Search Results for: Gestione dell’ictus acuto

Stroke, Volume 53, Issue Suppl_1, Page A96-A96, February 1, 2022. Introduction:The inflammatory response after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, and poor functional outcome. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. We investigated the pharmacodynamic efficacy and safety of eculizumab (a complement C5 antibody) in aSAH patients.Methods:We conducted a randomized, controlled, open-label, phase II clinical trial with blinded outcome assessment in the Netherlands. Patients were randomized (1:1) to receive eculizumab plus standard care or to standard care alone. Eculizumab (1200 mg) was administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group received prophylactic antibiotics for 4 weeks and prophylactic antifungal therapy if the patient had a central line or an external ventricular shunt and a positive fungal or yeast culture. The primary outcome was C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes included the occurrence of adverse events, eculizumab concentration and inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aimed to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group.Results:A total of 31 patients have been included, of which 26 with CSF samples.Conclusions:Final results will be presented at the conference.Trial registration:Netherlands Trial Register: NTR6752. European Clinical Trials Database (EudraCT): 2017-004307-51.

Stroke, Volume 53, Issue Suppl_1, Page ATP132-ATP132, February 1, 2022. 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 (rs) 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 (rs= -0.5), and positively correlated with IVH volume (rs= 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 (rs= 0.5), and correlated negatively with IVH volume (rs= -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 (rs= 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.

Stroke, Volume 53, Issue Suppl_1, Page AWP142-AWP142, February 1, 2022. Intracerebral hemorrhage (ICH), a devastating form of stroke, has a mortality of 40% and no available treatment. Inflammation contributes to the genesis and expansion of perihematomal edema (PHE) in ICH, thus driving secondary injury and subsequent neurological deterioration. This study was carried out to elucidate contributions of lymphocytes, specifically CD4+cells in the formation of PHE and ICH-induced neural injury. Upon examination of brain sections of ICH patients, we observed abundant CD4+T cells among the PHE-infiltrating immune cells as early as 24 hours post-ictus. Analogous findings in ICH mouse model induced with autologous blood or collagenase injection confirmed the phenomenon. Using anti-CD4 antibody to deplete CD4+T cells, we find that brain-infiltrating CD4+T cells exacerbates acute ICH injury in mice by reducing BBB integrity and promoting leukocytes recruitment with early and time-dependent CD4+T cells activation. Brain infiltrating CD4+T cells exhibit activated transcriptome signatures, promoting local inflammation via IL-17. In the hemorrhagic brain, CD4+T cells induces CD31+endothelial cell apoptosis via death receptor-ligands TRAIL-DR5 pathway; specific ablation of CD4+T cells with depleting antibody results in reduced PHE volume and improved long-term neurological outcome. In all, these data sheds new lights on T cell-mediated immune responses contributing to PHE and brain injury in ICH.