Diagnostic value of isolated plasma biomarkers and its combination in neurodegenerative dementias: A multicenter cohort study.

BACKGROUND: Plasma amyloid-ß (Aß), phosphorylated tau-181 (p-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) potentially aid in the diagnosis of neurodegenerative dementias. We aim to conduct a comprehensive comparison between different biomarkers and their combination, which is lacking, in a multicenter Chinese dementia cohort consisting of Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). METHODS: We enrolled 92 demented patients [64 AD, 16 FTD, and 12 PSP with dementia] and 20 healthy controls (HC). Their plasma Αß, p-tau181, NfL, and GFAP were detected by highly sensitive-single molecule immunoassays. Αß pathology in patients was measured by cerebrospinal fluid or/and amyloid positron emission tomography. RESULTS: All plasma biomarkers tested were significantly altered in dementia patients compared with HC, especially Aß42/Aß40 and NfL showed significant performance in distinguishing AD from HC. A combination of plasma Aß42/Aß40, p-tau181, NfL, and GFAP could discriminate FTD or PSP well from HC and was able to distinguish AD and non-AD (FTD/PSP). CONCLUSIONS: Our results confirmed the diagnostic performance of individual plasma biomarkers Aß42/Aß40, p-tau181, NfL, and GFAP in Chinese dementia patients and noted that a combination of these biomarkers may be more accurate in identifying FTD/PSP patients and distinguishing AD from non-AD dementia.

Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1.

Chronic obstructive pulmonary disease (COPD) is commonly caused by smoking. FUN14 domain-containing protein 1 (FUNDC1) plays a fundamental role in mitochondrial autophagy and apoptosis in cigarette smoke extract (CSE)-treated BEAS-2B cells. The present study investigated the mechanism of action of FUNDC1 in mitochondrial dysfunction and apoptosis in CSE-treated BEAS-2B cells. The interaction between ubiquitin-specific peptidase 19 (USP19) and FUNDC1 was analyzed using co-immunoprecipitation. Effects of USP19 knockdown and/or FUNDC1 overexpression on the survival, apoptosis, mitochondrial membrane potential, and oxygen consumption rate (OCR) of BEAS-2B cells treated with 15% CSE were determined. In BEAS-2B cells, CSE inhibited cell survival, promoted apoptosis, increased the expression of USP19 and FUNDC1, increased the ratio of LC3 II to LC3 I (LC3 II/I), and decreased mitochondrial membrane potential and TOM20 levels. In CSE-treated BEAS-2B cells, USP19 knockdown reduced FUNDC1 and LC3 II/I, increased the levels of TOM20, improved cell survival, mitochondrial membrane potential, and OCR, and inhibited apoptosis. USP19 deubiquitinates FUNDC1. FUNDC1 overexpression inhibited the effect of USP19 knockdown in CSE-treated BEAS-2B cells. Overall, decreasing USP19 expression alleviates CSE-induced mitochondrial dysfunction in BEAS-2B cells by downregulating FUNDC1, providing novel insights into the molecular mechanism of FUNDC1 regulation in COPD.

Stroke-like onset of calcified brain metastases with Wallerian degeneration: a case report and review of the literature.

INTRODUCTION: Metastatic brain tumors are a common complication of systemic cancer. They tend to have a chronic onset and are located at the gray-white junction of the cerebral hemispheres, those larger than 9.4 mm in diameter are often accompanied by substantial vasogenic edema. Herein, we report a rare case of calcified metastatic adenocarcinoma with Wallerian degeneration. In addition, we discuss the atypical manifestations of brain metastases. CASE REPORT: A 71-year-old man who went through stroke-like onset twice during 8 months with a history of resection of the left pulmonary adenocarcinoma 5 years prior was examined. Diffusion weighted magnetic resonance imaging of the brain showed an enlarged open-ring-shaped hyperintensity on the left periventricular white matter and basal ganglia, with Wallerian degeneration on the left cerebral peduncle. Brain computed tomography revealed nodular calcification of the lesion. The pathology of stereotactic biopsy indicated metastatic adenocarcinoma. CONCLUSION: When patients present with acute nervous system symptoms and a previous history of cancer, the possibility of metastases should be considered, even if neuroimaging is atypical.

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the chinese Han population.

BACKGROUND: Lifelong premature ejaculation (LPE) is one of the most common ejaculatory dysfunctions in men. The serotonin (5-HT) synthesis rate-limiting enzyme (TPH2) and receptor (HTR1A) in the 5-HT regulatory system may play a key role in the pathogenesis of LPE. However, there are few studies on the effects of TPH2 and HTR1A polymorphisms on LPE risk. We speculated that TPH2 and HTR1A polymorphisms may affect the occurrence and development of LPE in the Chinese Han population. METHODS: In this study, 91 patients with LPE and 362 normal controls aged 18 to 64 years were enrolled in the male urology department of Hainan General Hospital in China from January 2016 to December 2018. The SNPs in HTR1A and TPH2, which are related to 5-HT regulation, were selected as indexes to genotype the collected blood samples of participants. Logistic regression was used to analyze the correlation between SNPs of HTR1A and TPH2 with LPE susceptibility, as well as the relationship with leptin, 5-HT and folic acid levels. RESULTS: The results revealed that HTR1A-rs6295 increased LPE risk in recessive model. Rs11178996 in TPH2 significantly reduced susceptibility to LPE in allelic (odds ratio (OR) = 0.68, 95% confidence interval (95% CI) = 0.49-0.96, p = 0.027), codominant (OR = 0.58, 95% CI = 0.35-0.98, p = 0.040), dominant (OR = 0.58, 95% CI = 0.36-0.92, p = 0.020), and additive (OR = 0.71, 95% CI = 0.52-0.98, p = 0.039) models. Grs11179041Trs10879352 could reduce the risk of LPE (OR = 0.44, 95% CI = 0.22-0.90, p = 0.024) by haplotype analysis. CONCLUSION: HTR1A-rs6295 and TPH2-rs11178996 are associated with LPE risk in the Chinese Han population based on the finding of this study.

Effects of CYP24A1 polymorphisms on premature ejaculation: a case-control study.

Premature ejaculation (PE) is a common male sexual dysfunction disorder, and is considered to have the genetic predisposition. However, the internal regulation mechanisms is still unclear. Hence, this study intended to explore the effects of genetic polymorphisms of CYP24A1 on the risk of PE. This case-control study genotyped three SNPs of CYP24A1 (rs2762934, rs1570669 and rs6068816) from 139 PE patients and 372 healthy men using Agena MassARRAY platform. Collected data was then processed in SPSS 18.0. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression analysis to evaluate the associations between CYP24A1 polymorphisms and the PE risk. The results suggested that allele A of rs1570669 was significantly associated with the increased PE risk (OR=1.38, 95% CI=1.04-1.84, P=0.026). Meanwhile, we also identified rs1570669 as a risk factor of PE under the additive model (OR=1.47, 95% CI=1.02-2.11, P=0.039) by comparing the genotypic distributions between cases and controls, and genotype AA of rs1570669 was detected to be significantly related with an increased risk of PE under the codominant model (OR=2.26, 95% CI=1.06-4.83, P=0.036). This study is the first to proved that the genetic variants of CYP24A1 played essential role in affecting the susceptibility to PE in Chinese Han.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.

Occurrence of Intracranial Hemorrhage and Associated Risk Factors in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is thought to be a rare but probably underestimated presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We conducted a systematic review and meta-analysis with the aim of comprehensively revealing the occurrence of ICH in patients with CADASIL. METHODS: English-language studies published up to September 30, 2021 were searched for in the MEDLINE (PubMed), Web of Science, and Cochrane Library databases. The design, patient characteristics, occurrence rate of ICH, and associated risk factors were retrieved for each identified relevant study. RESULTS: We enrolled 13 studies in the final meta-analysis, which included 1,310 patients with CADASIL. The probability of ICH occurrence in patients with CADASIL was 10.1% (95% confidence interval [CI]=5.6%-18.0%, I²=85.1%). When stratified by geographic region, the occurrence rate of ICH was much higher in Asians (17.7%; 95% CI=11.0%-28.5%, I²=76.3%) than in Europeans (2.0%; 95% CI=0.4%-10.8%, I²=82.8%). A higher burden of cerebral microbleeds (CMBs) and a history of hypertension were the most commonly recorded risk factors for ICH, which were available for three and two of the included studies, respectively. CONCLUSIONS: Our study suggests that ICH is an important clinical manifestation of CADASIL, especially in Asians. A higher burden of CMBs and the existence of hypertension were found to be associated with a higher probability of ICH occurrence in patients with CADASIL.

The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of ß-amyloid peptide 1-42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of ß-amyloid peptide 1-42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.

New cerebral microbleeds in AF patients on non-vitamin K oral anticoagulants or warfarin: One-year follow-up.

ABSTRACT: Anticoagulant treatment increases the risk of intracerebral hemorrhage (ICH), but whether the treatment, more specifically non-vitamin K oral anticoagulants (NOACs), increases the risk of cerebral microbleeds (CMBs) remains uncertain. We performed this study to investigate the development of new CMBs due to NOACs or warfarin treatment in patients with atrial fibrillation (AF).We prospectively recruited AF patients before anticoagulation from June 2016 to June 2018. We performed susceptibility-weighted imaging (SWI) examinations on all enrolled AF patients and re-examined SWI 1 year later. We compared demographic features and new CMBs between the NOACs group and the warfarin group. Univariate analysis of clinical factors was performed according to the development of new CMBs; and age, a HAS-B(L)ED score, warfarin use, and the presence of baseline CMBs were then selected for inclusion in the multivariate logistic regression model.A total of 72 AF patients were recruited, 29 of whom were assigned to the NOACs group and 43 to the warfarin group. Finally, 1 patient in the NOACs group (3.4%) and 9 patients (20.9%) in the warfarin group developed new CMBs after 1 year follow-up (P = .08). Univariate analysis showed that age, a HAS-B(L)ED score ≥4, the presence of baseline CMBs were associated with the development of new CMBs (P < .05). And multivariate regression analysis showed baseline CMBs (P = .03, odds ratio = 6.37, 95% confidence interval 1.15-35.36) was independently related to the increase in new CMBs.AF patients treated with NOACs may have a decreased trend in the development of new CMBs compared with those treated with warfarin. Baseline CMBs increased the frequency of new CMBs during anticoagulant treatment. The development of new CMBs in AF patients with anticoagulation requires further longitudinal studies with longer follow-up in larger samples.

Genome-Wide Association Analysis to Search for New Loci Associated with Lifelong Premature Ejaculation Risk in Chinese Male Han Population.

PURPOSE: Genetic factors play an indispensable role in the pathogenesis of lifelong premature ejaculation (LPE). The susceptibility genes/SNPs that have been discovered are very limited and can only explain part of the genetic effects of LPE. Therefore, discovering more genetic polymorphisms associated with the occurrence and development of LPE will help reveal the pathogenesis of LPE. MATERIALS AND METHODS: We conducted a genome-wide association study of LPE in 486 Chinese male Han people (cases and controls). We used Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. Imputation was performed by IMPUTE2 software and the 1000 Genomes Project (Phase3) was used as reference for haplotype. Finally, logistic regression analysis was performed on all loci that passed the quality control. The odds ratio and 95% confidence interval were calculated to determine the association between each SNPs and Chinese male Han population LPE risk. RESULTS: The results showed that a total of 33 genetic variants in 13 genes (LACTBL1, SSBP3, ACOT11, LINC02486, TMEM154, LINC01098, NONE, HCG27, HLA-C, TNFSF8, TNC, FAM53B, SULF2) have a suggestively significant genome-wide association with LPE risk (p<5×10-6). CONCLUSIONS: This study is the first to conduct a GWAS on LPE in Chinese male Han population 33 genetic polymorphisms have a suggestive genome-wide association with LPE risk. This study have provided data supplement for the genetic loci of LPE risk, and laid a scientific foundation for the pathogenesis and the targeted therapy of LPE.

Association between plasminogen activator inhibitor-1 gene polymorphisms and susceptibility to Parkinson's disease in Chinese patients.

PURPOSE: Parkinson's disease (PD) is a neurodegenerative disease that usually leads to memory impairment, cognitive decline and dementia. Previous studies have reported that plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms play important roles in cardiovascular diseases, obesity, inflammation and other diseases. However, the role of PAI-1 in the diagnosis of Parkinson's disease has not been reported so far. METHODS: This study was a case-control study. This study included 131 PD patients and 97 healthy volunteers. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphic loci of five different regions in PAI-1 gene (rs2227631, rs1799889, rs6092, rs2227694 and rs7242). 60 PD patients and 60 healthy volunteers were selected to detect the plasma PAI-1 concentration. The allele and genotype frequencies of SNPs were assessed using the SHEsis program. RESULTS: We found that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in the PD patients. Statistically significant difference for rs1799889 could be observed in overdominant model. In subgroup analysis, a significant difference in genotype frequency distribution and allele frequency was found for rs2227631 and rs1799889 between early-onset PD group and the control group. For cognitive dysfunction, the subcomponent showed that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in normal cognition group. The codominant model of rs1799889 was significantly different between the cognitive impairment group and the control group. In addition, the expression of PAI-1 in plasma of PD patients was significantly higher than that of controls, and further analysis showed that the expression of PAI-1 in patients with cognitive impairment was significantly higher than that in patients with cognitive normal. CONCLUSION: Our results indicate that the PAI-1 gene rs2227631 and rs1799889 polymorphisms were significantly associated with PD susceptibility in the Chinese Han population. PAI-1 has the potential to become a new therapeutic target and diagnostic marker.

Choline Intake Correlates with Cognitive Performance among Elder Adults in the United States.

OBJECTIVE: This research attempted to explore the neuroprotective effect of choline and establish evidence for future dietary recommendations and nutritional interventions to maintain a proper cognitive function among elders aged >60 years in the US. METHOD: This cross-sectional study retrieved data of 2,393 eligible elderly participants from the 2011-2014 National Health and Nutrition Examination Survey. Combining dietary and supplement choline intake, total choline intake was evaluated using the 24-hour dietary recall method and the dietary supplement questionnaire. Total choline intake was categorized into tertiles, which ranged at <187.60 mg/day (T1), 187.60-399.50 mg/day (T2), and >399.50 mg/day (T3). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, Animal Fluency (AF) test, and Digit Symbol Substitution test (DSST) was used to measure cognitive function. Participants who scored the lowest 25th percentile in each cognitive test were classified in the low cognitive function (LC) group. Logistic regression models were implemented to examine the association between total choline intake and the incidence of LC. RESULTS: In the CERAD test, the risk of LC was significantly lower in T2 than T1 (OR: 0.668, 95% CI: 0.493-0.904, and P = 0.006) when adjusted for age, gender, BMI, alcohol consumption, and hypertension. Similarly, T2 was associated with a significantly lower risk of LC when assessed by the AF test (OR: 0.606, 95% CI: 0.580-0.724, and P < 0.001) and DSST (0.584, 95% CI: 0.515-0.661, and P < 0.001). In all three cognitive measures, the T3 of the total choline intake was not associated with cognitive function compared to T1. CONCLUSION: Total choline intake at 187.06-399.50 mg/day reduces the risk of LC by approximately 50% compared to intake at <187.6 mg/day. The findings of this research may be used to establish dietary recommendations and nutritional interventions to optimize the cognitive function among elders.

Rs9303628 and rs2054847 of SLC6A4 are protective factors for the onset of lifelong premature ejaculation among the Chinese population.

The purpose of this study was to investigate whether the polymorphisms of SLC6A4 gene affect the occurrence of lifelong premature ejaculation (LPE). In this case-control study, Agena MassARRAY was used to genotype SLC6A4 polymorphisms of 91 LPE patients and 362 controls. Then, genetic model and haplotype analysis were utilised to explore the correlation between SLC6A4 polymorphisms and LPE risk. The results showed that allele T, genotype T/T and C/T-T/T of rs9303628 were significantly correlated with a decreased risk of LPE in allele (p = .009), co-dominant (p = .025) and dominant (p = .014) model respectively. Allele T and genotype C/T-T/T of rs2054847 reduced the risk of LPE in co-dominant (p = .015) and dominant (p = .030) models respectively. Furthermore, there was a significant correlation between Ars9303628 Crs2054847 haplotype and the decreased the risk of LPE (p = .010). In conclusion, this study firstly proved that the presence of rs9303628 and rs2054847 in SLC6A4 gene was a protective factor for the occurrence of LPE in the Chinese Han population.

Efficacy of BPPV diagnosis and treatment system for benign paroxysmal positional vertigo.

OBJECTIVES: To evaluate the efficacy of automatic benign paroxysmal positional vertigo (BPPV) diagnosis and treatment system for BPPV compared with the manual repositioning group. METHODS: Two hundred thirty patients diagnosed as idiopathic BPPV who were admitted from August 2018 to July 2019 in Zhejiang Hospital were included. Among them, 150 patients of posterior semicircular canal BPPV(pc-BPPV), 53 patients of horizontal semicircular canal BPPV(hc-BPPV), and 27 patients of horizontal semicircular canal calculus (hc-BPPV-cu) were randomly treated with BPPV diagnosis and treatment system(the experimental group) or manual repositioning (the control group). Resolution of vertigo and nystagmus on the Dix-Hallpike and Roll test on day 3,day 7,day 14 and day 28 follow-up after first treatment was the main outcome measure to assess the efficacy of treatment. RESULTS: At 3-day and 7-day follow-up after treatment with BPPV diagnosis and treatment system, 79%, 91%had complete resolution of vertigo and nystagmus, the effective rate in the experimental group were significantly higher than those in the control group, the differences were statistically significant(P < .05). On day 14, the effective rate in the experimental group (96%) was slightly higher than that in the control group(91%), but there was no significant difference between the two groups. And at 28-day after the first treatment, the effective rate was 100% in the experimental group and the control group. The repositioning efficiency of pc-BPPV (the first, second, third treatment), hc-BPPV (the first, second, third treatment), hc-BPPV-cu(the first, second treatment) in the experimental group were higher than the control group, and the secondary reposition of pc-BPPV in the experimental group was significantly higher than the control group(96%vs.84%; P < .05). While for the hc-BPPV-cu patients, the effective rate of the third treatment in the experimental group was slightly lower than that of the control group, but the differences were not statistically significant. CONCLUSIONS: BPPV diagnosis and treatment system is effective for the treatment of BPPV, with a better effective rate than those treated with manual maneuver, and is safe and easy to perform on patients.

Aggregation of Vascular Risk Factors Modulates the Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment Patients.

Background: Several vascular risk factors, including hypertension, diabetes, body mass index, and smoking status are found to be associated with cognitive decline and the risk of Alzheimer's disease (AD). We aimed to investigate whether an aggregation of vascular risk factors modulates the amplitude of low-frequency fluctuation (ALFF) in patients with mild cognitive impairment (MCI). Methods: Forty-three MCI patients and twenty-nine healthy controls (HCs) underwent resting-state functional MRI scans, and spontaneous brain activity was measured by the ALFF technique. The vascular risk profile was represented with the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score, and each group was further divided into high and low risk subgroups. Two-way ANOVA was performed to explore the main effects of diagnosis and vascular risk and their interaction on ALFF. Results: The main effect of diagnosis on ALFF was found in left middle temporal gyrus (LMTG) and left superior parietal gyrus (LSPG), and the main effect of risk on ALFF was detected in left fusiform gyrus (LFFG), left precuneus (LPCUN), and left cerebellum posterior lobe (LCPL). Patients with MCI exhibited increased ALFF in the LMTG and LSPG than HCs, and participants with high vascular risk showed increased ALFF in the LFFG and LCPL, while decreased ALFF in the LPCUN. An interaction between diagnosis (MCI vs. HC) and FHS-CVD risk (high vs. low) regarding ALFF was observed in the left hippocampus (LHIP). HCs with high vascular risk showed significantly increased ALFF in the LHIP than those with low vascular risk, while MCI patients with high vascular risk showed decreased ALFF in the LHIP than HCs with high vascular risk. Interestingly, the mean ALFF of LHIP positively correlated with word recall test in HCs with high vascular risk (rho = 0.630, P = 0.016), while negatively correlated with the same test in MCI patients with high vascular risk (rho = -0.607, P = 0.001). Conclusions: This study provides preliminary evidence highlighting that the aggregation of vascular risk factors modulates the spontaneous brain activity in MCI patients, and this may serve as a potential imaging mechanism underlying vascular contribution to AD.

Genetic Variants of PICALM rs541458 Modulate Brain Spontaneous Activity in Older Adults With Amnestic Mild Cognitive Impairment.

Background: Phosphatidylinositol binding clathrin assembly protein (PICALM) rs541458 C allele has been identified and validated to be associated with a reduction of Alzheimer's disease (AD) risk. Nevertheless, the exact mechanisms through which the variant exert its disease-relevant association remain to be elucidated. This study is to determine whether PICALM rs541458 polymorphism modulates functional magnetic resonance imaging measured brain spontaneous activity in older adults with amnestic mild cognitive impairment (aMCI). Methods: Thirty five aMCI patients and twenty six healthy controls (HC) were enrolled in this study. Each individual was genotyped for rs541458 and scanned with resting-state functional magnetic resonance imaging. Each group was divided into two subgroups (C carriers and TT genotype). Brain activity was measured with amplitude of low-frequency fluctuation (ALFF). Results: The aMCI patients showed decreased ALFF in left inferior frontal gyrus, superior temporal gyrus and insula, while increased ALFF in right cuneus, calcarine, and bilateral posterior cingulate and precuneus. A significant interaction between diagnosis (aMCI vs. HC) and PICALM rs541458 genotype (C carriers vs. TT) on ALFF was observed mainly in the right frontal lobe, with aMCI C carriers and TT genotype in HC showing significantly lower ALFF than HC C carriers. While only negative correlation between ALFF and verbal fluency test was found in HC C carriers (r = -0.543, p = 0.030). Conclusions: This study provided preliminary evidences that PICALM rs541458 variations may modulate the spontaneous brain activity in aMCI patients.

Parkinsonism caused by Intracranial ependymoma: A rare case report and literature review.

BACKGROUND: Ependymomas, especially intracranial ependymomas, are rare neoplasms of the CNS. The clinical courses of patients with intracranial ependymomas can be quite variable. At present, data on parkinsonism caused by ependymomas are scarce. CASE PRESENTATION: A 13-year-old girl presented with parkinsonism symptoms of clumsiness in her left leg and hand. Her mother was diagnosed with Parkinson's disease at age 30, nine years previously. Magnetic resonance imaging showed a lesion in the temporal lobe with long-T1 signal, mixed-T2 signal. The patient was taken in for a right tumorectomy and was diagnosed as having an ependymoma postoperatively. The patient's symptoms fully resolved in the postoperative phase. CONCLUSION: The case describes the mechanism of intracranial ependymoma involving parkinsonism symptoms. Our findings suggest that in some patients presenting with atypical PD symptoms the underlying cause should not be overlooked; MRI examination is necessary.

Extrapontine myelinolysis associated with pituitrin: case report and literature review.

BACKGROUND: Hyponatremia is the most common electrolyte abnormality encountered in hospitalized patients, resulting from a varied spectrum of conditions. Both the primary disturbance and its correction can result in life-threatening neurological consequences. Extrapontine myelinolysis is one such complication that is associated with the rapid correction of hyponatremia. Here we describe a patient who developed extrapontine myelinolysis unexpectedly after the correction of hyponatremia, which involved the drug pituitrin. CASE PRESENTATION: A 24-year-old Chinese woman was transferred to our neurology department with the symptoms of dysarthria and quadriparesis developing one day after the correction of hyponatremia (from 118 mmol/L to 140 mmol/L), which followed with a continuous intravenous drip of pituitrin used to control hemoptysis in the emergency room. During the course, she developed involuntary movement. Magnetic resonance imaging changes were consistent with extrapontine myelinolysis. CONCLUSION: This present case describes the mechanism of profound hyponatremia involving pituitrin, and the subsequent development of extrapontine myelinolysis. Physicians may approach effective clinical management of patients through awareness of the adverse effect of pituitrin on serum sodium levels, and avoid rapid correction of hyponatremia in clinical practice.

Association of the interleukin 1 beta gene and brain spontaneous activity in amnestic mild cognitive impairment.

PURPOSE: The inflammatory response has been associated with the pathogenesis of Alzheimer's disease (AD). The purpose of this study is to determine whether the rs1143627 polymorphism of the interleukin-1 beta (IL-1ß) gene moderates functional magnetic resonance imaging (fMRI)-measured brain regional activity in amnestic mild cognitive impairment (aMCI). METHODS: Eighty older participants (47 with aMCI and 33 healthy controls) were recruited for this study. All of the participants were genotyped for variant rs1143627 in the IL1B gene and were scanned using resting-state fMRI. Brain activity was assessed by amplitude of low-frequency fluctuation (ALFF). RESULTS: aMCI patients had abnormal ALFF in many brain regions, including decreases in the inferior frontal gyrus, the superior temporal lobe and the middle temporal lobe, and increases in the occipital cortex (calcarine), parietal cortex (Pcu) and cerebellar cortex. The regions associated with an interaction of group X genotypes of rs1143627 C/T were the parietal cortex (left Pcu), frontal cortex (left superior, middle, and medial gyrus, right anterior cingulum), occipital cortex (left middle lobe, left cuneus) and the bilateral posterior lobes of the cerebellum. Regarding the behavioral significance, there were significant correlations between ALFF in different regions of the brain and with the cognitive scores of each genotype group. CONCLUSIONS: The present study provided evidence that aMCI patients had abnormal ALFF in many brain regions. Specifically, the rs1143627 C/T polymorphism of the IL1B gene may modulate regional spontaneous brain activity in aMCI patients.

Association study of candidate gene polymorphisms with amnestic mild cognitive impairment in a Chinese population.

To investigate the relationship between amnestic mild cognitive impairment (aMCI) and candidate gene polymorphisms in a Chinese population, 116 aMCI patients and 93 normal controls were recruited. Multi-dimensional neuropsychological tests were used to extensively assess the cognitive functions of the subjects. MassARRAY and iPLEX systems were used to measure candidate single nucleotide polymorohisms (SNPs) and analyse allelic, genotypic or haplotypic distributions. The scores of the neuropsychological tests were significantly lower for the aMCI patients than for the normal controls. The distributions of SNPs relating to the amyloid cascade hypothesis (TOMM40 rs157581 G and TOMM40 rs2075650 G), to the cholesterol metabolism hypothesis (ApoE rs429358 C, LDLR rs11668477 G and CH25H rs7091822 T and PLAU rs2227564 CT) and to the tau hypothesis (MAPT/STH rs242562 GG) in aMCI were significantly different than those in normal controls. Interactions were also found in aMCI amongst SNPs in LDLR rs11668477, PLAU rs2227564, and TOMM40 rs157581, between SNPs in TOMM40 rs157580 and BACE2 rs9975138. The study suggests that aMCI is characterised by memory impairment and associated with SNPs in three systems relating to the pathogenesis of AD--those of the amyloid cascade, tau and cholesterol metabolism pathways. Interactions were also observed between genes in the amyloid pathway and between the amyloid and cholesterol pathways.