Chia-Yi Lien

Salience Network and Depressive Severities in Parkinson’s Disease with Mild Cognitive Impairment: A Structural Covariance Network Analysis

Purpose: In Parkinson’s disease with mild cognitive impairment (PD-MCI), we investigated the clinical significance of salience network (SN) in depression and cognitive performance. Methods: Seventy seven PD-MCI patients that fulfilled multi-domain and non-amnestic subtype were included. Gray matter structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed based analysis. The patients were divided into two groups by psychiatric interviews and screening of Geriatric Depression Scale (GDS): PD-MCI with depression (PD-MCI-D) or without depression (PD-MCI-ND). The seed or peak cluster volume, or the significant differences in the regression slopes in each seed-peak cluster correlation, were used to evaluate the significance with the neurobehavioral scores. Results: This study is the first to demonstrate that the PD-MCI-ND group presented a larger number of voxels of structural covariance in SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak cluster of left lingual gyrus showed significant inverse correlation with the Geriatric Depression Scale (GDS; r = -0.231, P = 0.046). Conclusions: This study is the first to validate the clinical significance of the SN in PD-MCI-D. The right insular seed value and the SN correlated with the severity of depression in PD-MCI.

Epidemiologic trend of adult bacterial meningitis in southern Taiwan (2006–2015)

The purpose of this study is to analyze recent epidemiologic trend of adult bacterial meningitis (ABM) in Taiwan. The clinical features, laboratory data and therapeutic outcomes of 157 patients with ABM from 2006-2015 were analyzed. The results were compared with those of our previous two epidemiologic studies of ABM (1st study: 202 cases, January 1986-June 1999; 2nd study: 181 cases, July 1999-December 2005). Of the 157 patients with ABM, 96 were men and 61 women, and 68.2% (107/157) of them had a postneurosurgical state as the underlying condition. Monomicrobial infections and mixed infections were found in 92.4% (145/157) and 7.6% (12/145) of the cases, respectively. Of the implicated pathogens of monomicrobial infections, staphylococcal species were the most common, accounting for 27.6% (40/145) of them and Klebsiella species were the second common accounting for 13.8% (20/145) of them. The other common Gram-negative pathogens were Pseudomonas species and Acinetobacter species, accounting for 10.3% (15/145) and 7.6% (11/145), respectively. The overall mortality rate was 25.5% (40/157), and septic shock and liver cirrhosis were significant prognostic factors. This study revealed a change in the epidemiologic trend of ABM and the study results may offer important information for clinicians managing patients with ABM.

Anaerobic bacterial meningitis in adults

Anaerobic infection is a very uncommon condition in adult bacterial meningitis (ABM), and its clinical characteristics have yet to be clarified. We enrolled 540 patients with culture-proven bacterial meningitis during a study period of 30 years (1986-2015), of whom 13 (2.4%) had anaerobic infections. These 13 patients were eight men and five women, aged 22-77 years. Among them, 53.8% (7/13) had a postneurosurgical state as the preceding event, and 79.6% (10/13) had underlying medical conditions including diabetes mellitus, malignancy, liver cirrhosis, cerebral infarct and alcoholism. Nosocomial and mixed infections were found in 15.5% (2/13) and 46.1% (6/13) of the patients, respectively. A total of 14 anaerobic strains were isolated from cerebrospinal fluid specimens, including nine Gram-negative (G(-)) strains: Fusobacterium nucleatum (3), Prevotella species (3) and Bacteroides fragilis (3), and five Gram-positive (G(+)) strains: Propionibacterium acnes (3) and Peptostreptococcus micros (also known as Parvimonas micra) (2). All of the implicated G(+) anaerobic bacteria were susceptible to penicillin, and no multiple drug-resistant strains were found among the implicated G(-) anaerobic bacteria. Despite treatment, 30.8% (4/13) of the patients died. Of the nine survivors, 22.2% (2/9) had a full recovery, while the other 77.8% (7/9) had varying degrees of neurological deficits. Compared with the good outcome group (n = 6, modified Rankin scale (mRS) scores: 0-2), the poor outcome group (n = 7, mRS scores ≧3) had higher incidence of seizure. These results may offer a preliminary view of the clinical characteristics of anaerobic ABM.

Diffusion kurtosis imaging as a neuroimaging biomarker in patients with carbon monoxide intoxication

HighlightsCarbon monoxide intoxication is associated with decreased diffusion kurtosis.Kurtosis fractional anisotropy has a clinical significance in outcome prediction.Diffusion tensor image showed a higher sensitivity in detecting disease state. ABSTRACT Attempting suicide by burning charcoal can lead to carbon monoxide (CO) intoxication and cognitive deficits. Changes in white matter (WM) quantified by diffusion tensor imaging (DTI)‐derived parameters have been validated to reflect cognitive test scores. As diffusion kurtosis imaging (DKI) measures biological microstructures using non‐Gaussian diffusivity, we assessed the added‐information of DKI with neuropsychological test scores as the major outcome measure. A total of 45 patients were enrolled and compared with 30 age‐matched controls. The patients were stratified into acute or chronic phase according to the intervals of intoxication and assessments. WM status was assessed using tract‐based spatial statistics for DKI and DTI topographies, and the sensitivity/specificity of either model was tested using area under the curve (AUC) analysis. To evaluate their clinical significance, values of DKI‐ and DTI‐derived parameters were extracted from seven regions of interest (ROI) and correlated with neuropsychiatric scores. The kurtosis parameters were lower in the patients than in the controls but none of the parameters provided differentiations between the acute or chronic phase. Kurtosis fractional anisotropy (KFA) had a higher AUC than fractional anisotropy while the other 3 DTI parameters had higher AUC than the corresponding DKI ones. In clinical correlations, KFA value of right posterior WM correlated with visual memory (r = 0.326, p = 0.029), and KFA values of bilateral posterior WM correlated with the digit forward score (right: r = 0.302, p = 0.043; left: r = 0.314, p = 0.036). Although DTI was more sensitive in reflecting disease status, KFA may be more sensitive and specific than fractional anisotropy in cognitive test score predictions.

MAOA-VNTR Genotype Effects on Ventral Striatum-Hippocampus Network in Alzheimer’s Disease: Analysis Using Structural Covariance Network and Correlation with Neurobehavior Performance

Functional polymorphisms in the promoter region of the monoamine oxidase A (MAOA) gene are associated with brain MAOA activity and transcriptional efficiency in patients with Alzheimer’s disease (AD). This study investigated structural covariance networks mediated by MAOA-variable number tandem repeat (VNTR) genotypes in patients with AD, and assessed whether this effect was associated with sex. A total of 193 patients with AD were classified into four genotype groups based on MAOA transcriptional efficiency (female low [L], low-high + high activity groups [LH + H]; male L, male H groups). Structural covariance networks were constructed focusing on triple-network and striatal networks. Covariance strength was analyzed in the four groups, and the genotype and sex main effects and their interactions were analyzed. Significant peak cluster volumes were correlated with neurobehavioral scores to establish the clinical significance. MAOA genotypes mediated the structural covariance strength on the dorsolateral prefrontal cortex (dLPFC)-caudate axis in both sexes, but a higher covariance strength was shown in the female L group and male H group. The independent effect of male sex was related to higher covariance strength in the frontal medial superior region in the dLPFC, dorsal caudate (DC), and ventral superior striatum (VSs) seeds. In contrast, female sex had higher covariance strength in the frontal opercular areas anchored by the dLPFC, DC, and VSs seeds. Topographies showing higher covariance strength with sex interactions were found in the male H group and female L group in the dLPFC supplementary motor axis, DC-SMA, and DC-precentral axis. In our patients with AD, MAOA-VNTR polymorphisms and sex had independent and interactive effects on structural covariance networks, of which the dLPFC-, VSs-, and DC-anchored networks represented major endophenotypes that determined cognitive outcomes. The sex-genotype interaction model suggested that male high activity and female low activity may modulate brain morphometric connectivity and determine cognitive scores.

The clinical characteristics of adult bacterial meningitis caused by non-Pseudomonas (Ps.) aeruginosa Pseudomonas species: A clinical comparison with Ps. aeruginosa meningitis

Adult bacterial meningitis (ABM) caused by non‐Pseudomonas (Ps.) aeruginosa Pseudomonas (NPAP) species infection has rarely been reported. The clinical characteristics of 52 cases of Pseudomonas ABM (11 NPAP‐ and 41 Ps. aeruginosa‐related meningitis) collected during a 30‐year study period (1986–2015) were included. Eleven cases of NPAP ABM were identified in the literature, and their clinical data were also collected. Therefore, a total of 22 NPAP ABM cases were enrolled. The clinical characteristics of the NPAP ABM and Ps. aeruginosa ABM groups were compared. Of the implicated NPAP strains, Ps. putida and Ps. stutzeri were the most common (7 cases each), followed by Ps. mendocina in 4, Ps. fluorescens in 1, Ps. fulva in 1, Ps. alcaligenes in 1, and Ps. mosselii in 1. Of the 22 cases, 50% (11/22) had an underlying postneurosurgical state. Fever (77.3%, 17/22) and altered consciousness (45.5%, 10/22) were the most common clinical presentations. Antibiotic non‐susceptibility was found in 3 strains of Ps. putida and 1 Ps. mosselii strain. Compared to the patients with Ps. aeruginosa ABM, those with NPAP ABM had a higher incidence of spontaneous infections and a better survival rate. In conclusion, although Ps. putida, Ps. stutzeri and Ps. mendocina were the major implicated strains of NPAP ABM, the clinical characteristics of this specific group of ABM demonstrated marked heterogeneity. Even though the cases with NPAP ABM had better therapeutic results than those with Ps. aeruginosa ABM, further large‐scale studies are needed to better delineate this specific group of ABM.

Clinical characteristics of Citrobacter meningitis in adults: High incidence in patients with a postneurosurgical state and strains not susceptible to third-generation cephalosporins

Adult bacterial meningitis (ABM) caused by Citrobacter (C.) infection is very uncommon and the clinical characteristics of this specific infectious syndrome have not been analyzed in the literature. The clinical characteristics of six Citrobacter ABM patients collected during a study period of 30 years (1986-2015) were enrolled, and they accounted for 1.1% (6/540) of our ABM patients. In this study, a total of 14 patients with Citrobacter ABM (six collected from our hospital and eight from the literature) were included for analysis. The 14 patients were nine men, three women and two with unknown gender, aged 31-84 years (median: 64 years), of whom 78.6% (11/14) had an underlying postneurosurgical condition and 21.4% (3/14) belonged to mixed infections. The most common clinical manifestations were fever (50%, 7/14), altered consciousness (50%, 7/14), and headache (28.6%, 4/14). These clinical presentations were neither specific nor unique; therefore, cerebrospinal fluid studies including cultures were important for the diagnostic confirmation. Of the implicated Citrobacter strains, C, koseri was the most common (57.1%, 8/14), followed by C. freundii (21.4%, 3/14) and C. farmeri (7.1%, 1/14). Of the Citrobacter strains collected from CSF specimens of our six Citrobacter ABM patients, 33.3% (2/6) and 66.7% (4/6) were not susceptible to ceftazidime or ceftriaxone, respectively, but they were all susceptible to carbapenem. The therapeutic results showed a mortality rate of 21.4% (3/14).

Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer’s disease

BackgroundAlzheimer’s disease (AD) is a complex neurodegenerative disease, and genetic differences may mediate neuronal degeneration. In humans, a single-nucleotide polymorphism in the B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2) gene, rs956572, has been found to significantly modulate Bcl-2 protein expression in the brain. The Bcl-2 AA genotype has been associated with reduced Bcl-2 levels and lower gray matter volume in healthy populations. We hypothesized that different Bcl-2 genotype groups may modulate large-scale brain networks that determine neurobehavioral test scores.MethodsGray matter structural covariance networks (SCNs) were constructed in 104 patients with AD using T1-weighted magnetic resonance imaging with seed-based correlation analysis. The patients were stratified into two genotype groups on the basis of Bcl-2 expression (G carriers, n = 76; A homozygotes, n = 28). Four SCNs characteristic of AD were constructed from seeds in the default mode network, salience network, and executive control network, and cognitive test scores served as the major outcome factor.ResultsFor the G carriers, influences of the SCNs were observed mostly in the default mode network, of which the peak clusters anchored by the posterior cingulate cortex seed determined the cognitive test scores. In contrast, genetic influences in the A homozygotes were found mainly in the executive control network, and both the dorsolateral prefrontal cortex seed and the interconnected peak clusters were correlated with the clinical scores. Despite a small number of cases, the A homozygotes showed greater covariance strength than the G carriers among all four SCNs.ConclusionsOur results suggest that the Bcl-2 rs956572 polymorphism is associated with different strengths of structural covariance in AD that determine clinical outcomes. The greater covariance strength in the four SCNs shown in the A homozygotes suggests that different Bcl-2 polymorphisms play different modulatory roles.