Evaluating the Potential Pathology and Short-Term Outcomes of Cryptogenic Stroke Using the Etiological Classification System

Aim: Various embolic sources and pathogenetic mechanisms underlie cryptogenic stroke (CS). We investigated the association of etiological diversity with short-term outcomes in patients with CS using a modified atherosclerosis (A), small-vessel disease (S), cardiac pathology (C), other causes (O), and dissection (D) (ASCOD) system. Methods: Patients with CS who underwent transesophageal echocardiography were registered in this multicenter, observational study. In the modified classification system, O and D were inapplicable and thus excluded. Instead, atherosclerosis, small-vessel disease, cardiac pathology-CS classification was specifically constructed for the etiological diagnosis of CS. We utilized this system to explore the mechanism of CS by grading each pathology and evaluated its association with poorer modified Rankin Scale scores of 3–6 at hospital discharge. Results: A total of 672 patients (68.7±12.8 years, 220 females) were analyzed. In the multiple logistic regression model, female sex (odds ratio [OR], 1.87 [1.15–3.04];P =0.012), body mass index (OR, 0.93 [0.88–0.99];P =0.025), National Institute of Health Stroke Scale score (OR, 1.16 [1.12–1.21];P＜0.001), CHADS(2) score (OR, 1.56 [1.30–1.86];P＜0.001), D-dimer (OR, 1.04 [1.01–1.08];P =0.015), diffusion-weighted image (DWI) lesion size (OR, 1.44 [1.10–1.89];P =0.009), and S＋C score (OR, 1.26 [1.03–1.56];P =0.029) were associated with poor functional outcome at discharge whereas the S＋C score was marginally associated with poor functional outcome after excluding 137 patients with a premorbid modified Rankin Scale score of ≥ 3. Conclusions: The coexistence of small-vessel disease and cardiac pathology might be associated with poor in-hospital functional outcome in CS.