Abstract: OBJECTIVES: To characterize the subclinical atherosclerosis in a group of young and middle-aged patients with stroke of undetermined etiology, in relation to the stroke causal likelihood of patent foramen ovale (PFO). METHODS: We conducted a retrospective review of prospectively collected medical records of consecutive patients aged 18–60 years with a diagnosis of acute ischemic stroke of undetermined origin between January 2016 and June 2022. Patients were grouped by the PFO presence and the stroke-causal likelihood of PFO according to the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system. RESULTS: We included 157 patients with stroke of undetermined etiology (mean age 48.2 ± 8.7 years; 43.3% female). Of these, 75 patients presented PFO. After adjusting for age and sex, the PFO+ group presented a lower mean carotid intima-media thickness (cIMT; P = 0.046), carotid stenosis inside ( P = 0.016), and outside ( P = 0.003) the stroke territory. Plaques of any grade were associated with negative findings at the PFO investigation (odds ratios 0.271 [95% confidence interval: 0.134–0.547]). Risk of Paradoxical Embolism scores were inversely correlated to mean cIMT ( P = 0.028; Spearman’s rho = −0.257). cIMT was progressively lower in patients without PFO compared to those with low- and high-risk PFO ( P = 0.003) and across PASCAL categories ( P = 0.010). Among PFO+ patients, the presence of stenosis ipsilateral to stroke ( P = 0.001) and any plaque ( P = 0.001) was differently distributed across PASCAL categories. CONCLUSIONS: The burden of subclinical atherosclerosis is progressively lower in patients with unlikely, possible, and probable stroke-causative PFO. These results support the idea that atherosclerosis may play a significant causal role in some patients with stroke of undetermined origin with or without PFO.
Abstract: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of ischemic stroke and is encountered particularly often in Asian populations. Although intensive medical therapy is the foundation of treatment, the risk of recurrent stroke remains substantial. This review summarizes the four-decade development of endovascular therapy for ICAS. Early attempts were obstructed by high periprocedural complication rates, and the treatment strategies became more selective and evidence-driven after the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis trial. However, subsequent international studies suggested that changes in device selection, operator experience, perioperative management, and above all, patient selection began to alter the risk-benefit profile of intervention. In this evolving evidence base, studies from China have made important contributions alongside work from other regions. Trials such as CASSISS and BASIS have demonstrated that periprocedural risk can be effectively controlled through rigorous patient selection and standardized perioperative management, and refined endovascular techniques. The CASSISS trial established the safety boundary for delayed and carefully selected stenting, whereas the BASIS trial suggested that a stent-free strategy using plain balloon angioplasty plus intensive medical therapy significantly reduced the 1-year composite primary endpoint. These findings redefined the role of endovascular therapy as a feasible, precisely targeted option for a narrowly defined high-risk population. Future advances are expected to build upon these foundations, focusing on novel devices and advanced imaging modalities (e.g., high-resolution magnetic resonance vessel wall imaging, fractional flow reserve) to better refine lesion assessment, functional ischemia, and individualized risk stratification.
