Response to Letter by Urra and Chamorro
We completely agree with Urra and Chamorro that stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) and infarct volumes are very closely correlated. In our data, the application of infarct volumes instead of admission NIHSS improved the multiple regression model fit and thereby the accuracy of predicting stroke-associated infections. We absolutely assent that performing an NIHSS is done much quicker than applying infarct volumetry. This is particularly true for applying CT in hyperacute patients with stroke in which it may be impossible to predict final infarct volumes. This lack in early sensitivity of CT could be circumvented if, for example, multimodal MRI could be applied early on. Hereby, timing issues between the emergency application of NIHSS and estimates of infarct volumes may become less important. We admit that as long as multimodal MRI is not performed routinely within the first 24 hours after admission to measure infarct volumes, NIHSS is an excellent and easy-to-use substitute marker for the prediction of stroke-associated infections.
Conflicting results exist concerning the independent predictive value of reduced monocytic HLA-DR values for the development of stroke-associated infections. Harms and colleagues1 reported that reduced monocytic HLA-DR levels on Day 1 after stroke onset were independently predictive for stroke-associated infections even after controlling for admission NIHSS (in the placebo group). Urra et al2 did not measure HLA-DR levels on Day 1 but Day 2 after stroke onset and found no independent association between reduced HLA-DR levels and stroke-associated infections after controlling for stroke severity (NIHSS). We measured HLA-DR levels on Day 1 (28.7±1.1 hours) after stroke onset where reduced HLA-DR values were not independently predictive for stroke-associated infections after controlling for either NIHSS or infarct volume, respectively. Our results indeed reaffirm the findings by Urra et al.2
Because we did not aim for the analysis of specific monocyte subsets in our work, we agree with the comment that we were not able to acknowledge the whole complexity of human monocytes. Rather, we analyzed whole blood monocyte counts, monocytic HLA-DR levels, and ex vivo whole blood tumor necrosis factor-α production. Therefore, our data are just sufficient for the assertion that the rise in total monocyte counts after stroke is rather independent from infarct volumes, whereas lower HLA-DR levels and lower ex vivo tumor necrosis factor-α production are associated with infarct volumes.
In conclusion, we agree with Urra and Chamorro that a state of stroke-induced immunodepression exists, which (1) seems to be dependent on stroke severity/infarct volumes; and (2) renders patients susceptible for stroke-associated infections. Further research is warranted for a better understanding of the complex cellular and functional immunological alterations as well as the physiological role/benefit of this immunologic response in patients with acute stroke.
Harms H, Prass K, Meisel C, Klehmet J, Rogge W, Drenckhahn C, Gohler J, Bereswill S, Gobel U, Wernecke KD, Wolf T, Arnold G, Halle E, Volk HD, Dirnagl U, Meisel A. Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PLoS ONE. 2008; 3: e2158.
Urra X, Cervera A, Obach V, Climent N, Planas AM, Chamorro A. Monocytes are major players in the prognosis and risk of infection after acute stroke. Stroke. 2009; 40: 1262–1268.
Hug A, Dalpke A, Wieczorek N, Giese T, Lorenz A, Auffarth G, Liesz A, Veltkamp R. Infarct volume is a major determiner of post-stroke immune cell function and susceptibility to infection. Stroke. 2009; 40: 3226–3232.