Abstract TP132: Associations Of N-acetyl-aspartyl-glutamate With Intracerebral Hemorrhage Characteristics And Functional Outcomes: A Pilot Study

Abstract

Introduction: N-acetyl-aspartyl-glutamate (NAAG) is a peptide-based neurotransmitter that has been extensively studied in many neurological diseases. N-acetylaspartate (NAA) and NAAG are markers of neuronal integrity. Decreased NAA on MR-spectroscopy is associated with neuronal damage in ischemic and hemorrhagic stroke. We investigated serial plasma concentrations of NAA and NAAG in patients with ICH to examine correlations with ICH severity. Methods: Plasma from 38 consecutive patients with ICH was collected up to 8 days post-ictus. Days 1 and 2 were defined as time point 1 (T1), days 3 and 4 as T2, etc. Five patients underwent surgery and were analyzed separately. NAA and NAAG concentrations were assessed using mass spectrometry. ICH, intraventricular hemorrhage (IVH) and perihematomal edema (PHE) volumes were analyzed from CT scans using computerized volumetrics. Modified Rankin Scale (mRS) was collected at 90 days. Spearman rank correlations (r s ) were used to describe associations between changes in metabolite values and continuous measures. Results: Mean age was 63 ± 13 years, 58% male, and median [IQR] initial ICH and IVH volumes were 16 [7-35] and 0 [0-5.2] mL respectively. Mean NAA/NAAG levels at T1 were 114k ± 112k and 18k ± 30k ion counts respectively. Mean levels of NAA were stable and NAAG decreased over time. T1 levels of NAAG were higher in males than females (25k vs. 6k ion counts; p=0.02), negatively correlated with admission GCS (r s = -0.5), and positively correlated with IVH volume (r s = 0.7). T1 levels of NAA/NAAG did not correlate with ICH or PHE volume or admission NIHSS. Increases (percent change) in NAAG from T1 to T3 correlated with higher 90-day mRS (r s = 0.5), and correlated negatively with IVH volume (r s = -0.6 for both T1-T3 and T1-T2). Percent change in NAAG from T1 to T4 correlated positively with both ICH and PHE volume (r s = 0.98 and 0.9). These correlations were not significant for percent change in NAA. In patients who had hematoma evacuation, median level of NAAG 1-2 days post-op was lower than pre-surgery (18k vs. 16k; p > 0.05). Conclusions: Admission NAAG levels were associated with IVH volume, lower GCS, and male sex. Elevation of plasma NAAG following ICH correlated with worse 90-day outcomes and with higher ICH and PHE volumes.