Researchers Highlight Need for Pediatric-Specific Treatment, Research for MS

Compared with adult-onset multiple sclerosis (MS), pediatric-onset MS has few treatments directed at the condition, specifically those that promote remyelination, enhance neuroprotection, and remediate cognitive deficits, report investigators in The Lancet Neurology.

Central nervous system demyelination in children 18 years or younger—also known as acquired demyelinating syndrome (ADS)—can be an indication of 1 of 3 conditions: MS, myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), or aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD).

“However, doing clinical trials is challenging because of the rarity of these conditions in the pediatric age group,” the authors state.

The aim of the present review was to consolidate and solidify recommendations for guideline-based care, treatment, and research priorities to “meaningfully alter the projected outcomes of these diseases” in children and adolescents. They searched PubMed for articles published in English between January 1, 1975, and May 30, 2020, using multiple sclerosis, myelin oligodendrocyte glycoprotein, acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis combined with children or pediatric or paediatric or adolescent.

The authors note that the annual global incidence of pediatric ADS is estimated to be 0.87 (95% CI, 0.35-1.40) per 100,000 children and that 98% of MS cases in children are relapsing-remitting MS. Children also have higher rates of relapse during their first 4 years of MS (annualized relapse rate, 1.13 vs 0.40 in adults) and more T2 brain lesions on MRI, but their recovery from a clinical episode is quicker and few have permanent disability, specifically physical or neurological impairment.

Childhood-onset MOGAD also appears to be less severe in children, with study results demonstrating that 74% to 83% of children have just 1 demyelinating event and 58% of those with relapsing MOGAD have 1 relapse over a median 5 (range, 1-7) years. Relapses can vary in severity, however, with some children not regaining healthy neurological function or having moderate to severe neurological deficits.

The course of, and recovery from, AQP4-NMOSD seems to be worse in children compared with adults, especially with repeated optic nerve and spinal cord events, the authors said. Previous research shows that 25% of adults have long-term disability from the onset event, but onset in children is more frequently associated with cognitive impairment (P = .018) and poor visual outcome (P = .008).

Following their review, the authors came up with many recommendations for care of pediatric patients with these conditions. Among them are the following:

• A comprehensive, multispecialty care plan should include neuroimmune disorder and medication experts, social workers, neuropsychologists, psychologists, and psychiatrists.
• Prioritize the safety of chronic immunomodulation
• Disease-modifying therapies should be individualized to each patient by considering therapeutic potency, time to reach maximal efficacy, putative mechanism of action, mode of delivery, and short-term and long-term safety and tolerability.
• Develop more advanced assays that can detect immune responses to other CNS antigens beyond those that cause MS, MOGAD, and AQP4-NMOSD
• Develop newer MRI techniques capable of detecting as-of-yet unrecognized neuroimmune diseases
• Future studies that focus on why disease course, treatment response, and outcome can vary so widely among patients with the same disease

“The future for children and adolescents living with multiple sclerosis, MOGAD, or AQP4-NMOSD is far brighter than in years past,” the authors conclude, “and will be brighter still if successful therapies to promote remyelination, enhance neuroprotection, and remediate cognitive deficits can be further accelerated.”

Reference

Fadda G, Armangue T, Hacohen Y, Chitnis T, Banwell B. Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care. Lancet Neurol. 2021;20(2):136-149. doi:10.1016/S1474-4422(20)30432-4.