Ischemic stroke
ORIGINAL RESEARCH
Clinical outcomes of patients with acute minor stroke receiving rescue IA therapy following early neurological deterioration Joon-Tae Kim,1 Suk-Hee Heo,2 Woong Yoon,3 Kang-Ho Choi,1 Man-Seok Park,1 Jeffrey L Saver,4 Ki-Hyun Cho1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ neurintsurg-2015-011690). 1
Department of Neurololgy, Cerebrovascular Center, Chonnam National University Hospital, Gwangju, Korea 2 Department of Radiology, Chonnam National University Hwasun Hospital, Hwasun, Korea 3 Department of Radiology, Chonnam National University Hospital, Gwangju, Korea 4 Department of Neurology, Stroke Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA Correspondence to Dr Joon-Tae Kim, Department of Neurology, Chonnam National University Medical School, 8 Hak-dong, Dong-ku, Gwangju 501-757, Korea;
[email protected] Received 13 February 2015 Revised 1 April 2015 Accepted 6 April 2015
ABSTRACT Background Patients presenting with minor ischemic stroke frequently have early neurological deterioration (END) and poor final outcome. The optimal management of patients with END has not been determined. Objective To investigate rescue IA therapy (IAT) when patients with acute minor ischemic stroke develop END. Methods This was a retrospective study of consecutively registered patients with acute minor stroke and END. ‘END’ was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) scores by 1 or more points (or development of new neurological symptoms) and ‘ΔEND−NIHSS’ was defined as numerical difference between NIHSS scores at the time of END and before END. Rescue IAT following END was adjusted for the covariates to evaluate the association between IAT and favorable outcome at 3 months. Results Among 982 patients with acute minor ischemic stroke, END occurred in 232 (23.6%). Of the 209 patients with END with full data available, 87 (41.6%) had favorable outcomes at 3 months. Rescue IAT following END was performed in 28 (13.4%). Favorable 3-month outcomes were seen in 50% of patients undergoing rescue IAT, including 8/19 (42.1%) undergoing rescue IAT beyond 8 h. By multivariate logistic regression analysis, rescue IAT following END was independently associated with favorable outcome at 3 months (OR=10.9; 95% CI 3.06 to 38.84; p1. This study was approved by the institutional review board of Chonnam National University Hospital. Written informed consent was not obtained because of the retrospective design of this study.
Clinical assessment The following stroke risk factors were identified: age, sex, recent cigaret smoking (cigaret smoking within the past 5 years), hypertension, diabetes mellitus, dyslipidemia, and a previous history of stroke or transient ischemic attack. We assessed neurological status at admission and on each hospital day using NIHSS scores. Time intervals analyzed included FAT-to-hospital arrival time, FAT-to-END time (time of first END after FAT), FAT-to-IAT time, and END-to-IAT time. IAT time was defined as the time the clot was first accessed.
Kim J-T, et al. J NeuroIntervent Surg 2015;0:1–5. doi:10.1136/neurintsurg-2015-011690
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Ischemic stroke Stroke subtypes were stratified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria after complete diagnostic investigations.13 In the primary analysis, ‘END’ was defined as an increase in NIHSS scores by ≥1 points (or development of new neurological symptoms) and ‘delta END −NIHSS (ΔEND−NIHSS)’ was defined as the numerical difference between NIHSS scores at the time of END and before END. In sensitivity analysis, END was defined as an increase in NIHSS scores by ≥4 points. END was regularly diagnosed and registered by a physician while monitoring the patient. Scores of 0–2 on the mRS at 90 days were defined as a favorable outcome.
Imaging assessment The imaging protocol of acute ischemic stroke in our hospital has been previously described.5 Briefly, patients underwent emergency MRI at the emergency department immediately after admission. The MRI protocol consisted of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery, gradient echo (GRE) imaging, time-of-flight MR angiography (MRA), and perfusion-weighted imaging in sequence. In addition, DWI/ GRE imaging was also performed if neurological deterioration occurred. For this study, the images were analyzed by two neurologists ( J-TK and M-SP) who were blinded to the clinical data. Discrepancies were resolved by consensus conference. The lesion sites on DWI were categorized into anterior, posterior, or both circulations. The patterns of DWI lesions in anterior circulation were classified as perforating artery infarcts (PAI), pial infarcts (PI), borderzone infarcts (BI), territorial infarcts (TI), and lacunar infarcts (LI) by modifying previous studies.14 Hemorrhagic transformation (HT) was categorized as hemorrhagic infarcts (type 1 or 2) or parenchymal hematomas (type 1 or 2) according to a modified definition established by a previous study.15 We used GRE imaging for the categorization of HT. Arterial occlusion was defined as a complete loss of distal flow signal. Moderate to severe arterial stenosis was defined as a >50% narrowing of the lumen and focal signal loss in the presence of a distal flow signal. Arterial occlusion sites that supplied the acute ischemic region were defined as ‘relevant arterial occlusion’ and determined via analysis of the initial MR angiogram. IA recanalization at the end of the IAT procedure was defined as grade 2 or 3 of the Thrombolysis in Myocardial Infarction scale.
Management Management following END was decided at the discretion of the attending physicians. Addition of antiplatelets, administration of intravenous antithrombotic agents, such as tirofiban or argatroban, or rescue IAT were the management options for END. Decisions on rescue IAT were made on the basis of neurological symptoms, DWI at the time of END, and initial/ follow-up MRA. Rescue IAT was generally performed according to the following criteria: (1) catheter-accessible symptomatic arterial occlusion on MRA, (2) small DWI lesions on initial imaging and after END, and (3) the presence of cortical signs or symptoms. However, even if patients met the criteria for rescue IAT, physicians decided to carry out or not to carry out rescue IAT on the basis of their case-specific assessment of risk and benefit of IAT. Informed written consent for rescue IAT was given by each patient or family. Rescue IAT was performed using a variety of methods, including mostly mechanical thrombectomy (Solitaire devices). In addition, clot location was assessed during IAT. 2
Statistical analysis Data are presented as mean±SD or the frequency of categorical variables. Categorical variables were analyzed using the χ2 test and Fisher’s exact test, when appropriate. Continuous variables were analyzed using the independent sample t test or the Mann–Whitney U, test when appropriate. Multivariate logistic regression analysis was used to evaluate independent factors associated with favorable outcomes at 3 months (adjusted for age, baseline NIHSS, TOAST classifications, time from FAT to visit, diabetes mellitus, relevant arterial occlusion, ΔEND −NIHSS, and rescue IAT). For the sensitivity analysis, in patients with relevant arterial occlusion on initial MRA (n=92), rescue IAT was adjusted for the following covariates to evaluate the association between rescue IAT and favorable outcome at 3 months: model 1 was adjusted for age, initial NIHSS, and TOAST classifications; and model 2 was adjusted for age, initial NIHSS, TOAST classifications, and ΔEND−NIHSS. ORs and 95% CIs were calculated. A p value of 1. Among the resulting analytic population of 209 patients with minor ischemic patients and END, mean age was 68.0±11.6 years and 117 (56.0%) were male. Of the 209 patients, 87 (41.6%) had favorable outcomes at 3 months, and 92 (44.0%) had relevant arterial occlusion on initial MRA. END occurred a median of 19 h after FAT and 16 h and 3 min after hospital arrival. Rescue IAT was performed on 28 (13.4%).
Characteristics of patients undergoing rescue IAT Characteristics of patients undergoing and not undergoing rescue IAT after END are shown in table 1. ΔEND−NIHSS was significantly higher in patients undergoing rescue IAT. Patients with atrial fibrillation and relevant arterial occlusion on initial MRA also more frequently underwent rescue IAT. ΔEND −NIHSS values were higher and time from FAT to END was faster in patients treated with rescue IAT. Some patients with no initial steno-occlusion (n=2, 7.1%) or initial symptomatic stenosis (n=5, 17.9%) also underwent rescue IAT. END in the patients with relevant stenosis were treated with angioplasty (and stenting). The patients without relevant arterial steno-occlusion who were treated with rescue IAT had developed new interval occlusions. HT was non-significantly more common in patients undergoing rescue IAT, but most (5/7) were hemorrhagic infarction rather than frank hematoma. On univariate analysis, there were no significant differences in frequency of favorable outcomes at 3 months and death within 3 months between the two groups. Among the 28 patients undergoing rescue IAT, nine received IAT within 8 h from FAT to IAT. Six of these nine patients had favorable outcomes at 3 months. The other 19 patients received IAT beyond the 8 h time window (median 30 h; IQR 16) and 8/19 (42.1%) patients had favorable outcomes at 3 months (see online supplementary table S1). Some patients with no initial Kim J-T, et al. J NeuroIntervent Surg 2015;0:1–5. doi:10.1136/neurintsurg-2015-011690
Ischemic stroke Table 1 Characteristics of patients who underwent rescue IAT after END Characteristics Age (years), mean±SD Male Baseline NIHSS (median, IQR) FAT-to-visit time (min), mean±SD Risk factors Hypertension Diabetes mellitus Atrial fibrillation Dyslipidemia Smoking Previous stroke TOAST classifications LAA CE SVO UD Relevant arteries MCA ICA VBA Others Relevant arterial steno-occlusion No steno-occlusion Stenosis Occlusion Treatment before END Thrombolysis ΔEND−NIHSS (median, IQR) FAT-to-END time (h) (med, IQR) HT HI-1,2 PH-1,2 mRS≤2 at 3 months Death within 3 months
Conservative (N=181)
Rescue IAT (N=28)
67.82±11.65 104 (57.5) 2.0 (2.0) 164.45±88.23
68.89±11.53 13 (46.4) 2.0 (1.75) 189.57±120.70
116 (64.1) 64 (35.4) 32 (17.7) 50 (27.6) 49 (27.1) 26 (14.4)
18 (64.3) 7 (25.0) 11 (39.3) 6 (21.4) 5 (17.9) 5 (17.9)
108 (59.7) 28 (15.5) 19 (10.5) 26 (14.4)
14 (50.0) 10 (35.7) 0 4 (14.3)
p Value 0.481 0.310 0.687 0.426 >0.999 0.391 0.021 0.648 0.361 0.577 0.928
0.118 40 (22.1) 30 (16.6) 23 (12.7) 11 (6.1)
13 (46.4) 10 (35.7) 1 (3.6) 2 (7.1)
77 (42.5) 33 (18.2) 71 (39.2)
2 (7.1) 5 (17.9) 21 (75.0)
33 (18.2) 3.0 (4.0) 20 (26) 20 (11.0) 13 (7.2) 7 (3.9) 73 (40.3) 9 (5.0)
9 (32.1) 6.5 (6.0) 10 (16.3) 7 (25.0) 5 (17.9) 2 (7.1) 14 (50.0) 1 (3.6)
