Findings of a case-control study in France confirmed that both crude and residual body mass index (BMI) were significantly higher in boys with pediatric-onset multiple sclerosis (POMS), compared with non-neurologic controls (P <.01) and healthy controls (P <.01).

In girls, the crude and residual BMI did not differ from the non-neurological controls (P =.4), but they did differ from the healthy controls (P <.01). In boys, vitamin D levels demonstrated an inverse relationship with BMI such that lower vitamin D levels correlated with higher BMIs.

The investigators also observed that cerebrospinal fluid (CSF) inflammatory markers increased along with BMI in patients with POMS prior to reaching puberty. While obesity contributed to the initial inflammatory process in the CSF, it was not a factor in annual relapse rate, the age of diagnosis of the disease, or any of the clinical or radiological presentations at disease onset.


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Inflammatory Markers Contributing to POMS

One inflammatory marker the researchers observed was the oligoclonal band (OCB) in the CSF, which they discovered was related to the relationship between age at disease onset and residual BMI (gender did not impact this association). Patients younger than 14 years old demonstrated increased OCB correlating with increased weight, but this trend disappeared after age 14.

In addition to OCB, the 2 other markers of inflammation were hyperproteinorachia and pleocytosis, which also increased with residual BMI in younger children under the age of 14. Researchers speculate that this low-grade inflammation related to obesity contributes to neuroinflammation through blood-brain barrier disruption or activation of microglia in the central nervous system (CNS), which respond to adipokines released into the peripheral bloodstream.

How the Findings Were Reached

The investigators enrolled 60 patients (39 girls and 21 boys) with POMS under the age of 18 into the study along with 113 non-neurologic controls (68 girls and 45 boys) and 18,614 healthy controls (9271 girls and 9343 boys). They measured crude BMI and residual BMI (the actual measured BMI minus the expected BMI for age). The researchers categorized the patients using the International Obesity Task Force categories of normal, overweight, and obese. A BMI of less than 25 indicated normal range, from 25 to less than 30 was categorized as overweight, and equal to or greater than 30 indicated obesity.

The authors attributed the sexual dimorphism, with a higher risk of POMS development in obese young boys, to increased leptin. Leptin contributes to testosterone depletion by causing “downregulation of kisspeptin neurons and inhibition of the gonadotropic axis.”

They noted from other studies that testosterone depletion in adult males with MS corresponds with increased severity and progression of neuroinflammation. Testosterone has anti-inflammatory properties. Research indicates there is a balance during childhood between the sexes in MS incidence, but this becomes distorted toward females after puberty.

After analyzing their study’s findings, the authors stated, “BMI is related to initial inflammation in the CSF in prepubertal patients with POMS suggesting an interaction between excess body fat, sexual hormones, and POMS occurrence.”

Reference

Milles P, De Filippo G, Maurey H, Tully T, Deiva K. Obesity in pediatric-onset multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1044. doi:10.1212/NXI.0000000000001044