Preclusion of ischemic stroke patients from intravenous tissue plasminogen activator treatment for mild symptoms should not be based on low National Institutes of Health Stroke Scale Scores.

Intravenous tissue plasminogen activator (IV tPA) improves neurologic outcome after stroke, but is not recommended for patients with minor neurologic deficits commonly classified by a lower cutoff on the National Institutes of Health Stroke Scale (NIHSS). Because not all stroke signs are captured on the NIHSS, the use of a strict cutoff may exclude functionally impaired stroke patients from IV tPA treatment. We described functional impairment, safety, and clinical outcome in patients derived from our hospital thrombolysis database who had stroke that was considered disabling despite a neurologic deficit that was considered mild. We used 2 cutoffs: NIHSS score ≤ 4 and ≤ 3. Functional impairment was assessed with the modified Rankin Scale (mRS). Between 2008 and 2011, a total of 670 acute ischemic stroke patients received IV tPA in our institution. 107 (16%) of these patients presented with a NIHSS score ≤ 4; 65 (10%) patients presented with a NIHSS score ≤ 3. All of these patients were considered functionally impaired (mRS score ≥ 2). The most frequent symptoms were language impairment (two-thirds), distal (hand) paresis (one-third), and gait disorder in both groups. Symptomatic intracerebral hemorrhage occurred in 1 patient with a NIHSS score of 4 (1%). Despite IV tPA therapy, 26% had a nonfavorable outcome (mRS score 0-1) after 3 months, and 52% had persisting symptoms in both groups. Language impairment, distal (hand) paresis, and gait disorder are common disabling deficits in patients with low NIHSS scores. Judgment of whether a stroke is disabling should not be based on the NIHSS score but on the assessment of the individual neurologic deficits and their impact on functional impairment.

Wendt M ，Tütüncü S ，Fiebach JB ，Scheitz JF ，Audebert HJ ，Nolte CH ... -  《-》

Aphasia predicts unfavorable outcome in mild ischemic stroke patients and prompts thrombolytic treatment.

Patients with an acute ischemic stroke rated as mild, and for this reason not submitted to thrombolysis, have an unfavorable outcome in a non-negligible proportion. Whether selective presentation features help identify those at risk of bad outcome, and whether it could be recommended to treat only patients with such features, is poorly elucidated. We report our experience based on retrospective evaluation of a consecutive series of patients scoring 6 or less on baseline National Institutes of Health Stroke Scale (NIHSS), some of whom received thrombolysis. From the prospective Careggi Hospital Stroke Registry, Florence, Italy, we selected a series of patients who fulfilled the following criteria: (1) screening for treatment within 3 hours of symptom onset; (2) mild symptoms, defined as a score of 6 or less on NIHSS, with or without rapid improvement; (3) no other reason for exclusion from thrombolysis; (4) no previous disability; and (5) admission to the stroke unit. We choose a modified Rankin scale score of less than 2 to define a good 3-month functional outcome. We studied as potential outcome predictors: age, baseline NIHSS score, isolated aphasia, motor impairment with or without aphasia, thrombolysis, previous stroke or transient ischemic attack, and interactions between each of these factors and thrombolysis. Between February 2004 and June 2011, 128 patients fulfilled the selection criteria: 47 (36.7%) received tissue plasminogen activator, 81 (63.3%) did not. At 3 months, of the 81 patients not receiving tissue plasminogen activator, 14 (17.3%) had an unfavorable outcome, compared with 6 (12.8%) among the 47 treated. Hemorrhagic complications or death occurred in neither group. Adjusting for major confounders and for thrombolysis, the presence of aphasia on early assessment proved the only independent predictor of worse outcome. NIHSS score variation showed no effect. Aphasia is an early marker of unfavorable outcome in mild ischemic stroke patients. In these patients thrombolysis should be considered beyond the NIHSS scoring.

Nesi M ，Lucente G ，Nencini P ，Fancellu L ，Inzitari D ... -  《-》

Tissue plasminogen activator thrombolytic therapy for acute ischemic stroke in 4 hospital groups in Japan.

In October 2005 in Japan, the recombinant tissue plasminogen activator (tPA) alteplase was approved for patients with acute ischemic stroke within 3 hours of onset at a dose of 0.6 mg/kg. The present study was undertaken to assess the safety and efficacy of alteplase in Japan. Between October 2005 and December 2009, a total of 114 consecutive patients admitted to 4 hospitals received intravenous tPA within 3 hours of stroke onset. Clinical backgrounds and outcomes were investigated. The patients were divided into 2 chronological groups: an early group, comprising 45 patients treated between October 2005 and December 2007, and a later group, comprising 69 patients treated between January 2008 and December 2009. The mean time from arrival at the hospital to the initiation of treatment was significantly reduced in the later group, from 82.6 minutes to 70.9 minutes. Intracerebral hemorrhage (ICH) occurred in 26 patients (22.8%); compared with patients without ICH, these patients had a significantly higher prevalence of cardiogenic embolism (88.5% vs 58.0%); greater warfarin use (26.8% vs 6.8%); higher mean National Institutes of Health Stroke Scale (NIHSS) scores on admission (16 vs 10), at 3 days after admission (14 vs 5), and at 7 days after admission (13.5 vs 3); and a lower Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score (7.8 vs 9.1). Patients who received edaravone had a higher prevalence of cardiogenic embolism (70.9% vs 36.4%), a higher recanalization rate (77.7% vs 36.4%), and lower NIHSS scores on admission and at 3 and 7 days after admission compared with those who did not receive edaravone. Our data suggest that administration of intravenous alteplase 0.6 mg/kg within 3 hours of stroke onset is safe and effective, that the NIHSS and Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score are useful predictors of ICH after tPA administration, and that warfarin-treated patients are more likely to develop symptomatic ICH despite an International Normalized Ratio <1.7.

Kono S ，Deguchi K ，Morimoto N ，Kurata T ，Deguchi S ，Yamashita T ，Ikeda Y ，Matsuura T ，Narai H ，Omori N ，Manabe Y ，Yunoki T ，Takao Y ，Kawata S ，Kashihara K ，Abe K ... -  《-》

Validation of FLAIR hyperintense lesions as imaging biomarkers to predict the outcome of acute stroke after intra-arterial thrombolysis following intravenous tissue plasminogen activator.

Intravenous tissue plasminogen activator (tPA) given within 4.5 h of symptom onset is accepted as the standard treatment of ischemic stroke. Persistent occlusion of cerebral arteries despite intravenous thrombolysis and unremitting neurologic deficits lead us to consider additional intra-arterial approaches. The aim of this study was to elucidate the potential of fluid-attenuated inversion recovery (FLAIR) MRI performed during or immediately after intravenous thrombolysis for predicting clinical outcomes of subsequent intra-arterial thrombolysis. With a prospective stroke registry database of patients hospitalized in our institution from January 2004 to February 2010, we identified ischemic stroke patients with the following conditions: (1) presentation within 2.5 h of onset, (2) treated with intravenous tPA based on brain CT, (3) persistent occlusion on subsequent MRI/MR angiography, including a FLAIR sequence, and (4) eventually treated with intra-arterial thrombolysis. Demographic, clinical and laboratory findings including initial National Institutes of Health Stroke Scale (NIHSS), follow-up NIHSS at the 7th day or discharge, modified Rankin scale (mRS) score at 3 months, and symptomatic hemorrhagic transformation were captured. FLAIR images were reviewed by 2 investigators blinded to clinical information independently and dichotomized into the absence and presence of FLAIR change within the diffusion-restriction lesions. Of the 57 patients who met these conditions, FLAIR-hyperintense lesions (FHL) were observed in 32 (56.1%). The FHL-negative group was 69.1 ± 12.1 years old on average and the FHL-positive group 67.3 ± 11.0 years old. In both groups, hypertension was the most common vascular risk factor, cardioembolic stroke was the most common subtype, and distal middle cerebral artery was the most common site of occlusion. The incidence of symptomatic hemorrhagic transformation was 4.0% in the FHL-negative group and 9.4% in the FHL-positive group (p = 0.62). NIHSS scores of 0-1 on the 7th day of hospitalization or at discharge were observed in 36% of the FHL-negative group and in 9.4% of the FHL-positive group; mRS scores of 0-1 at 3 months was 32% in the FHL-negative group and 21% in the FHL-positive group. An ordinal logistic regression analysis showed that the presence of FHL was associated with higher 7-day NIHSS scores (adjusted for relevant covariates) but not with higher 3-month mRS scores. This study suggests that the FHL might be used as imaging biomarker to predict outcomes for additional intra-arterial thrombolysis in patients treated with intravenous tPA.

Chung JW ，Kim KJ ，Noh WY ，Jang MS ，Yang MH ，Han MK ，Kwon OK ，Jung C ，Kim JH ，Oh CW ，Lee JS ，Lee J ，Bae HJ ... -  《-》

Large-Vessel Occlusion Stroke: Effect of Recanalization on Outcome Depends on the National Institutes of Health Stroke Scale Score.

Arterial recanalization is currently considered the main standard of successful early management of acute ischemic stroke. Intravenous (IV) thrombolysis with tissue plasminogen activator (tPa) is the only Food and Drug Administration-approved medical treatment. Large-vessel occlusion, estimated to account for up to 40% of all acute ischemic strokes, is often refractory to IV thrombolysis and is associated with a poor patient outcome. Mechanical recanalization procedures are therefore increasingly used in the treatment of large-vessel occlusion refractory to, or presenting outside the accepted time window for, IV thrombolysis. The aim of this study was to investigate the effect of early vessel recanalization on clinical outcome in patients with large-vessel occlusion stroke. This is a single-center cohort study, analyzing prospectively collected data on 152 patients with large-vessel occlusion and acute ischemic stroke. Seventy-one patients received endovascular treatment (of whom 57.7% also received IV tPA), and 81 (55.6% of whom also received IV tPa) were not treated with endovascular therapy. Clinical outcome was compared for 2 cohorts: patients who recanalized (n = 46) and patients with persisting large-vessel occlusion (n = 106). Early recanalization was an independent predictor of a good clinical outcome in only those patients who presented with a severe ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score >15; P = .017). This was not the case for less severe strokes (NIHSS score ≤ 15) where recanalization did not lead to more patients with functional independence at 90-day follow-up (P = .21). In this study of acute large-vessel occlusion stroke, we found that clinical outcome following early recanalization was dependent on the patient's pretreatment NIHSS score. A non-negligible proportion of patients with milder strokes did well despite persistent large-vessel occlusion. These results may suggest that in patients who are able to maintain adequate collateral flow despite proximal arterial occlusion, effective adaptive mechanisms are present, which for some patients are long-lasting. This may influence the process of appropriate patient selection for endovascular therapy.

Skagen K ，Skjelland M ，Russell D ，Jacobsen EA ... -  《-》