Multiple Sclerosis Environmental Risk Factors for Pediatric Multiple Sclerosis Naila Makhani, MD1 and Brenda Banwell, MD2
1. Fellow, Pediatric Demyelinating Disease Program, The Hospital for Sick Children and University of Toronto; 2. Associate Professor of Pediatrics (Neurology), Associate Scientist, Research Institute, and Director, Pediatric Multiple Sclerosis Clinic, The Hospital for Sick Children and University of Toronto
Abstract
Multiple sclerosis (MS) is a common neurologic disorder that is likely the result of aberrant immune responses to key childhood environmental exposures in genetically predisposed individuals. This article discusses the current understanding of environmental risk factors implicated in MS with a focus on pediatric research. The study of children with MS is a powerful means of understanding MS biology and is highly relevant to the development of disease prevention strategies.
Keywords Multiple sclerosis, children, environmental risk factors, Epstein-Barr virus, vitamin D
Disclosure: The authors have no conflicts of interest to declare. Received: September 14, 2010 Accepted: November 22, 2010 Citation: US Neurology, 2010;6(2):96–101 Correspondence: Naila Makhani, MD, Division of Neurology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G 1X8 Canada. E:
naila.makhani@
sickkids.ca
Multiple sclerosis (MS) is a chronic inflammatory and degenerative disorder of the central nervous system (CNS). Up to 10% of adults with MS recall experiencing their first symptoms before 18 years of age, and between 2.5 and 5% of MS patients are formally diagnosed during childhood or adolescence.1–7
The pathobiologic mechanisms underlying
MS remain incompletely understood. However, there is increasing evidence that MS may be due to aberrant immunologic responses to environmental exposures experienced during childhood in genetically predisposed individuals.8
Owing to their young age, children with MS
have a shorter time window than adult patients between exposure to an environmental trigger and clinical disease onset. Appreciation of the key environmental factors is therefore vital to developing preventative strategies. In this article, we discuss the current understanding of environmental risk factors implicated in childhood-onset MS, with a focus on pediatric MS-based research.
Geography and Migration
The worldwide geographic distribution of adult-onset MS suggests a relationship between MS prevalence and increasing latitude9–11 (see Figure 1). Latitude gradients may be observed even within a single country as reported in Australia, France, and the US.12–14 children has been reported in many countries worldwide;1–4,15–27
MS in however,
large-scale international collaborations will be required to determine whether global geographic patterns observed in adult-onset disease hold true in the pediatric population.
Place of residence early in life may have a significant influence on future MS risk. The prevalence of MS in individuals immigrating to England from India or Pakistan was found to be highly dependent on age
96
at immigration, with MS being much more common in those who immigrated before 15 years of age.28
A Canadian study examining
country of birth, place of residence during childhood, and self-reported ancestry in 44 pediatric-onset and 573 adult-onset MS patients found that pediatric MS patients were more likely to report Caribbean (maternal p=0.0177; paternal p=0.0007) or Asian (maternal p<0.0001; paternal p<0.0001) ancestry compared with adult-onset MS patients, reflecting recent immigration patterns.29
In contrast to differences in
parental ancestry, there was a striking similarity in the proportion of adult-onset and pediatric-onset MS patients born in North America and in the proportion of MS patients who had spent some of or all of their childhood in Canada, suggesting that place of residence during childhood is a profound determinant of MS risk.
Vitamin D Background
Geographical variations in MS prevalence, including observed latitude gradients, may be explained by ambient sunlight exposure and vitamin D status. In humans, the primary source of vitamin D is via cutaneous conversion of 7-dehydrocholesterol to vitamin D3, a process requiring ultraviolet B (UVB) radiation. Vitamin D3 can also be obtained through the diet, predominantly through ingestion of oily fish and fortified foods. In the liver, vitamin D3 is converted to 25-hydroxyvitaminD3 [25(OH)D], the main circulating form of vitamin D and the most commonly used serum marker of vitamin D status.30,31
Epidemiology
Seasonal variations in vitamin D status may explain the month of birth relationship observed in MS patients.32,33
In a pooled analysis of 44,045 © TOUCH BRIEFINGS 2010
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132