Awareness of the problem was first raised with the 1922 publication by Wechsler which reviewed 73 cases described since the start of the 20th century and published 12 cases that seemed unquestionable. He concluded that paediatric MS is rare and difficult to diagnose, but that there is no doubt it exists. In 1946, Carter presented 79 cases and estimated that paediatric MS accounted for almost 10% of patients with MS. He noted that MS rarely occurs between the ages of 10 and 15 years and is significantly more frequent between the ages of 16 and 17 years. He suggested that young children are “protected” against MS but that they lose this protection with the changes to the immune system that take place with puberty.  

Puberty, a pivotal period

Since then, anecdotal cases have been published on a regular basis, leading to an awareness that paediatric MS is a real problem. These observations show that it exists in every country (even among black Americans), that the first symptoms can appear from the first year and that the diagnosis is difficult because both the radiological and the clinical symptoms may differ from those observed in adults. This explains why paediatric MS can usually only be diagnosed with certainty after several years, although it is not rare for a diagnosis of MS to be confirmed in adults within a few months of the initial consultation.

By definition, paediatric MS becomes apparent before the age of 18. To our knowledge, the youngest case (first symptoms at the age of 13 months) was published in Japan. The prevalence of paediatric MS still has to be specified, but it seems to account for around 5% of all cases of MS. One interesting observation is that paediatric MS is extremely rare before the age of 10. In this case, it concerns both boys and girls. However, in the years following puberty, a gradual increase is observed in the preponderance of MS among girls, with the rate coming into line with that of adults towards the age of 18 (F/M: 3/1). Puberty is therefore a pivotal period as regards the risk of MS and its sexual dimorphism.

The age of puberty has fallen gradually and steadily since the mid-19th century, particularly among girls, with the age at which the first periods begin (the menarche) dropping from 16 years in 1850 to 14 years in 1900 and 12.5 years at the moment. This fall in the age of the menarche exposes more girls to the risk of developing paediatric MS and is partly responsible for the increase in cases of MS among women observed since the end of the 20th century.  

The causes of this phenomenon are complex and involve genetic and environmental factors, in particular diet and toxins. The most obvious genetic risk factor is the menarche at a young age in the mother. The environmental risk factors are the same as for adults: obesity, passive smoking, infectious mononucleosis, hypovitaminosis D, etc. In terms of diet, our current habits clearly foster obesity among young people. Now, fatty tissues produce a hormone, leptin, that contributes towards triggering puberty. This hormone also has properties that stimulate the immune system and favour the development of MS. In girls, leptin production does not decline after puberty and the risk remains, whereas in boys, its production is halted by the onset of the secretion of testosterone. This difference partly explains the predominance of MS among women. As regards hypovitaminosis D, it has been demonstrated that high levels of vitamin D in paediatric MS reduce the frequency of attacks and the appearance of active lesions on MRI scans. Vitamin D could be a treatment that is inexpensive and well tolerated. As for the environmental toxic factors (ecotoxicity), two chemical compounds are targeted in particular: Bisphenol A and Phthalates. Both of these compounds are used to make a great many objects used in everyday life, from babies’ bottles to beer cans. These molecules are sex hormone inhibitors (endocrine-disrupting chemicals: EDC) whose harmful effect on the development of the child, and in particular the occurrence of breast cancers, has been demonstrated.

In cases of paediatric MS a distinction must be made between the juvenile form (before the age of 10) and the adolescent form (from 11 to 18 years). While the second of these forms shares several points of resemblance with the adult form of the condition, diagnosing the juvenile form is more difficult as it has certain symptoms in common with multifocal acute disseminated encephalomyelitis, a neurological disorder observed in particular after vaccinations or infectious illnesses.

Over 96% of cases of paediatric MS take the form characterised by attacks and remissions followed by a progressive phase. Cases in which the progressive forms occur straight away are exceptional. The attacks are impressive, but the patient recovers rapidly and often completely. Cognitive disorders are observed in one-third of cases of paediatric MS and frequently disrupt schooling. The gradual worsening of the handicap occurs later and more slowly than in adults but unfortunately these favourable characteristics of the progression do not offset the fact that it begins sooner. Ultimately, patients with paediatric MS are handicapped earlier than those with the adult forms.

There is no official treatment for paediatric MS. Attacks are usually treated with cortisone. While a number of treatments have been approved for adults for over twenty years, no controlled and randomised clinical study has yet been carried out into paediatric MS. A number of recent, non-controlled studies suggest that these treatments are as effective as in adults, that is they reduce the frequency of attacks by about 33% but hardly have any effect on the progression of the handicap.

Clinical research evolution

Over a period of decades, clinical and radiological criteria have gradually been refined as regards diagnosing MS in adults, but these have not proved to be very effective for paediatric MS. In 2006, the International Multiple Sclerosis Society  set up the International Pediatric MS Study Group which includes over 150 researchers and whose database already contains over 2,000 cases. The aim is to gain greater knowledge not only of paediatric MS but also of other disorders that result in the destruction of myelin in the central nervous system and that may pose differential diagnosis problems or lead to the implementation of specific treatments. In addition to perfecting specific clinical and radiological diagnosis criteria for paediatric MS, one of the main aims of this group is to put pressure on pharmaceutical companies to organise clinical studies under optimal safety conditions and applying effectiveness criteria specifically for paediatric MS. These should concern not only the approved treatments but also new molecules being studied in the adult forms. Finally, it may be hoped that the clinical, radiological and immunological data that will be gathered at a particularly early stage in the disorder will make it possible to move close towards understanding the causes of MS.

Richard E. Gonsette, MD, PhD