NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients.

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 (n=513 patients), NR2Ab (n=398) and CRP (n=510) 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%; P=0.007). Ninety-six percent (24/25) of patients with NR2Ab concentrations > or =2.0 ng/mL preoperatively had neurological complications within 48 hours post-CPB, versus only 5.4% (20/373) of patients with NR2Ab concentrations <2.0 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 (> or =2.0 ng/mL) preoperatively were nearly 18 times more likely to experience a postoperative neurological event than patients with a negative test (<2.0 ng/mL).

Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke.

BACKGROUND: Stroke is a multisystemic disorder that includes mechanisms of thrombosis and neurotoxic coupling. Key metabolites of the molecular cascade following biochemical events appear simultaneously in brain tissue, the blood-brain barrier, and brain vessels, activating the immune system and generating autoantibodies (aAbs) to brain-specific antigens. We developed an ELISA blood test to measure aAbs to a subtype of N-methyl-D-aspartate (NMDA) receptors, which are the key markers of neurotoxicity underlying cerebral ischemia. We investigated the diagnostic accuracy of serum aAbs to NR2A/2B, a subtype of NMDA receptors, in assessing transient ischemic attack (TIA) and ischemic stroke (IS) and its ability to distinguish cerebral ischemia from intracerebral hemorrhage (ICH). METHODS: Autoantibodies to NR2A/2B were measured in 360 serum samples: 105 from TIA/stroke patients and 255 from controls, including patients with controlled hypertension/atherosclerosis and gender- and age-matched healthy individuals. RESULTS: Patients with TIA (n = 56) and acute IS (n = 31) had significantly higher NR2A/2B aAb concentrations than controls (P <0.0001). The test sensitivities for TIA and IS were 95% and 97%, respectively, and predictive values were 86% and 91% at a cutoff point of 2.0 micro g/L. The area under the ROC curve was 0.99. Monitoring NR2A/2B aAbs within 72 h differentiated IS and ICH (P <0.001) and was confirmed by magnetic resonance imaging and computed tomography. CONCLUSIONS: NR2A/2B aAbs are independent and sensitive serologic markers capable of detecting TIA with a high posttest probability and, in conjunction with neurologic observation and neuroimaging, ruling out ICH. The test may help assess risk of TIA in routine general practice and may potentially be useful in assisting diagnosis of acute IS in the emergency setting.

Recombinant mu-delta receptor as a marker of opiate abuse.

The brain is particularly vulnerable to drugs of abuse changing the neuroreceptor functions. Opiates interact and overstimulate heterogeneous opioid receptors leading to their desensitization, internalization, and activation of recombinant opioid receptor. The molecular properties of rat and human brain recombinant mu-delta receptor were compared with those of purified mu- and delta-receptors. cDNA coding the unique fragment of recombinant mu-delta receptor was isolated and sequenced. We hypothesized that recombinant mu-delta receptor may be a hallmark of opiate abuse. Peptide fragments of the mu- (MOR), delta- (DOR), and recombinant mu-delta- (MDOR) receptors were used as antigens to assess the presence of autoantibodies in the blood of rats that self-administered heroin and cocaine, as well as drug abusers. Significant steady elevation of MDOR autoantibodies were measured in sera of rats that self-administered heroin compared to that for cocaine and vehicle animals. The appearance and increased level of MDOR autoantibodies in opiate abusers correlated with severity of the disorder and duration of drug exposure.