2.1. Study sample

Patients with first‐ever ischemic stroke admitted to the Tianjin Huanhu hospital from March 2013 to September 2018 were consecutively screened for the following study entry criteria: receiving MRI on admission, the NIH Stroke Scale (NHISS) < 3, having sufficient language, auditory, and visual abilities to allow the assessments. The diagnosis of acute ischemic stroke was defined as meeting the definition of acute ischemic stroke according to the American Heart Association/American Stroke Association World Health Organization (Sacco et al., 2013). Patients with atrial fibrillation and other potential sources of cardioembolism, history of previous TIA/stroke, dementia, or other neurological diseases were excluded.

All the stroke patients were screened for syphilis serology. When serology proves positive, all patients should undergo cerebrospinal fluid (CSF) examination. Patients who had positive syphilis serologies and met the following criteria were allocated to neurosyphilis (Timmermans & Carr, 2004; “1998 Guidelines for Treatment of Sexually Transmitted Diseases. Centers for Disease Control and Prevention,” 1998). 1) Positive cerebrospinal fluid VDRL (Venereal Disease Research Laboratory) or 2) Positive cerebrospinal fluid FTA‐abs (fluorescent treponemal antibody absorption test), with either abnormal CSF cell count (polymorphonuclear leucocytes and/or lymphocytes >5/ml), or CSF protein>0.45 g/L, or IgG index>0.6. We also enrolled a group of control subjects who matched patients (1:1) by sex and age (±3 years) and fulfilled the inclusion and exclusion criteria reported above during the same study period, except they had negative syphilis serology. During admission, demographic data, past medical history, and atherosclerotic risk factors were registered. TOAST classification in our study included large artery atherosclerosis (LAA), small vessel occlusion (SVO), stroke of other determined etiologies (SOE), and stroke of undetermined etiologies (SUE), because cardioembolism (CE) were excluded in our samples. Written informed consent was obtained from every patient, and this study protocol was approved by the Clinical Research Ethics Committee of Tianjin Huanhu Hospital and performed in accordance with the ethical standards in the Declaration of Helsinki.