Multiple Sclerosis increasing in teens – at least 2X in 9 years

---

Hospital admission rates for pediatric multiple sclerosis in the United States using the Pediatric Health Information System (PHIS) – 2016

Multiple Sclerosis and Related Disorders, September 2016, Pages 5 - 10
Amy M. Lavery ⁎, Brenda L. Banwell, Geraldine Liu and Amy T. Waldman
 Download the PDF from Vitamin D Life

Background
The onset of multiple sclerosis (MS) during childhood or adolescence is increasingly recognized in the United States. Administrative databases quantify healthcare utilization as measured by hospital admissions, providing insight into the impact of MS in the pediatric population.

Objective
We examine the frequency of hospital admissions for pediatric MS in the US using the Pediatric Health Information System (PHIS) database.

Methods
Data was extracted from the PHIS database using the ICD-9 code for MS (340.00) and reviewed to verify case ascertainment. Mean, median, and range values were determined for the number of inpatient hospitalizations per patient, number of days in the hospital, and cost of each encounter. A trend analysis was performed to evaluate the annual frequency of MS-related admissions over the study period.

Results
After case verification, the PHIS database extraction reported 2068 hospital inpatient encounters for 1422 unique pediatric MS patients between 2004 and 2013. The median number of hospitalizations per patient was 2 with a median hospital stay of 4 days. Admission rates for MS increased from 2.37 per 10,000 in 2004 to 4.13 per 10,000 in 2013.

Conclusion
The number of admissions due to pediatric MS has increased since the start of the PHIS database collection, concurrent with increased disease awareness and the establishment of dedicated pediatric MS centers.

Highlights
The Pediatric Health Information System database was extracted to determine the hospital admission rate for pediatric MS in the U.S.

• The hospital admission rate due to pediatric MS has increased from 2.37 per 10,000 patients in 2004 to 4.13 per 10,000 patients in 2013.
• Although the number of pediatric MS admissions has steadily increased in patients over 11, the number has remained relatively stable in the under 11 age group.
• Pediatric MS is a serious illness associated with frequent hospitalization and with substantive health care costs (costs averaged $38,000 per admission).

Clipped from PDF “. . . we have underestimated children with MS who were hospitalized for their incident MS attack, but not hospitalized subsequently once their MS diagnosis was confirmed (ie: none of their further relapses required hospital care)”

---

Pediatric-Onset Multiple Sclerosis: A Single Center Study – Dec 2017

Journal of Child Neurology, December 15, 2017, DOI: 10.1177/0883073817739789
Erin Yamamoto, BA, Matthew Ginsberg, MD, Mary Rensel, MD, ...

Pediatric-onset multiple sclerosis (POMS), once thought to be rare, is now being diagnosed in increasing numbers in children. Despite improvements to diagnostic criteria, the diagnosis and management of POMS remains challenging. The aim of this study is to retrospectively describe a growing POMS patient population seen at a single center over a 13 year period. Epidemiologic, clinical, neuroimaging, laboratory features and therapeutic management and outcome data were collected and analyzed. These data support associations between MS and environmental triggers such as obesity and vitamin D deficiency. Presenting symptoms, magnetic resonance imaging and laboratory findings were consistent with the existing literature; however, the prevalence of cortical lesions and abnormal saccadic pursuit is higher than other reports. Data also demonstrate a shift in practice from first- to second-line therapies over the observed period.
PDF of 2017 study is behind publisher paywall

References - 2017

• 1. Jacob, A. Multiple sclerosis: the history of a disease. Neurology. 2009;73(16):1340–1341. Google Scholar, Crossref
• 2. Chabas, D, Green, AJ, Waubant, E. Pediatric multiple sclerosis. NeuroRx. 2006;3(2):264–275. Google Scholar, Crossref, Medline
• 3. Bigi, S, Banwell, B. Pediatric Multiple Sclerosis. J Child Neurol. 2012;27(11):1378–1383. Google Scholar, Link
• 4. Chitnis, T, Tenembaum, S, Banwell, B. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler. 2012;18(1):116–127. Google Scholar, Link
• 5. Krupp, LB, Banwell, B, Tenembaum, S. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology. 2007;68(16 suppl 2): S7–12. Google Scholar, Crossref, Medline
• 6. Renoux, C, Vukusic, S, Mikaeloff, Y. Natural history of multiple sclerosis with childhood onset. N Engl J Med. 2007;356(25):2603–2613. Google Scholar, Crossref, Medline
• 7. Gianfrancesco, MA, Acuna, B, Shen, L. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors. Obes Res Clin Pract. 8(5):e435–47. Google Scholar, Crossref, Medline
• 8. Hedström, AK, Bomfim, IL, Barcellos, L. Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis. Neurology. 2014;82(10):865–872. Google Scholar, Crossref, Medline
• 9. Hedström, AK, Olsson, T, Alfredsson, L. High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women. Mult Scler. 2012;18(9):1334–1336. Google Scholar, Link
• 10. Langer-Gould, A, Zhang, JL, Chung, J. Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of children. Neurology. 2011;77(12):1143–1148. Google Scholar, Crossref, Medline
• 11. Krupp, LB, Tardieu, M, Amato, MP. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013;19(10):1261–1267. Google Scholar, Link
• 12. Mikaeloff, Y, Suissa, S, Vallée, L. First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr. 2004;144(2):246–252. Google Scholar, Crossref, Medline
• 13. Banwell, B, Ghezzi, A, Bar-Or, A, Mikaeloff, Y, Tardieu, M. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol. 2007;6(10):887–902. Google Scholar, Crossref, Medline
• 14. Waldman, A, Ness, J, Pohl, D. Pediatric multiple sclerosis. Neurology. 2016;87(9 suppl 2): S74–S81. Google Scholar, Crossref, Medline
• 15. Chitnis, T, Ghezzi, A, Bajer-Kornek, B. Pediatric multiple sclerosis: Escalation and emerging treatments. Neurology. 2016;87(9 suppl 2): S103–9. Google Scholar, Crossref, Medline  Download the PDF from Vitamin D Life

• 16. Suppiej, A, Cainelli, E. Cognitive dysfunction in pediatric multiple sclerosis. Neuropsychiatr Dis Treat. 2014;10:1385–1392. Google Scholar, Crossref, Medline
• 17. Harris, PA, Taylor, R, Thielke, R, Payne, J, Gonzalez, N, Conde, JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381. Google Scholar, Crossref, Medline
• 18. Munger, KL, Bentzen, J, Laursen, B. Childhood body mass index and multiple sclerosis risk: a long-term cohort study. Mult Scler. 2013;19(10):1323–1329. Google Scholar, Link
• 19. Langer-Gould, A, Brara, SM, Beaber, BE, Koebnick, C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology. 2013;80(6):548–552. Google Scholar, Crossref, Medline
• 20. Palavra, F, Almeida, L, Ambrósio, AF, Reis, F. Obesity and brain inflammation: a focus on multiple sclerosis. Obes Rev. 2016;17(3):211–224. Google Scholar, Crossref, Medline
• 21. Munger, KL, Chitnis, T, Ascherio, A. Body size and risk of MS in two cohorts of US women. Neurology. 2009;73(19):1543–1550. Google Scholar, Crossref, Medline
• 22. Simpson, S, Blizzard, L, Otahal, P, Van der Mei, I, Taylor, B. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry. 2011;82(10):1132–1141. Google Scholar, Crossref, Medline
• 23. Wingerchuk, DM, Lesaux, J, Rice, GPA, Kremenchutzky, M, Ebers, GC. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2005;76(9):1294–1296. Google Scholar, Crossref, Medline
• 24. Kimball, SM, Ursell, MR, O’Connor, P, Vieth, R. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr. 2007;86(3):645–651. Google Scholar, Medline
• 25. Mowry, EM, Krupp, LB, Milazzo, M. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol. 2010;67(5):618–624. Google Scholar, Medline see item below this one
• 26. Wortsman, J, Matsuoka, LY, Chen, TC, Lu, Z, Holick, MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690–693. Google Scholar, Medline
• 27. Brenton, JN, Koenig, S, Goldman, MD. Vitamin D status and age of onset of demyelinating disease. Mult Scler Relat Disord. 2014;3(6):684–688. Google Scholar, Crossref, Medline
• 28. Waubant, E, Mowry, EM, Krupp, L. Common viruses associated with lower pediatric multiple sclerosis risk. Neurology. 2011;76(23):1989–1995. Google Scholar, Crossref, Medline
• 29. Handunnetthi, L, Ramagopalan, SV, Ebers, GC. Multiple sclerosis, vitamin D, and HLA-DRB1*15. Neurology. 2010;74(23):1905–1910. Google Scholar, Crossref, Medline
• 30. Laursen, JH, Søndergaard, HB, Sørensen, PS, Sellebjerg, F, Oturai, AB. Association between age at onset of multiple sclerosis and vitamin D level-related factors. Neurology. 2015;86(1):88–93 Google Scholar, Crossref, Medline
• 31. Ait Ben Haddou, E, Alhyan, M, Aasfara, J. Multiple sclerosis: clinical characteristics and disability progression in Moroccan children. J Neurol Sci. 2014;346(1-2):128–132. Google Scholar, Crossref, Medline
• 32. Graves, J, Balcer, LJ. Eye disorders in patients with multiple sclerosis: natural history and management. Clin Ophthalmol. 2010;4:1409–1422. Google Scholar, Medline
• 33. Banwell, BL, Anderson, PE. The cognitive burden of multiple sclerosis in children. Neurology. 2005;64:891–894. Google Scholar, Crossref, Medline
• 34. Parrish, JB, Farooq, O, Weinstock-Guttman, B. Cognitive deficits in pediatric-onset multiple sclerosis: what does the future hold? Neurodegener Dis Manag. 2014;4(2):137–146. Google Scholar, Crossref, Medline
• 35. Amato, MP, Krupp, LB, Charvet, LE, Penner, I, Till, C. Pediatric multiple sclerosis. Cognitiun and mood. Neurology. 2016;87(9 suppl 2): S82–S87. Google Scholar, Crossref, Medline
• 36. MacAllister, WS, Christodoulou, C, Milazzo, M, Krupp, LB. Longitudinal neuropsychological assessment in pediatric multiple sclerosis. Dev Neuropsychol. 2007;32(2):625–644. Google Scholar, Crossref, Medline
• 37. Amato, MP, Goretti, B, Ghezzi, A. Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up. Neurology. 2010;75(13):1134–1140. Google Scholar, Crossref, Medline
• 38. Blaschek, A, Storm van’s Gravesande, K, Heinen, F. Neuropsychological aspects of childhood multiple sclerosis: an overview. Neuropediatrics. 2012;43(4):176–183. Google Scholar, Crossref, Medline
• 39. Banwell, B, Bar-Or, A, Giovannoni, G, Dale, RC, Tardieu, M. Therapies for multiple sclerosis: considerations in the pediatric patient. Nat Rev Neurol. 2011;7(2):109–122. Google Scholar, Crossref, Medline
• 40. Beres, SJ, Graves, J, Waubant, E. Rituximab use in pediatric central demyelinating disease. Pediatr Neurol. 2014;51(1):114–118. Google Scholar, Crossref, Medline
• 41. Ghezzi, A, Moiola, L, Pozzilli, C. Natalizumab in the pediatric MS population: results of the Italian registry. BMC Neurol. 2015;15:174. Google Scholar, Crossref, Medline
• 42. Chitnis, T. Disease-modifying therapy of pediatric multiple sclerosis. Neurotherapeutics. 2013;10(1):89–96. Google Scholar, Crossref, Medline
• 43. Cohen, JA, Barkhof, F, Comi, G. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–415. Google Scholar, Crossref, Medline
• 44. Hutchinson, M, Fox, RJ, Havrdova, E. Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison. Curr Med Res Opin. 2014;30(4):613–627. Google Scholar, Crossref, Medline
• 45. Rudick, RA, Stuart, WH, Calabresi, PA. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):911–923. Google Scholar, Crossref, Medline
• 46. Gorman, MP, Healy, BC, Polgar-Turcsanyi, M, Chitnis, T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009;66(1):54–59. Google Scholar, Crossref, Medline
• 47. McCabe, MP, Ebacioni, KJ, Simmons, R, McDonald, E, Melton, L. Unmet education, psychological and peer support needs of people with multiple sclerosis. J Psychosom Res. 2015;78(1):82–87. Google Scholar, Crossref, Medline

---

Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis - 2010

Ann Neurol. 2010 May;67(5):618-24. doi: 10.1002/ana.21972
Mowry EM1, Krupp LB, Milazzo M, Chabas D, Strober JB, Belman AL, McDonald JC, Oksenberg JR, Bacchetti P, Waubant E.
 Download the PDF from Vitamin D Life

OBJECTIVE:
We sought to determine if vitamin D status, a risk factor for multiple sclerosis, is associated with the rate of subsequent clinical relapses in pediatric-onset multiple sclerosis.

METHODS:
This is a retrospective study of patients with pediatric-onset multiple sclerosis or clinically isolated syndrome who were consecutively recruited into a prospective cohort at their clinical visit at the pediatric multiple sclerosis center of University of California, San Francisco or State University of New York at Stony Brook. Of 171 eligible patients, 134 (78%) with multiple sclerosis/clinically isolated syndrome were included in the cohort; a further 24 were excluded from this analysis due to lack of available serum (n = 7) or lack of follow-up (n = 17). Serum 25-hydroxyvitamin D(3) levels were measured and were adjusted to reflect a deseasonalized value. The adjusted serum 25-hydroxyvitamin D(3) level was the primary predictor in a multivariate negative binomial regression model in which the main outcome measure was the number of subsequent relapses.

RESULTS:
Among the 110 subjects, the mean unadjusted 25-hydroxyvitamin D(3) level was 22 +/- 9 ng/ml. After adjustment for age, gender, race, ethnicity, disease duration, disease-modifying therapy, and length of follow-up, every 10 ng/ml increase in the adjusted 25-hydroxyvitamin D(3) level was associated with a 34% decrease in the rate of subsequent relapses (incidence rate ratio, 0.66; 95% confidence interval, 0.46-0.95; p = 0.024).

INTERPRETATION:
Lower serum 25-hydroxyvitamin D(3) levels are associated with a substantially increased subsequent relapse rate in pediatric-onset multiple sclerosis or clinically isolated syndrome, providing rationale for a randomized controlled trial of vitamin D supplementation.