Wei Hung Chen

Gender differences and age-related white matter changes of the human brain: A diffusion tensor imaging study

Cerebral white matter undergoes various changes with normal aging. This study investigated the association between age, gender, and the global and regional fractional anisotropy (FA) and mean diffusivity (MD) in 145 adults (30 to 80 years old) using diffusion tensor magnetic resonance imaging. We studied sixteen regions of interest in both hemispheres to search for regions that display age- and gender-related white matter changes and also performed a complementary voxel-based analysis without any hypothesis a priori. On a global scale, our results indicate that the full brain FA was negatively correlated with age. The regional analysis showed that the anterior corpus callosum, the bilateral anterior and posterior internal capsule, and the posterior periventricular regions had the most significant age-related FA decrease. On the other hand, the FA in the temporal and occipital regions was not correlated with age. However, in contrast to males, females overall had a significantly lower FA in the right deep temporal regions. More gender differences in precentral, cingulate, and anterior temporal white matter areas were also found, suggesting that microstructural white matter organization in these regions may have a sexual dimorphism. Such differences were mainly due to the increase in diffusion perpendicular to fiber tracts.

Fibrinogen Independently Predicts the Development of Ischemic Stroke in a Taiwanese Population CVDFACTS Study

BACKGROUND AND PURPOSE Of few prospective studies that have focused on the relationship between fibrinogen and ischemic stroke (IS) in Asian populations, the findings were inconsistent with those conducted in Western countries. Therefore, we aimed to investigate the temporal relationship between fibrinogen levels (plus several related parameters) and IS in a community-based study in Taiwan. METHODS Baseline data from 3281 adults (>or=20 years of age) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental IS status derived from insurance claims and death certificate records. Hazard ratios and 95% CIs of clotting factors (fibrinogen, factor VII, factor VIII, and antithrombin-III) for IS events were estimated using Cox proportional hazard models. RESULTS With 10.4 years (average) follow-up, 128 persons developed IS (3.75 per 1000 person-years). As expected, elevated blood pressure and diabetes were independent predictors of IS events. A dose-response relationship was found in univariate analysis between IS risk and tertiles of fibrinogen (hazard ratio, 3.73; 2.19 to 1.00), factor VII (hazard ratio, 1.86; 1.35 to 1.00), and factor VIII (2.97; 1.70 to 1.00), respectively, but not for antithrombin-III. After adjusting for confounding and known risk factors, fibrinogen independently predicted IS events. A 72% increase (hazard ratio, 1.72; 1.02 to 2.90) in IS risk was observed for individuals with fibrinogen >or=8.79 mumol/L compared with those <7.03 micromol/L. CONCLUSIONS In addition to hypertension and diabetes, fibrinogen independently predicted future IS risk. We suggest that fibrinogen may be considered in the risk assessment model for IS in the Taiwanese population.

Reversible posterior leukoencephalopathy syndrome caused by blood transfusion: a case report.

This is a case report of a 32-year-old woman with chronic severe anemia who developed headaches and seizures 5 days after receiving a blood transfusion of eight units (1600 ml) of packed red blood cells. Magnetic resonance imaging indicated vasogenic edematous lesions bilaterally over the occipital lobes that were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Her blood pressure was normal, and no other contributing factors for RPLS were found. It is likely that the initiator was the large volume of transfused blood, which disrupted cerebral autoregulation and damaged the vasculoendothelial system. Similar cases of RPLS following transfusion have been reported, and all reports involved middle-aged females with chronic severe anemia who received large volumes of transfused blood within a short period of time. Although blood transfusion is a common procedure with rare neurological complications, great caution should be taken with chronic severely anemic patients because a rapid elevation in hemoglobin may precipitate RPLS.

Adults With Late Stage 3 Chronic Kidney Disease Are at High Risk for Prevalent Silent Brain Infarction A Population-Based Study

Background and Purpose— The close relationship between stroke and chronic kidney disease (CKD) has been well-documented. However, few studies have focused on silent brain infarction (SBI) in CKD. We investigated the prevalence of SBI in different stages of CKD. Methods— We included 1312 participants aged 30 to 93 years who came from either a random sample of residents or from a group of physically examined subjects in the same community. Basic information, clinical evaluations, laboratory tests, and MRI images were assessed. Subjects were divided into groups 1, 2, 3a, and 3b, corresponding to the estimated glomerular filtration rate (eGFR) levels of ≥90.0, 60.0 to 89.9, 45.0 to 59.9, and 30.0 to 44.9 mL/min/1.73 m2. Results— The crude prevalence was 4.7%: 2.6% (20 of 759 subjects) in group 1; 6.3% (32 of 506) in group 2; 12.9% (4 of 31) in group 3a; and 37.5% (6 of 16) in group 3b (P<0.001). Additionally, SBI also correlated with age, male sex, hypertension, diabetes, moderate carotid plaque, higher blood pressures, obesity, and levels of triglyceride, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and uric acid (all P<0.05). The effects for SBI risk in each eGFR group versus group 1 did not increase except for group 3b (OR, 9.34; P<0.001). Conclusions— A close association exists between SBI and eGFR. We have found a significant increase in prevalence of SBI when eGFR is between 30.0 and 44.9 mL/min/1.73 m2. Adults with late stage 3 CKD are at high risk for prevalent SBI.

Association of blood active matrix metalloproteinase-3 with carotid plaque score from a community population in Taiwan

OBJECTIVE Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of atherosclerosis. However, the relationship between blood levels of MMPs and the extent of carotid atherosclerosis remains uncertain. We assessed blood levels of active MMPs in relation to the extent of carotid plaque formation and intima-media thickness (IMT) in a community population in Taiwan. METHODS In 433 subjects from a community primary stroke prevention program, blood levels of active MMP-1, total and active MMP-3 and active MMP-9 were determined using enzyme-linked immunosorbent assays, carotid plaque score (PS) and IMT by high-resolution B-mode ultrasonography and the common MMP-1, MMP-3, and MMP-9 promoter low- and high-activity genotypes by polymerase chain reaction and restriction fragment length polymorphism. RESULTS Study subjects were separated into 3 groups based on PS: group 1 (PS=0), group 2 (PS=1-2) and group 3 (PS≥3). Blood levels of active and total MMP-3 bear a highly significant relationship with PS (both p<0.0001). A multiple ordinal logistic regression analysis revealed that blood levels of active MMP-3 are correlated with PS (OR, 1.4; 95% CI, 1.1-1.8; p=0.0038) but not IMT. MMP-3 -1612 6A6A is a dominant genotype in this population, which is associated with higher levels of blood active MMP-3. CONCLUSION Blood levels of active MMP-3 are associated with the extent of carotid atherosclerosis based on PS but not IMT in this community population in Taiwan and the MMP-3 -1612 6A6A genotype is associated with higher levels of blood active MMP-3.

Clinical Characteristics of MuSK Antibody-positive Myasthenia Gravis in Taiwan

Circulating antibodies of the acetylcholine receptor (AchRAb) are detectable in most patients with generalized myasthenia gravis (MG). A newly discovered antibody against muscle-specific kinase (MuSKAb) has been detected in 40-70% of AchRAb-negative MG patients. We report a series of Taiwanese MuSKAb-positive patients, and compare their clinical features with MuSKAb-negative patients and also with MuSKAb-positive Caucasians. Five out of 44 seronegative generalized MG patients (11.4%) were positive for MuSKAb. Patients with MuSKAb tended to have severe disability and bulbar involvement, and more often experienced crisis or impending crisis. Although all of these patients showed an initial response to immunosuppressant therapy, they had greater disability at follow-up. The clinical features of Taiwanese MuSKAb-positive patients were not different from those of Caucasians, except for a lower prevalence.

MuSK antibody clearance during serial sessions of plasmapheresis for myasthenia gravis

To evaluate the relationship of antibody clearance and clinical improvement for myasthenia gravis (MG) patients with MuSK antibody (MuSKAb) receiving one course of double-filtration plasmapheresis (DFP) treatment, we prospectively recorded their MG scores and measured MuSKAb concentrations before and after each DFP treatment session in two MuSKAb-positive patients. The clinical improvement trends roughly paralleled the reductions of MG score, except for the late rebound of MuSKAb in the 6th DFP treatment session, without concomitant clinical worsening in one patient. Longitudinal analysis on the serological changes during the serial sessions revealed that the levels of MuSKAb fell by 44%, 59%, 79%, 82%, 92%, and 71% in patient 1 and 52%, 70%, 78%, 87%, and 90% in patient 2. The titers of MuSKAb decreased constantly during the first 5 DFP treatment sessions. MuSKAb clearance per session for the 11 sessions ranged from 19% to 56%, with a mean of 45%. In conclusion, DFP was effective for MuSKAb removal and amelioration of clinical weakness for our two patients with MuSKAb. A 5-session protocol cleared 90% of serum MuSKAb.

Comparison of Transcranial Color‐Coded Sonography and Magnetic Resonance Angiography in Acute Ischemic Stroke

Background and Purpose. This study was designed to assess the accuracy of transcranial color‐coded sonography (TCCS) as compared to magnetic resonance angiography (MRA) for detecting intracranial arterial stenosis in patients with acute cerebral ischemia. Methods. The authors prospectively identified 120 consecutive patients admitted with acute ischemic stroke and performed both TCCS and MRA with a mean interval of 1 day. TCCS data (sampling depth, peak systolic and end diastolic angle‐corrected velocity, mean angle‐corrected velocity, and pulsatility index) for middle cerebral arteries (MCAs) were compared to MRA data and classified into 4 grades: normal (grade 1): normal caliber and signal; mild stenosis (grade 2): irregular lumen with reduced signal; severe stenosis (grade 3): absent signal in the stenotic segment (flow gap) and reconstituted distal signal; and possible occlusion (grade 4): absent signal. The cutoffs were chosen to maximize diagnostic accuracy. Results. Interobserver agreement for MRA grading resulted in a weighted‐kappa value of 0.776. The rate of poor temporal window was 37% (89/240). Doppler signals were obtained in 135 vessels, and the angle‐corrected velocities (peak systolic, end diastolic, mean) were significantly different (P= .001, P= .006, P < .001) among the MRA grades: grade 1 (100, 47, 68 cm/s), grade 2 (171, 72, 110 cm/s), grade 3 (226, 79, 134 cm/s), grade 4 (61, 26, 39 cm/s). Additionally, an angle‐corrected MCA peak systolic velocity ≥120 cm/s correlates with intracranial stenosis on MRA (grade 2 or worse) with high specificity (90.5%; 95% confidence interval = 78.5%∼96.8%) and positive predictive value (93.9%) but relatively low sensitivity (66.7%; 95% confidence interval = 61.2%∼69.5%) and negative predictive value (55.1%). Conclusion. Elevated MCA velocities on TCCS correlate with intracranial stenosis detected on MRA. An angle‐corrected peak systolic velocity ≥120 cm/s is highly specific for detecting intracranial stenosis as defined by significant MRA abnormality.

Plasmapheresis Does Not Affect Polysomnographic Parameters in Patients With Myasthenia Gravis: A Case Series Study

The purpose of this study was to evaluate the influence of plasmapheresis on sleep in patients with generalized myasthenia gravis and no respiratory symptoms. Seven myasthenia gravis patients, four women and three men, aged 24-52 years, underwent plasmapheresis treatment because of recent worsening of clinical weakness and poor response to previous treatments. We prospectively recorded the myasthenia gravis score, measured acetylcholine-receptor antibody concentration, performed polysomnography, and checked the Epworth Sleepiness Scale at baseline and 1 day after completion of the last session of plasmapheresis. Myasthenic weakness was ameliorated following plasmapheresis in all patients with a median decrease in myasthenia gravis score of 2 points (P = 0.0002) and a median clearance of 43.3% of acetylcholine-receptor antibody. However, there was no significant change in polysomnographic parameters, except for a trend toward shorter duration of the longest apnea period (P = 0.0763) following the treatment. Plasmapheresis did not affect polysomnographic parameters despite improved clinical weakness along with decreased myasthenia gravis score and acetylcholine-receptor antibody concentration.

Association of Estrogen Receptor α Genotypes/ Haplotypes With Carotid Intima-Media Thickness in Taiwanese Women

The estrogen receptor α gene (ESR1) is an important mediator of the atheroprotective effect of estrogen on the vasculature system. We examined the potential associations between common single nucleotide polymorphism (SNP) variants of ESR1 and intima-media thickness (IMT) in carotid arteries, a strong predictor of cardiovascular disease (CVD). A total of 760 study participants (343 men and 407 women), who had undergone a Duplex ultrasonographic examination of carotid artery, were investigated. Measurement of IMT was performed on a 10-mm segment of the common carotid artery (CCA). Fourteen sequence-validated SNPs of high frequency of Oriental origin were selected and genotyped by the method of Light-Cycler-480-assisted real-time polymerase chain reaction (PCR) followed by melting curve analysis. Results from multiple linear regression analyses showed significant associations of SNPs rs2228480 (Ex8+229G>A) and rs3798758 (Ex8+1988C>A) with the carotid IMT values in women but not in men. Women with SNP rs2228480 (Ex8+229G>A) A/A genotype had a 0.048 mm (7.1%) increase in IMT values versus the other genotypes combined (P = .030). In women who carried the rs3798758 (Ex8+1988C>A) CA+AA combined genotypes, their carotid IMT measures were 0.020 mm (2.9%) decreased as compared with those in women who carried C/ C genotype (P = .042). In haplotype analysis, women with the T-A haplotype versus C-C haplotype of combined rs3798577 (Ex8+1264T>C) and rs3798758 (Ex8+1988C>A) were also found to be associated with a decreased IMT value at a borderline significance (P = .057). Some common SNPs in the ESR1 could be important in modulating carotid atherosclerosis and thereby CVD susceptibility in Taiwanese women.