Faculty Bibliography

BACKGROUND: The clinical and MRI presentation differs between earlier- and later-onset pediatric multiple sclerosis (MS), whereas the effect of age on the CSF inflammatory profile is unknown and may contribute to delayed diagnosis. OBJECTIVES: To compare the CSF cellular and immunoglobulin G (IgG) profiles between earlier- and later-onset pediatric MS. METHODS: We queried the databases of 6 pediatric MS centers for earlier-onset (onset <11 years) and later-onset (> or = 11 and <18 years) patients with MS or clinically isolated syndrome who underwent CSF analysis within the first 3 months of presentation (observational study). We compared CSF white blood cell (WBC) differential count, IgG index, and IgG oligoclonal bands between age groups. RESULTS: We identified 40 earlier-onset (mean age at onset = 7.2 +/- 2.7 years, 60% females) and 67 later-onset pediatric MS patients (15.1 +/- 1.7 years, 63% females). Although WBC count tended to be higher in earlier-onset patients (median = 9/mm(3) [0-343] vs 6 [0-140], p = 0.15), they had a lower proportion of lymphocytes (70% [0-100] vs 93% [0-100] of WBCs, p = 0.0085; difference = +3% per 1-year increase of age, p = 0.0011) and higher proportion of neutrophils than later-onset patients (0.5% [0-75] vs 0% [0-50] of WBCs, p = 0.16; difference = -1% per 1-year increase of age, p = 0.033). In earlier-onset disease, fewer patients had an elevated IgG index than in the later-onset group (35% vs 68% of patients, p = 0.031). CONCLUSION: Age modifies the CSF profile at pediatric multiple sclerosis (MS) onset, which may mislead the diagnosis. Our findings suggest an activation of the innate rather than the adaptive immune system in the earlier stages of MS or an immature immune response.

Little is known about psychiatric aspects of pediatric demyelinating conditions. A total of 23 youths (6-17 years) with demyelinating conditions underwent semistructured psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Adolescents and parents completed the Child Symptom Inventory-4 and the Youth's Inventory-4. Fears and conceptions of their neurological problems were elicited. In all, 48% (n = 11) met criteria for current psychiatric diagnoses, including 27% (n = 3) with depressive disorders and 64% (n = 7) with anxiety disorders. Fears and conceptions of the illness were severe and diverse. Depressive and anxiety disorders are common in pediatric demyelinating disease. Clinicians should therefore screen for psychiatric comorbidity symptoms as part of the routine evaluation of such patients

Fatigue and quality of life are significant concerns in adult multiple sclerosis (MS) but little is known about these factors in pediatric MS. The present investigation evaluates fatigue and quality of life in 51 pediatric MS patients to determine the rate of fatigue and reduced quality of life and assesses the relations between these variables and clinical factors. Fatigue and quality of life were assessed by self- and parent-report via the PedsQL Multidimensional Fatigue Scale and the PedsQL Quality of Life Scale. One-sample t-tests determined if scores were below published data for healthy individuals. Moreover, scores falling one standard deviation from norms were considered mildly affected, with severe difficulties being defined as scores falling two or more standard deviations from norms. Associations between self- and parent-reported difficulties and clinical factors were examined via Pearson correlation analyses. In comparison with healthy samples, pediatric MS patients reported greater difficulties with respect to fatigue, sleep, cognition, physical limitations, and academics. In addition to significant difficulties on these factors, parents reported problems with respect to emotional functioning, and tended to report greater fatigue, sleep, and cognitive difficulties than were self-reported. Expanded Disability Status Scale score was the only neurologic variable significantly related to fatigue or quality of life scores. Fatigue was significantly correlated with reports of sleep difficulties, cognitive problems, and quality of life variables. These findings suggest that fatigue and poorer quality of life is a clear concern in pediatric MS, and is related to overall physical disability

Pediatric multiple sclerosis (MS) accounts for up to 5% of all MS cases. Work conducted over the past 5 years has provided new information about the treatment, pathogenesis, demographics, and natural history of this disorder. Genetic and environmental factors seem to exert critical influences on its development. Clinical, MRI and laboratory data from prepubertal and postpubertal children suggest differences between the immune response and/or CNS environment in younger compared with older children and adults with MS. Randomized, controlled treatment trials for pediatric MS have not yet been performed, but therapies used in adult MS have been evaluated in this population, and their use seems to be safe. This article provides a comprehensive review of current knowledge regarding pediatric MS, highlighting new advances in the field.