Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.
The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS, reports Medscape.
Researchers reviewed the MRI scans of 38 children aged seven to 17, who had radiologically isolated syndrome (RIS), a possible precursor to MS.
Like MS, RIS is characterised by destruction of the myelin. However, it is generally asymptomatic.
While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before the age of 16.
The children in the study probably received an MRI because of complaints of headaches or after having been diagnosed with a concussion, said the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.
Within an average of three years after the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.
MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue.
Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Dr Leslie Benson, assistant director of paediatric neuroimmunology at Massachusetts General Hospital and one of the study authors.
“The field is leaning toward (the question of), ‘Should we treat presymptomatic MS?’” said Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”
The findings were published in the journal Multiple Sclerosis and
Related Disorders.
According to Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.
“We don’t really know when MS first starts,” Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”
MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Dr Tanuja Chitnis, director of the Mass General Brigham Paediatric MS Centre in Boston, also one of the study’s co-authors.
“The concern of many practitioners is whether we should be treating at the first sign of MS,” Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”
Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.
“This may miss patients at risk for MS,” Benson said. “That idea of who do you diagnose and what criteria works to accurately diagnose RIS is really important."
For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.
“We need a better understanding of what criteria need to be met and how we can best risk stratify our patients,” Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”
“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Dr Naila Makhani, associate professor of paediatrics and neurology at the Yale School of Medicine and director of the Yale Paediatric Neuroimmunology Programme, in Connecticut. Makhani was not affiliated with the study.
Study details
Silent findings: Examination of asymptomatic demyelination in a pediatric US cohort
Vikram Bhise, Michael Waltz,Charles Casper, Gregory Aaen, Leslie Benson, Tanuja Chitnis, Mark Gorman, Manu Goyal, Yolanda Wheeler, Timothy Lotze, Soe Mar, Mary Rensel, Aaron Abrams, Moses Rodriguez, John Rose, Teri Schreiner, Nikita Shukla, Emmanuelle Waubant, Bianca Weinstock-Guttman, Jayne Ness, Jan Mendelt-Tillema.
Published in Multiple Sclerosis and Related Disorders in March 2023
Abstract
Background and objectives
Limited data is available on children with evidence of silent central nervous system demyelination on MRI. We sought to characterise the population in a US cohort and identify predictors of clinical and radiologic outcomes.
Methods
We identified 56 patients such patients who presented with incidental MRI findings suspect for demyelination, enrolled through our US Network of Paediatric Multiple Sclerosis Centres, and conducted a retrospective review of 38 patients with MR images, and examined risk factors for development of first clinical event or new MRI activity. MRI were rated based on published MS and radiologically isolated syndrome (RIS) imaging diagnostic criteria.
Results
One-third had a clinical attack and ¾ developed new MRI activity over a mean follow-up time of 3.7 years. Individuals in our cohort shared similar demographics to those with clinically definite paediatric-onset MS. We show that sex, presence of infratentorial lesions, T1 hypointense lesions, juxtacortical lesion count, and callosal lesions were predictors of disease progression. Interestingly, the presence of T1 hypointense and infratentorial lesions typically associated with worse outcomes were instead predictive of delayed disease progression on imaging in subgroup analysis. Additionally, currently utilised diagnostic criteria (both McDonald 2017 and RIS criteria) did not provide statistically significant benefit in risk stratification.
Conclusion
Our findings underscore the need for further study to determine if criteria currently used for paediatric patients with purely radiographic evidence of demyelination are sufficient.
Medscape article – Risk for MS in Children Often Missed (Open access)
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