BACKGROUND: Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFH Y402H) genes on incidence of neurocognitive dysfunction post-CEA. METHODS: This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery. RESULTS: 57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFH Y402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F- subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively). CONCLUSION: The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery.
BACKGROUND: Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFHY402H) genes on incidence of neurocognitive dysfunction post-CEA. METHODS: This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery. RESULTS: 57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFHY402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F- subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively). CONCLUSION: The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery.
Authors: J Mocco; David A Wilson; Ricardo J Komotar; Joseph Zurica; William J Mack; Hadi J Halazun; Raheleh Hatami; Robert R Sciacca; E Sander Connolly; Eric J Heyer Journal: Neurosurgery Date: 2006-05 Impact factor: 4.654
Authors: Ricardo J Komotar; Robert M Starke; Eric J Arias; Matthew C Garrett; Marc L Otten; Maxwell B Merkow; Benjamin Hassid; J Mocco; Michael E Sughrue; Grace H Kim; William J Mack; Andrew F Ducruet; E Sander Connolly Journal: Curr Vasc Pharmacol Date: 2009-07 Impact factor: 2.719
Authors: E J Heyer; D A Wilson; D H Sahlein; J Mocco; S C Williams; R Sciacca; A Rampersad; R J Komotar; J Zurica; A Benvenisty; D O Quest; G Todd; R A Solomon; E S Connolly Journal: Neurology Date: 2005-10-05 Impact factor: 9.910
Authors: J Mocco; David A Wilson; Ricardo J Komotar; Michael E Sughrue; Kristen Coates; Ralph L Sacco; Mitchell S V Elkind; E Sander Connolly Journal: Neurosurgery Date: 2006-07 Impact factor: 4.654
Authors: G G Ferguson; M Eliasziw; H W Barr; G P Clagett; R W Barnes; M C Wallace; D W Taylor; R B Haynes; J W Finan; V C Hachinski; H J Barnett Journal: Stroke Date: 1999-09 Impact factor: 7.914
Authors: E J Heyer; D C Adams; R A Solomon; G J Todd; D O Quest; D J McMahon; S D Steneck; T F Choudhri; E S Connolly Journal: Stroke Date: 1998-06 Impact factor: 7.914
Authors: Eric J Heyer; Robert DeLaPaz; Hadi J Halazun; Anita Rampersad; Robert Sciacca; Joseph Zurica; Alan I Benvenisty; Donald O Quest; George J Todd; Sean Lavine; Robert A Solomon; E Sander Connolly Journal: Neurosurgery Date: 2006-03 Impact factor: 4.654
Authors: Eric J Heyer; Joanna L Mergeche; Zirka H Anastasian; Minjae Kim; Kaitlin A Mallon; E Sander Connolly Journal: Neurosurgery Date: 2014-03 Impact factor: 4.654
Authors: Eric J Heyer; Joanna L Mergeche; Justin T Ward; Hani R Malone; Christopher Kellner; Samuel S Bruce; E Sander Connolly Journal: Neurosurgery Date: 2013-11 Impact factor: 4.654
Authors: Eric J Heyer; Christopher P Kellner; Hani R Malone; Samuel S Bruce; Joanna L Mergeche; Justin T Ward; E Sander Connolly Journal: J Neurosurg Date: 2013-05-10 Impact factor: 5.115
Authors: Alison R Clarke; Brandon R Christophe; Anadjeet Khahera; Justin L Sim; E Sander Connolly Journal: Front Immunol Date: 2019-07-30 Impact factor: 7.561