Higher neutrophil counts before thrombolysis for cerebral ischemia
DidierLeys, Prof., University of Lilledidier.leys@univ-lille2.fr
Ilaria Maestrini, Solene Moulin, Turgut Tatlisumak, Regis Bordet
Submitted October 07, 2015
We thank Zhu et al. for their comments on our recent study. [1] Our study did evaluate mechanisms and molecular level interactions. The underlying mechanisms are potentially important but more data are needed. The reasons why a higher neutrophil count is associated with worse outcomes could be that (i) the higher the neutrophil count in acute cerebral ischaemia, the higher the release of deleterious factors such as matrix metalloproteinase 9, [2] and (ii) severe ischaemic strokes are associated with a more severe systemic inflammatory response [3] that could include an early release of neutrophils even within the first 4.5 hours. To determine if these 2 hypotheses are correct, we are currently evaluating the kinetics of neutrophils within the first 4.5 hours and identifying mediators of this effect.
The reason why the neutrophil/lymphocyte ratio (NLR) is a better predictor of outcome than the neutrophil or leukocyte counts could be that the influence of lymphocytes takes more time and is low at this very early stage. Any normalization with a parameter that is not modified leads to an amplification of the effect. Therefore, the ratio amplifies the effect while the sum dilutes the effect, explaining a better accuracy to predict outcome.
1. Maestrini I, Strbian D, Gautier S, et al. Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology Epub 2015 Sep 11.
2. Inzitari D, Giusti B, Nencini P, et al. MMP9 variation after thrombolysis is associated with hemorrhagic transformation of lesion and death. Stroke 2013;44:2901-2903.
3. Audebert HJ, Rott MM, Eck T, Haberl RL. Systemic inflammatory response depends on initial stroke severity but is attenuated by successful thrombolysis. Stroke 2004;35:2128-2133.
For disclosures, please contact the editorial office at journal@neurology.org.
We thank Zhu et al. for their comments on our recent study. [1] Our study did evaluate mechanisms and molecular level interactions. The underlying mechanisms are potentially important but more data are needed. The reasons why a higher neutrophil count is associated with worse outcomes could be that (i) the higher the neutrophil count in acute cerebral ischaemia, the higher the release of deleterious factors such as matrix metalloproteinase 9, [2] and (ii) severe ischaemic strokes are associated with a more severe systemic inflammatory response [3] that could include an early release of neutrophils even within the first 4.5 hours. To determine if these 2 hypotheses are correct, we are currently evaluating the kinetics of neutrophils within the first 4.5 hours and identifying mediators of this effect.
The reason why the neutrophil/lymphocyte ratio (NLR) is a better predictor of outcome than the neutrophil or leukocyte counts could be that the influence of lymphocytes takes more time and is low at this very early stage. Any normalization with a parameter that is not modified leads to an amplification of the effect. Therefore, the ratio amplifies the effect while the sum dilutes the effect, explaining a better accuracy to predict outcome.
1. Maestrini I, Strbian D, Gautier S, et al. Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology Epub 2015 Sep 11.
2. Inzitari D, Giusti B, Nencini P, et al. MMP9 variation after thrombolysis is associated with hemorrhagic transformation of lesion and death. Stroke 2013;44:2901-2903.
3. Audebert HJ, Rott MM, Eck T, Haberl RL. Systemic inflammatory response depends on initial stroke severity but is attenuated by successful thrombolysis. Stroke 2004;35:2128-2133.
For disclosures, please contact the editorial office at journal@neurology.org.