The risk and outcome of malignant brain edema in post-mechanical thrombectomy: acute ischemic stroke by anterior circulation occlusion

The Institutional Review Board of the General Hospital of Northern Theatre Command approved the study. All hospitalized patients with anterior circulation LVO ischemic stroke who underwent MT during the period from June 2016 to December 2021 were recruited. Indications for MT followed the most recent treatment guidelines at the time of patient inclusion [7]. Baseline clinical information, imaging data, and periprocedural data of patients were collected and reviewed.

The inclusion criteria included: (1) adults aged at least 18 years; (2) anterior circulation LVOS comprising middle cerebral artery (MCA) occlusion (M1 or M2 segments) and terminal internal carotid artery (ICA) occlusion confirmed by digital subtraction angiography (DSA) prior to MT; (3) baseline Alberta Stroke Program Early CT Score (ASPECT) score ≥ 6, baseline NIHSS score ≥ 6, and pre-stroke mRS score ≤ 2; and (4) time from onset to puncture (OTP) ≤ 24 h. The exclusion criteria included: (1) patients with parenchymal hemorrhage (PH) after MT; (2) patients without complete clinical and imaging data. The flowchart of patient enrolment is shown in Fig. 1.

The baseline characteristics of the study participants were collected from the medical records. They included demographic data (age and sex), medical history (hypertension, diabetes mellitus, coronary heart disease, atrial fibrillation, and past history of stroke), habits and customs (smoking and alcohol use), TOAST, Trial of Org 10172 in Acute Stroke Treatment, radiographic data, and duration from stroke onset to imaging. The periprocedural parameters included occluded vessel region, intravenous thrombolytic therapy, OTP, remedial measures (balloon dilatation and stent implantation), the number of retrieval attempts, and revascularization of occluded vessels. A certified stroke neurologist assessed the severity of the neurological deficit and status of each patient using the NIHSS during admission at the emergency department.

Standard non-contrast computed tomography (NCCT) was performed using a US GE Discovery CT 750 HD scanner (GE Healthcare, Milwaukee, WI, USA). It was initially performed for all participants using the following parameters: 100 kV, 120 mA, 40 mm collimator width, 25 cm field of view, 5 mm layer thickness, and 5 mm layer spacing. Participants were placed in the supine position with their upper limbs lying flat on both sides of their bodies and head slightly inclined.

Image review was independently performed on a wide-screen high-resolution monitor with an adequate window and level setting. The imaging characteristics of all participants were evaluated by two experienced neuroimaging physicians with no prior knowledge of participants’ clinical information and conventional angiographic findings. In the case of a difference in opinion after assessment, an agreement was reached through consultation. The baseline ASPECT score, HMCAS, and signs of early infarct were assessed on the first NCCT at admission (time from onset to first NCCT ≤ 24 h). MBE was evaluated on NCCT within 72 h after MT. We used the standard ASPECT score to determine stroke burden (range from 0 to 10). A score of zero indicated diffuse cerebral infarction in the region of MCA blood supply, and a score of 10 indicated no new cerebral infarction. To objectively evaluate HMCAS, elliptical regions of interest were placed at MCA on both sides, and measure the attenuation of Hounsfield unit (HU). HMCAS was defined as the MCA attenuation > 43 HU and > 1.2 times of normal contralateral vascular density [8]. Baseline signs of early infarct refer to the observation of any of the following conditions: hypoattenuation in less than one-third of the middle cerebral artery area, blurred lenticular nucleus, disappearance of basal ganglia contour, disappearance of insular ribbon, blurring of sylvian fissure, or disappearance of cortical sulcus [9]. PH was defined as blood clots of the infarcted area with some slight space-occupying effect according to the ECASS (European Collaborative Acute Stroke Study) classification [10]. In previous studies, MBE was present if (1) > 50% of the MCA area had parenchymal hypodensity with signs of local brain swelling, such as disappearance of the sulci and gyri and compression of the lateral ventricle; and (2) midline shift of ≥   5 mm was present at the septum pellucidum or pineal gland with obliteration of the basal cisterns [11] (Fig. 2). The initial angiogram before the treatment allowed for collaterals assessment based on the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [12]. The score ≥ 3 was defined as favorable collateral status.

Intracranial arterial recanalization status was determined by DSA immediately after MT using the modified Thrombolysis in Cerebral Infarction (mTICI) grade. Successful recanalization was defined as an mTICI score of 2b to 3.

Clinical outcomes were measured using mRS at 90 days after onset. A favorable clinical outcome was defined as an mRS of 0–2. An mRS of 2 indicated slight disability (inability to perform all previous activities but cater for themselves without assistance), whereas an mRS ≥ 3 was considered a poor clinical outcome.

The data were analyzed using the SPSS software (version 22.6; IBM, Armonk, New York). Quantitative variables (age, NIHSS score at admission, baseline ASPECT score, time from stroke onset to imaging and OTP, the number of retrieval attempts) were reported as mean ± SD or median (interquartile range [IQR]). Categorical variables (sex, hypertension, diabetes mellitus, coronary heart disease, past history of stroke, atrial fibrillation, smoking, alcohol use, HMCAS, signs of early infarct, TOAST classification, occluded vessel region, intravenous thrombolytic therapy, angiographic favorable collaterals, balloon dilatation, stent implantation, and revascularization) were presented as frequencies and percentages. Normality of distributions was assessed using the Shapiro–Wilk test. The Student’s t test was used to compare two groups of normally distributed continuous data, whereas the Mann–Whitney test was used to compare two groups of non-normally distributed continuous data. Fisher’s exact test or χ² test was used to compare two groups of categorical data. Univariate and multivariate regression analyses were used to analyze the relationship between MBE and clinical outcomes and identify the predictors of MBE. Factors with P ≤ 0.1 in the univariate analysis were included in the logistic regression as independent variables for multivariate analysis. A P-value < 0.05 was considered statistically significant.

Two-hundred and eighty patients with LVO in the anterior circulation and had undergone MT were included in this study. Among these participants, 10 cases had preoperative ASPECT score < 6, 4 cases had NIHSS score at admission < 6, 4 cases had non-terminal occlusion of ICA, 58 cases had parenchymal hematoma, 49 cases lacked complete clinical and imaging data. Finally, 155 patients were included in this study (Fig. 1). The median age of the participants was 64 (IQR, 54–72) years, and 102 (65.8%) participants were male. 79 (51.0%) participants presented with HMCAS, and 81 (52.3%) participants presented with baseline signs of early infarct. Participants’ baseline ASPECT score was 8 (IQR, 8–10), and NIHSS score at admission was 14 (IQR, 11–17). 41 (26.5%) participants received MT and intravenous thrombolysis, and 130 (83.9%) participants were revascularized successfully. 68 (43.9%) participants had favorable 90-day clinical outcomes (mRS ≤ 2) (Table 1).

MBE was observed in 30 (19.4%) participants. The MBE group recorded a lower baseline ASPECT score than the non-MBE group (8 [6–9] vs 9 [8–10], P < 0.001). The MBE group had a lower HMCAS (20.0% vs 58.4%, P < 0.001), angiographic favorable collateral (16.7% vs 39.2%, P = 0.020) and revascularization rate (50.0% vs 92.0%, P < 0.001) than the non-MBE group. Additionally, the MBE group recorded higher baseline signs of early infarct (80.0% vs 45.6%, P = 0.001) and greater number of retrieval attempts (2 [1–4] vs 1 [1, 2], P = 0.018) than the non-MBE group.

No between-group differences were observed in age, sex, medical history, baseline NIHSS score, TOAST classification, intravenous thrombolytic therapy, stent implantation, and remedial measures including balloon dilatation. Additionally, no differences were observed in the occluded vessel region, time from onset of stroke to imaging, OTP, and medical history between both groups (P > 0.05) (Table 1).

Binary logistic regression analysis showed that low baseline ASPECT score (OR = 0.429, 95% CI 0.238–0.773, P = 0.005), absent HMCAS (OR = 4.576, 95% CI 1.352–15.485, P = 0.014), angiographic poor collaterals (OR = 5.346, 95% CI 1.322–21.628, P = 0.019), more retrieval attempt count (OR = 1.877, 95% CI 1.016–3.465, P = 0.044), and poor revascularization (mTICI < 2b) (OR = 11.937, 95% CI  2.932–48.602, P = 0.001) were independently associated with MBE after MT in patients with AIS caused by an anterior circulation LVO. Adjustment for the following confounding factors was performed before the analysis: NIHSS score at admission, baseline ASPECT score, absent HMCAS, baseline signs of early infarct, angiographic poor collaterals, poor revascularization, and number of retrieval attempts (Table 2).

In the univariate analysis, patients without MBE had better favorable 90-day clinical outcomes than patients with MBE (51.2% vs 13.3%, P < 0.001). Binary logistic regression analysis showed that patients with MBE (OR = 0.284, 95% CI  0.083–0.969, P = 0.044) were inversely associated with favorable 90-day clinical outcomes after adjusting for the NIHSS score at admission, angiographic favorable collaterals, number of retrieval attempts, revascularization, and presence of MBE (Tables 3 and 4).