Assessing the Relationship Between Obesity and Pediatric-Onset MS

New research published in Neurology, Neuroimmunology & Neuroinflammation details the associations between body mass index (BMI), including overweight and obesity, and pediatric-onset multiple sclerosis (POMS).

Around 3% to 10% of individuals with MS are affected by POMSl; the condition can occur before age 10 years in 1% of those with MS. In addition, “a higher relapse rate is observed in children despite better recoveries after relapses, and a slower evolution toward a secondarily progressive disease has been described” in this population, authors explained.

Low-grade inflammation mediated by obesity may lead to neuroinflammation through disruption of the blood-brain barrier (BBB) or the primary activation of microglia in the central nervous system in response to adipokines released into the peripheral circulation by fatty tissues, they added.

To analyze the link between high BMI in children and the occurrence of POMS in the French pediatric population and to compare the characteristics of those with POMS who had normal weight or who had a high BMI, researchers carried out a case-control study.

All study participants were under the age of 18 at MS diagnosis and were diagnosed between 2010 and 2018. Any patient who took treatments likely to influence BMI or who had other conditions likely to impact BMI were excluded.

Data from 60 patients (39 girls, 21 boys) with POMS, 113 nonneurologic controls (NNCs; serving as a local control population) (68 girls, 45 boys), and 18,614 healthy controls (HCs) (9271 girls, 9343 boys) were included in the final analysis.

Researchers used HC data “to model the mean corpulence (BMI) trajectories of healthy French boys and girls (data not shown), and these trajectories served as a reference against which to compare our patients with POMS and NNCs,” they explained.

International Obesity Task Force (IOTF) categories were used to define normal weight (BMI < 25), overweight (BMI between 25 and 30), and obesity (BMI > 30).

Analyses revealed:

• In boys, crude BMI (cBMI) and residual BMI (rBMI) were significantly higher in patients with POMS compared with NNCs (cBMI: +2.9; rBMI: +2.95; P < .01) and HCs (cBMI: +2.04; P < .01).
• In girls, cBMI or rBMI did not differ between POMS and NNCs patients (cBMI P = .4; rBMI P = .44) but with HCs (cBMI +0.99; P < .01).
• Cerebral spinal fluid (CSF) inflammatory markers increased with BMI in prepubertal patients (P < .01), whereas vitamin D level at diagnosis was lower in boys with higher BMI (P = .016).
• Increased BMI was not associated with clinical and radiologic disease characteristics.

“We observed a higher prevalence of overweight and obesity in our sample of French patients with POMS at diagnosis, and one of our findings is the possible sexual dimorphism, attributing a higher risk to male sex,” authors wrote. They continued, “We have also noticed that overweight and obesity were associated with a higher probability to observe CSF inflammatory markers in younger patients.”

Researchers hypothesized testosterone may account for the stronger association between POMS and obesity seen in boys in the current study, as the hormone is known for its anti-inflammatory actions at the cerebral level and is depleted during puberty. Furthermore, “In adult men with MS, testosterone depletion is associated with increased disease severity and neuroinflammation progression,” they explained. Future studies are needed to better explore this hypothesis.

Given the study’s sample size, results should be interpreted with caution and larger-scale studies are warranted to better clarify the role of sex hormones in POMS.

Overall, “overweight and obesity are observed more frequently in boys with POMS at the time of diagnosis compared with a local control population (NNC) and the healthy French pediatric population (HC),” authors concluded. “Excess body fat appears to influence initial inflammation in the CSF in prepubertal patients, but would not influence the annual relapse rate, the age of diagnosis of the pathology, or the initial clinical and radiologic parameters.”

Reference

Milles P, De Filippo G, Maurey H, Tully T, Deiva K. Obesity in pediatric-onset multiple sclerosis: a French cohort study. Neurol Neuroimmunol Neuroinflamm. Published online July 20, 2021. doi:10.1212/NXI.0000000000001044