title: Brain arteriovenous malformations: implications of CEACAM1-positive inflammatory cells and sex on hemorrhage.
abstract: Brain arteriovenous malformations (bAVMs) are severe conditions which, upon rupture, cause debilitating neurological deficits and even death. The exact cellular and molecular mechanisms associated with bAVM rupture are currently unclear. The objective of this study was to explore the potential role of CEA-related cell adhesion molecule-1 (CEACAM1) in bAVM pathophysiology. Expression and localization of CEACAM1 were assessed immunohistochemically in tissue microarrays from bAVM patients (n = 60). The association of CEACAM1 with clinical parameters was analyzed with Spearman's rank correlation coefficient and chi-square test. The predictive value of CEACAM1 was tested using logistic regression analysis. CEACAM1 was highly expressed in tissue-infiltrating neutrophil granulocytes. High levels of CEACAM1-positive cells were associated with bAVM rupture (hemorrhage), but not with arteriovenous malformation (AVM) size, preoperative embolization, or seizure. This association was significant (p = 0.029, chi-square) in male but not in female patients, and high CEACAM1-positive immune infiltration showed predictive significance for hemorrhage in male bAVM patients only (OR = 6.50, 95 % CI 1.09-38.63, p = 0.040). Within the ruptured bAVM group, patients with a short hemorrhage to surgery (HTS) time interval had higher levels of CEACAM1 immune infiltration than patients with long HTS. This decrease in the levels of CEACAM1 immune infiltration between the HTS short and HTS long groups was, however, significant only in female patients (p = 0.022, chi-square). Our findings substantiate the role of inflammation in the pathophysiology of bAVM and suggest the presence of sexual dimorphism in this disease.
authors.affiliation: Department of Neurosurgery, Nordstadt Hospital Hannover, Haltenhoffstrasse 41, 30167, Hannover, Germany.
authors.forename: Belal
authors.initials: B
authors.lastname: Neyazi
authors.affiliation: Department of Neurosurgery, Nordstadt Hospital Hannover, Haltenhoffstrasse 41, 30167, Hannover, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Herz
authors.affiliation: Department of Neurosurgery, Nordstadt Hospital Hannover, Haltenhoffstrasse 41, 30167, Hannover, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Stein
authors.affiliation: Department of Neurosurgery, Nordstadt Hospital Hannover, Haltenhoffstrasse 41, 30167, Hannover, Germany.
authors.forename: Islam
authors.initials: I
authors.lastname: Gawish
authors.affiliation: Department of Neuropathology, Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.affiliation: Department of Pathology, Nordstadt Hospital Hannover, Haltenhoffstrasse 41, 30167, Hannover, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wilkens
authors.affiliation: Institute of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstrasse 6, 97070, Wuerzburg, Germany.
authors.forename: Sueleyman
authors.initials: S
authors.lastname: Erguen
authors.affiliation: Department of Neurosurgery, Nordstadt Hospital Hannover, Haltenhoffstrasse 41, 30167, Hannover, Germany.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Dumitru
authors.affiliation: Department of Neurosurgery, Nordstadt Hospital Hannover, Haltenhoffstrasse 41, 30167, Hannover, Germany. erol.sandalcioglu@krh.eu.
authors.forename: I Erol
authors.initials: IE
authors.lastname: Sandalcioglu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001921:Brain / Q000503:physiopathology / Q000601:surgery*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002533:Cerebral Angiography / Q000009:adverse effects; D004621:Embolization, Therapeutic / Q000009:adverse effects; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000175:diagnosis / Q000601:surgery*; D020300:Intracranial Hemorrhages / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012727:Sex Characteristics; D014057:Tomography, X-Ray Computed / Q000009:adverse effects*
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules
keywords: Brain arteriovenous malformations; CEACAM1; Hemorrhage; Inflammation; Sexual dimorphism