NMDA Receptor Antibodies Predict Adverse Neurological Outcome After Cardiac Surgery in High-Risk Patients

Abstract

Background and Purpose-The goal of this study was to compare the predictive ability of S100B, N-methyl-D-aspartate (NMDA) receptor antibodies (NR2Ab) and C-reactive protein (CRP) for neurological deficits after cardiac surgery with cardiopulmonary bypass (CPB). Methods-We investigated 557 high-risk adult patients who underwent coronary artery or valve replacement surgery using CPB as a substudy of a prospective, blinded, multicenter clinical trial. Serum concentrations of S100B (nϭ513 patients), NR2Ab (nϭ398) and CRP (nϭ510) were measured preoperatively, 24 and 48 hours after CPB. Neurological adverse events were assessed at baseline and postoperative days 1 and 2; neurocognitive function (mini-mental status examination) was assessed at baseline and on postoperative days 1, 7 and 28. Results-Fifty-five (9.9%) patients had moderate or severe neurological adverse events (confusion/delirium, transient ischemic attack, or stroke) within 48 hours of CPB. Women had significantly more neurological complications than men (15.5% versus 7.8%; Pϭ0.007). Ninety-six percent (24/25) of patients with NR2Ab concentrations Ն2.0 ng/mL preoperatively had neurological complications within 48 hours post-CPB, versus only 5.4% (20/373) of patients with NR2Ab concentrations Ͻ2.0 ng/mL, resulting in a 17.9-fold increase (95% CI, 11.6 to 27.6) in postoperative neurological complications for patients with high levels of NR2A antibodies. Preoperative serum S100B and CRP did not predict neurological complications from CPB. Decreased mini-mental status examination scores for orientation, attention and recall were associated with neurological adverse events early after CPB. Conclusions-Preoperative serum concentrations of NR2Ab, but not S100B or CRP, are predictive of severe neurological adverse events after CPB. Patients with a positive NR2Ab test (Ն2.0 ng/mL) preoperatively were nearly 18 times more likely to experience a postoperative neurological event than patients with a negative test (Ͻ2.0 ng/mL). Key Words: brain ischemia Ⅲ cardiac surgery Ⅲ cardiopulmonary bypass N eurological complications after cardiac surgery are now recognized as a serious and costly healthcare problem. The incidence of stroke ranges between 1% and 5.2% during the perioperative period, 1-5 postoperative delirium occurs in 10% to 30%, 6 and cognitive changes are reported in 33% to 83% of patients. 3,4 The impact on the patient's family, postoperative care, prolonged hospitalization and costs are enormous. Roach et al 6 reported a 6.1% incidence of serious adverse neurological events in a survey of 2108 patients undergoing coronary artery bypass surgery (CABG) at 24 US hospitals. Patients experiencing neurological complications had significantly prolonged hospitalization and 47% were transferred to a chronic care facility. A blood test that can reliably predict who is at risk for neurological complications from heart surgery is presently not available.During the last decade several biomarkers to predict and diagnose brain injury have been proposed. Serum S100B, a c...

Stroke Biomarkers: Progress and Challenges for Diagnosis, Prognosis, Differentiation, and Treatment

“…Because the latter factors predict stroke risk, however, it was unclear whether the increased au-toantibody concentrations reflected current stroke episodes or were potential predictors of future cerebrovascular events. In a prospective, multicenter clinical trial, NR2Ab concentrations were evaluated for their ability to predict adverse neurological complications in 557 patients undergoing coronary surgery (88 ). Only 25 patients had an NR2Ab preoperative concentration Ն2.0 g/L, but 24 of 25 proceeded to develop neurological complications within 48 h postoperatively (RR 17.9, 95% CI 11.6 -27.6).…”

Incidence and predictors of delirium after cardiac surgery: Results from The IPDACS Study

“…Second, numerous prospective studies involve a modest number of participants, which does not provide strong statistical power to select patients with delirium and to detect the risk factors of this complication [12,13]. Unfortunately, studies with a greater number of patients often have methodological limitations (e.g., authors do not define the diagnostic criteria or tools they use to diagnose delirium) [14], assessment of patients is performed in a short or undefined period after surgery (delirium diagnosed on the first day or after the sixth day following cardiac surgery might not be directly connected to the surgery) [2,7,15] and the experience of persons who diagnose delirium is not specified [2,5]. Moreover, in a number of large cohort studies, only patients with overt symptoms of delirium (agitation, hallucinations and delusions) undergo psychiatric evaluation, and the evaluation is not made by investigators adhering to a protocol but rather by members of the medical staff involved in routine daily care [2,9].…”

NR2 antibodies: Risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events

“…Preoperative serum concentrations of NR2Ab have been shown to be predictive of severe neurological adverse events after cardiac surgery [16]. Patients with a positive NR2Ab level N2.0 ng/ml prior to surgery were nearly 18 times more likely to experience a postoperative neurological event than patients with a negative test [16].…”

“…Patients with a positive NR2Ab level N2.0 ng/ml prior to surgery were nearly 18 times more likely to experience a postoperative neurological event than patients with a negative test [16]. The NR2 peptide increases in association with microemboli during carotid endarterectomy and with postoperative neurological deficits following carotid endarterectomy [17,18].…”