scholarly journals Brain connectivity measures improve modeling of functional outcome after acute ischemic stroke

2019 ◽  
Author(s):  
Sofia Ira Ktena ◽  
Markus D. Schirmer ◽  
Mark R. Etherton ◽  
Anne-Katrin Giese ◽  
Carissa Tuozzo ◽  
...  

AbstractBackgroundThe ability to model long-term functional outcomes after acute ischemic stroke (AIS) represents a major clinical challenge. One approach to potentially improve prediction modeling involves the analysis of connectomics. The field of connectomics represents the brain’s connectivity as a graph, whose topological properties have helped uncover underlying mechanisms of brain function in health and disease. Specifically, we assessed the impact of stroke lesions on rich club (RC) organization, a high capacity backbone system of brain function.MethodsIn a hospital-based cohort of 41 AIS patients, we investigated the effect of acute infarcts on the brain’s pre-stroke RC backbone and post-stroke functional connectomes with respect to post-stroke outcome. Functional connectomes were created utilizing three anatomical atlases and characteristic path-length (L) was calculated for each connectome. The number of RC regions (NRC) affected were manually determined using each patient’s diffusion weighted image (DWI). We investigated differences inLwith respect to outcome (modified Rankin Scale score (mRS); 90-days; poor: mRS>2) and the National Institutes of Health Stroke Scale (NIHSS; early: 2-5 days; late: 90-day follow-up). Furthermore, we assessed the effect of including NRCandLin ‘outcome’ models, using linear regression and assessing the explained variance (R2).ResultsOf 41 patients (mean age (range): 70 (45-89) years), 61% were male. There were differences inLbetween patients with good and poor outcome (mRS). Including NRC in the backward selection models of outcome, R2increased between 1.3- and 2.6-fold beyond that of traditional markers (age and acute lesion volume) for NIHSS and mRS.ConclusionIn this proof-of-concept study, we showed that information on network topology can be leveraged to improve modeling of post-stroke functional outcome. Future studies are warranted to validate this approach in larger prospective studies of outcome prediction in stroke.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shuhong Yu ◽  
Yi Luo ◽  
Tan Zhang ◽  
Chenrong Huang ◽  
Yu Fu ◽  
...  

Abstract Background It has been shown that eosinophils are decreased and monocytes are elevated in patients with acute ischemic stroke (AIS), but the impact of eosinophil-to-monocyte ratio (EMR) on clinical outcomes among AIS patients remains unclear. We aimed to determine the relationship between EMR on admission and 3-month poor functional outcome in AIS patients. Methods A total of 521 consecutive patients admitted to our hospital within 24 h after onset of AIS were prospectively enrolled and categorized in terms of quartiles of EMR on admission between August 2016 and September 2018. The endpoint was the poor outcome defined as modified Rankin Scale score of 3 to 6 at month 3 after admission. Results As EMR decreased, the risk of poor outcome increased (p < 0.001). Logistic regression analysis revealed that EMR was independently associated with poor outcome after adjusting potential confounders (odds ratio, 0.09; 95% CI 0.03–0.34; p = 0.0003), which is consistent with the result of EMR (quartile) as a categorical variable (odds ratio, 0.23; 95% CI 0.10–0.52; ptrend < 0.0001). A non-linear relationship was detected between EMR and poor outcome, whose point was 0.28. Subgroup analyses further confirmed these associations. The addition of EMR to conventional risk factors improved the predictive power for poor outcome (net reclassification improvement: 2.61%, p = 0.382; integrated discrimination improvement: 2.41%, p < 0.001). Conclusions EMR on admission was independently correlated with poor outcome in AIS patients, suggesting that EMR may be a potential prognostic biomarker for AIS.


Stroke ◽  
2017 ◽  
Vol 48 (5) ◽  
pp. 1233-1240 ◽  
Author(s):  
Amber Bucker ◽  
Anna M. Boers ◽  
Joseph C.J. Bot ◽  
Olvert A. Berkhemer ◽  
Hester F. Lingsma ◽  
...  

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Dan-Victor V Giurgiutiu ◽  
Albert J Yoo ◽  
Kaitlin Fitzpatrick ◽  
Zeshan Chaudhry ◽  
Lee H Schwamm ◽  
...  

Background: Selecting patients most likely to benefit (MLTB) from intra-arterial therapy (IAT) is essential to assure favorable outcomes after intervention for acute ischemic stroke (AIS). Leukoaraiosis (LA) has been linked to infarct growth, risk of hemorrhage after IV rt-PA, and poor post-stroke outcomes. We investigated whether LA severity is associated with AIS outcomes after IAT. Methods: We analyzed consecutive AIS subjects from our institutional GWTG-Stroke database enrolled between 01/01/2007-06/30/2009, who met our pre-specified criteria for MLTB: CTA and MRI within 6 hours from last known well, NIHSS score ≥8, baseline DWI volume (DWIv) ≤ 100 cc, and proximal artery occlusion and were treated with IAT. LA volume (LAv) was assessed on FLAIR using validated, semi-automated protocols. We analyzed CTA to assess collateral grade; post-IAT angiogram for recanalization status (TICI score ≥2B); and the 24-hour CT for symptomatic ICH (sICH). Logistic regression was used to determine independent predictors of good functional outcome (mRS≤ 2) and mortality at 90 days post-stroke. Results: There were 48 AIS subjects in this analysis (mean age 69.2, SD±13.8; 55% male; median LAv 4cc, IQR 2.2-8.8cc; median NIHSS 15, IQR 13-19; median DWIv 15.4cc, IQR 9.2-20.3cc). Of these, 34 (72%) received IV rt-PA; 3 (6%) had sICH; 21 (44.7%) recanalized; and 23 (50%) had collateral grade ≥3. At 90 days, 15/48 (36.6%) were deceased and 15/48 had mRS≤ 2. In univariate analysis, recanalization (OR 6.2, 95%CI 1.5-25.5), NIHSS (OR 0.8 per point, 95%CI 0.64-0.95), age (OR 0.95 per yr, 95%CI 0.89-0.99) were associated with good outcome, whereas age (OR 1.1, 95%CI 1.01-1.14) and HTN (OR 5.6, 95%CI 1.04-29.8) were associated with mortality. In multivariable analysis including age, NIHSS, recanalization, collateral grade, and LAv, only recanalization independently predicted good functional outcome (OR 21.3, 95%CI 2.3-199.9) and reduced mortality (OR 0.15, 95%CI 0.02-1.12) after IAT. Conclusions: LA severity is not associated with poor outcome in patients selected MLTB for IAT. Among AIS patients considered likely to benefit from IAT, only recanalization independently predicted good functional outcome and decreased mortality.


2020 ◽  
Author(s):  
Mengyan Hu ◽  
Yinyao Lin ◽  
Xuejiao Men ◽  
Qiang Zhu ◽  
Danli Lu ◽  
...  

Abstract Background: High salt diet (HSD) is one of the major risk factors for acute ischemic stroke (AIS). As a potential mechanism, surplus salt intake primes macrophage towards a proinflammatory phenotype. The study investigated whether HSD could blunt efferocytosis of macrophage after ischemic stroke, which was a vital process that alleviated post stroke neuroinflammation. Besides, the underlying mechanism was explored.Methods: Wild type male C57/Bl6 mice were fed with fodder containing 8% sodium chloride for 4 weeks and subjected to transient middle cerebral occlusion (tMCAO). Disease severity, macrophage polarization as well as their efferocytic activities were evaluated. In in vitro study, bone marrow derived macrophages were cultured and the impact of high salinity environment on their efferocytic capacity, as well as their expression of phagocytic molecules were analyzed. The relationship of sodium concentration, macrophage phenotype, and disease severity in AIS patients with ischemic stroke was explored. Results: HSD-fed-mice displayed increased infarct volume and aggravated neurological deficiency. Mice fed with HSD suffered exacerbated neural inflammation as higher level of inflammatory mediators and immune cells infiltration were documented. Polarization shift towards pro-inflammatory phenotype impaired efferocytosis of infiltrated macrophages within stroke lesion in HSD-fed-mice were detected. As was uncovered by PCR array, macrophage expression of triggering receptor expressed on myeloid cells 2 (TREM2), a receptor relevant with phagocytosis, was down regulated in high salt environment. Enhancing TREM2 signaling restored the efferocytosis capacity and cellular inflammatory resolution of macrophages in high salinity environment. In AIS patients, high concentration of urine sodium was correlated with lower expression of TREM2 and detrimental stroke outcomes.Conclusions: HSD blunted efferocytic capacity of macrophages through down regulating the expression of TREM2, thus impeded inflammatory resolution after ischemic stroke. Enhancing TREM2 signaling in monocyte/macrophage could be a promising therapeutic strategy to enhance efferocytosis and promote post-stroke inflammatory resolution.


2017 ◽  
Vol 23 ◽  
pp. 2825-2832 ◽  
Author(s):  
Fan Gao ◽  
Cheng-Tai Wang ◽  
Chen Chen ◽  
Xing Guo ◽  
Li-Hong Yang ◽  
...  

Stroke ◽  
2019 ◽  
Vol 50 (10) ◽  
pp. 2761-2767 ◽  
Author(s):  
Sofia Ira Ktena ◽  
Markus D. Schirmer ◽  
Mark R. Etherton ◽  
Anne-Katrin Giese ◽  
Carissa Tuozzo ◽  
...  

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Timo Siepmann ◽  
Jessica Kepplinger ◽  
Charlotte Zerna ◽  
Ana Isabel Penzlin ◽  
Heinz Reichmann ◽  
...  

Background and Purpose: Treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) following acute ischemic stroke was shown to improve functional and motor recovery independently of depression, possibly mediated by long-term mechanisms such as increased brain plasticity. In animal studies, chronic SSRI treatment is superior over short-term SSRI in evoking neurogenesis but the applicability of this observation to humans remains unelucidated. We hypothesized that pre-treatment with SSRI in acute ischemic stroke patients is associated with improved recovery compared to post-stroke SSRI. Subjects and Methods: We performed an exploratory analysis in consecutive acute ischemic stroke patients who were pre-treated or treated de novo either with fluoxetine, citalopram or escitalopram. Effects of SSRI-pre-treatment on short-term clinical (total NIHSS and NIHSS motor items) and functional (mRS) outcome at discharge compared to post-stroke SSRI were assessed using bivariate and multivariate analyses. Results: Of 2653 patients screened, 239 were included (aged 69±14 years, mean±SD; 42% men, baseline median NIHSS 7 [IQR, 10]). Compared to post-stroke SSRI (n=188), in the SSRI pre-treatment group (n=51) favorable functional outcome at discharge (mRS≤2) was more frequent (41% vs. 20%; p=0.002), duration of hospitalization was shorter (median: 7 versus 11 days; p<0.0001), and there was a non-significant trend toward improved motor recovery (decrease in NIHSS motor items ≥2 points or 0-1 at discharge; 63% vs. 49%; p=0.08). However there was no such difference in total NIHSS recovery (≥4 points or 0-1 at discharge; p=n.s.). Pre-treatment with SSRI was an independent predictor of favorable functional outcome (mRS≤2) at discharge (OR: 4.00; 95%CI: 1.68-9.57; p=0.002) after adjusting for age, pre-stroke mRS, baseline NIHSS and IV-thrombolysis. Conclusions: Our data suggest that pre-treatment with SSRI may be linked to early clinical recovery after acute ischemic stroke and support the hypothesis that pre-stroke SSRI might be superior to post-stroke SSRI.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Amelia K Boehme ◽  
Andre D Kumar ◽  
Adrianne M Dorsey ◽  
James E Siegler ◽  
Michael J Lyerly ◽  
...  

Introduction: To date, few studies have assessed the influence of infection on neurological deterioration (ND) and other outcome measures in acute ischemic stroke. Methods: Patients admitted to our stroke center (07/08-12/10) were retrospectively assessed. Patients were excluded if they had an in-hospital stroke, unknown time of symptom onset, or delay from symptom onset to hospital arrival >48 hours. Positive blood or urine culture, or chest x-ray consistent with pneumonia were classified as infection and stratified according to whether the infection was diagnosed within the first 24 hours of admission or after 24 hours. ND was defined as an increase ≥2 points on the NIHSS score within a 24hr period. Poor functional outcome was defined as a mRS score of 3-6 on discharge. Results: Of the 334 patients included in this study, 78 had an infection (19 on admission). The majority of infections were found in the urinary tract (64%), while pneumonia (37%) and bacteremia (24%) were also common. Infection on admission was predictive of ND (Table 1; OR=2.79, 95% CI 1.18-6.64, p=0.0211) and poor functional outcome (OR=3.0, 95% CI 1.1-7.9, p=0.0182). Developing an infection during acute hospitalization was an even stronger predictor of ND (OR=11.9, 95% CI 5.8-24.5, p<0.0001) and poor functional outcome (OR=56.4, 95% CI 7.7-414, p<0.0001). After adjusting for age, NIHSS at baseline and glucose on admission, the development of an infection during acute hospitalization remained a significant predictor of ND (OR=8.9, 95% CI 4.2-18.6, p<0.0001) and poor functional outcome (OR=41.7, 95% CI 5.2-337.9, p=0.005) while an infection on admission was no longer predictive of ND (OR=1.5, 95%CI 0.59-3.99, p=0.3738) or poor functional outcome (OR=1.09, 95%CI 0.3-3.9, p=0.8984). Conclusion: Our data suggest that ischemic stroke patients who develop an infection during their acute hospitalization are at increased odds of experiencing ND and of being discharged with significant disability.


Stroke ◽  
2021 ◽  
Author(s):  
Praneeta Konduri ◽  
Henk van Voorst ◽  
Amber Bucker ◽  
Katinka van Kranendonk ◽  
Anna Boers ◽  
...  

Background and Purpose: Ischemic lesion volume can increase even 24 hours after onset of an acute ischemic stroke. In this study, we investigated the association of lesion evolution with functional outcome and the influence of successful recanalization on this association. Methods: We included patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) who received good quality noncontrast CT images 24 hours and 1 week after stroke onset. The ischemic lesion delineations included infarct, edema, and hemorrhagic transformation. Lesion evolution was defined as the difference between the volumes measured on the 1-week and 24-hour noncontrast CTs. The association of lesion evolution with functional outcome was evaluated using unadjusted and adjusted logistic regression. Adjustments were made for baseline, clinical, and imaging parameters that were associated P <0.10) in univariate analysis with favorable functional outcome, defined as modified Rankin Scale score of ≤2. Interaction analysis was performed to evaluate the influence of successful recanalization, defined as modified Arterial Occlusion Lesion score of 3 points, on this association. Results: Of the 226 patients who were included, 69 (31%) patients achieved the favorable functional outcome. Median lesion evolution was 22 (interquartile range, 10–45) mL. Lesion evolution was significantly inversely correlated with favourable functional outcome: unadjusted odds ratio, 0.76 (95% CI, 0.66–0.86; per 10 mL of lesion evolution; P <0.01) and adjusted odds ratio: 0.85 (95% CI, 0.72–0.97; per 10 mL of lesion evolution; P =0.03). There was no significant interaction of successful recanalization on the association of lesion evolution and favorable functional outcome (odds ratio, 1.01 [95% CI, 0.77–1.36]; P =0.94). Conclusions: In our population, subacute ischemic lesion evolution is associated with unfavorable functional outcome. This study suggests that even 24 hours after onset of stroke, deterioration of the brain continues, which has a negative effect on functional outcome. This finding may warrant additional treatment in the subacute phase.


2017 ◽  
Vol 7 (1) ◽  
pp. 21-34 ◽  
Author(s):  
Heather L. Flowers ◽  
Mohammed A. AlHarbi ◽  
David Mikulis ◽  
Frank L. Silver ◽  
Elizabeth Rochon ◽  
...  

Background: Due to the high post-stroke frequency of dysphagia, dysarthria, and aphasia, we developed comprehensive neuroanatomical, clinical, and demographic models to predict their presence after acute ischemic stroke. Methods: The sample included 160 randomly selected first-ever stroke patients with confirmed infarction on magnetic resonance imaging from 1 tertiary stroke center. We documented acute lesions within 12 neuroanatomical regions and their associated volumes. Further, we identified concomitant chronic brain disease, including atrophy, white matter hyperintensities, and covert strokes. We developed predictive models using logistic regression with odds ratios (OR) and their 95% confidence intervals (95% CI) including demographic, clinical, and acute and chronic neuroanatomical factors. Results: Predictors of dysphagia included medullary (OR 6.2, 95% CI 1.5–25.8), insular (OR 4.8, 95% CI 2.0–11.8), and pontine (OR 3.6, 95% CI 1.2–10.1) lesions, followed by brain atrophy (OR 3.0, 95% CI 1.04–8.6), internal capsular lesions (OR 2.9, 95% CI 1.2–6.6), and increasing age (OR 1.4, 95% CI 1.1–1.8). Predictors of dysarthria included pontine (OR 7.8, 95% CI 2.7–22.9), insular (OR 4.5, 95% CI 1.8–11.4), and internal capsular (OR 3.6, 95% CI 1.6–7.9) lesions. Predictors of aphasia included left hemisphere insular (OR 34.4, 95% CI 4.2–283.4), thalamic (OR 6.2, 95% CI 1.6–24.4), and cortical middle cerebral artery (OR 4.7, 95% CI 1.5–14.2) lesions. Conclusion: Predicting outcomes following acute stroke is important for treatment decisions. Determining the risk of major post-stroke impairments requires consideration of factors beyond lesion localization. Accordingly, we demonstrated interactions between localized and global brain function for dysphagia and elucidated common lesion locations across 3 debilitating impairments.


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