Managing the Intricacies and Age-Specific Challenges of Pediatric Multiple Sclerosis

Lauren B. Krupp, MD

MULTIPLE SCLEROSIS (MS) IS ESTIMATED to impact more than 2 million adults in the United States, with approximately 3% to 5% of all instances of disease onset occurring in individuals younger than 16 years of age.^1,2 This exclusively relapsing-remitting form of the disease is referred to as pediatric-onset MS, and those affected often experience 2 to 3 times more frequent clinical relapses than adults.^3,4

The disease has a number of additional differences for pediatric patients compared with adult patients, including the challenges associated with managing disease during youth. To discuss these differences and the overall approach to the care of this patient population, NeurologyLive® presented this Insights series, “Diagnosis and Management of Multiple Sclerosis in Pediatric Patients,” featuring Lauren B. Krupp, MD, Nancy Glickenhaus Pier Professor of Pediatric Neuropsychiatry, Department of Neurology, NYU Grossman School of Medicine, and Tanuja Chitnis, MD, associate neurologist, Brigham and Women’s Hospital, professor of neurology, Harvard Medical School.

The pair elucidated some of the contrasts between adults with MS and the pediatric population, as well as the clinical presentation of the disease, the challenges faced by young patients, and their treatment.

Differential Diagnosis of Pediatric MS

The McDonald criteria, the most recent iteration of which were published in 2017, have been largely adopted for the pediatric patient population in addition to the adult population. The differential diagnosis of pediatric disease, according to Chitnis, is fairly broad, with a variety of other autoimmune diseases needing to be ruled out. As well, autoimmune syndromes such as lupus and antiphospholipid antibody syndrome, among others, can mimic pediatric MS, making them critical to consider.

“This includes, but is not limited to, the emerging disease myelin oligodendrocyte glycoprotein-associated disease [MOGAD], which can be tested for by MOG antibodies; as well as neuromyelitis optica, which can also be tested for using aquaporin-4 antibodies,” Chitnis explained. “The other areas that one should consider are infectious diseases; rarely, some infectious diseases can mimic pediatric MS. I would examine the cerebrospinal fluid [CSF] very carefully for any evidence of viruses and/or bacteria or fungus infections.”

Tanuja Chitnis, MD

She also noted that occasionally, large tumefactive lesions can be present, making it important to rule out any sort of malignancies and tumors. As well, nutritional disorders including B12 deficiency and other ischemic disorders caused by autoimmune conditions can also be mimics of MS.

Krupp added that the biggest difference between the pediatric and adult age groups is the aforementioned rarity of a progressive disease course in younger patients. When pediatric patients present with a history of progressive decline—in school performance, walking, or dexterity—and there is no halt or improvement, she said, despite its similarities to primary progressive MS in adults, that subtype in the pediatric group is extraordinarily rare. “You want to rule out diagnoses like leukodystrophy or a genetic disorder that could present in that kind of fashion,” Krupp explained.

Clinical Presentation of Pediatric MS

In addition to differences in the frequency of clinical relapses, pediatric individuals with MS often also have more inflammatory lesions and tend to accumulate lesions more frequently. Krupp explained that prior to patients becoming clinically treated, it is not unlikely for them to have experienced more than 1 clinical event. Additionally, even when treated with a disease-modifying therapy (DMT), depending on the agent, pediatric patients may still experience several relapses.

“One of the interesting challenges among those with pediatric MS are the youngest patients,” Krupp said. “The majority of children are in the adolescent age range, but there are a number who are also quite young. The youngest patient I ever saw was 27 months old when I made the diagnosis. Children in that age group and in the preteen years are more likely to have an acute disseminated encephalomyelitis [ADEM]–like presentation. They can present with encephalopathy or change in mental status or behavioral changes and have lesions on the brain MRI that are large and fluffy.”

Those individuals are then reclassified as having MS upon the occurrence of a second event with characteristics of the disease. Additionally, Krupp noted that younger children tend to have more brain stem and cerebellar involvement. Previous research has suggested that younger individuals are less likely to have positive oligoclonal bands, but many patients with pediatric MS are now recognized to have MOG syndromes, leading to questions about the need to reassess the CSF profile differences.

Symptoms among the pediatric population are similar to those in adults, but as Krupp noted, they can sometimes be overlooked by nature of children’s behavior. “For example, a child may have optic neuritis but not say anything to their parents. It’s only when the second event of optic neuritis occurs in the other eye that the patient presents for clinical evaluation,” she explained. These individuals also often experience issues with balance, dexterity, gait, and strength. In certain cases, Krupp explained that they can also experience episodes of double vision and vertigo—symptoms referable to the brain stem or cerebellum.

“One of the differences between pediatric patients with MS and adults is that fortunately, kids tend to recover very well from their clinical attacks,” Krupp said. “It’s not uncommon in a day where I’m seeing only pediatric patients with MS for most of those children to have normal or nearly normal neurologic exams. In contrast, in the adult MS group, you might have patients using a cane or with much more obvious neurologic impairment.”

Many wonder if the cognitive function of these younger patients is affected by the disease, and Krupp explained that having MS naturally presents itself as a challenge for kids. As they seek connection in social environments while they grow up, feelings of being different or outside the norm can present a major emotional challenge for them. This, in turn, can lead to mood disturbance issues.

"One of the interesting challenges among those with pediatric MS are the youngest patients. The majority of children are in the adolescent age range, but there are a number who are also quite young. The youngest patient I ever saw was 27 months old when I made the diagnosis.”
—LAUREN B. KRUPP, MD

To this point, it has been estimated that up to 30% of pediatric patients with MS may have either cognitive slowing on speed tasks or other cognitive changes relative to the norms established in the literature. However, more studies are still needed with healthy controls to see if those prior reports are holding true. Krupp noted that MS specialists are hopeful that there may be less cognitive impairment than was previously thought in this modern era. More recently, early diagnosis and prompt initiation of DMT have been thought to aid those cognitive deficits.

“We and others have been concerned about the cognitive wellbeing of kids with MS. After all, pediatric patients with MS are in a living laboratory. They’re in school; they’re in the process of learning the tools that they need to become independent adults,” Krupp said. “Kids [can] have cognitive challenges, academic issues, or emotional stress. Early identification of cognitive involvement is really important. There, fortunately, are a variety of screening methods in which that can be done, even in the neurologist’s office.”

Emotional, Social, and Cognitive Challenges

For pediatric patients, approaching an MS diagnosis and management plan from a multidisciplinary standpoint is essential when possible. Although this is certainly not available to every individual, Krupp advises ensuring that at least nursing is involved in the patient’s care plan. Doing so gives parents reassurance about their child’s care.

“There is kindness and time and ability to answer all the questions that the neurologist will do their best to provide. But sometimes the needs are beyond what the time allotment is for the doctor,” Krupp explained. “The nursing staff, with experience on the disease-modifying therapies and the details of going for tests, can provide tremendous support.”

Patients with pediatric MS also experience challenges in the psychosocial sphere, particularly in the teenage years—a time that can be naturally challenging for all individuals. In this time, Krupp explained, young adults are often trying to differentiate from their parents and toward independence, which can make having to go in for office visits or testing an incredibly stressful experience. “They want to be with their friends; they don’t want to be different. Social workers or psychologists who can reach out to the families and try to help them cope constructively with the stresses that dealing with a chronic illness can bring can be very useful,” she said.

Additionally, existing learning impairment can occur in this patient population and can present as a challenging combination for the patient and their families. This can make access to neuropsychology critically important as a part of care, when available. Among other challenges are those of dexterity and cognition, which can lead to issues in schoolwork such as handwriting and exams. Some children can require occupational and physical therapy because of relapses causing limitations in walking, strength, dexterity, or hand use. Access to that expertise is also critically important from a care perspective. All of this can require the use of a 504 plan, or in more pronounced instances, an individualized educational program (IEP).

“A neuropsychologist can help in the identification of where the weaknesses and strengths are, so that cognitive rehabilitation, if needed, can be initiated early,” Krupp said. Chitnis noted that studies have shown that roughly one-third of pediatric MS patients might have 2 major areas of cognitive deficits, while the other two-thirds might have 1 area of deficit. She said neuropsychological testing can help in the implementation of an IEP. “

This can impact not only their everyday life, but also school, eventual job goals, or maybe college. It’s very important to address these cognitive issues as early as possible,” Chitnis said. “In terms of depression, it does vary; it ranges anywhere from 10% to 40% in different studies of patients with pediatric MS. It’s an important factor to consider, and we should always screen for depression, ask the question, and make sure that depression is managed and treated as well as possible.”

Another major problem for both pediatric and adult patients with MS is fatigue. With children, however, this symptom can be slightly more complicated. Pediatric patients may not be attuned to their fatigue levels, and when coupled with other common issues such as emotional distress, it can go beyond just a lack of awareness around it.

Krupp suggested that nonpharmacologic management is the best option to manage fatigue. Fatigue, she said, is best managed nonpharmacologically. Exercise, in this instance, cannot be emphasized too much and can be an excellent approach to help fatigue. Additionally, reviewing good sleep hygiene and sleep practices—simple techniques to improve sleep—can alleviate fatigue, which is otherwise at times quite challenging for physicians to manage.

“I think children today with MS, and even those without MS, have to be encouraged to exercise, to be physically active, to participate in team sports when team sports become available again, and not just be passive and sitting on the couch playing video games,” Krupp explained.

Support groups are available nationwide for pediatric MS, and Tanuja recommended utilizing the resources provided by the National Multiple Sclerosis Society. Additionally, she mentioned camps and similar events for patients with pediatric MS. As well, there are support groups for parents. “That’s a very important factor to remember and consider. Parents need support to help get their young person through this disease and treatment,” Chitnis explained.

REFERENCES
1. Belman AL, Krupp LB, Olsen CS, et al. Characteristics of children and adolescents with multiple sclerosis. Pediatrics. 2016;138(1):e20160120. doi:10.1542/peds.2016-0120
2. Chitnis T, Glanz B, Jaffin S, Healy B. Demographics of pediatric-onset multiple sclerosis in an MS center population from the northeastern United States. Mult Scler. 2009;15(5):627-631. doi:10.1177/1352458508101933
3. Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009;66(1):54-59. doi:10.1001/archneurol.2008.505
4. Benson LA, Healy BC, Gorman MP, et al. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord. 2014;3(2):186-193. doi:10.1016/j.msard.2013.06.004