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Pediatric Multiple Sclerosis
Director, NYU Langone Multiple Sclerosis Comprehensive Care Center
New York, New York
Hospital and Institute Affiliations
Pediatric Neurology, Multiple Sclerosis
What are the current challenges associated with diagnosing and treating patients with multiple sclerosis (MS)?
The first challenge is that even though we have wonderful tools to help us with a diagnosis of MS, there are still situations in which making the diagnosis is difficult.
Research has been helpful in terms of emphasizing what specifically a clinician should look for on magnetic resonance imaging. Research has also shed new light on some of the advantages of spinal cord examination. But even with all these tools, the incidence of MS misdiagnosis is notable.
The second issue is treatment. In contrast to before 1993 when there were no treatments to modify the MS disease course, now there are multiple disease-modifying therapies. The challenge is how do you pick which one?
The third thing that is challenging for healthcare providers, as well as people with the disease, is making it clear that there is a difference between improving symptoms and modifying the disease course. Symptomatic therapy might include physical therapy, yoga, meditation, exercise, and mindfulness. There are medications for stiffness and spasticity, and medications to improve walking speed. There are also techniques to enhance thinking.
Another treatment challenge is determining whether a clinician should start with the most efficacious medication as opposed to starting with a less efficacious medication, as there are going to be patients who will respond well with the latter. This strategy would translate to reserving the stronger guns for when you need them and giving them to patients who experience disease breakthrough.
What are the unique clinical considerations when treating pediatric-onset MS?
Children with MS are interesting. Although adults with MS often use canes or walkers, you’re almost never going to see that in pediatric MS patients because they tend to physically recover from the disease well. What is not yet known are the long-term consequences of MS as these children mature into adults. Although they will transition to a progressive phase more gradually than adults, they’ll also reach any given level of impairment at an earlier age.
If you examine a theoretical cohort of children who were diagnosed with MS before the age of 18 and a cohort of adults who were diagnosed with MS after the age of 18 and ask, “Who is going to be using a cane in 5, or 10, or 20 years?”, the children may end up using a cane in 25 years, whereas the adults may end up using a cane in 15 years. The cohort of children “got there” more slowly, but because they started out at such a young age they reach the same level of impairment at a younger age. So you can potentially have a lot of young people in their 30s with serious problems.
We know from a number of different studies, including a clinical trial using fingolimod that was initially conducted in adults and was repeated in pediatric patients with MS (ClinicalTrials.gov Identifier: NCT01892722), that there was an increase in disease relapses occurring in children compared with adults. There was also a lot of inflammatory activity noted in the children.
But it is difficult to compare studies, and you want to be careful when you do that. In general, pediatric patients experience more frequent relapse compared with adults as they have a high lesion burden and lesion accumulation. They may also have some cerebral volume loss. But physically, they “bounce back.” Although they look “pretty good” on the surface, they can have problems that are subtle and others that can become worse later on.
Children may also experience psychological and social struggles. They want to be like everybody else; however, after receiving an MS diagnosis, they have a chronic illness. If they have some cognitive slowing, that may increase the chance that they may experience depressive symptoms. They miss school because they have medical appointments and they have relapses. They need to take steroids and other medications on a chronic basis. All of that takes a toll, so one of the exciting opportunities that can be expanded in the future is exploring ways of delivering high-quality care to children through telemedicine and telerehabilitation.
Can you discuss cognitive dysfunction in MS and the challenges associated with identifying, measuring, and addressing it?
Some people with MS report they aren’t thinking as quickly, and they may describe having a very real problem with their cognition. Other people can adjust to the cognitive changes better. We have found that if someone is experiencing a significant amount of cognitive slowing, there is often an association with a broader array of difficulties. While we don’t have any Food and Drug Administration-approved therapy to make you think faster, there has been a lot of interest in helping people to think more efficiently, remember specific points better, and pay better attention. So the questions that we’ve been researching are: What is the best way for a clinician to determine when someone has been having an issue with cognition? How can you quickly identify cognitive issues? What is the basis for that cognitive difficulty? What can you do about it?
We have found that for cognitive screening measures to be effective, they have to be both easy to use and brief. They can be conducted on paper and pencil or they can be computerized, and there are advantages and disadvantages to both approaches.
I have been interested in trying to find ways of delivering interventions in the home that will improve cognitive functioning. These interventions can take the form of computer-mediated cognitive exercises. One of the research areas that I’m collaborating on with Leigh E. Charvet, PhD, here at NYU Langone Health, uses very gentle electrical stimulation to enhance the benefits that someone might get from doing either physical exercises or mental exercises.
Another very real question is whether the MS disease-modifying therapies we currently have affect cognition. For example, clinicians would not expect a patient to think faster when receiving disease-modifying therapy. What you may see is appropriate adaptations and compensations that address the negative effects associated with MS.
In total, what we want is an effective treatment that prevents further worsening and would allow those compensatory mechanisms to have an effect. However, we don’t really know how well the most effective agents work compared to the moderately effective agents in terms of preserving cognitive function. But my suspicion is that if you can control lesion burden and relapses, you can control volume loss, and that must be better for preserving cognition.
Lastly, there are many confounders — such as education, reading skills, and memory skills — in something as complex as cognition. Also, some people have occupations that involve more cognitive exertion than others. Some people probably also just have inherently better or worse ability to repair from damage, which has an effect on cognition.
So, there are a lot of different variables that influence that concept of cognition, and we have very divergent ways of measuring it. But again, I think that the more you control disease activity, the better it’s going to be in the long-term for cognition.
What are the current gaps in MS knowledge that future research has yet to address? What practical knowledge has to be studied that can have immediate effects on clinical practice?
From a very practical point of view for clinicians, we need to be more informed about the things that can help promote recovery, including specific diets and exercise. We need more guidance on how to pair up the best treatment option with a specific individual. An ultimate goal would be identifying biomarkers that will help us guide therapy. We need more biomarkers that will say that a particular person might have an increased risk for other problems down the road.
Two drugs were recently approved by the FDA to treat relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS). What effects will these drugs have on the future treatment of MS?
I think that in one case you’re dealing with a newer sphingosine-1 phosphate receptor agonist, which has the same mechanism of action as fingolimod. The advantage now is being able to escalate the dose of the medication, which may lower the risk for a cardiac effect where you can have transient bradycardia for 6 hours. Another advantage is the potential to wean patients to a lower dose before stopping the medication. Whether this will result in a decreased likelihood of rebound will be interesting to see.
Then there are the advantages of patients not having to go to an infusion center. The idea of prescribing pills instead of shots or commitment to infusion appointments is a definite improvement.