Myasthenia Gravis Learning Zone
Transcript: A case of MG in a child
Professor Nils Erik Gilhus
Interview recorded March 2025. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
Dear colleagues, I am professor Nils Erik Gilhus at Haukeland University Hospital and University of Bergen in Norway. I'm professor in neurology. And today I will present a 12-year-old boy for you with generalised myasthenia gravis. And this presentation is part of the case series study on myasthenia gravis given to you by Medthority. This boy was physically active until he started to feel muscle weakness. He was less active during his previously active days. He was an eager soccer player. He was top scorer for his boy team. But then he had to go into be a defensive player because he couldn't run as much as before. And after another couple of weeks, he had to be a goalkeeper. His parents took him to the local doctor because of his general weakness, legs, arms, he lost some weight. They feared a severe disease, malignancy perhaps. He was admitted to their local paediatrics hospital, but he was still undiagnosed for some weeks.
But then he started to develop diplopia and ptosis, and the paediatrician remembered myasthenia gravis as a disease. And they tested for acetylcholine receptor antibodies, which he had in a clearly elevated concentration. So then the diagnosis of myasthenia gravis was established with typical clinical symptoms and with this antibody finding, as you know, the acetylcholine receptor antibodies are highly specific. Positive result together with symptoms that can fit with myasthenia gravis means myasthenia gravis. In this boy, we thought it was not necessary to do any neurophysiological tests as the diagnosis was already established, and we did not test for MuSK antibodies as he had this clear positivity for acetylcholine receptor antibodies. His thymus was enlarged on thoracic CT, but thymus is at its biggest at age 12 in everyone. So the radiologists were not sure if it was larger than expected in this boy.
He had a diagnostic delay for a couple of months, and I've written here that the median time in a Norwegian material from symptom onset to diagnosis is six months in children. This reflects that myasthenia gravis is a rare disease, and neither patients, families, nor primary care doctors usually know about or remember myasthenia gravis as a diagnostic alternative. If you think about myasthenia as a possibility, it's not that difficult to diagnose in most patients. And as I already said, we have the antibody assays, and if they are negative, we have the neurophysiology that gives the diagnosis in these patients, also in children. For treatment, he started with pyridostigmine, and he had a typical clinical effect. He was much improved after two days with pyridostigmine. He was submitted to thymectomy. He had a videoscopic thymectomy only a few weeks after his diagnosis. Before treatment, before thymectomy, he got intravenous immunoglobulin to improve his condition further and to induce an improvement rapidly. He also got a very low dose of corticosteroids or prednisolone to improve his condition.
He was very well after surgery, and he continued to improve during the next months. And within six months, he played soccer again as, in attack. And then we did not follow it anymore, because he was transferred to the local hospital. But the reports say that he was in full pharmacological remission after one year. That means that he continued to use low dose of pyridostigmine. He did not any longer use prednisolone. He did not need this low dose, five milligrammes a day, and he did very well. We had, as always, a discussion with him and his parents regarding more general rules of how to live, recommend physical activity, training programmes. He should be as active as he managed, no restrictions regarding soccer or other physical activities. We talked about diet in a more general ways and a healthy way of living. We discussed future work, education, and we'll probably not recommend the most physically demanding working positions for him, but his prognosis was regarded as good. It's also a question about where to follow up patients like this. We generally recommend super specialists.
In our country, that would mean neurologists and not neuro paediatricians, but it has to be balanced with travel distance. And when he was in full pharmacological remission, he was transferred to his local paediatrics departments because of a long travel distance. These are some more general aspects of juvenile myasthenia gravis with onset below age 18 years. It's our Norwegian cohort published some years ago, and a cohort from our Chinese coworkers. We found this, identified 63 patients with debut of myasthenia before age 18 during 25 years time period. And our population, total population in Norway is five and a half million. So it's really a rare disease. You see that there are similarities in the Norwegian and Chinese cohort, but there are also some differences, especially regarding ocular myasthenia, purely ocular symptoms in only 1/3 of Norwegian patients, but in 2/3 of the Chinese patients. And also ocular debut was much more common in China, whereas 2/3 had that in Norway. As you remember, our patient did not have a ocular debut. Also, the seronegative patients are more common in China, probably reflecting a milder disease. MuSK antibodies are rare in both populations. Also, what is really perhaps the most crucial findings on this slide is that the Chinese cohort, one half of them had debut below eight years of age.
That was very rare in Norway. So in China, there is a subpopulation of children with very early onset myasthenia, mild ocular disease. In Norway and in Caucasian populations, the juvenile myasthenia gravis is not so different from other early onset myasthenia gravis patients. This is a list of therapy received in the same Norwegian population, and then in a more recent cohort from USA. You see that pyridostigmine was given to all children. Thymectomy was performed in the great majority in both these cohorts. And we would definitely recommend thymectomy also in children. And no worries of thymectomy at age 12 years as our patient. Prednisolone was used by some, but many did not need prednisolone. Azathioprine, mycophenolate mofetil was given to a small or to 1/3 of the Norwegian patients, and it is not clearly stated in the American cohort. Whereas immunoglobulin or plasma exchange was more commonly used in the children.
More than 1/2 of the patients received that, probably because this is an excellent short-term treatment, gives a short-term remission of a disease very fast and without any long-acting consequences for the immune system. Regarding treatment result, you see that in both cohorts, approximately 1/2 of the patients were either in drug-free remission or pharmacological remission. The difference in these two cohorts may be because in Norway, the children tended to continue on a low dose of pyridostigmine, even if they were symptom-free or nearly symptom-free. Whereas they probably stopped that treatment earlier on in the American cohort. And very few patients remained unchanged. So I think this slide is quite optimistic. It shows that most children do well. Many are in remission. And this is without very extensive immunosuppressive treatment, that's on pyridostigmine with thymectomy.
And in several of the patients, low-dose prednisone or prednisolone often given as short-term treatments. Then what about emerging therapies in children with myasthenia gravis? You are well aware of complement inhibitors, FcRn blockers, also B-cell therapies and T-cell therapies for myasthenia gravis. The completed trials are for adult patients only, but there are ongoing paediatric trials. We would expect that both effect and side effects would be similar in children with myasthenia. In adults, the disease mechanisms are the same, perhaps apart from this very early onset patients in China. But for the others, the disease mechanisms are similar. So the patients differ. They are children. They have immune system in development. So regarding safety and side effects, it might be a concern with immunosuppressive in general that is different from adult patients. But regarding effect, it would be expected to be similar.
These new emerging therapies, they have a more selective action in the immune system, and that might be an advantage also in the children. However, the actual use of these drugs in children will depend very much on rules for regulatory aspects and rules for refunding of expenses, for example. And so far, these therapies are generally not approved for children. And as we have also discussed, most children respond very well to standard therapies easily available today. So what I would recommend is early active treatment in myasthenia gravis in children with thymectomy. Short-term perspectives regarding immunosuppressive treatment, it can often be withdrawn after some months or perhaps a year or two because of improvement with thymectomy and good effect of pyridostigmine. So you should remember, myasthenia gravis in children, it's rare, but it's a possibility. And it's necessary to diagnose and treat active and early on. Thank you for your attendance.
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