Corrigendum: Staged use of ordinal and linear disability scales: a practical approach to granular assessment of acute stroke outcome.

[This corrects the article DOI: 10.3389/fneur.2023.1174686.].

Staged use of ordinal and linear disability scales: a practical approach to granular assessment of acute stroke outcome.

Background: The modified Rankin Scale (mRS) assessment of global disability is the most common primary endpoint in acute stroke trials but lacks granularity (7 broad levels) and is ordinal (scale levels unknown distances apart), which constrains study power. Disability scales that are linear and continuous may better discriminate outcomes, but computerized administration in stroke patients is challenging. We, therefore, undertook to develop a staged use of an ordinal followed by a linear scale practical to use in multicenter trials. Methods: Consecutive patients undergoing 3-month final visits in the NIH FAST-MAG phase 3 trial were assessed with the mRS followed by 15 mRS level-specific yes-no items of the Academic Medical Center Linear Disability Score (ALDS), a linear disability scale derived using item response theory. Results: Among 55 patients, aged 71.2 (SD ± 14.2), 67% were men and the entry NIHSS was 10.7 (SD ± 9.5). At 90 days, the median mRS score was 3 (IQR, 1-4), and the median ALDS score was 78.8 (IQR, 3.3-100). ALDS scores correlated strongly with 90 days outcome measures, including the Barthel Index (r = 0.92), NIHSS (r = 0.87), and mRS (r = 0.94). ALDS scores also correlated modestly with entry NIHSS (r = 0.38). At 90 days, the ALDS showed greater scale granularity than the mRS, with fewer patients with identical values, 1.9 (SD ± 3.2) vs. 8.0 (SD ± 3.6), p < 0.001. When treatment effect magnitudes were small to moderate, projected trial sample size requirements were 2-12-fold lower when the ALDS rather than the mRS was used as the primary trial endpoint. Conclusion: Among patients enrolled in an acute neuroprotective stroke trial, the ALDS showed strong convergent validity and superior discrimination characteristics compared with the modified Rankin Scale and increased projected trial power to detect clinically meaningful treatment benefits.

Corrigendum: How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis.

[This corrects the article DOI: 10.3389/fneur.2023.1103664.].

FLAIR vascular hyperintensity-DWI mismatch and DWI-FLAIR mismatch ASPECTS for prediction of good outcome after recanalization in anterior circulation stroke; multicenter observational study.

INTRODUCTION: Acute ischemic stroke is a medical emergency caused by decreased blood flow to the brain, leading cause of long-term disability. Recanalization, one of the most concerning difficulties linked with intracranial arterial occlusion, has been used to reduce mortality in ischemic stroke treatment. The mismatch concepts MR PWI-DWI or DWI-FLAIR can help identify patients for thrombolysis. PURPOSE: This paper introduces a novel method of predicting revascularization using the value of fluid-attenuated inversion recovery vascular hyperintensity FVH-DWI mismatch and DWI-FLAIR mismatch, which releases anterior circulation large vessel occlusion (LVO) after endovascular thrombectomy (EVT). Moreover, we present a new scoring system following anatomical region distributed for MCA territory called a DWI-FLAIR MISMATCH ASPECTS. RESULT: Statistical analysis was performed to predict revascularization and functional outcome with 110 patients with anterior circulation LVO treated with EVT. We found that FVH-DWI mismatch was present in 71 patients (89.9 %) with complete revascularization and present in 8 patients (10.1 %) with no/partial revascularization, which had no significant difference (p = 0.12), and there was no significant difference between good functional outcome and poor functional outcome. Moreover, in 76 patients with DWI-FLAIR mismatch ASPECTS of > 6 point-group, present FVH-DWI mismatch in 57 patients (83.8 %) with complete revascularization had a significant difference as compared to 11 patients (16.2 %) with absent FVH-DWI mismatch (p < 0.05). The clinical outcome in complete revascularization is better than no/partial revascularization, and complete revascularization is independently associated with good functional outcomes (p < 0.05). CONCLUSION: FVH-DWI mismatch paired with DWI-FLAIR mismatch ASPECTS > 6 points may be possible to predict revascularization in patients with anterior circulation LVO.

How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis.

Introduction: Long-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS), but occult AF is also found in some individuals without a stroke history and in patients with stroke of a known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal vs. incidental. Methods: Through a systematic search, we identified all case-control and cohort studies applying identical long-term monitoring techniques to both patients with CS and KS. We performed a random-effects meta-analysis across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients and across age subgroups. We then applied Bayes' theorem to determine the probability that occult AF is causal or incidental. Results: The systematic search identified three case-control and cohort studies enrolling 560 patients (315 CS, 245 KS). Methods of long-term monitoring were implantable loop recorder in 31.0%, extended external monitoring in 67.9%, and both in 1.2%. Crude cumulative rates of AF detection were CS 47/315 (14.9%) vs. KS 23/246 (9.3%). In the formal meta-analysis, the summary odds ratio for occult AF in CS vs. KS in all patients was 1.80 (95% CI, 1.05-3.07), p = 0.03. With the application of Bayes' theorem, the corresponding probabilities indicated that, when present, occult AF in patients with CS is causal in 38.2% (95% CI, 0-63.6%) of patients. Analyses stratified by age suggested that detected occult AF in patients with CS was causal in 62.3% (95 CI, 0-87.1%) of patients under the age of 65 years and 28.5% (95 CI, 0-63.7%) of patients aged 65 years and older but estimates had limited precision. Conclusion: Current evidence is preliminary, but it indicates that in cryptogenic stroke when occult AF is found, it is causal in about 38.2% of patients. These findings suggest that anticoagulation therapy may be beneficial to prevent recurrent stroke in a substantial proportion of patients with CS found to have occult AF.

Standardized Nomenclature for Modified Rankin Scale Global Disability Outcomes: Consensus Recommendations From Stroke Therapy Academic Industry Roundtable XI.

The modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability, is the most widely employed outcome scale in acute stroke trials. The scale's original development preceded the advent of modern clinimetrics, but substantial subsequent work has been performed to enable the mRS to meet robust contemporary scale standards. Prior research and consensus recommendations have focused on modernizing 2 aspects of the mRS: operationalized assignment of scale scores and statistical analysis of scale distributions. Another important characteristic of the mRS still requiring elaboration and specification to contemporary clinimetric standards is the Naming of scale outcomes. Recent clinical trials have used a bewildering variety, often mutually contradictory, of rubrics to describe scale states. Understanding of the meaning of mRS outcomes by clinicians, patients, and other clinical trial stakeholders would be greatly enhanced by use of a harmonized, uniform set of labels for the distinctive mRS outcomes that would be used consistently across trials. This statement advances such recommended rubrics, developed by the Stroke Therapy Academic Industry Roundtable collaboration using an iterative, mixed-methods process. Specific guidance is provided for health state terms (eg, Symptomatic but Nondisabled for mRS score 1; requires constant care for mRS score 5) and valence terms (eg, excellent for mRS score 1; very poor for mRS score 5) to employ for 23 distinct numeric mRS outcomes, including: all individual 7 mRS levels; all 12 positive and negative dichotomized mRS ranges, positive and negative sliding dichotomies; and utility-weighted analysis of the mRS.

A randomized controlled study of intravenous fluid in acute ischemic stroke.

OBJECTIVE: To compare the outcome of patients with acute ischemic stroke who received or did not receive intravenous fluid. PATIENTS AND METHODS: This study was a prospective, multicenter, randomized, open-label trial with blinded outcome assessment. We enrolled acute ischemic stroke patients without dehydration aged between 18 and 85 years with NIH Stroke Scale score (NIHSS) score from 1 to 18 who presented within 72h after onset. Patients were randomly assigned to receive 0.9% NaCl solution 100ml/h for 3days or no intravenous fluid. RESULTS: On the interim unblinded analysis of the safety data, significant excess early neurological deterioration was observed among patients in the non-intravenous fluid group. Therefore, the study was prematurely discontinued after enrollment of 120 patients, mean age 60 years, 56.6% male. Early neurological deterioration (increased NIHSS ≥3 over 72h) not of metabolic or hemorrhagic origin was observed in 15% of the non-IV fluid group and 3.3% of the IV fluid group (p=0.02). Predictors of neurological deterioration were higher NIHSS score, higher plasma glucose, and increased pulse rate. There was no difference in the primary efficacy outcome, NIHSS≤4 at day 7, 83.3% vs 86.7%, p=0.61 or secondary efficacy outcomes. CONCLUSION: Administration of 0.9% NaCl 100ml/h for 72h in patients with acute ischemic stroke is safe and may be associated with a reduced risk of neurological deterioration. These study findings support the use of intravenous fluid in acute ischemic stroke patients with NIHSS less than 18 who have no contraindications.

Adopting a Patient-Centered Approach to Primary Outcome Analysis of Acute Stroke Trials Using a Utility-Weighted Modified Rankin Scale.

BACKGROUND AND PURPOSE: Although the modified Rankin Scale (mRS) is the most commonly used primary end point in acute stroke trials, its power is limited when analyzed in dichotomized fashion and its indication of effect size challenging to interpret when analyzed ordinally. Weighting the 7 Rankin levels by utilities may improve scale interpretability while preserving statistical power. METHODS: A utility-weighted mRS (UW-mRS) was derived by averaging values from time-tradeoff (patient centered) and person-tradeoff (clinician centered) studies. The UW-mRS, standard ordinal mRS, and dichotomized mRS were applied to 11 trials or meta-analyses of acute stroke treatments, including lytic, endovascular reperfusion, blood pressure moderation, and hemicraniectomy interventions. RESULTS: Utility values were 1.0 for mRS level 0; 0.91 for mRS level 1; 0.76 for mRS level 2; 0.65 for mRS level 3; 0.33 for mRS level 4; 0 for mRS level 5; and 0 for mRS level 6. For trials with unidirectional treatment effects, the UW-mRS paralleled the ordinal mRS and outperformed dichotomous mRS analyses. Both the UW-mRS and the ordinal mRS were statistically significant in 6 of 8 unidirectional effect trials, whereas dichotomous analyses were statistically significant in 2 to 4 of 8. In bidirectional effect trials, both the UW-mRS and ordinal tests captured the divergent treatment effects by showing neutral results, whereas some dichotomized analyses showed positive results. Mean utility differences in trials with statistically significant positive results ranged from 0.026 to 0.249. CONCLUSIONS: A UW-mRS performs similar to the standard ordinal mRS in detecting treatment effects in actual stroke trials and ensures the quantitative outcome is a valid reflection of patient-centered benefits.

Association between genetic polymorphisms and sites of cervicocerebral artery atherosclerosis.

Ischemic stroke is a multifactorial disease with strong genetic elements. The purpose of this case-control study was to find relationships between apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR) genotypes and atherosclerosis of the extracranial internal carotid and intracranial arteries in the Thai population. Patients aged >45 years with significant intracranial stenosis (IC group) or extracranial carotid artery stenosis (EC group) diagnosed by duplex ultrasound and/or computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were studied. The control group comprised volunteers with no history of stroke and no evidence of significant cervicocerebral artery stenosis by ultrasound. Genomic DNA was extracted and genotyped for APOE isoforms, ACE insertion/deletion (I/D) polymorphism, and MTHFR C677T polymorphisms. There were 141 cases (83 in the IC group and 58 in the EC group) and 167 controls. The APOE ε3/ε4 genotype and APOE ε4 allele were significantly associated with extracranial carotid artery stenosis (odds ratio, 2.55; 95% confidence interval, 1.07-6.05 and odds ratio, 2.85; 95% confidence interval, 1.35-5.99, respectively). These associations were not observed in patients with intracranial atherosclerosis. There was no significant association between ACE and MTHFR polymorphisms and stenosis at any site. In a multivariate model, sex, diabetes mellitus, hypertension, ischemic heart disease, and APOE ε4 allele remained predictive of extracranial atherosclerosis. In our Thai population, the ε4 allele in the APOE gene contributes to the genetic susceptibility of extracranial internal carotid atherosclerosis. The low prevalence of extracranial carotid stenosis in this population might result from low frequencies of the APOE ε4 allele.

The association between risk factors for ischemic stroke and microalbuminuria.

OBJECTIVE: To determine the relationship between the risk factors for ischemic stroke and microalbuminuria. MATERIAL AND METHOD: We enrolled 173 patients older than 25 years who had at least two risk factors for stroke. The patients were assessed by questionnaire, blood pressure, microalbuminuria, height and weight measurement. The patients were given health education. RESULTS: The common risk factors were hypertension (80.3%), dyslipidemia (56.6%), and multiple cerebral infarction (39.9%). The hypertensive patients had 5 times risk of microalbuminuria 5.0 compared to normotensive patients (95% CI, 1.13-21.90; p-value < 0.05). Among diabetes patients had risk of microalbuminuria 27.1 times compared to non-diabetic patients (95% CI, 9.58-76.82; p-value < 0.01). However, the patients who had dyslipidemia had risk of microalbuminuria 1.784 times of who did not, but no statistically significant (95% CI, 0.79-4.03; p-value > 0.05). CONCLUSION: Diabetes mellitus and hypertension are significantly risk factor of ischemic stroke related to microalbuminuria.