Clinical features and the degree of cerebrovascular stenosis in different types and subtypes of cerebral watershed infarction

Patients with acute ischemic stroke admitted to the neurology department of Beijing Chao-Yang Hospital, Capital Medical University from August 2013 to January 2016 were identified. Only patients who met the following criteria were recruited: (1) admitted to the hospital within 7 days of symptom onset; (2) identified as WSI based on diffusion-weighted imaging(DWI) sequence; (3) completed evaluations including medical history, risk factors, cardiologic test, routine blood tests, stroke scales and cerebrovascular examinations. Potential sources of cardioembolism (PSCE) were identified if any of the following existed: recent myocardial infarction (<3 weeks), atrial fibrillation, dilated cardiomyopathy, acute bacterial endocarditis, mitral stenosis, prosthetic valve replacement, sick sinus syndrome or patent foramen [6].

Informed consent was obtained from patients for magnetic resonance imaging (MRI) and computed tomographic angiogram (CTA), and to the use of data for research. All medical procedures were performed only for clinical reasons. The study was approved by the Ethics Committee of Beijing Chao-Yang Hospital, Capital Medical University and was in accordance with the declaration of Helsinki.

MRI was performed on the same 3.0 T Siemens scanner (Erlangen, Germany). The parameters of MR examination were as follows: axial T2-weighted (repetition time, 4500 ms; echo time, 93 ms), axial T1-weighted imaging (repetition time, 2000 ms; echo time, 9.2 ms), axial diffusion-weighted imaging (repetition time, 3300 ms; echo time, 91 ms), and coronal fluid-attenuated inversion recovery sequences (repetition time, 8000 ms; echo time, 86 ms).

CTA was performed on a dual-source CT scanner (Somatom Definition; Siemens Medical Solutions, Forchheim, Germany). For head and neck CTA, 70–80 ml non-ionic contrast agent (350 mg iodine/ml ioversol, Optiray 350, Mallinckrodt Pharmaceuticals) was injected into the antecubital vein at 5 ml/s followed by a 40-ml saline flush also at 5 ml/s. The CTA covered the area from just below the aortic arch to the vertex. CTA was performed in a helical scan mode using the following parameters: 64 × 0.6 collimation, 0.65 pitch, 120 kV, automatic exposure control with standard deviation of 10 and exposure range 100–700 mA, 0.625 mm and 3.0 mm slice thickness, 0.33 s rotation time, reconstruction filter FC43 and standard AIDR3D. The bolus tracker was set at an absolute threshold of 180 HU at the level of the descending aorta in dual energy mode.

Two experienced neurologists (Lei Yang and Man Li) who were unaware of the patient’s clinical information typed the classification with templates [7]. CWI was defined as hyperintense areas on DWI sequence in the junctions of the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories, as a thin fronto-parasagittal wedge. CWI was further divided into anterior watershed infarction (AWI, between ACA and MCA), posterior watershed infarction (PWI, between MCA and PCA) and both-type infarction (AWI plus PWI). IWI was defined as hyperintense areas on DWI sequence between the deep and superficial perforating arteries of the MCA, and further divided into partial IWI (P-IWI, a single lesion or a chain-like, the so-called “rosary-like” pattern in the centrum semiovale) and confluent IWI (C-IWI, large cigar-shaped infarction alongside the lateral ventricle). A concurrence of CWI and IWI was identified as mixed-type infarction. Classifications of WSI, CWI and IWI is presented in Fig. 1.

We used North American Symptomatic Carotid Endarterectomy Trial (NASCET) method to measure the degree of cerebrovascular steno-occlusion as [8]: non-significant (< 50%), moderate (50% to 74%), severe (75% to 99%), or occluded. The critical stenosis was defined as >75% stenosis or occlusion. The κ-coefficient for interobserver agreement was 0.824 for the classification of WSI and 0.797 for the degree of cerebrovascular steno-occlusion.

The following clinical information was collected: sex, age, history of hypertension (defined as treatment with antihypertensive medications or BP > 140/90 mmHg measured on several separate occasions), diabetes mellitus (defined as treatment with antidiabetic medications or fasting plasma glucose >7.0 mmol/L), hyperlipidemia (based on history), smoking (continuously smoking >1 cigarette a day for 6 months), stroke or transient ischemic attack (TIA) and coronary artery disease (CAD, defined as a history of myocardial infarction or angina pectoris), blood pressure (BP, recorded at admission) and results of laboratory tests including level of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), glycosylated hemoglobin (HbA1c), albumin, plasma fibrinogen (Fib), homocysteine (HCY), high-sensitivity C-reactive protein (hs-CRP), serum creatinine (Cr) and uric acid (UA).

All patients received standard treatment in the stroke unit. The National Institutes of Health Stroke Scale (NIHSS) score was checked at day 1 and 7 after admission. The clinical course was defined by change of NIHSS score between the first and seventh day after admission as: 1) improved (NIHSS score decreased by ≥2 points); 2) stable (NIHSS score decreased by <2 points); and 3) deteriorated (NIHSS score increased after admission). Short-term clinical outcome was assessed by Modified Rankin Scale (mRS) 3 months after stroke onset via telephone follow-up and we defined poor outcome as mRS score > 3 points.

All statistics were presented as mean ± standard deviation (SD) for continuous variables with normal distribution, median and interquartile range for continuous variables with non-normal distribution, and counts and proportions for categorical variables. Differences among the groups and subgroups were examined using Pearson χ² test, one-way analysis of variance (ANOVA), or non-parametric test, depending on the nature of the variables being compared. The Bonferroni correction was used for post hoc comparisons to obtain an adjusted significance level for each domain-specific test: ≈0.05/3 = 0.017. Statistical significance was established at P < 0.05. Logistic regression analysis was applied to identify independent predictors of poor clinical outcome. Independent variables were age, sex, vascular risk factors, PSCE, clinical course, NIHSS score at admission, type of WSI, and the critical stenosis of ICA and MCA. The results were presented as estimates of relative risk by odds ratio (OR) with a 95% CI. Analysis was performed with Statistical Package for Social Sciences (SPSS version 24).

During the study, 351 WSI patients were identified, among whom 11 with incomplete examinations were excluded. As a result, 340 patients were recruited with 220 (64.70%) males. Among the 340 WSI patients, 92 (27.10%) had CWI, 112 (32.90%) had IWI and 136 (40.00%) had mixed-type infarction. Details of clinical and demographic features of the patients in each group are presented in Table 1. The age, sex, risk factors and laboratory data did not differ among three groups.

The incidence of critical stenosis of internal carotid artery (ICA) differed among three groups of WSI (P = 0.001), but that of other cerebral vessels did not. In further comparison, more patients in the IWI group were found to have critical ICA stenosis than those in the CWI group (43.80% vs. 19.60%; P < 0.001, Fig. 2). These results are presented in Additional file 1: Table S1.

Among 228 patients who had CWI (including 136 mixed-type patients), patients with AWI were more prone to critical ICA stenosis than those with PWI (39.40% vs. 20.70%; P = 0.011, Fig. 3). Among 248 patients who had IWI (including 136 mixed-type patients), critical ICA stenosis was more common in the P-IWI subgroup than in the C-IWI subgroup (44.10% vs. 30.40%; P = 0.026, Fig. 4).

Although NIHSS scores at admission did not differ significantly among the groups, clinical course during the first week after admission was significantly different: only 13.0% of CWI patients deteriorated compared with 33.9% of IWI patients and 25.7% of patients who had mixed-type infarction. Further analysis showed that patients with IWI were more prone to deterioration than those with CWI (P = 0.003). Follow-up prognosis 3 months after stroke showed significantly more IWI patients with a poor outcome than CWI patients (P = 0.014). Details of the clinical course and prognosis of the 3 groups are presented in Table 2.

After adjustment for confounding factors, multivariate logistic regression analysis revealed that the presence of IWI (OR, 5.231; 95% CI, 1.687 to 9.703; P = 0.008), critical stenosis of ICA (OR, 2.284; 95% CI, 1.376 to 5.662; P = 0.012), and the initial NIHSS score (OR, 1.877; 95% CI, 1.176 to 2.012; P = 0.004) were independently associated with poor outcome 3 months after stroke.