Soe Mar

Washington University in St. Louis | WUSTL , Wash U · Department of Neurology

Background and Objectives This survey study aimed to (1) identify patient/family research priorities in pediatric-onset multiple sclerosis (POMS), and (2) delineate optimized methods for research study/clinical trials design, engagement, and implementation. Methods Participants were as follows: (1) parents of a child (<18 years) with POMS enrolled...

Background Lipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this study, we performed an in-depth lipidomics analysis to identify lipids associated with injury and disease activity. Methods Plasma samples...

Background Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identif...

Background Cognitive decline in multiple sclerosis (MS) is common, but unpredictable, and increases with disease duration. As such, early detection of cognitive decline may improve the effectiveness of interventions. To that end, the Symbol Digit Modalities Test (SDMT) is effective in detecting slow processing speed as it relates to cognitive impai...

Background Understanding nutrition’s role in multiple sclerosis (MS) can guide recommendations and intervention-based studies. Objective Evaluate the association between nutrition and pediatric-onset MS outcomes. Methods Prospective longitudinal multicenter study conducted as part of the US Network of Pediatric MS centers. Predictors were collect...

Objective Adolescents with perinatally-acquired HIV (AWH) are at an increased risk of poor cognitive development but the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multi-morbidity in adults with HIV despite anti-retroviral therapy (ART), however, relationship between Gal-...

Background Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. Objective To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timin...

Background and Objective Prior Epstein–Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antige...

Myelin oligodendryocyte glycoprotein antibody-associated disease (MOGAD) has been implicated in a wide range of central nervous system encephalitis and myelitis presentations. We present a previously healthy 16-year-old female who presented with acute onset headaches that rapidly progressed to encephalopathy, flaccid paraparesis, lower extremity hy...

Background: The central vein sign (CVS) on brain magnetic resonance imaging (MRI) is a promising diagnostic marker for distinguishing adult multiple sclerosis (MS) from other demyelinating conditions, but its prevalence is not well-established in pediatric-onset multiple sclerosis (POMS) versus myelin oligodendrocyte glycoprotein antibody-associat...

Background: Treatment of pediatric-onset multiple sclerosis (POMS) is challenging given the lack of safety and efficacy data in the pediatric population for many of the disease-modifying treatments (DMTs) approved for use in adults with MS. Our objective was to describe the demographic features and clinical and radiologic course of patients with P...

Background: Pediatric patients with multiple sclerosis (POMS) and related disorders, clinically isolated syndrome (CIS), myelin oligodendrocyte glycoprotein antibody disorder (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), are commonly treated with immunosuppressants. Understanding the impact of SARS-CoV-2 infection in patients may in...

Background and objectives: Limited data is available on children with evidence of silent central nervous system demyelination on MRI. We sought to characterize the population in a US cohort and identify predictors of clinical and radiologic outcomes. Methods: We identified 56 patients such patients who presented with incidental MRI findings susp...

Background: Rare genetic variants are emerging as important contributors to the heritability of multiple sclerosis (MS). Whether rare variants also contribute to pediatric-onset multiple sclerosis (POMS) is unknown. Objective: To test whether genes harboring rare variants associated with adult-onset MS risk (PRF1, PRKRA, NLRP8, and HDAC7) and 52...

Background We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis. Methods Using a case–control paediatric multiple sclerosis study, gene–environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was...

Background and Objective Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3% to 5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD. Methods This retrospective coho...

We outline a case of a 6-year-old girl presenting with a two-week course of waxing and waning neurologic symptoms, including right-sided pain, weakness, dizziness, and difficulty walking. Her exam was notable for right-sided weakness, hyperreflexia, and dysmetria. Diagnostic evaluation was significant for MRI with numerous T2-hyperintense, T1-hypoi...

Objective Cognitive involvement in pediatric multiple sclerosis (MS) relative to adult MS is less defined. This study advances our understanding by measuring cognitive performances in pediatric MS, adult MS, and pediatric healthy controls. Methods Consecutive relapsing pediatric MS participants from the United States Network of Pediatric MS Center...

Objective: To determine the frequency of myelin oligodendrocyte glycoprotein (MOG)-IgG and aquaporin-4 (AQP4)-IgG among pediatric-onset multiple sclerosis (POMS) patients and healthy controls, determine whether seropositive cases fulfilled their respective diagnostic criteria, compare characteristics and outcomes in children with POMS vs MOG-IgG-a...

Background We previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. CD86 is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in res...

Objective This study aims to determine the contributions of sun exposure and ultraviolet radiation (UVR) exposure to risk of paediatric-onset multiple sclerosis (MS). Methods Children with MS and controls recruited from multiple centres in the USA were matched on sex and age. Multivariable conditional logistic regression was used to investigate th...

Objective To identify features of the gut microbiome associated with multiple sclerosis activity over time. Methods We used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric-onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes and networks identified from weighted genetic cor...

Background: The objective of this qualitative methods study was to develop the domains and items to support the content validity for the Pediatric Quality of Life Inventory (PedsQL) Multiple Sclerosis Module for youth with pediatric-onset multiple sclerosis. Methods: A literature review of multiple sclerosis-specific questionnaires and clinical...

Multiple sclerosis (MS), a chronic inflammatory disorder affecting the central nervous system, is well recognized to cause physical disability. MS also very commonly causes neuropsychiatric symptoms that, though disabling, are often under‐recognized by care providers. The most common neuropsychiatric symptoms, affecting over half MS patients, inclu...

Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days af...

Objective To characterize disease severity and distribution of disability in pediatric-onset multiple sclerosis (POMS) and to develop an optimized modeling scale for measuring disability we performed a multi-center retrospective analysis of disability scores in 873 persons with POMS over time and compared this to previously published data in adults...

Objective To assess real‐world effectiveness of initial treatment with newer compared to injectable disease‐modifying therapies (DMTs) on disease activity in pediatric MS and clinically isolated syndrome (CIS). Methods This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received init...

ACOX1 (acyl-CoA oxidase 1) encodes the first and rate-limiting enzyme of the very-long-chain fatty acid (VLCFA) β-oxidation pathway in peroxisomes and leads to H2O2 production. Unexpectedly, Drosophila (d) ACOX1 is mostly expressed and required in glia, and loss of ACOX1 leads to developmental delay, pupal death, reduced lifespan, impaired synaptic...

Inside Back Cover: The cover image is based on the Research Article Xq22 deletions and correlation with distinct neurological disease traits in females: Further evidence for a contiguous gene syndrome by Hadia Hijazi et al., https://doi.org/10.1002/humu.23902. Cover image © Hadia Hijazi & Ameerah Deyab Images.

Background Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. Objective To screen for cognitive impairment early in the course of POMS and ana...

Xq22 deletions that encompass PLP1 (Xq22‐PLP1‐DEL) are notable for variable expressivity of neurological disease traits in females ranging from a mild late‐onset form of Spastic Paraplegia type 2 [MIM# 312920], sometimes associated with skewed X‐inactivation, to an early‐onset neurological disease trait (EONDT) of severe developmental delay, intell...

Acute disseminated encephalomyelitis is an inflammatory disorder of the central nervous system. Uniform diagnostic criteria for acute disseminated encephalomyelitis did not exist until publication of expert-defined consensus definitions by the International Pediatric Multiple Sclerosis Society Group in 2007, with updates in 2013. In the expanding f...

The differential diagnosis of pediatric multiple sclerosis (MS) can be broad and pose diagnostic challenges, particularly at initial presentation. Among demyelinating entities, neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibodies (MOG-ab) associated disorders, and acute disseminated encephalomyelitis (ADEM...

Objective Onset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped‐MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specif...

Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European gen...

Children with pediatric-onset multiple sclerosis and pediatric controls were enrolled across 16 pediatric multiple sclerosis centers in the United States and completed questionnaires that addressed time of first unaided walking and acquisition of 2-word phrases. A total of 467 (308 female) cases and 428 (209 female) controls were enrolled. Pediatri...

Objective: To characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age. Methods: This is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric...

Background There is limited information about the potential associations of multiple sclerosis (MS) and commonly used household chemicals. Methods We performed a case‐control study of exposures to common household chemicals during childhood in children with MS and healthy pediatric controls. Exposures to household products were collected from a co...

Objective While prior Epstein–Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility...

Table S1. Number of subjects with available genetic ancestry data. Table S2. Summary of the genetic ancestry data for the subset of participants with available data.

Background We previously identified air quality as a risk factor of interest for pediatric multiple sclerosis. The purpose of this study is to more closely examine the association between the six criteria air pollutants and pediatric MS as well as identify specific areas of toxic release using data from the Toxic Release Inventory. Methods Pediatr...

Objective: We sought to determine if early infectious exposures such as daycare, early use of antibiotics, vaccinations and other germ exposures including pacifier use and playing on grass are associated with multiple sclerosis (MS) risk in children. Methods: This was a case-control study of children with MS or clinically isolated syndrome (CIS)...

Objective The role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers. Methods This is a multicentre study done at 11 paediatric MS centres in the USA....

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to PO...

Background Multiple sclerosis (MS) is a presumed autoimmune disease caused by genetic and environmental factors. It is hypothesized that environmental exposures (such as air and water quality) trigger the innate immune response thereby activating a pro-inflammatory cascade. Objective To examine potential environmental factors in pediatric MS using...

Background There are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disab...

Background: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset b...

We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic...

Objective: To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS). Methods: We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic varia...

OBJECTIVE Many patients with medically intractable epilepsy have mesial temporal sclerosis (MTS), which significantly affects their quality of life. The surgical excision of MTS lesions can result in marked improvement or even complete resolution of the epileptic episodes. Reliable radiological diagnosis of MTS is a clinical challenge. The purpose...

Background: Adherence to disease-modifying therapies (DMTs) in pediatric multiple sclerosis (MS) is not well understood. We examined the prevalence and risk factors for poor adherence in pediatric MS. Methods: This cross-sectional study recruited youth with MS from 12 North American pediatric MS clinics. In addition to pharmacy-refill data, pati...

Background: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. Objective: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort....

Background and purpose: Ethnicity-related differences in the incidence of acute disseminated encephalomyelitis (ADEM) and other demyelinating diseases including multiple sclerosis and neuromyelitis optica spectrum disorders have been reported. Little is reported on the influence of ethnicity and geographical location in ADEM. Methods: Medical re...

Figure S1. Scatterplots of age‐adjusted BMI z‐score for MS cases (A) and controls (B). For MS cases, height and weight measurements were taken at the clinic visit following first symptoms, excluding cases seen more than 1 year after first symptoms. For controls, BMI was taken at the time of enrollment.

Figure S2. Scatterplots and boxplots of age at first symptoms (y‐axis) and factors (x‐axes) included in statistical models to determine association between obesity (BMI z‐scores), puberty (menstrual age for girls, and advanced maturity for boys), and race/ethnicity. Post and prepubertal girls and boys were modeled separately.

Table S1. Comparison of MS cases to the US population estimates from NHANES dataset. Table S2. Mediation and Interaction of Menarcheal Age and the Effect of BMI on the Risk of MS. Table S3. Mediation and Interaction of Menarcheal Age and the Effect of BMI on Age at Onset among pubertal/postpubertal female MS patients. Table S4. Comparison of dem...

Objective The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS. Methods Case–control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex‐ and age‐stratified BMI perc...

Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients w...

Objective: To analyze the range of demographic, clinical, MRI, and CSF features of acute disseminated encephalomyelitis (ADEM), a rare, typically monophasic demyelinating disorder, and analyze long-term outcomes including time and risk factors for subsequent clinical events as well as competing diagnoses. Methods: We performed a retrospective, mul...