The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity

Abstract Background Several factors affect acute ischemic stroke (AIS) outcomes. Objective This study aimed to assess the role of the leukocyte count, neutrophil/lymphocyte ratio (NLR), and c reactive protein (CRP) as early predictors of outcome in AIS patients. Methods This study was conducted on 60 AIS patients. They were subjected to detailed history taking, clinical examination, brain imaging, and laboratory assessment including the CRP, white blood cell (WBC) count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and NLR which is calculated by dividing ANC by ALC. Neurological scales were used to assess the level of consciousness by the Glasgow Coma Scale (GCS) and stroke severity by the National Institute of Health Stroke Scale (NIHSS) at the first 48 h of stroke onset as well as 1 week and 2 weeks later for the assessment of short-term functional neurological outcome. Results Sixty percent of the patients had unfavorable outcomes assessed by the Modified Rankin Scale (mRS). Patients with unfavorable outcomes had higher NIHSS scores. NLR was positively correlated with WBC count, ANC, and CRP. The higher WBC, NLR, and NIHSS, the unfavorable the outcome was. Conclusion The higher WBC, the NLR, and the level of CRP at the onset of AIS, the more severe stroke and the poorer the short-term outcome are expected.

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Role of Acute Lesion Topography in Initial Ischemic Stroke Severity and Long-Term Functional Outcomes

Stroke ◽

10.1161/strokeaha.115.009643 ◽

2015 ◽

Vol 46 (9) ◽

pp. 2438-2444 ◽

Cited By ~ 60

Author(s):

Ona Wu ◽

Lisa Cloonan ◽

Steven J.T. Mocking ◽

Mark J.R.J. Bouts ◽

William A. Copen ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Outcomes ◽

Stroke Severity ◽

Acute Lesion ◽

Lesion Topography

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Genetic variation at the IGF1 locus shows association with post-stroke outcome and to circulating IGF1

Acta Endocrinologica ◽

10.1530/eje-13-0486 ◽

2013 ◽

Vol 169 (6) ◽

pp. 759-765 ◽

Cited By ~ 17

Author(s):

N David Åberg ◽

Sandra Olsson ◽

Daniel Åberg ◽

Katarina Jood ◽

Tara M Stanne ◽

...

Keyword(s):

Genetic Variation ◽

Ischemic Stroke ◽

Stroke Severity ◽

Stroke Outcome ◽

Nucleotide Polymorphisms ◽

Post Stroke ◽

Index Stroke ◽

Genetic Impact ◽

Major Allele ◽

Community Controls

ObjectiveIn humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome.Design/methodsPatients (n=844; 66% males, mean age 56 years) and community controls (n=668) were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Post-stroke outcome was evaluated with the modified Rankin Scale at 3 and 24 months after index stroke, and baseline stroke severity with the Scandinavian Stroke Scale. s-IGF1 was determined in patients and after random selection in 40 of the controls.ResultsEleven single nucleotide polymorphisms (SNPs) were selected in the IGF1 gene. In healthy controls the major allele of rs7136446 was associated with higher s-IGF1, whereas in patients no such association was found. No SNP was associated with IS, nor with stroke severity. After multivariate correction for presence of diabetes, smoking, and hypertension, the major allele of rs7136446 was associated with favorable functional outcome 24-months post-stroke (odds ratio 1.46; 95% CI 1.09–1.96).ConclusionVariation in rs7136446 of the IGF1 gene associates with post-stroke outcome in relatively young IS patients. Also, rs7136446 associates with s-IGF1 in controls but not in IS, which indicates that IS perturbs a normal genetic impact on s-IGF1 levels.

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Abstract T P307: Similar Rates of Early Cognitive Dysfunction after Intracerebral Hemorrhage and Acute Ischemic Stroke

Stroke ◽

10.1161/str.46.suppl_1.tp307 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

M. Carter Denny ◽

Suhas S Bajgur ◽

Kim Y Vu ◽

Rahul R Karamchandani ◽

Amrou Sarraj ◽

...

Keyword(s):

Logistic Regression ◽

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Acute Ischemic Stroke ◽

Cognitive Dysfunction ◽

Hospital Setting ◽

Stroke Severity ◽

Regression Analyses ◽

Post Stroke ◽

Poor Outcome

Introduction: Post-stroke cognitive dysfunction (CD) affects at least 1/3 of acute ischemic stroke (AIS) patients when assessed at 3 months. Limited data exists on CD in intracerebral hemorrhage (ICH). The role of early, in-hospital cognitive screening using the brief Montreal Cognitive Assessment (mini MoCA) is being investigated at our center. Hypothesis: We assessed the rates of early CD in ICH and AIS and hypothesized that even minor deficits from these disorders causes significant CD. Methods: 1218 consecutive stroke patients admitted from 2/13 to 12/13 were reviewed; 610, 442 with AIS and 168 with ICH, with admission NIHSS and mini MoCAs were included in the final analyses. CD was defined as mini MoCA <9 (max 12). Poor outcome was defined as discharge mRS 4-6. Stroke severity was stratified by NIHSS score of 0-5, 6-10, 11-15, 16-20, 21-42 as in ECASS-I . Chi-squared tests and univariate logistic regression analyses were performed. Results: Baseline characteristics are shown in table 1. AIS and ICH groups were similar with regard to race, gender and stroke severity. ICH patients were younger, had longer stroke service lengths of stay and poorer outcomes than AIS patients (p=0.03, p<0.001, p<0.001). No difference was seen in rates of CD between AIS and ICH patients (60% vs. 57%, p=0.36, OR 1.2 (CI 0.8-1.7)). CD rates ranged from 36% for NIHSS 0-5 to 96% for 21-42 (figure 1). Older patients were twice as likely to have CD (p<0.001, OR 2.2 (CI 1.6 - 3.0)). Patients with CD had five times the odds of having a poor outcome compared to the cognitively intact (p<0.001, OR 5.2 (CI 3.4-7.7)). In univariate logistic regression analyses, age was a significant predictor of CD in AIS, but not in ICH (p= <0.001, p=0.06). Conclusion: Post-stroke CD is common across all severities and occurs at similar rates in AIS and ICH. More than 1/3 of patients with minor deficits (NIHSS 0-5) had CD in the acute hospital setting. Whether early CD is predictive of long term cognitive outcomes deserves further study.

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Abstract 1122‐000122: The Role of the Venous System in Infarct Burden in Patients with Acute Ischemic Stroke

Stroke: Vascular and Interventional Neurology ◽

10.1161/svin.01.suppl_1.000122 ◽

2021 ◽

Vol 1 (S1) ◽

Author(s):

Shail S Thanki ◽

Elliot Pressman ◽

Shail S Thanki ◽

John D Mayfield ◽

Maximilian J Rabil ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

False Negative ◽

Transverse Sinus ◽

Sigmoid Sinus ◽

Venous Sinus ◽

Post Stroke ◽

Number Of Patients ◽

Ct Head

Introduction : Acute ischemic stroke (AIS) is a leading cause of disability internationally. Most therapies focus on intra‐arterial treatment to improve post‐stroke deficits and neurologic status. However, if a relationship between venous anatomy and post‐stroke deficits or infarct size can be shown, then venous augmentation strategies represent a possibility for future interventions as an adjunct to intra‐arterial treatment. Methods : We retrospectively reviewed all ischemic infarcts at our institution that underwent thrombectomy from January 2018 – October 2020. From these, we selected cases that were demonstrated as M1 occlusions on intra‐procedural angiogram and those who had a CT Head obtained within six hours of the patient’s last known normal (LKN). Patients without a CT Head or CT Angiogram of their head were excluded. Using axial and sagittal reconstructed views of 0.9mm slices, cross‐sectional area measurements were taken of the superior sagittal sinus 1cm above the Torcula, in three locations of the ipsilateral and contralateral transverse sinus, in three locations of the ipsilateral and contralateral sigmoid sinus, and of the ipsilateral and contralateral internal jugular vein (IJV) at the external surface of the skull. For the transverse and sigmoid sinuses, the three measurements were averaged together. These measurements were then compared against patient’s Alberta Stroke Program Early CT Score (ASPECTS). Results : 77 patients were identified in the study period. Average ASPECTS was 8.9, ranging from 5–10. There were three patients included with ASPECTS < 6. Average ipsilateral transverse sinus area was 34.4mm ± 3.34, average ipsilateral sigmoid sinus area was 32.8mm ± 2.74, average ipsilateral IJV area was 46.9 mm ± 5.00. Correlation tests to identify relationships between venous sinus area and ASPECTS was unremarkable (ipsilateral transverse sinus p = 0.574, ipsilateral sigmoid sinus p = 0.548, ipsilateral IJV p = 0.798). When assessed as a ratio of ipsilateral venous sinus area to contralateral sinus area to assess correlation with ASPECTS, results were unremarkable (transverse sinus p = 0.891, sigmoid sinus p = 0.292, IJV p = 0.499). Conclusions : Venous sinus size was not found to be predictive or associated with predominantly favorable ASPECTS for strokes found within six hours. We believe this may be due to our cohort lacking significant numbers of patients with low ASPECTS, yielding a false negative result. We are currently expanding this project to include a comparable number of patients with ASPECTS < 6 to determine the role of venous collateral system in infarct progression.

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Evaluating the Role of Oxidative Stress in Acute Ischemic Stroke

Journal of Neurosciences in Rural Practice ◽

10.1055/s-0039-3402675 ◽

2020 ◽

Vol 11 (01) ◽

pp. 156-159

Author(s):

Bindu Menon ◽

Krishnan Ramalingam ◽

Rajeev Kumar

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Lipid Membranes ◽

Demographic Data ◽

Stroke Severity ◽

Stroke Patients ◽

Antioxidant Power

Abstract Background The role of oxidative stress in neuronal injury due to ischemic stroke has been an interesting topic in stroke research. Malondialdehyde (MDA) has emerged as a sensitive oxidative stress biomarker owing to its ability to react with the lipid membranes. Total antioxidant power (TAP) is another biomarker to estimate the total oxidative stress in stroke patients. We aimed to determine the oxidative stress in acute stroke patients by measuring MDA and TAP. Materials and Methods MDA and TAP were determined in 100 patients with ischemic stroke and compared with that in 100 age- and sex-matched healthy adults. Demographic data, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), and disability measured by the Barthel index (BI) were recorded. The association of MDA and TAP with other variables was analyzed by paired t-test. Results Of the whole sample, 74% represented males. The mean NIHSS score was 13.11 and BI was 38.87. MDA was significantly higher in stroke patients (7.11 ± 1.67) than in controls (1.64 ± 0.82; p = 0.00). TAP was significantly lower in stroke patients (5.72 ± 1.41) than in controls (8.53 ± 2.4; p = 0.00). The lipid profile and blood sugar levels were also significantly higher in stroke patients. There was no association of MDA and TAP with other variables. Conclusion We found that oxidative stress was associated with acute ischemic stroke. However, we could not establish an association between oxidative stress and the severity of acute stroke.

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Functional Outcome of Hemorrhagic Transformation after Thrombolysis for Ischemic Stroke: A Prospective Study

Cerebrovascular Diseases Extra ◽

10.1159/000440737 ◽

2015 ◽

Vol 5 (3) ◽

pp. 103-106 ◽

Cited By ~ 5

Author(s):

Mariam Annan ◽

Marie Gaudron ◽

Jean-Philippe Cottier ◽

Xavier Cazals ◽

Maelle Dejobert ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Outcome ◽

Intravenous Thrombolysis ◽

Hemorrhagic Transformation ◽

University Hospital ◽

3 Tesla ◽

Stroke Severity ◽

Increased Risk ◽

3 Tesla Mri

Background/Aims: Hemorrhagic transformation (HT) is usually taken into account when symptomatic, but the role of asymptomatic HT is not well known. The aim of our study was to evaluate the link between HT after thrombolysis for ischemic stroke and functional outcome at 3 months, with particular emphasis on asymptomatic HT. Methods: Our study was performed prospectively between June 2012 and June 2013 in the Stroke Unit of the University Hospital Center of Tours (France). All patients treated with intravenous thrombolysis were consecutively included. HT was classified on susceptibility-weighted imaging (SWI) with 3-tesla MRI at 7 ± 3 days after treatment. We evaluated functional outcome at 3 months using the modified Rankin Scale (mRS). Dependency was defined as an mRS score of ≥3. Results: After 1 year, 128 patients had received thrombolytic therapy for ischemic stroke, of whom 90 patients underwent both 3-tesla MRI and SWI at day 7. Fifty-two had HT, including 8 symptomatic cases. At 3 months, 68% of those patients were dependent compared to 31% of patients without HT [OR 4.6 (1.9-11.4), p = 0.001]. In asymptomatic HT, the rate was 62% [OR 3.5 (1.4-8.9), p = 0.007], but did not reach significance after adjustment for stroke severity. Discussion: Our study found no statistically significant effect of HT on outcome after adjustment for initial stroke severity. However, the innocuousness of HT is not certain, and only few studies have already highlighted the increased risk of dependency. Using 3-tesla MRI with SWI allows us to increase the detection rate of small hemorrhage. Conclusion: HT after thrombolysis is very frequent on SWI, but the initial stroke severity is an important predictor to assess the role of HT for patient outcome.

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Low T3 Level and Prognosis of Acute Ischemic Stroke: A Comparative Analysis

Bangladesh Journal of Nuclear Medicine ◽

10.3329/bjnm.v18i2.35223 ◽

2018 ◽

Vol 18 (2) ◽

pp. 145-148

Author(s):

Hosne Ara Rahman ◽

Mahbub Ur Rahman ◽

Jasmine Ara Haque ◽

Samira Sharmin ◽

Anup Kumar Saha

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Neurological Impairment ◽

Functional Improvement ◽

Stroke Severity ◽

Cross Sectional ◽

Post Stroke ◽

Low T3 ◽

Level Group

Objectives: Neuroendocrine profile is significantly altered in acute ischemic stroke. Increasing evidences suggested that low T3 levels immediately following acute ischemic stroke is associated with greater stroke severity, higher mortality rates and poorer functional outcome. The objective of this study was to see the possible association of serum T3 level with severity of acute ischemic stroke as well as post stroke recovery.Material & Methods: It was a prospective cross sectional study. From October 2014 to June 2015 patients with acute ischemic stroke, presented within 48 hours of onset of symptoms having radiologically confirmed cerebral infarct were enrolled in this study. Blood for thyroid hormone estimation was collected within 48 hours of onset of symptom. Neurological impairment and improvement were assessed using National Institute of Health Stroke Scale (NIHSS) score together with modified Rankin Scale (mRS) on admission day and at 4 weeks post stroke follow-up visit.Result: A total 83 patients met all inclusion criteria were studied. Mean age was 63.4 ± 15.6 years (range 47-79 years). Among eighty three patients 49 (59%) had normal T3 level and rest 34 (41%) had low T3 level. Mean T3 level was 0.4 ± 0.3 ng/ml and 1.8 ±0.5 ng/ml in lowT3 and normal T3 level group respectively. Based on NIHSS scores on admission, a much higher portion of patients (73.5%) belonged to lowT3 level group fell into moderate-to-severe category while majority of patients (53.0%) fell into mild category for normal T3 level group. In post stroke follow up, about 63.2 % patients with normal T3 level showed favorable neurological functional improvement compared to 38.2% having low T3 level (Chi square=4.9, P<0.05).Conclusion: In patients with acute ischemic stroke lower T3 level elevated the risk of poor functional outcome.Bangladesh J. Nuclear Med. 18(2): 145-148, July 2015

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Relationship between Levels of Pre-Stroke Physical Activity and Post-Stroke Serum Insulin-Like Growth Factor I

Biomedicines ◽

10.3390/biomedicines8030052 ◽

2020 ◽

Vol 8 (3) ◽

pp. 52

Author(s):

N. David Åberg ◽

Gustaf Gadd ◽

Daniel Åberg ◽

Peter Hällgren ◽

Christian Blomstrand ◽

...

Keyword(s):

Physical Activity ◽

Ischemic Stroke ◽

Growth Factor ◽

Leisure Time ◽

Stroke Severity ◽

Insulin Like Growth Factor ◽

Post Stroke ◽

Factor I ◽

Igf I ◽

Linear Regressions

Physical activity (PA) and insulin-like growth factor I (IGF-I) have beneficial effects for patients who have suffered an ischemic stroke (stroke). However, the relationship between the levels of PA and IGF-I after stroke has not been explored in detail. We investigated the pre-stroke PA level in relation to the post-stroke serum IGF-I (s-IGF-I) level, at baseline and at 3 months after the index stroke, and calculated the change that occurred between these two time-points (ΔIGF-I). Patients (N = 380; 63.4% males; mean age, 54.7 years) with data on 1-year leisure-time pre-stroke PA and post-stroke s-IGF-I levels were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Pre-stroke, leisure-time PA was self-reported as PA1–4, with PA1 representing sedentary and PA2–4 indicating progressively higher PA levels. Associations between s-IGF-I and PA were evaluated by multiple linear regressions with PA1 as the reference and adjustments being made for sex, age, history of previous stroke or myocardial infarctions, cardiovascular risk factors, and stroke severity. PA correlated with baseline s-IGF-I and ΔIGF-I, but not with the 3-month s-IGF-I. In the linear regressions, there were corresponding associations that remained as a tendency (baseline s-IGF-I, p = 0.06) or as a significant effect (ΔIGF-I, p = 0.03) after all the adjustments. Specifically, for each unit of PA, ΔIGF-I increased by 9.7 (95% CI 1,1−18.4) ng/mL after full adjustment. This supports the notion that pre-stroke PA is independently related to ΔIGF-I.

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CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20909055 ◽

2020 ◽

Vol 40 (1_suppl) ◽

pp. S98-S116 ◽

Cited By ~ 4

Author(s):

Jordi Pedragosa ◽

Francesc Miró-Mur ◽

Amaia Otxoa-de-Amezaga ◽

Carles Justicia ◽

Francisca Ruíz-Jaén ◽

...

Keyword(s):

Bone Marrow ◽

Ischemic Stroke ◽

Functional Recovery ◽

Behavioral Performance ◽

Wild Type ◽

Ischemic Brain ◽

Arginase 1 ◽

Angiogenic Genes ◽

The Brain

Inflammatory Ly6ChiCCR2+ monocytes infiltrate the brain after stroke but their functions are not entirely clear. We report that CCR2+ monocytes and CCR2+ lymphocytes infiltrate the brain after permanent ischemia. To underscore the role of CCR2+ monocytes, we generated mice with selective CCR2 deletion in monocytes. One day post-ischemia, these mice showed less infiltrating monocytes and reduced expression of pro-inflammatory cytokines, markers of alternatively macrophage activation, and angiogenesis. Accordingly, Ly6Chi monocytes sorted from the brain of wild type mice 24 h post-ischemia expressed pro-inflammatory genes, M2 genes, and pro-angiogenic genes. Flow cytometry showed heterogeneous phenotypes within the infiltrating Ly6ChiCCR2+ monocytes, including a subgroup of Arginase-1+ cells. Mice with CCR2-deficient monocytes displayed a delayed inflammatory rebound 15 days post-ischemia that was not found in wild type mice. Furthermore, they showed reduced angiogenesis and worse behavioral performance. Administration of CCR2+/+ bone-marrow monocytes to mice with CCR2-deficient monocytes did not improve the behavioral performance suggesting that immature bone-marrow monocytes lack pro-reparative functions. The results show that CCR2+ monocytes contribute to acute post-ischemic inflammation and participate in functional recovery. The study unravels heterogeneity in the population of CCR2+ monocytes infiltrating the ischemic brain and suggests that pro-reparative monocyte subsets promote functional recovery after ischemic stroke.

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