Pathophysiology of multiple sclerosis damage and repair: Linking cerebral hypoperfusion to the development of irreversible tissue loss in multiple sclerosis using magnetic resonance imaging

Author:

Mascali Daniele12,Villani Alessandro12,Chiarelli Antonio M.12,Biondetti Emma12,Lipp Ilona34,Digiovanni Anna15,Pozzilli Valeria15,Caporale Alessandra S.12ORCID,Rispoli Marianna G.15,Ajdinaj Paola15,D'Apolito Maria15,Grasso Eleonora16,Sensi Stefano L.127,Murphy Kevin8,Tomassini Valentina1245ORCID,Wise Richard G.124ORCID

Affiliation:

1. Department of Neurosciences, Imaging, and Clinical Sciences G. d'Annunzio University of Chieti‐Pescara Chieti Italy

2. Institute for Advanced Biomedical Technologies G. d'Annunzio University of Chieti‐Pescara Chieti Italy

3. Department of Neurophysics Max Planck Institute for Human Cognitive and Brain Sciences Leipzig Germany

4. Cardiff University Brain Research Imaging Centre, School of Psychology Cardiff University Cardiff UK

5. MS Centre, Department of Clinical Neurology SS. Annunziata University Hospital Chieti Italy

6. Department of Paediatrics SS. Annunziata University Hospital Chieti Italy

7. Behavioral Neurology and Molecular Neurology Units, Centre for Advanced Studies and Technology G. d'Annunzio University of Chieti‐Pescara Chieti Italy

8. Cardiff University Brain Research Imaging Centre, School of Physics and Astronomy Cardiff University Cardiff UK

Abstract

AbstractBackground and purposeReduced cerebral perfusion has been observed in multiple sclerosis (MS) and may contribute to tissue loss both acutely and chronically. Here, we test the hypothesis that hypoperfusion occurs in MS and relates to the presence of irreversible tissue damage.MethodsIn 91 patients with relapsing MS and 26 healthy controls (HC), gray matter (GM) cerebral blood flow (CBF) was assessed using pulsed arterial spin labeling. GM volume, T1 hypointense and T2 hyperintense lesion volumes (T1LV and T2LV, respectively), and the proportion of T2‐hyperintense lesion volume that appears hypointense on T1‐weighted magnetic resonance imaging (T1LV/T2LV) were quantified. GM CBF and GM volume were evaluated globally, as well as regionally, using an atlas‐based approach.ResultsGlobal GM CBF was lower in patients (56.9 ± 12.3 mL/100 g/min) than in HC (67.7 ± 10.0 mL/100 g/min; p < 0.001), a difference that was widespread across brain regions. Although total GM volume was comparable between groups, significant reductions were observed in a subset of subcortical structures. GM CBF negatively correlated with T1LV (r = −0.43, p = 0.0002) and T1LV/T2LV (r = −0.37, p = 0.0004), but not with T2LV.ConclusionsGM hypoperfusion occurs in MS and is associated with irreversible white matter damage, thus suggesting that cerebral hypoperfusion may actively contribute and possibly precede neurodegeneration by hampering tissue repair abilities in MS.

Funder

Wellcome Trust

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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