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. 2014 Oct;71(10):1275-81.
doi: 10.1001/jamaneurol.2014.1668.

Impaired cerebrovascular reactivity in multiple sclerosis

Olga Marshall  1 , Hanzhang Lu  2 , Jean-Christophe Brisset  1 , Feng Xu  2 , Peiying Liu  2 , Joseph Herbert  3 , Robert I Grossman  1 , Yulin Ge  1
Affiliations

Impaired cerebrovascular reactivity in multiple sclerosis

Olga Marshall et al. JAMA Neurol. 2014 Oct.

Abstract

Importance: Cerebrovascular reactivity (CVR) is an inherent indicator of the dilatory capacity of cerebral arterioles for a vasomotor stimulus for maintaining a spontaneous and instant increase of cerebral blood flow (CBF) in response to neural activation. The integrity of this mechanism is essential to preserving healthy neurovascular coupling; however, to our knowledge, no studies have investigated whether there are CVR abnormalities in multiple sclerosis (MS).

Objective: To use hypercapnic perfusion magnetic resonance imaging to assess CVR impairment in patients with MS.

Design, setting, and participants: A total of 19 healthy volunteers and 19 patients with MS underwent perfusion magnetic resonance imaging based on pseudocontinuous arterial spin labeling to measure CBF at normocapnia (ie, breathing room air) and hypercapnia. The hypercapnia condition is achieved by breathing 5% carbon dioxide gas mixture, which is a potent vasodilator causing an increase of CBF.

Main outcomes and measures: Cerebrovascular reactivity was calculated as the percent increase of normocapnic to hypercapnic CBF normalized by the change in end-tidal carbon dioxide, which was recorded during both conditions. Group analysis was performed for regional and global CVR comparison between patients and controls. Regression analysis was also performed between CVR values, lesion load, and brain atrophy measures in patients with MS.

Results: A significant decrease of mean (SD) global gray matter CVR was found in patients with MS (3.56 [0.81]) compared with healthy controls (5.08 [1.56]; P = .001). Voxel-by-voxel analysis showed diffuse reduction of CVR in multiple regions of patients with MS. There was a significant negative correlation between gray matter CVR and lesion volume (R = 0.6, P = .004) and a significant positive correlation between global gray matter CVR and gray matter atrophy index (R = 0.5, P = .03).

Conclusions and relevance: Our quantitative imaging findings suggest impairment in functional cerebrovascular pathophysiology, by measuring a diffuse decrease in CVR, which may be the underlying cause of neurodegeneration in MS.

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Figures

Figure 1
Figure 1. Mean Gray Matter CVR Maps of Patients With Multiple Sclerosis and Controls
The mean gray matter cerebrovascular reactivity (CVR) maps of the control group (A) and multiple sclerosis group (B) show the diffuse decrease of CVR in the patients with multiple sclerosis. The color bar shows the range of CVR values (calculated as the percent increase of normocapnic to hypercapnic cerebral blood flow normalized by the change in end-tidal carbon dioxide).
Figure 2
Figure 2. Comparison of Global and Regional CVR Values for Patients With MS and Controls
A, Comparison of mean global gray matter (GM) cerebrovascular reactivity (CVR) values (calculated as the percent increase of normocapnic to hypercapnic cerebral blood flow normalized by the change in end-tidal carbon dioxide) between the multiple sclerosis (MS) group and the control group showing a significant decrease in CVR in patients compared with controls. Error bars indicate standard deviation. B, Surface rendering of voxel-based map on Montreal Neurological Institute brain template of significantly decreased CVR in the MS group vs control group (corrected P < .05) is shown in red, as generated by Statistical Parametric Mapping. The 6 surface rendering views shown are anterior/posterior (top row), lateral (middle row), and bottom/top (bottom row).
Figure 3
Figure 3. GM CVR Correlations With Lesion Volume and Atrophy
Correlation of gray matter (GM) cerebrovascular reactivity (CVR; calculated as the percent increase of normocapnic to hypercapnic cerebral blood flow normalized by the change in end-tidal carbon dioxide) in patients with multiple sclerosis with lesion volume (R = 0.6, P = .004) (A) and with fractional GM (fGM) atrophy index (R = 0.5, P = .03) (B).
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