Muke Zhou

Statin treatment reduces the risk of poststroke seizures

Objective: To examine the potential efficacy of statin treatment in reducing the risk of poststroke seizures. Methods: In this cohort study, patients with a first-ever ischemic stroke and no history of epilepsy before stroke were enrolled. After a mean follow-up period of 2.5 years, a follow-up assessment was performed to identify poststroke epilepsy. Logistic regression and Cox regression analyses were used to assess the relationship between statin use and poststroke early-onset seizures or poststroke epilepsy. Results: Of 1,832 enrolled patients, 63 (3.4%) patients had poststroke early-onset seizures and 91 (5.0%) patients had poststroke epilepsy. Statin use was associated with a lower risk of poststroke early-onset seizures (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.20–0.60, p < 0.001), and this reduced risk was seen mainly in patients who used a statin only in the acute phase (OR 0.36, 95% CI 0.20–0.62, p < 0.001). No significant association was found between statin use and poststroke epilepsy (OR 0.81, 95% CI 0.52–1.26, p = 0.349). In 63 patients who presented with early-onset seizures, statin use was associated with reduced risk of poststroke epilepsy (OR 0.34, 95% CI 0.13–0.88, p = 0.026). Conclusions: Statin use, especially in the acute phase, may reduce the risk of poststroke early-onset seizures. In addition, statin treatment may prevent the progression of initial poststroke seizure-induced neurodegeneration into chronic epilepsy. Because of the observational nature of the study, more studies are needed to confirm the results. Classification of evidence: This study provides Class III evidence that in patients with a first-ever ischemic stroke, the early use of statins reduces the risk of early poststroke seizures.

Pseudotumor Cerebri Syndrome and Giant Arachnoid Granulation: Treatment with Venous Sinus Stenting

The authors describe a patient with pseudotumor cerebri syndrome who showed at venography a giant arachnoid granulation in the left dominant transverse sinus and hypoplasia of the contralateral transverse sinus with high pressure proximal to the obstruction. Dilation of the left transverse sinuses with a stent reduced both the pressure gradient across the arachnoid granulation and the cerebral spinal fluid opening pressure with immediate symptomatic improvement, suggesting a causal relationship between venous outflow obstruction and pseudotumor cerebri syndrome.

Radix/Rhizoma Notoginseng extract (Sanchitongtshu) for ischemic stroke: A randomized controlled study

Agents of sanchi have been widely used as a complementary medicine for stroke in China. Sanchitongshu is a new Chinese patent medicine extracted from sanchi which has stronger anti-platelet activity than other agents of sanchi. Our aim was to investigate the synergistic action of low dose of aspirin combined with sanchitongshu capsule in the treatment of patients with light and moderate ischemic stroke in acute and subacute stages. This was a multi-center, double-blinded, randomized controlled clinical trial conducted in four hospitals in China from July 2004 to 2006. 140 patients of ischemic stroke in anterior cerebral circulation within 30 days of onset were enrolled. Participants were assigned either to receive aspirin (50mg per day) and sanchitongshu capsule (200mg three times a day) or aspirin (50mg per day) and placebo capsule. Low dose of aspirin combined with sanchitongshu capsule significantly ameliorated neurological deficit (increased score of ESS: t=-5.02, p<0.0001) and activities of daily living (increased score of BI: t=-2.4, p=0.0178) after treatment compared with aspirin alone. Adverse reaction which occurred equally in both arms, was light to moderate and disappeared without special treatment. Sanchitongshu capsule, as a complementary medicine to aspirin, was effective in improving outcomes after ischemic stroke. It was a safe drug in our trial.

Functional Alterations of Pain Processing Pathway in Migraine Patients with Cutaneous Allodynia

OBJECTIVE Cutaneous allodynia (CA) is a characteristic of central sensitization, predicting migraine progression, and poor response to therapy. The present study aimed to find out the cerebral functional alterations related to the establishment of central sensitization in migraineurs using functional magnetic resonance imaging (fMRI). DESIGN The experiment was performed in 15 migraineurs with Cutaneous allodynia (MWCA) and 19 patients without Cutaneous allodynia (MWoCA) in the interictal phase, and 20 matched healthy controls. Blood oxygen level dependent-fMRI was applied in all subjects when they were given transcutaneous electrical nerve stimulation at the left medial forearm, achieving to a predetermined level of pain sensation (i.e., visual analogue scale [VAS] = 40). Contrast images were then produced to determine whether this disorders present functional changes in the brain during pain processing. RESULTS Demographic and headache characteristics were balanced between groups. The contrast images of both migraine groups comparing to healthy controls exhibited weaker activation of various brain regions (e.g., cerebellum and insulae), which might be relevant to the pathophysiological procedure of migraine. The direct comparison between the two migraine groups revealed that activation in the dorsal pons and contralateral (right) inferior parietal lobule of MWCA subjects were significantly lower than it in MWoCA ones. CONCLUSIONS The interictal dysfunction of pain processing pathway may be responsible for (at least relevant to) central sensitization in migraine patients, via abnormal modulations of nociceptive transmission.

CRP gene polymorphism predicts post‐stroke functional outcome in Han Chinese

Stroke is a major cause of long‐term disability and morbidity worldwide. C‐reactive protein (CRP), an inflammatory marker, has been reported to be an independent predictor of functional outcome after ischemic stroke (IS). Because several single nucleotide polymorphisms (SNPs) at the CRP locus have been linked with elevated CRP levels, we hypothesized that CRP genetic variation might be associated with functional disability in patients after first‐ever IS.

Vertebral artery hypoplasia and vertebral artery dissection A hospital-based cohort study

Objective: To test the hypotheses that vertebral artery hypoplasia (VAH) is associated with an increased risk of ipsilateral spontaneous vertebral artery dissection (sVAD) and that hypoplastic vertebral arteries (VAs) are more prone than dominant VAs to dissection. Methods: In this case-control study, the population comprised 112 patients with sVAD and 224 age- and sex-matched controls treated at a high-volume center between 2005 and 2013. VAH and sVAD were diagnosed by digital subtraction angiography combined with noninvasive imaging findings. Conditional logistic regression was performed to identify independent risk factors for sVAD. Relationships between sVAD and VAH and the likelihood of ipsilateral (vs contralateral) presentation were also assessed. Results: VAH was more frequent in patients with sVAD than in controls in univariate analysis (30.4% vs 17.4%; odds ratio [OR] 2.1; 95% confidence interval [CI] 1.2–3.6; p = 0.008) and in multivariate regression analysis adjusted for migraine, hyperhomocysteinemia, smoking, trivial trauma, prior infection, and associated connective tissue/vascular disorders (OR 2.0; 95% CI 1.1–3.5; p = 0.017). Migraine, current smoking, and trivial trauma were associated with sVAD in multivariate models. sVAD was more frequently detected in hypoplastic than dominant VAs (68.0% vs 32.0%; OR 4.1; 95% CI 1.7–9.7; p = 0.002). Conclusions: sVAD is associated with ipsilateral VAH and occurs more frequently in hypoplastic VAs than in their normal counterparts.

Cognitive impairment and whole brain diffusion in patients with carotid artery disease and ipsilateral transient ischemic attack

Abstract Objectives: Transient ischemic attack (TIA) with carotid artery disease (CAD) can increase the risk of cognitive decline. However, the neural mechanisms of the disorder remain unclear. The aim of this study was, using diffusion tensor imaging (DTI), to detect microstructural changes in patients with symptomatic CAD presenting with TIA, and to explore their relationship with cognitive functions. Methods: In all, 35 patients with right-sided CAD and ipsilateral TIA and 35 healthy controls were investigated using cognitive tests and voxel-based analysis (VBA) of DTI. The whole brain DTI parameters, fractional anisotropy (FA) and mean diffusivity (MD), were calculate and compared between two groups. A correlation analysis was also performed to explore the relationship between cognitive test scores and whole brain FA and MD values in the patients. Results: We observed two interesting findings. First, compared with the controls, the patients showed significantly increased MD in the right anterior cingulate gyrus (ACG) and decreased FA in the right amygdala. Second, the MD values in the right ACG were negatively correlated with Montreal Cognitive Assessment (MoCA) in the patients. Conclusions: Diffusion tensor imaging parameters are altered in patients with CAD and ipsilateral TIA, which indicates the existence of microstructural abnormalities in the brain of the patients. The significant correlation between DTI abnormalities and cognition reveals the potential of DTI for investigating the pathophysiology mechanism related to the cognitive dysfunction of the disease.

Altered Resting-State Functional and White Matter Tract Connectivity in Stroke Patients With Dysphagia

Background. Swallowing dysfunction is intractable after acute stroke. Our understanding of the alterations in neural networks of patients with neurogenic dysphagia is still developing. Objective. The aim was to investigate cerebral cortical functional connectivity and subcortical structural connectivity related to swallowing in unilateral hemispheric stroke patients with dysphagia. Methods. We combined a resting-state functional connectivity with a white matter tract connectivity approach, recording 12 hemispheric stroke patients with dysphagia, 12 hemispheric stroke patients without dysphagia, and 12 healthy controls. Comparisons of the patterns in swallowing-related functional connectivity maps between patient groups and control subjects included (a) seed-based functional connectivity maps calculated from the primary motor cortex (M1) and the supplementary motor area (SMA) to the entire brain, (b) a swallowing-related functional connectivity network calculated among 20 specific regions of interest (ROIs), and (c) structural connectivity described by the mean fractional anisotropy of fibers bound through the SMA and M1. Results. Stroke patients with dysphagia exhibited dysfunctional connectivity mainly in the sensorimotor-insula-putamen circuits based on seed-based analysis of the left and right M1 and SMA and decreased connectivity in the bilateral swallowing-related ROIs functional connectivity network. Additionally, white matter tract connectivity analysis revealed that the mean fractional anisotropy of the white matter tract was significantly reduced, especially in the left-to-right SMA and in the corticospinal tract. Conclusions. Our results indicate that dysphagia secondary to stroke is associated with disruptive functional and structural integrity in the large-scale brain networks involved in motor control, thus providing new insights into the neural remodeling associated with this disorder.

The functional SNP rs4376531 in the ARHGEF gene is a risk factor for the atherothrombotic stroke in Han Chinese

The gene encoding RhoA guanine nucleotide exchange factor 10(ARHGEF10) has been reported to be a risk factor for atherothrombotic stroke (AS) in Japanese. The single-nucleotide polymorphism (SNP) rs4376531 in intron 16 on ARHGEF10 is associated with AS and may play a role in the disease pathology. In order to explore the nature of this association in greater detail and in a new ethnic group, we carried out a case-control study to determine whether the rs4376531 polymorphism in ARHGEF10 is a risk factor of AS in Han Chinese people. This study was carried out to assay the frequency of genotypes and alleles of SNP rs4376531 in ARHGEF10 in patients with ischemic stroke and healthy controls using the polymerase chain reaction and the restriction fragment length polymorphism (PCR-RFLP) technique. A total of 383 individuals with AS in West China Hospital and 214 unrelated healthy controls were recruited. The frequencies of the G allele and GG genotype of the rs4376531 polymorphism were higher in the patients with AS than in control individuals: frequency of G, 91.0% vs 83.4%, P<0.001; GG, 82.2% vs 67.8%, P<0.001. After adjusting for sex, age, and multiple cardiovascular risk factors, the homozygous GG genotype for this variant was associated with a higher risk of AS, with an adjusted odds ratio of 4.99 (95% CI, 2.55-7.81, P< 0.001). Our findings suggest that the rs4376531 polymorphism in the ARHGEF10 gene is a risk factor for AS in the Han Chinese population.

A novel SCN1A mutation identified in a Chinese family with familial hemiplegic migraine: A case report

Background Familial hemiplegic migraine (FHM) is a rare type of migraine with aura that is characterized by transient hemiparesis. Mutations in three genes (CACNA1A, ATP1A2, and SCN1A) have been found to cause FHM. Among these, nine SCN1A gene mutations were reported to cause familial hemiplegic migraine type 3 (FHM3). However, none of them was reported in China. Method The clinical manifestations of a Chinese FHM family were recorded and all coding exons and flanking intronic regions of the CACNA1A, ATP1A2, and SCN1A genes were tested for mutations. Results All FHM patients in the investigated family have typical hemiplegic migraine attacks characteristic of FHM. We identified a novel mutation (p.Leu1670Trp) of the SCN1A gene. The affected amino acid is highly conserved across different species and therefore likely plays an important role in SCN1A gene function. Conclusion The identification of a novel mutation in the SCN1A gene in the Chinese population may further aid in the understanding of FHM genetics.