Serum Anti-NMDA (N-Methyl-D-Aspartate)-Receptor Antibodies and Long-Term Clinical Outcome After Stroke (PROSCIS-B)

Stroke. 2019 Nov;50(11):3213-3219. doi: 10.1161/STROKEAHA.119.026100. Epub 2019 Sep 17.


Background and Purpose- NMDAR1-abs (anti-N-Methyl-D-Aspartate receptor GluN1 antibodies), predominantly known in the context of autoimmune encephalitis, have been observed in serum of healthy individuals. A previous study found smaller stroke magnetic resonance imaging lesion growth in seropositive patients, suggesting a neuroprotective effect of these antibodies. The impact of NMDAR1-abs seropositivity on long-term functional outcome and recurrent vascular events and death after first-ever stroke remains unclear. Methods- Data from the Prospective Cohort with Incident Stroke-Berlin were used. NMDAR1-abs (ie, IgM, IgA, and IgG) were measured in serum within 7 days after first stroke. Outcomes of interest included modified Rankin Scale at one year and the time-to-event of a combined end point (recurrent stroke, myocardial infarction, and all-cause mortality) within 3 years. We calculated odds ratios from adjusted partial proportional odds models and subsequently compared outcome of patients with low titers (1:10; 1:32; and 1:100), and high titers (1:320; 1:1000) to seronegative patients. Furthermore, we estimated hazard ratios for a secondary vascular event or death in NMDAR1-abs seropositive compared to seronegative patients in models adjusted for confounders. Results- The analyses included 583 patients with antibody measurements (39% female, median National Institutes of Health Stroke Scale:2, IQR:1-4), and NMDAR1-abs were observed in 76 (13%) patients. NMDAR1-abs seroprevalence was not associated with functional outcome (odds ratio=1.27; 95% CI, 0.77-2.09); sub-group analyses, however, showed worse outcome in patients with high titers (odds ratio=3.47; 95% CI, 1.54-7.80). Seropositive patients had an increased risk for a secondary vascular event or death (hazard ratios =1.83, 95% CI, 1.10-3.05). Conclusions- In our study, NMDAR1-abs seropositivity was not associated with functional outcome at one year after stroke, however, high titers (≥1:320) were associated with poor functional outcome. Furthermore, NMDAR1-abs seropositivity was associated with increased cardiovascular risk within 3 years after first stroke, independently from other risk factors. Clinical Trial Registration- URL: Unique identifier: NCT01363856.

Keywords: autoantibodies; cell death; epidemiology; ischemia; serum; stroke.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autoantibodies / blood*
  • Brain Ischemia / blood
  • Brain Ischemia / mortality
  • Brain Ischemia / therapy
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, N-Methyl-D-Aspartate*
  • Risk Factors
  • Stroke* / blood
  • Stroke* / mortality
  • Stroke* / therapy
  • Survival Rate


  • Autoantibodies
  • Receptors, N-Methyl-D-Aspartate

Associated data