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Background: Efferent visual dysfunction in children could lead to impaired quality of life at home and school. Eye-tracking can detect subtle efferent dysfunction missed on bedside examination but has not been validated in the pediatric multiple sclerosis population. Objective: We sought to determine the feasibility of eye-tracking in children and associations with multiple sclerosis. Methods: Participants meeting criteria for pediatric multiple sclerosis without acute efferent vision abnormalities and healthy controls were recruited. Multiple sclerosis participants underwent a clinical assessment and saccade and antisaccade testing paradigms. Intraclass correlation coefficients were generated for intertest repeatability. Adjusting for age and intereye correlations, generalized estimating equations compared latencies with case status, Expanded Disability Status Scale and Symbol Digit Modalities Test (SDMT) scores. Results: We eye-tracked 15 children with multiple sclerosis (n = 30 eyes, mean age 15.6 ± 2.1, mean disease duration 3.9 years, median Expanded Disability Status Scale 1.5) compared to 6 healthy controls (n = 12 eyes, age 14.3 ± .95). The intraclass correlation coefficient for repeated trials was 0.85. Adjusting for age, saccadic latency was 60 milliseconds (ms) longer for cases than controls (95% confidence interval = 26.4, 93.8; P = .0005). For antisaccadic latency, we observed a similar trend of 60 ms longer for cases than controls (P = .06). Conclusion: Eye-tracking is a short noninvasive examination, and high intertest repeatability supports use of eye-tracking technology in pediatric multiple sclerosis. Longer saccadic latencies were seen in children with multiple sclerosis despite short disease duration and low Expanded Disability Status Scale scores. [ABSTRACT FROM AUTHOR]

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588). Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10−16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10−16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS. [ABSTRACT FROM AUTHOR]

Introduction: The profile of psychiatric disorders associated with multiple sclerosis (MS) may differ in children. We aimed to assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa. Patients and methods: We analyzed linked English Hospital Episode Statistics, and mortality data, 1999-2011. Cohorts were constructed of children admitted with MS and other central nervous system (CNS) demyelinating diseases. We searched for any subsequent episode of care with psychiatric disorders in these cohorts and compared to a reference cohort. Results: Children with CNS demyelinating diseases had an increased rate of psychotic disorders (rate ratio (RR) = 5.77 (95% confidence interval (CI) = 2.48-11.41)); anxiety, stress-related, and somatoform disorders (RR = 2.38 (1.39-3.81)); intellectual disability (RR = 6.56 (3.66-10.84)); and other behavioral disorders (RR = 8.99 (5.13-14.62)). In analysis of the pediatric MS cohort as the exposure, there were elevated rates of psychotic disorders (RR = 10.76 (2.93-27.63)), mood disorders (RR = 2.57 (1.03-5.31)), and intellectual disability (RR = 6.08 (1.25-17.80)). In reverse analyses, there were elevated rates of a recorded hospital episode with CNS demyelinating disease after a previous recorded episode with anxiety, stress-related, and somatoform disorders; attention-deficit hyperactivity disorder (ADHD); autism; intellectual disability; and other behavioral disorders. Conclusion: This analysis of a national diagnostic database provides strong evidence for an association between pediatric CNS demyelinating diseases and psychiatric disorders, and highlights a need for early involvement of mental health professionals. [ABSTRACT FROM AUTHOR]

Background: Patients with paediatric-onset multiple sclerosis (POMS) could be at an increased risk for cognitive impairment (CI), given the potential harmful effects of disease activity in neurodevelopment. However, there is scarce information on their long-term cognitive outcomes. Objective: To compare the prevalence and profile of CI between adults with a history of POMS and those with classic, adult-onset multiple sclerosis (AOMS). Methods: Cognitive performance was assessed through the Brief Repeatable Battery (BRB) and the Stroop Test in consecutive patients referred to six Italian MS centres. CI was defined as impairment in ≥2 cognitive domains. Results: In all, 119 patients with POMS and 712 with AOMS were included in this analysis. The prevalence of CI was 48.0% in AOMS, 44.5% in POMS; with similar neuropsychological profile between the two groups. However, when adjusting for current age, we found a significantly increased risk for CI (odds ratio (OR) = 1.71; p = 0.02) and for impairment in information processing speed (OR = 1.86; p < 0.01) in patients with POMS. A higher Expanded Disability Status Scale (EDSS) was also identified in POMS (p = 0.03) compared with AOMS patients. Conclusion: Patients with a history of POMS appear to be at higher risk of physical and cognitive disability than AOMS patients, after correcting for age effects, with particular involvement of information processing speed. [ABSTRACT FROM AUTHOR]

Background: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, <4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging). The validated Block Kids Food Screener questionnaire was administered 2011–2016. Chi-squared test compared categorical variables, Kruskal–Wallis test compared continuous variables, and multivariable logistic regression analysis was performed. Results: In total, 312 cases and 456 controls were included (mean ages 15.1 and 14.4 years). In unadjusted analyses, there was no difference in intake of fats, proteins, carbohydrates, sugars, fruits, or vegetables. Dietary iron was lower in cases (p = 0.04), and cases were more likely to consume below recommended guidelines of iron (77.2% of cases vs 62.9% of controls, p < 0.001). In multivariable analysis, iron consumption below recommended guidelines was associated with MS (odds ratio = 1.80, p < 0.01). Conclusion: Pediatric MS cases may be less likely to consume sufficient iron compared to controls, and this warrants broader study to characterize a temporal relationship. No other significant difference in intake of most dietary factors was found. [ABSTRACT FROM AUTHOR]

We delineate the clinical characteristics, incidence, and prevalence of pediatric-onset multiple sclerosis in Abu Dhabi, United Arab Emirates, from 2010 to 2014. Eighty-two patients (65% female) were identified. Fifty-three (64.6%) were Emiratis (45 from Abu Dhabi and 8 from 5 other emirates) and 29 were expatriates. Mean age of onset was 15.9 years overall, 15.3 years in males and 16.3 years in females. Patients with onset before age 12 years presented with visual symptoms while those with onset after age 12 years presented with a mixture of visual, motor and sensory symptoms. Interferon beta-1a was the most frequently used disease-modifying therapy (48%). In Abu Dhabi Emirati nationals, the age- and sex-adjusted prevalences were 26/100 000 for males and 36/100 000 for females. The total incidence in Emirati nationals from 2010 to 2014 was 2.3/100 000 for ages 10 to 14 years and 7.2/100 000 for ages 15 to 19 years. By comparison with international cohorts, the incidence of pediatric-onset multiple sclerosis in Abu Dhabi is higher whereas gender distribution is similar. [ABSTRACT FROM AUTHOR]

Background: Adherence to disease-modifying therapies (DMTs) in pediatric multiple sclerosis (MS) is not well understood. We examined the prevalence and risk factors for poor adherence in pediatric MS. Methods: This cross-sectional study recruited youth with MS from 12 North American pediatric MS clinics. In addition to pharmacy-refill data, patients and parents completed self-report measures of adherence and quality of life. Additionally, patients completed measures of self-efficacy and well-being. Factor analysis and linear regression methods were used. Results: A total of 66 youth (mean age, 15.7 years) received MS DMTs (33% oral, 66% injectable). Estimates of poor adherence (i.e. missing >20% of doses) varied by source: pharmacy 7%, parent 14%, and patient 41%. Factor analysis yielded two composites: adherence summary and parental involvement in adherence. Regressions revealed that patients with better self-reported physical functioning were more adherent. Parents were more likely to be involved in adherence when their child had worse parentreported PedsQL School Functioning and lower MS Self-Efficacy Control. Oral DMTs were associated with lesser parental involvement in adherence. Conclusion: Rates of non-adherence varied by information source. Better self-reported physical functioning was the strongest predictor of adherence. Parental involvement in adherence was associated with worse PedsQL School Functioning and lower MS Self-Efficacy-measured confidence in controlling MS. [ABSTRACT FROM AUTHOR]

Background: The study of cognitive reserve (CR) in relationship with cognitive impairment (CI) in pediatric-onset multiple sclerosis (POMS) may provide cues to identifying subjects at higher risk of impairment and scope for therapeutic strategies. Objectives: To assess the potential impact of CR on cognition in a cohort of POMS patients. Methods: In all, 48 POMS patients were followed up for 4.7 ± 0.4 years. CI was defined as the failure of ⩾3 tests on an extensive neuropsychological battery. Change of neuropsychological performance was assessed through the Reliable Change Index (RCI) method. At baseline, CR was estimated by measuring the intelligence quotient (IQ). The relationships were assessed through multivariable regression analyses. Results: At baseline, CI was detected in 14/48 (29.2%) patients. Two out of 57 healthy control (HC; 3.5%) met the same criteria of CI (p < 0.001). A deteriorating cognitive performance using the RCI method was observed in 18/48 patients (37.6%). Among the 34 cases who were cognitively preserved at baseline, a higher reserve predicted stable/improving performance (odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.03–1.20; p = 0.006). Conclusion: Our results suggest that higher CR in POMS patients may protect from CI, particularly in subjects with initial cognitive preservation, providing relevant implications for counseling and rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Neurogenic lower urinary tract dysfunction (LUTD) in multiple sclerosis (MS) is highly prevalent in adults, but has not previously been described in paediatric MS. A total of 24 consecutive children with newly diagnosed MS were prospectively assessed for bladder and bowel problems early after diagnosis. Five of 24 children (21%) showed LUTD during assessment. One of these patients did not report voiding complaints. This high prevalence of LUTD indicates that all recently diagnosed patients with paediatric MS should be evaluated early in their disease and treated for urinary problems in order to prevent potential damage to the upper urinary tract. [ABSTRACT FROM AUTHOR]

Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. [ABSTRACT FROM AUTHOR]

The emotional and behavioral problems associated with pediatric multiple sclerosis remain unclear. Participants with pediatric multiple sclerosis or clinically isolated syndrome (n = 140; ages 5-18 years) completed self- and parent ratings using the Behavioral Assessment System for Children, Second Edition, neurologic exam, the Fatigue Severity Scale, and neuropsychological assessment. Mean self- and parent-ratings on the Behavioral Assessment System for Children, Second Edition, were in the typical range across all scales. However, 33.1% indicated a clinically significant problem on a least 1 scale. Although the type of clinical problems varied across participants, attention problems, somatization, and anxiety were found to be most common. Disease features including duration, age of onset, neurologic disability, and fatigue did not distinguish those with and without clinical problems. However, cognitive functioning significantly predicted the presence of a clinical problem (P = .02). Pediatric multiple sclerosis is associated with a range of nonspecific emotional and behavioral clinical problems, occurring more frequently in those patients with cognitive involvement. [ABSTRACT FROM AUTHOR]

It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors’ center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical and magnetic resonance imaging (MRI) features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-seropositive pediatric demyelinating syndromes. Methods: Serum samples collected from 74 children with suspected demyelinating disorders whom were being followed at Massachusetts General Hospital were incubated with control green fluorescent protein (GFP)- and MOG-GFP-transfected Jurkat cell clones. The binding ratios were calculated using flow cytometry. Using statistical analyses, we compared the demographic, clinical and radiological features in our seropositive and seronegative patients. Results: We found that 13 out of 74 (17.5%) patients were seropositive for MOG. The MOG-seropositive patients were younger than the seronegative patients (p = 0.049). No single disease category predominated among the seropositive patients, nor was one group more likely to have a polyphasic course. There were two out of four neuromyelitis optica (NMO) patients who had MOG antibodies; both were seronegative for aquaporin −4 (AQP4) antibodies. One had monophasic disease and the other had frequent relapses. There was a bimodal distribution of the MOG-seropositive patients by age at onset, with a distinct younger group (4–8 years) having a high prevalence of encephalopathy and an older group (13–18 years), whom presented almost exclusively with optic neuritis. MRI analysis demonstrated the absence of corpus callosum lesions in the seropositive patients (p = 0.012). The annualized relapse rate (ARR) and the Expanded Disability Status Scale (EDSS) results at 2 years did not differ between the seropositive and seronegative patients. Conclusion: MOG antibodies are found across a variety of pediatric demyelinating syndromes having some distinct clinical and MRI features. [ABSTRACT FROM AUTHOR]

Three-quarters of children with multiple sclerosis (MS) experience fatigue or depression, and progressive neurocognitive decline may be seen as early as two years after MS diagnosis. Furthermore, a higher magnetic resonance imaging disease burden is seen in pediatric-onset MS compared with adult-onset MS. To date, limited knowledge exists regarding behavioral methods for managing symptoms and disease progression in pediatric MS. To that end, this paper builds an evidence-based argument for the possible symptomatic and disease-modifying effects of exercise and physical activity in pediatric MS. This will be accomplished through: (a) a review of pediatric MS and its consequences; (b) a brief overview of physical activity and its consequences in children and adults with MS; and (c) a selective review of research on the neurological benefits of physical activity in pediatric populations. This topical review concludes with a list of 10 questions to guide future research on physical activity and pediatric MS. The objective of this paper is the provision of a research interest, focus and agenda involving pediatric MS and its lifelong management though exercise and physical activity behavior. Such an agenda is critical as the effects and maintenance of physical activity and exercise track across the lifespan, particularly when developed in the early stages of life. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) studies of the brain in pediatric patients frequently show abnormal white matter lesions, which may be concerning for demyelinating disease. This study aimed to determine the proportion of pediatric patients who have MRI lesions concerning for demyelinating disease at presentation and ultimately are diagnosed with a primary central nervous system demyelinating disease. A retrospective chart review was performed on MRI reports of patients who underwent imaging evaluation at a single tertiary pediatric hospital. Of 299 patients identified, 192 presented with acute neurologic complaints. In this group, ≥5 discrete lesions, African American race, and having brain stem, thalamic, cerebellar, or optic nerve lesions was associated with the patient being diagnosed with a disease that required further treatment. The other 107 patients underwent MRI for other indications. Among these subjects, having lesions within the corpus callosum or cerebellum was associated with being diagnosed with a disease requiring further treatment. [ABSTRACT FROM AUTHOR]

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. [ABSTRACT FROM AUTHOR]

We investigated the contribution of cortical lesions to cognitive impairment in 41 paediatric MS patients. Thirteen (32%) paediatric MS patients were considered as cognitively impaired. T2-hyperintense and T1-hypointense white matter lesion volumes did not differ between cognitively impaired and cognitively preserved MS patients. Cortical lesions number, cortical lesions volume and grey matter volume did not differ between cognitively impaired and cognitively preserved patients, whereas white matter volume was significantly lower in cognitively impaired versus cognitively preserved MS patients (p=0.01). Contrary to adult MS, cortical lesions do not seem to contribute to cognitive impairment in paediatric MS patients, which is likely driven by white matter damage. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the potential role of acute transverse myelitis (ATM) in children as a predictor of multiple sclerosis (MS). The clinical course and prognostic factors in the first episode of ATM in 30 children were assessed using clinical evaluation, treatment, and magnetic resonance imaging (MRI) data. MRI results reveal that initial presentation of acute partial transverse myelitis and brain MRI abnormalities are significantly predictive of a diagnosis of MS.

Multiple sclerosis in children is characterized by more frequent relapses than in adult patients. Diagnosing and treating youth with multiple sclerosis present a number of challenges including differentiating organic relapses from functional symptoms. However, there is no literature describing coexistence of functionality in pediatric multiple sclerosis. Here, we report 2 cases in which inconsistency between clinical history, physical examination, imaging, and atypical disease progression led to suspicion of functional relapses. The purpose of this study is to raise awareness of functional relapses, as prompt recognition can prevent overtreatment and iatrogenic risks in children and adolescents with multiple sclerosis. Underlying psychiatric issues also need to be addressed. [ABSTRACT FROM AUTHOR]

The article discusses a study regarding the psychiatric diagnoses and cognitive impairment in pediatric patients that suffer from multiple sclerosis (MS). Topics discussed include the psychiatric assessment of the children with MS, neurological examination, and neuropsychological test battery. Also mentioned are anxiety disorders, attention deficit hyperactivity disorder (ADHD), and mood disorders.

Cognitive dysfunction is common in pediatric-onset multiple sclerosis, but long-term data on cognitive maturation in these patients are sparse. We report the clinical features and cognitive trajectories in 4 pediatric-onset multiple sclerosis patients who were 10 years or younger at first attack and were followed between 1998 and 2010. Relapses in all 4 patients were frequent early in the disease and became infrequent or absent over time. Declines on neuropsychological testing were most pronounced on measures of processing speed, specifically visuomotor speed, and executive control requiring mental sequencing and set shifting, whereas global intellectual ability and phonemic fluency remained stable or improved over time. These case studies demonstrate a negative impact of multiple sclerosis on cognitive development in the long term and suggest that continued observation into adulthood is required to appreciate the vocational consequences of pediatric-onset multiple sclerosis. [ABSTRACT FROM PUBLISHER]

The article examines the risk of multiple sclerosis (MS) among children at the Children's Hospital at Westmead in Sydney, New South Wales during their first acute demyelinating syndrome between 1997 and 2010. The study shows the presence of well and poorly demarcated lesions as well as the contrast-enhancing lesions. It indicates the specificity and sensitivity of respective radiological criteria. It notes that the radiological features of MS are more predicted than its clinical features.

The article presents several abstracts related to multiple sclerosis (MS) including the articles "A quantitative study of the effects of white matter multiple sclerosis lesions on tissue segmentation methods," by S. Valverde and colleagues, "Precuneus damage is associated with cognitive impairment in paediatric multiple sclerosis," by M. A. Rocca and colleagues, and "Abnormalities of the brain connectome in patients with multiple sclerosis," by M. A. Rocca and colleagues.

The article presents abstracts on medical topics related to pediatric multiple sclerosis (MS) including the impact of exercise, fatigue and depression on MS patients, the association of genes to pediatric-onset MS, and the risk of progression of optic neuritis in children to MS.

The article presents abstracts related to the epidemiology of multiple sclerosis (MS) including "Nationwide incidence of multiple sclerosis in Sweden 2001- 2008," by C. Ahlgren, A. Oden and J. Lycke, "Stressful life-events in childhood and risk of multiple sclerosis," by N. M. Nielsen and colleagues, and "Clinical characteristics and disability of multiple sclerosis patients in Algeria," by N. Hecham and colleagues.

The article presents abstracts related to paediatric multiple sclerosis (MS) including "Sample size calculations for paediatric multiple sclerosis clinical trials using clinical relapse and MRI lesion endpoints," by L. H. Verhey and colleagues, "Clinical features of paediatric-onset multiple sclerosis among patients of Saint Petersburg, Russia," by E. Evdoshenko and colleagues, and "Imaging tissue damage in adult patients with paediatric-onset multiple sclerosis," F. Rossi and colleagues.

The article presents a study which aims to examine the diagnostic applicability of the altered 2010 McDonald diagnostic criteria in paediatric-onset multiple sclerosis (POMS) patients. The study shows that the initial magnetic resonance imaging (MRI) in 62% of POMS within four weeks after symptom onset was enough to diagnose MS according to altered McDonald criteria 2010. It reveals that 10% reached the dissemination in time (DIT) and dissemination in space (DIS) criteria.

The article presents a study which aims to revise the 2007 definitions of pediatric multiple sclerosis (MS) to integrated advances. Revised criteria are proposed for pediatric neuromyelitis, pediatric clinically isolated syndrome and pediatric acute disseminated encephalomyelitis. The criteria was approved by 93% of the 56 members of the International Pediatric Multiple Sclerosis Study Group (IPMSSG) who responded to the final survey.

The 2010 McDonald criteria allow the diagnosis of multiple sclerosis (MS) at first attack in children and adults provided that the first attack symptoms are typical of MS and that the magnetic resonance imaging (MRI) conforms to prescribed features. We evaluate whether meeting the 2010 McDonald criteria at onset correlates with a more aggressive clinical course in a cohort of pediatric MS patients. The Expanded Disability Status Scale (EDSS) and annualized relapse rate were not associated with positivity for 2010 McDonald criteria at onset. The 2010 McDonald criteria identify children with similar MS features to those identified by clinical or MRI evidence of dissemination over time. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the association of body mass index (BMI) with multiple sclerosis (MS) among 302,043 individuals in the Copenhagen School Health Records Register (CSHRR) in Denmark. Cox proportional hazards models was used to approximate the hazard ratios (HRs) and confidence intervals (CIs) of 95%. The study shows a one-unit increase in BMI z-score was related with an increase risk of MS among girls ages 7-13 years.

The article presents a study which the identifies copy number variations (CNVs) in multiple sclerosis (MS) pediatric patient. The study uses the Agilent Enzymatic labeling kit and the Agilent Microarray Scanner, to label the samples of genomic DNA and scanned, respectively. Results show that 10 CNVs were determined not overlapping with any CNV regions. It mentions that the singe rare CNV was a private variation holding the spastic ataxia Charlevoix-Saguenay (SACS) gene.

The article presents abstracts of articles related to multiple sclerosis including "Callosal atrophy in multiple sclerosis is related to cognitive speed," by G. Bergendal and colleagues, "The impact of cortical thinning on executive dysfunction in MS patients," by O. Geisseler and colleagues, and "Longitudinal evaluation of cognitive impairment in pediatric MS," by L. Charvet and colleagues.

The article presents a study on the antibody response to human leukocyte antigen (HLA)-DRBI, and common viruses in pediatric multiple sclerosis (MS), which aims to determine if antibodies in MS patients with viruses such as Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) are higher. Methods used include multivariate analysis, pediatric control, and polymerase chain reaction. Result shows that high antibody response is not associated with DRB1 positive patients.

Fatigue and depression have been shown to be significant problems in children with multiple sclerosis. The rate at which these conditions occur in children with other acquired demyelinating syndromes is unknown. In this cross-sectional study, the authors evaluated 49 children with demyelinating disorders (multiple sclerosis and acute disseminated encephalomyelitis) and 92 healthy controls for depression and/or fatigue using the Behavior Assessment System for Children, Second Edition behavior and mood rating scale and Varni PedsQL Multidimensional Fatigue Scale. The parents of acquired demyelinating syndrome patients were more likely to report elevated depressive symptoms (30.8% vs 10.8%, P = .008). Elevated parent and self-reported total fatigue (25% vs 0%, P < .001, 26.7% vs 8.6%, P = .024) was seen in the patient cohort. The authors conclude that fatigue and depression are far more common in children with acquired demyelinating syndromes than in controls. Clinical attention to and implementation of effective therapies oriented toward these conditions in children with acquired demyelinating syndromes is needed. [ABSTRACT FROM AUTHOR]

The article presents a study which compares the evolution of morphologic brain abnormalities between paediatric (p)and adult-onset multiple sclerosis (aMS). The study the examined the differences and similarities in the evolution of the T2- and T1-lesion load (LL), annualised brain volume change (aBVC), and the black hole ratio (BHR), between 21 pMS and aMS patients. Results showed higher compensatory capacity in pMS than aMS based on the observation of the disease evolution.

The article offers information on a research conducted to analyze the epidemiology of multiple sclerosis in childhood population in British Isles. It is mentioned that the study informs on the changes in the childhood nervous system in children with acquired demyelinating syndromes (ADSs). Also, for the study, pediatricians, and ophthalmologists were given a questionnaire on questions related to acute disseminated encephalomyelitis, clinically isolated syndrome, and neuromyelitis optica.

In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States Pediatric Multiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 ± 2.6 years of age and an average disease duration of 1.9 ± 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care. [ABSTRACT FROM AUTHOR]

The article presents a study on the relation of pediatric-onset multiple sclerosis (POMS) and chronic cerebrospinal venous insufficiency (CCSVI). The study uses statistical analysis of the evaluation of internal jugular veins, intracranial veins and vertebral veins. It also uses ultrasonography of 16 healthy and 15 POMS controls. Results show that CCSVI does not act as a cause of MS.

The article presents a study which analyzes the derived metrics of diffusion tensor imaging (DTI) of patients with multiple sclerosis (MS) since childhood. The study uses retrospective analysis of subject with DTI and were divided into three groups such as childhood onset MS, age-matched and monophasic illness controls. Results show that there was lower fractional anisotropy (FA) in the MS group.

The article offers information on the assessment of the 2010 McDonald multiple sclerosis criteria. It states that magnetic resonance imaging symptomatic criteria for children with multiple sclerosis (MS) has been made on the basis of brain imaging only but the McDonald criteria include spinal cord imaging in dectection lesions dissemination in space (DIS). It adds that the study evaluates whether spinal cord imaging provides extra value to the McDonald criteria.

Retinal atrophy is well known in adult-onset multiple sclerosis but remains unexplored in children. We aimed to determine retinal nerve fiber layer thickness and macular volume in pediatric patients, with and without optic neuritis and their relations with visual evoked potentials. We also examined macular volume changes at month 12. Retinal nerve fiber layer thickness of all quadrants and macular volume were measured in 28 relapsing remitting multiple sclerosis eyes and 30 control eyes using optical coherence tomography and were found reduced in patients compared with controls. This reduction was more prominent in eyes with longer time interval from optic neuritis. Retinal nerve fiber thickness was lower in eyes with delayed visual evoked potentials. Visual evoked potential amplitudes were reduced in affected eyes compared to patients without optic neuritis. Macular volume reduced nonsignificantly in patients at month 12. Retinal atrophy occurs in pediatric multiple sclerosis, and previous optic neuritis accelerates this atrophy. [ABSTRACT FROM AUTHOR]

Onset of multiple sclerosis in childhood occurs in 3-5% of patients. There is limited, but growing knowledge about the underlying pathobiology of pediatric MS. It is crucial to better understand this area in order to address central questions in the field: 1) Can pediatric multiple sclerosis inform us about factors related to disease initiation and propagation? 2) What are the biomarkers of disease course in pediatric multiple sclerosis; 3) Does pediatric multiple sclerosis pathogenesis differ from adult-onset multiple sclerosis; 4) How can we optimize treatment in pediatric demyelinating diseases? 5) Can pediatric multiple sclerosis provide insights into the environmental risk factors for multiple sclerosis in general? Here we review the current knowledge of the pathogenesis of multiple sclerosis in children, and address the five questions raised above. [ABSTRACT FROM AUTHOR]

Prevention of disability through disease-modifying therapies has been a source of significant attention among clinicians treating children and adolescents with multiple sclerosis (MS). In this article, we will review currently available literature on therapies and the management of pediatric-onset multiple sclerosis, with specific discussion of therapies for acute exacerbations and disease-modifying therapies that may prevent relapses and slow disease progression, and will include a brief discussion of future directions in symptomatic interventions for cognitive decline, fatigue, and depression in children and adolescents with multiple sclerosis. Our article will focus specifically on children and adolescents with relapsing-remitting multiple sclerosis, as 99% of cases of pediatric-onset multiple sclerosis are relapsing-remitting multiple sclerosis. [ABSTRACT FROM AUTHOR]

Pediatric multiple sclerosis has been increasingly recognized in the past 10 to 15 years; 3% to 5% of all multiple sclerosis patients experience their first attack in childhood. Childhood multiple sclerosis has a relapsing-remitting disease course. The first attack, or “acquired demyelinating syndrome,” consists of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and monofocal or polyfocal neurological deficits. The diagnosis of multiple sclerosis necessitates the clinical or magnetic resonance imaging confirmation of dissemination in space and time and exclusion of other disorders. The morbidity of childhood multiple sclerosis is significant; within the first 2 years from onset, 30% of children have significant cognitive impairment, 50% show signs of depression, and 75% are fatigued. The relapse rate in children with multiple sclerosis is higher than in adult-onset disease. Following acute treatment, recovery after the first attacks is usually excellent, but patients with childhood-onset multiple sclerosis reach permanent disability or enter the secondary progressive disease course 10 years younger than patients with adult-onset multiple sclerosis. [ABSTRACT FROM AUTHOR]

The new McDonald 2010 criteria have been recommended in paediatric multiple sclerosis (PMS). We aimed to assess the utility of McDonald 2010 criteria in comparison with 2007 International Paediatric Multiple Sclerosis Study Group (IPMSSG)-recommended criteria for PMS diagnosis. Retrospective analysis of 38 PMS cases from three UK demyelination clinics was conducted. Dissemination in space (DIS) and time (DIT) for both McDonald and IPMSSG criteria were noted on initial and follow-up magnetic resonance imaging (MRI). At first MRI scan, IPMSSG DIS criteria were fulfilled in 68% of scans and McDonald DIS criteria in 84%. In total, 11/18 children given gadolinium contrast fulfilled both McDonald DIS and DIT criteria on initial scan. The 2010 McDonald criteria appear more sensitive than IPMSSG and may allow PMS diagnosis at first presentation of CIS in at least a half of cases. [ABSTRACT FROM AUTHOR]

Background: There is limited information on fatigue and its clinical and psychosocial correlates in children and adolescents with multiple sclerosis (MS).Objective: To assess the relationships between fatigue, cognitive functioning and depression in paediatric MS.Methods: The study cohort consisted of patients with MS recruited for an Italian collaborative study on cognitive and psychosocial functioning in paediatric MS. The present assessment included evaluation of fatigue on the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale, cognitive functioning on an extensive neuropsychological battery and depression on the Children’s Depression Inventory (CDI). A psychiatric interview through the Kiddie-SADS-Present and Lifetime Version was also administered.Results: In total, 57 patients with relapsing–remitting MS were compared with 70 healthy controls. Percentages of fatigued patients ranged from 9% to 14% according to self-reports, and from 23% to 39% according to parent reports. Fatigue was significantly related with higher scores on the CDI (p < 0.03). Higher levels of self-reported cognitive fatigue were associated with impaired performance on a problem-solving test, whereas higher levels of parent-reported cognitive fatigue were associated with impairment on tests of verbal learning, processing speed, complex attention and verbal comprehension.Conclusions: Our data show that fatigue can affect a sizeable proportion of paediatric MS patients, and confirm the association between fatigue and depressive symptoms in MS. They also highlight the difficulties of fatigue assessment in the paediatric population and provide a few clues to further research in the field. [ABSTRACT FROM AUTHOR]

New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first- and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics. [ABSTRACT FROM AUTHOR]

Objective: T2 hypo-intensity on magnetic resonance imaging scans is thought to reflect pathological iron deposition in the presence of disease. In this pilot study, we evaluated the utility of the quantification of T2 hypo-intensities in paediatric patients by estimating deep grey matter (DGM) T2 hypo-intensities in paediatric patients with multiple sclerosis (MS) or clinically isolated syndromes (CIS), and their changes over 1 year.Methods: A dual-echo sequence was obtained from 45 paediatric patients (10 with CIS, 35 with relapsing–remitting MS, 8 with an onset of the disease before the age of 10 and 37 during adolescence) and 14 age-matched healthy controls (HC). Eleven patients were reassessed both clinically and with MRI after 1 year. Normalized T2 intensity in the basal ganglia and thalamus was quantified.Results: At baseline, DGM T2 intensity was similar between paediatric patients and HC in all the structures analysed, except for the head of the left caudate nucleus (p = 0.001). DGM T2 intensity of the head of the left caudate nucleus was similar between paediatric CIS and RRMS patients, but it was reduced in adolescent-onset paediatric patients versus HC (p = 0.002). In all patients, DGM T2 intensity of the head of the left caudate nucleus was correlated with T2 lesion volume (r = −0.39, p = 0.007). DGM T2 intensity in all the structures analysed with longitudinal assessment remained stable over the follow-up in the cohort of patients.Conclusions: The quantification of DGM T2 intensity in paediatric patients may provide surrogate markers of neurodegeneration. In paediatric MS, DGM is likely to be affected by iron-related changes, which are likely to be, at least partially, secondary to WM damage. [ABSTRACT FROM AUTHOR]

Background: The relative contribution and interaction of risk factors for multiple sclerosis (MS) have not been evaluated.Objectives: To determine whether vitamin D status is associated with antibody levels to common viruses in pediatric-onset MS or clinically isolated syndrome (CIS) patients and controls.Methods: We assessed whether vitamin D status was associated with viral antibody levels to Epstein–Barr virus, cytomegalovirus (CMV), and herpes simplex virus (HSV)-1 or -2 in subjects who demonstrated evidence of remote infection with these viruses and whether these associations differed depending on disease status.Results: In 140 subjects, vitamin D status was weakly associated with antibody levels to CMV but not to the other viruses. However, there were some interactions between vitamin D status and disease state. Among those with vitamin D sufficiency (≥30 ng/ml), MS/CIS patients had higher antibody levels to Epstein–Barr nuclear antigen-1 than controls. Vitamin D sufficiency was associated with higher CMV antibody levels in MS/CIS subjects but lower CMV antibody levels in controls. Higher vitamin D levels appeared to be associated with higher titers to HSV-2 in MS/CIS patients but not controls.Conclusions: Vitamin D status may be differentially associated with antibody levels to common childhood viruses among seropositive subjects. [ABSTRACT FROM AUTHOR]

Background: Children with multiple sclerosis (MS) can suffer significant cognitive deficits. This study investigates the sensitivity and validity in pediatric MS of two visual processing tests borrowed from the adult literature, the Brief Visuospatial Memory Test-Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT).Objective: To test the hypothesis that visual processing is disproportionately impacted in pediatric MS by comparing performance with that of healthy controls on the BVMTR and SDMT.Methods: We studied 88 participants (43 MS, 45 controls) using a neuropsychological assessment battery including measures of intelligence, language, visual memory, and processing speed. Patients and demographically matched controls were compared to determine which tests are most sensitive in pediatric MS.Results: Statistically significant differences were found between the MS and control groups on BVMTR Total Learning (t (84) = 4.04, p < 0.001, d = 0.87), BVMTR Delayed Recall (t (84) = 4.45, p < 0.001, d = 0.96), and SDMT (t (38) = 2.19, p = 0.035, d = 0.69). No significant differences were found between groups on confrontation naming or general intellectual ability. Validity coefficients exploring correlation between BVMTR, SDMT, and disease characteristics were consistent with the adult literature.Conclusions: This study found that BVMTR and SDMT may be useful in assessing children and adolescents with MS. [ABSTRACT FROM PUBLISHER]