients with the intraclass correlation coefficient.Results: Baseline spleen volume was higher in ICH patients than in healthy controls (233.2 [168.1–356.1] mL vs 181.4 [172.6–187.2] mL; p<0.001). Twenty-eight ICH patients (37.3%) died within 45 days. Of the deaths, 23 (82.1%) were attributed primarily to ICH or its neurological complications and 5 (17.9%) to medical or infectious causes. Those who died had a lower Glasgow Coma Scale score (8 [6–12] vs 15 [13–15]; p<0.001), a higher ICH Score (2 [2–3] vs 1 [0–1]; p<0.001), and more frequent intraventricular hemorrhage (42.9% vs 14.9%; p=0.007). Baseline spleen volume did not differ between those who died and survivors (208.1 [170.7–288.5] mL vs 252.7 [168.1–358.5] mL; p=0.626). In contrast, 72-hour spleen volume was higher in those who died (232.0 [171.5–410.7] mL vs 171.4 [128.0–215.5] mL; p=0.003). Spleen volume decreased by a median of 50.7 mL in survivors, whereas it increased by a median of 24.6 mL in those who died (p<0.001). Baseline and 72-hour hematoma volumes were 41.4 [18.1–139.2] and 75.9 [23.6–160.9] mL in those who died and 7.4 [3.5–18.5] and 5.6 [2.7–13.8] mL in survivors, respectively (p<0.001 for both). ΔHematoma was also higher in those who died (7.8 [−0.3–38.0] mL vs −1.4 [−3.6–−0.3] mL; p<0.001). ΔSpleen discriminated 45-day mortality with an AUC of 0.836 (95% confidence interval 0.732–0.940). The optimal threshold was ≥−6.9 mL, at which sensitivity was 71.4%, specificity 91.5%, and accuracy 84.0%. The AUC was 0.802 for ΔHematoma and 0.846 for the ICH Score. In the multivariable model, both the ICH Score and ΔSpleen remained independently associated with mortality. The adjusted odds ratio was 3.89 for each 1-point increase in the ICH Score (95% confidence interval 1.89–8.02; p<0.001) and 1.20 for each 10 mL increase in ΔSpleen (95% confidence interval 1.05–1.36; p=0.006). Adding ΔSpleen to the ICH Score raised the AUC from 0.846 to 0.921, an absolute increase of 0.075 (95% confidence interval 0.002–0.149; p=0.045). In the combined model, sensitivity rose from 75.0% to 92.9%, specificity from 74.5% to 80.9%, and accuracy from 74.7% to 85.3%. On internal validation, the mean optimism was 0.008, the optimism-corrected AUC was 0.913, and the corrected Brier score was 0.118. Interrater agreement was good (intraclass correlation coefficient 0.81; 95% confidence interval 0.75–0.84); the mean absolute measurement difference was 9.3 mL (Table 1 and 2).Discussion/Conclusion: In patients with spontaneous ICH who completed the serial assessments over the first 72 hours, median spleen volume decreased in survivors and increased in those who died. ΔSpleen remained associated with 45-day mortality after adjustment for the ICH Score and, when added to the ICH Score, improved the discrimination of mortality. The main strengths of the study are its prospective design, consecutive patient assessment, standardized timing of measurements, serial measurements, healthy control group, interrater reliability analysis, limited multivariable model, and bootstrap internal validation. However, the single-center design and relatively small sample, the limited number of events, the operator dependence of ultrasonography, unmeasured confounders, and the lack of external validation limit generalizability. In addition, excluding patients who died before the 72-hour measurement or whose serial imaging could not be completed may introduce selection and survivorship bias; the findings therefore reflect dynamic risk assessment in patients who completed the first 72 hours, not prognosis at presentation. The data-driven threshold of ≥−6.9 mL should not be used as a clinical decision limit before it is validated in independent cohorts. ΔSpleen is not a substitute for the ICH Score or other established clinical-radiological severity indicators; it should be regarded as a dynamic, extracerebral marker that may provide additional prognostic information, particularly beyond the ICH Score.Keywords:
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225781580
FWCI:
Cites:
Cited by:
Related to: