Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke

Objective:To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS).Methods:Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set at p < 0.05 for all analyses.Results:Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1–8), and median normalized WMHv was 6.19 cm3 (IQR 3.0–12.6 cm3). Admission stroke severity (β = 0.16, p < 0.0001) and small vessel stroke subtype (β = −1.53, p < 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (β = −9.74, p = 0.02), along with age, female sex, NIHSS score, and DWIv.Conclusions:FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.

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Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke

Frontiers in Neurology ◽

10.3389/fneur.2021.700616 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sungmin Hong ◽

Anne-Katrin Giese ◽

Markus D. Schirmer ◽

Anna K. Bonkhoff ◽

Martin Bretzner ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

Linear Regression Analysis ◽

Functional Independence ◽

White Matter Hyperintensity ◽

Stroke Severity ◽

Post Stroke

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke.Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons.Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively].Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.

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Prestroke statin use enhances collateralization in acute ischemic stroke patients

Restorative Neurology and Neuroscience ◽

10.3233/rnn-201012 ◽

2020 ◽

Vol 38 (4) ◽

pp. 311-321

Author(s):

Jiaying Zhu ◽

Mengmeng Ma ◽

Jinghuan Fang ◽

Jiajia Bao ◽

Shuju Dong ◽

...

Keyword(s):

Ischemic Stroke ◽

Middle Cerebral Artery ◽

Acute Ischemic Stroke ◽

Statin Therapy ◽

Cerebral Artery ◽

Functional Outcomes ◽

Collateral Circulation ◽

Stroke Severity ◽

Stroke Patients ◽

Statin Use

Background: Statin therapy has been shown to be effective in the prevention of ischemic stroke. In addition, recent studies have suggested that prior statin therapy could lower the initial stroke severity and improve stroke functional outcomes in the event of stroke. It was speculated that prestroke statin use may enhance collateral circulation and result in favorable functional outcomes. Objective: The aim of the study was to investigate the association of prestroke statin use with leptomeningeal collaterals and to determine the association of prestroke statin use with stroke severity and functional outcome in acute ischemic stroke patients. Methods: We prospectively and consecutively enrolled 239 acute ischemic stroke patients with acute infarction due to occlusion of the middle cerebral artery within 24 h in the neurology department of West China Hospital from May 2011 to April 2017. Computed tomographic angiography (CTA) imaging was performed for all patients to detect middle cerebral artery thrombus; regional leptomeningeal collateral score (rLMCS) was used to assess the degree of collateral circulation; the National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission; the modified Rankin scale (mRS) was used to measure outcome at 90 days; and premorbid medications were recorded. Univariate and multivariate analyses were performed. Results: Overall, 239 patients met the inclusion criteria. Fifty-four patients used statins, and 185 did not use statins before stroke onset. Prestroke statin use was independently associated with good collateral circulation (rLMCS > 10) (odds ratio [OR], 4.786; 95% confidence interval [CI], 1.195–19.171; P = 0.027). Prestroke statin use was not independently associated with lower stroke severity (NIHSS score≤14) (OR, 1.955; 95% CI, 0.657–5.816; p = 0.228), but prestroke statin use was independently associated with favorable outcome (mRS score≤2) (OR, 3.868; 95% CI, 1.325–11.289; P = 0.013). Conclusions: Our findings suggest that prestroke statin use was associated with good leptomeningeal collaterals and clinical outcomes in acute ischemic stroke (AIS) patients presenting with occlusion of the middle cerebral artery. However, clinical studies should be conducted to verify this claim.

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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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Abstract MP16: Excessive White Matter Hyperintensity Burden and Functional Outcomes After Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.mp16 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Sungmin Hong ◽

Anne-katrin Giese ◽

Markus D Schirmer ◽

Adrian V Dalca ◽

Anna Bonkhoff ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

Life Time ◽

Stroke Recovery ◽

White Matter Hyperintensity ◽

Brain Health ◽

Stroke Outcomes ◽

The Brain

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.

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Elevation of troponin I in acute ischemic stroke

PeerJ ◽

10.7717/peerj.1866 ◽

2016 ◽

Vol 4 ◽

pp. e1866 ◽

Cited By ~ 9

Author(s):

Yu-Chin Su ◽

Kuo-Feng Huang ◽

Fu-Yi Yang ◽

Shinn-Kuang Lin

Keyword(s):

Ischemic Stroke ◽

Hospital Mortality ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Barthel Index ◽

Troponin I ◽

Clinical Deterioration ◽

Stroke Severity ◽

Nihss Score ◽

Poor Outcome

Background. Cardiac morbidities account for 20% of deaths after ischemic stroke and is the second commonest cause of death in acute stroke population. Elevation of cardiac troponin has been regarded as a prognostic biomarker of poor outcome in patients with acute stroke.Methods. This retrospective study enrolled 871 patients with acute ischemic stroke from August 2010 to March 2015. Data included vital signs, laboratory parameters collected in the emergency department, and clinical features during hospitalization. National Institutes of Health Stroke Scale (NIHSS), Barthel index, and modified Rankin Scale (mRS) were used to assess stroke severity and outcome.Results.Elevated troponin I (TnI) > 0.01 µg/L was observed in 146 (16.8%) patients. Comparing to patients with normal TnI, patients with elevated TnI were older (median age 77.6 years vs. 73.8 years), had higher median heart rates (80 bpm vs. 78 bpm), higher median white blood cells (8.40 vs. 7.50 1,000/m3) and creatinine levels (1.40 mg/dL vs. 1.10 mg/dL), lower median hemoglobin (13.0 g/dL vs. 13.7 g/dL) and hematocrit (39% vs. 40%) levels, higher median NIHSS scores on admission (11 vs. 4) and at discharge (8 vs. 3), higher median mRS scores (4 vs3) but lower Barthel index scores (20 vs. 75) at discharge (p< 0.001). Multivariate analysis revealed that age ≥ 76 years (OR 2.25, CI [1.59–3.18]), heart rate ≥ 82 bpm (OR 1.47, CI [1.05–2.05]), evidence of clinical deterioration (OR 9.45, CI [4.27–20.94]), NIHSS score ≥ 12 on admission (OR 19.52, CI [9.59–39.73]), and abnormal TnI (OR 1.98, CI [1.18–3.33]) were associated with poor outcome. Significant factors for in-hospital mortality included male gender (OR 3.69, CI [1.45–9.44]), evidence of clinical deterioration (OR 10.78, CI [4.59–25.33]), NIHSS score ≥ 12 on admission (OR 8.08, CI [3.04–21.48]), and elevated TnI level (OR 5.59, CI [2.36–13.27]).C-statistics revealed that abnormal TnI improved the predictive power of both poor outcome and in-hospital mortality. Addition of TnI > 0.01 ug/L or TnI > 0.1 ug/L to the model-fitting significantly improvedc-statistics for in-hospital mortality from 0.887 to 0.926 (p= 0.019) and 0.927 (p= 0.028), respectively.Discussion.Elevation of TnI during acute stroke is a strong independent predictor for both poor outcome and in-hospital mortality. Careful investigation of possible concomitant cardiac disorders is warranted for patients with abnormal troponin levels.

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Neuroimaging risk factors for participation restriction after acute ischemic stroke: 1-year follow-up study

Journal of Investigative Medicine ◽

10.1136/jim-2020-001675 ◽

2021 ◽

pp. jim-2020-001675

Author(s):

Jian-Feng Qu ◽

Huo-Hua Zhong ◽

Wen-Cong Liang ◽

Yang-Kun Chen ◽

Yong-Lin Liu ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Activities Of Daily Living ◽

Acute Ischemic Stroke ◽

Daily Living ◽

Male Gender ◽

Perivascular Spaces ◽

Participation Restriction ◽

Nihss Score

The aim of the present study was to determine the neuroimaging predictors of poor participation after acute ischemic stroke. A total of 443 patients who had acute ischemic stroke were assessed. At 1-year recovery, the Reintegration to Normal Living Index was used to assess participation restriction. We also assessed the Activities of Daily Living Scale and modified Rankin Scale (mRS) score. Brain MRI measurement included acute infarcts and pre-existing abnormalities such as enlarged perivascular spaces, white matter lesions, ventricular-brain ratio, and medial temporal lobe atrophy (MTLA). The study included 324 men (73.1%) and 119 women (26.9%). In the univariate analysis, patients with poor participation after 1 year were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, with more histories of hypertension and atrial fibrillation, larger infarct volume, more severely enlarged perivascular spaces and MTLA, and more severe periventricular hyperintensities and deep white matter hyperintensities. Patients with participation restriction also had poor activities of daily living (ADL) and mRS score. Multiple logistic regression showed that, in model 1, age, male gender, NIHSS score on admission, and ADL on follow-up were significant predictors of poor participation, accounting for 60.2% of the variance. In model 2, which included both clinical and MRI variables, male gender, NIHSS score on admission, ADL on follow-up, and MTLA were significant predictors of poor participation, accounting for 61.2% of the variance. Participation restriction was common after acute ischemic stroke despite good mRS score. Male gender, stroke severity, severity of ADL on follow-up, and MTLA may be predictors of poor participation.Trial registration number ChiCTR1800016665.

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Abstract TP75: Normal Appearing White Matter Integrity and Motor Impairment Severity in Acute Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp75 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Carson Ingo ◽

Chen Lin ◽

James Higgins ◽

Yurany Arevalo ◽

Shyam Prabhakaran

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Motor Function ◽

Motor Impairment ◽

Internal Capsule ◽

Posterior Limb ◽

Normal Appearing White Matter ◽

Stroke Group ◽

Microstructural Integrity

Introduction: The effect of white matter hyperintensities (WMH) as measured by fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging on functional impairment and recovery after ischemic stroke has been investigated thoroughly. However, there has been growing interest to investigate normal-appearing white matter (NAWM) microstructural integrity following ischemic stroke onset with techniques such as diffusion tensor imaging (DTI). Methods: 52 patients with acute ischemic stroke and 36 without stroke were evaluated with a DTI and FLAIR imaging protocol and clinically assessed for severity of motor impairment using the Motricity Index within 72 hours of suspected symptom onset. Results: There were widespread decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) and radial diffusivity (RD) for the acute stroke group compared to the non-stroke group. As shown in the abstract figure with the blue voxels, there was a significant positive association between FA and motor function and a significant negative association between MD/RD and motor function. The NAWM regions of interest that were most sensitive to the Motricity Index were the anterior/posterior limb of the internal capsule in the infarcted hemisphere and the splenium of the corpus callosum, external capsule, posterior limb/retrolenticular part of the internal capsule, superior longitudinal fasciculus, and cingulum (hippocampus) of the intra-/contralateral hemisphere. Conclusion: The microstructural integrity of NAWM is a significant parameter to identify neural differences not only between those individuals with and without acute ischemic stroke, but also correlated with severity of acute motor impairment.

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Early Trajectory of Stroke Severity Predicts Long-Term Functional Outcomes in Ischemic Stroke Subjects

Stroke ◽

10.1161/strokeaha.116.014456 ◽

2017 ◽

Vol 48 (1) ◽

pp. 105-110 ◽

Cited By ~ 33

Author(s):

Tolulope T. Sajobi ◽

Bijoy K. Menon ◽

Meng Wang ◽

Oluwaseyi Lawal ◽

Ashfaq Shuaib ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Outcomes ◽

Stroke Severity

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ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2014-011125.rep ◽

2018 ◽

Vol 10 (Suppl 1) ◽

pp. i4-i7 ◽

Cited By ~ 17

Author(s):

Aquilla S Turk ◽

Don Frei ◽

David Fiorella ◽

J Mocco ◽

Blaise Baxter ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

National Institutes Of Health ◽

Nihss Score ◽

First Pass ◽

Procedural Complications ◽

Intracerebral Hemorrhages ◽

Stent Retrievers ◽

A New Technique

BackgroundThe development of new revascularization devices has improved recanalization rates and time, but not clinical outcomes. We report a prospectively collected clinical experience with a new technique utilizing a direct aspiration first pass technique with large bore aspiration catheter as the primary method for vessel recanalization.Methods98 prospectively identified acute ischemic stroke patients with 100 occluded large cerebral vessels at six institutions were included in the study. The ADAPT technique was utilized in all patients. Procedural and clinical data were captured for analysis.ResultsThe aspiration component of the ADAPT technique alone was successful in achieving Thrombolysis in Cerebral Infarction (TICI) 2b or 3 revascularization in 78% of cases. The additional use of stent retrievers improved the TICI 2b/3 revascularization rate to 95%. The average time from groin puncture to at least TICI 2b recanalization was 37 min. A 5MAX demonstrated similar success to a 5MAX ACE in achieving TICI 2b/3 revascularization alone (75% vs 82%, p=0.43). Patients presented with an admitting median National Institutes of Health Stroke Scale (NIHSS) score of 17.0 (12.0–21.0) and improved to a median NIHSS score at discharge of 7.3 (1.0–11.0). Ninety day functional outcomes were 40% (modified Rankin Scale (mRS) 0–2) and 20% (mRS 6). There were two procedural complications and no symptomatic intracerebral hemorrhages.DiscussionThe ADAPT technique is a fast, safe, simple, and effective method that has facilitated our approach to acute ischemic stroke thrombectomy by utilizing the latest generation of large bore aspiration catheters to achieve previously unparalleled angiographic outcomes.

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Structural integrity of white matter tracts as a predictor of acute ischemic stroke outcome

International Journal of Stroke ◽

10.1177/1747493020915251 ◽

2020 ◽

Vol 15 (9) ◽

pp. 965-972

Author(s):

Deepthi Rajashekar ◽

Pauline Mouchès ◽

Jens Fiehler ◽

Bijoy K Menon ◽

Mayank Goyal ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Support Vector Regression ◽

Support Vector ◽

Stroke Severity ◽

Lesion Volume ◽

White Matter Tract ◽

Support Vector Regression Model ◽

White Matter Tracts

Background and purpose Clinical assessment scores in acute ischemic stroke are only moderately correlated with lesion volume since lesion location is an important confounding factor. Many studies have investigated gray matter indicators of stroke severity, but the understanding of white matter tract involvement is limited in the early phase after stroke. This study aimed to measure and model the involvement of white matter tracts with respect to 24-h post-stroke National Institutes of Health Stroke Scale (NIHSS). Material and methods A total of 96 patients (50 females, mean age 66.4 ± 14.0 years, median NIHSS 5, interquartile range: 2–9.5) with follow-up fluid-attenuated inversion recovery magnetic resonance imaging data sets acquired one to seven days after acute ischemic stroke onset due to proximal anterior circulation occlusion were included. Lesions were semi-automatically segmented and non-linearly registered to a common reference atlas. The lesion overlap and tract integrity were determined for each white matter tract in the AALCAT atlas and used to model NIHSS outcomes using a supervised linear-kernel support vector regression method, which was evaluated using leave-one-patient-out cross validation. Results The support vector regression model using the tract integrity and tract lesion overlap measurements predicted the 24-h NIHSS score with a high correlation value of r = 0.7. Using the tract overlap and tract integrity feature improved the modeling accuracy of NIHSS significantly by 6% (p < 0.05) compared to using overlap measures only. Conclusion White matter tract integrity and lesion load are important predictors for clinical outcome after an acute ischemic stroke as measured by the NIHSS and should be integrated for predictive modeling.

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