Association of cerebrospinal fluid protein biomarkers with outcomes in patients with traumatic and non-traumatic acute brain injury: systematic review of the literature

Acute brain injuries are associated with high mortality rates and poor long-term functional outcomes. Measurement of cerebrospinal fluid (CSF) biomarkers in patients with acute brain injuries may help elucidate some of the pathophysiological pathways involved in the prognosis of these patients. We performed a systematic search and descriptive review using the MEDLINE database and the PubMed interface from inception up to June 29, 2021, to retrieve observational studies in which the relationship between CSF concentrations of protein biomarkers and neurological outcomes was reported in patients with acute brain injury [traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, status epilepticus or post-cardiac arrest]. We classified the studies according to whether or not biomarker concentrations were associated with neurological outcomes. The methodological quality of the studies was evaluated using the Newcastle-Ottawa quality assessment scale. Of the 39 studies that met our criteria, 30 reported that the biomarker concentration was associated with neurological outcome and 9 reported no association. In TBI, increased extracellular concentrations of biomarkers related to neuronal cytoskeletal disruption, apoptosis and inflammation were associated with the severity of acute brain injury, early mortality and worse long-term functional outcome. Reduced concentrations of protein biomarkers related to impaired redox function were associated with increased risk of neurological deficit. In non-traumatic acute brain injury, concentrations of CSF protein biomarkers related to dysregulated inflammation and apoptosis were associated with a greater risk of vasospasm and a larger volume of brain ischemia. There was a high risk of bias across the studies. In patients with acute brain injury, altered CSF concentrations of protein biomarkers related to cytoskeletal damage, inflammation, apoptosis and oxidative stress may be predictive of worse neurological outcomes.