Implication of Apolipoprotein E gene variants in pediatric-onset multiple sclerosis: Possible association with disease susceptibility and its clinical characteristics, in a Hellenic cohort.

BACKGROUND: Apolipoprotein E (ApoE) plays a major role in lipid homeostasis and myelination in the central nervous system. Although ApoE gene variants have been linked with cognitive impairment in the setting of Multiple sclerosis (MS), no association with disease susceptibility was found, while similar studies in pediatric-onset MS (POMS) are limited. OBJECTIVE: This study aims to explore the role of ApoE gene variants in the POMS susceptibility of a Hellenic cohort and any association with disease features. METHODS: 112 POMS, fulfilling the revised IPMSSG 2013 criteria, 391 adult-onset MS (AOMS) and 200 healthy controls (HCs), were enrolled. After DNA extraction, ApoE genotyping was performed by a polymerase chain reaction and sequence-specific-oligonucleotide technique. RESULTS: ApoE2/E3 genotype and ApoE2 allele were found to be significantly more frequent among POMS patients compared to HCs [(20.5% vs 11 %, OR [95 %]: 2.1 (1.1-4.0), p = 0.03)], and [(11% vs 5.3 %, OR [95 %]: 2.3 (1.2-4.1), p = 0.01)], respectively. Additionally, significantly lower frequencies of the ApoE3/E3 genotype and the ApoE3 allele were observed in POMS patients compared to HCs (59.8% vs 79 %, OR [95 %]:0.40 (0.24-0.65), p = 0.0005 and 79% vs 89 % 0.46, OR [95 %]: (0.30-0.73), p = 0.001)], respectively. CONCLUSIONS: The ApoE2 allele may represent a novel risk factor for POMS development.

Respiratory functions, respiratory muscle strength and fatigue in patients with pediatric-onset multiple sclerosis: a comparative cross-sectional study.

PURPOSE: To compare PwPOMS and healthy controls in terms of respiratory functions, respiratory muscle strength, and fatigue, and investigate the determining role of fatigue on respiratory parameters. METHODS: Twenty-five PwPOMS and 15 healthy controls were included in the study. Maximum inspiratory pressure (MIP) and expiratory pressures (MEP) were measured. Respiratory functions were evaluated using spirometry, and predicted values were recorded for FEV1, FVC, FEV1/FVC, and PEF. Fatigue levels were assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS). RESULTS: The FEV1%pred (p = 0.022), PEF%pred (p = 0.003), MIP (p = 0.001), and MEP (p = 0.019), cognitive fatigue self-reported score of PedsQL-MFS (p = 0.037), sleep-rest fatigue (p = 0.034), cognitive fatigue (p = 0.010), and total score (p = 0.005) of PedsQL-MFS Proxy Report were significantly decreased in PwPOMS compared with their healthy peers. Regression analysis showed that the general fatigue of self-reported PedsQL-MFS was a determinator for FEV1%pred (ß= -0.467) and PEF% (ß= -0.553), and total score PedsQL-MFS was a determinator for FEV1/FVC %pred (ß= -0.599). CONCLUSION: PwPOMS had decreased respiratory muscle strength, FEV1, and PEF, with preserved FEV1/FVC and higher fatigue levels than their healthy peers. In addition, self-reported fatigue had a determining role in respiratory functions but not respiratory muscle strength in PwPOMS. This trial is registered on ClinicalTrials.gov under "NCT05123924" available at: https://clinicaltrials.gov/ct2/show/NCT05123924 .

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.

Sexual Health Education and Quality of Counseling in Pediatric-Onset Multiple Sclerosis.

BACKGROUND: Disease-modifying therapies (DMTs) have revolutionized the management of multiple sclerosis (MS). Many DMTs have a risk of teratogenic outcomes, which is notable as MS disproportionally affects women of reproductive age and the rates of unplanned pregnancies among persons with MS (PwMS) are as high as 34%. Prior research suggests that patients' culture may influence their perspectives surrounding family planning. Given our institution's patient population, we compared the spectrum of knowledge in Hispanic and non-Hispanic patients with pediatric-onset MS (POMS) regarding DMTs and their associated risks during pregnancy and possible disparities in their treatment and counseling. METHODS: A small cohort of patients with POMS (n = 22) were surveyed on their knowledge and beliefs surrounding family planning and sexual health counseling. Odds ratios and 95% confidence intervals were used to evaluate the association between survey question responses and ethnicity. RESULTS: No significant differences in beliefs or knowledge regarding sexual health between Hispanic and non-Hispanic participants were identified, but many valuable themes emerged. Internet access and social relationships heavily influence participants' knowledge surrounding birth control and sexual health. Patients also desired continuous engagement in sexual health counseling. CONCLUSIONS: In this small pilot cohort, cultural views did not significantly influence whether adolescent and young adult patients with POMS seek sexual health resources. Future studies should aim to identify effective interventions for providers to educate PwMS about sexual health and family planning to address the elevated unplanned pregnancy rate in this population and provide the education these patients have vocalized a desire to receive.

The impact of HLA-DRB1 alleles in a Hellenic, Pediatric-Onset Multiple Sclerosis cohort: Implications on clinical and neuroimaging profile.

BACKGROUND: Pediatric-Onset Multiple Sclerosis (POMS) is considered a complex disease entity and several genetic, hormonal, and environmental factors have been associated with disease pathogenesis. Linkage studies in Caucasians have consistently suggested the human leukocyte antigen (HLA) polymorphisms, as the genetic locus most strongly linked to MS, with the HLA-DRB1*15:01 allele, being associated with both adult and pediatric MS patients. Here we aim to investigate the prevalence of the HLA-DRB1 alleles among a Hellenic POMS cohort and any possible associations with clinical and imaging disease features. MATERIALS AND METHODS: 100 POMS patients fulfilling the IPMSSG criteria, 168 Adult-Onset MS (AOMS) patients, and 246 Healthy Controls (HCs) have been enrolled. HLA genotyping was performed with a standard low-resolution sequence-specific oligonucleotide (SSO) technique. RESULTS: POMS patients display a significantly increased HLA-DRB1*03 frequency compared to both HCs [24% vs. 12.6%, OR [95%CI]: 2.19 (1.21-3.97), p=0.016) and AOMS (24% vs. 13.1%, OR [95%CI]: 2.1 (1.1-3.98), p=0.034] respectively. HLA-DRB1*03-carriers display reduced risk for brainstem lesion development (OR [CI 95%]:0.19 (0.06-0.65), p=0.011). A significantly lower frequency of HLA-DRB1*07 (4% vs 13.4%, OR (95% CI): 0.27 (0.09-0.78), p= 0.017) and HLA-DRB1*11 (37% vs 52%, OR [95% CI]: 0.54 (0.34-0.87), p= 0.016) was observed in POMS compared to HCs. CONCLUSION: The HLA-DRB1*03 allele was associated with a higher risk for POMS, replicating our previous findings, and with a lower risk for brainstem lesion development, a common clinical and neuroimaging feature in POMS, while HLA-DRB1*07 and HLA-DRB1*11 display a protective role. These findings expand the existing knowledge of HLA associations and POMS.

Navigating the Uncharted Territory of Pediatric-Onset Multiple Sclerosis in a 12-Year-Old Male: A Case Study.

This case report presents an atypical instance of pediatric-onset multiple sclerosis (MS) in a 12-year-old male, a demographic less commonly affected by this condition. The patient's clinical course was marked by severe and progressive symptoms, including lower limb weakness and loss of bowel/bladder control, diverging from the typical relapsing-remitting pattern observed in pediatric MS. Despite initial resistance to high-dose steroid treatment, his condition was ultimately stabilized through plasmapheresis, following the detection of myelin oligodendrocyte glycoprotein antibodies. Unique aspects of this case included the patient's young age, male gender, and the occurrence of osteopenia, as identified by a dual-energy X-ray absorptiometry scan. This report highlights the variability in MS presentations among pediatric patients and underscores the importance of a personalized, multidisciplinary approach to diagnosis and treatment. It contributes to the growing body of knowledge on pediatric MS, emphasizing the need for heightened clinical vigilance and tailored management strategies in young patients with this complex and lifelong disease.

Multiple sclerosis in a 4-year-old boy: a case report and literature review.

Pediatric onset multiple sclerosis (POMS) in the very young is a very rare entity and presents a difficult diagnostic challenge due to overlapping signs and symptoms with other diseases. We present a 4-year-old boy who initially presented with right-sided hemiparesis and demyelinating lesions on MRI. Follow-up MRI examinations 3 and 6 months later revealed new demyelinating lesions. Ten months after initial presentation, he presented with right-sided hemiparesis, central facial nerve palsy on the right side and new demyelinating lesions on MRI. Two clinical events and new MRI lesions on follow-up MRIs confirmed the diagnosis of POMS. He was treated with rituximab and experienced no further relapses or radiological progression during the follow-up period.

Managing pediatric-onset multiple sclerosis in an austere setting: A case report.

Pediatric-onset multiple sclerosis (POMS) is the most common demyelinating disease in children. Patients suffer from physical disability, cognitive impairment, and psychosocial challenges. Management requires a multidisciplinary care team. Here we present a case of an 11-year-old boy with POMS who relocated to Guam prior to initiation of a disease-modifying treatment and who experienced a flare without immediate access to an MRI or a child neurologist. Care required the combined efforts of ophthalmology, pediatrics, and emergency medicine in Guam, real-time remote guidance by child neurology, and asynchronous collaboration with cardiology and child neurology. As a result, the immediate flare was accurately diagnosed and treated with steroids, the patient was started on Fingolimod, and an emergency management plan for future flares was constructed. This case illustrates the nuances of both the acute and chronic management of multiple sclerosis in a resource-limited setting and how a combination of synchronous and asynchronous telemedicine was able to achieve a satisfactory treatment plan.

Well-being among parents of youth with multiple sclerosis: a preliminary longitudinal study.

Background: In 2021, the annual rate of pediatric-onset multiple sclerosis (POMS) in Israel among children was 1.5, and 4.5% among youth aged 14-18, out of a total of 5,000 multiple sclerosis cases nationwide. Children diagnosed with POMS often display various deficiencies across psychological, cognitive, sensory, and physical areas. As such, POMS poses significant challenges for parents' well-being, with heightened emotional, financial, and physical strains linked to both the immediate and long-term care requirements of their children. In this preliminary study, we examined changes over three time-points in two measures of well-being: satisfaction with life and psychological distress. In addition, the role of perceived social support (PSS) and coping flexibility was examined through a multilevel causal mediation model which suggested that PSS 1 month post-diagnosis would predict coping flexibility at 6 months post-diagnosis, which in turn would predict parents' life satisfaction and psychological distress at 12 months post-diagnosis. Methods: The research was conducted at a tertiary university-affiliated children's hospital in central Israel. Preliminary data were obtained from 36 parents at three times-points. Participants provided demographic information and filled out the following standardized self-report questionnaires: the Diener's Satisfaction with Life Scale, Kessler's inventory for measuring psychological distress (K6), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Perceived Ability to Cope with Trauma Scale (PACT) for measuring coping flexibility. Results: Over time (12 months), parents reported stable levels of PSS, coping flexibility, satisfaction with life, and psychological distress. In addition, mothers reported significantly greater PSS from friends than did fathers. Regarding the causal mediation model, greater PSS from friends at T1 was significantly associated with an increase in coping flexibility from T1 to T2. In turn, an increase in coping flexibility was associated with a decrease in psychological distress from T1 to T3 (after controlling for PSS). Yet the causal mediation path via coping flexibility to satisfaction with life was not significant. Conclusion: This preliminary study emphasizes the important role of both PSS and coping flexibility for the well-being of parents whose children are affected by POMS, a subject that merits heightened consideration among healthcare professionals dealing with long-term chronic diseases.

Incidence rate and prevalence of pediatric-onset multiple sclerosis in Sweden: A population-based register study.

BACKGROUND AND PURPOSE: Pediatric-onset multiple sclerosis (PoMS) is associated with high health care use. To plan resource allocation for this patient group, knowledge of the incidence rate and prevalence is important. However, such studies are scarce, few are population-based, and the methodology varies widely. We aimed to address this knowledge gap by performing a nationwide study of the incidence rate and prevalence of PoMS in Sweden, an area of high multiple sclerosis (MS) incidence and prevalence. METHODS: MS cases were identified by linking two nationwide registers, the National Patient Register and the Swedish MS Registry. MS cases having their first central nervous system demyelinating event or MS clinical onset before age 18 years were classified as pediatric onset. Incidence rate and prevalence were estimated annually over the study period (2006-2016) for the total population and stratified by sex and age group (<12, 12-15, and 16-17 years). Temporal trends and ratios between sexes and age groups were estimated. RESULTS: We identified 238 incident cases from 2006 to 2016, corresponding to an overall crude incidence rate of 1.12 per 100,000 person-years and an overall crude prevalence of 2.82 per 100,000 population. There was a higher incidence rate among females and the highest age category. The overall incidence rate and prevalence estimates remained stable during the study period. CONCLUSIONS: Sweden exhibits a consistently high incidence rate and prevalence of PoMS that has remained stable over time. This knowledge serves as a tool to aid in planning resource allocation and health services for this patient population.

Rituximab treatment in pediatric-onset multiple sclerosis.

BACKGROUND AND PURPOSE: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk-benefit profile of RTX in pediatric-onset multiple sclerosis are scarce. METHODS: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed. RESULTS: Sixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38-0.92) to 0.03 (95% CI 0.02-0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70-2.48) to 0.08 (95% CI 0.03-0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30-3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events. CONCLUSION: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.

Control of disease activity with large extended-interval dosing of rituximab/ocrelizumab in highly active pediatric multiple sclerosis.

Recent studies in adults suggested that extended-interval dosing of rituximab/ocrelizumab (RTX/OCR) larger than 12 months was safe and could improve safety. This was an observational cohort study of very active pediatric-onset multiple sclerosis (PoMS) (median (range) age, 16 (12-17) years) treated with RTX/OCR with 6 month standard-interval dosing (n = 9) or early extended-interval dosing (n = 12, median (range) interval 18 months (12-25)). Within a median (range) follow-up of 31 (12-63) months after RTX/OCR onset, one patient (standard-interval) experienced relapse and no patient showed disability worsening or new T2-weighted lesions. This study suggests that the effectiveness of RTX/OCR is maintained with a median extended-interval dosing of 18 months in patients with very active PoMS.

Pediatric Onset Multiple Sclerosis and Obesity: Defining the Silhouette of Disease Features in Overweight Patients.

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.

Pediatric Multiple Sclerosis: Changing the Trajectory of Progression.

PURPOSE OF REVIEW: Multiple sclerosis is a chronic inflammatory disease of the central nervous system. When seen in children and adolescents, crucial stages of brain development and maturation may be affected. Prompt recognition of multiple sclerosis in this population is essential, as early intervention with disease-modifying therapies may change developmental trajectories associated with the disease. In this paper, we will review diagnostic criteria for pediatric multiple sclerosis, outcomes, differential diagnosis, and current therapeutic approaches. RECENT FINDINGS: Recent studies have demonstrated the utility of newer structural and functional metrics in facilitating early recognition and diagnosis of pediatric MS. Knowledge about disease-modifying therapies in pediatric multiple sclerosis has expanded in recent years: important developmental impacts of earlier therapeutic intervention and use of highly effective therapies have been demonstrated. Pediatric MS is characterized by highly active disease and high disease burden. Advances in knowledge have led to early identification, diagnosis, and treatment. Lifestyle-related interventions and higher efficacy therapies are currently undergoing investigation.

Sleep, physical activity, and psychological outcomes in children and adolescents with pediatric onset multiple sclerosis.

BACKGROUND: Sleep, physical activity (PA) and sedentary behavior (SED) have bidirectional associations with mental health in children. The relationships among sleep, PA, SED, with depressive and fatigue symptoms have not been investigated in Pediatric Onset Multiple Sclerosis (POMS) but are needed to inform sleep and PA behavior change interventions. OBJECTIVES: (1) To describe sleep quality including: sleep efficiency, latency, total sleep time, number of awakenings, time in bed, and wake after sleep onset using actigraphy in children and adolescents ages 11 to 18 diagnosed with POMS, and to compare these sleep metrics to those of an age- and sex-matched non-MS group (2) To examine the relationship between time spent in sedentary, light (LIPA), moderate and vigorous PA (MVPA), sleep quality, with depression, fatigue, and quality of life in children and adolescents with POMS and an age and sex matched non-MS group. METHODS: A cross-sectional study recruited children and adolescents with POMS ages 11 to 18 years followed at a tertiary pediatric hospital (Toronto, Canada) and an age and sex matched non-MS group from the general population. Participants were consented prior to initiation of study procedures. Participants wore an Actiwatch monitor and GT3X accelerometer and completed standardized questionnaires validated to capture data on sleep disturbances, depression, fatigue, and quality of life. Objective sleep data were collected using an Actiwatch including sleep efficiency, total sleep time, number of awakenings, wake after sleep onset (WASO), and sleep latency. A GT3X accelerometer was used to collect PA data including time spent in SED, light (LPA), and moderate to vigorous (MVPA) PA. Correlational analyses and tests of difference were used to compare the groups. RESULTS: 25 POMS (21F; 16.6 years ±1.1 yrs., median Expanded Disability Status Scale (EDSS) =1.5, IQR=1) and 25 Non-MS (22 F; 16±1.3 yrs.) took part. POMS had higher BMI (T= -5.1, P<0.001) compared to Non-MS. No differences in sleep efficiency (MS mean = 87%, vs. 88%) sleep time (MS Mean = 7.3 hrs. vs. 7.4 hrs.,), WASO (MS mean=37 mins. vs. 36 mins), latency (MS mean=15 mins vs. 11 mins), SED (MS mean =763 mins. vs. 730 mins) or PA (MS, mean LPA = 68 mins. vs 60 mins; MS mean MVPA = 12.7 mins. vs. 12.4 mins). Within POMS, higher sleep efficiency was associated with more SED (SR= 0.4, p = 0.05), while higher sleep efficiency was associated with less SED in Non-MS (SR = -0.7, p< 0.0). In children with POMS, less sleep time, shorter sleep onset latency and more WASO was associated with more SED (SR range = -0.45 to -0.58, P< 0.01). Higher sleep efficiency was associated with less fatigue. Less WASO was associated with lower depression, lower fatigue (SR = 0.67, p<0.01) and better quality of life (SR= -0.6, p<0.01). Greater LPA was associated with lower sleep onset latency (-0.45, p<0.05). CONCLUSIONS: Children with POMS did not differ in Actiwatch monitored sleep quality metrics. However, within the POMS group sleep quality was associated with better fatigue, depression and QOL. Further, total sleep time, WASO and latency associated with time spent SED and LPA, which independently associate with mental health outcome. Longitudinal work should determine the temporal associations between WASO, sleep latency, sleep time, PA, and mental health outcomes and whether reallocation of specific sleep or PA behaviors (time to sleep, total sleep time, sedentary to MVPA) result in improved depression fatigue, or quality of life in children and adolescents with POMS.

Clinical and Epidemiological Findings of Pediatric Onset Multiple Sclerosis in East-Azerbaijan, Iran; A Population-based Study.

Objectives: Multiple sclerosis (MS) is among the most prevalent chronic immune-mediated inflammatory diseases. If MS onset is under 18, it is defined as pediatric-onset MS (POMS). This study aimed to determine the clinical and epidemiological aspects of POMS. Materials & Methods: This population-based study was conducted in East-Azerbaijan (EA) province and concerned POMS patients. The data concerning almost all of the POMS patients of the province was gathered from the only MS registry center in the university hospital of the Tabriz University of Medical Sciences by the end of 2017. The diagnosis of patients was based on McDonald's criteria. Results: Out of 2976 total cases of MS, eighty-five (2.85%) were POMS. The overall regional prevalence of POMS was 11.67 per 100,000 (95% CI:9.43-11.43). Sixty-seven cases were female (prevalence: 18.94 per 100,000 [95% CI:14.91-24.07], and eighteen were male (prevalence: 4.80 per 100,000 [95% CI:3.03-7.62]. The crude regional incidence in 2017 was 1.37/100,000 (95% CI:0.74-2.55). The mean age of onset was 15.81±1.33 years, with a minimum age of 12. 71.76% of the patients were diagnosed in the 16- or 17-years old age group. 7.05% had a positive family history, and 87.5% of the patients diagnosed the disease promptly. The most common first clinical presentations were blurred vision (43.75%), sensory (28.12%), cerebellar (15.62%), and brainstem (9.37%) symptoms. Conclusion: POMS is not a rare condition, and it mainly affects females. POMS prevalence increases significantly after age 15 years old, and the first manifestation of the disease is usually blurred vision.

Diagnostic challenge in children with an acquired demyelinating syndrome: an illustrative case report.

The clinical-radiological and biological overlap of the spectrum of pediatric demyelinating disorders makes the diagnostic process of a child with an acquired demyelinating syndrome truly challenging. We present a 9-year-old girl with subacute symptoms of severe decrease in bilateral visual acuity and gait ataxia. An urgent MRI showed inflammatory-demyelinating lesions affecting the periaqueductal gray matter, the cerebellar hemispheres, the area postrema as well as both optic nerves and chiasm. Likewise, multisegmental involvement of the cervical and dorsal spinal cord was found, with short and peripheral lesions. Anti myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs) were positive in cerebrospinal fluid (CSF) and weakly in serum. Oligoclonal bands (OB) were positive in CSF. Based on all this, the diagnosis of MOG antibody disease (MOGAD) with a neuromyelitis optica spectrum disorder (NMOSD)-like picture was made. Given the good clinical and radiological recovery after the acute phase treatment, and that anti MOG Abs became negative, it was decided to keep the patient without specific treatment. However, during follow-up, while the patient was asymptomatic, a control brain MRI showed the appearance of new lesions with morphology and topography suggestive of multiple sclerosis (MS). This, added to the presence of OB, made the diagnosis of pediatric-onset MS (POMS) likely. Immunosuppressive treatment was restarted with a good response since then. Unlike adult-onset MS, children with POMS may usually not have entirely typical clinical and radiological features at presentation. In many cases, the time factor and close clinical and radiological monitoring could be critical to make an accurate diagnosis.

Multiple Sclerosis-Related Dietary and Nutritional Issues: An Updated Scoping Review with a Focus on Pediatrics.

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.

The effects of online exercise training on physical functions and quality of life in patients with pediatric-onset multiple sclerosis.

BACKGROUND: Patients with pediatric-onset multiple sclerosis (PwPOMS) frequently experience motor, sensory, and cognitive problems. Although exercise is known to be effective in adult patients with MS, there are still no studies investigating the effectiveness of exercise in PwPOMS. To examine the effectiveness of online exercise training on physical activity, muscle strength, functionality, gait, fatigue, and quality of life in PwPOMS. METHODS: Twenty-one individuals were included and randomly divided into two groups. The online exercise training program (OETP) group received exercise training including aerobics, strengthening, and balance training for 8 weeks, and the control group received no intervention. Outcomes were assessed at baseline, 8 weeks, and 32 weeks. RESULTS: Significant improvements were recorded in physical activity, muscle strength, functionality, gait, fatigue, and quality of life in the OETP group after treatment (p<0.05). Between groups, the OETP group was superior to the control group in terms of physical activity, muscle strength, functionality, and quality of life (p<0.05). The OETP group remained superior to the control group in follow-up. CONCLUSION: OETP performed under the supervision of a physiotherapist is effective in PwPOMS. Even if these patients have no disabilities, it would be beneficial to refer them to rehabilitation from an early period.

First-line disease modifying treatments in pediatric-onset multiple sclerosis in Greece: therapy initiation at more advanced age is the main cause of treatment failure, in a retrospective observational study, with a cohort from a single Multiple Sclerosis Center.

OBJECTIVES: Long-term immunomodulatory therapy of pediatric onset-multiple sclerosis (POMS) is based mainly on published case series and internationally agreed guidelines. Relevant studies in the Greek population are absent from the literature. The purpose of this study is to present data on the efficacy and safety of the 1st line immunomodulatory drugs in the treatment of POMS patients. MATERIALS AND METHODS: The present study included 27 patients meeting the IPMSSG criteria for POMS and who are monitored at the outpatient clinic of the Multiple Sclerosis and Demyelinating Diseases Unit (MSDDU), of the 1st Neurological Department, University Hospital of Aeginition. All patients received 1st line immunomodulatory drugs as initial therapy. Clinical, laboratory, and imaging parameters of the disease were recorded before and after treatment. RESULTS: Post-treatment, a significant reduction of the relapse number (mean ± SD: 2.0 ± 1.0 vs 1.2 ± 1.6, p = 0.002), EDSS progression (mean ± SD: 1.5 ± 0.8 vs 0.9 ± 0.7, p = 0.005) and ARR (mean ± SD: 1.5 ± 0.7 vs 0.4 ± 0.5, p = 0.0001) was observed, while no changes were observed in the EDSS score, (mean ± SD: 1.8 ± 0.6 vs 1.9. 0.6, p = 0.60). Advanced age at treatment initiation increased the risk for drug discontinuation before 24 months of therapy (HR = 0.6, 95% CI (0.35-0.99), p = 0.04). CONCLUSIONS: Most pediatric patients are forced to switch to either more efficacious 1st line or 2nd line drugs. Additionally, our study suggests that older age at the time of the 1st line treatment initiation, contributes to earlier drug discontinuation.