Publications by authors named "Wen-Neng Chang"

213 Publications

The Clinical Features and Therapeutic Outcomes of Young Adults with Cryptococcal Meningitis.

Acta Neurol Taiwan 2021 Mar;30(1):11-20

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Objective: No previous study has reported on the clinical characteristics of cryptococcal meningitis (CM) focusing solely on young adults.

Patients And Methods: Ninety-nine adult patients with CM (64 men and 35 women) were enrolled, of whom 26 were classified into the young adult group (≤ 40 years) and 73 into the non-young adult group (> 40 years). The modified Rankin scale (mRS) was used to evaluate the outcomes of the survivors at the time of discharge and at 1 year of follow-up. The clinical characteristics and laboratory data between 1) the young adult CM patients with and without acquired immunecompromised syndrome and 2) the male and female young adult CM patients were compared. The prognostic factors of the young adult CM patients were also analyzed.

Results: The young adult group had a higher incidence of headache as the clinical presentation which may have been due to the higher intracranial pressure in this group. The overall mortality rate of the young adults with CM was high (38.5%, 10/26), but no significant prognostic factors were found. In followup studies of the neurologic deficits, the young adult survivors had better outcomes (mRS scores = 0-2) than the non-young adult group at discharge and 1 year after discharge.

Conclusion: The young adult CM patients had a higher incidence of headache as the clinical presentation. Although the mortality rate in the young adult CM patients was high, the survivors had better neurologic outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

Correlation between Hypovitaminosis D and Nutritional Status with The Severity of Clinical Symptoms And Impaired Cognitive Function in Patients with Parkinson's Disease.

Acta Neurol Taiwan 2021 Jun;30(2):63-73

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Purpose: To evaluate the relationship between the severity of clinical symptoms and cognitive function of patients with Parkinson's disease (PD) and the serum vitamin D level and nutrition status.

Methods: Thirty-three adult PD patient were included in the study (November 2016 to October 2018) and their clinical symptom severity (including the Hoehn and Yahr scale and unified Parkinson's disease rating scale (UPDRS)) and cognitive function (mini-mental state examination) were assessed in two visits (at time of enrollment and one year after the enrollment). In the meanwhile, their renal/liver function, serum level of vitamin D, vitamin B12, Folate and high-sensitive C-reactive protein were also measured for clinical correlation and comparisons.

Results: From the two visits, we found our patients divided into two group, the well-nourished status group and at risk or malnutrition status group. In both visits, we uncovered patients at risk of malnutrition status had worse clinical severity and more impaired memory. As for hypovitaminosis D, the vitamin D level alone made no significant correlation with the clinical severity and cognitive function.

Conclusion: This study revealed that PD patient with at risk of malnutrition status has impaired cognitive function but patients with abnormal serum vitamin D level did not have such influence. But PD patients with abnormal vitamin D level have a higher hs-CRP level which has an influence on the cognitive function of PD patients. Therefore, abnormal serum vitamin D level may have an indirect influence on the cognitive function of PD patients through the influence on the hs-CRP level. This study is limited by the small case-number and short follow-up time. Further large scale study and longer observation period are needed for a better delineation of the relationship between the serum vitamin D level and nutritional status with the clinical condition of the PD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2021

Using fiber tractography and diffusion kurtosis imaging to evaluate neuroimaging changes in patients with cerebrotendinous xanthomatosis after stopping chenodeoxycholic acid treatment for three years.

Biomed J 2021 Sep 17. Epub 2021 Sep 17.

Department of Neurology, Chang-Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

Background: The aim of this study was to use tractography and diffusion kurtosis imaging (DKI) to evaluate cerebral white matter (WM) changes in patients with cerebrotendinous xanthomatosis (CTX) after stopping chenodeoxycholic acid (CDCA) treatment.

Material And Methods: Two siblings with CTX aged 40 and 38 years, respectively, who had been diagnosed with CTX for 16 years were enrolled. They had received CDCA treatment from 2005 until 2015, after which CDCA was no longer available in Taiwan. Serial brain magnetic resonance imaging (MRI) studies were used to record brain changes, and a series of neuropsychiatric tests were used to evaluate cognitive changes 3 years after stopping CDCA treatment.

Results: The conventional MRI studies revealed progressive changes in dentate nuclei and surrounding cerebellar hemispheres, but no obvious changes in cerebral white matter (WM). Tractography captured in 2018 showed a general reduction in fiber density, especially involving frontal lobe fibers, compared to 2015. In addition, the DKI studies performed in 2018 showed a decreased axonal water fraction in diffuse WM structures and increased RadEAD in frontal WM. Comparisons of the neuropsychiatric test results between 2015 and 2018 showed a marked decline in executive function including design fluency, digit backward span and digit forward span, and this cognitive impairment highly suggested frontal lobe dysfunction.

Conclusions: This study may suggest that cerebral tractography and DKI study results can identify changes in cerebral WM in CTX patients shortly after stopping CDCA treatment, and that they may have a better correlation with the results of neuropsychiatric tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bj.2021.09.003DOI Listing
September 2021

Nationwide Population-Based Epidemiological Study for Outcomes of Adjunctive Steroid Therapy in Pediatric Patients with Bacterial Meningitis in Taiwan.

Int J Environ Res Public Health 2021 06 12;18(12). Epub 2021 Jun 12.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan.

Although corticosteroids can serve as an effective anti-inflammatory adjuvant therapy, the role of adjunctive steroid therapy in pediatric bacterial meningitis in Taiwan remains under-investigated. Cases of acute bacterial meningitis, aged between 1 month and 20 years, were divided into a steroid group (empirical antibiotics with adjunctive steroid therapy) and a non-steroid group (empirical antibiotics only). Data were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database using the International Classification of Diseases, Ninth Revision codes. Of the 8083 episodes enrolled in this study, 26% (2122/8083) and 74% (5961/8083) were divided into the steroid and non-steroid groups, respectively. The fatality rates were 7.9% in the steroid group and 1.7% in the non-steroid group during hospitalization ( < 0.0001). In the steroid and non-steroid groups, the median length of hospital stay was 13 and 6 days, respectively ( < 0.0001). Medical costs (median (interquartile range)) of hospitalization were 77,941 (26,647-237,540) and 26,653 (14,287-53,421) New Taiwan dollars in the steroid and non-steroid groups, respectively ( < 0.0001). The steroid group had a more fulminant course at baseline, a higher fatality rate, length of hospital stay, and medical cost of hospitalization. Therefore, the beneficial effects of the adjunctive use of corticosteroids in pediatric bacterial meningitis are inconclusive, and additional prospective multicenter investigations are required to clarify this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18126386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296207PMC
June 2021

Respiratory Muscle Training Improves Functional Outcomes and Reduces Fatigue in Patients with Myasthenia Gravis: A Single-Center Hospital-Based Prospective Study.

Biomed Res Int 2020 19;2020:2923907. Epub 2020 Mar 19.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: Myasthenia gravis (MG) is an immune-mediated disorder characterized by muscle fatigue and fluctuating weakness. Impairment in respiratory strength and endurance has been described in patients with generalized MG. We tested the hypothesis that respiratory muscle training (RMT) can improve functional outcomes and reduce fatigue in patients with MG.

Methods: Eighteen patients with mild to moderate MG participated in this study. The training group underwent home-based RMT three times a week for 12 weeks. Sixteen patients with MG without RMT were enrolled as a disease control group. Lung function, autonomic testing, Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and functional outcome measurement by using quantitative myasthenia gravis (QMG) score and myasthenia gravis composite (MGC) scale were measured before and after the 12-week RMT.

Results: The 12-week RMT significantly increased forced vital capacity (FVC) from 77.9 ± 12.6% to 83.8 ± 17.7% ( = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (.

Conclusion: The home-based RMT is an effective pulmonary function training for MG patients. The RMT can not only improve short-term outcomes but also reduce fatigue in patients with mild to moderate generalized MG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/2923907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114765PMC
January 2021

ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer's disease.

Alzheimers Res Ther 2019 12 12;11(1):103. Epub 2019 Dec 12.

Department of Neurology, Institute of translational research in biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta-Pei Road, Niaosung, Kaohsiung, 833, Taiwan.

Background: Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer's disease.

Methods: Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer's disease were included in this study. Memory was characterized and compared between APOE-ε4+ carriers and APOE-ε4 non-carriers within ABCA7 rs3764650T allele homozygous carriers and ABCA7 rs3764650G allele carriers, respectively. Two-way analysis of variance was used to identify a significant interaction effect between APOE (APOE-ε4+ carriers versus APOE-ε4 non-carriers) and ABCA7 (ABCA7 rs3764650T allele homozygous versus ABCA7 rs3764650G allele carriers) on memory scores and functional connectivity in each default mode network subsystem.

Results: In ABCA7 rs3764650G allele carriers, APOE-ε4+ carriers had lower memory scores (t (159) = - 4.879; P < 0.001) compared to APOE-ε4 non-carriers, but APOE-ε4+ carriers and APOE-ε4 non-carriers did not have differences in memory (P > 0.05) within ABCA7 rs3764650T allele homozygous carriers. There was a significant APOE-ABCA7 interaction effect on the memory (F3, 283 = 4.755, P = 0.030). In the default mode network anchored by the entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects (P = 0.00002) was correlated with the memory (ρ = 0.129, P = 0.030).

Conclusions: Genetic-biological systems may impact disease presentation and therapy. Clarifying the effect of APOE-ABCA7 interactions on the default mode network and memory is critical to exploring the complex pathogenesis of Alzheimer's disease and refining a potential therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-019-0563-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909474PMC
December 2019

Clinical and molecular genetic features of cerebrotendinous xanthomatosis in Taiwan: Report of a novel CYP27A1 mutation and literature review.

J Clin Lipidol 2019 Nov - Dec;13(6):954-959.e1. Epub 2019 Oct 10.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address:

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder associated with mutations in the CYP27A1 gene, and the genetic features of CTX in Taiwanese have not been examined before.

Objectives: We report a new CTX family with a novel mutation in the CYP27A1 gene and analyze the clinical and molecular genetic features of CTX in Taiwan.

Methods: The clinical and molecular genetic features of the two siblings from the new CTX family and the other 7 reported Taiwanese CTX patients were included for analysis. The clinical features of the enrolled CTX patients were recorded using the indicators that make up the suspicion index (SI).

Results: The age at CTX diagnosis of the two siblings in the new CTX family were in late 30s, and predominantly psychiatric features. Both siblings had compound heterozygous splicing mutations in the CYP27A1 gene, including one mutation in exon 2 (c.435G>T, cryptic splice site) and one mutation in intron 7 (c.1264A>G, canonical splice site). None of the CTX patients in Taiwan were diagnosed during childhood or adolescence, and the most common clinical features of the 9 Taiwanese CTX patients were tendinous xanthomas, followed by ataxia and/or spastic paraparesis, dentate nuclei signal alternation at magnetic resonance imaging, intellectual disability and/or psychiatric disturbance, and polyneuropathy. Mutations in the CYP27A1 gene in the Taiwanese population were most commonly observed in exon 2, followed by exon 8 and intron 7. Except for one CTX patient who had an SI score of 100, the SI scores ranged from 300 to 400 before the study of the CYP27A1 gene and diagnosis.

Conclusions: We reported two Taiwanese CTX siblings who had compound heterozygous mutations in CYP27A1. Exons 2 and 8 and intron 7 are the hotspots for Taiwanese CTX mutations. The diagnosis of CTX in Taiwan is usually delayed and is probably under-recognized based on statistical estimations. Early identification and genetic diagnosis may be helpful to CTX patients because early treatment can reduce the accumulation of cholestanol and slow disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacl.2019.10.001DOI Listing
July 2020

Neuropsychiatric symptoms in Parkinson's disease: association with caregiver distress and disease severity.

Int Psychogeriatr 2020 06 24;32(6):733-739. Epub 2019 Oct 24.

Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Objectives: The condition of caregivers is important to the quality of care received by people with Parkinson's disease (PD), especially at the late disease stages. This study addresses the distress placed on caregivers by participants' neuropsychiatric symptoms at different stages of PD in Taiwan.

Methods: This prospective study enrolled 108 people with PD. All participants were examined with the Unified Parkinson's Disease Rating Scale (UPDRS), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Clinical Dementia Rating (CDR) scale. Caregiver distress was measured using the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D). Statistical analysis was used to explore the PD-related factors that contribute to caregiver distress.

Results: The mean follow-up interval in the 108 PD participants were 24.0 ± 10.2 months with no participant lost to follow-up due to death. NPI-distress (the sum of NPI caregiver distress scale across the 12 domains of the NPI) was positively correlated with NPI-sum (the total score across the 12 domains of the NPI) (r = 0.787, p < 0.001), CDR (r = 0.403, p < 0.001), UPRDS (r = 0.276, p = 0.004), and disease duration (r = 0.246, p = 0.002), but negatively correlated with CASI (r = -0.237, p = 0.043) and MMSE (r = -0.281, p < 0.001). Multiple linear regression analysis showed that only NPI-sum and disease duration were independently correlated with NPI-distress.

Conclusion: The disease duration and NPI-sum are independent predictors of caregiver distress in Taiwanese populations with PD. Early detection and reduction of neuropsychiatric symptoms in people with PD can help decrease caregiver distress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1041610219001510DOI Listing
June 2020

Characterization of Fibrinogen as a Key Modulator in Patients with Wilson's Diseases with Functional Proteomic Tools.

Int J Mol Sci 2019 Sep 12;20(18). Epub 2019 Sep 12.

Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 33375, Taiwan.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by defects in the ATPase gene (ATP7B). The various clinical features result from the massive accumulation of copper in the liver, cornea and basal ganglia. Although WD can be effectively treated with proper medicine, this disease is difficult to clearly diagnose due to its indefinite symptoms. In the current study, we achieved a positive correlation between clinical symptoms and the enzymatic activity of ceruloplasmin in WD patients. Furthermore, proteome profiles of plasma as well as network analysis demonstrated that fibrinogen is a critical indicator which is significantly unregulated in WD subjects in comparison to healthy donors and closely linked to pathogenesis of WD. Here, we applied 2DE-immunoblots and immunohistochemistry to verify the protein level and localization in situ. The enhanced expression of fibrinogen in the plasma of WD subjects with respect to that of healthy controls and patients with distinct disorders was also confirmed by utilizing clinical samples. As expected, application of high dose of copper induced expression of fibrinogen, while knockdown of ceruloplasmin also resulted in upregulation of fibrinogen as well as elimination of superoxide dismutase (SOD), leading to increased oxidative stress in cells. In summary, the liver injury or oxidative stress induced by the progression of WD may account for the obvious increase of fibrinogen, which in turn triggers inflammatory responses and interferes coagulation cascades; this finding sheds light on the early detection and diagnosis of WD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20184528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770682PMC
September 2019

High incidence of severe neurological manifestations and high mortality rate for adult Listeria monocytogenes meningitis in Taiwan.

J Clin Neurosci 2020 Jan 22;71:177-185. Epub 2019 Aug 22.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

The clinical characteristics and therapeutic outcomes of adult Listeria monocytogenes meningitis are not commonly examined in isolation in the literature. During a study period of 19 years (2000-2018), 366 patients with culture-proven adult bacterial meningitis (ABM) were identified in the author's hospital (264 patients in 2000-2010 and 102 patients in 2011-2018). Of the 366 ABM patients, 330 had monomicrobial infections while the other 36 had mixed infections. L. monocytogenes infection was identified in 11 of the 330 patients with monomicrobial ABM (3 in 2000-2010 and 8 in 2011-2018). These 11 patients included 5 males and 6 females, aged 47 to 76 years (median age = 61.7). None of the 11 patients had a postneurosurgical state as the underlying cause, but 3 of them contracted the infection nosocomially. Common underlying conditions included liver cirrhosis (4), systemic malignancy (3), diabetes mellitus (3), and renal disease (2). The most common clinical manifestations were fever (11), altered consciousness (8), seizure (8), bacteremia (7) and hydrocephalus (5). The therapeutic result revealed a mortality rate of 72.7% (8/11), but no significant prognostic factors were identified. The clinical features of 8 additional Taiwanese L. monocytogenes ABM patients reported in the literature, were also included for analysis. The present study revealed an increase in L. monocytogenes ABM in recent years and most patients presented with severe neurological manifestations. The current study is a preliminary overview of L. monocytogenes meningitis in adults and a further large-scale study is needed for improved delineation of this specific infectious syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.08.072DOI Listing
January 2020

The clinical characteristics, implicated pathogens and therapeutic outcomes of culture-proven septic cavernous sinus thrombosis.

J Clin Neurosci 2019 Oct 19;68:111-116. Epub 2019 Jul 19.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

In this magnetic resonance imaging-based study, we investigated the clinical features, neuroimaging features and therapeutic outcomes of 14 adults (eight men and six women; mean age 60.4 years; range 37-77 years) with septic cavernous sinus thrombosis (CST). Of the underlying conditions, 10 had diabetes mellitus and 13 had concomitant sphenoid sinusitis. Headache (n = 13) and ophthalmoplegia (n = 13) were the most common clinical presentations, followed by fever (n = 9) and other neuro-vascular signs and symptoms. The duration from the onset of symptoms to diagnosis ranged from 1 to 61 days, and more than 64% (9/14) of the septic CST patients were diagnosed >7 days after symptom onset. Expansion of the cavernous sinus was the most common neuroimaging feature, followed by convexity of the lateral wall of the cavernous sinus (5) and filling defect of the cavernous sinus (4). Staphylococcal species (spp.) was the most commonly implicated pathogen, followed by Aspergillus spp. Despite treatment, 7% (1/14) of the patients died in the hospital and 67% (8/12) of the survivors had neurological deficits. The duration of onset-to-diagnosis and the presence of hemiparesis were significant prognostic factors. These results provide a preliminary view of this uncommon infectious syndrome. Further large-scale studies are needed to better delineate septic CST in adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.07.022DOI Listing
October 2019

Adjunctive statin therapy reduces intracranial hemorrhage and 1-year mortality in patients with atrial fibrillation after acute ischemic stroke: A population-based epidemiological study from Taiwan.

J Clin Neurosci 2019 Nov 18;69:224-229. Epub 2019 Jul 18.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

Background: Atrial fibrillation (AF)-related stroke causes severe disability and poor prognosis. Adjunctive statin therapy has been recommended for atherosclerotic-related stroke but not AF-related stroke. This study investigated the effects of statin in AF patients who experienced acute ischemic stroke.

Methods: Data from patients with AF experiencing first-ever ischemic stroke between 2001 and 2010 were collected from the Taiwan National Health Insurance Research Database and categorized into non-statin and statin groups. The statin group was further divided into pre-stroke statin (those who began statin therapy before stroke) and post-stroke statin (those who began statin therapy after stroke) groups. The risks for recurrent ischemic stroke, coronary artery disease (CAD), intracranial hemorrhage (ICH), and 1-year mortality were compared among the groups.

Results: A total of 43,242 patients were in the non-statin, 2858 in the pre-stroke statin and 4640 in post-stroke statin groups. Comparing the risk for recurrent stroke and CAD among the three groups, the pre-stroke statin and post-stroke statin groups did not exhibit a significant difference compared with the non-statin group. In terms of ICH risk, the statin group had a lower risk for ICH (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68-0.90; p = 0.0007) compared with the non-statin group. The overall 1-year mortality in both statin subgroups was lower than that in the non-statin group (pre-stroke statin, OR 0.55 [95% CI 0.49-0.61]; p < 0.0001 versus post-stroke statin, OR 0.53 [95% CI 0.48-0.58]; p < 0.0001).

Conclusions: Statin therapy reduced the risk of ICH and 1-year mortality in AF patients who experienced acute ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.07.045DOI Listing
November 2019

Klebsiella pneumoniae brain abscesses in an elderly patient without clinically evident neurological signs and symptoms.

Acta Neurol Taiwan 2019 Mar;28(1):12-16

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Purpose: It is difficult to diagnose a brain abscess if the patient does not have clinically evident neurological features. We present the diagnosis and therapeutic course of an elderly woman with multiple Klebsiella (K.) pneumoniae brain abscesses without neurological signs or symptoms.

Case Report: The patient was an 81-year-old woman without diabetes who had been discharged from our hospital about 7 days before this admission with a diagnosis of K. pneumoniae urinary tract and bloodstream infections. She did not have any clinically evident neurological features except for a fever, however focal suppurations were identified in the cerebral hemispheres and lungs by magnetic resonance imaging (MRI) and computed tomography, respectively. After an 11-week course of antibiotic treatment and serial cranial MRI follow-up studies, she was discharged in a stable condition with no neurological sequelae.

Conclusion: Cranial MRI should be performed to identify the presence of brain abscesses in elderly patients with K. pneumoniae bloodstream infections but without clinically evident neurological signs or symptoms. Serial MRI studies are important to monitor the therapeutic course.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2019

The clinical characteristics of adult cryptococcal meningitis patients who died within one year of treatment with a focus on those with early mortality.

J Clin Neurosci 2019 Sep 18;67:80-84. Epub 2019 Jun 18.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

Cryptococcal meningitis (CM) is a serious infectious disease of the central nervous system, and associated brain injuries can be found in the very early stage of disease. In this study, 92 adult CM patients (59 men, 33 women; median age 54.66 years, range 20-86 years) were enrolled, and their clinical, laboratory, neuroimaging features and therapeutic outcomes were analyzed. Two main clinical comparative analyses of the clinical characteristics and laboratory and neuroimaging features were made in this study. The first compared clinical differences between the survivors and non-survivors of all enrolled patients, and the second compared differences between the following three groups: Group I, the patients who died within 14 days of initiating treatment; Group II, the patients who died within 15 days to 1 year of initiating treatment, and Group III, the patients who survived for more than 1 year after initiating treatment. Prognostic factors including initial altered consciousness, increased cerebrospinal fluid (CSF) lactate level and the presence of cryptococcemia were significantly different between the different groups. The patients with early mortality had a higher CSF lactate level and higher rate of cryptococcemia. The presence of cryptococcemia was an important prognostic factor, and the patients with cryptococcemia had a higher incidence of positive CSF India ink stain. Further large-scale studies are needed to delineate the clinical and laboratory features of CM patients with early mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.06.015DOI Listing
September 2019

Genetic Interaction of and is Associated with Memory Impairment and Hippocampal Atrophy in Alzheimer's Disease.

Aging Dis 2019 Jun 1;10(3):510-519. Epub 2019 Jun 1.

1Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.

The and fibroblast growth factor 1 () have both been associated with amyloid β accumulation and neurodegeneration. Investigation the effect of interactions on episodic memory (EM) deficits and hippocampus atrophy (HA) might elucidate the complex clinical-pathological relationship in Alzheimer's disease (AD). EM performance and hippocampal volume (HV) were characterized in patients with mild AD based on -ε4 carrier status (-ε4 carriers versus non-carriers) and single nucleotide polymorphism (rs34011-GG versus rs34011-A-allele carriers). The clinical-pathological relationships within each genotypic group (ε4+/GG-carrier, ε4+/A-allele-carrier, ε4-/GG-carrier and ε4-/A-allele-carrier) were analyzed. There were no significant differences between the rs34011-GG and rs34011-A-allele carriers for the level of EM performance or HV (> 0.05). The bilateral HV was significantly smaller and EM impairment was significantly worse in ε4+/GG-carrier than in ε4-/A-allele-carrier, and an interaction effect of (-ε4 carriers versus non-carriers) with (rs34011-GG versus rs34011-A-allele carriers) predicted EM impairment (F4,92= 3.516, p= 0.018) and structural changes in voxel-based morphometry. Our data shows that concurrent consideration of and polymorphisms might be required to understand the clinical-pathological relationship in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14336/AD.2018.0606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538224PMC
June 2019

The Effect of Stroke Subtypes on Baroreceptor Sensitivity, a Predict for Acute Stroke Outcome.

Biomed Res Int 2019 18;2019:7614828. Epub 2019 Apr 18.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: Reduced baroreflex sensitivity (BRS) has been reported in patients with acute cardiovascular events. We tested the hypothesis that BRS varies in different subtypes of acute ischemic stroke (AIS) and that BRS is a predictor of clinical outcomes.

Methods: We examined autonomic parameters in 34 patients with AIS, including the small deep hemisphere infarction, the large hemisphere infarction, and the brainstem infarction groups on Day 1, Day 7, and Day 30 after AIS. Autonomic parameters were also evaluated in 18 age- and sex-matched healthy volunteers as a control group. The clinical outcomes were analyzed using the modified Rankin scale at 30 days after stroke.

Results: The BRS, Valsalva ratio, and heart rate response to deep breathing (HR-DB) were significantly lower in patients after AIS on admission than in controls (<0.01). The frequency domain of HRV (LF/HF ratio) was significantly increased in patients after AIS compared to controls (<0.05). BRS was significantly reduced in patients with large hemisphere infarction or brainstem infarction compared to patients with small deep hemisphere infarction on Day 1 after AIS (<0.01). Stepwise logistic regression showed that the levels of BRS and NIHSS are prognostic factors of 1-month outcomes in patients with AIS.

Conclusion: Beside NIHSS score on admission, BRS is a potential prognostic factor of 1-month outcomes in patients with AIS. Patients with large hemisphere infarction or brainstem infarction have more blunting BRS than do those with lacunar infarction, which provides some insight into which patients may be expected to have a poor outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/7614828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500628PMC
November 2019

The clinical characteristics of spontaneous Gram-negative bacterial meningitis in adults: A hospital-based study.

J Clin Neurosci 2019 Jun 17;64:101-105. Epub 2019 Apr 17.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

The epidemiologic trend of acute bacterial meningitis can change more dramatically than any other bacterial disease, and a decrease in spontaneous adult bacterial meningitis (ABM) has been noted in serial studies of the epidemiologic trend of ABM in Taiwan. The purpose of this study was to analyze the clinical characteristics, laboratory data and therapeutic outcomes of 149 patients with spontaneous Gram-negative (G(-)) ABM collected during a study period of 31 years (1986-2016). The 149 patients included 107 men and 42 women, aged 18-86 years. The common underlying conditions were diabetes mellitus, liver cirrhosis and alcoholism, and the leading clinical presentations were fever, altered consciousness and septic shock. Compared the clinical characteristics of the patients identified in the study period of 2001-2106 to the patients identified in the study period of 1986-2000, the former group of patients had a significantly higher incidence of systemic malignance. In the recent 16 years (2001-2016), Klebsiella pneumoniae, Pseudomonas spp. and Escherichia coli were the leading three implicated bacterial pathogens of spontaneous G(-) ABM, accounting for 61.3% (38/62), 11.3% (7/62) and 11.3% (7/62%) of all cases, respectively. The overall mortality rate from spontaneous G(-) ABM was high (47.0%, 70/149) and the presence of septic shock and lower cerebrospinal fluid glucose level were significant prognostic factors. Because of the decreasing incidence of spontaneous ABM in Taiwan, close examination of this specific infectious syndrome is important in order to monitor the epidemiologic trend and improve the therapeutic strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.03.047DOI Listing
June 2019

The clinical characteristics and therapeutic outcomes of cryptococcal meningitis in elderly patients: a hospital-based study.

BMC Geriatr 2019 03 25;19(1):91. Epub 2019 Mar 25.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung, Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Taiwan.

Background: The elderly, and especially those with an immuno-compromised status, are vulnerable to infectious diseases. The purpose of this study was to examine the clinical characteristics and therapeutic outcomes of cryptococcal meningitis (CM) in elderly patients in Taiwan.

Methods: Ninety-nine adult patients with CM were identified during a 15-year study period (2002-2016), of whom 38 elderly (≥ 65 years) patients (16 men and 22 women, median age 72.9 years; range 65-86 years) were included for analysis. The clinical characteristics and therapeutic outcomes of these patients were analyzed and compared to non-elderly adult patients (< 65 years) with CM.

Results: Among the 38 patients, diabetes mellitus was the most common underlying condition (15), followed by adrenal insufficiency (7), malignancy (6), hematologic disorders (5), chronic obstructive pulmonary disease (5), autoimmune diseases (3), liver cirrhosis (3) and acquired immunodeficiency syndrome (1). Altered consciousness (29), fever (21) and headache (17) were the leading clinical manifestations. Positive cerebrospinal fluid and blood cultures for Cryptococcus (C.) neoformans were found in 26 and 9 patients, respectively. There were significant differences in gender, altered consciousness and recent cerebral infarction between the elderly and non-elderly groups. The elderly group had a high mortality rate (36.8%, 14/38), and the presence of cryptococcemia was the most significant prognostic factor.

Conclusions: This study offers a preliminary view of the clinical characteristics of CM in the elderly. The results suggest that elderly patients (≥ 65 years) are more vulnerable to CM than adults aged < 65 years. Compared to the non-elderly group, the elderly group had female predominance, higher rates of altered consciousness and recent cerebral infarction as the clinical presentation. The presence of cryptococcemia was a significant prognostic factor in the elderly group. This study is limited by the small number of patients, and further large-scale studies are needed to better delineate this specific infectious syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12877-019-1108-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434878PMC
March 2019

Intra-family phenotype variations in familial neuromyelitis optica spectrum disorders.

Mult Scler Relat Disord 2019 May 4;30:57-62. Epub 2019 Feb 4.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address:

Background: The aim of the current study was to examine intra-family phenotype variations in familial neuromyelitis optica (NMO) spectrum disorder.

Methods: The clinical presentation and neuroimaging features of two family members (mother and daughter) from a NMO spectrum disorder family (index family) were analyzed. Multiplex polymerase chain reaction was performed based on targeted re-sequencing on the AQP4 gene and the human leukocyte antigen (HLA) loci. The clinical and neuroimaging features of the members of six other previously reported NMO spectrum disorder families were also included for analysis.

Results: In the core family, the mother was aged 39 at disease onset and the initial presentation was spinal cord involvement, whereas the daughter was 22 years old at disease onset and the initial presentation was brainstem involvement. No coding pathogenic variants or single nucleotide polymorphisms of the AQP4 gene were identified in the mother, daughter or father. As for HLA genotyping, the HLA-DRB1*03 and HLA-DPB1*04 alleles were shared by the mother and daughter. The HLA-DPB1*05 was present in the affected daughter and was inherited from the unaffected father. As for the other six reported families with familial NMO spectrum disorder, four mother-daughter pairs had a different age at disease onset and/or a different initial presentation. The other two affected family groups were sister-sister pairs; they had a similar age of onset and similar initial presentations.

Conclusion: The present study offers a preliminary view of the clinical and neuroimaging features of patients with familial NMO spectrum disorder. Clinical heterogeneities were found among the family members, especially the mother and daughter pairs. The presence of risk allele HLA-DR*03:01 may be an important genetic finding for familial NMO spectrum disorder patients. To the best of our knowledge, this clinical heterogeneity has not been previously examined or reported in the literature. For better delineation of the intra-familial phenotype variations in familial NMO spectrum disorder, further large-scale studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2019.02.002DOI Listing
May 2019

Altered Functional Network Affects Amyloid and Structural Covariance in Alzheimer's Disease.

Biomed Res Int 2018 2;2018:8565620. Epub 2018 Dec 2.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.

Background: We aimed to investigate how altered intrinsic connectivity networks (ICNs) affect pathologic changes of Alzheimer's disease (AD) at a network-based level.

Methods: Thirty normal controls (NCs), 23 patients with AD-mild cognitive impairment (MCI), and 20 patients with AD-dementia were enrolled. We compared the organization of grey matter structural covariance and functional connectivity in ICNs between NCs and all AD patients who were amyloid (A)-positive. We further used seed-based interregional covariance analysis to compare structural and A plaque covariance in default mode network (DMN) between AD-MCI and AD-dementia groups.

Results: The patients with AD had increased functional interregional covariance among the regions of the ICN anchored to dorsal caudate (DC) seeds compared to the NCs. The increased connectivity was associated with extended patterns of reduced A plaque covariance in the AD-dementia group compared to the AD-MCI group within the striatal network anchored to DC seeds. Patterns of lower A plaque covariance in the AD-dementia group compared to the AD-MCI group were more extended within the network anchored to DC seeds than within the DMN, which was undergoing functional failure in the patients with AD. Significant decreased structural covariance in the AD-dementia group compared to the AD-MCI group was more extended in the DMN during functional failure.

Conclusions: Functional connectivity in ICNs affects the topographic spread of molecular pathologies. The temporal trajectory of pathologic alterations can be well demonstrated by pathologic covariance comparisons between different clinical stages. Pathologic covariance can provide critical support to pathologic interactions at network and molecular levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/8565620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304529PMC
April 2019

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

Neuroimage Clin 2019 4;21:101621. Epub 2018 Dec 4.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan. Electronic address:

Purpose Of The Research: Although single nucleotide polymorphisms of membrane-spanning 4A (MS4A) (rs670139) and several other susceptibility genes have shown interaction effects on the risk of Alzheimer's disease (AD), little is known about the interaction effects of apolipoprotein E (APOE) with MS4A (rs670139) on cognitive performances, and the underlying pathogenesis is unclear. The study aimed to investigate the APOE-MS4A (rs670139) interaction effects on cognitive performances, cortical volumes, and functional connectivity (FC) in brain networks.

Principal Results: Cognitive performances were characterized in each genotypic group, and were compared between normal controls and patients in each genotypic group. APOE-MS4A interaction effects on memory and executive function scores, cortical volumes, and FC in brain networks were demonstrated. Significant effects of APOE-MS4A interactions on FC were observed in executive control network (ECN) (T maxima = 4.99, false discovery rate-corrected p < .001), the calculation score (F3, 87 = 6.218; p = .015), and the volume in prefrontal (F3, 87 = 4.374; p = .039) and orbitofrontal cortices (F3, 87 = 6.022; p = .016). The calculation score was correlated with each frontal volume (cc) (ρ = 0.304; p = .004) and genetic interaction-associated FC in ECN (ρ = 0.282; p = .008). Variations in genotypes affected the relationship between the calculation score and each frontal volume (cc).

Major Conclusions: These findings indicate that the genetic interaction effects on FC in ECN might contribute to pathogenic mechanisms underlying the interaction effects of APOE-MS4A on calculation ability in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2018.101621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411654PMC
December 2019

Outcomes of adjunctive steroid therapy in adult patients with bacterial meningitis in Taiwan: A nationwide population-based epidemiologic study.

J Clin Neurosci 2019 Mar 19;61:54-58. Epub 2018 Nov 19.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; Department of Center for Shockwave Medicine and Tissue Engineering, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Neurology, Xiamen Chang Gung Memorial Hospital, Xiamen, China. Electronic address:

Background: Although corticosteroids are an effective anti-inflammatory adjuvant therapy, the role of adjunctive steroid therapy in treating adult bacterial meningitis in Taiwan remains controversial.

Methods: Cases of acute bacterial meningitis were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database using International Classification of Diseases, Ninth Revision codes from January 2000 to December 2013. Patients were classified into two groups: (1) steroid group (adjunctive steroids and empirical antibiotics) and (2) placebo group (empirical antibiotics only).

Results: There were 15,037 patients enrolled in this study; of these, 57% (7175/15,037) and 52% (7862/15,037) were placed in the placebo and steroid groups, respectively. The case-fatality rates were 11.5% (826/7175) in the placebo group and 19.9% (1562/7862) in the steroid groups during hospitalization (P = 0.77). Further, the hazard ratio (relative to placebo group) of in-hospital and one-year case fatality rate were 0.923 (95% confidence interval [CI]: 0.846-1.007, P = 0.073) and 1.514 (95% CI: 1.425-1.608, P < 0.0001) according to the multivariate Cox model after adjustment for age and sex.

Conclusion: On the basis of these results, steroid group had a more fulminant clinical course (e.g., acute respiratory failure and pneumonia, etc.), and unfavorable outcomes than placebo group. Therefore, more prospective, randomized, double-blind trials are warranted to evaluate the efficacy of adjunctive steroid therapy in treating adult bacterial meningitis in Taiwan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2018.10.146DOI Listing
March 2019

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

Mol Neurobiol 2019 Jun 18;56(6):4518-4529. Epub 2018 Oct 18.

Department of General Neurology, Cognitive and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-018-1394-0DOI Listing
June 2019

Clinical Characteristics and Therapeutic Outcomes of Postneurosurgical Bacterial Meningitis in Elderly Patients over 65: A Hospital-based Study.

Acta Neurol Taiwan 2017 Dec;26(4):144-153

Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Purpose: To investigate the clinical characteristics, laboratory features and prognostic factors of elderly patients with postneurosurgical bacterial meningitis.

Methods: Five hundred and forty patients with adult bacterial meningitis (ABM) were collected from 1986-2015, of whom 167 were ≥ 65 years. Of these 167 elderly patients, 82 had postneurosurgical infections and 85 had spontaneous infections. Clinical, laboratory and therapeutic data of these two groups were compared.

Results: The 82 elderly ABM patients with postneurosurgical infections included 48 men and 34 women with a median age of 71 years (range: 65-84 years). In addition to the postneurosurgical condition, the other most common underlying conditions included diabetes mellitus (29.3%) and hydrocephalus (29.3%). The major clinical presentations were fever (80.5%), altered consciousness (50.0%), hydrocephalus (43.9%), seizure (24.4%) and septic shock (15.9%). Of the implicated pathogens, staphylococcal species (spp.) were the most common (31.7%), followed by Acinetobacter spp. (12.2%), Enterobacter spp. (7.3%), Pseudomonas spp. (7.3%), Enterococcus faecalis (7.3%) and Escherichia coli (6.1%). The implicated staphylococcal spp. had a high rate of non-susceptibility to methicillin (84.6%), and the implicated Acinetobacter spp. and Enterobacter spp. had non-susceptible rates to ceftazidime of 60% and 50%, respectively. The mortality rate was 28.1%, and septic shock was the most significant prognostic factor. Compared with the clinical characteristics of the other 85 elderly patients with spontaneous ABM, there were significant differences in underlying condition, clinical and laboratory features and therapeutic outcomes.

Conclusions: Elderly patients accounted for 30.9% of all cases of ABM, of whom 49.1% had postneurosurgical ABM. The clinical characteristics of the elderly patients with postneurosurgical ABM were non-specific, and cerebrospinal fluid studies were needed to confirm the diagnosis. The mortality rate of this group of patients was high, and septic shock was an important prognostic factor. The clinical and laboratory features and therapeutic outcomes were different between the elderly patients with postneurosurgical and spontaneous ABM.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2017

The prognostic factors of HIV-negative adult cryptococcal meningitis with a focus on cranial MRI-based neuroimaging findings.

J Clin Neurosci 2018 Sep 2;55:57-61. Epub 2018 Jul 2.

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

The prognostic significance of clinical characteristics and neuroimaging features, especially cranial magnetic resonance imaging (MRI)-based neuroimaging features, in patients with human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) has rarely been examined in the literature. We analyzed the clinical characteristics and MRI findings of 65 HIV-negative patients (43 men, 22 women, age 19-86 years) collected during a study period of 15 years (January 2001-December 2015). Their underlying conditions included diabetes mellitus, liver cirrhosis, hematologic disorders, autoimmune disorders, malignancy, chronic obstructive pulmonary disease, adrenal insufficiency and organ transplantation, and their clinical presentations included headache, altered consciousness, fever, seizure, visual disturbance and hearing impairment. The main cranial MRI findings were basal meningeal enhancement (44.6%, 29/65), dilated Virchow-Robin space/pseudocyst (43.1%, 28/65), "dirty" cerebrospinal fluid sign (38.5%, 25/65), hydrocephalus (36.9%, 21/65), acute/subacute cerebral infarct (ASCI, 21.5%, 14/65), cryptococcoma (9.2%, 6/65), and hazy brain base (1.5%, 1/65). The therapeutic results of the 65 patients were evaluated using the Glasgow Outcome Scale (GOS). A comparison of the good outcome group (GOS score = 4-5, n = 37) and poor outcome group (GOS score = 1-3, n = 28) revealed that both the presence of seizures and ASCI were significantly associated with the prognosis. A comparison of the groups with ASCI (n = 14) and without ASCI (n = 51) revealed that the presence of basal meningeal enhancement was a significant factor for the development of ASCI, and that this correlation may be associated with intense basal meningeal inflammation in adjacent small vessels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2018.06.044DOI Listing
September 2018

Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel.

Front Neurol 2018 6;9:515. Epub 2018 Jul 6.

Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Focal epilepsy is the most common subtype of epilepsies in which the influence of underlying genetic factors is emerging but remains largely uncharacterized. The purpose of this study is to determine the contribution of currently known disease-causing genes in a large cohort ( = 593) of common focal non-lesional epilepsy patients. The customized focal epilepsy gene panel (21 genes) was based on multiplex polymerase chain reaction (PCR) and sequenced by Illumina MiSeq platform. Eleven variants (1.85%) were considered as pathogenic or likely pathogenic, including seven novel mutations. There were three (p.Leu890Pro, p.Arg1636Ter, and p.Met1714Val), three (two p.Arg217Profs8 and p.Leu298Pro), two (p.Ser284Leu, p.Ile321Asn), one (p.Val516Ter) (p.Asp233Asn), and one (p.Ser414Ter) variants. Additionally, 16 other rare variants were classified as unknown significance due to inconsistent phenotype or lack of segregation data. Currently known focal epilepsy genes only explained a very small subset of focal epilepsy patients. This indicates that the underlying genetic architecture of focal epilepsies is very heterogeneous and more novel genes are likely to be discovered. Our study highlights the usefulness, challenges and limitations of using the multi-gene panel as a diagnostic test in routine clinical practice in patients with focal epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2018.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043663PMC
July 2018

Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel.

Front Neurol 2018 6;9:515. Epub 2018 Jul 6.

Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Focal epilepsy is the most common subtype of epilepsies in which the influence of underlying genetic factors is emerging but remains largely uncharacterized. The purpose of this study is to determine the contribution of currently known disease-causing genes in a large cohort ( = 593) of common focal non-lesional epilepsy patients. The customized focal epilepsy gene panel (21 genes) was based on multiplex polymerase chain reaction (PCR) and sequenced by Illumina MiSeq platform. Eleven variants (1.85%) were considered as pathogenic or likely pathogenic, including seven novel mutations. There were three (p.Leu890Pro, p.Arg1636Ter, and p.Met1714Val), three (two p.Arg217Profs8 and p.Leu298Pro), two (p.Ser284Leu, p.Ile321Asn), one (p.Val516Ter) (p.Asp233Asn), and one (p.Ser414Ter) variants. Additionally, 16 other rare variants were classified as unknown significance due to inconsistent phenotype or lack of segregation data. Currently known focal epilepsy genes only explained a very small subset of focal epilepsy patients. This indicates that the underlying genetic architecture of focal epilepsies is very heterogeneous and more novel genes are likely to be discovered. Our study highlights the usefulness, challenges and limitations of using the multi-gene panel as a diagnostic test in routine clinical practice in patients with focal epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2018.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043663PMC
July 2018

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

J Clin Neurosci 2018 Aug 12;54:83-87. Epub 2018 Jun 12.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2018.06.019DOI Listing
August 2018

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

Alzheimers Res Ther 2018 02 8;10(1):17. Epub 2018 Feb 8.

Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 123 Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan.

Background: Alzheimer'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.

Methods: Gray 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.

Results: For 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.

Conclusions: Our 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-018-0344-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806294PMC
February 2018

Anaerobic bacterial meningitis in adults.

J Clin Neurosci 2018 Apr 1;50:45-50. Epub 2018 Feb 1.

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2018.01.014DOI Listing
April 2018
-->