Two MS Scientific Research Foundation-funded studies shed new light on pediatric-onset MS
Although most cases of MS begin during adulthood, some estimates suggest that 2 - 5 % of all cases are diagnosed in individuals under the age of 18, and MS has on rare occasions been diagnosed in children as young as two years old. MS that has been diagnosed in children and adolescents – termed pediatric-onset MS – is similar in many ways to relapsing-remitting MS in adults; however, certain symptoms tend to be more common in children than adults, particularly lethargy and seizures. Proper diagnosis of pediatric-onset MS is further complicated by its similarity to other childhood disorders – such as acute disseminated encephalomyelitis (ADEM), acute central nervous system infection, and certain diseases of the blood vessels and mitochondria – as well as difficulty experienced by young children in describing their symptoms. To date, studies have shown that many disease-modifying therapies used to treat MS in adults are also generally safe to use in children, although the relative infrequency of pediatric-onset MS makes it difficult to systematically study this form of the disease and determine how it affects childhood development.
A pair of studies that set out to explore pediatric-onset MS in detail was published this past month by the Canadian Pediatric Demyelinating Disease Network, a group of over 20 pediatric health-care facilities in 17 cities across Canada that was formed with support from an MS Scientific Research Foundation (MSSRF) collaborative grant. The team of researchers that carried out both studies include MS Society-funded investigators Drs. Douglas Arnold and Brenda Banwell, who are leading scientific authorities in the fields of neurological imaging and pediatric-onset MS, respectively. The first study, published in the journal Neurology, investigated the impact of pediatric-onset MS on brain growth and development over time. The second study, featured in the journal Multiple Sclerosis, examined inflammatory lesions in the brains of both children and adults with MS, and compared the degree of tissue damage within lesions associated with pediatric- versus adult-onset MS.
Pediatric-onset MS negatively affects brain growth
In this study, a team of researchers used magnetic resonance imaging (MRI) scans to compare the changes in brain volume over time of 36 individuals with pediatric-onset, relapsing-remitting MS to those of healthy individuals (controls). The study followed the participants over a period ranging from 1 to 8 years. The participants were categorized based on sex in order to determine if changes in brain volume differed between males and females. In addition to measuring overall brain volume, the researchers also examined changes in the volumes of specific brain regions that are important for proper cognitive function.
The study found that onset of MS during childhood and adolescence leads not only to impaired age-expected brain growth, but also to an overall decline in brain volume, a phenomenon known as atrophy. Pediatric-onset MS affected the brain volumes of both males and females, although the growth trajectories were different, suggesting that sex is an important factor to consider when evaluating changes in brain development in children and adolescents with MS. Strikingly, a brain region called the thalamus was particularly vulnerable to impaired brain growth. Since the thalamus is considered the “gateway to consciousness” and serves as an important relay station for information traveling to the cerebral cortex (responsible for “higher order” functions like language and information processing) of the brain, the authors suggest that reduced size of the thalamus may be linked to cognitive impairments in individuals with pediatric-onset MS.
Tissue destruction in MS lesions differs between pediatric- and adult-onset MS
Researchers in this study set out to compare how inflammatory lesions in MS-affected brains differ between individuals with pediatric- versus adult-onset MS. The rationale for this study was based on observations that children seem to recover more quickly and effectively than adults from damage to the brain caused by stroke and trauma; thus, the authors speculated that the brains of children and adolescents with MS may be more resilient to the damage caused by inflammatory lesions. The researchers followed a group of 29 pediatric and 24 adult MS participants and compared data obtained from MRI scans; each participant had 3 scans taken one year apart. The researchers identified brain lesions on the second scan, and used a specific imaging marker to measure tissue damage before, during, and after formation of a given lesion. By quantifying changes in tissue damage, they were able to compare recovery of tissue within a lesion in children and adolescents versus adults with MS.
The research team found that, although both pediatric and adult participants with MS experienced partial recovery of tissue destruction in a given lesion, pediatric MS participants demonstrated a greater degree of lesional recovery, suggesting that children and adolescents with MS may have a greater capacity to repair tissue damage at lesion sites compared to individuals whose MS emerged during adulthood. For future directions, the authors plan to study this phenomenon further and attempt to draw a link between lesional recovery and improvement in symptoms like cognitive performance and physical functioning.
The pair of studies published by the Canadian Pediatric Demyelinating Disease Network sheds new light on some unanswered questions in pediatric-onset MS research; namely, what are some key differences in the disease mechanisms between pediatric- and adult-onset MS, and what are the implications of MS when diagnosed at an early age on an individual’s brain development? The news for those with pediatric-onset MS is mixed: on the one hand, children and adolescents appear to bounce back more easily from the tissue damage wrought by inflammatory lesions due to their greater capacity for repair. On the other hand, the brain’s resilience has its limits, and children and adolescents with MS are vulnerable to impaired brain growth compared to their healthy counterparts. These findings highlight the need to pursue further research into treatment strategies that both protect the brain from damage as early as possible and aggressively repair damage as it arises.
1. Auberte-Broche et al. Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth. Neurology. 2014. 83(23):2140-6
2. Ghassemi R et al. Quantitative measurement of tissue damage and recovery within new T2w lesions in pediatric- and adult-onset multiple sclerosis. Mult Scler. 2014. [Epub ahead of print]