Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.

Automated summary

Despite the high incidence and burden of stroke, biological biomarkers are not routinely used for diagnosing, determining progression, or predicting outcomes of acute ischemic stroke (AIS). However, cerebrospinal fluid (CSF) shows potential as a valuable source for biomarker development due to its direct interface with neural tissue. This systematic review identified 21 biomarkers and other multiomic proteomic markers, including S100B, inflammatory markers, and free fatty acids, that have been studied frequently. CSF has been shown to be an effective medium for acquiring biomarkers for AIS, although more large-scale trials studying the efficacy of biomarkers in altering clinical management are still needed.