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Abstract
Background Accumulating evidence indicates that neutrophil activation (NA) contributes to microvascular thromboinflammation in acute ischemic stroke (AIS) due to a large vessel occlusion. Preclinical data have suggested that intravenous thrombolysis (IVT) before endovascular therapy (EVT) could dampen microvascular thromboinflammation. In this study we investigated the association between NA dynamics and stroke outcome, and the impact of IVT on NA in patients with AIS treated with EVT.
Methods A single-center prospective study was carried out, including patients treated with EVT for whom three blood samples (before, within 1 hour, 24 hours post-EVT) were drawn to measure plasma myeloperoxidase (MPO) concentration as a marker of NA. Unfavorable outcome was defined as a modified Rankin score of 3–6 at 3 months.
Results Between 2016 and 2020, 179 patients were included. The plasma MPO concentration peaked significantly 1 hour post-EVT (median increase 21.0 ng/mL (IQR −2.1–150)) and returned to pre-EVT baseline values 24 hours after EVT (median change from baseline −0.8 ng/mL (IQR −7.6–6.7)). This peak was strongly associated with unfavorable outcomes at 3 months (aOR 0.53 (95% CI 0.34 to 0.84), P=0.007). IVT before EVT abolished this 1 hour post-EVT MPO peak. Changes in plasma MPO concentration (baseline to 1 hour post-EVT) were associated with unfavorable outcomes only in patients not treated with IVT before EVT (aOR 0.54 (95% CI 0.33 to 0.88, P=0.013). However, we found no significant heterogeneity in the associations between changes in plasma MPO concentration and outcomes.
Conclusions A peak in plasma MPO concentration occurs early after EVT and is associated with unfavorable outcomes. IVT abolished the post-EVT MPO peak and may modulate the association between NA and outcomes.
- Stroke
- Thrombectomy
- Inflammation
- Hemorrhage
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Footnotes
Twitter @BenjaminMaierMD
BM, LDM and J-PD contributed equally.
MM and BH-T-N contributed equally.
Collaborators Hocine Redjem, Stanislas Smajda, Simon Escalard, William Boissseau, Amira Al Raisi, Amelie Yavchitz, Chloé Le Cossec, Candice Sabben, Michael Obadia, Pierre Seners, Jean-Michel Devys, Simon Clariot, Pierre Trouiller, Nicolas Engrand.
Contributors Study concept and design: BM, LDM, JPD, MM, BHTN. Acquisition of data: BM, LDM, JPD, MSNJ, FD, MK, PB, VO, SD, TR, MH, JL, RB, MP, JMH, MM, BHTN. Analysis and interpretation of data: BM, LDM, JPD, MSNJ, FD, MK, PB, VO, SD, TR, MH, JL, RB, MP, JMH, MM, BHTN. Drafting of the manuscript: BM, JPD, JMH, MM, BHTN. Critical revision of the manuscript for important intellectual content: BM, LDM, JPD, MSNJ, FD, MK, PB, VO, SD, TR, MH, JL, RB, MP, JMH, MM, BHTN. Statistical analysis: MK, JL. Administrative, technical or material support: JPD, MM, BHTN. Study supervision and overall content guarantor: JPD, MM, BHTN. All authors read and approved the final manuscript.
Funding This work was supported by INSERM and by public grants overseen by the French National Research Agency (ANR) as part of the Investments for the Future program (PIA) under grant agreement No. ANR-18-RHUS-0001 (RHU Booster), ANR-21-CE17-0023-02 (ETHERISCH), and ANR INFLAME.
Competing interests MM reports personal fees from Boerhinger Ingelheim, Air Liquide, Acticor Biotech, Amgen, Novonordisk outside the submitted work. JL reports personal fees from Julien Labreuche during the conduct of the study. JMH reports personal fees from Alexion, grants and personal fees from Astra-Zeneca, personal fees from Bayer, personal fees from Boehringer Ingelheim france, personal fees from GSK, personal fees from MSD, personal fees from Novo, personal fees from Sanofi, personal fees from Servier, personal fees from Vifor Fresenius outside the submitted work.
Provenance and peer review Not commissioned; externally peer reviewed.
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