The core therapeutic goal of acute ischemic stroke is to salvage the ischemic penumbra. Although reperfusion therapy restores cerebral blood flow, the phenomenon of "futile recanalization" remains common, indicating that vascular recanalization alone cannot fully prevent ischemia-reperfusion brain injury. As an essential complementary strategy to reperfusion, brain cytoprotection therapy aims to mitigate reperfusion-related damage and enhance neurological recovery through multi-target interventions. This review summarizes recent advances in combined reperfusion and brain cytoprotection therapy for acute ischemic stroke based on high-quality clinical evidence, focusing on the latest findings and clinical applicability of pharmacological and non-pharmacological protective strategies. It also discusses the potential role and prospects of integrated multi-phase interventions in improving neurological outcomes, offering insights for optimizing brain cytoprotection strategies following reperfusion therapy in acute ischemic stroke.

To explore the application value and practical effect of case discussion in the standardized training of resident physicians in the department of neurology.

Resident physicians undergoing standardized training in the Department of Neurology at the First Affiliated Hospital of Harbin Medical University from January 2023 to January 2024 were randomly divided into a treatment group (n=16) and a control group (n=16). The control group only received conventional training, including theoretical lectures, clinical teaching, and skill operation training. On the basis of conventional training, the treatment group additionally conducted monthly case discussions, covering typical cases such as multiple sclerosis, autoimmune encephalitis, and neuromyelitis optica spectrum disorders. Each case discussion included case report, free discussion, and summary comments. Meanwhile, an annual case report meeting was held. The training effects were compared through theoretical assessment, clinical skill assessment, case analysis ability evaluation, questionnaire survey, and a 1-year follow-up. All assessment scores were independently scored by associate chief physicians using a double-blind method. Statistical analysis between the two groups was performed using independent samples t-test and chi-square test with SPSS 26.0 software.

Compared to control group, the treatment group showed significantly higher average scores in theoretical assessment (89.54±6.22 vs 78.29±7.51, t=4.624, P<0.001) and clinical skill assessment (91.23±5.81 vs 82.14±6.68, t=4.117, P<0.001). The excellent rate of case analysis ability was 81.25% (13/16) in the treatment group versus 43.75% (7/16) in the control group (χ²=4.800, P=0.028). After 1 year of follow-up, the proportion of resident physicians independently handling cases was 87.50% (14/16) in the treatment group versus 50.00% (8/16) in the control group (χ²=5.236, P=0.022). In the questionnaire survey, the scores of clinical thinking (4.42±0.54 vs 3.52±0.62), teamwork (4.51±0.44 vs 3.72±0.64), knowledge expansion (4.55±0.40 vs 3.75±0.68), learning interest (4.51±0.44 vs 3.61±0.66), and professional identity (4.31±0.59 vs 3.41±0.72) of resident physicians in the treatment group were significantly higher than those in the control group, with statistically significant differences (t=4.377, 4.102, 4.052, 4.508, 3.892; all P＜0.001).

Compared with traditional teaching methods, monthly case discussions can effectively improve the theoretical level, clinical skills, clinical thinking, and clinical decision-making ability of resident physicians receiving standardized training in neurology residents.

To investigate the current status, influencing factors, and potential interventions for job burnout among neurology residents.

A questionnaire survey on the job burnout status was conducted using the Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS) among neurology residents trained at Peking University Third Hospital and Peking University Sixth Hospital from February 2024 to January 2025. The cutoff scores for emotional exhaustion, depersonalization, and reduced personal accomplishment were >12, >7, and >18, respectively. Burnout severity was categorized as follows: 0 dimensions (no burnout), 1 dimension (mild), 2 dimensions (moderate), and 3 dimensions (severe). Differences between severe and non-severe burnout groups in age, gender, training status, duration, job position, leisure time availability, marital status, working hours, income satisfaction, and sleep duration were analyzed using t-tests, non-parametric tests, Chi-square tests, or Fisher's exact tests.

Among the 26 participants, 4 (15.4%) had no burnout, 22 (84.6%) had varying degrees of burnout, and 10 (38.5%) had severe burnout. A significant difference was observed in leisure time availability between the severe burnout group (10.0%) and non-severe group (56.3%, χ²=5.562, P=0.037). Seventeen suggestions for reducing burnout were collected: increased training (35.3%, 6/17), psychological counseling (23.5%, 4/17), team-building activities (17.6%, 3/17), simplified workflows (11.8%, 2/17), salary increases (5.9%, 1/17), and additional staffing (5.9%, 1/17).

Job burnout is prevalent among neurology residents, with a high proportion of severe cases. Interventions such as enhanced training, psychological support, team-building, workflow optimization, salary adjustments, and increased staffing may mitigate burnout.

To investigate the effect of chain process management on improving iodine contrast medium extravasation (CME) in multi-mode CT examination for acute stroke via the green channel.

A total of 864 patients with suspected stroke who underwent green channel multi-mode CT in the First Affiliated Hospital of Naval Medical University from June to November 2023 were enrolled. Based on the nursing management process implementation phase, 404 patients from June to August were assigned to the control group (routine nursing), and 460 from September to November to the treatment group (chain process management). CME incidence, grading, and time from admission to intravenous access establishment were compared using Chi-square test, Fisher's exact test, and one-way ANOVA, respectively.

The CME incidence was significantly lower in the treatment group than that in the control group [0.87% (4/460) vs 4.46% (18/404), χ²=11.146, P=0.001]. The treatment group had 3 cases of mild and 1 case of moderate iodine CME, and the control group had 3 cases of mild and 15 cases of moderate iodine CME. The grade of iodine CME in treatment groups was significantly lower than that in control group (P=0.046). The time from admission to venous access did not differ significantly between groups [(306.52±141.95) s in control vs (300.04±125.58) s in treatment (t=0.707，P=0.480)].

Chain process management effectively reduces the incidence and severity of CME in acute stroke patients undergoing multi-mode CT via the green channel, without delaying venous access establishment.

To evaluate the predictive value of baseline serum caveolin-1 (Cav-1) level for hemorrhagic transformation (HT) after bridging therapy in patients with anterior circulation large vessel occlusion.

Patients with anterior circulation large vessel occlusion who underwent bridging therapy at the First Hospital of Qiqihar from January 2022 to December 2024 were enrolled. They were divided into the hemorrhagic group (n=26) and non-hemorrhagic group (n=52) according to the presence of HT. Clinical data of the two groups were collected, including general information, cranial imaging findings, laboratory indicators, and baseline serum Cav-1 level. We analyzed whether baseline Cav-1 level could serve as an independent predictor of HT after bridging therapy. Additionally, the impact of baseline serum Cav-1 level on prognosis was evaluated based on whether the modified Rankin scale (mRS) score was ≤2 at 3 months and the mortality status of patients. The differences of measurement data were analyzed using independent sample t-test or Mann-Whitney U test. The Logistic analysis was used to identify the independent factors influencing intracranial HT, and the receiver operator characteristic (ROC) curve was plotted.

The hemorrhagic group had higher random blood glucose [8.28 (6.34, 10.99) mmol/L vs 6.22 (5.46, 8.28) mmol/L, Z=-2.459, P=0.014], lower baseline Cav-1 [109.50 (103.75, 117.25) ng/L vs 117.00 (111.50, 127.75) ng/L, Z=2.487, P=0.020], lower ASPECTS [8.00 (7.00, 10.00) vs 9.00 (8.00, 10.00), Z=-2.600, P=0.009], and higher National Institute of Health stroke scale (NIHSS) scores (15.65±2.62 vs 13.92±3.26, t=2.352, P=0.021). Multivariate analysis showed that baseline serum Cav-1 level (OR=0.90, 95%CI: 0.84-0.97, P=0.006), ASPECTS (OR=0.56, 95%CI: 0.33-0.92, P=0.022), NIHSS score (OR=1.34, 95%CI: 1.06-1.69, P=0.013), and systolic blood pressure (OR=1.03, 95%CI: 1.01-1.06, P=0.018) were all independent influencing factors for HT after bridging therapy in patients with anterior circulation large vessel occlusion. Results of the ROC curve indicated that the area under the curve (AUC) of the nomogram prediction model based on baseline serum Cav-1 level was the largest, at 0.71 (95%CI: 0.60-0.82). Higher baseline Cav-1 was associated with good prognosis [118.50 (111.00, 129.00) ng/L vs 113.00 (104.00, 117.00) ng/L, Z=-2.852, P=0.004] but not with mortality [114.00 (106.00, 116.50) ng/L vs 116.00 (108.00, 123.50) ng/L, Z=-1.127, P=0.260].

In the hemorrhagic group, baseline serum Cav-1 level and ASPECTS score were lower while NIHSS score and systolic blood pressure were higher; a low baseline serum Cav-1 level could predict HT after bridging therapy, while a high baseline serum Cav-1 level is associated with better prognosis at 3 months, without significant impact on mortality.

To evaluate the clinical efficacy and safety of edaravone dexborneol in patients with acute cerebral infarction without large artery occlusion or severe stenosis receiving intravenous alteplase thrombolysis.

Retrospective analysis was performed on 94 consecutive patients with acute ischemic stroke without large artery occlusion or severe stenosis admitted to the Stroke Center of the First Affiliated Hospital of Shihezi University between January 2022 and December 2024. Patients were divided into combination group (n=48) and thrombolysis-only group (n=46) according to whether they used edaravone-dexborneol. Baseline and post-treatment National Institutes of Health stroke scale (NIHSS) scores, modified Barthel index (BI) scores, and 90-day modified Rankin scale (mRS) scores were assessed. Symptomatic intracranial hemorrhage (sICH) incidence, mortality, and clinical efficacy at discharge were also compared. Between-group differences in NIHSS, BI, and mRS scores were analyzed with the rank sum test; sICH incidence, mortality and discharge outcomes were compared using the χ² test.

Before treatment, NIHSS, mRS and BI scores did not differ significantly between the two groups (all P>0.05). At discharge, the combination group exhibited lower NIHSS scores and lower 90-day mRS scores than the thrombolysis-only group [3 (2, 4) points vs 4 (3, 6) points; 2 (1, 3) points vs 3 (2, 4) points], and higher BI scores [75 (64, 90) points vs 68 (55, 80) points]; all differences were statistically significant (Z=-2.062, -2.269, -2.041; P=0.039, 0.023, 0.041). Moreover, the overall effective rate at discharge was significantly higher in the combination group than that in the thrombolysis-only group (81.25% vs 41.30%, χ²=17.411, P<0.001). The composite incidence of sICH and death was comparable between the two groups (4.17% vs 6.52%, χ²=0.002, P=0.961).

In patients with acute ischemic stroke who do not have large-artery occlusion or severe stenosis, the combination of edaravone-dexborneol and alteplase improves clinical outcomes and neurological function, with good safety.

To investigate the clinical efficacy of the suboccipital posterior median-telovelar approach for hypertensive pontine hemorrhage.

The clinical data of 8 patients with primary hypertensive pontine hemorrhage, who were treated by the suboccipital posterior media-telovelar approach from January 2023 to September 2023 in the Department of Neurosurgery at Zhongshan Hospital Xiamen University, were retrospectively analyzed. Univariate analysis assessed factors related to 6-month mortality, including age, gender, admission systolic blood pressure, admission diastolic blood pressure, preoperative Glasgow coma score (GCS), endotracheal intubation upon admission, time from onset to operation, hemorrhage volume, postoperative residual and hematoma clearance rate, and postoperative intracranial infection. Outcomes were assessed by the 6-month Glasgow outcome scale (GOS). Statistical analysis was performed using SPSS 26.0 software. Continuous variables were compared using the t-test or Mann-Whitney U test based on distribution characteristics; categorical variables were analyzed with Fisher's exact test.

Of the 8 patients included, 5 survived and 3 died within 6 months. No significant differences were observed between the nonsurvival group and the survival group in mean age, gender, admission systolic blood pressure, admission diastolic blood pressure, preoperative tracheal intubation, time from onset to operation, and intracranial infection (all P>0.05). Significant differences were observed between the nonsurvival and survival groups regarding preoperative GCS score [5.0 (5.0, 5.0) scores vs 4.0 (3.5, 4.0) scores, Z=2.037, P=0.042], postoperative residual [0.2 (0.2, 0.4) mL vs 1.4 (1.4, 1.5) mL, Z=2.263, P=0.024], hematoma volume [(6.30±1.04) mL vs (9.47±1.50) mL, t=3.563, P=0.012], and hematoma clearance [(95.37±3.13)% vs (84.21±3.00)%, t=4.945, P=0.003]. GOS scores at 6 months were distributed as follows: Grade Ⅰ in 3 patients, Grade Ⅱ in 1, Grade Ⅲ in 3, and Grade Ⅳ in 1.

The telovelar approach facilitates early decompression and improves hematoma evacuation in pontine hemorrhage. Preoperative GCS score, bleeding volume, postoperative residual, and hematoma clearance were significantly associated with 6-month mortality.

To explore the risk factors for early progression in patients with anterior circulation acute large vessel occlusion mild stroke (ALVO-MIS), and to evaluate the efficacy and safety of rescue endovascular treatment (REVT) after progression.

Patients with ALVO-MIS admitted to the Department of Neurology, Hanzhong Central Hospital from October 2020 to March 2024 were enrolled retrospectively. Demographic data, vascular risk factors, laboratory findings, clinical data, and 90-day outcomes were collected. The incidence of early progression in all ALVO-MIS patients was observed. Patients were categorized into a progression group (an increase of ≥4 points in the National Institutes of Health stroke scale [NIHSS] score within 3 days after optimal medical therapy, n=68) and a non-progression group (n=93). Multivariate Logistic regression were used to identify the influencing factors for early progression. According to the treatment method after early progression, patients with progression were further divided into a REVT group (n=35) and a medical therapy group (n=33). The proportion of favorable functional outcome [modified Rankin Scale (mRS) score 0-2], excellent functional outcome (mRS score 0-1), symptomatic intracranial hemorrhage (sICH), and mortality were further compared between the two groups by Chi-square test or Fisher's exact test.

Among 161 enrolled patients, 68 (42.2%) experienced early progression. Univariate analysis showed significant differences in D-dimer [(0.9±0.5) mg/L vs (0.7±0.5) mg/L], right lesion [58.8% (40/68) vs 38.7% (36/93)], diabetes mellitus [47.1% (32/68) vs 25.8% (24/93)] and M1 segment occlusion of middle cerebral artery [75.0% (51/68) vs 49.5% (46/93)] between the progressive group and the non-progressive group (t=2.507, χ²=6.376, 7.821, 9.656; P=0.013, 0.012, 0.005, 0.002 ). Multivariate regression analysis identified that diabetes (OR=4.550, 95% CI: 2.499-8.588, P=0.011) and middle cerebral artery M1 segment occlusion (OR=8.545, 95% CI: 4.708-15.500, P=0.001) as risk factors for early progression in patients with minor ischemic stroke due to anterior circulation acute large vessel occlusion. Among the 68 patients with early progression, 35 (51.5%) received REVT and 33 (48.5%) received medical treatment. Compared with the medical therapy group, the REVT group had significantly higher rates of favorable (54.3% vs 27.3%, χ²=5.117, P=0.024) and excellent (40.0% vs 9.1%, χ²=8.655, P=0.003) functional outcomes at 90 days. There were no significant differences in sICH after onset or 90-day mortality (5.7% vs 0, P=0.024; 8.6% vs 9.1%, χ²=0.124, P=0.724).

Early progression is common in ALVO-MIS patients. Diabetes and MCA M1 segment occlusion are independent risk factors. REVT may be a safe and effective treatment option following early progression.

To explore the medium- to long-term prognosis and its influencing factors in elderly patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) after stent retriever thrombectomy.

A total of 100 elderly patients with AIS-LVO who underwent stent retriever thrombectomy at Hebei Petro China Central Hospital from January 2020 to September 2022 were enrolled and followed up for 6 months. Prognosis was evaluated for prognosis by modified Rankin scale (mRS), with scores of 0-2 defined as good prognosis and 3-6 as poor prognosis. Patients were divided into elderly group (age ≥ 80 years old) and non-elderly group (age<80 years old) based on their age. Group comparisons were performed using t-tests or Chi-square tests. Factors affecting prognosis were analyzed using logistic regression.

Among 95 patients who completed follow-up, 51 (53.68%) had a good prognosis and 44 (46.32%) had a poor prognosis. Compared to the good prognosis group, the poor prognosis group had significantly higher proportions of patients aged ≥80 years, diabetes, coronary heart disease, carotid middle cerebral artery occlusion, poor reperfusion [modified cerebral infarction thrombolysis blood flow classification (mTICI)<2b], the National Institutes of Health stroke scale (NIHSS) score ≥15 at admission, NIHSS score>15 at 7 days post-operation, symptomatic intracranial hemorrhage (sICH), and cerebral hernia (all P<0.05). The onset-to-puncture time (OTP) and the puncture-to-reperfusion time (PTR) of poor prognosis group were significantly longer those in the good prognosis group, all the differences were statistically significant (all P<0.05). No significant differences were found in gender composition, underlying diseases, smoking history, alcohol consumption history, occluded site, trial of Org 10172 in acute stroke treatment (TOAST) classification, NIHSS score at admission, treatment methods, OTP, PTR, number of thrombus attempts, mTICI grading, sICH, and incidence of cerebral hernia formation between the elderly group and non-elderly group (all P>0.05), except that the good prognosis rate of the elderly group was significantly lower than that of the non-elderly group, and the NIHSS score at 7 days post-operation was significantly higher than that of the non-elderly group (P<0.05). Logistic regression analysis showed that age ≥ 80 years, diabetes, NIHSS score ≥ 15 at admission, NIHSS score>15 at 7 days post-operation, carotid middle cerebral artery occlusion, poor vascular recanalization (mTICI<2b) and sICH were independent risk factors for poor prognosis (all P<0.05).

Stent retriever thrombectomy for elderly AIS-LVO is safe and feasible, but patients aged ≥80 years benefit less. The diabetes, high NIHSS scores (admission and 7 days post-operation) carotid middle cerebral artery occlusion, poor vascular recanalization, and sICH are the main factors affecting the medium and long-term prognosis.

To investigate the role of pyroptosis in cerebral infarction and ischemia-reperfusion injury.

Twenty-four rats were randomly divided into three groups: sham-operation (Sham group, n=8), cerebral infarction (CI group, n=8), and cerebral ischemia-reperfusion (CI/R group, n=8). A focal cerebral ischemia and ischemia-reperfusion animal model was induced by the middle cerebral artery occlusion (MCAO) method. In the CI/R group, the filament was removed after 2 hours of ischemia to restore blood flow, whereas the filament was left in place in the CI group. Sham group only had surgery without inserting filament. Rats were sacrificed 24 hours post-surgery, and brain tissue and serum were collected for analysis. Pathological changes in brain tissue were observed using 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining. Western blot and immunohistochemistry were used to detect the expression of the pyroptosis-related protein Gasdermin D (GSDMD). Serum levels of interleukin (IL)-1β, S100, and neuron-specific enolase (NSE) were measured by enzyme-linked immunosorbent assay. Differences between groups were analyzed using one-way ANOVA, followed by LSD-t test for pairwise comparisons.

Compared with the Sham group, the CI group showed significantly reduced neurological function scores, extensive cerebral infarction, marked cellular edema in the infarct area, and numerous vacuoles. Compared to the CI group, the CI/R group exhibited improved neurological scores, worse infarct volume, alleviated cellular edema, and fewer vacuoles. GSDMD protein expression in the CI group [(77.07±4.18)%] was significantly higher than in the Sham group [(38.00±1.01)%], while the CI/R group [(49.33±3.42)%] showed reduced expression compared to the CI group (t=15.735, P<0.001; t=8.901, P<0.001). Serum levels of IL-1β, S100, and NSE in the Sham, CI, and CI/R groups were as follows: IL-1β [(2.69±0.83) pg/mL vs (11.63±0.93) pg/mL vs (7.42±1.06) pg/mL], S100 [(0.02±0.01) ng/mL vs (0.54±0.09) ng/mL vs (0.26±0.07) ng/mL], and NSE [(11.25±1.47) ng/mL vs (26.19±0.98) ng/mL vs (19.14±1.68) ng/mL]. The CI group had higher levels of IL-1β, S100, and NSE than the Sham group, while the CI/R group showed lower levels than the CI group, with statistically significant differences (t=6.193-18.330, all P<0.001).

Pyroptosis is involved in cerebral infarction and ischemia-reperfusion injury. Early recanalization of occluded blood vessels and restoration of cerebral blood flow can effectively inhibit pyroptosis, thereby alleviating brain damage.

To establish a cerebral ischemia-reperfusion (CIR) model in cynomolgus monkeys under digital subtraction angiography (DSA) guidance and to evaluate the application value of multimodal magnetic resonance imaging (MRI) in the modeling process.

Eight adult cynomolgus monkeys were selected, without cerebrovascular malformations or intracranial space-occupying lesions. The middle cerebral artery (MCA) was successfully embolized under DSA guidance to establish the CIR model. Multimodal MRI was performed at 1 h post-operation to confirm the embolization site and ischemic area. Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) was administered at 2.5 h, followed by serial multimodal MRI scans at 4 h, 24 h, and 7 d post-operation to assess therapeutic changes. Animals were sacrificed on day 8 for 2,3,5-triphenyltetrazolium chloride (TTC) staining of brain tissues.

Successful embolization was angiographically confirmed in six animals. Following thrombolytic reperfusion, the relative area of hyperintensity on diffusion-weighted imaging (DWI) gradually decreased at 4 h, 24 h, and 7 d, accompanied by continuously increasing apparent diffusion coefficient (ADC) values. Magnetic resonance angiography (MRA) demonstrated MCA recanalization with gradual enhancement of vascular signal intensity and increased visualization of distal branches. The relative area of TTC-unstained regions was significantly smaller than the DWI hyperintensity area at 4 h and was consistent with the MRI findings at 7 days.

A CIR model in cynomolgus monkeys can be successfully established under DSA guidance. Multimodal MRI (DWI, ADC, MRA) is valuable for dynamically evaluating vascular recanalization and changes in ischemic brain area in this model.

Acute ischemic stroke (AIS) remains one of the leading causes of mortality and long-term disability worldwide. Reperfusion therapy, as the cornerstone of AIS management, primarily includes intravenous thrombolysis (IVT) and mechanical thrombectomy (MT), both of which significantly improve outcomes by restoring blood flow to the ischemic area. In recent years, significant advances have been made in this field: ① the repertoire of IVT agents has expanded beyond alteplase to include tenecteplase, reteplase, and recombinant human prourokinase; ② imaging advancements have continuously extended the therapeutic time window; and ③ the indications for MT have broadened from anterior circulation large vessel occlusions to include posterior circulation occlusions and patients with large core infarcts. Furthermore, notable progress has been achieved in optimizing direct MT versus bridging therapy, managing reperfusion injury, and integrating artificial intelligence into diagnosis and treatment. However, persistent clinical challenges include precise the determination of the time window, management for special populations, inequitable access to medical resources, and complication mitigation. This article systematically reviews recent advances in IVT, MT, combined therapy, management of special populations, and technological innovations, aiming to provide a reference for clinical practice.

Ischemic stroke, as a major cause of disability and mortality worldwide, has a complex pathophysiological mechanism. However, current treatments such as intravenous thrombolysis and mechanical thrombectomy remain limited by narrow time windows and restricted eligibility. Therefore, it is urgent to explore new intervention targets. In recent years, circular RNA (circRNA) has gradually become a promising focus in the diagnosis and treatment of ischemic stroke due to its high stability, tissue specificity, and ability to regulate multiple pathways. Therefore, this article summarizes the regulatory role of circRNA in key links such as regulating astrocyte function and neuronal inflammatory injury, regulating apoptosis and ferroptosis, regulating cerebrovascular function and post-stroke vascular repair, and influencing endothelial cell function and blood-brain barrier integrity, in order to guide further research and explore new therapeutic targets for improving ischemic stroke.

With rising living standards and accelerated population aging, stroke has become the leading cause of premature death in China. Among all patients with ischemic stroke, about 30% of patients lack a clearly identifiable cause of the disease, known as cryptogenic stroke. In recent years, it has been found that right-to-left shunt (RLS) is closely related to cryptogenic stroke. This article reviews the recent progress in the study of the relationship between RLS and cryptogenic stroke.

Cardiogenic stroke, also defined as cardioembolic stroke (CES), accounts for 20%-30% of all ischemic stroke. Compared to ischemic stroke caused by other causes, CES has more severe clinical symptoms, poorer prognosis, and higher recurrence rate. Therefore, effective prevention and control of CES, especially the identification and intervention of its risk factors, has become a key clinical priority. This review summarizes recent advances in the understanding of risk factors for CES.