The trio of authors from Johns Hopkins discussed the findings of a study that imply that BMI is associated with accelerated rates of ganglion cell and inner plexiform layer atrophy in those with multiple sclerosis.
Angeliki G. Filippatou, MD
Recent data of a 522-patient cohort 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).
In total, the cohort consisted of 522 patients with MS, of which 9 were underweight and 153 were overweight in addition to 214 normal weight and 146 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).
Compared to patients with normal weight, those who were obese 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).
The data were compiled by Angeliki G. Filippatou, MD, neuroimmunology and neurological infections research fellow, Department of Neurology, Johns Hopkins University, and colleagues. To find out more about the study findings and their takeaways for the clinical community in MS, NeurologyLive reached out for insight from Filippatou and 2 additional authors from the Division of Neuroimmunology and Neurological Infections at Johns Hopkins, Shiv Saidha MBBCh, MD, MRCPI, and Jeffrey Lambe, MBBCh.
Angeliki G. Filippatou, MD: In this large cohort of MS patients, we found that elevated BMI was associated with accelerated rates of ganglion cell + inner plexiform layer thinning. Rates of GCIPL atrophy are likely clinically relevant in MS, since they are faster in patients with disease activity or disability progression, and mirror brain atrophy, and in particular gray matter atrophy, over time. Therefore, our work highlights that people with MS and comorbid obesity may be at risk for worse disease outcomes.
Nevertheless, it would be important to highlight that our study was observational and, by definition, does not prove causality. An important future direction would be to investigate whether weight optimization improves clinical outcomes in MS.
Shiv Saidha MBBCh, MD, MRCPI: Our findings were in line with prior studies demonstrating that elevated BMI is associated with accelerated brain atrophy and disease progression in MS. While we did not observe similar associations between BMI and other retinal layers, such as the peripapillary nerve fiber layer, this was unsurprising, since GCIPL has typically demonstrated superior structure-function relationships and reliability in MS.
Jeffrey Lambe, MBBCh: While our study findings add to the growing evidence that elevated BMI may be associated with worse disease outcomes in MS, the exact nature of the relationship between BMI and MS remains unclear. Specifically, the pathobiological mechanisms underlying the observed findings are poorly understood, and, given previous observations that an elevated BMI may be associated with reduced brain volumes in otherwise healthy adults, these processes may not be specific to MS.
Moreover, the effect of BMI on neurodegeneration is difficult to isolate due to metabolic comorbidities, such as diabetes mellitus and hyperlipidemia, that have an increased prevalence in the obese population and have been associated with worse outcomes in MS.
Shiv Saidha MBBCh, MD, MRCPI: While it may prove challenging to discern the complex interplay between BMI and metabolic syndrome in MS, BMI could be viewed as an imperfect surrogate of global metabolic health, encapsulating potential clinical and subclinical cardiovascular comorbidities that may contribute to more rapid disease progression. Important next steps in understanding the relationship between BMI and MS would be to determine whether the strength of the association between BMI and neuro-axonal degeneration differs between people with MS and healthy controls, as well as to evaluate whether the management of obesity, a modifiable risk factor, improves outcomes in MS.
Transcript edited for clarity.
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