Endogenous Deoxyribonuclease Activity and Cell-Free Deoxyribonucleic Acid in Acute Ischemic Stroke: A Cohort Study

Stroke ◽  
2022 ◽  
Author(s):  
Gerrit M. Grosse ◽  
Nicole Blume ◽  
Omar Abu-Fares ◽  
Friedrich Götz ◽  
Johanna Ernst ◽  
...  

Background and Purpose: Cell-free DNA (cfDNA) and endogenous deoxyribonuclease activity are opposing mediators and might influence the inflammatory response following acute ischemic stroke. In this cohort study, we investigated the relation between these markers, circulating inflammatory mediators and clinical course including occurrence of stroke-associated infections (SAI) in patients with acute stroke. Methods: Ninety-two patients with stroke due to large vessel occlusion undergoing mechanical thrombectomy were prospectively recruited at Hannover Medical School from March 2018 to August 2019. Deoxyribonuclease activity, cfDNA, damage-associated molecular patterns, and circulating cytokines were measured in venous blood collected immediately before mechanical thrombectomy and 7 days later. Reperfusion status was categorized (sufficient/insufficient). Clinical outcome was evaluated using the modified Rankin Scale after 90 days, where a score of 3 to 6 was considered unfavorable. To validate findings regarding SAI, another stroke cohort (n=92) was considered with blood taken within 24 hours after stroke onset. Results: Patients with unfavorable clinical outcome had higher cfDNA concentrations. After adjustment for confounders (Essen Stroke Risk Score, National Institutes of Health Stroke Scale, and sex), 7-day cfDNA was independently associated with clinical outcome and especially mortality (adjusted odds ratio: 3.485 [95% CI, 1.001–12.134] and adjusted odds ratio: 9.585 [95% CI, 2.006–45.790]). No association was found between reperfusion status and cfDNA or deoxyribonuclease activity. While cfDNA concentrations correlated positively, deoxyribonuclease activity inversely correlated with distinct biomarkers. Baseline deoxyribonuclease activity was lower in patients who developed SAI compared with patients without SAI. This association was confirmed after adjustment for confounding factors (adjusted odds ratio: 0.447 [95% CI, 0.237–0.844]). In cohort 2, differences of deoxyribonuclease activity between patients with and without SAI tended to be higher with higher stroke severity. Conclusions: The interplay of endogenous deoxyribonuclease activity and cfDNA in acute stroke entails interesting novel diagnostic and potential therapeutic approaches. We confirm an independent association of cfDNA with a detrimental clinical course after stroke due to large vessel occlusion. This study provides first evidence for lower endogenous deoxyribonuclease activity as risk factor for SAI after severe stroke.

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012827
Author(s):  
Adam de Havenon ◽  
Alicia Castonguay ◽  
Raul Nogueira ◽  
Thanh N. Nguyen ◽  
Joey English ◽  
...  

ObjectiveTo determine the impact of endovascular therapy for large vessel occlusion stroke in patients with pre-morbid disability versus those without.MethodsWe performed a post-hoc analysis of the TREVO Stent-Retriever Acute Stroke (TRACK) Registry, which collected data on 634 consecutive stroke patients treated with the Trevo device as first-line EVT at 23 centers in the United States. We included patients with internal carotid or middle cerebral (M1/M2 segment) artery occlusions and the study exposure was patient- or caregiver-reported premorbid modified Rank Scale (mRS) ≥2 (premorbid disability, PD) versus premorbid mRS score 0-1 (no premorbid disability, NPD). The primary outcome was no accumulated disability, defined as no increase in 90-day mRS from the patient’s pre-morbid mRS.ResultsOf the 634 patients in TRACK, 407 patients were included in our cohort, of which 53/407 (13.0%) had PD. The primary outcome of no accumulated disability was achieved in 37.7% (20/53) of patients with PD and 16.7% (59/354) of patients with NPD (p<0.001), while death occurred in 39.6% (21/53) and 14.1% (50/354) (p<0.001), respectively. The adjusted odds ratio of no accumulated disability for PD patients was 5.2 (95% CI 2.4-11.4, p<0.001) compared to patients with NPD. However, the adjusted odds ratio for death in PD patients was 2.90 (95% CI 1.38-6.09, p=0.005).ConclusionsIn this study of anterior circulation acute ischemic stroke patients treated with EVT, we found that premorbid disability was associated with a higher probability of not accumulating further disability compared to patients with no premorbid disability, but also with higher probability of death.Classification of EvidenceThis study provides Class II evidence that in anterior circulation acute ischemic stroke treated with EVT, patients with premorbid disability compared to those without disability were more likely not to accumulate more disability but were more likely to die.



Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2742-2751
Author(s):  
Yufei Wei ◽  
Yuehua Pu ◽  
Yuesong Pan ◽  
Ximing Nie ◽  
Wanying Duan ◽  
...  

Background and Purpose: We aimed to evaluate the impact of cortical microinfarcts (CMIs) on functional outcome after endovascular treatment in patients with acute ischemic stroke. Methods: In a multicenter registration study for RESCUE-RE (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization), eligible patients with large vessel occlusion stroke receiving endovascular treatment, who had undergone 3T magnetic resonance imaging on admission or within 24 hours after endovascular treatment were analyzed. We evaluated the presence and numbers of CMIs with assessment of axial T1, T2-weighted images, and fluid-attenuated inversion recovery images. The primary outcome was functional dependence or death defined as modified Rankin Scale scores of 3 to 6 at 90 days. Secondary outcomes included early neurological improvement, any intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality. We investigated the independent associations of CMIs with the outcomes using multivariable logistic regression in overall patients and in subgroups. Results: Among 414 patients (enrolled from July 2018 to May 2019) included in the analyses, 96 (23.2%) patients had at least one CMI (maximum 6). Patients with CMI(s) were more likely to be functionally dependent or dead at 90 days, compared with those without (55.2% versus 37.4%; P <0.01). In multivariable logistic regression analyses, presence of CMI(s) (adjusted odds ratio, 1.78 [95% CI, 1.04−3.07]; P =0.04) and multiple CMIs (CMIs ≥2; adjusted odds ratio, 7.41 [95% CI, 2.48−22.17]; P <0.001) were independently, significantly associated with the primary outcome. There was no significant difference between subgroups in the associations between CMI presence and the primary outcome. Conclusions: Acute large vessel occlusion stroke patients receiving endovascular treatment with CMI(s) were more likely to have a poor functional outcome at 90 days, independent of patients’ characteristics. Such associations may be dose-dependent. Registration: URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR1900022154.


Stroke ◽  
2021 ◽  
Author(s):  
Mahmoud H. Mohammaden ◽  
Diogo C. Haussen ◽  
Leonardo Pisani ◽  
Alhamza R. Al-Bayati ◽  
Nicolas Bianchi ◽  
...  

Background and Purpose: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. Methods: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. Results: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82–88] years, baseline National Institutes of Health Stroke Scale score of 19 [15–23], Alberta Stroke Program Early CT Score 9 [7–9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P =0.04) and less frequent hypertension (78.9% versus 90.3%, P =0.01) but more atrial fibrillation (64.5% versus 44.1%, P =0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409–1.974], P =0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715–2.618], P =0.34). Conclusions: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.


Author(s):  
Johannes M. Weller ◽  
Julius N. Meissner ◽  
Sebastian Stösser ◽  
Franziska Dorn ◽  
Gabor C. Petzold ◽  
...  

Abstract Purpose Intravenous thrombolysis and mechanical thrombectomy (MT) are standard of care in patients with acute ischemic stroke due to large vessel occlusion. Data on MT in patients with intracranial hemorrhage prior to intervention is limited to anecdotal reports, as these patients were excluded from thrombectomy trials. Methods We analyzed patients from an observational multicenter cohort with acute ischemic stroke and endovascular treatment, the German Stroke Registry—Endovascular Treatment trial, with intracranial hemorrhage before MT. Baseline characteristics, procedural parameters and functional outcome at 90 days were analyzed and compared to a propensity score matched cohort. Results Out of 6635 patients, we identified 32 patients (0.5%) with acute ischemic stroke due to large vessel occlusion and preinterventional intracranial hemorrhage who underwent MT. Risk factors of intracranial hemorrhage were head trauma, oral anticoagulation and intravenous thrombolysis. Overall mortality was high (50%) but among patients with a premorbid modified Rankin scale (mRS) of 0–2 (n = 15), good clinical outcome (mRS 0–2) at 90 days was achieved in 40% of patients. Periprocedural and outcome results did not differ between patients with and without preinterventional intracranial hemorrhage. Conclusion Preinterventional intracranial hemorrhage in acute ischemic stroke patients with large vessel occlusion is rare. The use of MT is technically feasible and a substantial number of patients achieve good clinical outcome, indicating that MT should not be withheld in patients with preinterventional intracranial hemorrhage.


2021 ◽  
pp. 197140092110091
Author(s):  
Hanna Styczen ◽  
Matthias Gawlitza ◽  
Nuran Abdullayev ◽  
Alex Brehm ◽  
Carmen Serna-Candel ◽  
...  

Background Data on outcome of endovascular treatment in patients with acute ischaemic stroke due to large vessel occlusion suffering from intravenous thrombolysis-associated intracranial haemorrhage prior to mechanical thrombectomy remain scarce. Addressing this subject, we report our multicentre experience. Methods A retrospective analysis of consecutive acute ischaemic stroke patients treated with mechanical thrombectomy due to large vessel occlusion despite the pre-interventional occurrence of intravenous thrombolysis-associated intracranial haemorrhage was performed at five tertiary care centres between January 2010–September 2020. Baseline demographics, aetiology of stroke and intracranial haemorrhage, angiographic outcome assessed by the Thrombolysis in Cerebral Infarction score and clinical outcome evaluated by the modified Rankin Scale at 90 days were recorded. Results In total, six patients were included in the study. Five individuals demonstrated cerebral intraparenchymal haemorrhage on pre-interventional imaging; in one patient additional subdural haematoma was observed and one patient suffered from isolated subarachnoid haemorrhage. All patients except one were treated by the ‘drip-and-ship’ paradigm. Successful reperfusion was achieved in 4/6 (67%) individuals. In 5/6 (83%) patients, the pre-interventional intracranial haemorrhage had aggravated in post-interventional computed tomography with space-occupying effect. Overall, five patients had died during the hospital stay. The clinical outcome of the survivor was modified Rankin Scale=4 at 90 days follow-up. Conclusion Mechanical thrombectomy in patients with intravenous thrombolysis-associated intracranial haemorrhage is technically feasible. The clinical outcome of this subgroup of stroke patients, however, appears to be devastating with high mortality and only carefully selected patients might benefit from endovascular treatment.


2021 ◽  
pp. neurintsurg-2021-017771
Author(s):  
Carlos Perez-Vega ◽  
Ricardo A Domingo ◽  
Shashwat Tripathi ◽  
Andres Ramos-Fresnedo ◽  
Samir Kashyap ◽  
...  

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; I2=13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; I2=0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; I2=0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.


Neurosurgery ◽  
2019 ◽  
Vol 86 (6) ◽  
pp. 802-807 ◽  
Author(s):  
Gabor Toth ◽  
Santiago Ortega-Gutierrez ◽  
Jenny P Tsai ◽  
Russell Cerejo ◽  
Sami Al Kasab ◽  
...  

Abstract BACKGROUND Prospective evidence to support mechanical thrombectomy (MT) for mild ischemic stroke with large vessel occlusion (LVO) is lacking. There is uncertainty about using an invasive procedure in patients with mild symptoms. OBJECTIVE To evaluate the safety and feasibility of MT in patients with mild symptoms and LVO. METHODS Our single-arm prospective pilot study recruited patients with LVO and initial National Institute of Health Stroke Scale (NIHSS) &lt;6, who underwent standard MT. Primary safety endpoints were symptomatic intracerebral hemorrhage (sICH), and/or worsening NIHSS by ≥4 points. Secondary endpoints included angiographic recanalization, NIHSS change, final infarct volume, and modified Rankin score (mRS). RESULTS We enrolled 20 patients (mean age 65.6 ± 12.3 yr; 45% females). Thrombolysis in Cerebral Ischemia 2B/3 thrombectomy was achieved in 95%. No patients suffered sICH. One patient (5%) had neurologic worsening within 24 h because of underlying intracranial stenosis. No other complications or safety concerns were identified. Median NIHSS was significantly better at discharge (0.5, P = .007) and at last follow-up (0, P &lt; .001) than before treatment (3). Mean post vs preintervention infarct volumes were small without significant difference (1.2 ml, P = .434). Most patients (85%) were discharged directly home. Excellent clinical outcome (mRS 0-1) at last follow-up was seen in 95% of patients. CONCLUSION This is one of the first specifically designed prospective studies showing that MT is safe and feasible in patients with low NIHSS and LVO. Chronic underlying vasculopathy may be a challenging dilemma. We observed excellent clinical and radiographic outcomes, but randomized controlled trials are needed to demonstrate the efficacy of MT in this unique cohort.


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