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

Abstract

Objective:We aimed to investigate whether serum anti-N-Methyl-D-Aspartate-receptor GluN1 antibodies (NMDAR1-abs) are associated with worse cognitive function over three years after first ischemic stroke. Methods: Data were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B;NCT01363856). NMDAR1-abs (IgM/IgA/IgG) were measured with cell-based assays from serum obtained within seven days after first-ever stroke. Seropositivity was defined as titers ≥1:10, low titers as ≤1:100 and high titers as >1:100. We assessed cognitive status annually up to three years after stroke with the Telephone Interview for Cognitive Status -modified (TICS-m) and used crude and adjusted linear mixed models to estimate the impact of NMDAR1-abs exposure on TICS-m over time. Results: Data on NMDAR1-abs (median day of sampling=4[IQR=2-5]) were available in 583 of 621 PROSCIS-B patients (39% female; median NIHSS=2[IQR=1-4]; median MMSE=28[IQR:26-30]; median mRS=2[IQR=1-3]) of whom 76(13%) were seropositive (IgM:n=48/IgA:n=43/IgG:n=2). TICS-m over time was not different in NMDAR1-abs seropositive compared to seronegative patients (βCrude=0.38[95%CI=-1.00 to 1.76]; adjusted βModel3=0.30[95%CI=-1.14 to 1.73]). In subgroups, TICS-m over time was not different in patients with low titers (βCrude=1.53[95%CI=-0.06 to 3.11]; adjusted βModel3=1.42[95%CI=-0.23 to 3.08]), however, in patients with high titers TICS-m was lower in the crude model (β=-2.54[95%CI=-4.99 to -0.08]), with a similar effect size after confounder adjustment (βModel3=-2.30[95%CI=-4.82 to 0.21]). All groups were compared to seronegative patients, respectively. All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

A systematic review and meta-analysis of serum cystatin C levels and acute ischemic stroke outcomes

“…2 However, if arterial flow does not recover promptly, ischemia may develop into irreversible infarction, and patients may experience an AIS. 2 Several neural substrates are thought to be involved in AIS, such as kynurenine, methylxanthine and N-methyl-D-aspartate, [4][5][6] and have been shown to be associated with cognitive functions, motor skills and emotions. [7][8][9][10][11][12][13] Poststroke cognitive dysfunction is a common symptom affecting 20-80% of patients and impacting neurological function recovery.…”