For decades, multiple sclerosis was considered an adult disease that didn’t show up until a person—usually a woman—was somewhere between 20 and 40 years old. Now it turns out that five percent of the 400,000 Americans who get diagnosed with this disabling neurological condition are children.
MS attacks the central nervous system, including the brain, spinal cord and optic nerves, and can cause a range of symptoms, including fatigue, tingling sensations, difficulty walking and vision and memory problems. Usually, these episodes come and go, but worsen over time. In children, MS can have profound effects on cognitive development, performance in school and relationships with friends and family.
Recently, ABILITY Magazine editor-in-chief Chet Cooper visited the West Coast’s only pediatric MS center, housed at the University of California, San Francisco, to talk with founder Dr. Emmanuelle Waubant.
Chet Cooper: How did you come to establish the pediatric MS clinic?
Emmanuelle Waubant: I’m an adult neurologist by training, and my research has been mainly in that and in immunology. I also study the link between them. MS is the main disease shared by both, so that’s how I got interested in it. I’ve been involved in pediatric MS for more than 10 years.
Since MS is not common in children, in the past, parents were lucky when their child got an accurate diagnosis right away. When they did not, they just saw one pediatrician after another. At the time, there were drugs that were approved for adults with MS, but not yet for children. Naturally we had to operate in that gray area for a long time, and when we told parents that we wanted to use certain adult drugs to prevent the disease from worsening in their children, they worried. That was when I started to connect with other pediatric neurologists throughout the country who were treating children with MS. We pooled our data on the safety of giving interferon to children. We actually published the first article on the subject.
Once I convinced parents that the drug was safe for adults and that a scaled-down dosage should be equally safe in children, then health insurance companies still denied children access to the medication. So that again pushed me to join forces with other physicians treating pediatric MS. Since then there’s been lots of change. We now have approved treatments for children.
CC: After you got the medications approved, what was your next challenge?
EW: That’s when it became pressing to identify the disease in children as early as possible. In the past five years, there’s been a greater effort to promote awareness of pediatric MS. Different groups have written papers about their experiences, as well as about the safety of various medications typically marketed to adults. Then, a couple of years ago, we got a grant to start a pediatric clinic for MS patients that would be staffed by a team of pediatric neurologists, as well as doctors with MS expertise.
We were lucky, because we were one of the only centers to be sponsored by the national MS Society, and we’re the only one on the West Coast. Eight of us work together part time. In the past year we’ve seen 65 to 70 patients. During a visit, patients are seen by a pediatric neurologist, an MS expert, a pediatric social worker and a pediatric nurse/psychologist. We get all these specialists together in the same exam room for the first visit, and then the family and the child split up and go with whomever they need to see. So the evaluation is very thorough. We take into account not only the symptoms of the child and his or her need to be diagnosed or treated, but also the family dynamic and potential problems the child faces in school. It’s very rewarding because we’re able to spend time with the family. We’re able to provide them with the important information they need to care for the child.
CC: How broad a range would you say you have?
EW: We are a regional pediatric MS center that sees all the patients on this side of the Rockies. The next closest facility is the Mayo Clinic in Rochester, MN. All the others are east of that. We try to be highly visible and increase awareness about pediatric MS, what it has in common with adult MS as well as how it is different.
CC: How is it the same and how is it different?
EW: What’s common between adult and pediatric MS is that most of the symptoms are going to be similar, such as loss of balance, double vision, decreased vision, weakness and numbness in different parts of the body. What’s different is that sometimes, if the symptoms are mild and the child is young, the awareness of what’s normal and abnormal is different. If a child is six and has mild decreasing vision in one eye, he or she is not always going to complain about it. If they have severe loss of vision in one eye, then a teacher may be the one to notice that something is wrong and call the parents. Sometimes that’s how the problem is identified.
One big difference is the potential impact of MS on a child’s thinking. That has much more complicated ramifications in kids than in adults, because most adults are functioning at a set level. Children are on the ascendant curve of their development. If that is affected then the consequences are much more significant than in people who are not facing the challenge of trying to learn for hours on a daily basis. There’s actually data that shows if you had MS early in life, you’re more likely to face academic problems. So if a child is diagnosed early, we can identify the problems and address them sooner.
There are also diseases that mimic MS. Some are metabolic diseases, which are typically genetically inherited diseases that we see mostly in younger patients. As an adult neurologist, I’m not trained to diagnose these. That’s why it’s very important for me to work with my pediatric neurologist colleagues. There’s another disease called ADM, which is an acronym for acute disseminating encephalomyelitis, which is basically an inflammation of the brain and spinal cord that typically comes after or during an infection. That is also more common in children than in adults, and early on it can look like MS. But typically there’s only one phase to that disease, as opposed to MS, which has relapses that come and go. In these children, at least a third will actually develop MS.
CC: In treating children, do you use a smaller dosage of the same medication that you use in adults?
EW: For children 10 or under, we often use a smaller dose to get started, so that tolerability is better and side effects are minimized. However, within a few months, most younger patients end up on the full dose that we would use in adults. There is no major difference.
CC: What is your preference: To observe a new patient over a period of, say, six months to see if there’s something going on, or to get them on medication immediately?
EW: It all depends. For instance, if we see a child who (1) has experienced his first episodes and we feel comfortable that it is MS and not ADM, and (2) there are not many abnormalities on the initial brain MRI and the child has had a mild relapse and has fully recovered, then most of the time we are going to follow up for the first six months or year with repeat clinical evaluation and MRI. However, if we see a child that has had one episode and did not recover well, and shows huge amounts of abnormality on the brain and MRI, we’re going to be more proactive. At the same time we have to take into account whether the child and the parents are ready for medication. If we see a child who has had several episodes with documented changes on the MRI, and these episodes have occurred over a relatively short period of time, it’s a no-brainer: We’ll recommend treatment.
CC: So you see lesions both on the brain and on the spine in both adults and children?
EW: In some instances, but we are still studying the differences and plan to develop additional research, because there are occurrences in children that may help us to advance our understanding and treatment of adult MS. For example, if there is really some kind of overlap between ADM and MS, why is it that one immune system can resist the next phase of the disease, while another immune system cannot? So if you find the answer to that, it’s a home run as far as developing a treatment.
We suspect that younger children’s brains may have the capacity for self-repair. So if we can find the MRI markers in their brains and begin to understand why they have this ability to heal themselves, then maybe we can get lesions to repair themselves in the adult brain. In children, around the age of puberty or younger, there’s a different sex ratio of who develops MS than is the case in adults. So in adults, you’ve probably heard that twothirds of the patients are women. But in children, up until the age of puberty, the sex ratio is 1 to 1.
CC: Do you think estrogen may be the reason more women than men get MS?
EW: Mm-hmm. There’s actually a clinical trial around MS and estrogen that a group at UCLA is doing.
CC: Is anybody doing research on vitamin D?
EW: We do know there are people who are looking at lack of vitamin D as a possible marker of susceptibility to MS. There’s a Toronto group in pediatric MS that is evaluating levels of the vitamin, because the days are so much shorter and colder during winter, so people don’t get as much exposure to the sun, say, as they do in southern California or even northern California. Recently that group measured vitamin D in the blood of children with MS, in children with osteoporosis and in healthy children. They found that they all had super-low vitamin D levels in the blood.
CC: Children with osteoporosis?
EW: Yes. That can happen. But in terms of measuring vitamin D levels, they did it at the worst time of the year weather-wise—towards the end of February—because the days have been shorter and it’s extremely cold so people stay inside. Now they’re going to try to evaluate whether they can dissect that information more carefully to see whether they can detect anything.
CC: Can you just take vitamin D tablets?
EW: You can, actually, but if you take too much vitamin D you can develop renal insufficiency, or calcification in different organs. Vitamin D is not a trivial vitamin. You really need to know the right dose to take. And there are also different types of food, like milk, that already have vitamin D supplements.
CC: I understand that you have patients come from as far away as Alaska. How do they afford it?
EW: Our mission is to see any child who needs to be seen, regardless of the family’s ability to pay. We see some children for free, and we can afford to do that because we have a grant that partly covers the salaries of people on the team. We can also use parts of the grant towards MRI scans or blood tests if a child’s insurance won’t cover it. We have money that can be used to cover travel and hotel accommodations as well. Until now we’ve been fairly lucky because, though we’ve had to do a fair amount of paperwork to make it happen, when we have contacted the airlines, we were able to secure free travel for several of our children and their families.
We hope to be able to work with different entities to do fundraising so we have sufficient money to continue offering these types of services, because clearly there’s a need. It’s actually interesting to see that there are multiple chronic diseases that are typically seen in adults but can sometimes affect very young patients. When that happens, whether it’s MS, lupus, or some other similar disease that has the potential to create a lot of disability, parents are distraught. It’s very hard to find somebody who can take that into account like we can.
CC: When you make the decision to give a child with MS drugs, how do you choose whether its interferon or Copaxone?
EW: We evaluate it on a case-by-case basis, and talk with the family and the patient about the implications of each. We discuss the realities of being on treatment and whether people prefer less-frequent injections or if they feel comfortable doing them daily. It’s very important early on to establish a clear plan with the family, the physician and the patient about what’s out there, how you use the different medications, what to expect, how fast it’s going to work, while you also try to avoid running into compliance problems. So we don’t force any type of treatment on the family.
CC: So for success in treating the child with either one of those drugs, you rely on the history of treating adults?
EW: Correct. The problem with all MS clinical trials— and I’ve run several-is that they only focus on adults, just because in some of the drugs, the safety profile is unknown. So it’s difficult. Drugs for MS, I believe, will always be developed for adults, because that is the main population. Once that drug is tolerated well in adults, we begin to use them in children. To really help the community, you need to be able to document very clearly the tolerability of these drugs.
For example, we find that the side effects of interferon treatment in children are similar to the ones found in adults, with the caveat that in young children, under the age of 11 or 12, they are more likely to develop liver problems. As a result, our entire network tests liver function more regularly during the first six months that the children take the drugs.
CC: How old is your youngest MS patient?
EW: We’re treating one now who is seven, but our youngest in the center is actually 18 months old. That child was referred because there was a suspicion of ADM, and we have a couple of others who are four and five who also have ADM.
CC: You’re diagnosing them as ADM, or you’re looking into it?
EW: Right, there’s a question mark. You have to be very careful and very modest when you give that diagnosis, because it can be wrong.
CC: Do you see more episodes in children than in adults?
EW: There have been a couple studies that reported that the younger you are, the more frequent the episodes are, and the older you get, the less frequent. It’s unclear why, but when we look at MRI scans of patients who have MS, there are more frequent changes in younger patients than in older ones.
CC: Have you noticed with MRIs that there are fewer lesions because the child’s brain self-repairs?
EW: My impression is that children who have MS tend to have lesions that totally go away, while in adults, most of the MS lesions that occur on the MRI leave some scars. What happens in children is that some of these scars don’t seem to form. In fact, it’s really very intriguing because it may tell us a lot about an immature central nervous system, and how differently it may react from the adult brain, or it may tell us that an immune attack against the brain may be a little different in children than in adults. So there’s a lot of research to be done.
CC: How do children tolerate the side effects of Avonex?
EW: Everybody’s different. We have patients who get sick as a dog with injections of interferon, even at low doses. And we have patients who get the full dose and experience no side effects. We don’t understand why. Some of the side effects seem to relate to how the body reacts, especially at the immune-system level, but we don’t fully understand. And it doesn’t seem like it has to do with the efficacy of the medication. In an article published recently on MS and children, a group of physicians pulled data together on the safety of using Betaseron. It was shocking. Most of the children who started on Betaseron, started on full doses. We never do that. We always start at a quarter dose. But it turns out that the children did all right. At some level, children are more resilient. They get a disease, but they don’t focus too much on its side effects.
CC: Do you see any evidence that women who have MS pass it to their children?
EW: You’re asking if there’s some genetic trait to MS? There is some. We know that. But it’s not only women to their children. It can be a father to his children. And sometimes you don’t have MS but you carry the genes, so that if you pass the wrong genes to your children, it’s going to make them susceptible. We know that if, for example, one person has MS, his or her siblings have 20 to 40 times the risk of developing MS. But over a lifetime, the risk is really small, in the ballpark of two percent to three percent in one’s lifetime. There is some genetic susceptibility, but there is also lots of environmental influence that has not yet been identified. We know that if there are environmental factors that have been promoting development of MS in adults, we know there’s probably been exposure within the first 15 years of life. We need to look at what type of vaccinations you had, what type of diet you ate as a kid and on and on. If you study that in children, it’s much easier because you study the disease closer to its probable biological onset. You often have the parents with the child. So we have developed a questionnaire to try to track environmental factors. I think it’s important to do that. But even then, you don’t know.
CC: The environmental connection is a small window.
EW: Correct. Some people would also argue that in utero, there may be toxic or viral factors.
CC: I’ve heard that as high as 30 to 50 percent of people with MS are dealing with clinical depression.
EW: I would say that is because of the status of the health care system in the US. Most of the time it’s very hard to provide comprehensive care to patients. For our adult patients, it can be extremely difficult to have them seen by a normal psychologist. Sometimes their insurance will not pay for it. So we’re trained to refer them, but sometimes it’s very, very difficult because health insurance will cover maybe 10 visits to a psychiatrist. If you have a severe depression, 10 visits are not going to cut it.
CC: Are there similarly high percentages of children diagnosed with MS who experience depression?
EW: We haven’t evaluated that. But there’s a fellow who is finishing her training in adult neurology and she’s going to work with me. She has a special interest in evaluating quality of life in children with MS and in patients with early diagnosis of MS. But in terms of depression, for the children we follow, we’re fortunate to have that extra pot of money that we can use for their care.