Video

Pathogenesis of Pediatric Multiple Sclerosis

Brenda L. Banwell, MD: Multiple sclerosis [MS] with onset in childhood is rare relative to adults. We estimate that somewhere between 3% and 10% of all individuals diagnosed with multiple sclerosis experience their first MS attack prior to age 18. It may not be recognized at that time as being the beginning of multiple sclerosis, but we estimate that at least 3% of patients, and maybe as high as 10%, do indeed actually begin their disease prior to their 18th birthday.

In terms of the actual prevalence of multiple sclerosis in any given world region, we have relatively little data about that. One of the reasons is that you are only a child up until a certain point. Then of course, you age into adulthood. And so, the time at which you are identified as having multiple sclerosis will influence where you’re counted in terms of the prevalence of the disease. The incidence, however, which is the number of newly recognized individuals per year, is about 100,000. That is the number of children who experience their first MS attack prior to age 18.

Prior to puberty, girls and boys experience MS about equally. After puberty, the ratio of girls to boys is 3:1. This is consistent with what we know about multiple sclerosis in adults, where there is also a much higher rate in women than men up until people get into their older years, where the ratio of males and females becomes more equal—in the rare number of people who experience their first MS attack in their 50s and 60s.

Multiple sclerosis in children is almost exclusively the relapsing/remitting type. What I mean by that is patients experience attacks that are consistent with a new area of injury in the brain, optic nerve or spinal cord, from which they typically have, at least in the beginning, very good recovery. Then they may have periods where they are not experiencing new neurological difficulties. That’s what’s called the relapsing or attack, and then a remission type of the disease. So it’s our estimation that 97% to 99% of all pediatric multiple sclerosis patients have relapsing/remitting disease at the beginning.

Primary progressive multiple sclerosis, which is a form of multiple sclerosis where patients experience worsening neurological disability from the beginning, often without very many relapses, is a disorder or a presentation that is fairly exclusive to adults.

Both pediatric and adult onset multiple sclerosis patients run the risk in their lifetime of entering into a phase of the disease that we call secondary progressive multiple sclerosis. In this stage of the disease, relapses become less common but increasing disability becomes more evident. What we all hope is that the therapies that we now have access to for both children and adults with multiple sclerosis will delay the time from disease onset to secondary disease progression, or maybe prevent it entirely.

When we look at how multiple sclerosis patients present, in terms of what those relapses actually look like, in general, the relapses in children and adults are very similar. Both groups can experience pain with eye movement, reduction in vision, and what we call optic neuritis. Patients can experience spinal cord attacks, where they may have numbness, tingling, and weakness, often involving both legs or even all 4 limbs, and sometimes with bowel or bladder difficulty.

They may have an attack that involves what’s called the brain stem, or the part of the brain that controls many different functions but particularly eye movement. And so, patients may have double vision. There are others, but those are the more common presentations. Children under the age of 12 who are experiencing their first multiple sclerosis attack may have an attack that is a little bit different than we see in adults. They may have multiple symptoms at once, and may even have some confusion or sleepiness, what we call encephalopathy.

Importantly, the majority of children who present under age 12 with those symptoms—encephalopathy and multiple neurological deficits—may have a disease called acute disseminated encephalomyelitis, or ADEM, which is not multiple sclerosis in the majority. So under the age of 12, one has to pay particular attention to the symptoms, to the MRI [magnetic resonance imaging] features, and then of course, to what happens over time to accurately identify whether a child has multiple sclerosis, whether they may have a single attack and never have other attacks in their lifetime. And now more recently, we’ve also identified that patients with demyelination, which is an attack of the immune system characteristic of multiple sclerosis and other disorders, some of those children and some adults can also have a disease that’s related to antibodies against what’s called myelin oligodendrocyte glycoprotein, or MOG, which is a distinct disorder, we believe, from multiple sclerosis.


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