Local cerebral neurofilament light chain during acute stage is associated with clinical outcomes in stroke patients receiving endovascular thrombectomy

 

ABSOLUTELY FUCKING USELESS! Predictions/'assessments' DO NOTHING to get survivors recovered! Solve the correct problem: 100% recovery protocols!

Local cerebral neurofilament light chain during acute stage is associated with clinical outcomes in stroke patients receiving endovascular thrombectomy

• Kunxin Lin, 
• Youliang Wang, 
• Wenlong Zhao, 
• Yiru Zheng, 
• Xiaohua Sun, 
• Ling Fang, 
• Ying Fu, 
• Ning Wang & 
• Qianqian Lin 

BMC Neurology volume 25, Article number: 285 (2025) Cite this article

Abstract

Background

Prediction of stroke outcomes is challenging due to limited predictive properties of clinical and radiological variables. We aimed to investigate whether local cerebral neurofilament light chain (NfL) could provide additional prognostic value.

Methods

We prospectively enrolled 110 consecutive patients with large vessel occlusion of the anterior circulation who underwent endovascular thrombectomy (EVT). We collected two different arterial blood samples during EVT: (1) Local: the region of the occluded vascular compartment; (2) Systemic: femoral artery. We used ultrasensitive single-molecule array assay to measure NfL levels, compare systemic and local NfL levels and explore the association of systemic and local NfL with imaging markers and clinical outcomes.

Results

Of the 220 blood samples from the 110 patients who received EVT, the local NfL levels was significantly lower than system levels. Compared with the lower level of local NfL, patients with higher local NfL were more likely male (74.5% vs. 54.5%, p = 0.017), had lower rate of intravenous thrombolysis (14.5% vs. 30.9%, p = 0.041), higher percentage of non-cardioembolic subtype (67.3% vs. 47.3%, p = 0.045). Neither system or local NfL levels correlated with baseline clinical-radiological variables including stroke severity, brain ischemic injury and collateral status. High local NfL could independently predict mortality (OR, 2.431; 95% CI, 1.099–5.378, p = 0.028) and functional outcome towards worse outcome at 90 days (OR, 2.596; 95% CI, 1.267–5.312, p = 0.009) after multivariable regression analysis.

Conclusions

Our study suggested that elevated baseline local NfL accumulated in the ischemic vasculature might be a promising predictor for increased adverse clinical outcome of patients receiving EVT.

Peer Review reports

Introduction

Endovascular thrombectomy (EVT) is currently crucial for acute ischemic stroke patients with large artery occlusion [1]. However, not all patients could benefit from EVT even with early successful recanalization [2,3,4]. Reliable prognosis was not only of great importance to the patients but also informs therapeutic strategies and improve clinical trial design. When patients had large infarct core volume, poor collateral circulation et al., there were limited benefits from EVT for patients [5, 6]. Neuroimaging has gradually become a powerful tool in predicting patients’ outcomes, ranging from basic Alberta Stroke Program Early CT Score (ASPECTS) for estimating infarct lesion, to advanced CT perfusion or magnetic resonance perfusion for calculating infarct core and ischemic penumbra, and dynamic CT angiography for evaluating collateral circulation et al. [7,8,9]. However, neuroimaging tools were limited by imaging quality, neurologists and radiologists’ experiences, specific condition for formula calculation et al., which could be at risk of bias. Therefore, it is important to explore other methods added to neuroimaging to predict clinical outcomes.

Biomarkers that could reflect brain injury may have additional value for EVT. Neurofilament, an integral protein of the neuronal cytoskeleton, has been considered as a promising candidate biomarker for neuroaxonal injury as they are exclusively expressed in neurons and specific for neuronal cell damage [10]. Measurement of neurofilament light chain (NfL) in cerebrospinal fluid and serum, one of the neurofilament protein, was as a marker of axonal injury for monitoring disease progress and assessing efficacy of treatment in many neurological diseases, including amyotrophic lateral sclerosis, Parkinson’s disease, multiple sclerosis et al. [11,12,13]. Meanwhile, several previous studies had investigated the associations of NfL levels in peripheral blood with clinical outcomes (Supplemental Table 1) [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. Most studies had found the higher level of NfL was correlated with unfavorable outcomes like larger infarct volume, hemorrhage transformation, functional dependence and mortality. However, the majority of these studies included all types of ischemic stroke and the sampling time was often within at least 24 h after stroke onset which could not reflect the hyperacute stage. Moreover, NfL has only been studied in the peripheral location and nothing known about NfL levels in the brain vessel. Therefore, we sought to help fill this gap in knowledge of NfL in the local cerebral ischemic region by obtaining blood sample during EVT. Moreover, NfL has only been studied in the peripheral location and nothing known about NfL levels in the brain vessel. We sought to help fill this gap in knowledge of NfL in the local cerebral ischemic region by obtaining blood sample during EVT. A limited number of research teams [31,32,33] including our own, have developed a specific protocol for sampling cerebral blood from within the ischemic region during LVO strokes using microcatheter-aspiration. In this study, we aimed to measure NfL in local ischemic region, compare the NfL levels in systemic and local region, explore the impact factors of local NfL during acute stage and whether it could independently predict stroke outcomes.

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