Association of plaque characteristics with long-term stroke recurrence in patients with intracranial atherosclerotic disease: a 3D high-resolution MRI-based cohort study.

OBJECTIVES: To evaluate the predictive ability of plaque characteristics for long-term stroke recurrence among patients with symptomatic intracranial atherosclerotic disease (ICAD). METHODS: This cohort study included 132 patients with acute ischemic stroke (AIS) attributed to ICAD who were recruited between July 2017 and December 2020 and followed until stroke recurrence or December 2021. Plaque surface irregularity, degree of stenosis, plaque burden, remodeling ratio, enhancement ratio, and intraplaque hemorrhage were assessed with 3-dimensional high-resolution magnetic resonance vessel wall imaging (3D HR-MRI). Data were analyzed using Cox models, receiver operating characteristic (ROC) curves, and Kaplan-Meier survival analysis. RESULTS: Of the 132 patients, during a median follow-up of 2.8 years, stroke recurrence occurred in 35 patients. The multivariable-adjusted hazard ratio (95% confidence interval) of stroke recurrence was 3.15 (1.34-7.42) per 10% increase in plaque burden and 2.17 (1.27-3.70) for enhancement ratio. The area under the curve (AUC) to predict stroke recurrence was 0.725 (95% CI 0.629-0.822) for plaque burden, 0.692 (95% CI 0.593-0.792) for enhancement ratio, and only 0.595 (95% CI 0.492-0.699) for the Essen stroke risk score. The Kaplan-Meier survival analysis further demonstrated significant differences in survival of free recurrent stroke between patients with plaque burden or enhancement ratio below and above the optimum cut-offs (both p < 0.001). CONCLUSION: Higher plaque burden and enhancement ratio are independent risk factors for long-term stroke recurrence among patients with symptomatic ICAD, and valuable imaging markers for predicting and stratifying risk of stroke recurrence. CLINICAL RELEVANCE STATEMENT: In patients with symptomatic ICAD, the results of this high-resolution magnetic resonance vessel wall imaging study have potential implications for optimal management of intracranial plaques and secondary prevention of stroke recurrence based on plaque burden and enhancement ratio. KEY POINTS: • Identification of intracranial plaque characteristics responsible for stroke recurrence is essential to preventing stroke recurrence in patients with symptomatic intracranial atherosclerotic disease. • Higher plaque burden and enhancement ratio are independent risk factors for stroke recurrence. • Plaque burden and enhancement ratio are valuable imaging markers in the prediction and stratification of the risk of stroke recurrence.

Association of visceral adiposity index with asymptomatic intracranial arterial stenosis: a population-based study in Shandong, China.

BACKGROUND AND OBJECTIVE: The visceral adiposity index (VAI), as a composite indictor to evaluate visceral adipose function, has been demonstrated to be correlated with atherosclerosis. The study objective was to explore the association between asymptomatic intracranial arterial stenosis (aICAS) and VAI in Chinese rural dwellers. METHODS: The cross-sectional study consisted of 1942 participants ≥ 40 years old who were living in Pingyin County, Shandong Province and free from history of clinical stroke and transient ischemic attack. The aICAS in the study was diagnosed by transcranial doppler ultrasound combined with magnetic resonance angiography. The multivariate logistic regression models were deployed to explore the correlation of VAI with aICAS, and receiver operating characteristic (ROC) curve were plotted to compare the performance of models. RESULTS: The participants with aICAS comparing to those without had a significantly higher VAI. After adjusting for confounding factors including age, hypertension, DM, sex, drinking habit, LDL-C, hsCRP, and smoking habit, the VAI-Tertile 3 (vs. VAI-Tertile 1) was positively associated with aICAS (OR, 2.15; 95% CI, 1.25-3.65; P = 0.005). The VAI-Tertile 3 was still markedly associated with aICAS among the underweight and normal weight (BMI ≤ 23.9 kg/m2) participants (OR, 3.17; 95% CI, 1.15-8.71; P = 0.026) with an AUC = 0.684. A similar relationship between VAI and aICAS was obtained among the participants with no abdominal obesity (WHR < 1, OR, 2.03; 95% CI, 1.14-3.62; P = 0.017). CONCLUSIONS: The possible correlation between VAI and aICAS was found to be positive for the first time among Chinese rural residents over 40 years old. A higher VAI was found to be significantly associated with aICAS among the participants who were underweight or normal weight, and these results may provide additional risk stratification information for aICAS.

Primary Central Nervous System Lymphomatoid Granulomatosis: Systemic Review.

Lymphomatoid granulomatosis (LYG) is an infrequent lymphoproliferative disease that typically involves the lungs, but may also affect the central nervous system (CNS). Isolated CNS involvement is very rare, and its clinicopathological features have not been fully elucidated. Here, we systematically reviewed the English literature through PubMed to collect all relevant case reports and small case series with pathologically confirmed primary CNS-LYG. A total of 29 relevant articles with 40 cases were included in this systemic review. In cases where T cells and B cells were compared, T cells were predominant in 19 (79.2%), and B cells were predominant in 5 (20.8%). The overall infection rate of EBV was 48.1% (13/27), among which the infection rate was 40.9% (9/22) in immunocompetent patients and 80% (4/5) in immunodeficient (HIV-infected) patients. Among the patients who underwent pathological grading, 35.7% (5/14) were at grade I, 42.9% (6/14) were at grade II, and 21.4% were at grade III. In conclusion, primary CNS-LYG is closely related to EBV infection and some cases may be predominantly T-cell phenotype. Surgical resection may be effective for mass-like lesions, although there is still a lack of standard therapeutic regimen. Accurate grading of lesions is essential for treatment selection and prognosis evaluation.

Effects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model.

OBJECTIVES: To study the effects of diet on disease progression and activity levels of adenosine monophosphate-activated protein kinase (AMPK), and its downstream targets, in an amyotrophic lateral sclerosis (ALS) animal model. METHODS: AMPK activity was measured in cerebral cortex, spinal cord, cerebellum and hindlimb muscle tissue using immunohistochemistry in transgenic mice overexpressing human superoxide dismutase-1 (SOD1(G93A)) fed a high-fat (HFD), standard ad libitum (AL) or calorie-restricted (CR) diet; AMPK activity was also measured in wild-type (SOD1(WT)) mice. Activity of AMPK and phospho-AMPK, acetyl coenzyme-A carboxylase (ACC), phospho-ACC and heat shock protein-70 (Hsp70) were also measured using Western blot. Food intake and grip strength were recorded; body composition was analysed using dual energy X-ray absorptiometry. Motor neuron survival was observed using Nissl staining. RESULTS: AMPK activity increased and Hsp70 expression decreased in AL SOD1(G93A) mice compared with SOD1(WT) mice in spinal cord and hindlimb muscle. Compared with AL SOD1(G93A) mice, CR SOD1(G93A) mice showed increased AMPK activity, downregulated Hsp70 expression, reduced motor neuron survival in spinal cord and hindlimb muscle and reduced lifespan; HFD SOD1(G93A) mice showed opposite effects. CONCLUSIONS: In this mouse model, increased AMPK activity seems to play a negative role in motor neuron survival, possibly through a novel mechanism involving Hsp70 downregulation. These changes can be modified by diet. Inhibition of AMPK may provide a therapeutic strategy for ALS.

Adenosine monophosphate-activated protein kinase activation enhances embryonic neural stem cell apoptosis in a mouse model of amyotrophic lateral sclerosis.

Alterations in embryonic neural stem cells play crucial roles in the pathogenesis of amyotrophic lateral sclerosis. We hypothesized that embryonic neural stem cells from SOD1(G93A) individuals might be more susceptible to oxidative injury, resulting in a propensity for neurodegeneration at later stages. In this study, embryonic neural stem cells obtained from human superoxide dismutase 1 mutant (SOD1(G93A)) and wild-type (SOD1(WT)) mouse models were exposed to H2O2. We assayed cell viability with mitochondrial succinic dehydrogenase colorimetric reagent, and measured cell apoptosis by flow cytometry. Moreover, we evaluated the expression of the adenosine monophosphate-activated protein kinase (AMPK) α-subunit, paired box 3 (Pax3) protein, and p53 in western blot analyses. Compared with SOD1(WT) cells, SOD1(G93A) embryonic neural stem cells were more likely to undergo H2O2-induced apoptosis. Phosphorylation of AMPKα in SOD1(G93A) cells was higher than that in SOD1(WT) cells. Pax3 expression was inversely correlated with the phosphorylation levels of AMPKα. p53 protein levels were also correlated with AMPKα phosphorylation levels. Compound C, an inhibitor of AMPKα, attenuated the effects of H2O2. These results suggest that embryonic neural stem cells from SOD1(G93A) mice are more susceptible to apoptosis in the presence of oxidative stress compared with those from wild-type controls, and the effects are mainly mediated by Pax3 and p53 in the AMPKα pathway.