Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients.

Background: Recent years have seen the emergence of disease-modifying therapies in multiple sclerosis (MS), such as anti-cluster of differentiation 20 (anti-CD20) monoclonal antibodies, aiming to modulate the immune response and effectively manage MS. However, the relationship between anti-CD20 treatments and immunoglobulin G (IgG) levels, particularly the development of hypogammaglobulinemia and subsequent infection risks, remains a subject of scientific interest and variability. We aimed to investigate the intricate connection between anti-CD20 MS treatments, changes in IgG levels, and the associated risk of hypogammaglobulinemia and subsequent infections. Method: PubMed, Scopus, Embase, Cochrane, and Web of Science databases have been searched for relevant studies. The "R" software utilized to analyze the occurrence of hypogammaglobulinemia, infections and mean differences in IgG levels pre- and post-treatment. The subgrouping analyses were done based on drug type and treatment duration. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. Results: Thirty-nine articles fulfilled our inclusion criteria and were included in our review which included a total of 20,501 MS patients. The overall prevalence rate of hypogammaglobulinemia was found to be 11% (95% CI: 0.08 to 0.15). Subgroup analysis based on drug type revealed varying prevalence rates, with rituximab showing the highest at 18%. Subgroup analysis based on drug usage duration revealed that the highest proportion of hypogammaglobulinemia occurred in individuals taking the drugs for 1 year or less (19%). The prevalence of infections in MS patients with a focus on different infection types stratified by the MS drug used revealed that pulmonary infections were the most prevalent (9%) followed by urinary tract infections (6%), gastrointestinal infections (2%), and skin and mucous membrane infections (2%). Additionally, a significant decrease in mean IgG levels after treatment compared to before treatment, with a mean difference of 0.57 (95% CI: 0.22 to 0.93). Conclusion: This study provides a comprehensive analysis of the impact of anti-CD20 drugs on serum IgG levels in MS patients, exploring the prevalence of hypogammaglobulinemia, based on different drug types, treatment durations, and infection patterns. The identified rates and patterns offer a foundation for clinicians to consider in their risk-benefit. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=518239, CRD42024518239.

Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson's disease in an Egyptian cohort.

Introduction: Parkinson's disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which some have reported lower phenylalanine and tyrosine levels in PD patients compared to controls. Methods: In this study, we have collected plasma from 27 PD patients, 18 reference controls, and 8 high-risk controls to perform a metabolomic study using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Results: Our findings revealed higher intensities of trans-cinnamate, a phenylalanine metabolite, in patients compared to reference controls. Thus, we hypothesize that phenylalanine metabolism has been shifted to produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead of producing tyrosine, a dopamine precursor, via phenylalanine hydroxylase (PAH). Discussion: Given that these metabolites are precursors to several other metabolic pathways, the intensities of many metabolites such as dopamine, norepinephrine, and 3-hydroxyanthranilic acid, which connects phenylalanine metabolism to that of tryptophan, have been altered. Consequently, and in respect to Metabolic Control Analysis (MCA) theory, the levels of tryptophan metabolites have also been altered. Some of these metabolites are tryptamine, melatonin, and nicotinamide. Thus, we assume that these alterations could contribute to the dopaminergic, adrenergic, and serotonergic neurodegeneration that happen in the disease.

The relationship between alexithymia, emotion regulation, and sleep problems in school-aged children: A multicentric study.

OBJECTIVES: Alexithymia, mood dysregulation, and sleep quality have complicated effects on children's development. The current study aimed to investigate the relationship between alexithymia, emotion regulation, psychiatric problems, and sleep problems among Egyptian school-aged children. METHODS: A total of 564 Egyptian children, aged 6 to 14, were divided into two groups based on their total Children's Sleep Habits Questionnaire abbreviated score: group 1 (N = 300) with sleep problems and group 2 (N = 264) with non-sleep problems. Their parents completed the Strengths and Difficulties Questionnaire (SDQ) and subjectively assessed the children's emotions using the Children's Alexithymia Measure (CAM) and the Clinical Evaluation of Emotional Regulation-9 (CEER-9). RESULTS: Males were more proportional in the sleep problems group than others. The sleep problem group was significantly younger and had a longer daily sleep duration than the non-sleep problem group. Alexithymia and emotion dysregulation had the highest mean in the sleep problem group. Furthermore, alexithymia, emotion dysregulation, emotion difficulty, conduct, and prosocial problems were the most significant contributing factors and risk factors for sleep problems in children. CONCLUSION: Sleep problems in children were associated with younger male children with lengthy daily sleep duration and emotional, behavioural, and prosocial difficulties. Furthermore, alexithymia and emotion dysregulation are significant contributors and risk factors for sleep problems in school-aged children.

Relationship between time spent playing internet gaming apps and behavioral problems, sleep problems, alexithymia, and emotion dysregulations in children: a multicentre study.

BACKGROUND: Internet gaming addiction (IGA) is a serious condition that can significantly impact personal and social functioning. Many studies of IGA have been conducted in adolescents and young adults, but there are limited data available in children. We investigated the time spent using internet gaming apps in children and its association with behavioral problems, sleep problems, alexithymia, and emotional regulation. METHODS: The research populations (N = 564) were categorized based on the number of hours spent using online gaming applications. The Strengths and Difficulties Questionnaire, the Children's Sleep Habits Questionnaire Abbreviated, the Children's Alexithymia Measure (CAM), and the Clinical Evaluation of Emotional Regulation-9 were used to assess all participants. RESULTS: Compared to other groups, children who used internet gaming applications for more than 6 h had a higher proportion of abnormal responses on the emotional symptoms and hyperactivity scales. Children who used internet gaming applications for more than 6 h had the poorest sleep quality (75%), while children who used internet gaming applications for 1-2 h had the best (36.7%). Participants who used internet gaming apps for 1-2 h had significantly lower mean total scores on the emotional regulation scale and total CAM, whereas those using internet gaming apps for more than 6 h had the highest mean scores in the CAM. CONCLUSIONS: Excessive use of internet gaming apps during childhood may be associated with hyperactivity, peer problems, high socioeconomic level, alexithymia concerns, shorter daytime sleep duration, and a delayed morning wake-up.

Relation between internet gaming addiction and comorbid psychiatric disorders and emotion avoidance among adolescents: A cross-sectional study.

INTRODUCTION: Internet Gaming Disorder has been a controversial subject. Even though internet addiction has been studied among adolescents, there is a lack of evidence regarding Internet Gaming Disorder. The purpose of this study was to assess the prevalence rate of Internet Gaming Disorder and the relationship between Internet Gaming Disorder, comorbid psychiatric disorders, and emotion avoidance among adolescents. METHODS: Four hundred seven adolescents aged 11 to 18 years old were recruited. Participants were divided into two groups based on the internet gaming addiction scale-Adolescents with IGA (N = 40) and adolescents without IGA (N = 367). All participants were evaluated for demographic data, the Strengths and Difficulties Questionnaire (SDQ), socioeconomic scale, and the Emotional Avoidance Strategy Inventory for Adolescents (EASI-A). RESULTS: The adolescent with IGA had a higher mean of the number of hours and devices using Internet gaming apps than an adolescent without IGA. Regarding SDQ, adolescents with IGA had a significantly higher mean value for all subscales of SDQ except the prosocial scale and all subscales of EASI-A compared with adolescents without IGA. CONCLUSIONS: Adolescents with IGA had more hours and devices using Internet gaming apps; more comorbid psychiatric disorders and problems in emotional expression inform of using avoidance techniques than adolescents without IGA.