Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy.

STUDY OBJECTIVES: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. METHODS: Diffusion tensor imaging was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. RESULTS: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). CONCLUSIONS: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.

Experiences from COVID-19 vaccination in patients with epilepsy.

OBJECTIVE: This study aimed to investigate the safety of coronavirus disease 2019 (COVID-19) vaccination in patients with epilepsy (PWE) and their willingness to undergo vaccination. METHODS: This study was a survey the survey questionnaire, which included general, epilepsy-specific, and COVID-specific questions, was completed by patients of the outpatient clinic and hospital ward at The Third Xiangya Hospital in 2021. RESULTS: A total of 120 valid questionnaires were returned. Eighty-nine of 120 responders (74.2%) were not vaccinated, and 31 (25.8%) were vaccinated against COVID-19. Of the 31 vaccinated PWE, one (3.2%) had worsening of seizures and four (12.9%) had adverse reactions that were characteristic of the COVID-19 vaccine. The other 26 patients (83.9%) reported no adverse reactions, Moreover, there was no significant difference between the 18 PWE with well-controlled seizures and the 13 PWE with poorly-controlled seizures. Of the 89 unvaccinated PWE, 69.7% (62/89) were willing to receive the COVID-19 vaccine, 28.1% (25/89) were unsure, and 2.2% (2/89) declined to be vaccinated. SIGNIFICANCE: Among PWE, few adverse reactions occurred following the COVID-19 vaccination. Most PWE were willing to receive the COVID-19 vaccine. COVID-19 vaccination is safe for PWE.

EEG Microstate Features as an Automatic Recognition Model of High-Density Epileptic EEG Using Support Vector Machine.

Epilepsy is one of the most serious nervous system diseases; it can be diagnosed accurately by video electroencephalogram. In this study, we analyzed microstate epileptic electroencephalogram (EEG) to aid in the diagnosis and identification of epilepsy. We recruited patients with focal epilepsy and healthy participants from the Third Xiangya Hospital and recorded their resting EEG data. In this study, the EEG data were analyzed by microstate analysis, and the support vector machine (SVM) classifier was used for automatic epileptic EEG classification based on features of the EEG microstate series, including microstate parameters (duration, occurrence, and coverage), linear features (median, second quartile, mean, kurtosis, and skewness) and non-linear features (Petrosian fractal dimension, approximate entropy, sample entropy, fuzzy entropy, and Lempel-Ziv complexity). In the gamma sub-band, the microstate parameters as a model were the best for interictal epilepsy recognition, with an accuracy of 87.18%, recall of 70.59%, and an area under the curve of 94.52%. There was a recognition effect of interictal epilepsy through the features extracted from the EEG microstate, which varied within the 4~45 Hz band with an accuracy of 79.55%. Based on the SVM classifier, microstate parameters and EEG features can be effectively used to classify epileptic EEG, and microstate parameters can better classify epileptic EEG compared with EEG features.

Automatic Recognition of High-Density Epileptic EEG Using Support Vector Machine and Gradient-Boosting Decision Tree.

BACKGROUND: Epilepsy (Ep) is a chronic neural disease. The diagnosis of epilepsy depends on detailed seizure history and scalp electroencephalogram (EEG) examinations. The automatic recognition of epileptic EEG is an artificial intelligence application developed from machine learning (ML). PURPOSE: This study compares the classification effects of two kinds of classifiers by controlling the EEG data source and characteristic values. METHOD: All EEG data were collected by GSN HydroCel 256 leads and high-density EEG from Xiangya Third Hospital. This study used time-domain features (mean, kurtosis and skewness processed by empirical mode decomposition (EMD) and three IMFs), a frequency-domain feature (power spectrum density, PSD) and a non-linear feature (Shannon entropy). Support vector machine (SVM) and gradient-boosting decision tree (GBDT) classifiers were used to recognize epileptic EEG. RESULT: The result of the SVM classifier showed an accuracy of 72.00%, precision of 73.98%, and an F1_score of 82.28%. Meanwhile, the result of the GBDT classifier showed a sensitivity of 98.57%, precision of 89.13%, F1_score of 93.40%, and an AUC of 0.9119. CONCLUSION: The comparison of GBDT and SVM by controlling the variables of the feature values and parameters of a classifier is presented. GBDT obtained the better classification accuracy (90.00%) and F1_score (93.40%).

Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation.

OBJECTIVE: We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and central nervous system immunoinflammatory mediators contributes to neurocognitive impairment (NCI). DESIGN: Cross-sectional. SETTING: Six Academic Centers. PARTICIPANTS: One hundred fifty-two patients with plasma HIV RNA <1000 copies per milliliter had clinical evaluations and cognitive function quantified by global deficit scores (GDS). OUTCOME MEASURES: GDS, waist circumference (WC) and plasma IL-6, sCD163, and sCD14 and CSF sCD40L, sTNFrII, MCP-1, sICAM, and MMP-9. RESULTS: WC and plasma IL-6 levels positively correlated with GDS; the WC correlation was strongest in the high tertile of IL-6 (ρ = 0.39, P = 0.005). IL-6 correlated with GDS only if WC was ≥99 cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (ρ = 0.60, P < 0.0001). Across 3-5 visits within ±1 year of the index visit, GDS remained worse in patients with IL-6 levels in the high versus low tertile (P = 0.02). Path analysis to explore potential mediators of NCI produced a strong integrated model for patients in the high CSF sCD40L tertile. In this model, WC affected GDS both directly and through a second path that was mediated by IL-6. Inclusion of plasma sCD14 levels strengthened the model. NCI was more common in men and for individuals with components of the metabolic syndrome. CONCLUSIONS: Neurocognitive function was significantly linked to abdominal obesity, systemic inflammation (high IL-6), and immune activation in plasma (high sCD14) and CSF (high sCD40L). Abdominal obesity, inflammation, and central nervous system immune activation are potential therapeutic targets for NCI in HIV-positive patients.

Interrater reliability of the Wolf Motor Function Test-Functional Ability Scale: why it matters.

BACKGROUND: One important objective for clinical trialists in rehabilitation is determining efficacy of interventions to enhance motor behavior. In part, limitation in the precision of measurement presents a challenge. The few valid, low-cost observational tools available to assess motor behavior cannot escape the variability inherent in test administration and scoring. This is especially true when there are multiple evaluators and raters, as in the case of multisite randomized controlled trials (RCTs). One way to enhance reliability and reduce variability is to implement rigorous quality control (QC) procedures. OBJECTIVE: This article describes a systematic QC process used to refine the administration and scoring procedures for the Wolf Motor Function Test (WMFT)-Functional Ability Scale (FAS). METHODS: The QC process, a systematic focus-group collaboration, was developed and used for a phase III RCT, which enlisted multiple evaluators and an experienced WMFT-FAS rater panel. RESULTS: After 3 staged refinements to the administration and scoring instructions, we achieved a sufficiently high interrater reliability (weighted κ = 0.8). CONCLUSIONS AND IMPLICATIONS: A systematic focus-group process was shown to be an effective method to improve reliability of observational assessment tools for motor behavior in neurorehabilitation. A reduction in noise-related variability in performance assessments will increase power and potentially lower the number needed to treat. Improved precision of measurement can lead to more cost-effective and efficient clinical trials. Finally, we suggest that improved precision in measures of motor behavior may provide more insight into recovery mechanisms than a single measure of movement time alone.

Periodized resistance training with and without supplementation improve body composition and performance in older men.

PURPOSE: To examine the effects of 12 weeks of periodized resistance training (RT) with and without combined creatine and whey protein supplementation on changes in body composition, muscular strength, and functional performance. METHODS: Twenty-two male volunteers (68.1 ± 6.1 years) were randomly assigned to one of three groups: RT plus supplementation (RTS, n = 7); RT only (RT, n = 7); or control (C, n = 8). RTS consumed 0.3 g/kg/day of creatine for 5 days followed by 0.07 g/kg/day. RTS also consumed one 35 g liquid protein ready-to-drink daily. RT and RTS trained 3 days/week. RESULTS: Following 12 weeks of training, there were no significant differences in the main measured outcome variables between RT and RTS. RTS increased relative (% change) lean body mass (LBM, 3.3 ± 3.1 %) compared with C (p = 0.01). Compared to baseline, RT increased LBM at week 6 (60.2 ± 8.3 to 61.6 ± 9.4 kg; p < 0.05), and decreased fat mass (20.8 ± 4.2 to 19.0 ± 3.9 kg; p = 0.05) and percentage body fat at week 12 (25.7 ± 3.8 to 23.8 ± 4.0 %; p = 0.05); RTS increased LBM at week 6 (p < 0.01) and week 12 (56.4 ± 4.3 to 58.2 ± 3.4 kg; p < 0.01), and decreased percentage body fat at week 12 (23.9 ± 4.4 to 22.0 ± 4.4 %; p < 0.01). In addition, compared to C, relative bench press 1-RM increased for RTS (72.4 ± 62.2 %; p < 0.01) and RT (50.1 ± 21.5 %; p = 0.05); relative leg press 1-RM increased for RTS (129.6 ± 39.4 %; p < 0.0001) and RT (112.9 ± 22.7 %; p < 0.0001); RTS increased relative Margaria stair-climbing power (38.3 ± 30.4 %; p < 0.05); and, relative 400-m walk time decreased for RT (-11 ± 9.2 %; p < 0.05) and RTS (-9.6 ± 9.4 %; p = 0.05). RT increased estimated VO2Max at week 6 (p < 0.01) and 12 (34.6 ± 1.9 to 36.4 ± 2.7 ml/kg/min; p = 0.01) compared to baseline. Lastly, RTS increased estimated VO2Max at week 12 (36.3 ± 2.7 to 37.5 ± 3.3 ml/kg/min; p = 0.05) compared to baseline. CONCLUSION: Creatine and whey protein supplementation may not provide additional benefits in older adults performing periodized RT to augment muscular and functional performance.

Value of measuring muscle performance to assess changes in lean mass with testosterone and growth hormone supplementation.

We hypothesized that treatment with testosterone (T) and recombinant human growth hormone (rhGH) would increase lean mass (LM) and muscle strength proportionally and an in a linear manner over 16 weeks. This was a multicenter, randomized, controlled, double-masked investigation of T and rhGH supplementation in older (71 ± 4 years) community-dwelling men. Participants received transdermal T at either 5 or 10 g/day as well as rhGH at 0, 3.0 or 5.0 µg/kg/day for 16 weeks. Body composition was determined by dual-energy X-ray absorptiometry (DEXA) and muscle performance by composite one-repetition maximum (1-RM) strength and strength per unit of lean mass (muscle quality, MQ) for five major muscle groups (upper and lower body) at baseline, week 8 and 17. The average change in total LM at study week 8 compared with baseline was 1.50 ± 1.54 kg (P < 0.0001) in the T only group and 2.64 ± 1.7 (P < 0.0001) in the T + rhGH group and at week 17 was 1.46 ± 1.48 kg (P < 0.0001) in the T only group and 2.14 ± 1.96 kg (P < 0.0001) in the T + rhGH group. 1-RM strength improved modestly in both groups combined (12.0 ± 23.9%, P < 0.0001) at week 8 but at week 17 these changes were twofold greater (24.7 ± 31.0%, P < 0.0001). MQ did not significantly change from baseline to week 8 but increased for the entire cohort, T only, and T + rhGH groups by week 17 (P < 0.001). Despite sizeable increases in LM measurements at week 8, tests of muscle performance did not show substantive improvements at this time point.

Whole-body and muscle protein metabolism are not affected by acute deviations from habitual protein intake in older men: the Hormonal Regulators of Muscle and Metabolism in Aging (HORMA) Study.

BACKGROUND: Acute deviations in protein intake before the quantification of protein kinetics in older humans may explain the controversy over the effects of older age on muscle protein synthesis and proteolysis rates. OBJECTIVE: We hypothesized that an acute decrease in protein intake from the habitual intake is associated with lower muscle protein synthesis and higher proteolysis rates, whereas an acute increase in protein intake from the habitual intake is associated with higher muscle protein synthesis and lower proteolysis rates. DESIGN: In 112 community-dwelling healthy men aged 65-90 y, we quantified resting whole-body [1,2-(13)C(2)]leucine kinetics, muscle mixed protein fractional synthesis rates (FSRs), and muscle proteasome proteolytic enzyme activities after participants consumed for 3 d controlled research meals (0.9-1.1 g protein · kg(-1) · d(-1)) that contained more or less protein than that habitually consumed and that induced alterations in nitrogen balance. RESULTS: Protein kinetic parameters were not significantly different between the groups, despite controlled research protein intakes that were lower (-0.2 to -0.3 g · kg(-1) · d(-1)) or higher (+0.2 g · kg(-1) · d(-1)) than habitual intakes and that induced negative (-22 to -25 mg · kg(-1) · d(-1)) or positive (22-25 mg · kg(-1) · d(-1)) nitrogen balance. Within these acutely altered protein intake and nitrogen balance boundaries, a reduction in protein intake from habitual intake and induction of negative nitrogen balance were not associated with higher proteolysis or lower muscle FSR, and an acute increase in protein intake from habitual intake and induction of positive nitrogen balance were not associated with lower proteolysis or higher muscle FSR. A higher quantitative insulin sensitivity check index was associated with lower whole-body proteolysis rates. CONCLUSIONS: The practice of acutely controlling protein intake, even at intakes lower than habitual intakes that induce negative nitrogen balance, before quantifying human protein kinetics does not significantly reduce muscle protein synthesis or increase proteolysis. Factors other than protein intake explain lower muscle protein synthesis rates with advanced age. This trial is registered at clinicaltrials.gov as NCT00183040.

Durability of the effects of testosterone and growth hormone supplementation in older community-dwelling men: the HORMA Trial.

OBJECTIVES: To determine the durability of anabolic effects and adverse events (AEs) after stopping testosterone and growth hormone supplementation in older men. DESIGN: Secondary analysis of a double-masked, randomized controlled trial of testosterone gel (5 or 10 g/daily) plus rhGH (0, 3 or 5 µg/kg/day) with follow-up of outcomes 3 months later. PARTICIPANTS: A total of 108 community-dwelling 65- to 90-year-old men. MEASUREMENTS: Testosterone and IGF-1 levels, body composition (DEXA), 1-repetition maximum (1-RM) strength, stair-climbing power, quality-of-life (QOL) and activity questionnaires, AEs. RESULTS: Despite improvements in body composition during treatment, residual benefits 3 months later (week 28) were variable. For participants with improvements exceeding their week-17 median changes, benefits were sustained at week 28 for lean body mass (1·45 ± 1·63 kg, 45% of week-17 values, P < 0·0001 vs baseline), appendicular skeletal muscle mass (ASMM, 0·71 ± 1·01 kg, 42%, P < 0·0001), total fat (-1·06 ± 2·18 kg, 40%, P < 0·0001) and trunk fat (-0·89 ± 1·42 kg, 50%, P < 0·0001); retention of ASMM was associated with greater week-16 protein intake (P = 0·01). For 1-RM strength, 39%-43% of week-17 improvements (P ≤ 0·05) were retained and associated with better week-17 strength (P < 0·0001), change in testosterone from week 17-to 28 (P = 0·004) and baseline PASE (P = 0·04). Framingham 10-year cardiovascular risks were low (~14%), did not worsen and improved by week 28 (P = 0·0002). The hypothalamic-pituitary-gonadal axis recovered completely. CONCLUSIONS: Durable improvements in muscle mass, strength and fat mass were retained 3 months after discontinuing hormone supplementation in participants with greater than median body composition changes during treatment, but not in others with smaller gains. AEs largely resolved after intervention discontinuation. Additional strategies may be needed to sustain or augment muscle mass and strength gains achieved during short-term hormone therapy.

Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial.

BACKGROUND: In the HORMA (Hormonal Regulators of Muscle and Metabolism in Aging) Trial, supplemental testosterone and recombinant human growth hormone (rhGH) enhanced lean body mass, appendicular skeletal muscle mass, muscle performance, and physical function, but there was substantial interindividual variability in outcomes. METHODS: One hundred and twelve men aged 65-90 years received testosterone gel (5 g/d vs 10 g/d via Leydig cell clamp) and rhGH (0 vs 3 vs 5 µg/kg/d) in a double-masked 2 × 3 factorial design for 16 weeks. Outcomes included lean tissue mass by dual energy x-ray absorptiometry, one-repetition maximum strength, Margaria stair power, and activity questionnaires. We used pathway analysis to determine the relationship between changes in hormone levels, muscle mass, strength, and function. RESULTS: Increases in total testosterone of 1046 ng/dL (95% confidence interval = 1040-1051) and 898 ng/dL (95% confidence interval = 892-904) were necessary to achieve median increases in lean body mass of 1.5 kg and appendicular skeletal muscle mass of 0.8 kg, respectively, which were required to significantly enhance one-repetition maximum strength (≥ 30%). Co-treatment with rhGH lowered the testosterone levels (quantified using liquid chromatography-tandem mass spectrometry) necessary to reach these lean mass thresholds. Changes in one-repetition maximum strength were associated with increases in stair climbing power (r = .26, p = .01). Pathway analysis supported the model that changes in testosterone and insulin-like growth factor 1 levels are related to changes in lean body mass needed to enhance muscle performance and physical function. Testosterone's effects on physical activity were mediated through a different pathway because testosterone directly affected Physical Activity Score of the Elderly. CONCLUSIONS: To enhance muscle strength and physical function, threshold improvements in lean body mass and appendicular skeletal muscle mass are necessary and these can be achieved by targeting changes in testosterone levels. rhGH augments the effects of testosterone. To maximize functional improvements, the doses of anabolic hormones should be titrated to achieve target blood levels.