Dietary salt intake and time to relapse in paediatric multiple sclerosis.

BACKGROUND: Salt intake was reported to be associated with increased clinical and MRI activity in adult patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To determine if salt intake is associated with time to relapse in patients with paediatric-onset MS. METHODS: Paediatric-onset MS and patients with clinically isolated syndrome (CIS) within 4 years of disease onset were recruited from 15 paediatric MS centres in the USA as part of a case-control study. Patients with available prospective relapse data subsequent to enrolment were included in this project. Dietary sodium intake was assessed by self-report questionnaire using the validated Block Kids Food Screener. Cox proportional-hazards regression models were employed to determine the association of sodium density, excess sodium intake and sodium density tertiles with time to relapse following study enrolment, adjusting for several confounders. RESULTS: 174 relapsing-remitting MS/CIS patients were included in this analysis (mean age of 15.0 years, and 64.9% females). Median duration of follow-up was 1.8 years. In an unadjusted analysis, density of daily sodium intake was not associated with time to relapse, and patients with excess sodium intake had no decrease in time to relapse as compared with patients with non-excess sodium intake. The multivariable analysis demonstrated that patients in the medium and high tertile of sodium density had a HR of 0.69 (95% CI 0.37 to 1.30, p=0.25) and 1.37 (95% CI 0.74 to 2.51, p=0.32) compared with patients in the lowest tertile, respectively. CONCLUSIONS: Higher salt intake was not associated with decreased time to relapse in patients with paediatric-onset MS.

Menarche increases relapse risk in pediatric multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) predominantly affects women with a sex ratio of 3:1 in contrast with a 1:1 sex ratio seen in pre-pubertal onset. Thus, puberty may influence MS risk differentially in males and females. How puberty may be associated with MS clinical features and disease course remains unknown. OBJECTIVE: The objective of this paper is to determine the association of menarche with disease course in girls with MS. METHODS: This is a longitudinal retrospective study from the UCSF Regional Pediatric MS Center database. We categorized patients by time of disease onset: pre-menarche, peri-menarche and post-menarche. Poisson regression models were used for within-subject relapse analyses offset by follow-up time. RESULTS: Seventy-six girls were included (pre-menarche onset = 17; peri-menarche onset = 9; post-menarche onset = 50). Age of menarche was similar in all groups (Kruskal-Wallis p = 0.19). Relapse rate was the same in all three groups during the first two years of follow-up. In girls with follow-up overlapping at least two time periods, within-subject analyses showed increased relapses during the peri-menarche compared to post-menarche period (adjusted IRR = 8.5, 95% CI 2.5-28.7, p = 0.001). CONCLUSION: Pubertal status may influence MS course at least in female patients. Understanding how puberty influences MS clinical features may offer new insights into important factors regulating disease processes.

Puberty onset and pediatric multiple sclerosis activity in boys.

OBJECTIVES: To determine the association of age of onset and puberty with relapse rate in boys with pediatric multiple sclerosis (MS). BACKGROUND: While sex steroid hormones have been shown to have immune effects, it is not known how age or puberty influence disease course in boys with MS. We have previously shown an association in girls with menarche and risk of relapse. METHODS: Patients from the UCSF Regional Pediatric MS Center were included in this retrospective study. Age of disease onset was used to stratify patients into three groups approximating pubertal stage: age less than 11 years, between 11-14 years, and greater than 14 years, corresponding to pre-, peri-, and post-puberty, respectively. Negative binomial regression was used to determine the association between pubertal status at disease onset with relapse rate. RESULTS: 58 male pediatric patients with onset of relapsing-remitting MS before 18 years of age participated to the analyses (<11 onset, n = 21; 11-14 onset, n =21; >14 onset, n = 16). 60% of patients identified as White, and 43% as Hispanic. Median follow-up was 3.17 years (IQR 1.42-5.35). Univariate negative binomial regression models demonstrated a 2.4 fold increased relapse rate for boys with disease onset in the peri-puberty age group compared to the post-puberty age group (IRR = 2.43, 95% CI 1.33-4.47, p = 0.004). Adjustments for race, ethnicity, and use of disease-modifying therapy did not change these results (IRR = 2.39, 95% CI 1.20-4.79, p = 0.014). No differences in relapse rate between the pre-pubertal onset group and post-pubertal onset group were found. CONCLUSIONS: Pubertal onset of MS may be associated with increased relapses in boys. Further investigation is indicated to understand the intersection of pubertal effects and MS pathophysiology.

A case-control study of dietary salt intake in pediatric-onset multiple sclerosis.

BACKGROUND: High salt intake may be associated with pro-inflammatory changes in the immune response, and increased clinical and MRI activity in adults with relapsing-remitting multiple sclerosis. OBJECTIVE: We sought to determine if dietary salt intake is associated with pediatric-onset MS risk in a multicenter, case-control study. METHODS: Pediatric-onset CIS/MS cases within four years of onset and controls less than 22 years old recruited from 14 pediatric-MS centers were studied. Dietary sodium intake was assessed using the validated Block Kids Food Screener (NutritionQuest). Sodium intake, excess sodium, and sodium terciles were compared between cases and controls. Logistic regression models were adjusted for age, gender, ethnicity, body mass index, and socioeconomic status. RESULTS: Among 170 cases (mean age=15.2±3.5) and 331 controls (mean age=14.0±3.7), no significant difference in unadjusted mean sodium intake was found between cases (2044mg/d) and controls (2030mg/d, p=0.99). The proportion of subjects consuming excess sodium, based on the adequate intake for age and gender, was similar between cases and controls (65% versus 69%, p=0.34). There were no increased odds of higher sodium intake among cases as compared to controls (for each 100mg/d increase in sodium, OR=1.00, 95% CI 0.98, 1.02; p=0.93, for excess sodium intake, OR=1.05, 95% CI 0.67, 1.64; p=0.84). CONCLUSIONS: Our results show no strong association between dietary salt intake and pediatric-onset MS risk, suggesting that salt intake may not play a prominent role in susceptibility to MS in children.

Treatment adherence and transitioning youth in pediatric multiple sclerosis.

BACKGROUND: Transitioning youth with multiple sclerosis (MS) represent a vulnerable group to potentially poor outcomes. It is unknown how pediatric MS patients transition into adult care. OBJECTIVES: To describe self-management skills that include adherence to disease-modifying therapies, quality of life measures, illness perception, transition readiness and healthcare skills assessments in patients with pediatric MS and associations with clinical and cognitive outcomes. METHODS: This is a prospective cross-sectional study at the pediatric MS center and transitional MS clinic at the University of California, San Francisco. Patients and one of their parents completed validated surveys for self-management skills. Non-adherence is defined as not taking their medication more than 20% of the time in the past 1 month. Wilcoxin matched-pairs rank test and McNemar's tests were used for comparison of patient and parent responses. Univariate and multivariate regression models were used for analyses adjusting for disease duration and socio-economic status. RESULTS: Thirty patients were enrolled with a mean (+/-SD) age of 15.8 years+/-2.8, 53% was female and 47% Hispanic. The rate of non-adherence was 37%. The most common reason for non-adherence was forgetting to take their medication reported in 50% of patients. In adjusted regression models, higher EDSS was associated with a lower score on patient's quality of life (13 points decrease, 95% CI 6­18, p<0.0001), and lower healthcare skills (15 points decrease, 95% CI5­26, p=0.006). Four points increase in Symbol Digit Modalities Test score was associated a 0.1 increase in transition readiness score (95% CI0.07­0.2, p=0.001) and 3.9 points increase in health care skills scores (95% CI 1.7­6, p=0.008).

Humoral-targeted immunotherapies in multiple sclerosis.

The continuous improvements of our understanding of the pathophysiological changes that occur in multiple sclerosis (MS) have translated into many novel therapeutic agents at different stages of development. These agents target more specifically the innate or the adaptive immune response. We will review agents available or under development that target the humoral pathways of the adaptive immune response. As such, humoral targeted immunotherapies that are being developed for MS are discussed herein: rituximab, ocrelizumab, and ofatumumab show promise as B-cell depleting agents. Other agents, such as atacicept were suspended during development in MS due to increased inflammatory activity versus the placebo. Although most agents were tested in relapsing-remitting forms of MS, rituximab and ocrelizumab have both been studied in progressive MS, whereas ocrelizumab only is currently moving forward in primary progressive MS trials. We provide an overview of agents available and under development that target the humoral response and include their mechanisms of action, safety profiles, and results of clinical trials.