Neutrophil Count Predicts Malignant Cerebellar Edema and Poor Outcome in Acute Basilar Artery Occlusion Receiving Endovascular Treatment: A Nationwide Registry-Based Study

Abstract

Background: Acute basilar artery occlusion (ABAO) is known to have a poor outcome with a high rate of morbidity and mortality despite endovascular treatment (EVT), highlighting the necessities of exploring factors to limit the efficacy of EVT in these patients. Cerebellar infarctions in ABAO might progress to malignant cerebellar edema (MCE), a life-threatening complication after reperfusion, posing a secondary injury to the brainstem by mass effects. Therefore, the present research aimed to explore the impacts of MCE on a long-term outcome and investigate the prognostic factors for MCE among ABAO after EVT.

Methods: In the national BASILAR registry, a total of 329 ABO patients with cerebellar infarctions treated by EVT met the inclusion criteria. The presence of MCE defined by the Jauss scale ≥4 points, was evaluated on the computed tomography performed 72 h after EVT. The adjusted odds ratio and 95% CI were obtained by logistic regression models. A favorable outcome was defined as a 90-day modified Rankin Scale score of 0-3.

Results: MCE was statistically associated with the decreased incidence of a favorable outcome [adjusted odds ratio, 0.35(95% CI, 0.18-0.68), P=0.002]. The baseline National Institutes of Health Stroke Scale score, collateral circulation, neutrophil count at admission, and recanalization status were predictors for MCE and a favorable functional status at 90 days (all P<0.05). Among all inflammatory factors, the neutrophil count achieved the highest accuracy, sensitivity, and specificity for MCE. Adding the neutrophil count status into the baseline model obviously enhanced its prediction ability for MCE and favorable outcome by increasing the area under curve and achieving both net reclassification and integrated discrimination improvement (all P<0.05). Mediation analysis indicated that MCE mediated the association between the increased neutrophil count and worse functional outcome (P=0.026).

Discussion: MCE acted essential roles in worsening prognosis for ABAO after EVT. A high neutrophil count at admission was linked to MCE and a poor outcome among ABAO patients, which could be further incorporated into the clinical decision-making system and guide immunomodulation therapy.

Keywords: acute basilar artery occlusion; endovascular treatment; malignant cerebellar edema; neutrophil count; outcome.

Figure 1

Predictive values of neutrophil count (Neu), leukocyte count (Lym), platelet count (PTL), PLR, and NLR for 4 endpoints including MCE, long-term favorable outcome, sICH, and any hemorrhage.

Figure 2

The impacts of neutrophil count on clinical outcome. (A) Distribution of the MCE across patients with different neutrophil count status; (B) Distribution of the mRS scores at 90 days according to the trichotomized neutrophil count status. (C) Adjusted logistic regression models evaluated the associations between neutrophil level with outcomes. ^a Change from NIHSS at admission from NIHSS at 24 h after EVT. ^b Change from NIHSS at admission from NIHSS at 5-7 days after EVT. ^cAdjusted common OR; adjusted estimates of outcome were calculated using multiple regression, taking the following variables into account: baseline NIHSS score, baseline PC-ASPECTS, neutrophil count, mTICI, PC-CS score, occlusion sites, and onset to recanalization time. ^dß-values were estimated from a multivariable linear regression model; adjusted estimates of outcome were calculated using multiple regression, taking the following variables into account: baseline NIHSS score, baseline PC-ASPECTS, neutrophil count, mTICI, PC-CS score, occlusion sites, and onset to recanalization time. NIHSS, National Institutes of Health Stroke Scale; mRS, modified Rankin Scale score at 90 days.

Figure 3

Incremental effect of the neutrophil count level on the predictive value of the baseline model for favorable outcome and MCE. (A) ROC curves for baseline model and novel model count level when predicting long-term outcome. (B) ROC curves for baseline model (ROC1) and novel model (ROC2: adding neutrophil count level into the baseline model) when predicting MCE. (C) Results from DeLong’s test, the NRI, and IDI by comparing ROC curves in (A, B), separately. (D) Mediation analysis by MCE of the associations between neutrophil count level and clinical outcome. a, regression coefficient of the association between neutrophil count and MCE; b, regression coefficient of the association between MCE and clinical outcome; c, regression coefficient of the association between neutrophil count level and clinical outcome; c’, regression coefficient of the association between neutrophil count level and clinical outcome, using neutrophil count level and MCE as additional independent variables. The percentage difference of the coefficients (1-c/c’) is shown. a, b, c, and c’ were evaluated by adjusted OR, taking the following variables into account: baseline NIHSS score, baseline PC-ASPECTS, mTICI, PC-CS score, occlusion sites, and onset to recanalization time.