Change In National Institutes Of Health Stroke Scale Score Research Articles

Dynamic Changes of Asymmetric Cortical Veins Relate to Neurologic Prognosis in Acute Ischemic Stroke.

Background Cerebral oxygenation is closely related to neural function in acute ischemic stroke (AIS) and can be measured noninvasively from asymmetrically prominent cortical veins (APCVs) using quantitative susceptibility mapping (QSM). Purpose To quantify venous oxygen saturation (SvO2) using brain MRI with QSM in patients with AIS, to analyze its change at 2-week follow-up, and to assess the influence of SvO2 in clinical prognosis. Materials and Methods Between 2016 and 2020, consecutive patients with AIS who underwent brain MRI within 24 hours from symptom onset and 2 weeks after treatment were retrospectively enrolled. The SvO2 of APCVs was quantified using QSM. The independent sample t test was used to compare the SvO2 between patients with and patients without APCVs. The paired sample t test was used to assess the dynamic change in SvO2. Pearson and Spearman correlation analysis was used to explore the relationship among dynamic change in SvO2 and hypoperfusion, National Institutes of Health Stroke Scale (NIHSS) score change, and 90-day modified Rankin Scale (mRS) score. The independent sample t test was used to compare the dynamic change in SvO2 between different clinical prognoses and outcome subgroups. Results APCVs were detected in 39 of 73 patients (mean age, 70 years ± 10 [standard deviation]; 49 men) at admission and disappeared in 35 patients at 2-week follow-up MRI. The mean SvO2 increased from 35.0% ± 5.8 to 64.5% ± 10.0 (P < .001) in 39 patients. For the 35 patients with APCVs that disappeared, the dynamic change in SvO2 negatively correlated with change in NIHSS score (r = -0.37, R2 = 0.19, P = .03) and 90-day mRS score (r = -0.54, R2 = 0.27, P = .001), and the dynamic change in SvO2 in the subgroup with good 90-day outcomes (n = 19) was greater than that in the subgroup with poor 90-day outcomes (n = 16) (mean, 34.5% ± 5.8 vs 29.7% ± 6.3; 95% CI: 0.6, 8.9; P = .03). Conclusion Improved oxygen saturation of asymmetric cortical veins detected using brain MRI with quantitative susceptibility mapping corresponded with better acute ischemic stroke outcomes for patients with asymmetrically prominent cortical veins that disappeared at 2-week follow-up MRI. © RSNA, 2021 Online supplemental material is available for this article.

Smoking-Induced Sex Differences in Clinical Outcomes in Patients Undergoing Mechanical Thrombectomy for Stroke

Ischemic stroke is the fifth leading cause of death in the United States. Smoking accelerates the onset of stroke by 10 years. The effects of smoking status on percent change in National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and edema volume were examined following mechanical thrombectomy for large vessel occlusion in patients with acute ischemic stroke. Subjects (N= 90; >18 years old) were divided into 3 groups based on smoking status: current smokers, previous smokers (defined as having quit >6 months before the ischemic event), and nonsmokers. Percent change in NIHSS score was defined as score at admission minus score at discharge divided by score at admission and was used as a predictor of functional outcome. Linear regression analysis was performed based on infarct or edema volume versus percent change in NIHSS score and separated by sex. Consistent with previous findings, smokers experienced a stroke 10 years earlier than nonsmokers (P= 0.004). Statistically significant linear regressions existed between infarct volume or edema volume in relation to worsening change in NIHSS score with female smokers only. Stroke-induced tissue damage, as measured by magnetic resonance imaging or computed tomography, was predictive of functional recovery only in female smokers. These findings are valuable for patient counseling, particularly for women, for smoking cessation.

Optimal thresholds to predict long-term outcome after complete endovascular recanalization in acute anterior ischemic stroke

BackgroundDespite complete endovascular recanalization, a significant percentage of patients with acute anterior stroke do not achieve a good clinical outcome. We analyzed optimal thresholds of relevant parameters to discern functional...

Effect of Endovascular Contact Aspiration vs Stent Retriever on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion

The benefits of endovascular revascularization using the contact aspiration technique vs the stent retriever technique in patients with acute ischemic stroke remain uncertain because of lack of evidence from randomized trials. To compare efficacy and adverse events using the contact aspiration technique vs the standard stent retriever technique as a first-line endovascular treatment for successful revascularization among patients with acute ischemic stroke and large vessel occlusion. The Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) study was a randomized, open-label, blinded end-point clinical trial conducted in 8 comprehensive stroke centers in France (October 2015-October 2016). Patients who presented with acute ischemic stroke and a large vessel occlusion in the anterior circulation within 6 hours of symptom onset were included. Patients were randomly assigned to first-line contact aspiration (n = 192) or first-line stent retriever (n = 189) immediately prior to mechanical thrombectomy. The primary outcome was the proportion of patients with successful revascularization defined as a modified Thrombolysis in Cerebral Infarction score of 2b or 3 at the end of all endovascular procedures. Secondary outcomes included degree of disability assessed by overall distribution of the modified Rankin Scale (mRS) score at 90 days, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, all-cause mortality at 90 days, and procedure-related serious adverse events. Among 381 patients randomized (mean age, 69.9 years; 174 women [45.7%]), 363 (95.3%) completed the trial. Median time from symptom onset to arterial puncture was 227 minutes (interquartile range, 180-280 minutes). For the primary outcome, the proportion of patients with successful revascularization was 85.4% (n = 164) in the contact aspiration group vs 83.1% (n = 157) in the stent retriever group (odds ratio, 1.20 [95% CI, 0.68-2.10]; P = .53; difference, 2.4% [95% CI, -5.4% to 9.7%]). For the clinical efficacy outcomes (change in NIHSS score at 24 hours, mRS score at 90 days) and adverse events, there were no significant differences between groups. Among patients with ischemic stroke in the anterior circulation undergoing thrombectomy, first-line thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful revascularization rate at the end of the procedure. clinicaltrials.gov Identifier: NCT02523261.

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.

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.

Internal Cerebral Vein Asymmetry on Follow-up Brain Computed Tomography after Intravenous Thrombolysis in Acute Anterior Circulation Ischemic Stroke Is Associated with Poor Outcome

Identifying early predictors of functional outcome after acute ischemic stroke (AIS) is important for planning rehabilitation strategies. Internal cerebral veins (ICV) drain deep parts of brain, run parallel to each other, and consistently seen on computed tomography angiography (CTA). Even minor asymmetry in their filling can be identified. We hypothesized that venous drainage would be impaired in patients with acute occlusion of internal carotid artery or middle cerebral artery. Because systemic thrombolysis can alter the vascular findings, we evaluated the relationship between ICV asymmetry on follow-up CTA and functional outcome. Consecutive AIS patients treated with intravenous thrombolysis between 2007 and 2010 were included. ICV asymmetry was assessed by 2 independent blinded stroke neurologists/neuroradiologists. Functional outcome was assessed by the modified Rankin Scale (mRS) at 3months, dichotomized as good (0-1) and poor (2-6). Data were analyzed for predictors of functional outcome. Of 2238 patients with AIS, 226 (10.1%) anterior circulation AIS patients received intravenous thrombolysis. The median age was 65years (range 19-92), 44% were men, and median National Institutes of Health Stroke Scale (NIHSS) score was 16 points (range 4-32). Hypertension was the commonest risk factor in 173 (76.5%) patients, whereas 78 (34.5%) had atrial fibrillation. ICV asymmetry on follow-up CTA was assessed in 103 (45.5%) patients. Admission NIHSS score (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.079-1.201, P=.046), change in NIHSS score during first 24hours (OR .737; 95% CI .672-.807, P<.0001), and ICV asymmetry on follow-up CTA (OR 20.3; 95% CI 4.67-52.07, P<.0001) independently predicted poor outcome at 3 months. ICV asymmetry on follow-up CTA after intravenous thrombolysis is an early predictor of poor functional outcome.

Persistence of Hyperdense Middle Cerebral Artery Sign on Follow-Up CT Scan after Intravenous Thrombolysis Is Associated with Poor Outcome

Background: The rates and extent of recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA) remain highly variable. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment unenhanced computerized tomography (CT) of the brain represents the presence of thrombus, often associated with severe neurological deficits and poor clinical outcome at 3 months. However, HMCAS is reliable only in AIS patients managed conservatively. In patients treated with systemic thrombolysis, HMCAS may disappear (representing clot dissolution) or persist (persisting clot) on the follow-up CT scan of the brain. We aimed at evaluating whether disappearance or the persistence of HMCAS on follow-up CT scan of the brain can predict the final outcome at 3 months. Methods: Data from consecutive AIS patients treated with IV-tPA, in a standardized protocol, from January 2007 to March 2010 were included in the prospective thrombolysis registry at our tertiary care center. For this evaluation, posterior circulation stroke was excluded. HMCAS was assessed on admission as well as follow-up CT by 2 independent stroke neurologists, blinded to the patient data or outcomes. Functional outcomes assessed by the modified Rankin Scale (mRS) at 3 months were dichotomized as good (mRS score 0–1) and poor (mRS score 2–6). The data were analyzed for the early predictors of poor functional outcome with SPSS version 19 for Windows. Results: Of the total of 2,238 patients admitted during the study period, 226 (11%) with anterior circulation AIS treated with intravenous thrombolysis were included. Median age of the patients was 65 years (range 19–92), 63% were males and they had a median National Institutes of Health Stroke Scale (NIHSS) score of 16 points (range 4–32). HMCAS was observed on admission CT scan in 109 (48.2%) patients and persisted on follow-up CT in 52 (47.7%) of them. Overall, 108 (47.8%) patients achieved poor functional outcome at 3 months. Admission NIHSS score (OR per 1-point increase = 1.241; 95% CI = 1.151–1.337, p < 0.0005), lesser change in NIHSS score at 24 h (OR per 1-point reduction = 0.730; 95% CI = 0.666–0.800, p < 0.0005) and persistence of HMCAS on follow-up CT scan (OR = 3.352; 95% CI = 1.991–11.333, p = 0.039) were associated with poor outcome at 3 months. Conclusion: Persistence of HMCAS on the follow-up CT scan of the brain in acute ischemic stroke patients treated with IV-tPA can be used as an early predictor of poor functional outcome.

DP-b99, a Membrane-Activated Metal Ion Chelator, as Neuroprotective Therapy in Ischemic Stroke

DP-b99 is a chelator of zinc and calcium ions that acts selectively within cell membranes and has neuroprotective properties in animal models of stroke. We present the results of a multicenter, double-blind, placebo-controlled, randomized trial to assess the safety and potential protective effects of DP-b99 in acute ischemic stroke. One hundred and fifty stroke patients with signs of cortical involvement and a National Institutes of Health Stroke Scale (NIHSS) score of 7 to 20 received a 4-day course of intravenous 1 mg/kg per day DP-b99 or placebo within 1 to 9 hours of stroke onset. Treatment with recombinant tissue plasminogen activator was not allowed. No major differences in mortality rate, causes of death, adverse events, safety laboratory tests, and ECG parameters were found between the 2 groups. The baseline NIHSS score of the 72 DP-b99- and 75 placebo-treated patients in the intent-to-treat cohort was (mean+/-SD) 12.2+/-4.0 and 12.6+/-3.3, respectively; the time to needle (mean+/-SD) was 6:36+/-1:47 and 6:28+/-1:33 hours, respectively; and the age (mean+/-SD) was 73.3+/-9.9 and 72.0+/-9.6 years, respectively. The 90-day median change from baseline (the primary end point) was -6.0 and -5.0 NIHSS points in the DP-b99 and placebo groups, respectively (nonsignificant). At 90 days, there was a significantly better outcome in the DP-b99 group compared with the placebo group (modified Rankin scale score of 0, 1, or same as prestroke): 30.6% and 16.0%, respectively (P=0.05). The recovery rate was unaffected by the time to needle. Further analyses indicated that the 90-day median change from baseline in patients with an entry NIHSS score of 10 to 16 was 8.0 and 5.0 points in the DP-b99 and placebo groups, respectively (P=0.03). In this small-scale study, the primary end point of change in NIHSS score from baseline to 90 days was not met. However, secondary end points demonstrated a significantly improved 90-day recovery rate with treatment with DP-b99 when compared with placebo. In addition, in patients with baseline NIHSS scores of 10 to 16, a significant post hoc change in NIHSS score from baseline to day 90 was observed. No major safety problems were identified. These findings need to be confirmed with a larger prospective study of strokes involving the cortex.

Size Matters

This study defines significant thrombolysis associated intracranial hemorrhage (ICH) by identifying an objective threshold volume that predicts clinical deterioration attributable to ICH. Prospectively collected clinical and radiographic information, from 103 consecutive patients who underwent intraarterial thrombolysis for acute ischemic stroke, was reviewed. Multiple paired comparisons between stratified hematoma volume and change in National Institutes of Health Stroke Scale (NIHSS) score by 24 to 36 hours and by time of hospital discharge was used to identify significant differences. Associations between hemorrhage volume and infarct volume in relation to clinical outcomes were examined. Rates of hemorrhagic transformation (HT), symptomatic hemorrhage, and parenchymal hematoma involving over 30% of the infarct were compared with hemorrhage volume. Multivariate regression analysis was used to determine the relationship between change in discharge NIHSS score and hemorrhage volume adjusting for known predictors of clinical outcomes. Multiple paired comparisons indicate that hemorrhage greater than 25 mL (HV25) had a more distinct impact on NIHSS score by time of hospital discharge than at 24 to 36 hours. Twenty-seven (26.2%) patients had HT and 12 (11.7%) had HV25. Among symptomatic hemorrhage, parenchymal hematoma involving over 30% of the infarct, and HV25, HV25 appeared more reflective of clinical deterioration from ICH. Hemorrhage volume increased with infarct volume but they were independently associated with change in NIHSS score on regression analysis. Clinical deterioration from ICH and ischemic injury are more effectively distinguished at time of hospital discharge. The authors propose to define significant hemorrhage associated with thrombolysis as hemorrhage volume greater than 25 mL.

Infrared Laser Therapy for Ischemic Stroke: A New Treatment Strategy

The NeuroThera Effectiveness and Safety Trial-1 (NEST-1) study evaluated the safety and preliminary effectiveness of the NeuroThera Laser System in the ability to improve 90-day outcomes in ischemic stroke patients treated within 24 hours from stroke onset. The NeuroThera Laser System therapeutic approach involves use of infrared laser technology and has shown significant and sustained beneficial effects in animal models of ischemic stroke. This was a prospective, intention-to-treat, multicenter, international, double-blind, trial involving 120 ischemic stroke patients treated, randomized 2:1 ratio, with 79 patients in the active treatment group and 41 in the sham (placebo) control group. Only patients with baseline stroke severity measured by National Institutes of Health Stroke Scale (NIHSS) scores of 7 to 22 were included. Patients who received tissue plasminogen activator were excluded. Outcome measures were the patients' scores on the NIHSS, modified Rankin Scale (mRS), Barthel Index, and Glasgow Outcome Scale at 90 days after treatment. The primary outcome measure, prospectively identified, was successful treatment, documented by NIHSS. This was defined as a complete recovery at day 90 (NIHSS 0 to 1), or a decrease in NIHSS score of at least 9 points (day 90 versus baseline), and was tested as a binary measure (bNIH). Secondary outcome measures included mRS, Barthel Index, and Glasgow Outcome Scale. Primary statistical analyses were performed with the Cochran-Mantel-Haenszel rank test, stratified by baseline NIHSS score or by time to treatment for the bNIH and mRS. Logistic regression analyses were conducted to confirm the results. Mean time to treatment was >16 hours (median time to treatment 18 hours for active and 17 hours for control). Time to treatment ranged from 2 to 24 hours. More patients (70%) in the active treatment group had successful outcomes than did controls (51%), as measured prospectively on the bNIH (P=0.035 stratified by severity and time to treatment; P=0.048 stratified only by severity). Similarly, more patients (59%) had successful outcomes than did controls (44%) as measured at 90 days as a binary mRS score of 0 to 2 (P=0.034 stratified by severity and time to treatment; P=0.043 stratified only by severity). Also, more patients in the active treatment group had successful outcomes than controls as measured by the change in mean NIHSS score from baseline to 90 days (P=0.021 stratified by time to treatment) and the full mRS ("shift in Rankin") score (P=0.020 stratified by severity and time to treatment; P=0.026 stratified only by severity). The prevalence odds ratio for bNIH was 1.40 (95% CI, 1.01 to 1.93) and for binary mRS was 1.38 (95% CI, 1.03 to 1.83), controlling for baseline severity. Similar results held for the Barthel Index and Glasgow Outcome Scale. Mortality rates and serious adverse events (SAEs) did not differ significantly (8.9% and 25.3% for active 9.8% and 36.6% for control, respectively, for mortality and SAEs). The NEST-1 study indicates that infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety and effectiveness is warranted.

Comparison of serum S-100 protein levels following stroke and traumatic brain injury

Temporal changes in serum S-100 protein levels were compared between patients with ischemic stroke, transient ischemic attack (TIA) and traumatic brain injury (TBI). In addition, S-100 levels were correlated with clinical severity and outcome. Measurements were done with a LIA-mat ® Sangtec ® 100 using an automated immunoluminometric assay. Serum S-100 was measured in 21 stroke patients, 18 TIA patients and ten TBI patients on days 1 (0–24 h), 2, 3, 4, 5 or 6 and 8 or 9. In a control group of 28 healthy volunteers one measurement was done. For the stroke and TIA patients, National Institutes of Health Stroke Scale (NIHSS) scores were obtained on admission and on day 10. For the TBI patients, Glasgow Coma Scale (GCS) scores were obtained on admission and Glasgow Outcome Scale (GOS) scores were obtained after 6 months. Changes in serum S-100 levels over the first 3 days were significantly different between stroke and TBI patients ( P=0.014) and between stroke and TIA patients ( P=0.006). Peak concentrations of S-100 were most often observed on day 3 or 4 after stroke and on day 1 or 2 after TBI. In the stroke patients individual S-100 peak levels correlated well with the NIHSS score on admission ( r=0.58 P=0.014) and the change in NIHSS score between day 10 and day 1 ( r=0.65, P=0.005). In the TBI patients a good correlation between individual peak levels of S-100 and the GCS score on admission ( r=−0.81, P=0.010) and the GOS score 6 months after the trauma was found ( r=−0.87, P=0.004). We conclude that there is a significant difference in temporal changes of S-100 levels between ischemic stroke and TBI patients. This suggests different pathophysiological mechanisms. The results of this study further confirm that peak levels of serum S-100 correlate with neurological deficit resulting from either stroke or TBI.