The robust association between cognitive function and reduced size of thalamus and global brain volume in pediatric-onset MS patients implicate neurodegenerative processes early in the disease course, and suggest that plasticity of an immature central nervous system is not sufficient to protect patients from the deleterious consequences of MS on cognitive neural networks. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

IMPORTANCE The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear. OBJECTIVE To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort. DESIGN, SETTING, AND PARTICIPANTS This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019. EXPOSURES Maternal urinary fluoride (MUF SG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women. MAIN OUTCOMES AND MEASURES Children's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score. RESULTS Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUF SG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUF SG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUF SG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUF SG was associated with a 4.49-point lower IQ score (95% CI, −8.38 to −0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, −2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, −7.16 to −0.14) in boys and girls. CONCLUSIONS AND RELEVANCE In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.

No abstract

Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth.Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2-11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age-and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects.Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p , 10 24 ). These findings indicate a failure of agenormative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions:Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS. Neurology ® 2014;83:2140-2146 GLOSSARY EDSS 5 Expanded Disability Status Scale; FOV 5 field of view; MS 5 multiple sclerosis; NC 5 normally developing controls; NIHPD 5 NIH MRI Study of Normal Brain Development; PDW 5 proton density-weighted; RF 5 radiofrequency; T1W 5 T1-weighted; T2W 5 T2-weighted; TE 5 echo time; TR 5 repetition time.In multiple sclerosis (MS), focal inflammatory white matter lesions are the most visible aspect of pathology but represent only one component of the disease. There is growing evidence that the disease is also characterized by a neurodegenerative component.1 In adult-onset MS, deep gray matter atrophy is measurable even within the first few years after the first attack. 2In cross-sectional analyses, patients with MS with disease onset prior to age 18 years have been shown to have reduced thalamic 3-5 and brain volumes 3,5,6 relative to age-and sexmatched healthy controls. As MS is a chronic progressive illness, and childhood and adolescence are key periods of brain growth, 7 longitudinal analysis is required to define the impact of MS disease on brain development, in order to determine whether these differences in brain volumes are due to failure of normal age-related brain growth or to progressive loss of volume, or both.In this study, we used longitudinal MRI data to compare the growth trajectory of the brain and ...

Lower rates of improvement in the pediatric MS group may be suggestive of a lack of age-appropriate cognitive development and warrant further evaluation over time.

No abstract

In comparison with the large body of evidence on cognitive functioning in adults with multiple sclerosis (MS), there is limited information on cognition in pediatric-onset MS (POMS). Unique vulnerabilities in POMS can derive from having a disease that occurs during key periods of ageexpected brain growth, active myelination in the CNS, and maturation of neural networks during the learning curve and key formative years in the academic career of the patient. Therefore, the consequences of MS on developing cognitive faculties can be assessed only in the pediatric population and cannot be simply extrapolated from studies carried on in the adult population. Until the last decade, research in the pediatric population was mainly represented by small clinical series, often limited by the narrow scope of neuropsychological assessment and lack of adequate control groups. Over the last decade, however, cognitive functioning and mood-related difficulties have become an increasing concern as awareness of this population has grown. A few specialized MS centers have begun performing more systematic research in the field in order to assess the prevalence of cognitive impairments and mood-related difficulties in patients with POMS, to better characterize the neuropsychological pattern and determine the functional consequences of these problems. This chapter summarizes our current understanding of cognitive and moodrelated difficulties in POMS and highlights perceived gaps in knowledge and priorities for future research. Neurology ® 2016;87 (Suppl 2):S82-S87 GLOSSARY BNBC 5 Brief Neuropsychological Battery for Children; CIS 5 clinically isolated syndrome; CL 5 cortical lesions; EDSS 5 Expanded Disability Status Scale; FC 5 functional connectivity; fMRI 5 functional MRI; GM 5 gray matter; MS 5 multiple sclerosis; POMS 5 pediatric-onset multiple sclerosis; SDMT 5 Symbol Digit Modalities Test; WM 5 white matter.Patients with pediatric-onset multiple sclerosis (POMS) may be particularly vulnerable to inflammation, demyelination, and axonal damage associated with multiple sclerosis (MS). 1The concurrence of these changes with myelination in the developing CNS that can go on through the third decade of life can damage networks involved in cognition.2 Research suggests loss of myelin in POMS can adversely affect cognition and academic skills.2,3 Whether brain plasticity and compensatory abilities can mitigate against disease-related pathologic changes remains unclear: answers will ultimately emerge through careful long-term studies of cognitive outcomes in POMS.PREVALENCE, NEUROPSYCHOLOGICAL PROFILE, AND CLINICAL CORRELATES Across differing test batteries and definitions of cognitive impairment, cognitive impairment is consistently reported in approximately one-third of patients with POMS (table 1). In interpreting different thresholds used to classify cognitive impairment, it is useful to note that the 5th percentile equates to 1.67 SD.In a US study of 37 POMS cases, 4 35.1% of the patients showed cognitive impairment, defined ...

Youth with MS are at risk of difficulties in behavioral and emotional health. Relations with parents emerged as a key factor influencing the emotional well-being of youth with MS, suggesting an important role for family-centered care in this population.