Recurrent risk of ischemic stroke due to Vertebrobasilar Dolichoectasia

Consecutive patients with first acute IS within 7 days of stroke onset from September 1, 2015 to August 31, 2016 were included in this study. All ischemic stroke events were confirmed by magnetic resonance imaging (MRI) or computerized tomography (CT). We excluded patients with brain hemorrhage, subarachnoid hemorrhage, traumatic brain injury, venous sinus thrombosis, cardioembolic stroke, or treated with percutaneous transluminal angioplasty and stent; patients who died within 7 days were also excluded because their diagnosis of stroke recurrence was mostly undetermined. Besides, patients were excluded if they had no brain MRI/MRA or CT/CTA or digital subtraction angiography (DSA) which would be needed for the measurement of intracranial arterial diameter and determining if intracranial arterial dolichoectasia (IADE) or intracranial atherosclerosis (ICAS) is present. A flowchart of patient enrollment is shown in Fig. 1.

The diameter of main seven intracranial arteries, include the basilar artery (BA) at mid-pons, the intracranial vertebral arteries (VA) (R and L) at the V4 segment, the internal carotid arteries (ICA) (R and L) at the intracavernous segment and the middle cerebral arteries (MCA) (R and L) at the M1 segment, were measured. We focused on the basilar artery in this study because it is the most commonly affected dolichoectasia artery [8]. VBD is defined according to widely accepted criteria [9, 10]. Ectasia was diagnosed if the BA diameter ≥ 4.6 mm and elongated or enlarged over its entire course; not including segmental saccular enlargement or giant aneurysms (diameter > 25 mm) which were described as translational type [11]. A semi-quantitative four-point scale was used to determine the elongation of BA: the height of BA bifurcation was scored as 0 (at or below the dorsum sellae), 1 (within the suprasellar cistern), 2 (at the third ventricle floor) and 3 (indentation and elevation of the third ventricle floor). The laterality of BA was scored as 0 (midline throughout), 1 (R or L, the medial-to-lateral margin of clivus or dorsum sellae), 2 (R or L, the lateral-to-lateral margin of clivus or dorsum sellae) and 3 (R or L, at cerebellopontine angle cistern). Dolichos was diagnosed if the height of BA bifurcation or laterality of BA ≥2 scale. Diagnosed criteria for anterior circulation dolichoectasia is limited; we defined this condition if ICA or MCA was circuitous or enlargement on visual impression and an ICA diameter ≥ 7 mm or a MCA diameter ≥ 4 mm according to a previous study [1]. Diffuse intracranial dolichoectasia was defined with dilation of at less two intracranial arterial supply system (for example, vertebrobasilar system, left or right anterior circulation) [12]. Intra-rater and inter-rater reliability for determinate the existing of VBD or not were 0.821 and 0.796, respectively.

Intracranial arterial stenoses on ICA distal to the ophthalmic artery, anterior cerebral artery (ACA) A1/A2, MCA M1/M2, posterior cerebral artery (PCA) P1/P2, BA, and intracranial VA were measured on 3D-TOF MRA, CTA, or DSA. Stenoses were grouped as < 50, 50 to 69%, 70 to 99%, and occlusion according to previous established criteria [13]. The extracranial arterial stenosis was examined by CTA, contrast-enhanced MRA, or DSA [14]. If a patient experienced with more than one radiological spectrum, the degree of cerebral artery stenosis calculated on DSA image was finally adopted. We defined the presence of ICAS or extracranial atherosclerosis (ECAS) once a cerebral artery has ≥50% stenosis or occlusion.

Baseline demographics, vascular risk factors, in hospital treatment, and medical records were retrieved. Vascular risk factors including hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease and smoking was recorded. All patients had brain MRI (sequences included axial T1-weighted, axial T2-weighted, axial diffusion-weighted imaging, fluid-attenuated inversion recovery, and in most cases, 3D time-of-flight MRA) in either a 3.0-T (MAGENTOM Trio, Siemens, Erlangen, Germany) or a 1.5-T (GE Medical Systems, Milwaukee, WI) system. The image data was stored in Digital Imaging Communications in Medicine (DICOM) format for further analysis in Centricity Enterprise Web 3.0 Client (GE Medical Systems, Milwaukee, WI). All MRI source and maximum intensity projection (MIP) images were evaluated by two neurologists who were blinded to clinical information.

Patients were offered either a face-to-face interview or a telephone interview every 3 months by trained research doctors. The guardians were contacted if patients were died or can’t help themselves with the inquiry. The follow-up interval was defined as the time between the stroke onset and contact or decease. The primary endpoint was IS recurrence. Each recurrence was verified by a stroke specialist’s review of the medical records, including confirmation by CT or MRI, especially to rule out any stroke mimics [15].

Continuous variables were recorded as mean ± SD or as median [IQR]. Categorical variables were presented as proportions. Between-group comparisons of the distribution of continuous variables were performed using the independent samples t-test or Mann–Whitney U test. Comparisons of categorical variables were performed using the χ² test or Fisher-exact test. Risk factors with a P value of < 0.1 in the univariate analysis were included in multivariate Cox proportional hazards regression forward: LR model, to analyze levels of hazard ratio (HR) of recurrence. All statistical testing was two-tailed; P < 0.05 was considered statistically significant. All analyses were performed in PASW Statistics 18.0 (SPSS Inc., Chicago, IL).