Markus Breu

Pediatric-onset multiple sclerosis (POMS) represents the earliest manifestation of chronic inflammatory demyelination of the central nervous system and accounts for only a small proportion of all multiple sclerosis (MS) cases

Background/Objectives: Pediatric-onset multiple sclerosis (POMS) accounts for 3–10% of all multiple sclerosis (MS) cases and represents the earliest manifestation of chronic autoimmune demyelination of the central nervous system. While increasing incidence rates have been reported in Europe, no regional data exist for Austria. This study aimed to determine the incidence, prevalence, and clinical characteristics of POMS in Tyrol, Austria, over a 10-year period. Methods: All patients diagnosed with MS before 18 years of age between 1 January 2015 and 31 December 2024, were included. Diagnoses were confirmed according to the 2010 and 2017 McDonald criteria and re-evaluated using the 2024 revisions. Demographic, clinical, cerebrospinal fluid (CSF), and MRI data were systematically reviewed. Incidence and prevalence rates were calculated with 95% confidence intervals (CI) using the exact Clopper–Pearson method. Results: Twenty-nine patients were newly diagnosed with POMS (26 female; median age 15 years, range 11–17), corresponding to a pooled 10-year incidence of 2.19 per 100,000 person-years (95% CI 1.47–3.14) and a point prevalence of 6.7 per 100,000 children (95% CI 3.1–12.8) as of 31 December 2024. Sensory (55%) and visual (31%) symptoms predominated at onset. Pleocytosis was found in 93%, and all CSF samples showed positive oligoclonal bands. MRI revealed supratentorial lesions in 97%, infratentorial in 69%, and spinal in 73%. The median annualized relapse rate was 0.67, and all patients had an EDSS of 0 at last follow-up. Conclusions: This first regional analysis of pediatric-onset MS in Austria demonstrates a higher incidence than most previously reported European cohorts, positioning Tyrol within the upper European range. The findings highlight the impact of early recognition, structured diagnostics, and timely initiation of disease-modifying therapy on favorable short-term outcomes.

Background: Therapeutic plasma exchange (TPE) is an established treatment for immune-mediated neurological diseases in adults, but pediatric-specific data remain limited. This retrospective single-center study investigates the safety, complication profile, and clinical outcomes of TPE in children with pediatric neuroimmunological disorders (PNID). Methods: Medical records of pediatric patients who underwent TPE at the Medical University of Vienna between April 2006 and October 2022 were reviewed. Inclusion criteria required TPE initiation before the age of 18 years. Data collected included diagnoses, pre-TPE therapy, TPE characteristics, complications and clinical outcomes based on retrospective documentation. Results: A total of 53 patients (60% female, median age 13 years) were included and underwent 378 TPE procedures. Most common diagnoses were pediatric-onset multiple sclerosis (23%) and autoimmune encephalitis (19%). TPE was preceded by corticosteroids and/or intravenous immunoglobulin in 83% of patients. Complications occurred in 81% of patients and 23% of procedures and were predominantly rated mild to moderate (CTCAE I–II), including nausea, hypotension, and catheter-related issues. Severe complications (CTCAE III–IV) occurred in 11% of patients; no deaths were reported. Clinical improvement was documented in 84% of patients, with 42% showing significant improvement. Conclusions: TPE is a generally well-tolerated and effective treatment in PNID, with a high rate of clinical improvement and predominantly mild complications. The higher reported complication rate compared to other studies likely reflects more comprehensive documentation of minor adverse events. These findings support the use of TPE in PNID, particularly in cases refractory to first-line therapies. Standardized reporting of outcomes and complications is essential to improve comparability across studies and guide future clinical practice.

Background: Therapeutic plasma exchange (TPE) is an established treatment for im-mune-mediated neurological diseases in adults, but pediatric-specific data remain limited. This retrospective single-center study investigates the safety, complication profile, and clinical outcomes of TPE in children with pediatric neuroimmunological disorders (PNID). Methods: Medical records of pediatric patients who underwent TPE at the Medical University of Vienna between April 2006 and October 2022 were reviewed. Inclusion criteria required TPE initiation before the age of 18 years. Data collected included di-agnoses, pre-TPE therapy, TPE characteristics, complications and clinical outcomes based on retrospective documentation. Results: A total of 53 patients (60% female, median age 13 years) were included and underwent 378 TPE procedures. Most common diagnoses were pediatric-onset multiple sclerosis (23%) and autoimmune encephalitis (19%). TPE was preceded by corticosteroids and/or intravenous immunoglobulin in 83% of patients. Complications occurred in 81% of patients and 23% of procedures and were predominantly rated mild to moderate (CTCAE I–II), including nausea, hypotension, and catheter-related issues. Severe complications (CTCAE III–IV) occurred in 11% of patients; no deaths were reported. Clinical improvement was documented in 84% of patients, with 42% showing significant improvement. Conclusion: TPE is a generally well-tolerated and effective treatment in PNID, with a high rate of clinical improvement and predominantly mild complications. The higher reported complication rate compared to other studies likely reflects more comprehensive documentation of minor adverse events. These findings support the use of TPE in PNID, particularly in cases refractory to first-line therapies. Standardized reporting of outcomes and complications is essential to improve comparability across studies and guide future clinical practice.

Acquired demyelinating syndromes associated with serum antibodies against myelin oligodendrocyte glycoprotein have been recognized as MOG-IgG-associated disorders (MOGADs). Patients with MOGAD show distinct features compared with individuals with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSDs). Up to 50% of patients experience relapsing disease courses, usually associated with persisting high MOG-IgG titers. However, further biomarkers are needed to discriminate monophasic from multiphasic MOGAD. Recently, lowered levels of tumor necrosis factor α-induced protein 3 (TNFAIP3, or A20) have been shown to be associated with attack in a small group of pediatric patients with MOGAD. The aim of this study was to evaluate A20 as a possible biomarker discriminating attack from remission in a larger cohort of pediatric patients with MOGAD. In this cohort study, we tested 162 serum samples from 62 pediatric patients with MOGAD for A20 levels using commercially available ELISA kits. To compare A20 levels with those in non-MOGAD patients, we further included 46 serum samples from 37 pediatric patients with MS, NMOSD with AQP4-IgG, clinically isolated syndrome, or other neurologic disorders. In grouped analysis, A20 serum levels were significantly lower during attack compared with remission in patients with monophasic MOGAD. In grouped analysis of patients with multiphasic MOGAD, there was no such significant difference in A20 levels at attack vs remission. Among patients (n = 10) with paired attack and remission time points, there was a significant difference in A20 levels (p = 0.029). A20 levels were tendentially higher in patients on immunomodulatory treatments compared with untreated patients. Reflecting the anti-inflammatory role of A20, its relative decrease during attacks might even start before the patient's first symptoms. Thus, longitudinal evaluation of A20 at (yet to identifiable) standardized time points might have prognostic implications. Serum A20 levels in pediatric patients with MOGAD may help to distinguish attacks from remission in monophasic disease courses. Consequently, A20 needs to be prospectively investigated in standardized multicentric longitudinal study designs, with a focus on diagnostic, prognostic, and therapeutic implications.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1_381-452 region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1_381-452-specific antibodies can serve as a biomarker to identify at-risk individuals for MS. We quantify EBNA-1_381-452-specific antibody titers from 324 relapsing-remitting MS patients and 324 matched controls in longitudinal follow-up plasma samples, starting from the individual’s EBV-seroconversion. In MS patients, significantly elevated EBNA-1_381-452-specific IgG titers are identified that are increased already as early as nine months after EBV-seroconversion (OR:5.7; 95% CI: 4.1-8.1; P < 0.0001) and a median 5.4 years prior to MS diagnosis. Especially, the presence of continuously high EBNA-1_381-452-specific antibody titers is associated with a more rapid MS diagnosis after EBV-seroconversion (P < 0.0001). Thus, the quantification of EBNA-1_381-452-specific IgG antibody levels may provide a prognostic biomarker to determine the individual’s risk for the diagnosis of MS.

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.