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The aim of this case report is to highlight new possible treatment methods for concomitant juvenile idiopathic arthritis and multiple sclerosis in young patients. Promising results of using ofatumumab, secukinumab and dimethyl fumarate, both in the clinical case of a 22-year-old patient and mentioned literature, allows the belief that there is a chance for improving the quality of life of those who suffer from coexisting autoimmune diseases. However, it is crucial to perform further research in terms of the necessity and safety of the mentioned therapies, especially in the paediatric population, among whom there often exists difficulty in using treatment not registered for under-aged patients. Furthermore, the higher risk of side-effects caused by combined treatment of two autoimmune diseases should also be taken into consideration. [ABSTRACT FROM AUTHOR]

Objective: Multiple sclerosis (MS) is an autoimmune disease affecting both adults and children, often accompanied by various psychiatric disorders. Research on psychiatric symptoms in pediatric MS is relatively limited in comparison with adult-onset MS. To evaluate depression and anxiety levels in pediatric MS patients and compare them to healthy controls, and to assess the impact of clinical and sociodemographic variables on these levels. Materials and Methods: A cross-sectional study was conducted involving 15 pediatric MS patients and 15 age and socioeconomic-matched healthy controls. Anxiety and depression levels were assessed using the State-Trait Anxiety Inventory (STAI) and Children's Depression Inventory (CDI). Results: No significant difference was observed between the MS group and controls in terms of CDI scores, STAI state, and anxiety trait scores. Nevertheless, individuals in the MS group exhibited higher levels of trait anxiety. The average disability score among MS participants was low (0.33), potentially explaining the comparable psychiatric symptom levels with the controls. Sociodemographic data revealed a significant difference in fathers' education levels between the groups. Conclusion: Depression and anxiety levels in pediatric MS patients were similar to healthy controls, possibly attributed to the low disability levels in the MS group. Extensive research is crucial to understand better psychiatric comorbidities and their correlation with disability progression in pediatric MS. [ABSTRACT FROM AUTHOR]

Pediatric-onset multiple sclerosis (MS) can lead to cognitive impairment (CI). In general, in early-onset MS, there are disturbances in cognitive processes, such as information processing speed, attention, and controlling functions. Also, unlike adults with MS, children show a failure in various spheres of speech activity. The age of onset in MS, its duration and recurrence rate can affect not only the accumulation of a stable neurological deficit, but also the state of the cognitive sphere.Objective: to study of the features of CI in children and adolescents with MS; to assess the relationship of CI to clinical characteristics, such as age at onset in the disease and its duration.Patients and methods. The study involved 45 pediatric and adolescent patients with an established diagnosis of MS, who underwent a general neuropsychological examination of the cognitive sphere (Luria’s tests) with transfer to a point system; in addition, psychometric techniques were used to assess attention, controlling functions, memory, verbal fluency, and various types of thinking. Clinical characteristics, such as age at onset in MS and its duration at the time of the examination, were also taken into account.Results and discussion. The leading factors that combine certain symptom complexes of CI in children and adolescents with MS were established. These factors include attention, controlling functions, auditory-verbal and visuospatial memories, various spheres of speech activity. Early-onset MS (at age of 5–8 years) was ascertained to have a greater impact on the formation of speech and controlling functions than adolescence- onset (at age of 13–16-years).Conclusion. The risk of cognitive deficit and subsequent disability was found to be highest in early-onset MS.

The differential diagnosis of pediatric multiple sclerosis (MS) presents a wide spectrum of diseases. Sjögren syndrome (SS) is also a rare cause of this disease. Neurological involvement in SS ranges from peripheral neuropathies to the central nervous system (CNS). We report the case of a 5-year-old boy with a possible diagnosis with SS based on positive minor salivary gland biopsy findings and positive anti-smooth muscle antibodies, also fulfilling the 2017 McDonald criteria. If a patient is younger and meets the MS criteria clinically and radiologically, it is suggested to carefully examine the CNS demyelination in a patient for autoimmune diseases, particularly SS. [ABSTRACT FROM AUTHOR]

Introduction: In this study, clinical and demographic features of childhood multiple sclerosis(MS) diagnosed in a single center for 10 years are presented. Materials and Methods: In this study files of 23 patients with multiple sclerosis who were admitted to Department of Pediatric Neurology between January 2006 and January 2016 were investigated retrospectively. The data of 19 cases were evaluated since 3 cases were excluded due to lack of attending the control visits for more than 2 years and 1 case died in a traffic accident. Gender, current age, family history of MS, onset ages of symptoms, age at diagnosis, duration of disease follow-up, initial symptoms, magnetic resonance(MR) findings, cerebrospinal fluid(CSF) oligoclonal band positivity, visual evoked potential(VEP), somatosensory evoked potential(SEP) findings, treatments and a number of attacks were evaluated. Results: Of the 19 patients diagnosed with multiple sclerosis, 13 were female (68.4%), 6 were male (31.5%), and the female/male ratio was 2.16. The mean age of onset of symptoms was 14.09 years. The mean age of diagnosis was 15.2 years, and the mean follow-up period was 2.17 years. Family history was positive in 3 patients (15.7%). When the initial symptoms of our patients were examined, motor, sensory and brainstem findings were present in 11(57.8%), 9 (47.3%) and 7 cases (36.8%), respectively. Two patients (10.5%) presented with cerebellar findings and 6 patients (31.5%) with visual impairment. The oligoclonal band of CSF was found to be positive in 17 (89.4%) of the cases. Conclusions: In this study, gender, age, family history, age at onset of symptoms, initial symptoms, MR findings, CSF findings, VEP, SEP findings, treatments used, and the number of episodes were evaluated. Multicenter, prospective, and longitudinal studies with larger study populations are needed to understand multiple sclerosis onset in the pediatric period. [ABSTRACT FROM AUTHOR]

Background: The current landscape and treatment patterns of disease-modifying therapy (DMT) use in pediatric patients with multiple sclerosis (MS) are not yet well understood. This study examined DMT utilization and treatment patterns in pediatric patients newly diagnosed as having MS. Methods: Pediatric patients (<18 years old) with two MS diagnosis claims from January 1, 2010, to December 31, 2016, were identified from the MarketScan Commercial Database. The index date was defined as the date of first MS diagnosis, and patients were followed up for 1 year post-index date. Outcomes evaluated included percentage of patients who initiated treatment after MS diagnosis, different DMTs initiated, treatment discontinuation, and switching treatment during follow-up. Results: Of 182,057 patients newly diagnosed as having MS, 288 pediatric patients (mean age, 14 years; 61% female) were identified. Within the first year of diagnosis, 188 patients (65.3%) did not receive any DMT. The most common first-initiated treatments were interferons and glatiramer acetate (83%), but 28% of patients switched or discontinued from first-initiated treatment within 6 months of treatment initiation. Conclusions: This study suggests that a considerable proportion of pediatric patients with MS remain untreated within 1 year of diagnosis. Patients most commonly initiated injectables as their first DMT. Overall, therapy failed early in approximately one in three patients. Thus, the study warrants urgency in treating these patients with currently approved treatment options. [ABSTRACT FROM AUTHOR]

Cognitive impairment is increasingly recognized as an important clinical issue in pediatric multiple sclerosis (MS). However, variations regarding its assessment and remediation are noted in clinical arena. This scoping review aims to collate available evidence concerning cognitive assessment tool and cognitive rehabilitation for pediatric MS. We performed a systematic search of electronic databases (MEDLINE, PubMed, CINAHL Plus, and Web of Science) from inception to February 2020. Reference lists of included articles and trial registers were also searched. We included original studies published in English that addressed cognitive assessment tools or cognitive rehabilitation for pediatric-onset MS. Fourteen studies fulfilled our inclusion criteria. Among them, 11 studies evaluated the psychometric aspects of various cognitive assessment tools in the context of pediatric MS, and different neuro-cognitive domains were emphasized across studies. There were only three pilot studies reporting cognitive rehabilitation for pediatric-onset MS, all of which used home-based computerized programs targeting working memory and attention, respectively. Overall, more systematic research on cognitive assessment tools and rehabilitation for pediatric MS is needed to inform evidence-based practice. Computer-assisted cognitive assessment and rehabilitation appear feasible and deserve further studies. [ABSTRACT FROM AUTHOR]

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]

Aim: The International Paediatric Multiple Sclerosis Study Group (IPMSSG) has proposed criteria for acute disseminated encephalomyelitis (ADEM) not evaluated in clinical practice. Our objective was to assess epidemiological implications of the IPMSSG criteria for ADEM in a cohort study using prospectively collected data.Method: We identified all diagnosed cases of ADEM in Denmark between 2008 and 2015 from the Danish National Patient Register by International Classification of Diseases 10 codes assigned to acute demyelinating episodes, and we reviewed all medical records to validate ADEM.Results: We found 52 children up to the age of 18 years with a verified clinical diagnosis of ADEM (incidence rate 0.54/100 000 person-years; all had abnormal brain magnetic resonance imaging). Only 18 (35%) fulfilled the IPMSSG criteria regarding encephalopathy and polyfocal neurological deficits. Among all 52 children with ADEM, 33 per cent had clinical sequelae after a median follow-up of 4 years 6 months (range: 10mo-8y 3mo). Surprisingly, none progressed to multiphasic ADEM or multiple sclerosis, but median age at end of follow-up was only 10 years 9 months (range: 2y-24y 3mo).Interpretation: Among 52 children with ADEM, none converted to multiphasic ADEM or multiple sclerosis (median follow-up: 4y 6mo; range: 10mo-8y 3mo). Applying the IPMSSG criteria to all children with a diagnosis of ADEM leaves 65 per cent of the cases without a diagnosis and lowers the incidence rate of paediatric ADEM.What This Paper Adds: The incidence of paediatric acute disseminated encephalomyelitis (ADEM) was 0.54 per 100 000 person-years in children younger than 18 years. Only 35 per cent of children with ADEM fulfilled the International Paediatric Study Group consensus criteria. ADEM in clinical practice was primarily based on magnetic resonance imaging findings. Paediatric neurologists diagnosed ADEM in the absence of encephalopathy. None of the children with ADEM progressed to multiple sclerosis/multiphasic ADEM during follow-up. [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]

Some epidemiological studies have implied a pathogenetic association between varicella zoster virus (VZV) and multiple sclerosis (MS); this, however, remains controversial. The present report describes a case involving an immunocompetent 10-year-old girl who developed relapsing-remitting MS following the prolonged reactivation of VZV inside the first branch of the trigeminal nerve, exhibiting herpes zoster ophthalmicus with severe optic neuritis. Symptoms related to herpes zoster ophthalmicus and MS appeared consecutively in the 10-week period after the appearance of vesicles. This suggests that the onset of MS was triggered by some mechanism involving VZV reactivation in the first branch of the trigeminal nerve. To the best of our knowledge, this report is the first to describe a relationship between the onset of MS and herpes zoster ophthalmicus. Early diagnosis and aggressive antiviral therapy are important in cases of herpes zoster ophthalmicus to prevent the possible development of MS as well as visual impairment as sequela. [ABSTRACT FROM AUTHOR]

Objective: Decreased health-related quality of life (HRQOL) in pediatric patients with multiple sclerosis is established, but little research has examined HRQOL in the broader pediatric demyelinating disease population, and predictors of reduced HRQOL are largely unexplored. We sought to (1) compare generic HRQOL and fatigue of pediatric patients with relapsing (i.e., multiple sclerosis and neuromyelitis optica) versus monophasic demyelinating diseases (i.e., acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, clinically isolated syndrome) and (2) examine the extent to which disability, relapsing disease, and fatigue predict HRQOL.Methods: Child and/or parent-proxy reports of generic and fatigue-related HRQOL were collected for 64 pediatric patients with demyelinating diseases. HRQOL of the sample was compared with published healthy child norms. Independent samples t-tests compared HRQOL and fatigue for children with monophasic versus relapsing diseases. Regression analyses examined disability, disease presentation, and fatigue as potential predictors of HRQOL.Results: Compared with healthy child norms, generic HRQOL was significantly lower for the demyelinating disorder group, for both child and parent reports across multiple domains. As hypothesized, the relapsing disease group reported lower overall HRQOL and more fatigue than the monophasic group. Disability and relapsing disease predicted lower HRQOL for both parents and children, whereas fatigue was only predictive per the child perspective.Conclusions: Children with demyelinating diseases evidence significantly lower HRQOL than healthy peers, supporting need for intervention. Those with relapsing disease appear particularly at risk; targeting disability and fatigue may be fruitful areas for intervention. [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]

Objective To identify the demographics, clinical characteristics, disease course, treatment patterns, and disability levels of multiple sclerosis (MS) patients with onset under the age of 10 years (early onset multiple sclerosis, EOMS). Methods EOMS patients were reviewed retrospectively in detailed records from 27 child neurology centers. Patients with preschool (≤7 years) and school age (>7 years) onset were compared. Results There were 30 children (16 girls, 14 boys) who have disease onset between 4 and 10 (mean8.1 ± 1.8) years. MS was relapsing--remitting in 29 (96.7%) and primary progressive in one (3.3%) of the patients. In patients with onset ≤7 years, motor symptoms (54.5%) and encephalopathy (45.5%) predominated, while in those with onset >7 years brainstem (42.1%), sensory (26.3%), and optic nerve (26.3%) involvement were the most frequent presentations. Conclusions MS starting ≤7 years differs fromthe 7-10-year-old group by the higher rate of motor symptoms and more attacks in the first year: the latter suggests a more inflammatory character for EOMS. [ABSTRACT FROM AUTHOR]

Objective: The role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers.Methods: This is a multicentre study done at 11 paediatric MS centres in the USA. Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) with disease onset before 18 years of age and duration of less than 4 years were included in this study. Dietary intake during the week before enrolment was assessed with the validated Block Kids Food Screener. The outcome of the study was time from enrolment to the next relapse. 219 patients with paediatric RRMS or CIS were enrolled. Each 10% increase in energy intake from fat increased the hazard of relapse by 56% (adjusted HR 1.56, 95% CI 1.05 to 2.31, p=0.027), and in particular each 10% increase in saturated fat tripled this hazard (adjusted HR: 3.37, 95% CI 1.34 to 8.43, p=0.009). In contrast, each additional one cup equivalent of vegetable decreased the hazard of relapse by 50% (adjusted HR: 0.50, 95% CI 0.27 to 0.91, p=0.024). These associations remained with mutual adjustment and persisted when adjusting for baseline 25(OH) vitamin D serum level. Other studied nutrients were not associated with relapse.Conclusions: This study suggests that in children with MS, high energy intake from fat, especially saturated fat, may increase the hazard to relapse, while vegetable intake may be independently protective. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Although cognitive impairment has been well established in adult patients with MS, its occurrence in patients with pediatric-onset MS has recently been reported. In this review, I discuss the main features of cognitive impairment in pediatric MS as determined by long-term follow-up studies, neuropsychiatric test batteries, and the results of neuroradiological imaging studies that investigated the pathogenesis of pediatric MS. The most commonly affected cognitive domains in adults are attention, processing speed, and visuomotor skills; language and intelligence are also affected in pediatric MS. A young age at disease onset is the strongest risk factor for these impairments, which may be due to the effect of inflammatory demyelination and neurodegeneration on the developing central nervous system and neural networks in children. Cognitive impairment has long-term effects on patients’ academic life and the quality of their social life. Therefore, all patients with pediatric MS should be screened and monitored for cognitive impairment. This review also highlights the need for neuropsychological test batteries that assess different cognitive domains in children and adolescents with multiple sclerosis and for cognitive rehabilitation programs to improve the quality of their academic and social life. [ABSTRACT FROM AUTHOR]

Background: Risk of multiple sclerosis (MS) is influenced by environment and genetics. Infant breastfeeding appears protective against some childhood autoimmune disorders, but its impact on risk of MS in childhood is unknown. The objective of this study is to analyze the association of breastfeeding in infancy on future risk of pediatric-onset MS.Basic Procedures: Biological mothers of 36 consecutive pediatric-onset MS patients completed a questionnaire on history of breastfeeding and various birth and demographic factors. The control group consisted of 72 otherwise healthy patients with a diagnosis of migraine and normal brain magnetic resonance imaging obtained less than 12 months before enrollment. Inverse probability of treatment weighting was used to reduce selection bias and balance the covariates between breastfed and non-breastfed children.Main Findings: Demographics (with the exception of body mass index) and birth factors were not significantly different between groups. Whereas 36% of cases were breastfed, 71% of controls were breastfed (P = 0.001). The median duration of breastfeeding was 0 weeks (range: 0 to 40 weeks) for cases and 16 weeks (range: 0 to 216 weeks) for controls. Lack of infant breastfeeding was associated with future diagnosis of pediatric-onset MS (odds ratio = 4.43; 95% confidence interval, 1.68 to 11.71; P = 0.003). This association remained significant after correcting for covariates, such as body mass index and age at diagnosis.Conclusions: These data demonstrate that absence of infant breastfeeding has an association with an increased risk of pediatric-onset MS diagnosis. [ABSTRACT FROM AUTHOR]

Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15) in comparison with age- and disability-matched AOMS patients (n = 14) and to normal controls (NC, n = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term. [ABSTRACT FROM AUTHOR]

Introduction. Pediatric multiple sclerosis (pMS) is a rare demyelinating disorder with an onset before the age of 18 years. In this study, we aimed to investigate the characteristics of pMS in Tunisian children. Patients and Methods. We conducted a retrospective study over 11 years (2005–2016) including all patients diagnosed with pMS according to the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria of 2012 and followed up in a tertiary care research center. Epidemiological, clinical, neuroimaging, laboratory, and therapeutic data were collected and analyzed. Results. There were 21 patients. The male-female ratio was 1 : 3. Mean age at onset was 11 years (range: 3–17 years). Three patients had type 1 diabetes. Polyfocal presentation was preponderant (81%) with motor dysfunction in 57% of patients. Paroxysmal dystonia was noticed in 24%. All patients were diagnosed with relapsing-remitting form. Interferon beta was prescribed in 80% with a reduction of annual relapse rate. Conclusion. The annual incidence of pMS in Tunisian children aged below 18 years could be estimated as 0.05 per 100,000. Singular features in our cohort were the frequent association with type 1 diabetes and the increased occurrence of dystonia. Greater awareness of pMS may be helpful to improve management strategies of children and their families. [ABSTRACT FROM AUTHOR]

Background The clinical features of patients with very early-onset acquired demyelinating syndrome (ADS) with the anti-myelin oligodendrocyte glycoprotein (MOG) antibody are unknown. We investigated the clinical characteristics and described detailed treatment of weekly intramuscular interferon β-1a (IFNβ-1a) in children aged <4 years with ADS and the anti-MOG antibody. Methods We conducted a retrospective chart review of patients with anti-MOG positivity who were diagnosed as having multiple sclerosis (MS) at <4 years of age. Results Subjects comprised 2 boys and 2 girls. Initial symptoms included ataxia, facial paresis, status epilepticus, and encephalopathy. Abnormal lesions on magnetic resonance imaging scans were often detected in the brainstem and cerebellum as well as the cerebrum. All patients started receiving IFNβ-1a at age 3.1–3.5 years. The initial doses ranged from 3 to 6 μg, which were 1/10–1/5 doses, respectively, for adults. During 0.6–4.3 years of IFNβ-1a administration, all patients had flu-like symptoms, and 1 patient had an increased liver enzyme level. Although 1 patient discontinued IFNβ-1a therapy because of frequent relapses, no patient discontinued therapy due to severe adverse events. Conclusions This case series adds novel information regarding the clinical features of children <4 years old with ADS and the anti-MOG antibody. [ABSTRACT FROM AUTHOR]

Objective To investigate how atrophy is distributed over the cross section of the upper cervical spinal cord and how this relates to functional impairment in multiple sclerosis ( MS). Methods We analysed the structural brain MRI scans of 54 patients with relapsing-remitting MS (n=22), primary progressive MS (n=9), secondary progressive MS (n=23) and 23 age- and sex-matched healthy controls. We measured the cross-sectional area ( CSA), left-right width ( LRW) and anterior-posterior width ( APW) of the spinal cord at the segmental level C2. We tested for a nonparametric linear relationship between these atrophy measures and clinical impairments as reflected by the Expanded Disability Status Scale ( EDSS) and Multiple Sclerosis Impairment Scale ( MSIS). Results In patients with MS, CSA and APW but not LRW were reduced compared to healthy controls ( P<.02) and showed significant correlations with EDSS, MSIS and specific MSIS subscores. Conclusion In patients with MS, atrophy of the upper cervical cord is most evident in the antero-posterior direction. As APW of the cervical cord can be readily derived from standard structural MRI of the brain, APW constitutes a clinically useful neuroimaging marker of disease-related neurodegeneration in MS. [ABSTRACT FROM AUTHOR]

Processing speed is a frequently affected cognitive domain in pediatric multiple sclerosis (MS) and is commonly assessed using the Symbol Digit Modalities Test (SDMT). The objective of this study was to determine maturational trajectories in SDMT performance and baseline factors affecting trajectories in a sample of 82 pediatric MS individuals. Performance on the SDMT increased with age in patients with pediatric MS followed by a subsequent decline. Furthermore, patients who were older at disease onset and had a higher IQ showed greater gains with age, suggesting that these factors may be protective with respect to cognitive maturation in pediatric MS. [ABSTRACT FROM PUBLISHER]

Background: Cortical pathology in multiple sclerosis (MS) has been associated with prolonged and progressive disease. 7T magnetic resonance imaging (MRI) provides enhanced visualization of cortical lesions (CLs). Hence, we conducted a pilot study to explore whether CLs occur early in MS, as evidenced by pediatric-onset patients.Methods: A total of 8 pediatric-onset MS patients were imaged using 7T MRI. CLs were annotated on T1-weighted magnetization-prepared rapid acquisition of gradient echoes images as leukocortical (LC), intracortical, or subpial. Total CLs, age at onset, age at scan, disease duration, total relapses, and Expanded Disability Status Scale (EDSS) score were recorded.Results: A median of 120 (range: 48-144) CLs was identified in 8 MS patients (3 female, all with relapsing remitting MS, mean age at scan 21 years ± 3.5 SD, mean age of disease onset 15 years ± 2.3 SD, mean disease duration 5.3 years ± 3.4 SD, median EDSS 2.0). Nearly all the lesions identified were LC.Conclusions: Many CLs are detectable using 7T MRI in patients with pediatric-onset MS despite relatively brief disease duration, absence of progressive disease, and very limited physical disability-supporting early cortical involvement in MS. [ABSTRACT FROM AUTHOR]

The vast majority of drugs for the treatment of multiple sclerosis (MS) have been developed and approved for the adult patient population. The place of these drugs in the treatment of children remains undefined not only in Russia, but also throughout the world. Despite the fact that studies of new drugs in the pediatric patient population is part of the routine practice of large pharmaceutical agencies such as the FDA and the EMA, treatment recommendations FOR pediatric MS patients are based less on long-term systematized experience of clinical studies as on a professional consensus of international expert associations, particularly the International Pediatric Multiple Sclerosis Study Group (IPMSSG). Clinical trials include small numbers of patients of pediatric age, minor compared with the number of participants in adult studies. There is therefore a need to develop new assessments evidencing the efficacy and safety of drugs for the treatment of MS in children and adolescents. This article presents the views of the IPMSSG on the treatment of pediatric MS, taking account of the characteristics of the Russian legislation and experience of Russian specialists. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. Objective: To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). Methods: Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. results: Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset (r = -0.30, p = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) (r = -0.25, p = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). conclusion: Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS. [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]

Background Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. Objective To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. Methods The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). Results We included 271 cases (mean age at disease onset of 15.7 years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p = 0.01). Conclusions While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies. [ABSTRACT FROM AUTHOR]

Decreased information processing speed (IPS) is frequently reported in pediatric multiple sclerosis (MS) patients. The computerized version of the Symbol Digit Modalities Test (c-SDMT) measures IPS over eight consecutive trials per session and additionally captures changes in performance within the session. Here, we establish normative c-SDMT performance and test-retest reliability in healthy children (HC) and explore differences in the overall c-SDMT-performance between HC and MS patients. This cross-sectional study included 478 HC (237 female, 49.5%) divided into five age groups (2 years each), and 27 MS patients (22 female, 81.5%) aged 8-18 years. The average time to complete the c-SDMT increased with age (|r| 0.70, 95% CI -0.74, -0.64). Test-retest reliability was high (ICC = 0.91) in HC. The total time to complete the c-SDMT did not differ between children with MS and sex- and age- matched HC (p = 0.23). However, MS patients were less likely to show faster performance across all the successive eight trials compared to HC (p = 0.0001). Healthy children demonstrate faster IPS with increasing age, as well as during successive trials of the c-SDMT. The inability of pediatric MS patients to maintain the increase in processing speed over successive trials suggests a reduced capacity for procedural learning, possibly resulting from cognitive fatigue. [ABSTRACT FROM AUTHOR]

Background and purpose Clinically isolated syndrome ( CIS) is a first demyelinating event of the central nervous system and can be a single event. After CIS, a chronic disease course with ongoing inflammation and relapses might occur, resulting in a diagnosis of multiple sclerosis ( MS). As yet, there has been no prospective exploration of whether children and adults with CIS have the same disease course. Methods Patients with CIS, whose age ranged from 1 to 50 years, were prospectively followed. We divided the patients into three different age groups, i.e. 1-10, 11-17 and 18-50 years old. Demographic data, disease course, time to MS diagnosis and annualized relapse rates ( ARRs) were compared among these groups. Results We included 383 patients with CIS, of whom 218 (56.9%) were diagnosed with MS. Children of between 11 and 17 years old had the highest rate of MS conversion (83.5% vs. 50.0% in the other age groups together, P < 0.01) and the shortest time to MS diagnosis [median time 2.6 months (interquartile range, 0.6-6.0) vs. 8.2 months (interquartile range, 1.9-28.2) in the other age groups together, P < 0.01). ARRs corrected for follow-up were higher in children of <18 years old than in adults of ≥18 years old with MS (mean ARR, 0.65 vs. 0.43, P < 0.01). Conclusion Children with CIS tend to have a more inflammatory disease course appearing from higher ARRs in all children and the highest rate of MS conversion in 11-17-year-old children. This supports early initiation of disease-modifying therapy in children, perhaps even at the first event in children at high risk for MS in line with clinical practice in adults. [ABSTRACT FROM AUTHOR]

Multiple sclerosis ( MS) is a complex immune-mediated disease characterized by recurrent demyelinating episodes of the central nervous system, which typically occurs in young adults. It is the most common disabling neurological disease of young people; however, pediatric MS, defined as onset of MS before the age of 18 years, has been increasingly recognized worldwide in the past two decades. Pediatric MS might represent up to 10% of all patients with MS. As in adults, the diagnosis of pediatric MS rests on the demonstration of dissemination of lesions in both space and time, and the exclusion of alternative diagnosis. However, it can be more difficult to distinguish MS accurately from other conditions in children compared with the adult population, because there is considerable overlapping of clinical and magnetic resonance imaging features between pediatric MS and other acquired demyelinating disorders of the central nervous system. In view of therapeutic strategies, although interferon-beta and glatiramer acetate are the most commonly used disease-modifying drugs for pediatric MS so far, none of the current available disease-modifying drugs were tested in pediatric MS by randomized controlled trials, and thus there is limited information regarding the efficacy and safety. The present review article describes the epidemiology, clinical features, consensus definition and treatment strategy of pediatric MS. [ABSTRACT FROM AUTHOR]

The article offers information on the Third Annual Meeting of the Multiple Sclerosis (MS) Summer College held at the Kobe Portpia Hotel in Kobe, Japan from August 6-7, 2016. Topics discussed include pathomechanisms of neuromyelitis optica (NMO), role of fingolimod in bone resorption in female patients with MS, and diagnosis and treatment strategies in pediatric MS patients. Associate Professor Monika Bradl of the Medical University of Vienna in Austria gave the opening lecture on NMO.

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment. The treatment of children with MS has to be multidisciplinary and include pediatric neurologists, ophthalmologists, psychologists, physiotherapists, and if necessary, pediatric psychiatrists and pharmacologists. The basis of MS therapy should rely on drugs that are able to modify the course of the disease, i.e. immunomodulatory drugs. These drugs can be subdivided into two general categories: first-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, glatiramer acetate) and second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab). Treatment of relapses involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis. We summarize here the current available information related to the etiology and treatment options in MS. Early administration of immunomodulatory therapy is beneficial in adults, while more studies are needed to prove their effectiveness in pediatric populations. Therefore, pediatric MS still represents a great challenge for both, the early and correct diagnosis, as well as its treatment. [ABSTRACT FROM AUTHOR]

Background: Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process.Methods: The study cohort of 22 162 eligible patients from 21 countries was extracted from the MSBase registry. Only patients with MS aged ≥16 years were included. To reduce heterogeneity, only centres of largely European descent were included for analysis. AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination. Predictors of AAO were evaluated by linear regression.Results: Compared with those living in lower latitudes (19.0-39.9°), onset of symptoms was 1.9 years earlier for those at higher latitudes (50.0-56.0°) (p=3.83×10-23). A reciprocal relationship was seen for ambient ultraviolet radiation (UVR), with a significantly increasing AAO for patients with MS per each quartile increment of ambient UVR (p=1.56×10-17). We found that the AAO of female patients was ∼5 months earlier than male patients (p=0.002). AAO of progressive-onset patients with MS were ∼9 years later than relapsing-onset patients (p=1.40×10-265).Conclusions: An earlier AAO in higher latitude regions was found in this worldwide European-descent cohort and correlated inversely with variation in latitudinal UVR. These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations. [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]

Little is known about the impact of parental multiple sclerosis (MS) on offspring's educational attainment. The objective of the study was to examine educational achievements in offspring of parents with MS compared with matched children of parents without MS in a nationwide register-based cohort study. Children of all Danish-born residents with onset between 1950 and 1986 were identified by linking the Danish Multiple Sclerosis Registry with the Civil Registration System. Twins, children with MS, and emigrated persons were excluded. The reference cohort consisted of randomly drawn individuals from the Civil Registration System without parental MS matched 8:1 to the MS offspring by sex and year of birth. Information about education was linked to the cohorts from nationwide educational registries. We included 4177 children of MS parents and 33,416 reference persons. Children of MS parents achieved statistically significant higher average grades than the reference cohort in their final exam of basic school with a mean grade difference of 0.46 (95 % CI 0.22-0.69; p = 0.0002). We found no difference in achievement of educational level above basic school (OR 1.04; 95 % CI 0.98-1.10; p = 0.20). There was a trend toward more MS offspring attaining health-related educations (OR 1.10; 95 % CI 1.00-1.21; p = 0.06). In conclusion, children of MS parents showed a small advantage in grade point average in final examinations in basic school, and they more often tended toward health-related educations. This study revealed no negative consequences of parental MS on grades and highest educational level achieved. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to the articles in the previous issues including the "Hackers Spy Scientists," "Concomitant Infections Should not Deter Clinicians from Diagnosing Kawasaki Disease," and "Pediatric Multiple Sclerosis."

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]

Although multiple sclerosis is predominantly regarded as a disease of young adulthood, up to 5% of MS patients are diagnosed prior to age eighteen. The predominant form of MS is relapsing–remitting characterized by exacerbations of symptoms followed by periods of remission. The majority of disease modifying drugs target T cell proliferation or block migration into the central nervous system. Although these treatments reduce relapses, disease progression still occurs, warranting therapeutic strategies that protect the CNS. Biomarkers to indicate relapses would facilitate a personalized approach for add-on therapies that protect the CNS. A multiplex cytokine bead array was performed to detect T cell associated cytokines in sera from patients 6–20 years of age with pediatric onset MS clinically diagnosed in relapse or remission compared to healthy control patients. Of the 25 cytokines evaluated, 17 were increased in patients clinically diagnosed in relapse compared to sera from control patients in contrast to only 9 cytokines in the clinically diagnosed remission group. Furthermore, a linear regression analysis of cytokine levels in the remission population showed 12 cytokines to be statistically elevated as a function of disease duration, with no effect observed in the relapse population. To further explore this concept, we used a multivariable stepwise discriminate analysis and found that the following four cytokines (IL-10, IL-21, IL-23, and IL-27) are not only a significant predictor for MS, but have important predictive value in determining a relapse. Since IL-10 and IL-27 are considered anti-inflammatory and IL-21 and IL-23 are pro-inflammatory, ratios of these cytokines were evaluated using a Duncan's multiple range test. Of the six possible combinations, increased ratios of IL-10:IL-21, IL-10:IL-23, and IL-10:IL-27 were significant suggesting levels of IL-10 to be a driving force in predicting a relapse. [ABSTRACT FROM AUTHOR]

Aim: Granulomatosis with polyangiitis (GPA), extremely rare in children, is a disease characterized by granulomatous inflammation and necrotizing vasculitis that involves medium and small vessels. Central nervous system (CNS) involvement in GPA is not common and often appears at a later stage of the disease. The CNS manifestation of pediatric GPA was fragmentally discussed. Herein, we reported a case of relapsing-remitting pediatric GPA with prominent CNS involvement as initial symptoms. Method: The patient was a 9-year-old female. The first episode manifested as uroclepsia and bilateral lower extremity weakness, resulting from diffused dot-enhanced large lesions within bilateral anterior cerebral artery territory on magnetic resonance (MR). This was followed by three recurring episodes of visual impairment as a result of optic neuritis. MR in the last episode indicated bilateral sphenoid sinus inflammation adjacent to the left optical nerve. All four episodes were combined with upper respiratory tract symptoms and slight urine abnormality. She responded well to large doses of corticosteroids and immunoglobulins. However, the patient had long been suspected of having multiple sclerosis and had not received appropriate maintenance treatment. Result: After being diagnosed with GPA, the patient received small doses of glucocorticoids and mycophenolate mofetil for maintenance, which generated a favorable outcome. Conclusion: CNS involvement in pediatric GPA is rare. Single large or multifocal insults involving one or more lobes consistent with the distribution of cerebral arteries could be a typical feature on MR. Early diagnosis and proper treatments help to improve the prognosis. [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]