Background and Purpose— Peripheral immune cells are activated after stroke and may in turn influence the fate of ischemic brain tissue, thus exerting a dual role in ischemic stroke. We evaluated the contribution of neutrophil and lymphocyte counts to hemorrhagic complications and functional outcome in stroke patients treated with mechanical thrombectomy (MT) with varying degrees of collateral circulation and reperfusion. Methods— We retrospectively analyzed 433 consecutive ischemic stroke patients treated with MT. Neutrophil and lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) were collected before MT and 1 day after symptom onset. Outcome measures included categories of hemorrhagic transformation, symptomatic intracerebral hemorrhage, 3-month functional dependence (modified Rankin Scale, 3–6), and mortality. Patients were categorized according to their baseline collateral status and the degree of reperfusion after MT. Results— Neutrophil counts and NLR increased, whereas lymphocyte counts decreased after MT ( P <0.001), and changes in neutrophils and NLR at day 1 were significantly greater in patients with poor reperfusion. Neutrophil counts and NLR were significantly higher already at admission in patients with poor 3-month outcome. In adjusted analysis, the impact of neutrophilia on poor functional outcome was more substantial in patients with good collaterals achieving successful reperfusion (aOR, 3.09 per quartile; 95% CI, 1.95–4.90), whereas admission lymphopenia (aOR, 4.08 per decreasing quartile; 95% CI, 1.56–10.64) and higher NLR (aOR, 3.76 per quartile; 95% CI, 1.44–9.79) predicted subsequent symptomatic intracerebral hemorrhage in patients with poor collaterals and successful reperfusion. Conclusions— In patients treated with MT, neutrophil and lymphocyte counts are dynamic parameters associated with hemorrhagic complications and long-term outcome. The extent of collateral circulation and the success of brain reperfusion influence the strength of these associations and highlight the dual role of leukocytes in acute stroke.
The prognostic relevance of strokes in different locations is debated. For example, insular strokes have been associated with increased mortality, but this association could reflect their greater severity. In two independent cohorts of patients with supratentorial ischemic stroke (n = 90 and 105), we studied the prognostic consequences of lesion size and location using voxel-based lesion-symptom mapping before and after volume control, which better accounts for total lesion volume. Strokes affecting the insula were larger than non-insular strokes (28 vs 2cc and 25 vs 3cc, p < 0.001 in both cohorts). A number of supratentorial areas (mainly in the left hemisphere), including the insula, were associated with poor functional outcome in both cohorts before (4014 voxels) and after volume control (1378 voxels), while the associations with death were greatly reduced after volume control (from 8716 to 325 voxels). Exploratory analyses suggested that the method of lesion volume quantification, the National Institutes of Health Stroke Scale hemispheric bias and patient selection can result in false associations between specific brain lesions and outcomes. In conclusion, death in the first months after stroke is mainly explained by large infarct volumes, whereas lesions of specific supratentorial structures, mostly in the left hemisphere, also contribute to poor functional outcomes.
Objective- Hemorrhagic transformation is a serious complication of ischemic stroke after recanalization therapies. This study aims to identify mechanisms underlying hemorrhagic transformation after cerebral ischemia/reperfusion. Approach and Results- We used wild-type mice and Selplg and Fut7 mice defective in P-selectin binding and lymphopenic Rag2 mice. We induced 30-minute or 45-minute ischemia by intraluminal occlusion of the middle cerebral artery and assessed hemorrhagic transformation at 48 hours with a hemorrhage grading score, histological means, brain hemoglobin content, or magnetic resonance imaging. We depleted platelets and adoptively transferred T cells of the different genotypes to lymphopenic mice. Interactions of T cells with platelets in blood were studied by flow cytometry and image stream technology. We show that platelet depletion increased the bleeding risk only after large infarcts. Lymphopenia predisposed to hemorrhagic transformation after severe stroke, and adoptive transfer of T cells prevented hemorrhagic transformation in lymphopenic mice. CD4 memory T cells were the subset of T cells binding P-selectin and platelets through functional P-selectin glycoprotein ligand-1. Mice defective in P-selectin binding had a higher hemorrhagic score than wild-type mice. Adoptive transfer of T cells defective in P-selectin binding into lymphopenic mice did not prevent hemorrhagic transformation. Conclusions- The study identifies lymphopenia as a previously unrecognized risk factor for secondary hemorrhagic transformation in mice after severe ischemic stroke. T cells prevent hemorrhagic transformation by their capacity to bind platelets through P-selectin. The results highlight the role of T cells in bridging immunity and hemostasis in ischemic stroke.
ObjectiveStroke patients with good collateral circulation achieve the best recovery after mechanical thrombectomy (MT) but strict imaging selection may result in untreated patients that could benefit from MT. We assessed whether the extent of collaterals had modifying effects on the amount of ischemic tissue saved from infarction with MT over best medical treatment (BMT).MethodsThis was a single center cohort of consecutive patients (n=339) with proximal occlusions in the carotid territory. Patients were categorized according to a four point category scale on CT angiography as having good (scores 2–3) or poor (scores 0–1) collaterals. The primary outcome measure was the interaction between collaterals and MT on infarct growth. The secondary outcome assessed the treatment effect of MT over BMT on functional status in relation to collateral status. Safety outcomes were mortality and symptomatic intracranial hemorrhage.ResultsCollaterals had a modifying effect of MT on infarct growth (P=0.004), with a greater reduction in 96 patients with poor collaterals (38.8 mL) than in 243 patients with good collaterals (1.9 mL). There was also a significant (P<0.001) interaction between the effect of MT and functional outcome in relation to collateral status, with more benefits of MT in patients with poor collaterals. MT was associated with lower mortality than BMT in patients with poor collaterals only.ConclusionCompared with BMT, the use of MT in the early time window in large vessel stroke results in a more substantial limitation of infarct growth in patients with poor collaterals.
Hypoperfusion is the typical perfusion pattern associated with recent small subcortical infarcts of the brain, but other perfusion patterns may be present in patients with these infarcts. Using CT perfusion, we studied 67 consecutive patients who had a small subcortical infarct at a follow-up MRI study to investigate the correlation between the perfusion pattern and the clinical and radiological course. On CT perfusion map analysis, 51 patients (76%) had focal hypoperfusion, 4 patients (6%) had hyperperfusion and the remaining 12 patients (18%) showed no abnormalities. On dynamic sequential imaging analysis obtained from the source perfusion images, 32 patients (48%) had a sustained hypoperfusion pattern, 11 patients (16%) had a reperfusion pattern, and 18 patients (27%) had a delayed compensation pattern. Systolic blood pressure was higher in patients with sustained hypoperfusion although the perfusion pattern was independent of the final volume of infarction. These results reinforce the notion that mechanisms other than hypoperfusion are at play in patients with small subcortical infarcts including the intervention of compensatory sources of blood flow. The ultimate clinical significance of these perfusion patterns remains to be determined in larger series of patients assessed longitudinally.
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