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This article, published in the journal Neuropediatrics, examines the outcome and brain volume changes over time in children with MOG-encephalitis (MOG-E), a rare clinical phenotype of MOGAD. The study included 21 children with MOG-E, who presented with symptoms such as encephalopathy, headache, focal neurological signs, seizures, or CSF pleocytosis. The results showed that the majority of children had a good clinical outcome, with resolution of MRI changes and decreasing MOG antibodies over time. However, brain volumetry measurements indicated a decrease in whole brain volume, particularly in gray matter, after onset. [Extracted from the article]

This article, published in the journal Neuropediatrics, discusses the use of MRI imaging in 10 children with enterovirus-associated acute flaccid myelitis (AFM). AFM is characterized by limb weakness, decreased muscle tone, and cranial nerve involvement, and is predominantly caused by enterovirus infections. The MRI findings in these patients showed longitudinal spinal cord lesions mainly affecting the gray matter, as well as lesions in the brainstem and cerebellum. Supratentorial involvement was uncommon. The study confirms previous findings about the MRI imaging findings in enterovirus-associated AFM. [Extracted from the article]

This article, published in the journal Neuropediatrics, explores the clinical course and final diagnosis of Acute Disseminated Encephalomyelitis (ADEM) without MOG antibodies. ADEM is a rare inflammatory disorder of the central nervous system (CNS), and MOG antibodies are found in 50% of children with ADEM. The study collected data from 40 children with MOG-negative ADEM and found that in 72.5% of cases, the diagnosis remained ADEM at the last follow-up. However, in 27.5% of cases, the diagnosis was revised to conditions such as multiple sclerosis (MS), glioblastoma, CNS vasculitis, leukoencephalopathy, and autoimmune encephalitis. The study highlights the importance of considering alternative diagnoses in cases of MOG-negative ADEM. [Extracted from the article]

Background: We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity., Objective: To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM., Patients and Methods: In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n = 34), MS (n = 20), NMOSD (n = 5) and in double seronegative children (n = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test., Results: Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P < 0.001)., Conclusion: Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD., Competing Interests: Declaration of competing interest Ines El Naggar: received travel grants from UCB. Eva-Maria Wendel: received travel grants from UCB. Annikki Bertolini: received travel grants from UCB. Markus Reindl: was supported by research grants from the Austrian Science Fund (FWF projects P32699 and IPN170), the Austrian Research Promotion Agency and Roche. Deiva Kumaran: received honoraria for invited talks for Biogen, Alexion, Sanofi and serves as consultant for Novartis and Horizon. Rinze Neuteboom: participated in pharmacological studies in demyelinating disorders with Roche, Horizon, Novartis and Sanofi-Genzym. Funding from Dutcht MS research foundation, Dreams Foundation, Postcode Loterij, Vrienden Sophia Foundation. Kevin Rostásy: received honoraria for invited talks from Horizon, UCB and serves as a consultant in the OperettaII study. Robert Cleaveland, Andreas Panzer, Sandy Molenaar, Laetitia Giorgi, Michael Karenfort, Charlotte Thiels, Zuzana Libá, Matthias Baumann, Steffen Leiz, Adela Della Marina, Jan G. Hengstler, members of the BIOMARKER study group (Steffen Berweck, Astrid Blaschek, Matthias Eckenweiler, Astrid Eisenkölbl, Tobias Geis, Annette Hackenberg, Verena Kraus, Heinz Lauffner, Daniela Pohl, Martin Pritsch, Michela Salandin, Torsten Sandrieser, Mareike Schimmel, Christoph von Kleist-Retzow, Gert Wiegand): no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Glial fibrillary acidic protein (GFAP) antibodies (abs) have been described primarily in adults with a spectrum of autoimmune-mediated diseases. In children, data on clinical and neuroradiologic features of children with autoimmune GFAP astrocytopathy are limited. The aim of this study was to describe the clinical and radiologic features in children with GFAP-ab-associated diseases., Methods: We retrospectively recruited children from 13 clinical centers between 2020 and 2023 who (1) tested positive for GFAP-ab in serum and/or CSF and (2) of whom a complete clinical and MRI data set was available., Results: We identified and included 15 children (5 girls, 10 boys). The median age at onset was 9.9 years (range: 2-16 years). All children presented with features of AE or meningitis, acute cerebellitis, or transverse myelitis. CSF pleocytosis was common (13/15, median 245 cells/μL), and 13 (87%) of 15 harbored GFAP-abs in their CSF, 8 (53%) of whom did not have detectable GFAP-abs in their serum. MRI was abnormal in 15 (100%) of 15 children: Specific patterns included confluent lesions in the pons or caudate nucleus (11/15; 73%), peri-aqueductal regions (13/15; 87%), and spinal cord (6/10; 60%). 12 children had a favorable outcome (mRS score of

Background and Objectives: Acute disseminated encephalomyelitis (ADEM) is the most common phenotype in pediatric myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease. A previous study demonstrated impaired brain growth in ADEM. However, the effect of MOG antibodies on brain growth remains unknown. Here, we performed brain volume analyses in MOG-positive and MOG-negative ADEM at onset and over time., Methods: In this observational cohort study, we included a total of 62 MRI scans from 24 patients with ADEM (54.2% female; median age 5 years), of which 16 (66.7%) were MOG positive. Patients were compared with healthy controls from the NIH pediatric MRI data repository and a matched local cohort. Mixed-effect models were applied to assess group differences and other relevant factors, including relapses., Results: At baseline and before any steroid treatment, patients with ADEM, irrespective of MOG antibody status, showed reduced brain volume compared with matched controls (median [interquartile range] 1,741.9 cm3 [1,645.1-1,805.2] vs 1,810.4 cm 3 [1,786.5-1,836.2]). Longitudinal analysis revealed reduced brain growth for both MOG-positive and MOG-negative patients with ADEM. However, MOG-negative patients showed a stronger reduction (-138.3 cm 3 [95% CI -193.6 to -82.9]) than MOG-positive patients (-50.0 cm 3 [-126.5 to -5.2]), independent of age, sex, and treatment. Relapsing patients (all MOG positive) showed additional brain volume loss (-15.8 cm 3 [-68.9 to 37.3])., Discussion: Patients with ADEM exhibit brain volume loss and failure of age-expected brain growth. Importantly, MOG-negative status was associated with a more pronounced brain volume loss compared with MOG-positive patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Transverse myelitis (TM) occurs isolated or within other acquired demyelinating syndromes (ADS) such as neuromyelitis optica spectrum disorders (NMOSD), multiple sclerosis (MS) or myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD)., Objective: To describe and compare clinical and MRI features of children with ADS presenting with TM grouped according to antibody status and diagnosis of MS and NMOSD., Patients and Methods: Children with TM, radiological involvement of the myelon, MOG and aquaporin-4 antibody status were elegible., Results: 100 children were identified and divided into MOGAD (n=33), NMOSD (n=7), double seronegative TM (n=34), and MS (n=26). MOGAD children had mainly acute disseminated encephalomyelitis + TM/ longitudinally extensive TM (LETM) (42%) or isolated LETM (30%). In MOGAD, LETM was present in more than half of all children (55%) with predominant involvement of only the grey matter (73%). Leptomeningeal enhancement was highly predictive of MOGAD (16/30; p=0.003). In MS patients spinal MRI showed single (50%) or multiple short lesions (46%) with involvement of grey and white matter (68%). Double seronegative children presented with LETM (74%) and brain lesions were less frequent compared to the other groups (30%)., Conclusion: Children with ADS presenting with TM reveal important radiological differences such as LETM with predominant involvement of spinal grey matter and leptomeningeal enhancement in MOGAD., Competing Interests: Declaration of Competing Interest IN, RC, EW, ABe, KS, CTh, ADM, MSch, SL, AWP, NB, BB, SB, MBl, ABl, CC, KD, ME, AE, WF, TG, AH, KH, JK, BK, MN, DP, MP, MSa, TS, SS, JS, GW report no conflict of interest. Michael Karenfort served as consultant for Novartis. Christian Lechner has received compensation for consulting services from Roche. Matthias Baumann has received compensation for consulting services from Sanofi. Markus Reindl was supported by a research support from Euroimmun and Roche. The University Hospital and Medical University of Innsbruck (Austria, employer of Dr. Reindl) receive payments for antibody assays (MOG-, AQP4-, and other autoantibodies) and for MOG-and AQP4-antibody validation experiments organised by Euroimmun (Lübeck, Germany). Kevin Rostásy served as a consultant for the PARADIGM-Study/Novartis without payment and received honoraria for lectures given for MERCK. Andrea Klein did advisory activities for Novartis Gene Therapies, Biogen, Pfizer, Roche, Sarepta and Santhera and received speakers honoraria from Biogen, Roche, Sarepta and Santhera., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To describe the presentations, radiologic features, and outcomes of children with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs)., Methods: Identification of children fulfilling the diagnostic criteria for possible autoimmune encephalitis (AE) and testing positive for serum MOG abs. Chart review and comprehensive analysis of serum MOG abs using live cell assays and rat brain immunohistochemistry., Results: Ten children (4 girls, 6 boys) with AE and serum MOG abs were identified. The median age at onset was 8.0 years (range: 4-16 years). Children presented with a combination of encephalopathy (10/10), headache (7/10), focal neurologic signs (7/10), or seizures (6/10). CSF pleocytosis was common (9/10, median 80 white cell count/μL, range: 21-256). Imaging showed cortical and deep gray matter involvement in all in addition to juxtacortical signal alterations in 6/10 children. No involvement of other white matter structures or contrast enhancement was noted. MOG abs were detected in all children (median titer 1:640; range: 1:320-1:10,540). Nine children had a favorable outcome at discharge (modified Rankin scale of < 2). Five of 10 children had up to 3 additional demyelinating relapses associated with persisting MOG abs. One child had NMDA receptor (NMDAR) abs at initial presentation. A second child had a third demyelinating episode with MOG abs with overlapping NMDAR encephalitis., Discussion: AE associated with serum MOG abs represents a distinct form of autoantibody-mediated encephalitis in children. We therefore recommend including MOG abs testing in the workup of children with suspected AE., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Paediatric multiple sclerosis (pedMS) patients at a single site were shown to have reduced brain volumes and failure of age-expected brain growth compared to healthy controls. However, the precise time of onset of brain volume loss remains unclear., Objective: To longitudinally study brain volumes in a multi-centre European cohort at first presentation and after 2 years., Methods: Brain volumes of high-resolution magnetic resonance imaging (MRI) data from 37 pedMS patients at first presentation prior to steroid therapy and at 2-year follow-up ( n = 21) were compared to matched longitudinal MRI data from the NIH Paediatric MRI Data Repository., Results: Patients showed significantly reduced whole brain, grey and white matter and increased ventricular volumes at initial presentation and at follow-up compared to controls. Over 2 years, patients exhibited significant reduction of whole brain and white matter volumes, accompanied by increased ventricular volume. Brain volume loss at follow-up correlated with a higher number of infratentorial lesions, relapses and an increased Expanded Disability Status Scale (EDSS) score., Conclusions: In pedMS patients, brain volume loss is present already at first clinical presentation and accelerated over 2 years. Increased disease activity is associated with more severe brain volume loss. MRI brain volume change might serve as an outcome parameter in future prospective pedMS studies.

Objective: Software-based devices have increasingly become an important part of several clinical scenarios. Due to their critical impact on human life, medical devices have very strict safety requirements. It is therefore necessary to apply verification methods to ensure that the safety requirements are met. Verification of software-based devices is commonly limited to the verification of their internal elements without considering the interaction that these elements have with other devices as well as the application environment in which they are used. Medical guidelines define clinical procedures, which contain the necessary information to completely verify medical devices. The objective of this work was to incorporate medical guidelines into the verification process in order to increase the reliability of the software-based medical devices., Materials and Methods: Medical devices are developed using the model-driven method deterministic models for signal processing of embedded systems (DMOSES). This method uses unified modeling language (UML) models as a basis for the development of medical devices. The UML activity diagram is used to describe medical guidelines as workflows. The functionality of the medical devices is abstracted as a set of actions that is modeled within these workflows. In this paper, the UML models are verified using the UPPAAL model-checker. For this purpose, a formalization approach for the UML models using timed automaton (TA) is presented., Results: A set of requirements is verified by the proposed approach for the navigation-guided biopsy. This shows the capability for identifying errors or optimization points both in the workflow and in the system design of the navigation device. In addition to the above, an open source eclipse plug-in was developed for the automated transformation of UML models into TA models that are automatically verified using UPPAAL., Conclusions: The proposed method enables developers to model medical devices and their clinical environment using clinical workflows as one UML diagram. Additionally, the system design can be formally verified automatically.