Serum neurofilament light chain: a predictive marker for outcomes following mild-to-moderate ischemic stroke

 Oh fuck, when will leadership stop with the research that predicts failure to recover and do useful research like maybe: GETTING SURVIVORS RECOVERED!

Serum neurofilament light chain: a predictive marker for outcomes following mild-to-moderate ischemic stroke

Chongxi Xu^1†Tong Yi^2†Ting Qing³Yongliang Jiang¹Xingyang Yi⁴Jianguo Xu¹Junpeng Ma^1*

• ¹Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
• ²Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
• ³Department of Neurology, The Second People’s Hospital of Deyang City, Deyang, Sichuan, China
• ⁴Department of Neurology, People’s Hospital of Deyang City, Deyang, Sichuan, China

Background: Biomarkers that reflect brain damage or predict functional outcomes may aid in guiding personalized stroke treatments. Serum neurofilament light chain (sNfL) emerges as a promising candidate for fulfilling this role.

Methods: This prospective, observational cohort investigation included 319 acute ischemic stroke (IS) patients. The endpoints were the incidence of early neurological deterioration (END, an elevation of two or more points in the National Institute of Health stroke scale score within a week of hospitalization compared with the baseline) and functional outcome at 3 months (an mRS score of >2 at 3 months was categorized as an unfavorable/poor functional outcome). The association of sNfL, which was assessed within 24 h of admission, with END and unfavorable functional outcomes at follow-up was assessed via multivariate logistic regression, whereas the predictive value of sNfL for unfavorable functional outcomes and END was elucidated by the receiver operating characteristic curve (ROC).

Results: Of 319 IS individuals, 89 (27.90%) suffered from END. sNfL not only reflects the severity of stroke measured by NIHSS score (p < 0.05) but also closely related to the severity of age-related white matter changes. Higher initial NIHSS score, severe white matter lesions, diabetes mellitus, and upregulated sNfL were significant predictors of END. Similarly, the multivariate logistic regression analysis results showed that elevated sNfL, a higher baseline NIHSS score, and severe white matter lesions were substantially linked with unfavorable outcomes for 3 months. Similarly, sNfL was valuable for the prediction of the 3 months of poor outcome (95%CI, 0.504–0.642, p = 0.044). Kaplan–Meier analysis shows that patients with elevated sNfL levels are more likely to reach combined cerebrovascular endpoints (log-rank test p < 0.05).

Conclusion: This investigation suggests that sNfL can serve as a valuable biomarker for predicting END and 3-month poor functional outcomes after an IS and has the potential to forecast long-term cardiovascular outcomes.

Introduction

Stroke is a global disease characterized by a high incidence and disability and mortality rates (1, 2). Given the substantial global burden imposed by ischemic stroke (IS), it becomes imperative to identify a circulating biomarker that can serve as a reflection of brain injury (3). Neurofilament light chain (NfL) is a highly expressed neuronal cytoplasmic protein in large-caliber myelinated axons (4), and its concentration in both cerebrospinal fluid (CSF) and blood significantly increases during neuronal damage (5, 6). Although recent studies have shown that levels of NfL in blood are influenced by other confounding factors such as patient age, blood volume, body mass index (BMI), and renal function (7), and elevated levels are also observed in non-primary neurological disorders, for example, elevated levels of NfL have been observed in COVID-19 patients during the acute phase, correlating with clinical severity and adverse outcomes (8). However, its application as a biomarker of neuronal axonal injury in patients with primary neurological diseases profoundly changes current diagnostic and prognostic approaches to neurological disorders. Consequently, assessing NfL levels in cerebrospinal fluid or serum holds great potential for diagnosing, prognosticating, and monitoring neurologic disorders (4, 5). The literature has indicated that increased NfL levels are linked with the severity of Alzheimer’s disease (9), multiple sclerosis (10), amyotrophic lateral sclerosis (11), etc. Much research has focused on the role of NfL in cerebrovascular disease, particularly IS. Tiedt et al. (12). demonstrated that ischemic stroke (IS) individuals have higher serum NfL (sNfL) levels than healthy individuals. Uphaus et al. found a clear link between sNfL levels and the degree of functional outcome after IS. Overall, evidence suggests that measuring sNfL can offer valuable prognostic insights into long-term cardiovascular outcomes in patients with IS.

Early neurological deterioration (END) is a frequently observed manifestation of the acute phase after IS (9, 10), and the incidence of which varies ranging from 12 to 42% (13). Additionally, the prognosis of IS patients with END is poor (12, 14). However, few studies have investigated the association of sNfL with END after IS. NfL level increases with age (15), and advanced age is substantially linked with substandard prognosis in IS patients (16). Therefore, whether the predictive value of sNfL in IS patients was affected by age remains unclear. Moreover, small vessel disease has been confirmed to be related to the recurrence of strokes in acute IS patients (17, 18). Whether sNfL can be a biomarker for small vessel disease-induced white matter lesions (WMLs) still requires validation. This investigation defined END as an elevation of two or more points in NIHSS score within a week after admission (17). Moreover, this investigation aimed to elucidate the association of upregulated sNfL with END occurrence and long-term prognosis in patients with IS.

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