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

Abstract

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.

The protective effects of ligustrazine on ischemic stroke: a systematic review and meta-analysis of preclinical evidence and possible mechanisms

“…In the hyperacute window after ischemia, resident microglia are recruited from the site of cellular injury due to the action of various cytokines such as TNF-α, IL-6, and IL-1β. This localized inflammation then triggers systemic inflammation, resulting in the breakdown of the BBB, brain edema, and neuronal death ( Jin et al, 2010 ; Naik et al, 2023 ). The findings of this study demonstrate that ligustrazine can effectively modulate TNF - α, IL-6, and IL-1β levels in animals with ischemic stroke, thereby improving the damage caused by the stroke.…”

Lumbar Puncture

“…CSF sampling is also used as a diagnostic tool to investigate for neoplasms affecting the CNS (Pentsova et al, 2016), biomarkers for stroke (Naik et al, 2023), autoimmune conditions, or dementia (Costerus et al, 2018). Although these tests may not be a priority in the initial ED evaluation, the emergency nurse practitioner (ENP) should collaborate with consultants, if appropriate, to see whether sampling is indicated.…”

“…As with other invasive procedures, the patient should undergo a brief period of observation in the ED following LP to assess vital signs and check for any postprocedural symptoms. There is no specific time frame to hold a patient, and no current evidence to support a required period of bed rest for prevention of PDPH (Arevalo-Rodriguez et al, 2016;Li et al, 2022;Ridgway & Lafferty, 2022), although this can alleviate headache if it does occur. Patients should be encouraged to take oral fluids.…”

“…PDPH typically resolves within 2 weeks and can be managed with oral or parenteral fluids, caffeine, and gabapentin. Patients with debilitating symptoms may be referred to anesthesia for regional nerve blockade or a blood patch (ClinicalKey, n.d.;Li et al, 2022).…”

Current status and quality of radiomics studies for predicting outcome in acute ischemic stroke patients: a systematic review and meta-analysis

“…Radiomics is a rapidly evolving field of research that involves extracting quantitative metrics, known as radiomic features, from medical images ( 11 – 13 ). Computed tomography (CT) and magnetic resonance imaging (MRI) are primary diagnostic tools ( 14 , 15 ), while their radiomic features also hold great potential for prognosis prediction ( 16 , 17 ). Given the complexity of radiomics data, machine learning (ML) algorithms play a vital role in its application ( 18 – 21 ), particularly in acute stroke imaging ( 22 , 23 ).…”