Search Results (29)

Background/Objectives: Pediatric acquired demyelinating syndromes (ADSs) encompass a heterogeneous group of disorders, including multiple sclerosis (MS), MOG antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), with distinct clinical trajectories and prognoses. While analyzed collectively at baseline to reflect real-world diagnostic uncertainty, outcome predictors were also examined according to final diagnosis. Identifying early predictors is crucial for optimizing long-term outcomes. Methods: We retrospectively analyzed 30 pediatric patients (mean onset age: 11.3 years) with ADSs. Clinical, radiological, CSF, antibody, and neurophysiological data were collected and analyzed alongside treatment strategies. Outcomes—EDSS scores, neuroradiological changes, and clinical status—were evaluated over a 3-year period. Results: Final diagnoses included MOGAD (36.6%), MS (33.3%), NMOSD (6.6%), ADEM (10%), and other ADSs (13.3%). At onset, ≥3 brain lesions were present in 76.7% of patients. Disease-modifying therapies (DMTs) were used in 37% and acute immunotherapy in 90%. EDSS progression was significantly associated with DMT use at multiple timepoints, with additional predictors including MRI lesion type, CSF findings, antibody status, and evoked potentials. At 3 years, neurocognitive function predicted clinical outcome. Conclusions: Early immunotherapy and baseline instrumental findings are key predictors of outcome in pediatric ADSs. MOGAD showed a more favorable course, while MS and NMOSD were associated with greater long-term disability. A comprehensive, early diagnostic approach is essential for improving prognosis. Full article

Background: Pediatric-onset multiple sclerosis (POMS) is a rare but often more aggressive form of multiple sclerosis, associated with early cognitive impairment and significant impact on quality of life. Multiple sclerosis and primary headaches, particularly migraine, are well established in adults, but data on pediatric populations remain limited. Methods: The purpose of this retrospective study was to examine 64 POMS patients, divided into groups with and without headaches, to determine potential correlations between headache presence, age at POMS onset, and MRI lesion burden. Results: Headaches were reported by 78% of patients, predominantly migraines (68%), with a significantly higher prevalence in females (74%). No significant differences were found in age at MS onset or lesion load on brain MRI between patients with and without headaches. Among those with headaches, migraines represented a higher frequency of attacks and a greater need for prophylactic treatment compared to other headache types. Headache characteristics, including pain location and associated symptoms, showed no correlation with age at MS onset or lesion burden. Conclusions: These findings indicate that while headaches are common in POMS and more frequent in females, their presence and features do not appear to directly influence the clinical or neuroradiological course of the disease. Further research with larger cohorts and longitudinal follow-up is warranted to better understand the underlying mechanisms and long-term impact of headaches in pediatric MS. Full article

Background: Pediatric-onset multiple sclerosis (POMS) is a rare and heterogeneous condition, with clinical features, progression, and therapeutic response varying significantly according to age at onset. Early-onset MS (<10 years) presents particular diagnostic and management challenges due to atypical presentations and more active inflammatory profiles. Objectives: To identify age-related clinical, radiological, and therapeutic characteristics of pediatric MS, with a specific focus on early-onset cases, and to compare them with intermediate (10–12 years) and late-onset (>12 years) forms. Methods: We conducted a retrospective analysis of medical records from 120 pediatric patients diagnosed with MS at a tertiary neurology center between 2018 and 2024. Patients were grouped by age at onset and assessed for clinical presentation, number and timing of relapses, EDSS scores, imaging findings, and treatment patterns. Results: Early-onset MS was associated with atypical symptoms, delayed diagnosis, more frequent relapses, and multifocal brainstem and cerebellar involvement. The diagnosis was significantly delayed in younger children compared to adolescents. EDSS scores tended to remain stable in the first 2–3 years, but early-onset patients showed a notable decline after the fourth year. While most patients received disease-modifying therapies, high-efficacy agents were underused due to age-related restrictions. Intermediate-onset patients presented overlapping features of both early and late-onset MS and had the highest proportion of fully preserved motor function (EDSS 0) at the end of follow-up. MRI findings revealed more extensive and confluent lesions in younger patients, particularly in the first two years after onset. Conclusions: Age at disease onset is a key determinant of clinical course and treatment response in pediatric MS. Early recognition and timely initiation of appropriate therapy—especially high-efficacy agents—may improve outcomes and reduce long-term disability. Further multicenter studies with standardized imaging and cognitive assessment protocols are needed to optimize care for this vulnerable population. Full article

Pediatric-onset multiple sclerosis (POMS) is a rare yet increasingly recognized demyelinating disease of the central nervous system, characterized by a highly inflammatory disease course and an elevated relapse rate compared to adult-onset MS (AOMS). Given the unique immunopathogenesis of POMS, recent therapeutic strategies have shifted toward early initiation of high-efficacy disease-modifying therapies (DMTs) to minimize irreversible neurological damage. Among these, B-cell-targeting therapies, particularly anti-CD20 monoclonal antibodies, have shown efficacy in adult MS and are emerging as promising candidates for POMS treatment. The present review summarizes the current knowledge of the role of B-cells in POMS pathophysiology and evaluates the therapeutic potential of anti-CD-20 agents. It also highlights ongoing clinical trials and future perspectives, including novel B-cell-directed approaches such as anti-CD19 therapies, Bruton’s tyrosine kinase (BTK) inhibitors, and BAFF-targeting agents. Full article

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

Background/Objectives: Sleep disorders (SDs) and Restless Legs Syndrome (RLS) have been reported with high prevalence in Multiple Sclerosis (MS), but data on Pediatric-Onset MS (POMS) are scarce. This study aims to assess the prevalence of SDs, particularly RLS, in a POMS cohort and examine associated clinical features. Methods: We recruited POMS patients who attended the POMS Center of the Bambino Gesù Children’s Hospital between September 2021 and February 2023; they were evaluated for SDs using the Pittsburgh Sleep Quality Index (PSQI) or the Sleep Disturbance Scale for Children (SDSC) and screened for RLS. Correlations with demographical, clinical, neuroradiological, and laboratory findings were analyzed. Results: We recruited 44 POMS patients, of whom 39% were classified as “good sleepers” and 61% were identified as “poor sleepers.” RLS was diagnosed in 10 patients (22.7%). Those with RLS were older and had higher Expanded Disability Status Scale (EDSS) scores compared to non-RLS patients (p = 0.028; p = 0.03). The presence of RLS did not show any significant correlation with MRI lesion load or laboratory data. Conclusions: Our findings suggest an increased rate of SDs and RLS in pediatric MS patients compared to the general pediatric population. Clinical data could support a secondary form of RLS in this population, but results need further confirmation. Full article

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

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

Using a pediatric-focused lens, this review article briefly summarizes the presentation of several demyelinating and neuroinflammatory diseases using conventional magnetic resonance imaging (MRI) sequences, such as T1-weighted with and without an exogenous gadolinium-based contrast agent, T2-weighted, and fluid-attenuated inversion recovery (FLAIR). These conventional sequences exploit the intrinsic properties of tissue to provide a distinct signal contrast that is useful for evaluating disease features and monitoring treatment responses in patients by characterizing lesion involvement in the central nervous system and tracking temporal features with blood–brain barrier disruption. Illustrative examples are presented for pediatric-onset multiple sclerosis and neuroinflammatory diseases. This work also highlights findings from advanced MRI techniques, often infrequently employed due to the challenges involved in acquisition, post-processing, and interpretation, and identifies the need for future studies to extract the unique information, such as alterations in neurochemistry, disruptions of structural organization, or atypical functional connectivity, that may be relevant for the diagnosis and management of disease. Full article

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, leading to the dysregulation of the mammalian target of rapamycin (mTOR) pathway. This dysregulation results in the development of benign tumors across multiple organ systems and poses significant neurodevelopmental challenges. The clinical manifestations of TSC vary widely and include subependymal giant cell astrocytomas (SEGAs), renal angiomyolipomas (AMLs), facial angiofibromas (FAs), and neuropsychiatric conditions such as autism spectrum disorder (ASD). mTOR inhibitors, notably everolimus, have become central to TSC management, with documented efficacy in reducing the sizes of SEGAs and AMLs and showing promise in addressing additional TSC-related symptoms. Case Presentation: We report the case of an 11-year-old male diagnosed with TSC, presenting with hallmark features including hypopigmented macules, early-onset infantile spasms, SEGA, and AMLs. Initial interventions included adrenocorticotropic hormone (ACTH) therapy and sodium valproate for seizure management and a minimally invasive keyhole craniotomy for SEGA reduction. At age 12, oral everolimus therapy was introduced to address both SEGA recurrence risk and ASD-related social deficits. Over the course of 24 weeks, a reduction in the size and erythema of the patient’s FAs was observed, alongside improvements in social engagement, suggesting potential added benefits of systemic mTOR inhibition beyond tumor control. Results: Treatment with everolimus over a 24-month period led to significant reductions in both FA and AML size, as well as measurable improvements in ASD-associated behaviors. Therapeutic drug monitoring maintained serum levels within the effective range, minimizing adverse effects and underscoring the tolerability and feasibility of long-term everolimus administration. Conclusions: This case underscores the efficacy of oral everolimus in reducing FA size in a pediatric TSC patient, with broader therapeutic benefits that support the potential of mTOR inhibition as a multi-targeted strategy for TSC management. Further studies are needed to explore the full range of applications and long-term impact of mTOR inhibitors in TSC care. Full article

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

Antigen presentation is a crucial mechanism that drives the T cell-mediated immune response and the development of Multiple Sclerosis (MS). Genetic alterations within the highly variable Major Histocompatibility Complex Class II (MHC II) have been proven to result in significant changes in the molecular basis of antigen presentation and the clinical course of patients with both Adult-Onset MS (AOMS) and Pediatric-Onset MS (POMS). Among the numerous polymorphisms of the Human Leucocyte Antigens (HLA), within MHC II complex, HLA-DRB1*15:01 has been labeled, in Caucasian ethnic groups, as a high-risk allele for MS due to the ability of its structure to increase affinity to Myelin Basic Protein (MBP) epitopes. This characteristic, among others, in the context of the trimolecular complex or immunological synapsis, provides the foundation for autoimmunity triggered by environmental or endogenous factors. As with all professional antigen presenting cells, macrophages are characterized by the expression of MHC II and are often implicated in the formation of MS lesions. Increased presence of M1 macrophages in MS patients has been associated both with progression and onset of the disease, each involving separate but similar mechanisms. In this critical narrative review, we focus on macrophages, discussing how HLA genetic alterations can promote dysregulation of this population’s homeostasis in the periphery and the Central Nervous System (CNS). We also explore the potential interconnection in observed pathological macrophage mechanisms and the function of the diverse structure of HLA alleles in neurodegenerative CNS, seen in MS, by comparing available clinical with molecular data through the prism of HLA-immunogenetics. Finally, we discuss available and experimental pharmacological approaches for MS targeting the trimolecular complex that are based on cell phenotype modulation and HLA genotype involvement and try to reveal fertile ground for the potential development of novel drugs. Full article

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, this review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS. Full article

Obesity has been suggested as an environmental risk factor for multiple sclerosis (MS) and may negatively effect the progression of the disease. The aim of this study is to determine any correlation between overweight/obesity and the clinical and neuroradiological features at the onset of pediatric onset multiple sclerosis (POMS). Were included patients referred to the POMS Unit of the Bambino Gesù Children’s Hospital between June 2012 and June 2021. The diagnosis of MS with an onset of less than 18 years was required. For all included subjects, we considered for the analysis the following data at the onset of symptoms: general data (age, sex, functional system compromised by neurological signs, weight and height), brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid exams. We identified 55 pediatric cases of POMS and divided them into two groups according to the body mass index (BMI): 60% were healthy weight (HW) and 40% were overweight/obese (OW/O). OW/O patients experienced a two-year age difference in disease onset compared to the HW patients (12.7 ± 3.8 years vs. 14.6 ± 4.1 years; p < 0.05). Onset of polyfocal symptoms was seen more frequently in OW/O patients than in HW (72.7% vs. 21.2%; p < 0.05). The pyramidal functions were involved more frequently in the OW/O group than in the HW group (50% vs. 25%; p < 0.005). Black holes were detected more frequently in OW/O patients in onset MRI scans compared to the HW group (50% vs. 15.5%; p < 0.05). Our findings suggest that being overweight/obese affects the risk of developing MS at an earlier age and is associated with an unfavorable clinical–radiological features at onset. Weight control can be considered as a preventive/therapeutic treatment. Full article

Purpose. Lifestyle/dietetic habits play an important role in the development and progression of multiple sclerosis (MS) disease. Here, we examine the basic pathomechanisms underlying intestinal and brain barrier modifications in MS and consider diets and dietary supplementations proposed over time to complement pharmacological therapies for improving disease outcome both in adults and in children. Methods. Scoping literature search about evidence-based findings in MS-related gut-brain axis (GBA) pathophysiology and nutritional issues at all ages. Findings. Data show that (1) no universal best diet exists, (2) healthy/balanced diets are, however, necessary to safeguard the adequate intake of all essential nutrients, (3) diets with high intakes of fruits, vegetables, whole grains, and lean proteins that limit processed foods, sugar, and saturated fat appear beneficial for their antioxidant and anti-inflammatory properties and their ability to shape a gut microbiota that respects the gut and brain barriers, (4) obesity may trigger MS onset and/or its less favorable course, especially in pediatric-onset MS. Vitamin D and polyunsaturated fatty acids are the most studied supplements for reducing MS-associated inflammation. Conclusions. Pending results from other and/or newer approaches targeting the GBA (e.g., pre- and probiotics, engineered probiotics, fecal-microbiota transplantation), accurate counseling in choosing adequate diet and maintaining physical activity remains recommended for MS prevention and management both in adults and children. Full article