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Objectives: The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome., Methods: Thirty-six patients with ADS (mean age=12.2 years, SD=2.7, range: 7-16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls., Results: Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5 SD below normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed among 6/32 patients, but this did not differ significantly from controls. Twelve of 36 patients received a diagnosis of MS within 3 years post-ADS. Patients with MS did not differ from children with monophasic ADS in terms of cognitive performance at the 6-months follow-up. Fatigue symptoms were reported in 50% of patients, irrespective of MS diagnosis. Presence of brain lesions at onset and 6 months post-incident demyelinating event did not associate with cognitive outcome., Conclusions: Children with ADS experience a favorable short-term neurocognitive outcome, even those confirmed to have MS. Longitudinal evaluations of children with monophasic ADS and MS are required to determine the possibility of late-emerging sequelae and their time course. (JINS, 2016, 22, 1050-1060).

Cognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1-9).

Studies in adults with multiple sclerosis (MS) have associated regional brain abnormalities with memory impairment. While memory problems in children with MS are often reported, little is known about the neural correlates that may contribute to these difficulties. We measured verbal and nonverbal memory using the Test of Memory and Learning (TOMAL-2) in 32 children and adolescents with MS and 26 age- and sex-matched healthy controls. Memory performance was correlated with volumetric measures of the whole brain, hippocampus, amygdala, and thalamus. Brain volumes were normalized for age and sex using magnetic resonance imaging (MRI) data from the National Institutes of Health MRI Study of Normal Brain development. With the exception of story recall, performance on memory tests was similar to that of the control group. Relative to controls, patient with MS showed reduced volume in the whole brain (p < .001), amygdala (p < .005), and thalamus (p < .001), but not the hippocampus. In the patient group, word-list learning correlated with whole brain volume (r = .53) and hippocampal volume (r = .43), whereas visual recognition memory correlated with thalamic volume (r = .48). Findings are consistent with the well-established role of the hippocampus in learning and consolidation and also highlight the importance of diffuse brain pathology on memory function.