Expert Voices: Understanding Pediatric Multiple Sclerosis Research and Care
Medical expert notes difficulties in diagnosing pediatric MS
Chitnis is a board-certified neurologist specializing in multiple sclerosis-related neuroimmunological disorders. Chitnis’s interest in children with MS led her to create the Pediatric Multiple Sclerosis Center at Mass General Hospital for Children in 2004, where she is now director. Between 2010–18, she served as the elected chair of the International Pediatric MS Study Group, where she has led several initiatives in the study of MS in children, including the launch of the first pediatric MS clinical trials that led to the first FDA-approved therapy for this patient population.
Chitnis serves as a professor, lead scientist, and the director of multiple centers and studies. She has authored more than 250 publications and reviews related to MS and demyelinating disorders, and is the recipient of several awards, including the 2018 Milestones in Research Award from the National MS Society.
Can you detail the difficulties of diagnosing children with MS?
First of all, it hasn’t been well recognized that children can get multiple sclerosis. Until about 10 years ago, it was almost unheard of to diagnose MS in childhood. But thanks to the work of many organizations, including the International Pediatric MS Study Group, the National MS Society, and many other MS societies around the world, it became clear that children do get multiple sclerosis. We’ve now developed diagnostic criteria for multiple sclerosis in children through the International Pediatric MS Study Group.
But it is still a challenge to disseminate this information to those who might be seeing children on the frontlines, including pediatricians, pediatric emergency room physicians, even pediatric neurologists.
When a child presents with a symptom such as weakness, it might go unrecognized by both parents and the child. Children might just think it’s growing pains or something not worth bringing to parents’ attention, while parents might think the child is weak because they bumped their knee or fell.
I had a case of a young girl who had fallen and had leg weakness, and so it was thought that the leg weakness was due to the fall. She was treated for trauma and knee injuries, but it became apparent that she fell because she was weak from a neurological disease. Those are some of the challenges: understanding from the patient, from the parents, from the healthcare system, from society, from diagnostic definitions. These must be addressed through the dissemination of information.
How might the care team for pediatric MS differ from adult MS?
The care team is similar in many ways. There’s, of course, a neurologist usually at the center of the care team. But because pediatric MS is a rare disease, there are not a lot of neurologists who have expertise in treating this disorder. An adult patient could go to an MS center in their community or nearby, whereas that might not be the case for a pediatric MS patient.
Having a school liaison or an educational liaison on the care team is helpful, as the MS diagnosis might impact school performance in a couple of ways. A child might encounter physical issues, though fortunately children do recover well from their relapses compared to adults, and we generally see that children do well physically. But the child will also face major challenges in cognition and mood. The large lesions that tend to occur in pediatric MS can affect cognitive performance, induce fatigue, and overall affect school performance.
One might also include a neuropsychologist who specializes in pediatric neurological diseases, and ideally in pediatric MS. They help to evaluate the cognitive domains that may be affected in pediatric MS, and can help in developing a school plan such as an Individualized Education Plan or a 504 Plan.
How does the disease course of pediatric-onset MS differ from that adult-onset MS?
Pediatric-onset MS tends to be more inflammatory than adult-onset MS. Children have two-to-three times as many relapses as adults do. Their MRI lesions are also larger and tend to be quite diffuse. This does indicate that pediatric MS is a very inflammatory disease. And this is not just isolated to children: a 20-year-old MS patient will have a higher relapse rate than a 40-year-old patient. Along that vein, a teenager with MS will have an even higher inflammatory or relapse rate than a 20-year-old adult patient.
The good news is that, overall, there is a good recovery from relapses in pediatric patients, which is good given this high relapse rate. But if injury upon injury keep occurring, then that could lead to accrued disability and a higher risk for disability down the road.
A third difference is that the disability accrual in pediatric-onset MS patients tends to be a bit slower than in adult patients. So that means that over a 10-year period of having MS, the pediatric MS patient will have a lower expanded disability status scale score than an adult patient. But the caveat: a 30-year-old, pediatric-onset patient will have more disability than a typical 30-year-old adult-onset patient, who might have had their onset five years ago as opposed to 15 years ago.
Another difference is that we’re seeing more cognitive deficits in children with MS than adults. And this is why kids need support school-wise and cognitively, as well as more treatment. We’ve recently realized that when they reach adulthood, younger-onset patients tend to have more difficulties with continuous employment and work-related metrics compared to adult-onset patients. I think this because their disease affects them in their key educational and formative years, as opposed to acquiring a skillset and then later on being diagnosed with the disease.
Do MRIs look different for pediatric-onset MS compared to adult-onset MS?
Yes, absolutely. The pediatric-onset patients have more inflammatory-appearing MRIs, which reflects their higher relapse rate. The lesions are larger and there’s a higher T2 lesion volume. Also, the new gadolinium-enhancing lesions, which indicate areas of active inflammation, are typically higher in children compared to adults.
Do the rates of each MS type (relapsing, primary progressive, or secondary progressive) for pediatric-onset MS differ from adult MS populations?
Yes. The pediatric-onset patients have a very, very low incidence of primary progressive MS. In adults, somewhere in the range of 10% are primary progressive (PPMS) at onset, whereas in pediatric-onset MS, it’s very rare to diagnose a PPMS patient. For pediatric-onset patients, about 99% of them are relapsing-remitting at onset.
How might treatment differ between pediatric-onset and adult-onset MS?
Currently, we only have one FDA-approved therapy for pediatric MS, Gilenya (fingolimod), and that’s approved for treating children ages 10 to 18. This is one of the higher efficacy treatments. The [PARADIGMS] clinical trial that supported approval showed there was an 82% reduction in annualized relapse rates in the Gilenya-treated patients compared to the Avonex-treated patients.
This does indicate that there is a need for highly effective treatment in pediatric-onset MS patients. And given their high relapse rates and the potential for disability and cognitive and work-related issues down the road, I think it’s very important to treat patients with a highly effective therapy.
There are a number of clinical trials ongoing for pediatric MS; they’re testing B-cell depleting therapies and other forms of sphingosine-1-phosphate (S1P) receptor modulators. Now there are published studies for oral therapies including dimethyl fumarate as well as teriflunomide.
Some gaps still remain in terms of treatment. There’s still a lot of off-label use medications for pediatric MS. That leads to questions such as to which dose is appropriate for different ages of children. And although we are generally seeing that these medications have a similar side effect profile in children compared to adults, it’s important that this be evaluated in large-enough, well-conducted studies. But most expert pediatric MS specialists are treating their patients with either oral or infusion therapies, or injectables, that are highly effective.
What aspects of pediatric MS need more research?
We certainly need better understanding of the impact of MS on short- and long-term outcomes, not only in regard to disability and relapses, but also on cognition, quality of life, development, and psychosocial outcomes.
We also need more understanding of non-pharmaceutical modifications that may help children — such as nutrition, exercise therapy, physical therapy — and the impact of those on the disease course for pediatric-onset MS patients.
We’ve made strides in diagnostic definitions, but these need to be further updated, especially around differentiating pediatric MS from similar disorders.
Further dissemination of all of these results also is needed: to pediatric specialists, pediatricians, pediatric neurologists. Lastly, we need to research the etiology, or cause, of pediatric MS. Why does it occur? And can we learn more about the risk factors and etiology of MS in general by studying pediatric MS?
Has any research about pediatric MS surprised you?
The big surprise early on was that this was a very inflammatory disease. And if we go back over 15 years ago to the history of the study of pediatric MS, it was sort of touted as a very benign disease and a mild disease, maybe not one that needed treatment. But once we started looking at these children and really comparing their course to adults, it did turn out to be a very inflammatory disease that requires treatment.
Another surprise is the fact that it’s occurring in children more frequently. Maybe this is due to better diagnostics, but there are other factors that may predispose to pediatric-onset MS, including obesity in childhood, which is a factor that can be addressed.
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