TY - JOUR
T1 - Immunodepression, Infections, and Functional Outcome in Ischemic Stroke
AU - Westendorp, Willeke F.
AU - Dames, Claudia
AU - Nederkoorn, Paul J.
AU - Meisel, Andreas
N1 - Funding Information: Dr Nederkoorn received funding from ZonMW and Dutch Heart Foundation for the Preventive Antibiotics in Stroke Study. Dr Westendorp worked as a PhD student on this project. Dr Meisel received funding from German Research Foundation (SFB/TRR167; ME 1562/4-1), Einstein Foundation (A-2017-406) and Foundation Leducq (19CVD01). Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Stroke remains one of the main causes of mortality and morbidity worldwide. Immediately after stroke, a neuroinflammatory process starts in the brain, triggering a systemic immunodepression mainly through excessive activation of the autonomous nervous system. Manifestations of immunodepression include lymphopenia but also dysfunctional innate and adaptive immune cells. The resulting impaired antibacterial defenses render patients with stroke susceptible to infections. In addition, other risk factors like stroke severity, dysphagia, impaired consciousness, mechanical ventilation, catheterization, and older age predispose stroke patients for infections. Most common infections are pneumonia and urinary tract infection, both occur in ≈10% of the patients. Especially pneumonia increases unfavorable outcome and mortality in patients with stroke; systemic effects like hypotension, fever, delay in rehabilitation are thought to play a crucial role. Experimental and clinical data suggest that systemic infections enhance autoreactive immune responses against brain antigens and thus negatively affect outcome but convincing evidence is lacking. Prevention of poststroke infections by preventive antibiotic therapy did not improve functional outcome after stroke. Immunomodulatory approaches counteracting immunodepression to prevent stroke-associated pneumonia need to account for neuroinflammation in the ischemic brain and avoid further tissue damage. Experimental studies discovered interesting targets, but these have not yet been investigated in patients with stroke. A better understanding of the pathobiology may help to develop optimized approaches of preventive antibiotic therapy or immunomodulation to effectively prevent stroke-associated pneumonia while improving long-term outcome after stroke. In this review, we aim to characterize epidemiology, risk factors, cause, diagnosis, clinical presentation, and potential treatment of poststroke immunosuppression and associated infections.
AB - Stroke remains one of the main causes of mortality and morbidity worldwide. Immediately after stroke, a neuroinflammatory process starts in the brain, triggering a systemic immunodepression mainly through excessive activation of the autonomous nervous system. Manifestations of immunodepression include lymphopenia but also dysfunctional innate and adaptive immune cells. The resulting impaired antibacterial defenses render patients with stroke susceptible to infections. In addition, other risk factors like stroke severity, dysphagia, impaired consciousness, mechanical ventilation, catheterization, and older age predispose stroke patients for infections. Most common infections are pneumonia and urinary tract infection, both occur in ≈10% of the patients. Especially pneumonia increases unfavorable outcome and mortality in patients with stroke; systemic effects like hypotension, fever, delay in rehabilitation are thought to play a crucial role. Experimental and clinical data suggest that systemic infections enhance autoreactive immune responses against brain antigens and thus negatively affect outcome but convincing evidence is lacking. Prevention of poststroke infections by preventive antibiotic therapy did not improve functional outcome after stroke. Immunomodulatory approaches counteracting immunodepression to prevent stroke-associated pneumonia need to account for neuroinflammation in the ischemic brain and avoid further tissue damage. Experimental studies discovered interesting targets, but these have not yet been investigated in patients with stroke. A better understanding of the pathobiology may help to develop optimized approaches of preventive antibiotic therapy or immunomodulation to effectively prevent stroke-associated pneumonia while improving long-term outcome after stroke. In this review, we aim to characterize epidemiology, risk factors, cause, diagnosis, clinical presentation, and potential treatment of poststroke immunosuppression and associated infections.
KW - antibiotics
KW - dysphagia
KW - immunomodulation
KW - lymphopenia
KW - pneumonia
KW - risk factors
UR - http://www.scopus.com/inward/record.url?scp=85129337672&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/STROKEAHA.122.038867
DO - https://doi.org/10.1161/STROKEAHA.122.038867
M3 - Review article
C2 - 35341322
SN - 0039-2499
VL - 53
SP - 1438
EP - 1448
JO - Stroke
JF - Stroke
IS - 5
ER -