Infectious Triggers

Children with MS have been shown to have a significantly increased likelihood, relative to healthy age-matched peers, of being previously infected with Epstein-Barr virus (EBV) (Alotaibi et al., 2004).  EBV infection leads to persistent B-cell infection, and B-cells are known to play a role in MS.  Study of children enrolled from geographical regions has confirmed that the association of EBV with MS, suggesting that the association of EBV with MS is common among multiple world regions (Banwell, Krupp et al., 2007).  Immunological studies specifically exploring T- and B-cell behaviour in EBV-positive MS patients, may provide insights into how EBV infection influences the immune system in people with MS (Ascherio et al., 2007). 

Sunlight Exposure, Vitamin D, and MS

The increased prevalence of MS in temperate regions has prompted consideration of the role of vitamin D and sunlight exposure as potential non-infectious environmental risk factors for MS.  Exposure to sunlight is the primary source of vitamin D, and as such, in the winter months very little, if any, cutaneous vitamin D synthesis occurs.  Individuals with MS have been shown to have lower vitamin D levels as compared to age-matched healthy controls (Nieves et al., 1994), although this finding is confounded by the potential limit in outdoor activity of patients with MS.  An inverse relationship has also been demonstrated between serum concentrations of 25-hydroxyvitamin D obtained from young adults entering the military and their risk of MS diagnosis in mid-adulthood (Munger et al., 2006).  The potential role for vitamin D supplementation in the primary prevention, or amelioration, of MS is an exciting area of ongoing research. 

The First Attack

MS in both children and adults is characterized by multiple episodes of neurological dysfunction secondary to inflammatory demyelination of the central nervous system (CNS).  Just as in adults, however, not all children who experience an initial acute demyelinating syndrome (ADS) will develop MS.  The term "clinically isolated syndrome or CIS" has also been applied to persons experiencing a first demyelinating event, although many authors restrict the term CIS to patients with an initial demyelinating event at high risk for future diagnosis of MS.  As such, the term "CIS" is not universally applied across the entire spectrum of ADS events, particularly those considered to have a low risk of relapses. 

An ADS is classified as "monofocal" if the clinical features were referable to a single CNS lesion, such as optic neuritis, transverse myelitis, or brainstem, cerebellar, or hemispheric dysfunction; and as polyfocal if the clinical features are localized to more than one CNS location.  This is based on the physician's clinical examination, rather than MRI findings (which could show asymptomatic lesions).  "Polyfocal" features refer to more than one CNS lesion and when accompanied by problems with thinking, is termed, acute disseminated encephalomyelitis (ADEM) (Krupp, Banwell, & Tenembaum, 2007). 

Transverse Myelitis:

Transverse myelitis (TM), or attack of the immune cells on the spinal cord, leads to loss of strength and sensation of the limbs and difficulty with bowel and bladder control.  TM was the presenting feature of MS in only 14% of children enrolled in a multinational pediatric MS Study (Banwell, Teller et al., 2005). 

Optic Neuritis:

Optic neuritis (ON), an attack of the immune system on the optic nerve from the eye, results in reduced vision, pain with eye movements, and difficulty seeing color.  It has been thought that bilateral ON is more common in children and unilateral ON more common in adults.  This may simply reflect, however, that young children may not notice or report loss of vision in one eye.  In one study of childhood ON, in which some patients were followed for 40 years, 26% were ultimately diagnosed with MS (Lucchinetti et al.  1997).  In a review of ON at SickKids, in Ontario, Canada (www.sickkidsfoundation.com), bilateral ON was more common than monocular ON, and was associated with a greater likelihood of MS diagnosis (Wilejto et al., 2006).  Of the 36 children enrolled, 13 (36%) were diagnosed with MS within the two years of ON, an outcome that was highly correlated with MRI evidence of white matter lesions in the brain. 

Acute Disseminated Encephalomyelitis (ADEM):

For a diagnosis of ADEM, there must be a multiple neurological symptoms plus trouble thinking (encephalopathy).  The demyelinating event in some children may be accompanied by fever, drowsiness or even coma, and neck stiffness. 

What happens to children with ADS:

In a review of 296 children with acquired demyelination in France,

­      57% were diagnosed with MS, while the remaining

­      43% appeared to have a monophasic illness (Mikaeloff, Suissa et al., 2004). 

­      The children in this study were followed for a mean of 2.9 years (range 0.5- 14.9 years). 

Since patients can develop their second MS-defining attack years after their first attack, it is possible that the percentage of children in the French study ultimately diagnosed with MS will increase as the duration of follow-up lengthens.