High glycemic variability: An underestimated determinant of stroke functional outcome following large vessel occlusion

Background and purposeEarly glycemic variability (GV) in diabetic patients is a poor prognosis factor following cardiovascular events. However, its influence on the course of acute ischemic stroke (AIS) with large vessel occlusion remains unclear. We investigated the relationship between high GV during acute stroke and three-month functional outcome among patients treated with combined intravenous thrombolysis and endovascular therapy for large vessel occlusion.MethodsA single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent thrombolysis and mechanical thrombectomy between January 2015 and May 2017. Early GV was assessed using standard deviation (SD) of blood glucose levels for the first 24 hours. The main outcome was functional status at three months as defined by the modified Rankin scale (mRS). Secondary outcomes were change in NIHSS score from baseline to 24 hours and occurrence of severe hemorrhagic transformation. Multivariate logistic regression analyses including GV, admission glycemia and mean glycemia were performed.ResultsAmong the 93 patients evaluated, 26 had early high GV (≥ 20.9 mg/dl). High GV was associated with poor functional outcome (OR = 8.00; 95%CI [1.34–47.89]; P = 0.02) unlike admission glycemia and mean glycemia (OR = 2.92; 95%CI [0.51–16.60]; P = 0.23 and OR = 0.36; 95%CI [0.05-2.6]; p = 0.31, respectively). High GV was not associated with NIHSS at 24 hours or hemorrhagic transformation.ConclusionAcute high GV contributes to poorer functional outcome following AIS related to large vessel occlusion and should be considered as a new target in acute stroke management.     

Direct admission of stroke in MRI room reduces in-hospital delays and improves recovery

PurposeEfficacy of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) is strongly time dependent in acute stroke management. We investigated the impact of a direct magnetic resonance imaging (MRI) room admission protocol in order to reduce in-hospital delays.MethodsWe implemented a protocol of direct MRI room admission, bypassing the Emergency Department. We compared in-hospital delays, clinical and functional outcomes using National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores, between patients hospitalized via this protocol and those admitted via the standard workflow and treated by IVT and/or MT. The primary endpoint was the proportion of patients with door-to-needle time (DTN) ≤ 60 minutes.ResultsAmong 308 consecutive patients included, 62 underwent direct MRI room admission. The proportion of patients with DTN ≤ 60 minutes was higher in the intervention group compared to the control group (82.5% vs. 17.8%, P < 0.001), and median DTN was lower (45 min vs. 75 min, P < 0.001). Despite a functional benefit at discharge on dichotomized mRS (mRS [0-2, as independence]: 66.1% vs. 51.2%, P = 0.003), the difference was no longer statistically significant at six months (68.4% vs. 57.4%, P = 0.10).ConclusionDirect MRI room admission of stroke alerts is associated with an important reduction of treatment times and improves functional outcomes.     

Clinical predictors for favorable outcomes from endovascular recanalization in wake-up stroke

Background and purposePatients who have acute stroke symptoms present on awakening are ineligible for standard intravenous thrombolysis due to the unclear onset time of symptoms. Some of these wake-up stroke (WUS) patients may benefit from endovascular recanalization. This study aimed to evaluate clinical predictors of outcomes from endovascular recanalization in WUS patients.MethodsForty-one WUS patients with internal carotid (ICA) or middle cerebral artery (MCA) occlusion treated with endovascular recanalization were reviewed. Regression analysis was performed to measure clinical predictors of outcomes from endovascular recanalization in WUS patients.ResultsThe mean initial NIHSS score was 16.41 ± 4.96 (5–24). The mean symptom recognition-to-door time (SRDT) was 108.85 ± 65.80 (19–230) min. Successful recanalization (TICI 2b-3) was achieved in 29 patients (70.7%). Thirty-four patients improved on NIHSS (amount 7.59 ± 4.84, range; 1–17) at 7 days after recanalization. At 90 days after recanalization, a mRS of ≤2 was achieved in 19 patients (46.3%) and a mRS of ≤3 was achieved in 24 patients (58.5%). No symptomatic intracerebral hemorrhage occurred. Multivariate regression analysis identified SRDT (P = 0.019), successful recanalization (P = 0.005), and hypertension (P = 0.013) were factors associated with an improvement of the NIHSS score. For a good functional outcome at 90 days, SRDT (P = 0.036) and initial NIHSS score (P = 0.016) were found to be significant predictors.ConclusionsThe results of this study suggest that the SRDT is an independent predictor of both an improvement of NIHSS score and a good functional outcome in endovascular recanalization for WUS patients.     

Oxfordshire Community Stroke Project classification but not NIHSS predicts symptomatic intracerebral hemorrhage following thrombolysis

BackgroundThe Oxfordshire Community Stroke Project (OCSP) classification is a simple tool to categorize clinical stroke syndromes. We compared the outcomes of stroke patients after intravenous thrombolysis stratified by the baseline National Institutes of Health Stroke Scale (NIHSS) score or by the OCSP classification.MethodsWe assessed the safety of thrombolysis in consecutive stroke patients who received intravenous thrombolysis within 3 h after onset. The patients were grouped by the NIHSS score into mild to moderate stroke (≤ 20) and severe stroke (> 20), and also by the OCSP classification as having total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), posterior circulation infarcts (POCI), or lacunar infarcts (LACI). Symptomatic intracerebral hemorrhage (SICH) was used as the primary outcome.ResultsOf the 145 patients included in the study, 45 had a baseline NIHSS score > 20. Their stroke syndromes were as follows: 78 with TACI, 29 with PACI, 16 with POCI, and 22 with LACI. The proportion of SICH was comparable between patients with high or low NIHSS score (11.1% vs. 9.0%, P = 0.690). The chance of SICH was highest in patients with TACI (15.4%), followed by LACI (4.5%), PACI (3.4%), and POCI (0%). After adjustment for age, baseline glucose, and use of antiplatelet agents before admission, SICH was significantly increased in patients with TACI relative to those with non-TACI (odds ratio 5.92; 95% confidence interval 1.24–28.33, P = 0.026).ConclusionsThe OCSP clinical classification may help clinicians evaluate the risk of SICH following intravenous thrombolysis.     

Impact of recanalisation by mechanical thrombectomy in mild acute ischemic stroke with large anterior vessel occlusion

BackgroundThe net clinical benefit of mechanical thrombectomy (MT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS–LVO) and mild neurological deficit is uncertain.AimsTo investigate efficacy and safety of MT in patients with acute AIS–LVO and mild neurological deficit by evaluating i) the influence of recanalisation on three-month outcome and ii) mortality, symptomatic intracerebral hemorrhage (sICH) and procedural complications.MethodsWe included consecutive patients with acute AIS–LVO and National Institute of Stroke Scale (NIHSS) score < 8, treated by MT at Lille University Hospital. Recanalisation was graded according to modified thrombolysis in cerebral infarction (mTICI) score, mTICI 2b/2c/3 being considered successful. We recorded procedural complications and classified intra-cerebral hemorrhages (ICH) and sICH according with European Cooperative Acute Stroke Study (ECASS) and ECASS2 criteria. Three-month outcome was evaluated by modified Rankin scale (mRS). Excellent and favourable outcomes were respectively defined as mRS 0–1 and 0–2 (or similar to pre-stroke).ResultsWe included 95 patients. At three months, 56 patients (59. 0%) achieved an excellent outcome and 69 (72, 6%) a favourable outcome, both being more frequent in patients with successful recanalisation than in patients without (excellent outcome 71, 1% versus 10, 5%, P < 0.001 and favourable outcome 82.9% versus 31.6%, P < 0.001). The difference remained unchanged after adjustment for age and pre-MT infarct volume. Similar results were observed in patients with pre-MT NIHSS ≤ 5. Death occurred in five patients (5.3%), procedural complications in 12 (12.6%), any ICH in 38 (40.0%), including 3 (3.2%) sICH.ConclusionsAchieving successful recanalisation appears beneficial and safe in acute AIS–LVO patients with NIHSS < 8 before MT.     

Prediction of favorable outcome by percent improvement in patients with acute ischemic stroke treated with endovascular stent thrombectomy

Our objective was to investigate a method for assessing early improvement and its predictive value for 3-month functional outcome in patients treated with EST. A total of 97 consecutive AIS patients undergoing EST were prospectively collected and retrospective reviewed. Data on demographics, vascular risk factors, admission National Institutes of Health Stroke Scale (NIHSS) score, 24-h NIHSS score, reperfusion and collateral formation were collected. Percent improvement was defined as ([baseline NIHSS score − 24-h NIHSS score]/baseline NIHSS score × 100%), while absolute improvement was calculated by the difference between scores (baseline NIHSS score − 24-h NIHSS score). A 3-month functional outcome was assessed using the modified Rankin Scale (mRS). Favorable outcome was defined as a mRS score of 0–2. Areas under the receiver-operating characteristic (ROC) curve (AUC) for percent improvement and absolute improvement in predicting favorable outcome was compared. Finally, we investigated the independent predictors of improvement at 24 h after EST and its relationship with favorable outcome. Pairwise comparison of ROC curves revealed that percent improvement had larger AUC than absolute improvement (p = 0.004). Rapid neurological improvement (RNI), defined as percent improvement ⩾30%, was a powerful predictor of favorable outcome (odds ratio [OR] 7.63, confidence interval [CI]: 2.65–21.96; p < 0.001). Good collaterals (OR 2.86; 95% CI: 1.11–7.38; p = 0.030) and short onset-to-reperfusion time (ORT) (OR 3.02, 95% CI: 1.17–7.80; p = 0.022) were independent predictors of RNI. RNI predicted 3-month favorable outcome in AIS patients treated with EST. Good collaterals and short ORT are independent predictors of RNI.     

Feasibility and outcomes of intravenous thrombolysis 3–4.5 hours after stroke in Chinese patients

The time window for intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke (AIS) patients has been extended to 4.5 hours. But little is known about the safety and efficacy of IV rt-PA treatment in the 3–4.5 hour time window in Chinese patients with AIS. A total of 119 patients who were treated with standard IV rt-PA therapy within 4.5 hours after symptom onset were included in this study: 85 were treated within 0–3 hours and 34 were treated within 3–4.5 hours. Favorable outcome was defined as a modified Rankin scale (mRS) score of 0–1 at 6 months. The safety of IV rt-PA treatment was assessed by the rate of mortality, symptomatic intracerebral hemorrhage (SICH) and other common complications. There were no significant differences in SICH rates (2.94% versus 2.35%; p = 0.85) at 24–36 hours, mortality (5.88% versus 3.53%; p = 0.56), other complications (14.71% versus 11.76%; p = 0.66), National Institutes of Health Stroke Scale (NIHSS) score improvement at 24 hours (41.18% versus 45.88%; p = 0.64) and favorable mRS at 6 months (52.94% versus 54.12%; p = 0.91) between the two time window groups. Multivariate analysis showed that advanced age, lower admission NIHSS score and shorter time from symptom onset to treatment were associated with a favorable clinical outcome. This finding showed an additional 29% of patients received IV rt-PA because of the treatment window expansion to 4.5 hours. IV rt-PA was feasible and safe for treating AIS patients in the 3–4.5 hour time window in our Chinese population.     

Thrombolysis safety and effectiveness in acute ischemic stroke patients with pre-morbid disability

IntroductionRecombinant tissue plasminogen activator (rt-PA) is the first-line therapy demonstrated to be safe and effective in acute ischemic stroke. People with pre-existing severe dementia or physical disability are usually excluded from rt-PA. The aim of our study was to investigate rt-PA safety and effectiveness in acute stroke with pre-existing disability (mRS ≥ 2).MethodsThe study encompassed 35 acute ischemic stroke patients with mRS ≥ 2 treated with rt-PA. In order to assess the differences in clinical outcome in three disability groups (mRS = 2; 3; 4/5), the following parameters were evaluated: intracerebral hemorrhage, mortality, NIHSS, ΔNIHSS and mRS.ResultsBaseline-NIHSS and age were not significantly different among groups. Mortality was higher in the pre-morbid mRS 4/5 group (44%) than in the pre-morbid mRS 2 (16.7%) and mRS 3 groups (21.4%). In survived patients, median ΔNIHSS% was higher in the mRS 2 and 3 groups (-63.3% and −92.3%, respectively) than in the mRS 4/5 group (−9.1%). The 247 rt-PA treated subjects with mRS < 2 in the same period showed lower mortality rate (4.7%), lower sICH (5%), lower mRS at discharge (median 1; range 0–6) and similar ΔNIHSS% (−75%).ConclusionPatients with mRS 2 and 3 may benefit from rt-PA with a moderate risk of sICH and mortality.     

Estimated number of eligible patients for mechanical thrombectomy based on NIHSS and population-based Brest stroke registry

BackgroundSince 2015, mechanical thrombectomy (MT) is indicated as a treatment for patients with large vessel occlusion (LVO) at the acute phase of ischemic stroke. However, the number of stroke patients eligible for MT is poorly known.ObjectiveThe objective of our study was to estimate the number of patients eligible for thrombectomy within the first 24 hours of an ischemic stroke, based on the clinical National Institute of Health Stroke Scale (NIHSS).MethodOur study concerned all ischemic strokes which occurred between January 2013 and December 2016 recorded in the population-based Brest Stroke Registry (BSR). Based on positive predictive value and negative predictive value from articles evaluating the performance of a defined NIHSS threshold to identify LVO, we first estimated the frequency of patients with LVO and then the frequency of patients eligible for MT depending on pre-stroke modified Rankin score (mRS). Our results were extrapolated to regions of metropolitan France. Two scenarios were considered: one called “stringent criteria” with mRS ≤ 1 and one called “real-life” criteria with mRS ≤ 2.ResultWe analyzed data from 2,025 ischemic strokes with symptom onset ≤ 24 hours. No statistical difference between patient characteristics according to the time of hospital admission (≤ 6H vs. 6–24H) was observed. Based on NIHSS scores, between 23.90% and 44.20% of ischemic strokes admitted within the first six hours had LVO clinical characteristics. Among them, 14.53% to 26.87% met the ``stringent eligibility'' criteria for MT and 16.9 to 31.25% for ``real-life'' criteria. Eligible patients represented 6.32% to 11.70% of all ischemic strokes, irrespective of admission time. In France, 75 to 162 persons per million inhabitants per year were eligible for endovascular therapy, depending on including criteria. Based on activity levels recorded by the French Neuroradiology Society (SFNR) in 2018, the estimated needed increase in MT showed a heterogeneous pattern region-by-region, with the greatest need in Brittany, Pays de la Loire, and Corsica.ConclusionBased on NIHSS, our study provides coherent information concerning the estimated number of MT procedures to be performed in France: 4,877 to 10,494 ischemic strokes would be eligible each year in metropolitan France compared to the 6,596 thrombectomy procedures actually performed in 2018. Depending on the region, an estimated 10–20% to 90–100% increase in MT activity would be necessary to meet patient needs. These data suggest that there is still room for improvement in thrombectomy activity, particularly in certain regions of France, to allow equal access to MT to the entire French population.     

External validation of the ability of the DRAGON score to predict outcome after thrombolysis treatment

Easy-to-perform and valid assessment scales for the effect of thrombolysis are essential in hyperacute stroke settings. Because of this we performed an external validation of the DRAGON scale proposed by Strbian et al. in a Danish cohort. All patients treated with intravenous recombinant plasminogen activator between 2009 and 2011 were included. Upon admission all patients underwent physical and neurological examination using the National Institutes of Health Stroke Scale along with non-contrast CT scans and CT angiography. Patients were followed up through the Outpatient Clinic and their modified Rankin Scale (mRS) was assessed after 3 months. Three hundred and three patients were included in the analysis. The DRAGON scale proved to have a good discriminative ability for predicting highly unfavourable outcome (mRS 5–6) (area under the curve-receiver operating characteristic [AUC-ROC]: 0.89; 95% confidence interval [CI] 0.81–0.96; p < 0.001) and good outcome (mRS 0–2) (AUC-ROC: 0.79; 95% CI 0.73–0.85; p < 0.001). When only patients with M1 occlusions were selected the DRAGON scale provided good discriminative capability (AUC-ROC: 0.89; 95% CI 0.78–1.0; p = 0.003) for highly unfavourable outcome. We confirmed the validity of the DRAGON scale in predicting outcome after thrombolysis treatment.     

Direct access to a hospital offering intravenous thrombolysis therapy improves functional outcome of acute ischemic stroke patients

Referral from other hospitals is one of the primary causes of delayed thrombolysis therapy after acute ischemic stroke (AIS). We aimed to evaluate whether direct access to a hospital offering intravenous thrombolysis therapy was associated with good functional outcome in AIS patients treated with thrombolysis. We enrolled patients who received intravenous thrombolysis within 3 hours of symptom onset at our stroke center. We divided these patients into two groups: those with a direct admission to our stroke center and those with indirect admission by referral from other community hospitals. We investigated onset-to-door time and onset-to-recombinant tissue plasminogen activator (rtPA) time according to admission mode. We then assessed the association between a direct admission and favorable outcome at 90 days. A total of 232 patients (mean age of 66.6 years, median National Institutes of Health Stroke Scale score of 10) were included. A total of 48.7% of AIS patients treated with intravenous thrombolytic therapy were transferred from other hospitals. Patients who were directly admitted to our stroke center had a shorter onset-to-door time (61 versus 120 minutes, p < 0.001) and onset-to-rtPA time (103 versus 155 minutes, p < 0.001) than those referred from other hospitals. Direct admission was associated with a good outcome with an odds ratio of 2.03 (95% confidence interval 1.051–3.917, p = 0.035), after adjusting for baseline variables. Thrombolysis after direct admission to a hospital offering intravenous thrombolysis therapy could shorten onset-to-rtPA time and improve stroke outcome in patients with AIS.     

Trombectomía mecánica más allá de 6 horas en ictus isquémico agudo con oclusión de gran vaso en territorio carotídeo: experiencia en un hospital terciario

IntroductionThrombectomy in the carotid artery territory was recently shown to be effective up to 24 hours after symptoms onset.MethodsWe conducted a retrospective review of a prospective registry of patients treated at our stroke reference centre between November 2016 and April 2019 in order to assess the safety and effectiveness of mechanical thrombectomy performed beyond 6 hours after symptoms onset in patients with acute ischaemic stroke and large vessel occlusion in the carotid artery territory.ResultsData were gathered from 59 patients (55.9% women; median age, 71 years). In 33 cases, stroke was detected upon awakening; 57.6% of patients were transferred from another hospital. Median baseline NIHSS score was 16, and median ASPECTS score was 8, with 94.9% of patients presenting > 50% of salvageable tissue. Satisfactory recanalisation was achieved in 88.1% of patients, beyond 24 hours after onset in 5 cases. At 90 days of follow-up, 67.8% were functionally independent; those who were not were older and presented higher prevalence of atrial fibrillation, greater puncture-to-recanalisation time, and higher NIHSS scores, both at baseline and at discharge.ConclusionIn our experience, mechanical thrombectomy beyond 6 hours was associated with good 90-day functional outcomes. Age, NIHSS score, puncture-to-recanalisation time, and presence of atrial fibrillation affected functional prognosis. The efficacy of the treatment beyond 24 hours after onset merits study.     

IV t-PA therapy in acute stroke patients with atrial fibrillation

Background and purposeAtrial fibrillation (AF) is a predictor for severe stroke. Intravenous administration of tissue plasminogen activator (t-PA) can improve clinical outcomes in patients with acute ischemic stroke. We investigated clinical characteristics and patient outcome in patients with and without AF after t-PA therapy.MethodsConsecutive ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. MRI examinations, including diffusion weighted imaging and MRA, were performed before t-PA thrombolysis. NIHSS scores were obtained before and 7 days after t-PA infusion. The patients were divided into two groups (AF group and Non-AF group). Their clinical characteristics and outcome 7 days and 3 months after t-PA therapy were compared.Results85 patients (56 males, mean age, 73.4 ± 11.5 years) were enrolled in the present study. The AF-group had 44 patients, and the Non-AF group had 41 patients. Fewer patients with AF had dramatic improvement at 7 days and favorable outcome (mRS 0–1) at 3 months after t-PA therapy than patients without AF (31.8% vs. 61.0%, P = 0.007, and 15.9% vs. 46.3%, P = 0.002). On the other hand, worsening at 7 days and poor outcome (mRS > 3 and death) at 3 months after t-PA therapy were more frequently observed in AF group than Non-AF group (22.7% vs. 9.8%, P = 0.107, and 70.5% vs. 41.5%, P = 0.007). After adjusting age and gender, patients with AF more frequently had worsening and poor outcome than those without AF (adjusted OR; 4.54, 95% CI 1.04–19.75, P = 0.044, and adjusted OR; 2.8, 95% CI 1.10–7.28, P = 0.032).ConclusionThe present study found that acute ischemic stroke patients with AF more frequently had poor outcome after IV-t-PA therapy compared with those without AF.     

Intravenous alteplase for Chinese patients with stroke and borderline eligibility

Lack of efficacy and safety data among Chinese patients with stroke have contributed to the slow development of stroke thrombolysis as standard-of-care for these patients. We examined a retrospective cohort of 57 patients who received intravenous alteplase for acute ischemic stroke to identify predictors of outcome, including age, stroke severity, onset-to-treatment time, and early ischemic changes on brain CT scan. Overall, the mean National Institute of Health Stroke Scale (NIHSS) score was 15.7 and the mean onset-to-treatment time was 142 minutes. Twenty-nine (51%) patients had a favorable outcome with modified Rankin Scale (mRS) score of ?2 at three months. Ten (17.5%) patients were deceased at three months. Four (7%) patients developed symptomatic intracranial hemorrhage (sICH). For patients aged >80 years (n = 18), five (28%) achieved favorable outcome, six (33%) were deceased at three months and three (17%) had sICH. Prognosis was worst for patients with NIHSS score >25 (n = 5); one (20%) was dependent (mRS 4) and the other four (80%) were deceased. Multivariate analysis found that the Alberta Stroke Program Early CT Score (ASPECTS) was associated with favorable outcome (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1–3.0), and mortality (OR 0.5, 95% CI 0.3–0.9). Our findings showed advanced age and severe stroke were associated with less favorable outcome in Chinese patients receiving intravenous alteplase, ASPECTS can be used reliably to identify patients at risk of poor outcomes. Further studies are warranted.     

A randomized pilot study of patients with tandem carotid lesions undergoing thrombectomy

Background and purposeThe optimal management of patients with tandem lesions (TL), or cervical internal carotid artery (c-ICA) steno-occlusive pathology and ipsilateral intracranial occlusion, who are undergoing endovascular thrombectomy (EVT) remains unknown. We sought to establish the feasibility of a trial designed to address this question.Materials and methodsThe Endovascular Acute Stroke Intervention (EASI) study was a single-centre randomized trial comparing EVT to medical therapy for large-vessel occlusion stroke. Patients with TL receiving EVT were randomly allocated to acute c-ICA stenting or no stenting. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0–2 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) at 24 hours and mortality at 90 days.ResultsOf 301 patients included in EASI between 2013 and 2018, 24 (8.0%) with TL were randomly allocated to acute stenting (n = 13) or no stenting (n = 11). Baseline characteristics were balanced. Eight (61.5%; 95% CI 35.5%–82.3%) and 7 (63.6%; 95% CI 35.4%–84.9%) patients, respectively, had a favorable outcome (mRS 0–2; P = 1.0). One non-stented patient had a symptomatic intracerebral hemorrhage.ConclusionsThis pilot trial of patients with TL undergoing EVT suggests that a sufficiently powered larger TL trial comparing acute c-ICA stenting to no stenting is feasible.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02157532.     

Leukoaraiosis and earlier neurological outcome after mechanical thrombectomy in acute ischemic stroke

Background and purposeThe aim of the study was to evaluate whether leukoaraiosis (LA) severity is associated with earlier neurological outcome in acute stroke patients undergoing mechanical thrombectomy.Materials and methodsIn this retrospective multicenter study, we evaluated 273 acute stroke patients treated with mechanical thrombectomy. LA severity was graded as 0–2 (absent-to-moderate) versus 3–4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of early neurological improvement and early neurological deterioration. Early neurological improvement was defined as a decrease of ≥ 4 points on the NIHSS, or an NIHSS score of zero 24 hours after baseline assessment. Early neurological deterioration was defined as an increase of ≥ 4 points on the NIHSS 24 hours after baseline assessment.ResultsThere was a significantly lower early neurological improvement rate (17.1% versus 39.2%; P = 0.006) and non-significantly higher early neurological deterioration rate (29.3% versus 17.7%; P = 0.084) in patients with severe LA (sLA) compared with patients with absent-to-moderate LA. In multivariable analysis, sLA was inversely associated with early neurological improvement (OR, 0.31; 95% CI, 0.13–0.78; P = 0.012). There was no significant association of sLA with early neurological deterioration. However, in patients without symptomatic intracranial hemorrhage, sLA was an independent predictor of early neurological deterioration (OR, 2.65; 95% CI, 1.09–6.45; P = 0.032).ConclusionssLA is a significant negative predictor of early neurological improvement and is an independent predictor of early neurological deterioration in patients without symptomatic intracranial hemorrhage.     

Efficacy and safety of different doses of intravenous tissue plasminogen activator in Chinese patients with ischemic stroke

Intravenous tissue plasminogen activator (tPA) at 0.9 mg/kg improves outcome in acute ischemic stroke. The dose response to tPA may be different in Chinese patients compared with Western populations, but this has not been systematically examined. We aimed to compare the efficacy and safety of different doses of tPA in Chinese stroke patients. We included all acute ischemic stroke patients treated with tPA within 4.5 hours of onset. Patients were treated with three dose regimens of tPA (0.6–0.7 mg/kg, 0.8 mg/kg, 0.9 mg/kg). The following data were collected: patient demographics; vascular risk factors; neuroimaging results; time of tPA administration; clinical assessment before treatment, at 24 hours and 3 months; and modified Rankin Scale (mRS) score at 3 months. A total of 105 patients with stroke of Han Chinese origin were included in the study. The baseline characteristics of the three dose groups were well matched. In the 0.9 mg/kg group (n = 51), 51.1% had favorable outcome at 3 months, compared with 38.7% of patients in the 0.8 mg/kg group (n = 31) (odds ratio [OR] to 0.9 mg/kg group, 0.57; 95% CI, 0.19–1.73; p = 0.32) and 34.8% in the 0.6–0.7 mg/kg group (n = 23) (OR to 0.9 mg/kg group, 0.31; 95% CI, 0.08–1.16; p = 0.08). There were no statistically significant differences in the incidence of symptomatic intracerebral hemorrhage and mortality rate. There was a higher proportion of patients with good functional outcomes in the 0.9 mg/kg group. Although not significant, these results strongly support the feasibility and urgent need for a dose ranging trial to establish an optimal tPA dose in Chinese stroke patients.     

Cerebral venous sinus thrombosis in pregnancy and puerperium: A pooled,systematic review

Pregnancy and puerperium are risk factors for cerebral venous sinus thrombosis (CVST); however studies describing diagnosis and management in this population are limited. The objective of this study was to amalgamate published case reports and series regarding diagnosis and management of CVST in pregnancy and puerperium. Searches of PubMed and the Cochrane library were performed using search terms “pregnancy”/“puerperium” and “sinus occlusion”/“sinus thrombosis”. Studies were included in our pooled analysis if they included individual patient symptoms, management approach and follow-up condition. Multivariate regression was utilized to assess the effect of non-modifiable factors on excellent outcome (mRS 0). Sixty-six patients were included. Mean duration of symptom onset to diagnosis was 5.9 days (95% CI 4.2–7.6). Clot involvement of the superior sagittal sinus was seen in 67% of cases, the transverse/sigmoid in 64% and of the deep venous system in 15% of cases. Management approaches included anticoagulation (91% of patients), IA (intra-arterial) thrombolysis alone (26%), and IA thrombectomy with IA thrombolysis (8%). Fifty-nine percent of patients were mRS 0 at follow-up; 94% were mRS 0-2. Presentation with headache alone was associated with excellent outcome on multivariate analysis (p = 0.04); coma/obtundation predicted against excellent outcome (p = 0.03). As compared to IA thrombolysis alone, patients undergoing IA thrombolysis with IA thrombectomy demonstrated a trend toward better outcome (p = 0.10).     

Direct admission to stroke centers reduces treatment delay and improves clinical outcome after intravenous thrombolysis

We aimed to examine whether direct access to hospitals offering intravenous thrombolysis is associated with functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. We enrolled patients who received intravenous thrombolysis within 4.5 hours of symptom onset using a prospective multicenter registry database. Patients referred directly from the field to organized stroke centers were compared with those who were transferred from non-thrombolysis-capable hospitals in terms of clinical outcomes at 90 days after intravenous recombinant tissue plasminogen activator treatment. We also investigated onset-to-door time and onset-to-needle time according to admission mode. A total of 820 patients (mean age of 67.3 years and median National Institutes of Health Stroke Scale score of 9) were enrolled. Seventeen percent of patients with AIS who received intravenous thrombolytic therapy at 12 hospitals (n = 142) were transferred from other hospitals. The direct admission group had a shorter median onset-to-admission time (63 versus 121 minutes, P < 0.001) and onset-to-needle time (110 versus 161 minutes, P < 0.001) as compared with the indirect admission group. Direct admission was associated with a good outcome with an odds ratio of 1.57 (95% confidence interval: 1.02–2.39, P = 0.036) after adjustment for baseline variables. Direct admission to a hospital with intravenous thrombolysis facilities available at all times was associated with shorter onset-to-needle time and better outcome in patients with AIS undergoing thrombolytic therapy. Our findings support the implementation of regional stroke care programs transporting patients directly to stroke centers to promote faster treatment and to achieve better outcomes.     

Shorter time to intervention improves recanalization success and clinical outcome post intra-arterial intervention for basilar artery thrombosis

Basilar artery thrombosis is associated with poor clinical outcomes and high mortality rate if untreated. Clinical outcome correlates with recanalization success. As arterial clot composition undergoes organization over time and may become more resistant to recanalization therapy, we postulate that recanalization success is time-dependent. We aim to investigate whether time to intervention predicts recanalization success leading to improved clinical outcomes. Forty-nine consecutive patients with basilar artery thrombosis treated with intra-arterial (IA) therapy between 1993 and 2011 were included. Patient demographics, clinical features, clot location, time to intervention and post-procedural thrombolysis in myocardial infarction (TIMI) scores were collected. Recanalization success was defined as a score of TIMI 2–3. Clinical outcome was measured using the 90-day modified Rankin Scale (mRS) score, with good neurological outcome defined as mRS 0–2. The mean patient age was 59.8 years ± 17.9 and 36.7% were females. IA therapy was commenced within 6 hours of stroke onset in 17/49 (34.7%) patients. Of this 6-hour onset group, 17/17 (100%) demonstrated recanalization success (TIMI 2–3) and 10/17 (58.8%) achieved good neurological outcome at 90-days. IA therapy was commenced after 6 hours of stroke onset in 32/49 (65.3%) patients, with 24/32 (75%) and 6/32 (18.75%) patients achieving recanalization success and good outcome, respectively. A shorter delay to IA therapy is significantly associated with recanalization success (p = 0.038) and good neurological outcome at 90 days (p = 0.009) in patients with acute basilar artery thrombosis. We recommend a systematic approach to minimize time delay to IA therapy for this condition.