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Background: In children, multiple sclerosis (MS) is the ultimate diagnosis in only 1/5 to 1/3 of cases after a first episode of central nervous system (CNS) demyelination. As the visual pathway is frequently affected in MS and other CNS demyelinating disorders (DDs), structural retinal imaging such as optical coherence tomography (OCT) can be used to differentiate MS. Objective: This study aimed to investigate the utility of machine learning (ML) based on OCT features to identify distinct structural retinal features in children with DDs. Methods: This study included 512 eyes from 187 (neyes = 374) children with demyelinating diseases and 69 (neyes = 138) controls. Input features of the analysis comprised of 24 auto-segmented OCT features. Results: Random Forest classifier with recursive feature elimination yielded the highest predictive values and identified DDs with 75% and MS with 80% accuracy, while multiclass distinction between MS and monophasic DD was performed with 64% accuracy. A set of eight retinal features were identified as the most important features in this classification. Conclusion: This study demonstrates that ML based on OCT features can be used to support a diagnosis of MS in children. [ABSTRACT FROM AUTHOR]

Objective: Fatigue is common in pediatric-onset multiple sclerosis (POMS), yet causal factors and correlates of fatigue are poorly understood in this population. A 2016 review suggested an association between fatigue and emotional difficulties, sleep disturbance, and reduced quality of life in POMS. Information regarding the potential association between fatigue and cognitive challenges is limited and mixed. Through this systematic review, we searched for relationships between fatigue, cognition, and mental health. Participants and Methods: Systematic review methodology and PRISMA guidelines were followed. Five electronic databases were searched: Ovid: Medline, Ovid: EMBASE, Ovid: PsycInfo, Web of Science and CINAHL. Search terms were specific to each database. Reference lists of included studies were also hand-searched. We included empirical studies that were published in English after 2001, included a sample with confirmed diagnoses of POMS using McDonald criteria, and measured fatigue, cognition and clinical factors including mental health outcomes. Cognition had to be assessed using a standardized assessment tool and studies must have examined associations between outcomes of interest either descriptively or by assessing bivariate or multivariate relationships. Covidence was used to complete the screening, extraction, and quality assessment. Two independent researchers (i.e., T.L.F, and/or S.D, and/or M.G) reviewed each paper included in the title and abstract screen and full text review. S.D and M.G completed the extraction and quality assessments. Conflicts at all stages were resolved by the lead author (T.L.F). The University of Adelaide JBI critical appraisal checklist for analytical cross-sectional studies was used to ensure the scientific rigor of each included study. Sample characteristics and measures of fatigue, clinical and cognitive variables were extracted. A narrative synthesis was conducted. Results: We identified 1025 abstracts through our initial search and retained 119 articles for full text review. One hundred and six of these studies were excluded during the full text review including six studies which did not examine the relationship between the outcomes of interest. Fifty-one additional studies were identified from hand-searching reference lists of included studies, of which 24 were retained for full text review. A total of 15 studies were extracted and analyzed. Overall, a positive relationship was found between fatigue and mental health outcomes (i.e., anxiety and depression), whereas results were mixed regarding the association between fatigue and performance-based measures of cognition as well as fatigue and other clinical characteristics (e.g., disease duration, EDSS, treatment with DMDs, relapse rate, age at disease onset). In some studies, fatigue and executive functioning performance were negatively related; the relationship was less clear in others (e.g., both fatigued and non-fatigued MS patients demonstrated cognitive challenges, an association between fatigue and executive functioning was identified at follow-up but not baseline). Eleven of the 15 included studies (73%) did not identify associations between fatigue and cognition. Conclusions: While studies are mixed, fatigue in children has been associated with aspects of cognition. Understanding the relationship between fatigue, cognition, and mental health and identifying gaps in the existing literature, have implications for informing interventions for this clinical population. [ABSTRACT FROM AUTHOR]

See Hacohen et al. (doi:10.1093/awx075) for a scientific commentary on this article. Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants. Fifty-three participants with demyelinating syndromes eventually received a diagnosis of paediatric-onset multiple sclerosis. Diffusion tensor imaging measures properties of water diffusion through tissue, which normally becomes increasingly restricted and anisotropic in the brain during childhood and adolescence, as fibre bundles develop and myelinate. In the healthy paediatric participants, our data demonstrate the expected trajectory of more restricted and anisotropic white matter diffusivity with increasing age. However, in participants with multiple sclerosis, fractional anisotropy decreased and mean diffusivity of non-lesional, normal-appearing white matter progressively increased after clinical presentation, suggesting not only a failure of age-expected white matter development but also a progressive loss of tissue integrity. Surprisingly, patients with monophasic disease failed to show age-expected changes in diffusion parameters in normal-appearing white matter, although they did not show progressive loss of integrity over time. Further analysis demonstrated that participants with monophasic disease experienced different post-onset trajectories in normal-appearing white matter depending on their presenting phenotype: those with acute disseminated encephalomyelitis demonstrated abnormal trajectories of diffusion parameters compared to healthy paediatric participants, as did patients with non-acute disseminated encephalomyelitis presentations associated with lesions in the brain at onset. Patients with monofocal syndromes such as optic neuritis, transverse myelitis, or isolated brainstem syndromes in whom multifocal brain lesions were absent, showed trajectories more closely approximating normal-appearing white matter development. Our findings also suggest the existence of sexual dimorphism in the effects of demyelinating syndromes on normal-appearing white matter development. Overall, we demonstrate failure of white matter maturational changes and progressive loss of white matter integrity in paediatric-onset multiple sclerosis, but also show that even a single demyelinating attack-when associated with white matter lesions in the brain-negatively impacts subsequent normal-appearing white matter development. [ABSTRACT FROM AUTHOR]

ABSTRACT OBJECTIVE To investigate differences in region-specific gray matter (GM) damage between adults with pediatric-onset (PO) multiple sclerosis (MS) and adult-onset (AO) MS. METHODS Twenty-four relapsing-remitting (RR) adults with POMS (mean age = 35 years, mean disease duration = 18.4 years) were compared to 23 age-matched (AOA, mean age = 33.9 years, mean disease duration = 2.4 years) and 24 disease-duration matched (AOD, mean age = 45.9 years, mean disease duration = 18.5 years) RRMS adults who developed MS after the age of 18. Three-dimensional-T1-weighted images were acquired on a 1.5 T MRI. Image analysis was conducted using voxel-based morphometry (Statistical Parametric Mapping 8). RESULTS There were no regional GM atrophy differences between POMS and AODMS groups. No regional GM atrophy differences were found between POMS and AOAMS patients when disease duration was included as a covariate. CONCLUSIONS Regional GM differences were not found between POMS adults and MS controls matched for age or disease duration. Although of limited sample size, these findings suggest that there are no regional GM atrophy differences between RR POMS and AOMS. [ABSTRACT FROM AUTHOR]