Artikel
Early brain injury – an important contributor for secondary inflammatory brain injury after aneurysmal subarachnoid hemorrhage
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Veröffentlicht: | 2. Juni 2015 |
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Gliederung
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Objective: After aneurysmal subarachnoid hemorrhage (aSAH) ~30-50% of patients suffer from life-threatening infections during hospital stay. In particular initiation of delayed ischemic deficits (DCI) and Early-Onset (EO) Infections may contribute to unfavorable outcome. Purpose of the study was to confirm if CNS injury-associated immunodeficiency syndrome (CIDS) with increased susceptibility for infections exists early after aSAH.
Method: Consecutive aSAH patients prospectively included in the ongoing CoOperative Study on Brain Injury Depolarisations and Immunodepression, underwent clinical and immunological monitoring for 15 days and follow-up at day 180. Clinical course, onset of symptomatic vasospasm and DCI, adverse events, and infections were recorded daily. On days 1/3/6/9/12/15 and 180 post aSAH, immune markers were measured by flow cytometry: human leukocyte antigen-DR (HLA-DR), tumor necrosis factor alpha, interferon gamma (IFN-γ), interleukin (IL)-2, 4, 5, 6, 8, 10 in vivo, and after stimulation.
Results: Currently n=75 patients with aSAH have been included. 52.0% of them developed pneumonia with peak of incidence at days 2-3, while CIDS with pathologically low HLA-DR expression occurred in 78.1% of cases, significantly pronounced in symptomatic and infectious patients. Kaplan-Meier analysis showed significantly higher mortality in patients with early EO-Infections. Those were predicted [sensitivity/specificity: 0.838/0.429] in multiple logistic regression model by Acute Focal Neurological Deficits (AFND) [OR 7.245 p=0.024] and a low IFN-γ/IL-4-Ratio at day 3 [OR 0.597, p=0.049]. Multivariate analysis of variance identified World Federation of Neurosugical Societies (WFNS) grade ≥ 4, AFND, and intracranial pressure >20mmHg as source of detrimental patterns of immune markers.
Conclusions: This study confirms the existence of CIDS after aSAH and its relation to early brain injury, reflected clinically as acute neurological deficits. Immune monitoring can HLA-DR and T Helper Cell cytokines are promising markers to identify aSAH patients at higher risk of infection and to evaluate prophylactic antiinfectious therapy strategies after aSAH.
Funding DFG SA 888/4-1, DFG DR 323/5-1.