TMAO as a Novel Predictor of Major Adverse Vascular Events and Recurrence in Patients with Large Artery Atherosclerotic Ischemic Stroke.

OBJECTIVES: To explore the association of plasma trimethylamine N-oxide (TMAO) concentration with large artery atherosclerotic (LAA) ischemic stroke and its role in predicting neurological outcome and major vascular event recurrence. MATERIALS AND METHODS: We performed a case-control study that included patients with first-ever LAA stroke as cases (n = 291) and asymptomatic patients as controls (n = 235). Clinical data and venous blood samples were collected within 72 hours after stroke. All subjects were followed for 3 months. TMAO level was detected by liquid chromatography mass spectrometry (LC-MS). Logistic and Cox proportional hazard regression were performed to evaluate plasma TMAO concentration as a predictor of LAA stroke and major vascular event recurrence, respectively. Kaplan-Meier survival analysis was performed to compare major vascular event recurrence between patients with high and low TMAO concentration. RESULTS: After adjusting for traditional stroke risk factors, the plasma TMAO level was significantly higher in the LAA stroke group than the control group (OR = 1.031, 95% CI 1.024-1.037, P < .001). At a cutoff level of 106.9 pg/ml, TMAO had a sensitivity of 63.23% and specificity of 80.00% in discriminating the LAA stroke subjects from the controls in Receiver operator characteristic (ROC) analysis. Kaplan-Meier survival analysis demonstrated TMAO plasma concentration was significantly relevant with recurrent vascular events (Log Rank, P = .006). Moreover, this association was still existed after adjusting for traditional risks (adjusted HR, 3.128; 95% CI, 1.018-9.610) in Cox regression model. But TMAO plasma levels were not relevant with functional disability after 3 months of the LAA stroke. CONCLUSION: Elevated plasma TMAO concentration was independently associated with LAA ischemic stroke. The risk of major vascular event recurrence increased by 2.128 times in the LAA stroke subjects with plasma TMAO level higher than 126.83 pg/mL. Plasma TMAO concentration might be a potential biomarker of major vascular event recurrence.

Characteristics of the ischemic stroke patients whose seizures occur at stroke presentation at a single institution in Eastern China.

PURPOSE: We compared clinical characteristics and outcomes of the early-onset seizure post-stroke patients who had seizures occurring at stroke presentation (SSP) with other patients without SSP at a single institution in Eastern China. METHODS: We reviewed 20,947 ischemic stroke patients in our hospital electronic medical records system from January 2007 to December 2016. Among them, there were 91 (0.43%) patients with early-onset seizure post-stroke. Among these 91 patients, there were 35 (0.16%) SSP patients and another 56 (0.27%) were designated as non SSP patients because they also had early-onset seizure post-stroke, but without SSP. We compared the clinical presentations of the SSP patients with those of the non SSP patients including baseline stroke risk factors, and 10-year Kaplan-Meier death risk after their first stroke. RESULTS: In the SSP patients, 25.7% of them presented with posterior circulation infarction, whereas only 12.5% of the non SSP patients had this condition (P<0.05). In contrast, 17.1% of the SSP patients were being treated with antiepileptic drugs at discharge whereas 37.5% of the non SSP patients received such treatment (P<0.05). The percentage of SSP patients with temporal lobe lesions was less than in non SSP patients (P<0.05). However, brain stem and thalamus lesions were more frequently seen in SSP patients than non in SSP patients (P<0.05). The risk factors for ischemic stroke including a history of hypertension, diabetes mellitus, hyperlipidemia and atrial fibrillation were the same in these two groups (P>0.05). In the SSP patients group, the 10-year risk of death was 36.9% after the initial seizure incident, and in the non SSP patients group, the 10-year death risk was 40.1%, but this difference between the two groups was not significant (P>0.05). CONCLUSIONS: Ischemic stroke patients with SSP had some unique signs that included a higher incidence of posterior circulation infarction than non SSP patients.

Eight-and-a-half syndrome caused by a pontine haemorrhage: a case report and review of the literature.

BACKGROUND: Eight-and-a-half syndrome is caused by a lesion in the dorsal tegmentum of the caudal pons involving parapontine reticular formation and median longitudinal fasciculus, as well as the nucleus and/or the fasciculus of the facial nerve. It is characterized by one-and-a-half syndrome and an ipsilateral cranial nerve VII palsy. Also, many variants of eight-and-a-half syndrome have been described, including nine syndrome, thirteen-and-a-half syndrome and fifteen-and-a-half syndrome. METHODS: We describe a case of a 49-year-old man who presented with eight-and-a-half syndrome combined with contralateral hemiparesis. We reviewed the literature describing the related spectrum of eight-and-a-half syndrome associated with various etiologies. RESULTS: Brain computed tomography scan revealed a hyperdensity located in the left paramedian aspect of the dorsal pons. T2-weighted magnetic resonance imaging at the 11-month follow-up showed hyperintensity and enlargement of the inferior olivary nuclei, which were compatible with a diagnosis of hypertrophic olivary degeneration. In light of our observations and cases reported in the literature, we categorize the spectrum of eight-and-a-half syndrome into three types, namely classic eight-and-a-half syndrome, eight-and-a-half syndrome variants and eight-and-a-half plus syndrome. Besides, the clinical feature and outcome of the three types are discussed in this article. CONCLUSIONS: Recognition of the spectrum of eight-and-a-half syndrome allows precise anatomic localization of the lesion to pontine tegmentum region.

Association of Matrix Metalloproteinase-1 and Matrix Metalloproteinase-3 Gene Variants with Ischemic Stroke and Its Subtype.

BACKGROUND: Genetic variations in the genes of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of ischemic stroke (IS). Here we investigate the association between MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A genetic polymorphisms and etiological subtypes of IS in the Han Chinese population. METHODS: A total of 640 eligible patients with IS and 637 age- and gender-matched apparently healthy volunteers were enrolled. Subtypes of IS were classified by Trial of Org 10172 in Acute Stroke Treatment criteria. MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of the 5A/6A + 5A/5A genotypes and 5A allele were significantly higher in patients with IS than in controls (P <.001, P <.001, respectively). No association was found between MMP-1 1G/2G polymorphism and overall IS. In subgroup analyses, MMP-1 1G/2G and 2G/2G genotypes increased the risk of small-artery occlusion (SAO) subtype (multivariate-adjusted, P <.001, P = .002, respectively), and MMP-3 5A/6A + 5A/5A genotypes were related with large-artery atherosclerosis (LAA) subtype (multivariate-adjusted, P <.001). Haplotype analyses indicated that 2G-6A and 1G-5A increased the risk of SAO (multivariate-adjusted, P = .029) and LAA (multivariate-adjusted, P <.001), respectively. CONCLUSIONS: MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms may contribute to different subtypes of IS susceptibility.

Five-year experience of 101 adult patients with moyamoya disease at a single institution in Eastern China.

This retrospective study included 101 adult moyamoya disease (MMD) patients of whom 58 were females and 43 were males in Wenzhou, China. Clinical and diagnostic features, surgical treatment, follow-up information and outcomes constitute this review. The modified Rankin Scale (mRS) was used to determine the neurological functional outcome. The Kaplan-Meier method was used to estimate recurrent stroke and mortality risk based on drug treatment alone or in combination with revascularization. The mean age at symptom onset was 43.3 (range, 18-64)years. The initial symptom was either hemorrhage, ischemia or transient ischemic attack (TIA) in 90, 6 and 5 patients, respectively. The median follow-up time in 84 patients was 26.5 (range, 6-62)months. Ten patients were treated with revascularization. In the remaining drug-treated group, the 5-year risk of recurrent stroke and death was 8% following onset of initial symptoms, while it was 25% in the revascularization group. However, the difference between these two groups was not significant (p>0.05). There was also no difference in mRS between these two groups upon patient discharge, but in the revascularization group was lower than that in the drug-treated group at their last follow-up (p<0.05). Adult MMD patients were most ikely to present with hemorrhage and had a better neurological functional outcome after revascularization than from medical therapy. However, revascularization did not decrease the recurrent stroke incidence or mortality risk. These results are different from those reported by other Chinese and foreign institutions.

Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent atherosclerotic ischemic stroke in Chinese.

Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (-1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09-2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (-1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy.