Cerebrovascular hemodynamics association with brain structure and function in Multiple Sclerosis

Abstract

Background: Vascular risk factors seem to contribute to disease progression in Multiple Sclerosis (MS), but the mechanistic connection between vascular risk and MS is unknown. Understanding cerebrovascular hemodynamics (CVH) in MS may help advance our understanding of the link between vascular risk and MS.

Objectives: Examine the relationship between CVH [dynamic cerebral autoregulation (dCA) and vasoreactivity (VR)] and brain structure (MRI) and function (cognition, and gait) in individuals with MS.

Methods: Transcranial Doppler ultrasound (TCD) was utilized to assess two key markers of CVH: dCA and VR. dCA (reported as phase and gain) is calculated from the spontaneous blood pressure and flow velocity oscillations. VR is calculated as the slope of change in cerebral blood flow velocity in response to end-tidal CO₂. Global gray matter (GM), white matter (WM), WM hyperintensity (WMH) volumes and WM lesion counts were measured from brain MRI. All participants underwent detailed cognitive and gait assessments.

Results: Eighty participants were included (age 44 ± 11, 26 % male); 75 had relapsing-remitting MS (94 %), with disease duration of 8 (11) years [median (IQR)] since MS diagnosis and an Expanded Disability Status Scale (EDSS) of 2.0 (4.0). Higher phase (better dCA) was associated with greater GM volume, lower WHM burden and higher cognitive scores in the memory and global cognitive domains (all P values <0.05). There was no relationship between CVH and gait speed in our study participants. There was no relationship between VR and any measures of brain structure and function.

Conclusions: More efficient cerebral autoregulation is associated with better brain structure (larger GM and lower WMH volumes) and function (cognition, but not gait) in patients with MS.

Keywords: Cerebral autoregulation; Cognition; MRI; Multiple Sclerosis; Transcranial Doppler ultrasound.

Fig. 1.

Transfer function measures of dynamic cerebral autoregulation using transcranial Doppler ultrasound. Dynamic cerebral autoregulation is the mechanism by which spontaneous fluctuations in arterial blood pressure (ABP) induce transient responses in mean flow velocity (MFV) at the level of cerebral vessels. Transfer function analysis derives gain and phase measures to evaluate cerebral autoregulation. Gain is the magnitude of transmission from arterial blood pressure to cerebral blood flow velocity. The phase shift reflects the temporal delay between transmissions of oscillations from arterial blood pressure to cerebral blood flow velocity. Abbreviations: ABP = arterial blood pressure; MFV = mean flow velocity.

Fig. 2.

Association between cerebral hemodynamics and MRI measurements. β represents unstandardized regression coefficients. dCA: phase in radians, gain in cm/s*mmHg. VR in cm/s*mmHg CO₂. MRI measures % of ICV except for WM lesion count (absolute number). All analyses were adjusted for age, sex, race, years of MS duration and vascular risk score. WM hyperintensities and WM lesion count values were log-transformed due to a non-normal distribution. *Indicates a P-value <0.05. Abbreviations: CI = confidence interval; dCA = dynamic cerebral autoregulation; GMV = gray matter volume; ICV = intracranial volume; MRI = magnetic resonance imaging; VR = vasoreactivity; WM = white matter; WMV = white matter volume.

Fig. 3.

Association between cerebral hemodynamics and cognition. β represents unstandardized regression coefficients. dCA: phase in radians, gain in cm/s*mmHg. VR in cm/s*mmHg CO₂. All analysis were adjusted for age, sex, race, years of MS duration, education, and vascular risk score. *Indicates a P-value <0.05 Abbreviations: CI = confidence interval; dCA = dynamic cerebral autoregulation; VR = vasoreactivity.

Fig. 4.

Association between cerebral hemodynamics and gait velocities. β represents unstandardized regression coefficients. dCA: phase in radians, gain in cm/s*mmHg. VR in cm/s*mmHg CO2. Gait self and fast paces velocities in cm/s. All analysis were adjusted for age, sex, race, years of MS duration, and height. Abbreviations: CI = confidence interval; dCA = dynamic cerebral autoregulation; VR = vasoreactivity.

Fig. 5.

Dynamic cerebral autoregulation association with brain structure. A. More efficient cerebral autoregulation (higher phase shift) is associated with higher gray matter volume and lower white matter hyperintensities. B. Multiple Sclerosis patients with worse autoregulation (lower phase shift) had brain atrophy caused by lower cortical and subcortical gray matter volumes and a larger amount of white matter hyperintensities. Abbreviations: ABP = arterial blood pressure; MFV = mean flow velocity; WMH = white matter hyperintensities.