Recent Advances in Pediatric-Onset Multiple Sclerosis

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Neurology & Neurodevelopmental Disorders".

Deadline for manuscript submissions: 10 November 2025 | Viewed by 7534

Special Issue Editors


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Guest Editor
Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria
Interests: neuroinflammation; pediatric onset multiple sclerosis; myelitis; pediatric neurology

E-Mail Website
Guest Editor
Division of Pediatric Neurology, Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Innsbruck, Austria
Interests: neuroimmunology

Special Issue Information

Dear Colleagues,

In 2–5% of patients with multiple sclerosis, the first clinical symptoms manifest before the age of 18. Although patients with pediatric-onset multiple sclerosis (POMS) have a longer interval until they reach irreversible disability, this occurs at a younger age than in patients with adult-onset disease. In addition, patients with pediatric-onset multiple sclerosis show a higher inflammatory activity with a 2-3-fold increased frequency of relapses compared to patients with adult-onset multiple sclerosis. In contrast to the widely used hesitant treatment approach with the start of injectable therapies and step-wise escalation, recent studies suggest that applying newer disease-modifying therapies (DMTs) as initial treatment improves disease control. A wide range of DMTs are available for adult use; however, in the pediatric population, only three DMTs (fingolimod, teriflunomide, and dimethyl fumarate) are currently approved for treatment. Observational studies suggest similar effects and side effects in pediatric and adult-onset cohorts; therefore, off-label use of other DMTs is widely applied.

This Special Issue aims to gather scientific evidence relating to new advances in POMS with special focus on new treatment regimens, advances in diagnostic tools, neuropsychological aspects, and follow-up.

We welcome all researchers to take part in this effort and share their experience and novel and ongoing research through this Special Issue.

Dr. Markus Breu
Dr. Christian Lechner
Guest Editors

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Keywords

  • multiple sclerosis
  • pediatric
  • POMS
  • inflammation
  • demyelination
  • pediatric neurology

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Published Papers (7 papers)

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Research

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16 pages, 1838 KiB  
Article
Pediatric-Onset Multiple Sclerosis (POMS) and Epilepsy: Exploring Etiological Complexity—Outcomes from a Single-Center Experience
by Alice Denisa Dică, Dana Craiu, Catrinel Iliescu, Marcel-Alexandru Găină, Carmen Sandu, Cristina Pomeran, Diana Bârcă, Niculina Butoianu, Carmen Burloiu, Ioana Minciu, Alexandra-Maria Găină, Dana Șurlică, Cristina Moțoescu, Oana Tarța-Arsene, Cristina Cazacu, Andreea Badea, Alexandru Ștefan Niculae and Daniela Adriana Ion
Children 2025, 12(5), 631; https://doi.org/10.3390/children12050631 - 14 May 2025
Viewed by 456
Abstract
This article examines the complex relationship between seizures, epilepsy, and multiple sclerosis (MS) in pediatric patients, based on detailed findings from a single-center study. Background: Although multiple sclerosis is primarily recognized as an adult-onset disease, its occurrence in children presents distinctive challenges, [...] Read more.
This article examines the complex relationship between seizures, epilepsy, and multiple sclerosis (MS) in pediatric patients, based on detailed findings from a single-center study. Background: Although multiple sclerosis is primarily recognized as an adult-onset disease, its occurrence in children presents distinctive challenges, especially related to seizure disorders. Methods: We reviewed 120 pediatric MS patients evaluated over 7 years; six of these (5%) experienced seizures (including one case of acute status epilepticus), and five were diagnosed with epilepsy according to the latest International League Against Epilepsy (ILAE) classification. This study aimed to evaluate the occurrence rates and types of seizures while investigating their management strategies in this specific group. Results: Through a detailed case analysis and patient follow-up, we identified key factors contributing to seizure onset and explored implications for treatment and care. In our cohort, children with MS and seizures showed a higher risk for disease progression and greater cumulative disability, evidenced by a significantly higher last Expanded Disability Status Scale (EDSS) score (after a minimum 2-year follow-up) in the seizure group (p < 0.006). The analysis recognized early MS onset and highly active disease types as further risk factors that led to worse health outcomes. Conclusions: Genetic causes of epilepsy in children are common and may interact with MS-related inflammation in the same patient; our observations underscore the need to investigate how these two conditions interact. This work contributes to the broader understanding of epilepsy comorbid with MS among pediatric patients, seeking to facilitate the creation of improved interdisciplinary clinical practices in pediatric neurology. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)
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8 pages, 184 KiB  
Article
The Presence of MRZ Reactions Improves the Prediction of Multiple Sclerosis in Children with Optic Neuritis
by Franziska Kauth, Sophie Chen, Eva-Maria Wendel, Markus Reindl, Nicole Heußinger and Kevin Rostásy
Children 2025, 12(4), 497; https://doi.org/10.3390/children12040497 - 13 Apr 2025
Viewed by 432
Abstract
Background/Purpose: Optic neuritis (ON) is a rare disease that may remain a single episode or transform into MS. OCBs and spinal MRI lesions have already been identified as prognostic factors. Aim: Our aim was to evaluate if the presence of more than one [...] Read more.
Background/Purpose: Optic neuritis (ON) is a rare disease that may remain a single episode or transform into MS. OCBs and spinal MRI lesions have already been identified as prognostic factors. Aim: Our aim was to evaluate if the presence of more than one elevated antibody index of measles, rubella, and/or varicella-zoster (MRZ) is an indicator of risk of conversion. Methods: In total, 228 patients diagnosed with ON between 1990 and 2013 were included in this retrospective study. All children had a data set consisting of age, sex, ON type, MRI, and detailed CSF studies, including the presence of OCBs and MRZ reactions and a follow-up of at least 1.5 years. Children were then divided into two groups: those who developed MS according to the McDonald criteria 2010 (n = 92) and those who did not (n = 136). Binary logistic regression analysis was used to assess the relationship between the different prognostic factors and conversion to MS. Positive (PPV) and negative predictive values were calculated. Results: Binary logistic regression analysis revealed that an MS-like MRI (p < 0.001), positive OCBs (p = 0.002), and a positive MRZ reaction (p < 0.001) were significant prognostic factors for conversion to MS after ON. Calculated PPVs showed a positive MRZ reaction alone to already be a good predictor (PPV 0.90 (95%CI: 0.82 to 0.95), p < 0.001). The best prediction was possible with a combination of cMRI, the presence of OCBs, and a positive MRZ reaction (PPV 1.00 (0.93 to 1.00), p < 0.001). Conclusions: Our findings show that a positive MRZ reaction alone already has a high predictive value for future conversion to MS and should be included in the workup of a child with an initial demyelinating event. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)
12 pages, 758 KiB  
Article
Long-Term Socioeconomic and Neurologic Outcome for Individuals with Childhood-Onset Multiple Sclerosis
by Moritz Tacke, Iris Hannibal, Katharina Vill, Michaela V. Bonfert, Wolfgang Müller-Felber and Astrid Blaschek
Children 2024, 11(8), 1024; https://doi.org/10.3390/children11081024 - 21 Aug 2024
Cited by 1 | Viewed by 936
Abstract
Intorduction: Most studies on the progression of childhood-onset multiple sclerosis (MS) involve relatively short follow-up periods, focusing primarily on neurological outcomes and disability progression. The influence of these and other factors on the health-related quality of life is not known. To gain a [...] Read more.
Intorduction: Most studies on the progression of childhood-onset multiple sclerosis (MS) involve relatively short follow-up periods, focusing primarily on neurological outcomes and disability progression. The influence of these and other factors on the health-related quality of life is not known. To gain a comprehensive understanding of early-onset MS, it is crucial to evaluate the effects of treatment and the disease on quality of life. Method: This pilot project aimed to evaluate the feasibility of using an online survey tool for long-term follow-up data collection from patients with childhood-onset MS. An anonymized, monocentric, prospective survey was conducted on a convenience cohort of patients treated at a certified centre for neuromuscular diseases in childhood between 2007 and 2019. Results: A total of 27 patients completed the survey. There were no mandatory items, therefore some patients chose not to answer all the questions in the questionnaire. Patients exhibited promising educational achievements, low neurological disease burden, and high resilience. However, anxiety, depression, and pain significantly impacted their perceived health status. Conclusion:This single-centre study has yielded new insights into childhood-onset MS. To enable more accurate comparisons across different centres and countries, it is essential to establish a minimum data set and questionnaire subset for patients with paediatric-onset MS transitioning into adulthood. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)
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12 pages, 666 KiB  
Article
Unveiling the Psychological Consequences of Illness Perception in Pediatric Multiple Sclerosis: A Parent–Child Study
by Roy Aloni, Gaya Asher, Amichai Ben-Ari and Shay Menascu
Children 2024, 11(8), 929; https://doi.org/10.3390/children11080929 - 31 Jul 2024
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Abstract
Background: 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 [...] Read more.
Background: 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. Method: 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. Results: 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%. Discussion: 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. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)
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9 pages, 568 KiB  
Article
Epidemiology and Healthcare Utilization in Pediatric Multiple Sclerosis and Neuromyelitis Optica: A Nationwide Population-Based Study in South Korea (2016–2020)
by Hyewon Woo, Junho Hwang, Sun Ah Choi and Soo Ahn Chae
Children 2024, 11(5), 553; https://doi.org/10.3390/children11050553 - 5 May 2024
Viewed by 1974
Abstract
Pediatric multiple sclerosis (MS) and neuromyelitis optica (NMO) are rare acquired demyelinating syndrome with limited epidemiological data available, particularly in non-Western setting. This study aimed to demonstrate the epidemiology of pediatric MS and NMO in South Korea and to analyze of healthcare utilization [...] Read more.
Pediatric multiple sclerosis (MS) and neuromyelitis optica (NMO) are rare acquired demyelinating syndrome with limited epidemiological data available, particularly in non-Western setting. This study aimed to demonstrate the epidemiology of pediatric MS and NMO in South Korea and to analyze of healthcare utilization and economic burden associated with these conditions. Using a nationwide population-based database from the Korean Health Insurance Review and Assessment Service database, we identified pediatric cases (age < 20 years) of MS and NMO from 2016 to 2020. We analyzed incidence, prevalence, healthcare utilization and medical costs. The study found low age-standardized incidence and prevalence rates for pediatric MS and NMO in South Korea. There was a marked disparity in healthcare utilization between urban and rural areas. Most healthcare interactions occurred in tertiary hospitals in urban settings, particularly in Seoul. The study also highlighted the substantial economic burden associated with the management of rare diseases, with annual variability in medical costs. Pediatric MS and NMO are extremely rare in South Korea, with significant regional disparity in healthcare utilization. The findings emphasize the need for targeted healthcare policies to improve access and reduce disparities, particularly for chronic and rare diseases requiring specialized care. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)
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Review

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13 pages, 276 KiB  
Review
Therapeutic Advances in Pediatric Multiple Sclerosis
by Rachel Walsh and Tanuja Chitnis
Children 2025, 12(3), 259; https://doi.org/10.3390/children12030259 - 20 Feb 2025
Viewed by 1281
Abstract
Pediatric-onset multiple sclerosis (POMS) is a chronic, immune-mediated disorder that affects the central nervous system in children and adolescents. Approximately 3–10% of MS patients have an onset that occurs before the age of 18. The vast majority of pediatric MS cases are characterized [...] Read more.
Pediatric-onset multiple sclerosis (POMS) is a chronic, immune-mediated disorder that affects the central nervous system in children and adolescents. Approximately 3–10% of MS patients have an onset that occurs before the age of 18. The vast majority of pediatric MS cases are characterized by a relapsing-remitting course with a high burden of disease activity. Pediatric MS patients were historically treated off-label with varying degrees of success. With the approval of many new therapies for adult-onset MS, alternative treatments in pediatric MS have rapidly started to emerge. In this narrative review, we will discuss therapeutic advancements in pediatric multiple sclerosis, including the seminal trials of PARADIGMS, which evaluated fingolimod use in pediatric MS patients, CONNECT (dimethyl fumarate), TERIKIDS (teriflunomide), OPERETTA I (ocrelizumab), and LEMKIDS (alemtuzumab). We will also review the safety and efficacy of different monoclonal antibodies that are commonly prescribed for multiple sclerosis. We will then examine induction versus escalation treatment strategies and conclude with discussions on treatment considerations in POMS patients. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)

Other

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15 pages, 2859 KiB  
Case Report
Overtime Challenges of Diagnosis and Treatment in Two Pediatric Patients with Extensive Cerebral Tumefactive Lesions Indicative of Baló’s Type Multiple Sclerosis
by Alice Denisa Dică, Dana Craiu, Catrinel Iliescu, Marcel-Alexandru Găină, Carmen Sandu, Cristina Pomeran, Carmen Burloiu, Alexandra-Maria Găină and Daniela Adriana Ion
Children 2025, 12(5), 630; https://doi.org/10.3390/children12050630 - 14 May 2025
Viewed by 342
Abstract
Background: Baló’s concentric sclerosis stands out as a rare form of multiple sclerosis that features large tumor-like demyelinating lesions, which resemble brain tumors and create significant diagnostic and therapeutic obstacles for pediatric patients. Case Presentations: We present two case studies of pediatric patients, [...] Read more.
Background: Baló’s concentric sclerosis stands out as a rare form of multiple sclerosis that features large tumor-like demyelinating lesions, which resemble brain tumors and create significant diagnostic and therapeutic obstacles for pediatric patients. Case Presentations: We present two case studies of pediatric patients, aged 11 and 15, diagnosed with extensive cerebral tumefactive inflammatory lesions indicative of Balo’s type multiple sclerosis (MS). Both cases highlight the unique challenges faced in the diagnosis and treatment of this rare form of MS, characterized by the presence of large, tumor-like lesions that can mimic primary brain tumors. We will explore the diagnostic complexities, including the need for advanced imaging techniques, MR (Magnetic Resonance) spectroscopy, along with the time needed for differential diagnoses, which might delay the start of proper treatment. Current therapies, such as corticosteroids and immunomodulators, require customization to individual patients, carefully monitoring of clinical outcomes and possible side effects. This paper emphasizes that handling these cases requires a multidisciplinary approach, addressing not only the medical treatment but also the psychosocial needs of affected children and their families. By sharing these experiences, we aim to increase awareness about Balo’s type MS in pediatric populations and provide clinical insights into effective management strategies for similar cases in clinical practice. Conclusions: Timely detection of atypical demyelinating lesions together with immediate treatment intervention plays a crucial role in pediatric Baló-type MS. These cases demonstrate the essential role of advanced imaging and immunological testing in precise diagnosis while showcasing successful treatment approaches through corticosteroids and second-line immunotherapies, which improve patient outcomes in this atypical MS variant. Full article
(This article belongs to the Special Issue Recent Advances in Pediatric-Onset Multiple Sclerosis)
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