Leukoaraiosis is associated with pneumonia after acute ischemic stroke

We retrospectively collected a consecutive series of patients with acute ischemic stroke who visited our stroke center between Jan 2011 and Mar 2013 (n = 1120). Patients were excluded when they met the following criteria: a delay of >24 h from symptom onset to visiting our center (n = 793); age under 18 years (n = 8); and patients without brain magnetic resonance imaging (MRI) (n = 11). Finally, a total of 308 patients remained for secondary analyses (Fig. 1).

We assessed the following baseline demographic information and risk factors of stroke in all participants: age, sex, hypertension, diabetes, hyperlipidemia [11], atrial fibrillation, and smoking. We also collected initial clinical factors including stroke subtype, stroke location, stroke severity, presence of dysphagia, level of consciousness, and use of thrombolysis therapy. Stroke severity was evaluated using the National Institute of Health Stroke Scale (NIHSS) score on admission and discharge date by trained neurologists. Dysphagia was assessed using a bedside non-instrumented diagnostic test consisting of 3 sequentially performed subtests (semisolid, liquid, and solid textures) [12]. Level of consciousness was dichotomized into normal (NIHSS 1a = 0) and impaired (NIHSS 1a = 1–3). Mechanisms of stroke were classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. The location of the stroke lesions was categorized as either supratentorial or infratentorial. We also collected the information about clinical outcomes including hospitalization duration, discharge NIHSS score, presence of in-hospital mortality, and event of intubation. Patients underwent routine laboratory examination within 24 h from admission including white blood cell count and high sensitivity C-reactive protein levels.

All participants underwent brain MRI and magnetic resonance angiography within 24 h of the visit with a 3.0-Tesla MR scanner (Achieva 3.0; Philips, Eindohovenm, the Netherlands). The MRI protocol included diffusion-weighted images (DWI) [repetition time (TR)/echo time (TE) = 3000/44 ms], T1-weighted images [TR/TE = 300/10 ms], T2-weighted images [TR/TE = 3000/100 ms], fluid attenuated inversion recovery images [TR/TE = 11,000/120 ms], T2 fast field echo images [TR/TE = 530/16 ms] and three-dimensional time of flight (TOF) MRA images [TR/TE = 24/3.5 ms]. The field of view data in all MRI sequences were 240 × 240 mm. The slice thickness was equally 5.0 mm, excepting 3.0 mm in DWI and 1.2 mm in TOF images. We assessed the severity of the LA using the Fazekas scale in both the periventricular (0–3) and subcortical areas (0–3) [13]. We then summed the grade from the Fazekas scale in both areas and dichotomized this grade into mild LA (sum of grade, 0–2) and severe LA (sum of grade, 3–6) [14]. Two trained neurologists (K.W.N. and J.S.L.) without clinical information graded the severity of LA and the inter-rater reliability coefficient was 0.93. Disagreements were resolved by discussion with a third reviewer (H.M.K.). We also evaluated for the presence of lacunar infarcts and cerebral microbleeds (CMBs). CMBs were divided into lobar CMBs and deep or infratentorial CMBs according to the location of the lesion [15].

A patient was diagnosed as SAP if the lower respiratory tract infection, which met the modified Centers for Disease Control (CDC) and Prevention criteria, occurred within the first 7 days after stroke onset (Additional file 1) [16]. The evaluation of presence of SAP was conducted retrospectively by the neurologists (K.W.N. and H.M.K.), who were blinded to other clinical and radiological factors. Additionally, the chest x-ray was evaluated by one of the study neurologist (K.W.N.) and a specialized radiologist (S.W.P.), with an acceptable inter-rater reliability (kappa coefficient, P = 0.915). We did not categorize the burden of chest x-ray finding into probable and definite SAP, considering the retrospective study design. During the initial three to four days, we observed all participants closely in our specialized stroke unit. After they were transferred to the general ward, we continued to check for the occurrence of SAP.

All continuous variables were tested for normal distribution, and skewed variables were transformed to log-scale for further statistical analyses. Continuous variables with normal distribution were presented as the mean ± SD, while nonparametric ones were presented using the median value and interquartile range [IQR]. In univariate analyses, we used Student’s t-test for normally distributed variables and the Mann-Whitney U-test for nonparametric variables. For categorical values, we used the chi-square test and Fisher’s exact test. In multivariate analyses, we used binary logistic regression to evaluate independent predictors of SAP. Based on the result from the univariate analyses, variables of P < 0.05 were selected for the multivariate analysis. We combined prognostic variables of age, atrial fibrillation, dysphagia, male sex, and initial stroke severity into the A2DS2 score to avoid overfitting, considering the small number of SAP events (Additional file 2). The A2DS2 score was dichotomized into low A2DS2 score (0–4) and high A2DS2 score (5–10) [17]. Level of consciousness was excluded due to close correlation with stroke severity (Pearson correlation coefficient, P < 0.001). All statistical analyses were conducted using SPSS 20 (IBM SPSS, Chicago, IL, USA). A value of P < 0.05 was considered significant.