Anusha Yeshokumar , MD & James Sumowski , PhD
13 Aug 2019 | ~4:55 Engagement Time
What is Pediatric-Onset Multiple Sclerosis (MS)?
Pediatric-Onset MS is defined as having an onset of MS symptoms prior to the age of 18 years. MS, which affects about 2.5 million people worldwide, is the most common cause of non-traumatic neurologic disability in young adults. It is estimated that there are about 2,000-4,000 cases of pediatric-onset MS worldwide, however, about 10% of people with MS recall in hindsight that their first symptoms starting prior to the age of 18 years.
Pediatric-Onset MS is an exclusively relapsing-remitting type of MS. Relapses occur with corresponding new lesions on MRI of the brain, however, lesion development on imaging can also occur in the absence of clinical symptoms. Relapses and new lesions are thought to occur because of injury from inflammation.
How is Pediatric-Onset MS Different from Adult-Onset?
There are many features that make pediatric-onset MS different from adult-onset. Children and adolescents will often have a large number of lesions on their MRIs at the time of diagnosis. They are also noted to have more frequent relapses early on, particularly in the first year after diagnosis, which also means less time in between relapses. As described further below, there are unique treatment considerations given the specific challenges that children and adolescents face in their daily lives. Finally, there is special attention now being given to the study of cognition in pediatric-onset MS, which can be affected even in the absence of physical disability.
Age, Sex, and Clinical Presentations
While there are reports of pediatric-onset MS being diagnosed in toddlers through adolescents, symptom onset before 10 years of age is rare, and the overall frequency increases dramatically after the 12 years of age. Overall, there are about two girls for every boy diagnosed with pediatric-onset MS, but this does vary by age. In younger children, the ratio is closer to one to one girls to boys, whereas in older children, the ration is closer to 2.5 girls to 1 boy. All of this data suggests that factors related to puberty strongly influence the development of MS.
Pediatric-onset MS at diagnosis and during relapses can present with optic neuritis (ON), transverse myelitis (TM), brainstem syndromes, or acute disseminated encephalomyelitis (ADEM).
This presents with rapid onset of visual loss and pain with eye movement. Neurologists may note reduced visual acuity (vision), abnormal blind spots, loss of red color vision, and optic disc swelling on examination.
This may present with limb numbness or tingling, limb weakness, Lhermitte’s sign (often describe as an electrical zap down the spine, particularly when the neck is turned), and urinary or bowel dysfunction. Neurologists may note limb motor deficits, limb sensory loss, sensory level (a point in the back below which sensation is disturbed), and asymmetric reflexes on examination.
This may present with dysfunction of the nerves that control the face (such as eye movement abnormalities, facial sensory loss, and/or dizziness) or problems with coordination and balance. Neurologists will find corresponding deficits on examination.
This may present with encephalopathy (a term for altered mental status and/or lethargy), seizures, and/or multiple, focal neurologic deficits. Neurologists will find corresponding deficits on examination.
Genetic and Environmental Risk Factors
There is some evidence that there is a genetic component that predisposes to the development of pediatric-onset MS. This entity is slightly more common when there is a first degree relative that has it, and identical twins are more likely to both have it than other sibling pairs. A genetic marker that has been associated with pediatric-onset MS is HLA-DR1501.
There is also evidence that environmental factors can increase risk for the development of pediatric-onset MS. Compared to other children and adolescents, those with pediatric-onset MS generally have lower levels of vitamin D, higher rates of exposure to the Epstein-Barr Virus (the virus that causes infectious mononucleosis, commonly referred to as “Mono”), higher rates of cigarette smoking and exposure to second-hand smoke, and higher rates of obesity.
Diagnosis and Relapse Course
The new McDonald Criteria for MS, which were published in 2017, have improved the accuracy of diagnosis across the age span, particularly because of the inclusion of markers from cerebrospinal fluid. They capture more cases of pediatric-onset MS than the older criteria, meaning that diagnosis can be reached sooner. They also have better application to children less than 12 years of age.
As described above, children and adolescents with pediatric-onset MS will often have a large number of lesions on their MRIs at the time of diagnosis. Compared to adult-onset MS, they are also noted to have more frequent relapses early on, particularly in the first year after diagnosis, which also means less time in between relapses. Finally, they are more likely to have lesions in the brainstem and other parts of the lower, back of the brain, called the posterior fossa.
When selecting a medication for children and adolescents with pediatric-onset MS, neurologists must consider the frequency of injections, size of the needle, frequency of blood work needed, and side effects. This is especially important given the many decades for which they may be on medication.
A sense of immortality, need of autonomy, and need for peer acceptance are some of the unique challenges that children and adolescents face in their daily lives. While they may not be able to legally make their medical decisions, it is important to recognize and support their role in participating in decision-making to improve their medication and medical management compliance as well as their well-being.
Motor and Cognitive Outcomes
Even though children and adolescents with pediatric-onset MS have a higher number of relapses, they develop motor disability more slowly than those with adult-onset MS. Large studies have shown that children and adolescents with pediatric-onset MS take longer to reach the same disability as those with adult-onset MS, but due to their obviously younger age at symptom onset, they reach this disability about ten years younger than those with adult-onset MS.
A similar phenomenon is seen with cognition. Problems with attention and learning difficulties are common in pediatric-onset MS, which can make it difficult to perform in school and can negatively affect self-esteem. If not adequately addressed, these early cognitive difficulties can set a negative trajectory for higher education, employment, and quality of life.
It is important to remember that many of these outcomes represent the average performance of children and adolescents with pediatric-onset MS. This means that there are still many individuals who perform well above the average of the comparison group (either those with adult-onset MS or other children without MS). And perhaps even more children and adolescents with pediatric-onset MS could do so as well!
Those with pediatric-onset MS, their caregivers and supporters, and their physicians need to take charge! There is increasing evidence that the prevention and treatment of obesity, sleep problems, mood, and psychological resilience (particularly in combination with medical management and personalized accommodations/resources at school and employment) may improve outcomes in pediatric-onset MS.