Inflammatory Markers in Severity of Intracerebral Hemorrhage II: A Follow Up Study

Introduction Spontaneous intracerebral hemorrhage (ICH) results in significant morbidity and mortality. The pathogenesis of brain injury after ICH is thought to be due to mechanical damage followed by ischemic, cytotoxic, and inflammatory changes in the underlying and surrounding tissue. Various inflammatory and non-inflammatory biomarkers have been studied as predictors and potential therapeutic targets for intracerebral hemorrhage. Our prior study showed an association with low vascular endothelial growth factor (VEGF) levels and increased mortality. This current study looks to expand on our prior results and will look at the relationship between tumor necrosis factor alpha (TNF alpha), C-reactive protein (CRP), VEGF, Homocysteine (Hcy), and CRP to albumin ratio (CAR) in predicting outcomes and severity in spontaneous intracerebral hemorrhage. Methods We conducted a retrospective chart review of patients with spontaneous intracerebral hemorrhage with TNFa, CRP, VEGF, Hcy levels drawn on admission. Albumin and CRP levels on admission were used to calculate CAR. Ninety-nine patients were included in the study. Primary outcomes included death, early neurologic decline (END), and hemorrhage size. Secondary outcomes included late neurologic decline (LND), Glasgow Coma Scale (GCS) on admission, GCS on discharge, ICH score, change in hemorrhage size, need for surgical intervention, and length of ICU stay. Results A total of 99 patients were included in this study, with 42% requiring surgical intervention and an overall mortality of 16%. Basal ganglia hemorrhage was seen in 41% of patients. Hcy and CAR were significantly correlated with ICH size in basal ganglia patients (r-=0.36, p=0.03; r=0.43, p=0.03, respectively). CAR was significantly correlated with ICH score (r=0.33, p=0.007874). Admission VEGF levels less than 45 pg/ml had 8.4-fold increase in mortality (odds ratio [OR] 8.4545, p=0.0488). Patients with TNFa levels greater than 1.40 pg/ml had a 4.1-fold increase in mortality (OR 4.1, p=0.04) Conclusion Our study demonstrated that low levels (<45 pg/ml) of VEGF were associated with an 8.4-fold increase in mortality, supporting the neuroprotective effect of this protein. Elevated Hcy and CAR levels were associated with an increase in hemorrhage size in patients with basal ganglia hemorrhages. TNFa levels greater than 1.40 pg/ml were associated with a 4.1-fold increase in mortality, and this together with CAR being correlated with increased hemorrhage size and ICH score further demonstrate the inflammatory consequences after intracerebral hemorrhage. Future studies directed at lowering CRP, TNF alpha, and Hcy and/or increasing VEGF in intracerebral hemorrhage patients are needed and may be beneficial.