Pediatric Multiple Sclerosis Research Articles

Vaccination as a risk factor for pediatric multiple sclerosis: Insights from a retrospective case-control study.

This study evaluated the association between pediatric multiple sclerosis and vaccinations within 5 years before diagnosis using German ambulatory claims data. Children with multiple sclerosis (n = 346) aged 9-17 were analyzed with logistic and Poisson regression. Control groups included children with Crohn's disease, psoriasis, and no autoimmune diseases. The results indicated a negative association between vaccinations and pediatric multiple sclerosis, with no significant risk identified. This negative relationship was consistent in sensitivity and clinically isolated syndrome analyses. Overall, the study's findings do not support the hypothesis that vaccination is a risk factor for pediatric multiple sclerosis.

Pediatric onset multiple sclerosis in Kuwait

Pediatric onset multiple sclerosis in Kuwait

A 7-year-boy with Recurrent Acute Disseminated Encephalomyelitis: A Case Report

Acute Disseminated Encephalomyelitis (ADEM) is one form of inflammatory demyelinating disorder of central nervous system affecting the children following an idiopathic course of onset and usually monophasic. Recurrent ADEM is a rare entity and will arise a confusion about its diagnosis. There is no definite clinical criteria and treatment protocol for the management of ADEM. Here we report a case of recurrent ADEM where a 6 year old boy presented with recurrent episodes of low grade fever, difficulty in walking, altered sensorium and focal seizure. MRI of brain showed reappearance of demyelinating lesion on the previous site. The gap between first and second episode was six months. After the first attack of ADEM patient were completely recovered both clinically and neuroradiologically with immunotherapy. But after 7 months of disease free remission, patient again developed same features. So we diagnosed the baby as recurrent ADEM based on the consensus criteria of International Pediatric MS study group (IPMSSG). BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 51-54

Idiopathic Basal Ganglia Calcifications in a Patient with Pediatric Onset Multiple Sclerosis

Idiopathic Basal Ganglia Calcifications in a Patient with Pediatric Onset Multiple Sclerosis

Monoaminergic network abnormalities are associated with fatigue in pediatric multiple sclerosis

Monoaminergic network abnormalities are associated with fatigue in pediatric multiple sclerosis

Clinical utility of brief screening measures during neuropsychological consultation for pediatric onset multiple sclerosis.

Pediatric-onset multiple sclerosis (POMS) accounts for approximately 2 to 5% of all individuals with MS and is associated with an increased risk for cognitive impairment. In recent years, neuropsychological screening questionnaires have been increasingly utilized for pediatric populations in multidisciplinary settings. This study examines the clinical utility of the Colorado Learning Difficulties Questionnaire (CLDQ) and Pediatric Perceived Cognitive Functioning (Peds PCF) screening measures for identifying cognitive impairment in persons with POMS during a target neuropsychological evaluation. Retrospective data was gathered from electronic medical records at a single pediatric hospital. Forty-nine participants were included (69% female; 43% Hispanic/Latinx; mean age = 16.1 years old, range = 9.9 to 20.6 years old). Correlation analyses demonstrated strong interrelatedness between caregiver ratings on screening measures and performance on traditional neuropsychological measures. Effect sizes were medium across comparisons (CLDQ: Spearman's rho = -.321 to -.563; PedsPCF: Spearman's rho = .308 to .444). Exploratory cut-points using receiver operating characteristic analysis and Youden indices are also discussed. Comparison of scores across caregiver rating questionnaires and on a targeted neuropsychological battery suggests that the screening surveys alone may not be sensitive enough to identify children with cognitive impairments, but ratings may provide qualitatively meaningful information along with neuropsychological testing. This study illustrates how pediatric neuropsychologists can leverage screening tools to focus consultative interviews and effectively triage referrals for evaluation within an academic medical setting.

Assessment of central vein sign and paramagnetic rim lesions in pediatric multiple sclerosis.

The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work-up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%-rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS-based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.

Patient and family views on research priorities and design of clinical trials and research studies in pediatric multiple sclerosis.

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. Participants were as follows: (1) parents of a child (<18 years) with POMS enrolled in a national registry, (2) adolescents (13-17 years) with POMS in the registry, and (3) adults (18-40 years) with POMS receiving care at a registry affiliated clinic. Of 293 eligible participants, 192 completed surveys. Experiences with health care and medications were generally positive but there remain areas of priority improvement. Incentives to participate in clinical trials included medications previously tested and in pill form, bloodwork/study visits required ⩾ every 3 months, cognitive testing ⩽1 hour, compensation for travel and time, ability to continue current multiple sclerosis (MS) medication, option to take study medication if on placebo, and individualized study feedback. Priorities for clinical research were (1) psychosocial impact, (2) cognitive/academic impact, (3) environmental risk, and (4) nutrition. Results highlighted the importance of a holistic approach to study design and a focus on the impact of disease on daily life to best engage patients and families in POMS clinical trials and research.

The Multiple Sclerosis Prodrome in a Retrospective Pediatric Cohort

BackgroundEvidence suggests a prodromal phase in multiple sclerosis (MS), with increased health care use preceding the first demyelinating event (FDE). Although prior studies have explored this in adults, limited data exist for pediatric cases. We aimed to analyze health care utilization and prodromal symptoms in the two years before FDE in patients with pediatric-onset MS (POMS). MethodsFrom 122 patients at the Pediatric Multiple Sclerosis & Demyelinating Diseases Center at Washington University School of Medicine from 2011 to 2021, 37 POMS cases were identified. Of these, 21 with at least two years of records preceding FDE were included. Retrospective analysis covered symptoms and health care utilization in the two-year period before FDE, including ambulatory visits, hospital admissions, and office calls. ResultsPatients showed increased health care utilization in the year preceding FDE (period B; 96 interactions) compared with the prior year (period A; 77 interactions) and an increase in the percentage of neurology-related encounters (P < 0.001). There was an increase in all office calls from period A to period B (P = 0.01). Neurological complaints included headaches (28.6%), visual (19.0%), sensory (14.3%), and balance (14.3%) in the two years before FDE, and 28.6% of patients presented for psychiatric complaints. Common non-neurological complaints included infection, dermatologic, and musculoskeletal issues and injury. ConclusionsOur POMS cohort showed increased health care use before FDE, consistent with population-based data. This study emphasizes diverse symptoms in prodromal POMS, with headaches being the most common neurological symptom in the two-year period before FDE.

The kappa free light chains index is an accurate diagnostic biomarker for paediatric multiple sclerosis.

Multiple sclerosis (MS) may occur before the age of 18. Differentiation between paediatric MS (PedMS) and other demyelinating syndromes (ODSs) is challenging. In adult with MS, the kappa free light chain (KFLC) index has proven to be a reliable marker of intrathecal Ig synthesis. To assess the diagnostic value of the KFLC index in a cohort of patients with paediatric-onset, inflammatory disorders of the CNS. We included 73 patients and divided them into four groups: PedMS (n = 16), ODS (n = 17), encephalitis and/or inflammatory epilepsy (EE, n = 15), and controls without inflammatory CNS diseases (n = 25). The KFLC index was calculated and compared with the results of the oligoclonal bands determination. The KFLC index was higher in the PedMS group (median (interquartile range (IQR)): 150.9 (41.02-310.6)) than in the ODS (3.37 (2.22-8.11)), the EE (5.53 (2.31-25.81)) and the control group (3.41 (2.27-5.08)), respectively. The best KFLC index cut-off for differentiating between patients with PedMS and controls was 6.83 (sensitivity: 100%; specificity: 92%). A KFLC index over 93.77 indicated that the patient is very likely to have PedMS (sensitivity: 68%; specificity: 100%). The KFLC index is a reliable tool for the diagnosis of MS in a paediatric population.

Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity. This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage. MS cases (64% female, mean age 15.4 years, SD 2.8) were demographically similar to controls (60% female, mean age 14.9 years, SD 3.9). Cases were less likely to have a mother with a bachelor's degree or higher (OR 0.42, 95% CI 0.22-0.80, p = 0.009) and were more likely to experience childhood neighborhood disadvantage (OR 1.04 for each additional point on the neighborhood socioeconomic disadvantage score, 95% CI 1.00-1.07; p = 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS. Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.

Disability trajectories by progression independent of relapse activity status differ in pediatric, adult and late-onset multiple sclerosis

BackgroundTo compare Expanded Disability Status Scale (EDSS) trajectories over time between Multiple Sclerosis (MS) groups with pediatric (POMS), adult (AOMS) and late (LOMS) onset, and between patients with and without progression independent of relapse activity (PIRA).MethodsPatients with a first visit within 1 year from onset, ≥ 5-year follow-up and ≥ 1 visit every 6 months were selected from the Italian MS Register. Adjusted disability trajectories were assessed by longitudinal models for repeated measures. Comparisons between groups and between patients with and without PIRA in subgroups were performed by evaluating the yearly differences of mean EDSS score changes versus baseline (delta-EDSS).A first CDA event was defined as a 6-months confirmed disability increase from study baseline, measured by EDSS (increase ≥ 1.5 points with baseline EDSS = 0; ≥ 1.0 with baseline EDSS score ≤ 5.0 and ≥ 0.5 point with baseline EDSS > 5.5).PIRA was defined as a CDA event occurring more than 90 days after and more than 30 days before the onset of a relapse.Results3777 MS patients (268 POMS, 3282 AOMS, 227 LOMS) were included. The slope of disability trajectories significantly diverged in AOMS vs POMS starting from the second year of follow-up (Year 2: delta2-EDSS 0.18 (0.05; 0.31), p = 0.0054) and then mean delta2-EDSS gradually increased up to 0.23 (0.07; 0.39, p = 0.004) at year 5. Patients with PIRA had significant (p < 0.0001) steeper increase in EDSS scores than those without PIRA in all groups, although in POMS, the disability trajectories began to diverge later and at a lesser extent with delta-EDSS score of 0.48 vs 0.83 in AOMS and 1.57 in LOMS, at 3 years after the first PIRA.ConclusionsAge is relevant in determining disability progression in MS. POMS shows a less steep increase in EDSS scores over time than older patients. The effect of PIRA in accelerating EDSS progression is less pronounced in POMS than in AOMS and LOMS.

Unveiling the Psychological Consequences of Illness Perception in Pediatric Multiple Sclerosis: A Parent-Child Study.

Previous research has emphasized the significant role of illness perception in chronic diseases, including Multiple Sclerosis. Limited research has been conducted on exploring illness perception in Pediatric Onset Multiple Sclerosis (POMS), parental illness perception, and the impact of differences in their illness perceptions on the emotional well-being of the child. This study included 65 dyads of children aged 10-17 and their parents, divided into the following two groups: (I) 32 dyads of children with POMS and their parents; and (II) 33 dyads of healthy children and their parents. Overall, 73.1% and 43.8% of the children with POMS met the criteria for probable anxiety and depression, respectively, compared to 27.3% and 0% of the healthy children. Differences were found between the dimensions of illness perception in the POMS children and their parents, in the areas of consequences, personal control, identity, and control factors. Multinomial Logistic Regression indicated that differences in child-parent illness perception increased the likelihood of comorbid anxiety and depression by 37%. These findings underscore the importance of alignment between children with POMS and their parents in illness perception. Healthcare providers should prioritize interventions that address illness perceptions and be mindful of the potential impact on depression and anxiety comorbidity.

Lesion phenotyping based on magnetic susceptibility in pediatric multiple sclerosis.

Pediatric multiple sclerosis (MS) displays different pathological features compared to adult MS, which can be studied in vivo by assessing tissue magnetic susceptibility with 3T-MRI. We aimed to assess different white matter lesions (WMLs) phenotypes in pediatric MS patients using quantitative susceptibility mapping (QSM) and susceptibility mapping weighted imaging (SMWI) over 12 months. Eleven pediatric MS patients [female: 63.6%; mean ± standard deviation (SD) age and disease duration: 16.3 ± 2.2 and 2.4 ± 1.5; median (range) Expanded Disability Status Scale (EDSS) 1 (0-2)] underwent 3 Tesla-MRI exams and EDSS assessments at baseline and after 1 year. QSM and SMWI were obtained using 3-dimensional (3D)-segmented echo-planar-imaging with submillimetric spatial resolution. WMLs were classified according to their QSM appearance and SMWI was used to identify QSM hyperintensities ascribable to veins. Total brain volumes at baseline and follow-up were computed using high-resolution 3D T1-weighted images. Mean ± SD paramagnetic rim lesions (PRLs) prevalence was 7.0% ± 9.0. Fifty-four percent (6/11) of patients exhibited at least one PRL, with one patient exhibiting ≥ 4 PRLs. All patients showed QSM-iso-/hypo-intense lesions, which represented a mean ± SD of 65.8% ± 22.7 of total WMLs. QSM-hyperintense WMLs showed a positive correlation with total brain volume reduction at follow-up (r = 0.705; p = .02). No lesion was classified as different between baseline and follow-up. Chronic compartmentalized inflammation seems to occur early in pediatric MS patients with short disease duration. A high prevalence of iso-/hypo-intense lesions was found, which could account for the higher remyelination potential in pediatric MS.

Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease

BackgroundMyelin 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...

No one really plans to have multiple sclerosis: Transition readiness and quality of life in paediatric multiple sclerosis.

We sought to explore the experiences and perceptions of the quality of life of adolescents with pediatric-onset multiple sclerosis and assess their readiness for academic, employment and/or health care-related transitions. Adolescents with pediatric-onset multiple sclerosis face unique challenges in managing a chronic illness while navigating future scholastic, social and occupational goals. We conducted a qualitative study with in-depth, semi-structured interviews from July 2017 to March 2019. Adolescents with pediatric-onset multiple sclerosis were recruited from a pediatric neurology subspeciality practice until reaching data saturation. A total of 17 interviews were completed via telephone with participants ages 15 through 26. Through content analysis of the interviews, we identified five major themes: (1) receiving a new diagnosis; (2) adapting to life with pediatric-onset multiple sclerosis; (3) evaluating education/career transition preparedness; (4) adjusting within family life and establishing support systems; and (5) assessing current medical services and preparedness for adult medical care. Autonomy in health care management, adequate control of physical symptoms and sufficient family support impacted perceptions of quality of life. Implementing a dedicated transition visit, including the parent(s) of those with pediatric-onset multiple sclerosis, early in adolescence may provide an avenue for appropriate anticipatory guidance regarding available services, independent medical management and continuity of care.

Association of nutritional intake with clinical and imaging activity in pediatric multiple sclerosis

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 collected using a food screener estimating intake of various dietary food groups (e.g. dairy and fruits) and additional calculated indices (e.g. Healthy Eating Index (HEI)). Outcomes included time-from-enrollment to clinical relapse, new magnetic resonance imaging (MRI) T2 lesions, and Expanded Disability Status Scale (EDSS) increase. Results: 353 children with MS were enrolled (mean ± SD age 15.4 ± 2.9, follow-up 3.9 ± 2.6 years). Multivariable analysis demonstrated that increased dairy by 50% of recommended intake was associated with increased relapse risk by 41% (adjusted hazard ratio (HR) 1.41, 95% CI 1.07–1.86), and risk of T2 progression by 40% (1.40, 1.12–1.74). Increased intake of fruit or vegetable above recommended, and every five-point HEI increase decreased relapse risk by 25% (0.75, 0.60–0.95), 45% (0.55, 0.32–0.96), and 15% (0.84, 0.74–0.96), respectively. No associations were found with EDSS. Conclusion: This work supports the influence of dietary intake on MS course, particularly with dairy intake. Future prospective study is required to establish causation.

Impact of race and socioeconomic deprivation on clinical outcomes and healthcare utilization in pediatric multiple sclerosis.

Health disparities in adult-onset multiple sclerosis have been identified in the Black/African American (AA) population. A higher relapse rate has been suggested in Black/AA patients with pediatric-onset MS (POMS), but little work explores healthcare utilization and social determinants of health (SDOH). To evaluate racial, ethnic, and socioeconomic disparities in POMS outcomes. Retrospective chart review identified 31 eligible patients diagnosed with POMS at Children's of Alabama between 2013 and 2023. Demographics, outcomes, and healthcare utilization over 2 years from diagnosis were collected. Patient addresses were connected to SDOH measures from the US Census. Bivariate analysis was performed using Fisher's Exact Test, Wilcoxin Test, and 2-sided t-test. Black/AA children had a higher Expanded Disability Status Scale (EDSS) at first presentation (p = 0.0276) and were more likely to initiate fingolimod vs. glatiramer acetate (p = 0.0464). Living further from Children's of Alabama was associated with a higher most recent EDSS (p = 0.0301) and fewer neurology appointments (p = 0.0167). Families living in more socioeconomically deprived census tracts had significantly more hospital admissions. Black/AA POMS patients had a more severe initial presentation and were started on higher efficacy medication. We identified disparities in EDSS and healthcare utilization based on SDOH data linked to a child's home address.

Glial fibrillary acidic protein and neurofilament light chain as biomarkers in pediatric multiple sclerosis.

Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury, and serum glial fibrillary acidic protein (sGFAP) reflects reactive astrogliosis. In adult multiple sclerosis (MS), sNfL correlates with relapsing disease activity while sGFAP correlates with progressive disease. We evaluate sNfL and sGFAP as biomarkers in pediatric-onset MS (POMS) compared to pediatric healthy controls (PHC), and correlations with the disease course. In this single-center observational cross-sectional study, we extracted data from a longitudinal database and measured NfL and GFAP from bio-banked serum using single-molecule array technology. The analysis included 61 POMS patients and 45 PHC. Controlling for age and BMI, sNfL was 414% higher and sGFAP was 42.3% higher in POMS. Disability (EDSS) is associated with higher sNfL (β = 0.32, p = 0.002) and higher sGFAP (β = 0.11, p = 0.03). sNfL is associated with MRI lesion burden, recent disease activity (β =0.95, p < 0.001), and untreated status (β = 0.5, p = 0.006). sNfL and sGFAP are elevated in POMS compared to PHC. Both biomarkers are associated with clinical disability. Elevated sGFAP may reflect early neurodegeneration in POMS, while sNfL reflects disease activity and DMT response. Elevated sNfL among some clinically and radiographically stable POMS patients suggests ongoing neuroaxonal injury with a potential role for sNfL monitoring disease stability.

Astrocytic stress response is induced by exposure to astrocyte-binding antibodies expressed by plasmablasts from pediatric patients with acute transverse myelitis

BackgroundPediatric acute transverse myelitis (ATM) accounts for 20–30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical presentation of a relapsing ADS such as multiple sclerosis (MS). B cells have been strongly implicated in the pathogenesis of adult MS. However, little is known about B cells in pediatric MS, and even less so in pediatric ATM. Our lab previously showed that plasmablasts (PB), the earliest B cell subtype producing antibody, are expanded in adult ATM, and that these PBs produce self-reactive antibodies that target neurons. The goal of this study was to examine PB frequency and phenotype, immunoglobulin selection, and B cell receptor reactivity in pediatric patients presenting with ATM to gain insight to B cell involvement in disease.MethodsWe compared the PB frequency and phenotype of 5 pediatric ATM patients and 10 pediatric healthy controls (HC) and compared them to previously reported adult ATM patients using cytometric data. We purified bulk IgG from the plasma samples and cloned 20 recombinant human antibodies (rhAbs) from individual PBs isolated from the blood. Plasma-derived IgG and rhAb autoreactivity was measured by mean fluorescence intensity (MFI) in neurons and astrocytes of murine brain or spinal cord and primary human astrocytes. We determined the potential impact of these rhAbs on astrocyte health by measuring stress and apoptotic response.ResultsWe found that pediatric ATM patients had a reduced frequency of peripheral blood PB. Serum IgG autoreactivity to neurons in EAE spinal cord was similar in the pediatric ATM patients and HC. However, serum IgG autoreactivity to astrocytes in EAE spinal cord was reduced in pediatric ATM patients compared to pediatric HC. Astrocyte-binding strength of rhAbs cloned from PBs was dependent on somatic hypermutation accumulation in the pediatric ATM cohort, but not HC. A similar observation in predilection for astrocyte binding over neuron binding of individual antibodies cloned from PBs was made in EAE brain tissue. Finally, exposure of human primary astrocytes to these astrocyte-binding antibodies increased astrocytic stress but did not lead to apoptosis.ConclusionsDiscordance in humoral immune responses to astrocytes may distinguish pediatric ATM from HC.