Creatine mapping of the brain at 3T by CEST MRI.

PURPOSE: To assess the feasibility of CEST-based creatine (Cr) mapping in brain at 3T using the guanidino (Guan) proton resonance. METHODS: Wild type and knockout mice with guanidinoacetate N-methyltransferase deficiency and low Cr and phosphocreatine (PCr) concentrations in the brain were used to assign the Cr and protein-based arginine contributions to the GuanCEST signal at 2.0 ppm. To quantify the Cr proton exchange rate, two-step Bloch-McConnell fitting was used to fit the extracted CrCEST line-shape and multi-B1 Z-spectral data. The pH response of GuanCEST was simulated to demonstrate its potential for pH mapping. RESULTS: Brain Z-spectra of wild type and guanidinoacetate N-methyltransferase deficiency mice show a clear Guan proton peak at 2.0 ppm at 3T. The CrCEST signal contributes ∼23% to the GuanCEST signal at B1 = 0.8 µT, where a maximum CrCEST effect of 0.007 was detected. An exchange rate range of 200-300 s-1 was estimated for the Cr Guan protons. As revealed by the simulation, an elevated GuanCEST in the brain is observed when B1 is less than 0.4 µT at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B1 is greater than 0.4 µT with the same pH drop. CONCLUSIONS: CrCEST mapping is possible at 3T, which has potential for detecting intracellular pH and Cr concentration in brain.

A Low-cost Creatinine Biosensor by Differential Optical Signal Readout for the Whole Blood Analysis.

This study developed a low-cost paper-based biosensor for point-of-care (POC) detection of blood creatinine by using differential optical signal readout. Dual-channel photochemical paper-based test strips were fabricated with stackable multilayer films containing pre-immobilized enzymes and reagents for the identification and conversion of creatinine and creatine. Enzyme-linked reactions generated hydrogen peroxide (H2O2), which formed a blue oxidized condensate with aniline derivatives. The color depth was quantified via the differential optical signal of the two channels and positively correlated with the concentration of the analyte. This method was first proposed to address the issue of endogenous interferences in the enzymatic assay of creatinine, greatly improving the detection accuracy. The proposed biosensor was calibrated with spiked blood samples, and achieved a wide detection range of 31-1483 µmol/L, showing superior detection performance to general enzymatic methods, especially in the low concentration range. Creatine interference testing demonstrated that the biosensor could resist the interference of ≤ 300 µmol/L endogenous creatine. It is believed that the proposed optical differential biosensor for blood creatinine could enable to pave the way for a daily monitoring system for renal diseases.Clinical Relevance- This stackable multilayer paper-based biosensor provides an enzymatic colorimetric assay of creatinine in whole blood, which can be read out by the differential optical signal to exclude interference from endogenous creatine.

Simultaneous derivatization and extraction of amphetamine and methamphetamine using dispersive liquid-liquid microextraction prior to their analysis using GC-FID in creatine supplements.

This study was focused on the development of a sensitive, reliable, and efficient extraction procedure for the determination of amphetamine and methamphetamine utilized in the adulteration of creatine sports supplements. The separation and detection of the analytes were conducted using the gas chromatography-flame ionization detection method. In this study, the analytes were extracted from a supplement powder into a proper solvent by sonication. Then, the extract was mixed with butyl chloroformate to obtain their butylated derivatives and then concentrated by a dispersive liquid-liquid microextraction procedure. The method was performed in a short time. Under optimized extraction conditions, a linear range of 2.01-500 ng g-1 was obtained by a coefficient of determination ≥0.996. Low detection (0.22 ng g-1 and 0.61 ng g-1 for amphetamine and methamphetamine, respectively) and quantification (0.73 ng g-1 and 2.01 ng g-1 for amphetamine and methamphetamine, respectively) limits, good precision (relative standard deviations ≤8.2%), and high extraction recoveries (79% and 86% for amphetamine and methamphetamine, respectively) were achieved. The usefulness of the method in the analysis of the target compounds was confirmed by studying the matrix effect and analysis of the analytes in different real samples.

Creatine Chemical Exchange Saturation Transfer (Cr-CEST) Imaging Can Evaluate Cisplatin-induced Testicular Damage.

PURPOSE: This study aimed to investigate the ability of creatine-chemical exchange saturation transfer (Cr-CEST) technique assessed through 7-T MRI to evaluate cisplatin-induced testicular damage. METHODS: We used 8-10 weeks C57BL/6 mice (n = 10) that were divided into a control group (n = 5) and a cisplatin-treated group (n = 5). The cisplatin group received cisplatin at a dose of 15 mg/kg, via intraperitoneal injection, while the control group received saline. MR images of mouse testes were acquired under anesthesia 18 days after the injection using a horizontal 7-T scanner. The pulse sequence consisted of rapid acquisition with a relaxation enhancement (RARE) with magnetization transfer. The Z-spectra were collected using a 2000-ms saturation pulse at a B1 amplitude of 1.2 µT, with frequencies varying from -4.8 to +4.8 parts per million (ppm). Maps of magnetization transfer ratio with asymmetric analysis (MTRasym) were reconstructed at a Cr metabolite concentration of 1.8 ppm. RESULTS: The Cr-CEST effect was significantly reduced in the cisplatin-treated group compared to the control group (MTRasym of control mice vs. cisplatin-treated mice: 6.9 [6-7.5] vs. 5.2 [4-5.5], P = 0.008). Correlation analysis revealed a strong correlation between the Cr-CEST effect and the pathological score (ρ = 0.93, P < 0.001). CONCLUSION: Cr-CEST MRI can be useful for the evaluation of cisplatin-induced testicular damage in mice.

Raw to charred: Changes of precursors and intermediates and their correlation with heterocyclic amines formation in grilled lamb.

This work aimed to investigate the changes and correlations of precursors, intermediates and heterocyclic amines (HCAs) in lamb during charcoal grilling. 28 chemical compounds were detected by high-performance liquid chromatography and gas chromatography-mass spectrometry in grilled lamb from raw to charred. Results demonstrated the types and contents of HCAs were increased during grilling, of which 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) was dominant and accounted for 61% at the end of grilling (42 min). Glucose and creatine (P < 0.05) decreased with grilling time, creatinine (P < 0.05) and total free amino acid increased. The types and contents of four intermediates (formaldehyde, acetaldehyde, phenylacetaldehyde, 2,5-dimethylpyrazine) increased during grilling. Glucose, creatine, creatinine, ten free amino acids and four intermediates showed significant correlation to HCAs. Also, the ratios of four precursors were significantly correlated with HCAs (P < 0.05), besides creatine/glucose ratio. These results suggested that the time of charcoal grilling should not exceed 14 min at 145 °C in order to reduce the formation of harmful compounds in lamb meat.

Muscular carnosine is a marker for cardiorespiratory fitness and cardiometabolic risk factors in men with type 1 diabetes.

PURPOSE: Muscle is an essential organ for glucose metabolism and can be influenced by metabolic disorders and physical activity. Elevated muscle carnosine levels have been associated with insulin resistance and cardiometabolic risk factors. Little is known about muscle carnosine in type 1 diabetes (T1D) and how it is influenced by physical activity. The aim of this study was to characterize muscle carnosine in vivo by proton magnetic resonance spectroscopy (1H MRS) and evaluate the relationship with physical activity, clinical characteristics and lipoprotein subfractions. METHODS: 16 men with T1D (10 athletes/6 sedentary) and 14 controls without diabetes (9/5) were included. Body composition by DXA, cardiorespiratory capacity (VO2peak) and serum lipoprotein profile by proton nuclear magnetic resonance (1H NMR) were obtained. Muscle carnosine scaled to water (carnosineW) and to creatine (carnosineCR), creatine and intramyocellular lipids (IMCL) were quantified in vivo using 1H MRS in a 3T MR scanner in soleus muscle. RESULTS: Subjects with T1D presented higher carnosine CR levels compared to controls. T1D patients with a lower VO2peak presented higher carnosineCR levels compared to sedentary controls, but both T1D and control groups presented similar levels of carnosineCR at high VO2peak levels. CarnosineW followed the same trend. Integrated correlation networks in T1D demonstrated that carnosineW and carnosineCR were associated with cardiometabolic risk factors including total and abdominal fat, pro-atherogenic lipoproteins (very low-density lipoprotein subfractions), low VO2peak, and IMCL. CONCLUSIONS: Elevated muscle carnosine levels in persons with T1D and their effect on atherogenic lipoproteins can be modulated by physical activity.

The effect of creatine ingestion on urinary creatinine concentration: Does supplementation mask a heavy dilution?

A high volume of fluid can strongly reduce a drug's concentration in urine. Therefore, to detect diluted samples, the concentration of creatinine in urine is determined during testing drugs of abuse. If the concentration is below 20 mg creatinine/dl urine, the urine sample is usually rejected for drug testing. It should be examined whether creatine or creatinine ingestion can mask urine dilution by increasing the creatinine concentration. A total of 18 subjects drank 1.3 L of water and 0.2 L of orange juice on each of the three testing days: (1) without creatine, (2) with 20 g of creatine, and (3) with 20 g of creatine following incubation for 4 days in orange juice at room temperature; an acidic environment should promote conversion of creatine to creatinine. The lowest creatinine concentrations in urine were observed on average 2 h after fluid intake. At that time, ingestion of fluid without creatine, with creatine, and with creatine(ine)-orange juice mixture resulted in mean values of 11.6, 22.5, and 28.3 mg creatinine/dl urine, respectively. It can be concluded that ingestion of creatine or creatinine can increase the concentration of creatinine in urine and thus mask dilution of a sample. The conversion of creatine in orange juice further increases availability of creatinine as it is obvious from urine creatinine concentration. Therefore, creatine ingestion during drug testing will give rise to negative results due to matrix adulteration. In a case of suspected creatine supplementation, the creatine content of the sample should be determined in addition to creatinine.

Comparación clínica y laboratorial de la fiebre amarilla severa versus dengue grave en Perú / Clinical and laboratory differences between severe yellow fever and severe dengue in emergency patients

En los centros de Emergencia con poco apoyo de laboratorio, es difícil diferenciar a los pacientes con dengue grave y fiebre amarilla severa. El objetivo fue comparar el perfil clínico y de laboratorio de los pacientes con dengue grave y fiebre amarilla severa en Urgencias. Se realizó un estudio observacional retrospectivo de pacientes con diagnóstico confirmado de dengue y fiebre amarilla en el período 2018 a 2020 atendidos en la Unidad de Emergencia del Hospital Carrión, Huancayo-Perú. Se evaluaron un total de 35 pacientes, 11 pacientes (31,4%) fueron diagnosticados con fiebre amarilla severa y 24 pacientes (68,5%) con dengue grave. La media de los resultados de laboratorio con fiebre amarilla severa fueron bilirrubina indirecta 4,7 ml/dL, aspartato transaminasa 4463 UI/L, transaminasa aminotransferasa 4329 UI/L, creatinina 4,9 mg/dl. En pacientes con dengue grave el hematocrito promedio fue 51,8, hemoglobina 17,6 g/dl, plaquetas 24 × 103/mm. En pacientes con síndrome ictérico-febril la presencia de bradicardia, bilirrubina indirecta elevada y transaminasas muy elevadas debe hacer sospechar de fiebre amarilla; mientras que los pacientes que acuden por ascitis, derrame pleural, aumento de hematocrito y deficiencia de plaquetas, se debe tratar como dengue grave sobre todo en Unidades de Emergencia con poco apoyo de laboratorio(AU)

In Emergency centers with little laboratory support, differentiating patients with dengue and yellow fever is difficult. The Aim was to compare the clinical and laboratory profile of patients with severe dengue and severe yellow fever in the Emergency unit. We conducted a retrospective observational study of patients with a confirmed diagnosis of dengue and yellow fever in the period 2018 to 2020 treated in the Emergency Unit of the Carrión hospital, Huancayo-Peru. A total of 35 patients were evaluated, 11 patients (31.4%) were diagnosed with severe yellow fever and 24 patients (68.5%) with severe dengue. The mean laboratory results in patients with severe yellow fever were indirect bilirubin 4.7 ml/dL, aspartate transaminase 4463 IU/L, transaminase aminotransferase 4329 IU/L, creatinine 4.9 mg / dl. In patients with severe dengue were hematocrit 51.8, hemoglobin 17.6 g / dl, platelets 24 × 103 / mm. In patients with syndrome jaundice and fever the presence of bradycardia, elevated indirect bilirubin, and very elevated transaminases should be suspicious for yellow fever; while in patients who come for ascites, pleural effusion, increased hematocrit and platelet deficiency, it should be treated as severe dengue especially in Emergency Units with little laboratory support(AU)

Evaluation of recombinant human erythropoietin responsiveness by measuring erythrocyte creatine content in haemodialysis patients.

BACKGROUND: One of the main causes of anaemia in patients with end-stage renal disease is relative deficiency in erythropoietin production. Eythropoiesis stimulating agent (ESA), a potent haematopoietic growth factor, is used to treat anaemia in haemodialysis patients. The effect of ESA is usually assessed by haematological indices such as red blood cell count, haemoglobin concentration and haematocrit, but erythrocyte indices do not provide information of the rapid change in erythropoietic activity. As erythrocyte creatine directly assess erythropoiesis, the aim of this study was to evaluate the effect of ESA in haemodialysis patients by measuring the erythrocyte creatine content. METHODS: ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the entire study period. Erythrocyte creatine was measured with haematologic indices in 83 haemodialysis patients. Haemoglobin was also measured 3 months after. RESULTS: ESA dose (152.4 ± 62.9 vs. 82.2 ± 45.5 units/kg/week, P = 0.0001) and erythrocyte creatine (2.07 ± 0.73 vs. 1.60 ± 0.41 µmol/gHb, p = 0.0003) were significantly higher in 27 patients with haemoglobin <10 g/dL compared to 56 patients with haemoglobin ≥10 g/dL. There was a fair correlation between ESA dose and the concentration of creatine in the erythrocytes (r = 0.55, P < 0.0001). Increase in haemoglobin (>0.1 g/dL) was observed in 37 patients, whereas haemoglobin did not increase in 46 patients. Erythrocyte creatine levels were significantly higher in those patients with an increase in haemoglobin compared to those without (2.04 ± 0.64 vs. 1.52 ± 0.39 µmol/gHb, p < 0.0001). When 8 variables (ESA dose, erythropoietin resistance index, C-reactive protein, intact parathyroid hormone, iron supplementation, presence of anaemia, erythrocyte creatine and reticulocyte) were used in the multivariate logistic analysis, erythrocyte creatine levels emerged as the most important variable associated with increase in haemoglobin (Chi-square = 6.19, P = 0.01). CONCLUSION: Erythrocyte creatine, a useful marker of erythropoietic capacity, is a reliable marker to estimate ameliorative effectiveness of ESA in haemodialysis patients.

1H-NMR-Based Metabolomics: An Integrated Approach for the Detection of the Adulteration in Chicken, Chevon, Beef and Donkey Meat.

Meat is a rich source of energy that provides high-value animal protein, fats, vitamins, minerals and trace amounts of carbohydrates. Globally, different types of meats are consumed to fulfill nutritional requirements. However, the increasing burden on the livestock industry has triggered the mixing of high-price meat species with low-quality/-price meat. This work aimed to differentiate different meat samples on the basis of metabolites. The metabolic difference between various meat samples was investigated through Nuclear Magnetic Resonance spectroscopy coupled with multivariate data analysis approaches like principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). In total, 37 metabolites were identified in the gluteal muscle tissues of cow, goat, donkey and chicken using 1H-NMR spectroscopy. PCA was found unable to completely differentiate between meat types, whereas OPLS-DA showed an apparent separation and successfully differentiated samples from all four types of meat. Lactate, creatine, choline, acetate, leucine, isoleucine, valine, formate, carnitine, glutamate, 3-hydroxybutyrate and α-mannose were found as the major discriminating metabolites between white (chicken) and red meat (chevon, beef and donkey). However, inosine, lactate, uracil, carnosine, format, pyruvate, carnitine, creatine and acetate were found responsible for differentiating chevon, beef and donkey meat. The relative quantification of differentiating metabolites was performed using one-way ANOVA and Tukey test. Our results showed that NMR-based metabolomics is a powerful tool for the identification of novel signatures (potential biomarkers) to characterize meats from different sources and could potentially be used for quality control purposes in order to differentiate different meat types.

Wild Bornean orangutans experience muscle catabolism during episodes of fruit scarcity.

Pronounced temporal and spatial variation in the availability of food resources can produce energetic deficits in organisms. Fruit-dependent Bornean orangutans face extreme variation in fruit availability and experience negative energy and protein balance during episodes of fruit scarcity. We evaluate the possibility that orangutans of different sexes and ages catabolize muscle tissue when the availability of fruit is low. We assess variation in muscle mass by examining the relationship between urinary creatinine and specific gravity and use the residuals as a non-invasive measure of estimated lean body mass (ELBM). Despite orangutans having a suite of adaptations to buffer them from fruit scarcity and associated caloric deficits, ELBM was lower during low fruit periods in all age-sex classes. As predicted, adult male orangutans had higher ELBM than adult females and immatures. Contrary to expectation, flanged and unflanged males did not differ significantly in ELBM. These findings highlight the precarity of orangutan health in the face of rapid environmental change and add to a growing body of evidence that orangutans are characterized by unique metabolic traits shaped by their unpredictable forest environment.

An investigation of glutamate quantification with PRESS and MEGA-PRESS.

Glutamate is an important neurotransmitter. Although many studies have measured glutamate concentration in vivo using magnetic resonance spectroscopy (MRS), researchers have not reached a consensus on the accuracy of glutamate quantification at the field strength of 3 T. Besides, there is not an optimal MRS protocol for glutamate measurement. In this work, both simulation and phantom scans indicate that glutamate can be estimated with reasonable accuracy (<10% error on average) using the standard Point-RESolved Spectroscopy (PRESS) technique with TE 30 ms; glutamine, however, is likely underestimated, which is also suggested by results from human scans using the same protocol. The phantom results show an underestimation of glutamate and glutamine for PRESS with long TE and MEGA-PRESS off-resonance spectra. Despite the underestimation, there is a high correlation between the measured values and the true values (r > 0.8). Our results suggest that the quantification of glutamate and glutamine is reliable but can be off by a scaling factor, depending on the imaging technique. The outputs from all three PRESS sequences (TE = 30, 68 and 80 ms) are also highly correlated with each other (r > 0.7) and moderately correlated (r > 0.5) with the results from the MEGA-PRESS difference spectra with moderate to good shimming (linewidth < 16 Hz).

Vitreous metabolomics profiling of proliferative diabetic retinopathy.

AIMS/HYPOTHESIS: Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. METHODS: We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. RESULTS: We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). CONCLUSIONS/INTERPRETATION: These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.

Chemical exchange rotation transfer imaging of phosphocreatine in muscle.

In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate. Correcting for these effects while maintaining reasonable acquisition times is challenging. As an alternative approach to overcome these problems, here we evaluate chemical exchange rotation transfer (CERT) imaging of PCr in muscle at 9.4 T. Specifically, the CERT metric, AREXdouble,cpw at 2.6 ppm, was measured in solutions containing the main muscle metabolites, in tissue homogenates with controlled PCr content, and in vivo in rat leg muscles. PCr dominates CERT metrics around 2.6 ppm (although with nontrivial confounding baseline contributions), indicating that CERT is well-suited to PCr specific imaging, and has the added benefit of requiring a relatively small number of acquisitions.

Neonatal brain metabolite concentrations: Associations with age, sex, and developmental outcomes.

Age and sex differences in brain metabolite concentrations in early life are not well understood. We examined the associations of age and sex with brain metabolite levels in healthy neonates, and investigated the associations between neonatal brain metabolite concentrations and developmental outcomes. Forty-one infants (36-42 gestational weeks at birth; 39% female) of predominantly Hispanic/Latina mothers (mean 18 years of age) underwent MRI scanning approximately two weeks after birth. Multiplanar chemical shift imaging was used to obtain voxel-wise maps of N-acetylaspartate (NAA), creatine, and choline concentrations across the brain. The Bayley Scales of Infant and Toddler Development, a measure of cognitive, language, and motor skills, and mobile conjugate reinforcement paradigm, a measure of learning and memory, were administered at 4 months of age. Findings indicated that postmenstrual age correlated positively with NAA concentrations in multiple subcortical and white matter regions. Creatine and choline concentrations showed similar but less pronounced age related increases. Females compared with males had higher metabolite levels in white matter and subcortical gray matter. Neonatal NAA concentrations were positively associated with learning and negatively associated with memory at 4 months. Age-related increases in NAA, creatine, and choline suggest rapid development of neuronal viability, cellular energy metabolism, and cell membrane turnover, respectively, during early life. Females may undergo earlier and more rapid regional developmental increases in the density of viable neurons compared to males.

Creatine transporter deficiency, an underdiagnosed cause of male intellectual disability.

X-linked creatine transporter deficiency is caused by the deficiency of the creatine transporter encoded by the SLC6A8 gene on Xq28. We here report a 3-year-old boy with global developmental delay, autism and epilepsy. He had a normal MRI of the brain. Brain magnetic resonance spectroscopy (MRS) subsequently showed an abnormally small creatine peak. His high urine creatine/creatinine ratio further suggested the diagnosis, later confirmed by hemizygous mutation detected in the SLC6A8 gene. His mother was also heterozygous for the same mutation. Supplementation with creatine monohydrate, arginine, and glycine (precursors of creatine) and supportive therapies, resulted in modest clinical improvement after 12 months. This case highlights the importance of doing MRS for boys with global delay/intellectual disability, autism and epilepsy even with a normal MRI of the brain, to pick up a potentially treatable cause.

pH Mapping of Skeletal Muscle by Chemical Exchange Saturation Transfer (CEST) Imaging.

Magnetic resonance imaging (MRI) is extensively used in clinical and basic biomedical research. However, MRI detection of pH changes still poses a technical challenge. Chemical exchange saturation transfer (CEST) imaging is a possible solution to this problem. Using saturation transfer, alterations in the exchange rates between the solute and water protons because of small pH changes can be detected with greater sensitivity. In this study, we examined a fatigued skeletal muscle model in electrically stimulated mice. The measured CEST signal ratio was between 1.96 ppm and 2.6 ppm in the z-spectrum, and this was associated with pH values based on the ratio between the creatine (Cr) and the phosphocreatine (PCr). The CEST results demonstrated a significant contrast change at the electrical stimulation site. Moreover, the pH value was observed to decrease from 7.23 to 7.15 within 20 h after electrical stimulation. This pH decrease was verified by 31P magnetic resonance spectroscopy and behavioral tests, which showed a consistent variation over time.

Neurochemistry of hyponatremic encephalopathy evaluated by MR spectroscopy.

MR spectroscopy in a patient with hyponatremic encephalopathy due to the syndrome of inappropriate secretion of antidiuretic hormone revealed decreased N-acetyl-aspartate, creatine plus phosphocreatine, choline-containing compounds, and myo-inositol, with normal glutamate and increased glutamine, which normalized after Na normalization. The decreased concentrations of creatine plus phosphocreatine, choline-containing compounds and myo-inositol are explained by their release as osmolytes from brain cells to adapt to hypo-osmolality induced cerebral edema. Increased glutamine, which not only acts as an osmolyte but also protects neurons under excitotoxic conditions, may suggest that a disrupted glutamate-glutamine cycle may play an important role in the pathogenesis of hyponatremic encephalopathy.

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration.

INTRODUCTION: Traumatic brain injury (TBI) is the most relevant external risk factor for dementia and a major global health burden. Mild TBI (mTBI) contributes to up to 90% of all TBIs, and the classification "mild" often misrepresents the patient's burden who suffer from neuropsychiatric long-term sequelae. Magnetic resonance spectroscopy (MRS) allows in vivo detection of compromised brain metabolism although it is not routinely used after TBI. OBJECTIVE: Thus, we performed a systematic review and meta-analysis to elucidate if MRS has the potential to identify changes in brain metabolism in adult patients after a single mTBI with a negative routine brain scan (CCT and/or MRI scan) compared to aged- and sex-matched healthy controls (HC) during the acute or subacute postinjury phase (≤90 days after mTBI). METHODS: A comprehensive literature search was conducted from the first edition of electronic databases until January 31, 2020. Group analyses were performed per metabolite using a random-effects model. RESULTS: Four and 2 out of 5,417 articles met the inclusion criteria for the meta-analysis and systematic review, respectively. For the meta-analysis, 50 mTBI patients and 51 HC with a mean age of 31 and 30 years, respectively, were scanned using N-acetyl-aspartate (NAA), a marker for neuronal integrity. Glutamate (Glu), a marker for disturbed brain metabolism, choline (Cho), a marker for increased cell membrane turnover, and creatine (Cr) were used in 2 out of the 4 included articles. Regions of interests were the frontal lobe, the white matter around 1 cm above the lateral ventricles, or the whole brain. NAA was decreased in patients compared to HC with an effect size (ES) of -0.49 (95% CI -1.08 to 0.09), primarily measured in the frontal lobe. Glu was increased in the white matter in 22 mTBI patients compared to 22 HC (ES 0.79; 95% CI 0.17-1.41). Cho was decreased in 31 mTBI patients compared to 31 HC (ES -0.31; 95% CI -0.81 to 0.19). Cr was contradictory and, therefore, potentially not suitable as a reference marker after mTBI. CONCLUSIONS: MRS pinpoints changes in posttraumatic brain metabolism that correlate with cognitive dysfunction and, thus, might possibly help to detect mTBI patients at risk for unfavorable outcome or posttraumatic neurodegeneration early.

Effects of Endovascular Stent-Assisted Angioplasty on Cellular Metabolism in the Hippocampus of Elderly Patients with Symptomatic Vertebrobasilar Artery Stenosis.

BACKGROUND Cerebral artery stenosis is closely related to cognitive function, and angioplasty can improve the cognitive function of elderly patients with vertebrobasilar artery stenosis. The specific mechanism, however, is not clear. This study explored the effect of angioplasty on cellular metabolism in the hippocampus of elderly patients with symptomatic vertebrobasilar artery stenosis. MATERIAL AND METHODS Eighteen elderly patients with symptomatic vertebrobasilar artery stenosis who underwent endovascular stent-assisted angioplasty (ESAA) in our department were studied. The changes in cellular metabolism (NAA / Cr, CHO / Cr, NAA / CHO) in bilateral hippocampal areas were detected by MRS before and at 6 months and 12 months after the ESAA. The Montreal Cognitive Assessment Scale (MoCA), Hamilton Depression Self-assessment Scale (HAMD), and Hamilton Anxiety Self-assessment Scale (HAMA) were also used to evaluate the cognition, depression, and anxiety of patients at different time points of the study, and analyzed the correlation between the changes of cellular metabolism in the hippocampus and the scores of MoCA, HAMD, and HAMA. RESULTS The levels of NAA/Cr in left/right hippocampal areas were significantly higher at 6 and 12 months after the ESAA than before (1.01±0.17/1.22±0.26 vs. 1.10±0.20/1.05±0.26 vs. 0.82±0.10/0.84±0.11, respectively) (P<0.01). MoCA scores were positively correlated with the levels of NAA/Cr in the left/right hippocampal areas (P<0.05 and P<0.01, respectively). CONCLUSIONS ESAA can improve cognitive function of patients by changing the cellular metabolism of the hippocampus in elderly patients with symptomatic vertebrobasilar artery stenosis.