Change In National Institutes Of Health Stroke Scale Research Articles

Redefining CT perfusion-based ischemic core estimates for the ghost core in early time window stroke.

In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients. Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short-term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long-term outcome was 90-day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p-value ≤.05. Among 73 patients, median age was 66 (interquartile range 54-76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes. Our multisite analysis shows that favorable short-term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger-scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients.

Endovascular treatment of acute tandem lesions in patients with mild anterior circulation stroke

BackgroundIn patients with mild strokes the risk–benefit ratio of endovascular treatment (EVT) for tandem lesions has yet to be evaluated outside of current guideline recommendations. This study investigates the frequency...

Association of the 24‐Hour National Institutes of Health Stroke Scale After Mechanical Thrombectomy With Early and Long‐Term Survival

Background The National Institutes of Health Stroke Scale (NIHSS) obtained 24 hours after ischemic stroke is a good indicator for functional outcome and early mortality, but the correlation with long‐term survival is less clear. We analyzed the correlation of the NIHSS after 24 hours (24h NIHSS) and early clinical neurological development after mechanical thrombectomy with early and long‐term survival as well as its predictive power on survival. Methods We reviewed a prospective observational registry for all patients undergoing mechanical thrombectomy between January 2010 and December 2018. Vital status was extracted from the Swiss Population Registry. Adjusted hazard ratio (aHR) and crude hazard ratios were calculated using Cox regression. To assess predictive power of the 24h NIHSS, different Random Survival Forest models were evaluated. Results We included 957 patients (median follow‐up 1376 days). Patients with lower 24h NIHSS and major early neurological improvement had substantially better survival rates. We observed significantly higher aHR for death in patients with 24h NIHSS 12 to 15 (aHR, 1.78; 95% CI, 1.1–2.89), with 24h NIHSS 16 to 21 (aHR, 2.54, 95% CI, 1.59–4.06), and with 24h NIHSS &gt;21 (aHR, 5.74; 95% CI, 3.47–9.5). The 24h NIHSS showed the best performance predicting mortality (receiver operating characteristic area under the curve at 3 months [0.85±0.034], at 1 year [0.82±0.029], at 2 years [0.82±0.031], and at 5 years [0.83±0.035]), followed by NIHSS change. Conclusions Patients with acute ischemic stroke achieving a low 24h NIHSS or major early neurological improvement after mechanical thrombectomy had markedly lower long‐term mortality. Furthermore, 24h NIHSS had the best predictive power for early and long‐term survival in our machine learning–based prediction.

National Institutes of Health Stroke Scale as an Outcome in Stroke Research: Value of ANCOVA Over Analyzing Change From Baseline.

National Institutes of Health Stroke Scale (NIHSS), measured a few hours to days after stroke onset, is an attractive outcome measure for stroke research. NIHSS at the time of presentation (baseline NIHSS) strongly predicts the follow-up NIHSS. Because of the need to account for the baseline NIHSS in the analysis of follow-up NIHSS as an outcome measure, a common and intuitive approach is to define study outcome as the change in NIHSS from baseline to follow-up (ΔNIHSS). However, this approach has important limitations. Analyzing ΔNIHSS implies a very strong assumption about the relationship between baseline and follow-up NIHSS that is unlikely to be satisfied, drawing into question the validity of the resulting statistical analysis. This reduces the precision of the estimates of treatment effects and the power of clinical trials that use this approach to analysis. ANCOVA allows for the analysis of follow-up NIHSS as the dependent variable while adjusting for baseline NIHSS as a covariate in the model and addresses several challenges of using ΔNIHSS outcome using simple bivariate comparisons (eg, a t test, Wilcoxon rank-sum, linear regression without adjustment for baseline) for stroke research. In this article, we use clinical trial simulations to illustrate that variability in NIHSS outcome is less when follow-up NIHSS is adjusted for baseline compared to ΔNIHSS and how a reduction in this variability improves the power. We outline additional, important clinical and statistical arguments to support the superiority of ANCOVA using the final measurement of the NIHSS adjusted for baseline over, and caution against using, the simple bivariate comparison of absolute NIHSS change (ie, delta).

The Stockholm Stroke Triage Project: Outcomes of Endovascular Thrombectomy Before and After Triage Implementation.

The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study. We prospectively recruited patients transported by Code Stroke ambulance within the Stockholm region under the SSTS, treated with EVT during October 2017 to October 2019, and compared to EVT patients from 2 previous years. shift in modified Rankin Scale (mRS) scores, mRS score 0 to 1, mRS score 0 to 2, and death (all 3 months), National Institutes of Health Stroke Scale (NIHSS) score change 24-hour post-EVT, recanalization (Thrombolysis in Cerebral Infarction 2b-3), and symptomatic intracranial hemorrhage. mRS outcomes were adjusted for age and baseline NIHSS. Patients with EVT in the SSTS group (n=244) were older and had higher baseline NIHSS versus historical controls (n=187): median age 74 (interquartile range, 63-81) versus 71 (61-78); NIHSS score 17 (11.5-21) versus 15 (10-20). During SSTS, median onset-to-puncture time was 136 versus 205 minutes (P<0.001). Adjusted common odds ratio for lower mRS in SSTS patients was 1.7 (95% CI, 1.2-2.3) versus controls. During SSTS, 83/240 (34.6%) versus 44/186 (23.7%) reached 3-month mRS score 0 to 1 (P=0.014), adjusted common odds ratio 2.3 (95% CI, 1.4-3.6). Median NIHSS change 24-hour post-EVT was 6 versus 4 (P=0.005). Differences in Thrombolysis in Cerebral Infarction, symptomatic intracranial hemorrhage, and death were nonsignificant. With an onset to arterial puncture time reduction by 69 minutes, outcomes in thrombectomy-treated patients improved significantly after region-wide large artery occlusion triage system implementation. These results warrant replication studies in other geographic and organizational circumstances.

Aspiration-Retriever Technique for Stroke with Large Bore Intermediate Catheter : A Single Center Experience

ObjectiveEarly successful reperfusion is associated with favorable outcomes in acute ischemic stroke (AIS). The purpose of this study was to achieve successful recanalization by a combined mechanical thrombectomy technique, the Aspiration-Retriever Technique for Stroke (ARTS), which is composed of a flexible large lumen distal access catheter and a retrievable stent as the first-line strategy of mechanical thrombectomy. MethodsWe retrospectively reviewed 62 patients with AIS who underwent mechanical thrombectomy from 2018 to 2019 at our institute by a senior neurointerventionalist. Among them, patients who were treated using the ARTS technique with the soft torqueable catheter optimized for intracranial access (SOFIA®; MicroVention-Terumo, Tustin, CA, USA) as the first-line treatment were included. Patients who had tandem occlusions or underlying intracranial artery stenosis were excluded. The angiographic and clinical outcomes were evaluated. The angiographic outcome was analyzed by the rate of successful recanalization, defined as a Thrombolysis in Cerebral Infarction score of 2b or 3 at the end of all procedures and the rate of successfully achieving the first pass effect (FPE), defined as complete recanalization with a single pass of the device. The clinical outcomes included the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS), and mortality. ResultsA total of 27 patients (mean age, 59.3 years) fulfilled the inclusion criteria. The successful recanalization rate was 96% (n=26) while the FPE rate was 41% (n=11). The mean post-procedural NIHSS change was -3.0. Thirteen patients (48%) showed good clinical outcomes after thrombectomy with the ARTS technique (mRS at 90 days ≤2). Postoperative complications occurred in seven of 25 patients : hemorrhagic transformation in six patients (22%) and distal embolization in one patient (4%). Mortality was 15% (n=4). ConclusionAlthough the clinical outcomes using the ARTS technique with a flexible large lumen distal access catheter performed as the frontline thrombectomy in patients with AIS were not significantly superior than those of other studies, this study showed a high rate of successful endovascular recanalization which was comparable to that of other studies. Therefore, ARTS using the SOFIA® catheter can be considered as the first choice of treatment for AIS due to large vessel occlusion.

Autotitrating Bilevel Positive Airway Pressure in Large Vessel Steno-Occlusive Stroke Patients With Suspected Sleep Apnea: A Multicenter Randomized Controlled Study.

Background: We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke.Methods: In a multicenter, randomized, controlled trial patients with large vessel steno-occlusive stroke and clinically suspected sleep apnea were allocated to auto-BPAP or standard stroke care alone. Auto-BPAP was initiated within 24 h from stroke onset and performed over 48 h during diurnal and nocturnal sleep. Sleep apnea was assessed using cardiorespiratory polygraphy. Primary endpoint was early neurological improvement on National Institutes of Health Stroke Scale (NIHSS) score at 72 h. Safety and tolerability of BPAP, functional independence [modified Rankin Scale (mRS) 0–2], stroke recurrence, and mortality at 90 days were assessed.Results: Due to low recruitment, the trial was prematurely stopped after 24 patients had been randomized (auto-BPAP, n = 14; control, n = 10): median baseline NIHSS 13 (5.5–18), 88% large vessel occlusion, and 12% large vessel stenosis. Polygraphy confirmed sleep apnea in 64% of auto-BPAP and 88% of control patients (p = 0.34). Adherence to auto-BPAP was achieved by 9 of the 14 (64%) patients. Between auto-BPAP and control patients, no differences were observed in early neurological improvement (median NIHSS change: −2.0, IQR = 7 points vs. −0.5, IQR = 3 points), 90 days functional independence (21 vs. 30%, p = 0.67), stroke recurrence (0 vs. 20%, p = 0.16), and death (14 vs. 20%, p = 1.0). No safety concerns were identified.Conclusions: In this prematurely terminated trial, auto-BPAP was safe but did not show an effect on short-term clinical outcomes in selected ischemic stroke patients. Its tolerability, however, may be limited in hyperacute stroke care and needs to be improved before larger trials are conducted.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01812993.

An Index From Transcranial Doppler Signals for Evaluation of Stroke Rehabilitation Using External Counterpulsation.

This study aimed to develop a sensitive index from transcranial Doppler (TCD) signals for quantitatively evaluating the effects of long-term external counterpulsation (ECP) treatment on stroke rehabilitation. We recruited 27 patients with unilateral ischemic stroke and a good acoustic window within 7 days of stroke onset. 15 of them received 35 daily 1-hour ECP treatment (ECP group) and the others underwent conventional therapy without ECP treatment (No-ECP group). We monitored blood flow in middle cerebral arteries on both sides by TCD, and analyzed them via discrete wavelet analysis method. The overall changes of National Institutes of Health Stroke Scale (NIHSS) and Barthel Index were assessed. A 'big-wave' phenomenon was observed in TCD signals of patients in ECP group after 35 days' treatment, with significant fluctuation in frequency interval from 0.010 to 0.034 Hz as main feature. A new index, which was denoted as I , was derived from this phenomenon. The I was significantly higher for patients in ECP group than that for patients in No-ECP group after 35-days' treatment ( 0.01). And the I was positively correlated with NIHSS change in ECP group ( ). The new index could be used as an effective indicator for evaluating enhancement of endothelial metabolism and neurogenic activity after long-term ECP treatment.

Redefined Measure of Early Neurological Improvement Shows Treatment Benefit of Alteplase Over Placebo.

Background and Purpose- The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods- We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score-24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score-24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95-100 and modified Rankin Scale score of 0-1), good 3-month functional outcome (modified Rankin Scale score of 0-2), and 3-month infarct volume. Results- There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P=0.045) but not median delta NIHSS (3 versus 2; P=0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROCpercent) was better than delta NIHSS (ROCdelta) and admission NIHSS (ROCadmission) with regards to excellent 3-month Barthel Index (ROCpercent, 0.83; ROCdelta, 0.76; ROCadmission, 0.75), excellent 3-month modified Rankin Scale (ROCpercent, 0.83; ROCdelta, 0.74; ROCadmission, 0.78), and good 3-month modified Rankin Scale (ROCpercent, 0.83; ROCdelta, 0.76; ROCadmission, 0.78). Conclusions- In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

Evaluation of Patients with High National Institutes of Health Stroke Scale as Thrombectomy Candidates Using the Kentucky Appalachian Stroke Registry

Introduction: Mechanical thrombectomy has become standard of care for emergent large vessel occlusive stroke. Estimates of incidence for thrombectomy eligibility vary significantly. National Institutes of Health Stroke Scale (NIHSS) of 10 or greater is highly predictive of large vessel occlusion. Using our Kentucky Appalachian Stroke Registry (KApSR), we evaluated temporal trends in stroke admissions with NIHSS ≥10 to determine patient characteristics among that group along with effects and needs in thrombectomy utilization. Methods: Using the KApSR database that captures patients throughout the Appalachian region in our stroke network, we evaluated patients admitted with ischemic stroke with NIHSS ≥10. We recorded demographics, comorbidities, treatment (thrombectomy, decompressive craniectomy), and county of origin. Change in NIHSS from admission to discharge was used as an indicator of inpatient outcome. Results: Between 2010 and 2016, 1,510 patients were admitted with NIHSS ≥10. 87.2% had high blood pressure, 69.6% had dyslipidemia, and 41.7% used tobacco. There were significant sex differences in the types of patients presenting with NIHSS ≥10 with females being older on average and having more atrial fibrillation and obesity. There was an increase in thrombectomy utilization from 2010 to 2016, but only 7.5% of the potentially eligible patients underwent the procedure. In comparison to the period 2010–2014, the 2015–2016 period had higher rates of obesity and tobacco abuse. Conclusion: Among patients with significant burden of ischemic stroke, the most common coexisting medical condition was high blood pressure. Patients who underwent thrombectomy had significantly better inpatient clinical improvement. These data support the need to maximize utilization of thrombectomy along with need to devote increased resources on modifiable stroke risk factors.

Effectiveness of emergency physician determinations of the need for thrombolytic therapy in acute stroke

An increased emphasis on stroke care has led to a proliferation of specialized stroke teams despite relatively few trials demonstrating their efficacy. Our academic stroke center incorporated a unique setup allowing for the comparison between stroke teams and emergency physicians. During weekday working hours, a stroke team would respond to the emergency department for stroke activations. During all other times, the emergency physician caring for the patient would make all treatment decisions. We sought to determine whether there was any difference in treatment and outcomes between these two groups. We conducted a retrospective review of all stroke activations from January 2015 to June 2016 and compared the thrombolytic administration rates, modified Rankin Scale (mRS) at discharge, and change in National Institutes of Health Stroke Scale (NIHSS). A total of 415 stroke activations were identified. Of those, 69 of 262 patients (26.3%) seen by emergency physicians and 60 of 153 patients (39.2%) seen by neurologists received thrombolysis (P = 0.006). No significant difference was found in the discharge mRS or change in NIHSS between the two groups. Emergency physicians administered significantly less thrombolytics than did neurologists. No significant difference was observed in outcomes, including mRS and admission-to-discharge change in NIHSS.

Overlap in the Genetic Architecture of Stroke Risk, Early Neurological Changes, and Cardiovascular Risk Factors.

Background and Purpose- The genetic relationships between stroke risk, stroke severity, and early neurological changes are complex and not completely understood. Genetic studies have identified 32 all stroke risk loci. Polygenic risk scores can be used to compare the genetic architecture of related traits. In this study, we compare the genetic architecture of stroke risk, stroke severity, and early neurological changes with that of 2 stroke risk factors: type 2 diabetes mellitus (T2DM) and hypertension. Methods- We assessed the degree of overlap in the genetic architecture of stroke risk, T2DM, hypertension, and 2 acute stroke phenotypes based on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 for no stroke symptoms to 21 to 42 for a severe stroke: baseline (within 6 hours after onset) and change in NIHSS (ΔNIHSS=NIHSS at baseline-NIHSS at 24 hours). This was done by (1) single-nucleotide polymorphism by single-nucleotide polymorphism comparison, (2) weighted polygenic risk scores with sentinel variants, and (3) whole-genome polygenic risk scores using multiple P thresholds. Results- We found evidence of genetic architecture overlap between stroke risk and T2DM ( P=2.53×10-169), hypertension ( P=3.93×10-04), and baseline NIHSS ( P=0.03). However, there was no evidence of overlap between ΔNIHSS and stroke risk, T2DM, or hypertension. Conclusions- The genetic architecture of stroke risk is correlated with that of T2DM, hypertension, and initial stroke severity (NIHSS within 6 hours of stroke onset). However, the genetic architecture of early neurological change after stroke (ΔNIHSS) is not correlated with that of ischemic stroke risk, T2DM, or hypertension. Thus, stroke risk and early neurological change after stroke have distinct genetic architectures.

Abstract WP109: Early Neurological Decline in Acute Ischemic Stroke Patients Receiving Thrombolysis With Large Vessel Occlusion and Initial Mild Deficits

Introduction: One quarter of ischemic stroke patients with initial mild deficits will have poor outcome. We sought to determine the rate of early neurological decline in acute ischemic stroke patients with large vessel occlusion (LVO) presenting with mild deficits. Methods: Among 322 acute ischemic stroke patients who received intravenous tissue plasminogen activator (IVtPA) from July 1, 2016 to July 1, 2017, we identified 76 (23.6%) with imaging confirmed anterior circulation LVO, defined as M1, M2, or carotid terminus (ICAT). Basilar artery occlusions were excluded. Mild deficits were defined as National Institutes of Health Stroke Scale (NIHSS) &lt; 7. Data was abstracted on demographics, neuroimaging, need for intra-arterial therapy (IAT) revascularization, final Thrombolysis in Cerebral Infarction score (TICI), and clinical presentation. Early neurological decline was defined as NIHSS worsening of &gt; 4 points within 24 hours. Results: Among 76 patients with LVO, we identified 22 (29%) who presented with initial low NIHSS (&lt; 7). The mean age was 64.7 years (range 26 to 93). IVtPA time from last known well (LKN) was a mean 2.7 hours (range 1.3 to 4.9). Most patients (91%) were transfers from outside facilities. LVO sites were as follows: 4 (18%) ICAT, 7 (32%) M1, and 11 (50%) M2. Most (19/22 86%) had CT perfusion imaging, and large mismatch was seen in 6/8 with worsening and 6/11 without worsening. Among the 22 patients with mild deficits initially, 9 (41%) had early neurological decline. Patients with early neurological decline were significantly older (77.8 vs 55.7 years, p=0.0008). Among 9 patients with decline, the mean change in NIHSS was 9 points (range, 4 to 18) and 3 (13.6%) underwent rescue therapy with IAT with TICI 2b (1) and TICI 3 (2) revascularization. On hospital discharge, LVO patients with neurological decline were significantly less likely to be discharged home compared with patients without decline (22% vs 69%, p=0.03). Conclusions: Among LVO patients who received IVtPA, 29% presented with mild deficits (NIHSS &lt;7). Among these patients with mild deficits, early neurological decline occurred in 41% despite receiving IVtPA and was associated with older age. CTP mismatch did not accurately predict which patients would worsen.

Abstract WP42: Early Dramatic Improvement on the National Institutes of Health Stroke Scale Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study

Introduction: Thrombectomy in late time windows leads to improved outcomes in patients with ischemic stroke due to large vessel occlusion (LVO). We determined if patients with a dramatic improvement in their National Institutes of Health Stroke Scale (NIHSS) score 24 hours (24h) after thrombectomy were more likely to have a favorable clinical outcome than patients without a dramatic change in NIHSS in the DEFUSE 3 study. Methods: All patients who underwent thrombectomy in DEFUSE 3 were included. Dramatic improvement (DI) was defined as a reduction of ≥8 NIHSS or NIHSS 0-1 24h after thrombectomy. Clinical outcomes were assessed by an ordinal analysis modified Rankin Scale (mRS) score and a dichotomous analysis for functional independence (mRS 0-2) at 90 days. Pre- and post-thrombecotmy core infarction was quantified by the DEFUSE 3 core laboratory. Results: 91 patients in DEFUSE 3 underwent thrombectomy with follow up data; 31 patients (34%) experienced DI (DI+) after thrombectomy and 60 patients (66%) did not (DI-). There were no differences in age, medical comorbidities, right sided infarction, LVO location, presentation NIHSS, treatment with intravenous tPA, or time of thrombectomy treatment between DI+ and DI-. Presentation ASPECTS and baseline infarct core and penumbra volumes were similar between these groups. Reperfusion (TICI IIB-III) after thrombectomy was achieved in 26 (84%) DI+ and 43 (72%) DI- (p=0.2). Symptomatic intracranial hemorrhage occurred in no DI+ and 8% of DI- patients (p=0.2). DI was associated with a favorable mRS shift at day 90 (OR 3.8 [CI 1.7-8.6]; p=0.001) and higher rates of mRS 0-2 (61% vs 37%) OR 2.7 [CI 1.1-6.7]; p=0.03. Mortality was 3% in DI+ vs 18% in DI- (p=0.05). DI+ patients has lower median 24h NIHSS (5 [IQR 1-7] vs 13 [IQR 7.5-21]; p&lt;0.001), smaller 24h infarction volume (21 ml [IQR 5-32] vs 65 [IQR 27-145]; p&lt;0.001), and less 24h infarct growth (8 ml [IQR 1-18] vs 37 [IQR 16-105]; p&lt;0.001) compared to DI- patients. Hospital stay was shorter in DI+, 3.7 days [IQR 2.9-7.1] vs 7.4 [IQR 5.2-12.1] in DI-, p&lt;0.001. Conclusions: DI following thrombectomy correlates with favorable clinical and radiographic outcomes and reduced hospital length of stay. DI was a favorable prognostic sign following late window thrombectomy in the DEFUSE 3 cohort.

Prediction of Outcome in Patients With Acute Ischemic Stroke Based on Initial Severity and Improvement in the First 24 h.

Stroke severity measured by the baseline National Institutes of Health Stroke Scale (NIHSS) is a strong predictor of stroke outcome. Early change of baseline severity may be a better predictor of outcome. Here, we hypothesized that the change in NIHSS in the first 24 h after stroke improved stroke outcome prediction. Patients from the Leuven Stroke Genetics Study were included when the baseline NIHSS (B-NIHSS) was determined on admission in the hospital and NIHSS after 24 h could be obtained from patient files. The delta NIHSS, relative reduction NIHSS, and major neurological improvement (NIHSS of 0-1 or ≥8-point improvement at 24 h) were calculated. Good functional outcome (GFO) at 90 days was defined as a modified Rankin Scale of 0-2. Independent predictors of outcome were identified by multivariate logistic regression. We performed a secondary analysis after excluding patients presenting with a minor stroke (NIHSS 0-5) since the assessment of change in NIHSS might be more reliable in patients presenting with a moderate to severe deficit. We analyzed the outcome in 369 patients. B-NIHSS was associated with GFO (odds ratio: 0.82; 95% CI 0.77-0.86). In a multivariate model with B-NIHSS and age as predictors, the accuracy [area under the curve (AUC): 0.82] improved by including the delta NIHSS (AUC: 0.86; p < 0.01). In 131 patients with moderate to severe stroke, the predictive multivariate model was more accurate when including the RR NIHSS (AUC: 0.83) to the model which included B-NIHSS, age and ischemic heart disease (AUC: 0.77; p = 0.03). B-NIHSS is a predictor of stroke outcome. In this cohort, the prediction of GFO was improved by adding change in stroke severity after 24 h to the model.

Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial

Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18-83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8-20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24-48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov, number NCT01436487. The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 [99%] of 65 patients in the multipotent adult progenitor cell group vs 59 [97%] of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 [95% CI 0·55-2·09], p=0·83). Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Athersys Inc.

Spontaneous Recovery of Upper Extremity Motor Impairment After Ischemic Stroke: Implications for Stem Cell-Based Therapeutic Approaches

Preclinical studies suggest that stem cell therapy (SCT) may improve sensorimotor recovery after stroke. Upper extremity motor impairment (UEMI) is common after stroke, often entailing substantial disability. To evaluate the feasibility of post-stroke UEMI as a target for SCT, we examined a selected sample of stroke patients potentially suitable for SCT, aiming to assess the frequency and recovery of UEMI, as well as its relation to activity limitations and participation restrictions. Patients aged 20–75 years with first-ever ischemic stroke, and National Institutes of Health Stroke Scale (NIHSS) scores 1–18, underwent brain diffusion-weighted MRI within 4 days of stroke onset (n = 108). Survivors were followed up after 3–5 years, including assessment with NIHSS, Fugl-Meyer assessment of upper extremity (FMA-UE), modified Rankin Scale (mRS), and Stroke Impact Scale (SIS). UEMI was defined as NIHSS arm/hand score ≥1. UEMI recovery was evaluated with change in NIHSS arm/hand scores between baseline and follow-up. Of 97 survivors, 84 were available to follow-up. Among 76 subjects (of 84) without recurrent stroke, 41 had UEMI at baseline of which 10 had residual UEMI at follow-up. The FMA-UE showed moderate-severe impairment in seven of 10 survivors with residual UEMI. UEMI was correlated to mRS (rs = 0.49, p < 0.001) and the SIS social participation domain (rs = −0.38, p = 0.001). Nearly 25% of the subjects with UEMI at baseline had residual impairment after 3–5 years, whereas about 75% showed complete recovery. Most of the subjects with residual UEMI had moderate-severe impairment, which correlated strongly to dependency in daily activities and social participation restrictions. Our findings suggest that SCT targeting post-stroke UEMI may be clinically valuable with significant meaningful benefits for patients but also emphasize the need of early prognostication to detect patients that will have residual impairment in order to optimize patient selection for SCT.

Early Trajectory of Stroke Severity Predicts Long-Term Functional Outcomes in Ischemic Stroke Subjects: Results From the ESCAPE Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

The trajectory of neurological improvement after stroke treatment is clinically likely to be an important prognostic signal. We compared the accuracy of early longitudinal National Institutes of Health Stroke Scale (NIHSS) measurement versus other early markers of stroke severity post treatment in predicting subjects' 90-day stroke outcome. Data are from the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Stroke severity was assessed at baseline, 1, 2, 5, 30, and 90 days. Subjects' functional outcome was assessed using the modified Rankin Scale at baseline, 30 days, and 90 days. Group-based trajectory model was used to identify distinct subgroups of longitudinal trajectories of NIHSS measured over the first 2, 5, and 30 days. The accuracy of baseline NIHSS, infarct volume, 24-hour change in NIHSS, infarct volume, and disease severity trajectory subgroups in predicting 90-day stroke outcome were assessed using logistic regression analysis. Group-based trajectory model of the 2-day longitudinal NIHSS data revealed 3 distinct subgroups of NIHSS trajectories-large improvement (41.6%), minimal improvement (31.1%), and no improvement (27.3%) subgroups. Individuals in the large improvement group were more likely were more likely to exhibit good outcomes after 90 days than those in the minimal improvement or no improvement subgroup. Among candidate predictors, the 2-day trajectory subgroup variable was the most accurate in predicting 90-day modified Rankin Scale at 84.5%. Early trajectory of neurological improvement defined by 2-day longitudinal NIHSS data predicts functional outcomes with greater accuracy than other common variables. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Trends in C-Reactive Protein Levels Are Associated with Neurological Change Twenty-Four Hours after Thrombolysis for Acute Ischemic Stroke

Elevated inflammatory markers such as C-reactive protein (CRP) are associated with worse outcomes in patients thrombolysed for acute ischemic stroke (AIS). To investigate whether changes in CRP levels are associated with neurological change after thrombolysis for AIS. Retrospective analysis of a single-center database of consecutive thrombolysis cases for AIS from October 18, 2011, to June 15, 2015, inclusive. Multivariate regression analysis was used to investigate the relationship between change in CRP 12-24 hours after thrombolysis and change in NIHSS (National Institutes of Health Stroke Scale) score 24 hours after thrombolysis. The other potentially confounding predictor variables included in the model were CRP on admission and NIHSS score before thrombolysis. Complete data were available for 108 out of possible 435 eligible patients. Increases in CRP levels 12-24 hours after thrombolysis were negatively associated with reduction in NIHSS score 24 hours after thrombolysis (coefficient .08, 95% confidence interval .031-.129, P = .002). Thus, on average, for every 12.5 mg/L additional increase in CRP 12-24 hours after thrombolysis, NIHSS score at 24 hours improved by 1 point less. While it was previously known that elevated CRP levels are associated with worse outcomes in patients thrombolysed for AIS, the current work demonstrates that changes in CRP levels after thrombolysis also relate to neurological change, and thus may have scope for use as prognostic markers.

Abstract TMP28: Upper Extremity Motor Impairment After Ischemic Stroke - Implications for Stem Cell Therapy

Introduction: Experimental studies show that stem cells can improve motor recovery in animal stroke models. In humans, upper extremity motor impairment (UEMI) is a major consequence following stroke and can entail substantial disability. As stem cell therapy (SCT) may become clinically applicable to promote arm/hand motor recovery after stroke, we aimed to examine the frequency and recovery of UEMI, as well as its’ correlation to functional status and health-related quality of life (HRQoL), in a selected sample of stroke patients potentially suitable for SCT. Methods: Consecutive first-ever ischemic stroke patients (n=108) were included in the Lund Stroke Recovery Study in 2009-2011 if: they were aged 20-75 years; underwent brain DW-MRI within 4 days of stroke onset; and their baseline stroke severity was 1-18 according to the National Institutes of Health Stroke Scale (NIHSS). All survivors were invited to a clinical follow-up after 3.5-5.5 years, including: NIHSS arm and extended NIHSS hand items to assess UEMI; Fugl-Meyer upper extremity section (FM-UE) to thoroughly examine UEMI; Action Research Arm Test (ARAT) to evaluate arm/hand function; Modified Rankin Scale (mRS) to assess functional status; and Stroke Impact Scale (SIS) to evaluate HRQoL. UEMI was defined as ≥1 on NIHSS arm/hand items. UEMI recovery was assessed by the change in NIHSS arm/hand scores between baseline and follow-up (ΔNIHSS arm/hand). Results: Of 97 stroke survivors, 83 participated in the follow-up. Among survivors without recurrent stroke (n=76), 54% had UEMI at baseline and 28% had remaining UEMI at follow-up. The median ΔNIHSS arm/hand was [-1] (range=[-4] - 1). FM-UE scores were strongly correlated to ARAT (r s =0.68, p &lt;0.01), mRS (r s =[-0.67], p &lt;0.01), SIS strength domain (items 1a+1b; r s =0.68, p &lt;0.01), and SIS hand function domain (r s =0.71, p &lt;0.01). Conclusions: UEMI may be an appropriate target for SCT in stroke as UEMI is prevalent, and strongly correlates to long-term functional status and HRQoL. Our findings confirm previously reported heterogeneity in UEMI recovery, the mechanisms of which need to be addressed in future studies to optimize patient selection for SCT.