Serum anti-NMDA-receptor antibodies and cognitive function after ischemic stroke (PROSCIS-B)

We aimed to investigate whether serum anti-N-methyl-D-aspartate-receptor GluN1 (previously NR1) antibody (NMDAR1-abs) seropositivity impacts cognitive function (CF) in the long term following ischemic stroke.

Data were used from the PROSpective Cohort with Incident Stroke-Berlin. NMDAR1-abs (IgM/IgA/IgG) were measured with cell-based assays from serum obtained within 7 days after the first-ever stroke. Seropositivity was defined as titers ≥ 1:10, low titers as ≤ 1:100 and high titers as > 1:100. We assessed CF at 1, 2 and 3 years after stroke with the Telephone Interview for Cognitive Status-modified (TICS-m) and used crude and propensity score adjusted inverse probability weighted generalized linear models to estimate the impact of NMDAR1-abs serostatus on TICS-m.

Data on NMDAR1-abs (median day of sampling = 4[IQR = 2-5]) were available in 583/621 PROSCIS-B patients (39% female; median NIHSS = 2[IQR = 1-4]; median MMSE = 28[IQR:26-30]), of whom 76(13%) were seropositive (IgM: n = 48/IgA: n = 43/IgG: n = 2). Any NMDAR1-abs seropositivity had no impact on TICS-m compared to seronegative patients (βcrude = 0.69[95%CI = - 0.84 to 2.23]; βadjusted = 0.65[95%CI = - 1.00 to 2.30]). Patients with low titers scored better on TICS-m compared to seronegative patients (βcrude = 2.33[95%CI = 0.76 to 3.91]; βadjusted = 2.47[95%CI = 0.75 to 4.19]); in contrast, patients with high titers scored lower on TICS-m (βcrude =  -2.82[95%CI = - 4.90 to - 0.74], βadjusted = - 2.96[95%CI = - 5.13 to - 0.80]), compared to seronegative patients.

In our study, NMDAR1-abs seropositivity did not affect CF over 3 years after a first mild to moderate ischemic stroke. CF differed according to NMDAR1-abs serum titer, with patients with high NMDAR1-abs titers having a less favorable cognitive outcome compared to seronegative patients.