Case report: Hyponatremia is an initial presentation of Neuromyelitis optica spectrum disorder.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) is often misdiagnosed or delayed because of the complex and diverse clinical manifestations, especially the atypical initial presentation. Hyponatremia can be an infrequently isolated initial presentation of NMOSD and is associated with hypothalamus involvement. Awareness of this mechanism will help clinicians to identify NMOSD early, treat it in time and improve the prognosis. METHODS: We describe a 36-year-old woman who developed repeated hyponatremia and then experienced diplopia. Serum AQP4, MOG, MBP and GFAP antibody were detected, and NMOSD was finally diagnosed. RESULTS: She responded well to high-dose glucocorticoids. Sequential treatment with mycophenolate mofetil (MMF) was prescribed. Two-month follow-up revealed full recovery. So far, after 10 months, the patient still has no recurrence. CONCLUSION: For young patients, repeated hyponatremia, with or without slight fever, and no evidence of obvious infection, brain magnetic resonance imaging (MRI) and serum AQP4/MOG antibody detection may be useful to determine whether there is a possibility of NMOSD.

Interaction between aluminum exposure and ApoEε4 gene on cognitive function of in-service workers.

The occurrence and development of cognitive impairment, the early stage of AD, may be affected both by factors of environmental (aluminum exposure) and genetic (ApoEε4 gene). But whether there is an interaction between the two factors on cognitive function is still unknown. To explore the interaction between the two factors on cognitive function of in-service workers. A total of 1121 in-service workers in a large aluminum factory were investigated in Shanxi Province. Cognitive function was assessed by the Mini-mental State Examination (MMSE), the clock-drawing test (CDT), the Digit Span Test (DST, including DSFT and DSBT), the fuld object memory evaluation (FOM), and the verbal fluency task (VFT). The plasma-Al (p-Al) concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS) as an internal exposure indicator, and the participants were divided into four Al exposure groups according to the quartile of p-Al concentrations, namely Q1, Q2, Q3, and Q4. ApoE genotype was determined by Ligase Detection Reaction (LDR). The multiplicative model was fitted using non-conditional logistic regression and additive model was fitted using crossover analysis to analyze the interaction between p-Al concentrations and the ApoEε4 gene. Finally, a dose-response relationship between p-Al concentrations and cognitive impairment was observed, with the p-Al concentrations increased, cognitive function performance gradually becomes worse (Ptrend＜0.05), and the risk of cognitive impairment gradually increases (Ptrend＜0.05), mainly in executive/visuospatial impairment, auditory memory impairment (particularly the working memory impairment). And ApoEε4 gene may be a risk factor for cognitive impairment, while no association between the ApoEε2 gene and cognitive impairment is observed. Additionally, an additive but no multiplicative interaction between p-Al concentrations and ApoEε4 gene is observed, and when the two factors work together, the risk of cognitive impairment further increased, of which 44.2% can be attributed to the interaction effect.

Diffusion Kurtosis Imaging in Evaluating the Mild Cognitive Impairment of Occupational Aluminum Workers.

RATIONALE AND OBJECTIVES: To investigate whether diffusion kurtosis imaging (DKI) can distinguish mild cognitive impairment (MCI) from normal controls (NC) in aluminum (Al)-exposed workers, and to explore the association of DKI with cognitive performance and plasma Al concentration. MATERIALS AND METHODS: 28 patients with MCI and 25 NC at Al factory were enrolled in this study. All subjects underwent conventional MRI and DKI scans. The mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr), mean diffusivity (MD) and fractional anisotropy (FA) parameters of the hippocampus, substantia nigra, red nucleus, thalamus, anterior cingulate gyrus, genu and crus of the corpus callosum, frontal, parietal and temporal lobe were measured. To compare the parameters between the two groups, the Mann-Whitney rank sum test was used. The correlation of parameter values with cognitive performance and plasma Al concentration was analyzed using Spearman correlation analysis. The receiver operating characteristic (ROC) curve and the Z-scores were used to evaluate the diagnostic efficacy of each parameter. RESULTS: Compared with the NC group, the MK, Ka, Kr, and FA values in the MCI group were significantly decreased, and the MD values were significantly increased (p<0.05). For the diagnosis of MCI, MK in the right hippocampus showed the largest AUC (0.924). The MK, Kr, MD and FA values were correlated with the Montreal Cognitive Assessment (MoCA) scores, and MK values in the right hippocampus showed the greatest correlation with MoCA scores (r=0.744, p <0.001). Plasma Al in the MCI group was higher than that in the NC group, although there was no significant difference in plasma Al between the two groups (p=0.057). There was no correlation between DKI parameters and plasma Al. CONCLUSION: The DKI method might be a sensitive imaging biomarker to discriminate MCI from NC, and could preliminarily assess the severity of cognitive impairment in Al-exposed workers. MK in the right hippocampus appeared to be the best independent predictor. The mechanism of cognitive decline is an important content of aluminum exposure research. This study indicates that the DKI technique could provide valuable information for the diagnosis of MCI.

Hypothyroidism combined with anti-signal recognition particle immune-mediated necrotizing myopathy: A case report and review of the literature.

Immune-mediated necrotizing myopathy (IMNM) is characterized by proximal limb weakness, elevated creatine kinase (CK) levels, and myofiber necrosis without or with only a small amount of inflammatory cell infiltrate. There is only 1 report of hypothyroidism combined with antibody-negative IMNM to date. We aimed to describe a rare case of hypothyroidism combined with anti-signal recognition particle (SRP) IMNM for the first time and review the previous literature. A 50-year-old male, who had a 4-year history of hypothyroidism treated with levothyroxine replacement therapy, presented with progressive symmetrical proximal muscle weakness. Laboratory testing showed an elevated CK level of 6,106 U/L. Electrophysiological examination elicited carpal tunnel syndrome and myogenic damage. Muscle MRI revealed diffuse abnormal signals in both lower limbs. Given that muscle symptoms are widely recognized among hypothyroid patients, hypothyroid myopathy was initially suspected, and thyroid hormone tablets were added for a week. However, muscle weakness persisted along with an even higher CK (7,020 U/L). Quadriceps muscle biopsy was performed and indicated inflammatory myopathy. Myositis specific antibodies (MSAs) detection revealed that anti-SRP was positive. A diagnosis of hypothyroidism combined with anti-SRP IMNM was finally made. Treatment of corticosteroid and immunosuppressive agents achieved a positive clinical and biochemical response. This case indicates that hypothyroidism combined with anti-SRP IMNM is a rare clinical entity, possibly caused by a general immunologic dysregulation.

Standardized nursing management of enzyme replacement therapy for late-onset Pompe disease.

ABSTRACT: Pompe disease or glycogen storage disease type II is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme a-glucosidase. Although enzyme replacement therapy (ERT) with 2 weekly intervals following was considered an effective treatment for Pompe disease in 2006, few patients can afford to receive treatment in China because of the high cost. This study aimed to examine the standard management of enzyme replacement therapy for late-onset Pompe disease among patients over the age of 14 years from a nursing perspective in order to assess operating procedures. ERT injection fluid dispensing and infusion procedures using different methods were analyzed and compared in 3 patients with advanced Pompe disease for forming standard operation procedures. In addition, the impact of different methods on time consumption was analyzed by 1-way analysis of variance. There were significant differences in time consumption between different dispensing and infusion methods. The time of dispensing and infusing the injection fluids using the cooperative method was 15.97 minutes shorter than that using the conventional method (95% CI: 4.51-27.43, P = .012); the time using the modified method was 20.93 minutes shorter than that using the conventional method (95% CI: 9.47-32.39, P = .012); and there was no significant difference between the cooperative and modified methods (P = .431). Enzyme replacement therapy entails frequent treatment and strict nursing requirements related to the intravenous infusion process. In this context, a standard operating procedure can be used to control nursing times and labor costs effectively while ensuring a safe and effective infusion process.

Late-onset multiple acyl-CoA dehydrogenase deficiency with cardiac syncope: A case report.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an uncommon autosomal recessive disorder of mitochondrial fatty acid beta-oxidation. Syncope is a transient loss of consciousness due to acute global cerebral hypoperfusion. Late-onset MADD with syncope has not been reported previously. CASE SUMMARY: We report a 17-year-old girl with exercise intolerance and muscle weakness. She felt palpitation and shortness of breath after short bouts of exercise. She also suffered from a transient loss of consciousness many times. Muscle biopsy showed lipid storage. Genetic mutation analysis indicated a compound heterozygous mutation c.250G > A (p.A84T) and c.872T > G (p.V291G) in the ETFDH gene. The results of Holter electrocardiogram monitoring showed supraventricular tachycardia when the patient experienced a loss of consciousness. After treatment with riboflavin and carnitine, muscle weakness and palpitation symptoms improved rapidly. No loss of consciousness occurred, and the Holter electrocardiogram monitoring was normal. CONCLUSION: Late-onset MADD with supraventricular tachycardia can cause cardiac syncope. Carnitine and riboflavin supplement were beneficial for treating the late-onset MADD with cardiac syncope. Attention should be paid to the prevention of cardiac syncope when diagnosing late-onset MADD.

A meta-analysis and systematic review of Leigh syndrome: clinical manifestations, respiratory chain enzyme complex deficiency, and gene mutations.

Leigh syndrome (also called Leigh disease or subacute necrotizing encephalomyelopathy) is a rare inherited neurometabolic disorder, which affects the central nervous system. This meta-study systematically analyzed clinical manifestations, respiratory chain enzyme complex deficiency, and gene mutations.Literature was searched for publications in MEDLINE, EMBASE, and the China National Knowledge Infrastructure database for meta-analyses of the incidence of clinical symptoms, laboratory assessments, imaging data, muscle biopsy histochemical staining, activity of the mitochondrial respiratory chain enzyme complex, gene mutations, and the association between age at disease onset and type of gene mutations.This study included 5 studies with 385 Leigh syndrome patients. The most common clinical features of Leigh syndrome included elevated blood and/or cerebrospinal fluid (CSF) levels of lactate (72%), developmental retardation (57%), hypotonia (42%), followed by respiratory dysfunction (34%), epileptic seizures (33%), poor feeding (29%), and weakness (27%). Approximately 80% of the patients had deficiencies of the respiratory chain enzyme complex or isolated complex I deficiency (35%), 32% had mitochondrial DNA (mtDNA) mutations, and 38% had nuclear DNA (nDNA) mutations. Patients with nDNA mutations were younger than those with mtDNA mutations (8.82 ± 13.88 vs 26.20 ±â€Š41.11 years, P = .007).The data from the current meta-analysis demonstrated a variety of clinical and molecular manifestations of Leigh syndrome, with upregulated lactate levels in the blood or CSF being the most common feature. Diagnosis of Leigh syndrome could be confirmed using combined enzymatic and genetic analyses.

Aluminum-Induced Synaptic Plasticity Impairment via PI3K-Akt-mTOR Signaling Pathway.

Aluminum (Al) is an environmental neurotoxin with extensive exposure by humans, but the molecular mechanism of its toxicity is still unclear. Several studies have indicated that exposure to aluminum can impair learning and memory function. The purpose of this study was to investigate the mechanism of LTP injury and the effect of aluminum exposure on related signal pathways. The results showed that the axonal dendrites of neurons in the hippocampal CA1 area of rats exposed to maltol aluminum showed neuritic beading and the dendritic spines were reduced. This resulted in dose-dependent LTP inhibition and led to impaired learning and memory function in rats. The PI3K-Akt-mTOR pathway may play a crucial role in this process.

The Relationship between Plasma Al Levels and Multi-domain Cognitive Performance among In-service Aluminum-exposed Workers at the SH Aluminum Factory in China: A Cross-sectional Study.

BACKGROUND: Aluminum (Al) exerts neurotoxic effects following overexposure. We previously reported worse cognitive performance in workers exposed to Al than non-exposed individuals. Cognition involves multiple domains. The effect of Al on multi-domain cognition has been studied for decades, but still remains controversial. OBJECTIVE: To explore the relationship between plasma Al levels and multi-domain cognitive performance among in-service aluminum-exposed workers at the SH Aluminum Factory in China and identify possible types of early cognitive damage caused by exposure to aluminum. METHODS: Eight hundred thirty-one in-service aluminum-exposed workers at the SH Aluminum Factory in China were investigated. The plasma Al concentrations were measured using inductively coupled plasma-mass spectrometry (ICP-MS) and served as an internal exposure indicator. The participants were divided into four subgroups based on the quartiles of plasma Al concentrations, namely, the Q1, Q2, Q3, and Q4 subgroups. Cognitive function was assessed using the Mini-mental State Examination (MMSE) and the clock-drawing test (CDT). Multi-domain cognition was evaluated using sub-tests of the MMSE and the CDT. RESULTS: The average plasma Al concentration was 15.26 (8.28, 27.02) µg/L. The neurobehavioral tests showed negative correlations between plasma Al levels and total CDT scores and executive/visuospatial cognitive performance, and a positive correlation between plasma Al levels and CDT-position errors (all P<0.05). Additionally, dose-response relationships between higher plasma Al levels and lower total CDT scores, worse executive/visuospatial cognitive performance, and more error rates in the CDT-position were observed (all Ptrend<0.05). However, no significant correlations or trends were observed between plasma Al levels and other cognitive domains (all P>0.05). The results from the multivariate logistic regression model and restricted cubic spline models of dose-response relationships were consistent with the results obtained from the general linear model. All potential confounders, such as age, marital status, education, income, type of work, and smoking and drinking habits, were considered. CONCLUSION: Based on the results, aluminum exposure may exert a substantial effect on impairing executive/visuospatial functions in multi-domain cognition at the early stage, particularly the identification of spatial positions.

The relationship between cognitive impairment and homocysteine in a B12 and folate deficient population in China: A cross-sectional study.

Alzheimer disease (AD) is the most common neurodegenerative disease in the world. The relationship between AD and homocysteine (Hcy) is contradictory.A community-based investigation was conducted to find patients with AD in a vitamin B deficient population (≥55 years old) in Lüliang area in China. Venous blood samples were collected. Serum Hcy, folate, and vitamin B12 were measured. For each case, 4 controls were selected matched with age to evaluate the relationship between Hcy and AD.The crude prevalence of AD among people ages 55 years or older in this area was 8.60%. There were significant differences in serum Hcy and B12 between the case and control groups. We found that the higher level of serum Hcy was associated with a high risk of AD, and higher education level, higher folate and B12 concentration were protective factors to AD.Adjustment of diet structure and supplementation of folate and B12 may offer potential therapeutic measures in this area.

Cognitive impairment of workers in a large-scale aluminium factory in China: a cross-sectional study.

OBJECTIVES: To investigate the prevalence of mild cognitive impairment and the relationship with plasma aluminium among aluminium workers. DESIGN: This was a cross-sectional case-control study in the SH Aluminium Factory, China. SETTING: The university and affiliated hospital cooperated in the study. PARTICIPANTS: There were 910 aluminium workers on duty, among whom 853 participated in our study. Participants, such as those with cerebral vascular disease, epilepsy, brain trauma, Parkinson's and mental diseases, aluminium-containing drug and mental drug use, and any family history of dementia in first-degree relatives were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Blood samples were collected, and plasma aluminium was measured by inductively coupled plasma-mass spectrometry. For each case, four age-matched controls were evaluated to determine the relationship between aluminium exposure and mild cognitive impairment. Conditional logistic regression was used to explore influential factors in mild cognitive impairment. RESULTS: Among 910 workers, 93.74% participated in stage 1; 53 cases were finally diagnosed. The crude prevalence of mild cognitive impairment among aluminium workers on duty was 6.21%. There was a significant difference in plasma aluminium concentration between the two groups. In the multivariate analysis, we found that a higher level of plasma aluminium was associated with a high risk of cognitive impairment when compared with a lower aluminium level (AOR=2.24, 95% CI=1.17 to 4.26), and a high education level was a protective factor (AOR=0.36, 95% CI=0.18 to 0.70). No other factor was statistically significant. CONCLUSIONS: Mild cognitive impairment is no longer a disease specific to elderly people. High plasma aluminium exposure might be associated with an increased risk of cognitive impairment, but a reduced risk was observed with a high education level. The cognitive function of aluminium workers on duty must be considered seriously.

A novel thymidine phosphorylase mutation in a Chinese MNGIE patient.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder associated with mitochondrial alterations. MNGIE is characterized by severe gastrointestinal dysmotility, cachexia, ophthalmoplegia, ptosis, peripheral neuropathy, and leukoencephalopathy. The condition is caused by mutation of the TYMP gene. We studied the clinical and biochemical characteristics of a family with MNGIE. The proband was a 48-year-old male presenting with diarrhea and progressive weight loss. He also had ptosis and exhibited eyeball fixation. His blood and cerebrospinal fluid lactate levels were elevated. Magnetic resonance imaging of the brain revealed diffuse leukoencephalopathy. Ragged red fibers and cytochrome c oxidase-deficient fibers were apparent on muscle biopsy. His vision and ptosis deteriorated significantly during follow-up. Our clinical diagnosis of MNGIE was confirmed by TYMP gene analysis. We discovered a homozygous TYMP c.1193-1216 dup-GGGCGCTGCCGCTGGCGCTGGTGC mutation (a duplication). Some of the family members were heterozygous for the mutation but had no clinical features. We predicted the function of this mutation using PredictProtein and found that the secondary structure had changed in the region of the helix and strand, the transmembrane region, and the protein-protein binding sites. The family described herein exhibited biochemically, genetically, and functionally confirmed MNGIE syndrome.

Erythropoietin activates Keap1-Nrf2/ARE pathway in rat brain after ischemia.

rhEPO has previously been shown to exert neuroprotective action in focal cerebral ischemia. However, its mechanism is not clear. We established the model of permanent focal cerebral ischemia. rhEPO was administered (5000 IU/kg i.p.) 2 h later after the successful ischemia model in rhEPO group and increased translation of Nrf2 and HO-1 and decreased the H2O2 concentration in the brain confirming activation of the Keap1-Nrf2/ARE pathway. The results show that rhEPO activate Keap1-Nrf2/ARE pathway after ischemia to protect the brain tissue.