Why do children develop demyelination and MS?

Biological reasons

Our current understanding of the biological reasons why children develop autoimmune conditions of the central nervous system (CNS – the brain and spinal cord) and multiple sclerosis is limited.

Children who develop MS seem to share the same genetic and environmental risk factors that have been found to contribute to the risk of adults developing MS. This suggests that MS in children is, in general, the same condition as MS in adults.

The normal immune system has several main jobs, including fighting infections, preventing development of tumors, and providing help during tissue repair. To accomplish its multiple jobs, the immune system is made up of different types of white blood cells (such as T cells, B cells and others) that communicate with each other and release various substances (such as cytokines, antibodies etc.) that influence neighboring cells.

In order for the normal immune system to do its jobs properly, it must be able to recognize anything that is strange or foreign, as opposed to parts one’s own body (‘self’). In some people, this ability is impaired. For reasons that are not entirely clear, the immune system in these individuals mistakenly attacks self, resulting in an ‘autoimmune’ condition. For example, when the autoimmune condition attacks the joints, the person can get arthritis, if the cells that make insulin are attacked, the person can get type 1 diabetes, and if the attack is against the CNS, the person can get MS or a related condition.

While many questions remain, our simple understanding of how MS attacks occur in adults is that immune cells (such as particular types of T cells) get inappropriately activated outside of the CNS, then make their way into the CNS. This results in local inflammation (activated immune cells releasing various substances) that can injure the cells of the CNS (the oligodendrocytes which make myelin, and the fibers (axons) that the myelin wraps). The current thinking is that a similar sequence of immune events occurs in children with MS.

There are, however, some very important differences to consider when it comes to children developing MS or related disorders. One difference is that the immune system and CNS in children is still developing. With this in mind, the strength and pattern of immune attacks in young people, the recovery potential of the injured CNS, and the benefits and risks of emerging treatments are all among the important questions that need to be answered.

Read the IPMSSG article on treatment.

 

Genetic and environmental risk factors for pediatric MS

 

The onset of multiple sclerosis (MS) occurs in childhood in about 5% of all people with MS. The disease in adults appears to result from a complex interaction of genetic and environmental factors. One of the main genetic risk factors, also confirmed in pediatric MS, is HLA DRB1*1501. This is one common gene variation among a group of genes that play an important role in immune responses, called HLA – human leukocyte antigen. HLA genes in essence place flags on a person’s individual cells, and those flags help the immune system distinguish between the body’s own cells and those of a foreign invader, such as bacteria or viruses.

In addition to genetic factors, environmental factors such as low vitamin D levels, exposure to cigarette smoke and remote Epstein-Barr virus (EBV) infection significantly contribute to a person’s risk of MS. In children, both exposure to cigarette smoke and prior EBV infection have consistently been reported as risk factors for MS. To date, the role of vitamin D has not been confirmed in this age category.

Some of the risk factors for MS have also been associated with disease course modification, such as low 25(OH) vitamin D serum levels in pediatric and adult MS. Age also modifies the ways MS appears clinically, in the cerebrospinal fluid (CSF) and on magnetic resonance imaging (MRI) in children.

Future studies will have to clarify whether interventions such as vitamin D supplementation can modify pediatric and adult MS susceptibility and disease course.

Read an IPMSSG article on Vitamin D here.