Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study

Abstract

Background This exploratory study investigated the time-course of lectin complement pathway (LCP) initiators in cerebrospinal fluid (CSF) and plasma in patients with subarachnoid hemorrhage (SAH), as well as their relationship to delayed cerebral ischemia (DCI) and functional outcome. Methods Concentrations of ficolin-1, ficolin-2, ficolin-3, and mannose-binding lectin (MBL) were analyzed in CSF and plasma from patients with SAH. Samples were collected daily from admission until day 9 (CSF; N_PATIENTS = 63, n_SAMPLES = 399) and day 8 (plasma; N_PATIENTS = 50, n_SAMPLES = 358), respectively. Twelve neurologically healthy patients undergoing spinal anesthesia and 12 healthy blood donors served as controls. The development of DCI during hospitalization and functional outcome at 3 months (modified Rankin Scale) were registered for patients. Results On admission, CSF levels of all LCP initiators were increased in SAH patients compared with healthy controls. Levels declined gradually over days in patients; however, a biphasic course was observed for ficolin-1. Increased CSF levels of all LCP initiators were associated with a poor functional outcome in univariate analyses. This relationship persisted for ficolin-1 and MBL in multivariate analysis after adjustments for confounders (age, sex, clinical severity, distribution and amount of blood on CT-imaging) and multiple testing (1.87 ng/mL higher in average, 95% CI, 1.17 to 2.99 and 1.69 ng/mL higher in average, 95% CI, 1.09 to 2.63, respectively). In patients who developed DCI compared with those without DCI, CSF levels of ficolin-1 and MBL tended to increase slightly more over time (p_interaction = 0.021 and 0.033, respectively); however, no association was found after adjustments for confounders and multiple testing (p-adj_interaction = 0.086 and 0.098, respectively). Plasma ficolin-1 and ficolin-3 were lower in SAH patients compared with healthy controls on all days. DCI and functional outcome were not associated with LCP initiator levels in plasma. Conclusion Patients with SAH displayed elevated CSF levels of ficolin-1, ficolin-2, ficolin-3, and MBL. Increased CSF levels of ficolin-1 and MBL were associated with a poor functional outcome. Trial registration This study was a retrospective analysis of samples, which had been prospectively sampled and stored in a biobank. Registered at clinicaltrials.gov (NCT01791257, February 13, 2013, and NCT02320539, December 19, 2014).

“Atypical” Mild Clinical Presentation in Elderly Patients With Ruptured Intracranial Aneurysm: Causes and Clinical Characteristics

“…This hypothesis was supported by a previous observational study showing high prevalence of unmatched low-grade Hunt-Hess (74%∼89%) score accompanying with high grade Fisher score (79%∼88%) in elderly SAH population (11). Moreover, in comparison to their middle-aged counterparts, the similar low grade "atypical" group of SAH patients only accounted from 12.7% (in younger age group) to a maximum of 40% (not excluding the elder population) in previous cohorts (12)(13)(14)(15). Therefore, we speculate the typical clinical symptoms might only occur in elder patients upon a more massive blood diffused in subarachnoid space, in comparison to their younger counterparts (16).…”

Systemic Inflammation after Aneurysmal Subarachnoid Hemorrhage

“…Higher plasma ficolin-1 levels were associated with worse initial clinical state, vasospasm, and DCI [ 226 ]. Studies demonstrated that patients with worse mRS scores at 3-month follow-up had higher CSF ficolin-1 and MBL levels (+1.87 and +1.69 ng/mL, respectively) [ 227 ]. The membrane attack complex (MAC, C5-C9 protein) was proposed to be particularly important in the inflammatory reaction.…”

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An “Heparin Oriented” Systematic Review

“…Given the uniform distribution of the negative charges and large size, UFH is able to stoichiometrically bind four oxyhemoglobin molecules neutralizing the toxic effects of free hemoglobin and related free radicals production in the CSF [168]. Furthermore, UFH has a number of anti-oxidant effects demonstrating a strong direct scavenging antioxidant effect neutralizing reactive oxygen species as occurred in several in vitro studies [56,57,[169][170][171]. In addition, UHF is able to increase the synthesis and release of extracellular SOD into circulating fluids [172,173].…”

“…Similarly, the initiators of lectin complement pathway (LCP), including ficolin-1, ficolin-2, ficolin-3, and mannose-binding lectin (MBL), have previously been investigated in SAH patients with inconclusive results that overall seem to suggest an association between plasma levels and severity of brain injury [53][54][55][56]. Matzen et al analysed the time-course of LCP initiator levels in CSF [57]. They found that LCP initiators increased during the first week after SAH and gradually declined over time.…”