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Unfavorable neurological outcome in diabetic patients with acute ischemic stroke is associated with incomplete recanalization after intravenous thrombolysis Huan Tang,1 Sheng Zhang,1 Shenqiang Yan,1 David S Liebeskind,2 Jianzhong Sun,3 Xinfa Ding,3 Minming Zhang,3 Min Lou1 1
Department of Neurology, The Second Afﬁliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China 2 University of California-Los Angeles Stroke Center, Los Angeles, California, USA 3 Department of Radiology, The Second Afﬁliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China Correspondence to Dr Min Lou, Department of Neurology, The Second Afﬁliated Hospital of Zhejiang University, School of Medicine, #88 Jiefang Road, Hangzhou 310009, China; [email protected] Received 31 December 2014 Revised 8 February 2015 Accepted 11 February 2015
ABSTRACT Objective To assess the impact of diabetes on neurological outcome and recanalization in acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods Clinical data of 419 consecutive patients with AIS who received IVT between June 2009 and April 2014. Based on the medical history and new diagnosis, the patients were divided into groups with and without diabetes. Neurological outcomes at 24 h, 7 days and 3 months after IVT were evaluated. Favorable outcome was deﬁned as National Institutes of Health Stroke Scale (NIHSS) score decrease ≥4 points from baseline or 0 at 24 h, NIHSS decrease ≥8 points or 0 at day 7, or modiﬁed Rankin scale ≤1 at 3 months after IVT. Recanalization on non-invasive imaging was evaluated in patients with large vessel occlusion (LVO) according to thrombolysis in myocardial infarction grades. Results Among 419 patients, 98 (23.4%) had diabetes. Multivariable analyses showed that comorbidity of diabetes was an independent predictor of unfavorable outcome at 24 h (OR=0.534, 95% CI 0.316 to 0.903, p=0.019), at day 7 (OR=0.382, 95% CI 0.220 to 0.665, p=0.001), and at 3 months (OR=0.464, 95% CI 0.266 to 0.808, p=0.007). In patients with LVO, diabetes was an independent predictor of incomplete recanalization 24 h after IVT (OR=0.268, 95% CI 0.075 to 0.955, p=0.042). Conclusions Diabetic patients with AIS had unfavorable neurological outcome, potentially linked to incomplete recanalization after IVT.
To cite: Tang H, Zhang S, Yan S, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2014-011643
Diabetes and ischemic stroke are common diseases in China, with increased incidence and mortality year by year.1 People with diabetes have more than double the risk of ischemic stroke after adjustment for other risk factors.2 3 Moreover, patients with stroke and diabetes are more likely have an unfavorable neurological outcome.4 Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is a proven beneﬁcial treatment for acute ischemic stroke (AIS) when given within 4.5 h of symptom onset.5 Although patients with AIS and diabetes can achieve substantial beneﬁt from IVT,6 an association between diabetes or hyperglycemia and unfavorable outcome after IVT has been reported, in comparison with
AIS without diabetes.7 8 However, the speciﬁc mechanism of such poor outcome remains elusive. The beneﬁcial impact of IVT on clinical outcomes of patients with AIS is mechanistically linked to arterial recanalization and downstream tissue reperfusion after thrombolysis, and prompt recanalization is associated with early neurologic improvement.9 Diabetes may alter the cerebral circulation via atherosclerosis, which results in chronic inﬂammation and injury to the arterial wall.10 We therefore hypothesized that AIS in diabetic patients with large vessel occlusion (LVO) may fail to achieve complete recanalization after IVT, subsequently linked to an unfavorable neurological outcome. Our goal was to estimate the impact of diabetes on neurological outcome and recanalization in AIS after IVT.
METHODS Ethics statement Consent was obtained from each patient or an appropriate family member. The protocol of this study had been approved by the human ethics committee of the local hospital. All clinical investigations have been conducted according to the principles expressed in the Declaration of Helsinki.
Selection of patients This study was conducted between June 2009 and April 2014 in our hospital. We collected the clinical data of 419 consecutive patients with AIS who received intravenous recombinant tissue plasminogen activator (Alteplase 0.9 mg/kg up to a maximum of 90 mg; 10% of the total dosage as a bolus and the rest over 1 h) according to standard guidelines.5 Patients were selected using the following criteria: (1) age >18 years; (2) diagnosis of AIS according to the clinical symptoms and imaging; (3) received IVT within 6 h of onset; (4) underwent multimodal CT imaging for onset-to-door time within 3 h before IVT, including non-contrast CT, volumetric perfusion CT (VPCT); or underwent multimodal magnetic resonance (MR) imaging for onset-to-door time of 3–6 h before IVT,11 including diffusion-weighted imaging, time-of-ﬂight magnetic resonance angiography (TOF-MRA), perfusionweighted imaging (PWI); (5) underwent follow-up TOF-MRA or CT angiography (CTA) at 24 h after IVT; (6) baseline modiﬁed Rankin scale (mRS) ≤1.
Tang H, et al. J NeuroIntervent Surg 2015;0:1–5. doi:10.1136/neurintsurg-2014-011643
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Ischemic stroke The exclusion criteria were according to the standard IVT guidelines.5 We also excluded patients who were receiving endovascular therapy.
Imaging protocol MR imaging was performed on a 3.0 T system (Signa Excite HD; GE Healthcare, Milwaukee, Wisconsin, USA) equipped with an eight-channel phased array head coil. The MRI protocol included diffusion-weighted imaging (TR=4000 ms, TE= 69.3 ms, b-value=1000 s/mm, acquisition matrix=160×160, FOV=240 mm, slice thickness=5 mm, interslice gap=1 mm, duration=32 s), TOF-MRA (TR=20 ms, TE=3.2 ms, ﬂip angle=15°, acquisition matrix=320×224, slice thickness=1.4 mm, three slabs, duration=3 min 46 s), PWI (TR=1500 ms, TE=30 ms, acquisition matrix=128×128, dynamic scans=50, FOV=240 mm, slice thickness=5 mm, section gap=1 mm, gadolinium dose=15 mL, contrast speed=4–5 mL/s, duration=l min 15 s). Multimodal CT imaging was performed on a SOMATOM Deﬁnition Flash CT imaging system (Siemens Healthcare Sector, Forchheim, Germany). The sequences included non-contrast CT, VPCT. VPCT consisted of 26 consecutive spiral acquisitions of the brain (100 mm in the z-axis, 4 s delay after start of contrast medium injection, 67.98 s total imaging duration, 80 kV, 120 mA, slice thickness 1.5 mm, collimation 32×1.2 mm). A 60 mL bolus of contrast medium (iopamidol; Braccosine, Shanghai, China) was used at a ﬂow rate of 6 mL/s, followed by a 20 mL saline chaser at 6 mL/s. CTA was reconstructed on Siemens workstation after VPCT with acquisition from the base of the skull to the top of the lateral ventricles.
2=mild-to-moderate stenosis of the symptomatic arterial lesion and signiﬁcant reduction of ﬂow signal of distal vessels; 3=normal arterial caliber. A TIMI grade of 3 points was deﬁned as complete recanalization and TIMI≤2 points was deﬁned as incomplete recanalization.17
Statistical analysis Statistical analysis was performed using SPSS V.17.0 (SPSS Inc, Chicago, Illinois, USA). Fisher’s exact test was used to compare the dichotomous variables between groups, while independent samples two-tailed t test or Mann–Whitney U test was used for the continuous variables, as appropriate. Variables with a twotailed p value of
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