Interaction Effect of Baseline Serum Glucose and Early Ischemic Water Uptake on the Risk of Secondary Hemorrhage After Ischemic Stroke

Abstract

Background and Purpose: Intracerebral hemorrhage (ICH) after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains a major complication and its early prediction is of high relevance. Baseline serum glucose (BGL) is a known predictor of ICH, but its interaction with early ischemic changes remains uncertain. We hypothesized that BGL interacts with the effect of tissue water uptake on the occurrence of ICH. Methods: Three hundred and thirty-six patients with acute ischemic stroke treated with MT were retrospectively analyzed. ICH was diagnosed within 24 h on non-enhanced CT (NECT) and classified according to the Heidelberg Bleeding Classification. Early tissue water homeostasis has been assessed using quantitative lesion net water uptake (NWU) on admission CT. Multivariate logistic regression was used to identify predictors of ICH. Results: One hundred and seven patients fulfilled the inclusion criteria of which 37 (34.6%) were diagnosed with ICH. Patients with ICH had a significant higher BGL on admission (median 177 mg/dl, IQR: 127-221.75, P < 0.001). In patients with low BGL (<120 mg/dl), higher NWU was associated with 1.34-fold increased likelihood of ICH, while higher NWU was associated with a 2.08-fold increased likelihood of ICH in patients with a high BGL (>200 mg/dl). In multivariable logistic regression analysis, BGL (OR: 1.02, 95% CI: 1.00-1.04, P = 0.01) and NWU (OR: 2.32, 95% CI: 1.44-3.73, P < 0.001) were significantly and independently associated with ICH, showing a significant interaction (P = 0.04). Conclusion: A higher degree of early tissue water uptake and high admission BGL were both independent predictors of ICH. Higher BGL was significantly associated with accelerated effects of NWU on the likelihood of ICH. Although a clear causal relationship remains speculative, stricter BGL control and monitoring may be tested to reduce the risk of ICH in patients undergoing thrombectomy.

Keywords: edema; glucose; intracerebral hemorrhage; outcome; stroke.

Figure 1

Patient flowchart. CT, computed tomography; NIHSS, National Institutes of Health Stroke Scale (NIHSS); TICI, thrombolysis in cerebral infarction.

Figure 2

Interaction analysis of BGL and NWU on the occurrence of ICH. Occurrence of secondary intracerebral hemorrhage (ICH, y-axis) according to trichotomized NWU (net water uptake; low NWU: <7%; intermediate NWU: 7–12%; high NWU: >12%) and BGL (baseline glucose level; glucose in mg/dl, x-axis). The interaction term between NWU and BGL was significant.

Figure 3

Illustrative example of a patient with baseline glucose and water uptake and secondary ICH after successful thrombectomy. Illustration of a patient with high early baseline blood glucose and high ischemic water uptake, with subsequent secondary intracerebral hemorrhage after thrombectomy. On the left, patient admission images are displayed with admission non-enhanced CT and ROIs for ischemic hypoattenuation (D_ischemic) and on the contralateral side (D_normal) as well as relative CBV (rCBV). The rCBV map (ml per 100 ml) is inferred from a quantitative assessment of the partial volume averaging in each pixel. In the middle, follow-up non-enhanced CT images at 24 h are displayed with secondary intracerebral hemorrhage (parenchymal hematoma; grade 1). On the right, follow-up non-enhanced CT images at 48 h are displayed with secondary intracerebral hemorrhage (parenchymal hematoma; grade 2). rCBV, relative cerebral blood volume; NECT, non-enhanced CT; PH1, parenchymal hematoma grade 1; PH2, parenchymal hematoma grade 2.

Figure 4

Relationship of BGL and NWU on the occurrence of ICH. Occurrence of secondary intracerebral hemorrhage (ICH) according to baseline NWU (net water uptake) and BGL (baseline glucose level), separately for patients with low and high BGL (based on the median BGL) and trichotomized NWU based on relative distribution of NWU within the patient cohort (low NWU: <7%; intermediate NWU: 7–12%; high NWU: >12%).

Figure 5

Receiver operating curve (ROC) analysis for the prediction of secondary hemorrhage after successful mechanical recanalization. ASPECTS, Alberta Stroke Program Early CT Score; AUC, area under the curve; 95% CI, 95% confidence interval; NWU, net water uptake; BGL, baseline glucose level.