title: Ficolin-1 Levels in Patients Developing Vasospasm and Cerebral Ischemia After Spontaneous Subarachnoid Hemorrhage.
abstract: Activation of the inflammatory generating complement system might play a pathogenic role in spontaneous subarachnoid hemorrhage (SAH). We studied whether plasma and cerebrospinal fluid (CSF) levels of complement proteins were associated with angiographic vasospasm and cerebral ischemic lesions after SAH. Ficolin-1 (M-ficolin), ficolin-3 (H-ficolin), mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), MASP-3, and MAp44 were analyzed in plasma of 45 SAH patients at 24 h after bleeding. Additionally, ficolin-1 levels were measured in cerebrospinal fluid (CSF) samples obtained 24 h after bleeding in 19 patients with external ventricular drainage placement. Angiographic vasospasm was identified using transcranial Doppler or angio-CT and considered symptomatic when new focal deficits or ischemic lesions appeared in follow-up neuroimaging. Functional outcome was assessed using modified Rankin scale (mRS) at 90 days. Higher plasma ficolin-1 levels (ng/ml) at 24 h were associated with poor Hunt and Hess (HH) grade at admission (mean 1158 (SD 360) vs 1654 (871), p = 0.004) and were higher in patients developing angiographic vasospasm (1119.44 (374) vs 1514 (755), p = 0.025) and cerebral ischemia (1067 (325) vs 1610 (766), p = 0.003). In multivariate models adjusted for confounders, higher ficolin-1 remained associated with brain ischemic lesions (OR per 100 ng/ml 1.34, 95 %CI 1.04-1.73, p = 0.026) and vasospasm (OR per 100 ng/ml of increase 1.26, 95 %CI 1.02-1.56, p = 0.031). Patients with angiographic vasospasm and cerebral ischemic lesions had non-significantly lower ficolin-1 concentration in the CSF. Plasma ficolin-1 emerged as a marker of clinical severity and brain ischemia after SAH. Larger studies will be required to establish the therapeutic implications of this finding.
authors.affiliation: Neurology Service, Hospital Clinic, Comprehensive Stroke Center, Villarroel 170, 08036, Barcelona, Spain. blllull@clinic.ub.es.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0002-1464-2237
authors.initials: L
authors.lastname: Llull
authors.affiliation: Department of Biomedicine, Health Aarhus University, Aarhus, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.affiliation: Neurology Service, Hospital Clinic, Comprehensive Stroke Center, Villarroel 170, 08036, Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Amaro
authors.affiliation: Neurosciences Department, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Cervera
authors.affiliation: Department of Brain Ischemia and Neurodegeneration IIBB-CSIC, IDIBAPS, Barcelona, Spain.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.affiliation: Neurology Service, Hospital Clinic, Comprehensive Stroke Center, Villarroel 170, 08036, Barcelona, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Chamorro
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D002533:Cerebral Angiography; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D037102:Lectins / Q000097:blood*; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism; D008875:Middle Aged; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D017585:Ultrasonography, Doppler, Transcranial; D020301:Vasospasm, Intracranial / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D000097604:Ficolins
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C109662:FCN3 protein, human; C084067:MASP1 protein, human; C105296:MASP2 protein, human
keywords: Brain ischemia; Ficolin; Subarachnoid hemorrhage; Vasospasm