Systemic Inflammatory Response Depends on Initial Stroke Severity but Is Attenuated by Successful Thrombolysis

Background and Purpose— To determine whether body temperature, c-reactive protein (CRP), and white blood cell (WBC) count within the first days after stroke onset correlate with infarct size and stroke severity, and to examine whether successful thrombolysis reduces poststroke inflammation. Methods— Out of 1500 consecutive acute ischemic stroke patients, 346 cases (43 patients with thrombolysis) were selected according to the following criteria: admission to hospital ≤24 hours after event, absence of prestroke and poststroke infectious disease, no intracerebral hemorrhage or brain stem stroke, and data availability. Body temperature, WBC within 3 days, and CRP within 5 days of event were determined daily. Lesion volume was measured by planimetry on computed tomography or MRI scans. Successful thrombolysis was defined as improvement on the National Institutes of Health Stroke Scale of ≥4 points within 24 hours. Results— Increase of inflammatory parameters correlated significantly with lesion volume and stroke severity. This was shown for body temperature on days 2 and 3 (P <0.001), CRP on days 1 to 5 (P <0.05), and WBC on days 1 to 3 (P <0.01). Patients with successful thrombolysis had reduced body temperature on day 3, WBC on days 2 and 3, and CRP on days 3 to 5 (P <0.05). Conclusions— Patients with a larger stroke volume and more severe stroke deficits have higher body temperature, CRP, and WBC count in the acute phase after stroke. Successful thrombolysis is related to a significantly attenuated inflammatory response.

[1]  M. Kaste,et al.  European Stroke Initiative (EUSI) Recommendations for 
Stroke Management
The European Stroke Initiative Writing Committee , 2000, European journal of neurology.

[2]  K. Ohlsson,et al.  Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. , 1996, Stroke.

[3]  GiuseppeAzzimondi,et al.  Fever in Acute Stroke Worsens Prognosis , 1995 .

[4]  M. Kaste,et al.  European Stroke Initiative: recommendations for stroke management. Organisation of stroke care. , 2000, Journal of neurology.

[5]  T. Wieloch,et al.  Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an anti-inflammatory/antipyretic drug. Evidence for chronic encephalopathic processes following ischemia. , 1996, Stroke.

[6]  P. Kochanek,et al.  Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. , 1986, Stroke.

[7]  Gudrunboysen,et al.  Stroke Severity Determines Body Temperature in Acute Stroke , 2001 .

[8]  L. Vignatelli,et al.  Fever in Acute Stroke Worsens Prognosis A Prospective Study , 1995 .

[9]  H. Audebert,et al.  Progression in Lacunar Stroke Is Related to Elevated Acute Phase Parameters , 2004, European Neurology.

[10]  G. Bernardi,et al.  Leukocyte Count and Aggregation during the Evolution of Cerebral Ischemic Injury , 1998, Cerebrovascular Diseases.

[11]  C. Levi,et al.  Influence of admission body temperature on stroke mortality. , 2000, Stroke.

[12]  C. Kao,et al.  Leukocyte Infiltration in Acute Hemispheric Ischemic Stroke , 1993, Stroke.

[13]  U. Dafni,et al.  Aetiology of fever in patients with acute stroke * , 1999, Journal of internal medicine.

[14]  G. Steinberg,et al.  Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation. , 1998, Stroke.

[15]  P. Kochanek,et al.  Polymorphonuclear Leukocytes and Monocytes/Macrophages in the Pathogenesis of Cerebral Ischemia and Stroke , 1992, Stroke.

[16]  G. Bernardi,et al.  Leucocyte aggregation in acute cerebrovascular disease , 1992, Acta Neurologica Scandinavica.

[17]  M. Di Napoli,et al.  Inflammation, Hemostatic Markers, and Antithrombotic Agents in Relation to Long-Term Risk of New Cardiovascular Events in First-Ever Ischemic Stroke Patients , 2002, Stroke.

[18]  W. Hacke,et al.  Fever and infection early after ischemic stroke , 1999, Journal of the Neurological Sciences.

[19]  Y. Yamasaki,et al.  Inflammation of the brain after ischemia. , 1996, Acta neurochirurgica. Supplement.

[20]  M. Di Napoli,et al.  C-Reactive Protein in Ischemic Stroke: An Independent Prognostic Factor , 2001, Stroke.

[21]  T. Olsen,et al.  Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome , 1996, The Lancet.

[22]  K. Cornetta,et al.  Preferential sequestration in vitro of BCR/ABL negative hematopoietic progenitor cells among cytokine nonresponsive CML marrow CD34+ cells , 1997, Bone Marrow Transplantation.

[23]  S. Rogers,et al.  Inflammatory Cytokines IL-1α, IL-1β, IL-6, and TNF-α Impart Neuroprotection to an Excitotoxin Through Distinct Pathways , 1999, The Journal of Immunology.

[24]  C. Iadecola,et al.  Cerebral ischemia and inflammation , 2001, Current opinion in neurology.

[25]  W. Reinhart,et al.  C-reactive protein (CRP) in cerebro-vascular events. , 1999, Atherosclerosis.

[26]  T. Olsen,et al.  What determines good recovery in patients with the most severe strokes? The Copenhagen Stroke Study. , 1999, Stroke.

[27]  M. Ross,et al.  The Cyclooxygenase-2 Inhibitor NS-398 Ameliorates Ischemic Brain Injury in Wild-Type Mice but not in Mice with Deletion of the Inducible Nitric Oxide Synthase Gene , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  H. Fukuda,et al.  Body tempreture correlates with functional outcome and lesion size of cerebral infarction , 1999 .

[29]  J. Castillo,et al.  Predictors of deteriorating cerebral infarct: role of inflammatory mechanisms. Would its early treatment be useful? , 2001, Cerebrovascular diseases.

[30]  T Brott,et al.  The ABCs of measuring intracerebral hemorrhage volumes. , 1996, Stroke.

[31]  B. Conrad,et al.  Prognostic Relevance of Early Serial C-Reactive Protein Measurements After First Ischemic Stroke , 2002, Stroke.

[32]  N. Rothwell,et al.  An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis , 2003, Journal of Neuroimmunology.

[33]  W. Kozubski,et al.  [Leukocytosis in the first day of acute ischemic stroke as a prognostic factor of disease progression]. , 2001, Wiadomosci lekarskie.

[34]  W Hacke,et al.  Brain temperature monitoring and modulation in patients with severe MCA infarction , 1997, Neurology.

[35]  K. Lees,et al.  C-reactive protein and outcome after ischemic stroke. , 1999, Stroke.

[36]  D. Busija,et al.  Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets , 2001, Neuroreport.

[37]  A. Dávalos,et al.  Body Temperature and Fibrinogen Are Related to Early Neurological Deterioration in Acute Ischemic Stroke , 1997 .

[38]  N. Simonian,et al.  Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage. , 1996, Stroke.

[39]  Á. Chamorro,et al.  Cytokine-induced inflammation and long-term stroke functional outcome , 1999, Journal of the Neurological Sciences.

[40]  G. Hankey,et al.  European Stroke Initiative Recommendations for Stroke Management , 2000, Cerebrovascular Diseases.

[41]  R. DʼAlessandro,et al.  Fever in acute stroke worsens prognosis. A prospective study. , 1996, Stroke.

[42]  Á. Chamorro,et al.  Inflammation-Mediated Damage in Progressing Lacunar Infarctions: A Potential Therapeutic Target , 2002, Stroke.

[43]  M. Di Napoli,et al.  Prognostic Influence of Increased C-Reactive Protein and Fibrinogen Levels in Ischemic Stroke , 2001, Stroke.

[44]  S. Rogers,et al.  Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. , 1999, Journal of immunology.

[45]  J. Marrugat,et al.  Timing for fever-related brain damage in acute ischemic stroke. , 1998, Stroke.

[46]  H. Fukuda,et al.  Body temperature correlates with functional outcome and the lesion size of cerebral infarction. , 2000, Acta neurologica Scandinavica.

[47]  A. Dávalos,et al.  Aggravation of Acute Ischemic Stroke by Hyperthermia Is Related to an Excitotoxic Mechanism , 1999, Cerebrovascular Diseases.

[48]  G. D. del Zoppo,et al.  Inflammation after stroke: is it harmful? , 2001 .

[49]  S. Hajat,et al.  Effects of poststroke pyrexia on stroke outcome : a meta-analysis of studies in patients. , 2000, Stroke.