Vascular Comorbidity in MS Linked to Atrophy, Functional Decline

Nancy A. Melville

November 06, 2020

Vascular comorbidities, including diabetes and hypertension, are linked to significantly lower measures of neurologic function in people with multiple sclerosis (MS) vs patients without these comorbidities, new research shows. The research also shows that these comorbidities were linked to lower gray matter volume in the brain in patients with MS.

"The findings show that overall vascular comorbidity burden may contribute to reduced neuroperformance as well as lower brain and gray matter compartment volumes," said first author Kathryn Fitzgerald, ScD, an assistant professor at Johns Hopkins University School of Medicine in Baltimore, MD, presenting the findings as part of the American Neurological Association's ANA2020 Virtual Annual Meeting.

"Observed associations with gray matter volume are particularly notable due to its likely relevance to neurodegeneration and long-term disability," she added.

The findings, though not altogether surprising, should serve as a call to action to clinicians and patients alike that such comorbidities should be taken seriously from the very start with MS, Florian P. Thomas, MD, PhD, professor and founder of the Multiple Sclerosis Center at Hackensack University Medical Center, Hackensack, New Jersey, told Medscape Medical News.

"Once MS patients are obese and have glucose intolerance and high cholesterol, the train has essentially left the station," he cautioned.

"Our strategies should be to try to avoid these things and intervene right from the start, from the first MS attack," he said.

In general, vascular comorbidity is linked to neurodegeneration in the overall population; however, in MS, the process could be intensified, Fitzgerald explained.

"Vascular comorbidity may contribute to an increased underlying inflammatory state or could affect capability to resist chronic injury and accelerate neurodegenerative processes in people with MS," she said.

Meanwhile, vascular conditions are reported in a higher proportion of people with MS, and are suspected to be linked to more adverse outcomes in the often variable MS course of disease.

Most studies investigating the issue, however, have involved smaller, single-center cohorts.

To evaluate the issue on a larger scale, Fitzgerald and colleagues turned to the MS Partners Advancing Technology and Health Solutions (MS PATHS) network, providing extensive detail on neurofunction and neuroimaging measures in people with MS.

Of the 11,507 patients with MS that were identified, 8.9% had diabetes, as many as 34.8% had hypertension and 24.9% had dyslipidemia.

Overall, 1881 of the patients had two or more comorbidities and, among them, 1130 were included in the quantitative MRI analysis.

The most common combination of comorbidities were hypertension and dyslipidemia, occurring in 11.9% (n = 1,374) of participants.

Overall, the participants had an average age of 47.6 years, 75% were women, and 23% were non-White. Their mean age at symptom onset was about 34 years, and mean duration of disease was about 15 years.

Approximately 60% had relapsing-remitting MS and about 29% had progressive MS.

In terms of clinical measures, participants with two or more vascular comorbidities had slower walking speed (-0.49 SD times slower; 95% CI, -0.78 to -0.19; P = .001), slower manual dexterity (-0.41 times slower; 95% CI, -0.57 to -0.26; P < .0001), and fewer correct scores on cognitive processing speed (-0.11 SD; -0.20 to -0.02; P = .03) compared with those with none of the comorbidities.

Neuroimaging outcomes, assessed with quantitative MRI, showed that participants with two or more comorbidities had lower brain parenchymal fraction (-0.41%, 95% CI, -0.64% to -0.17%) and gray matter fractions (-0.30%, 95% CI, -0.49 to -0.10), both key measures of brain atrophy.

They also had lower cortical gray matter volume (-10.10 mL, 95% CI, -15.42 to -4.78) and deep gray matter volumes (-0.44 mL, 95% CI, -0.84 to -0.04), vs no comorbidities.

No significant associations were seen between comorbidity burden and T2 lesion volume.

Individual Comorbidity Risks Vary

A further investigation of the clinical effects of the comorbidities on an individual basis showed that participants with diabetes had significantly lower walking speed and manual dexterity (both P < .0001), and processing speed was also lower, to a smaller extent (P = .05), compared with those with MS but without diabetes.

Hypertension, interestingly, showed no significant association with any of the three measures. And while dyslipidemia was not linked to a significant reduction in walking speed, manual dexterity (P = .01) and processing speed (P = .006) were significantly lower.

And in terms of the neuroimaging outcomes with the individual comorbidities, diabetes alone was associated with significantly lower brain parenchymal fraction (P = .004), gray matter fraction (P = .03) and cortical gray matter volume (P = .05).

Hypertension only was significantly associated with T2 lesion volume (P = .01), while dyslipidemia was linked to lower brain parenchymal fraction (P = .04), gray matter fraction (P = .04) and cortical gray matter volume (P = .01).

The findings show that "overall, vascular comorbidity burden may contribute to reduced neuroperformance as well as lower brain and gray matter compartment volumes," Fitzgerald said.

She told Medscape Medical News that key questions include the role of vascular comorbidity in predicting progression of symptoms.

"A key limitation is that the study was cross-sectional, so assessment of vascular comorbidity and MS outcomes, including brain volume and neuroperformance, occurred at the same time, so it's difficult to say whether vascular comorbidity can predict change in MS outcomes," she said.

"We are hoping to explore in future studies whether optimal comorbidity management in people with MS might mitigate some of the potential associations."

In the meantime, Fitzgerald agreed that the findings suggest the need for clinicians to keep the comorbidities on their radar in the management of patients with MS.

"I think screening for diabetes or dyslipidemia may be helpful, since these disorders may be underdiagnosed, at least in the US, and may help patients establish routine care with a primary care physician who can help them navigate the results of these tests," Fitzgerald said.

"It may also be important to emphasize maintaining a healthy weight," she noted, "since being obese or overweight is strongly associated with developing vascular comorbidity and has also been linked to worse MS outcomes in longitudinal studies."

Fitzgerald, study coauthors, and Thomas have disclosed no relevant financial relationships.

American Neurological Association's ANA2020 Virtual Annual Meeting: Presented October 9, 2020.


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