An identified association between accelerated rates of ganglion cell and inner plexiform layer atrophy in the absence of overt metabolic comorbidities suggests that obesity may affect accelerated neurodegeneration in those with multiple sclerosis.
Angeliki G. Filippatou, MD
Data published in the Multiple Sclerosis Journal suggest that in the absence of overt metabolic comorbidities, body mass index (BMI) might be associated with accelerated rates of ganglion cell and inner plexiform layer (GCIPL) atrophy in patients with multiple sclerosis (MS).
The authors, including Angeliki G. Filippatou, MD, neuroimmunology and neurological infections research fellow, Department of Neurology, Johns Hopkins University, noted that the findings suggest that obesity—a modifiable risk factor—may have an impact on accelerated neurodegeneration in MS.
Compared to patients with normal weight (n = 214), those who were obese (n = 146) displayed significantly higher rates of GCIPL atrophy per year (obese: —0.57% per year [95% CI, –0.65 to 0.48]; normal weight: –0.42% per year [95% CI, –0.49 to –0.35]; P = .012). Additional analysis showed that each 1 kg/m2 higher BMI was associated with an accelerated GCIPL atrophy of —0.011% per year (95% CI, –0.019 to –0.004; P = .003).
Notably, the GCIPL atrophy rate was not markedly different between overweight (—0.47% per year) and normal-weight patients (–0.42% per year; P = .41).
“To our knowledge, this is the first large-scale longitudinal study to investigate the association of BMI with rates of retinal layer atrophy in MS,” Filippatou and colleagues wrote. “While it would be necessary to independently validate our findings, our observations are likely clinically relevant and may be suggestive of a relationship between metabolic health and disease progression in MS. These findings support the rationale for future studies to investigate whether the modification of obesity may improve outcomes in MS.”
In total, the cohort consisted of 522 patients with MS, of which 9 were underweight and 153 were overweight in addition to the aforementioned 360 normal weight and obese patients. The median duration of follow-up was 4.4 years, and there were 4710 eye-visits with optical coherence tomography (OCT) measures. Each patient had a median of 4 visits (interquartile range [IQR], 3—6), and the median interval between visits was 314 days (IQR, 192–510).
At baseline, those with normal weight had lower GCIPL thickness compared to overweight (P = .018) and obese patients (P =.021). The investigators wrote that these differences seemed to be driven mostly by more severe prior ON events in the normal weight cohort, resulting in lower GCIPL thickness in prior ON eyes in normal-weight patients compared to those who were overweight (difference, —3.77μm; 95% CI, –6.90 to –0.65; P = .018) and obese (difference, —2.88μm; 95% CI, –6.11 to 0.35; P = .08). Although, they did note that analyses excluding eyes with prior ON resulted in lower baseline GCIPL thickness in normal weight as compared to obese patients.
Filippatou and colleagues observed that black patients also had accelerated GCIPL atrophy (—0.16% per year; 95% CI: –0.28 to –0.04; P = .009), which was the only significant difference identified between cohorts when analyzing atrophy rates. As well, being of male sex (—0.13% per year; 95% CI, –0.23 to –0.02; P = .021) and having a progressive MS subtype (—0.18% per year; 95% CI, –0.29 to –0.08; P = .001) were both independently associated with accelerated GCIPL atrophy, which is consistent with already known negative prognostic factors in MS.
In an accompanying editorial, Fiona Costello, MD, and Axel Petzold, MD, PhD, called the study thought-provoking and noted that Filippatou et al. “should be commended taking a novel approach to investigate a relevant topic, namely, the association between obesity and retinal neuroaxonal atrophy in MS.” They wrote that the study highlights the utility of peri-papillary retinal nerve fiber layer [pRNFL] and macular GCIPL as outcome measures and “illustrates the importance of addressing confounders known to affect these OCT parameters.”2
Costello and Petzold also detailed that neuroaxonal injury and progressive disability in MS patients may be worsened by factors associated with metabolic syndrome, independent of disease pathobiology, which is important to keep in mind, as higher BMI may broadly impact the health and vulnerability of many patient populations—not just those with MS.
This data are not the first to suggest an association between BMI and MS disease status, as the body of literature has grown to showcase an association between metabolic pressure, autoimmunity, and neurodegeneration in chronic inflammatory conditions. Last year, a single-site, cross-sectional study from Mario Stampanoni Bassi, MD, and colleagues suggested that the presence of obesity and an altered lipid profile may be related to both aggravated central inflammation and higher clinical disability in patients with relapsing MS.3
Bassi et al. showed a positive correlation between BMI and Expanded Disability Status Scale (EDSS) score in 140 patients with MS. The patients who were obese (BMI >30; n = 24) prior to therapeutic intervention had higher EDSS scores (median, 3; IQR, 2 to 3.4) than those with a normal BMI (18.5 to 24.9; n = 83; median, 1.5; IQR, 1 to 2.75; B-H adjusted P = .015).
Additionally, research presented at the 2019 American Academy of Neurology (AAN) Annual Meeting by Elisa Meier-Gerdingh, MD, et al. implied a link between sugar-sweetened beverages and greater disability status in MS, though no association was observed between overall diet quality and disability status. In that assessment, with respect to individual Dietary-Approaches-to-Stop-Hypertension (DASH) score factors, those in the highest quartile of sugar-sweetened beverage consumption displayed a higher risk for severe disability (odds ratio [OR] 5.01; 95% CI, 1.03- 24.37; P = .01) compared with mild-to-moderate disability.4
1. Filippatou AG, Lambe J, Sotirchos ES, et al. Association of body mass index with longitudinal rates of retinal atrophy in multiple sclerosis. Mult Scler J. Published online April 16, 2020. doi: 10.1177/1352458519900942
2. Costello F, Petzold A. Weighting evidence in MS: Obesity and neurodegeneration. Mult Scler J. Published online April 16, 2020. doi: 10.1177/1352458520912171
3. Bassi MS, Iezzi E, Buttari F, et al. Obesity worsens central inflammation and disability in multiple sclerosis. Mult Scler J. Published online June 4, 2019. doi: 10.1177/1352458519853473
4. Meier-Gerdingh E, Fitzgerald K, Gold R, Hellwig K. Dietary Intake and the Effect on Disease Progression in People with Multiple Sclerosis. Presented at AAN 2019; Philadelphia, PA; May 4 to 9, 2019. Abstract 3248.