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Abstract

Background:

Cognitive impairment affects 40%–68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS.

Methods:

Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant.

Results:

No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale–Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04).

Conclusion:

Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Keywords

Multiple sclerosis relapsing/remitting demyelination MRI quantitative MRI

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References

Damasceno

Cendes

Subclinical MRI disease activity influences cognitive performance in ms patients. Mult Scler Relat Disord 2015; 4: 137–143.

Calabrese

Poretto

Favaretto

. Cortical lesion load associates with progression of disability in multiple sclerosis. Brain 2012; 135: 2952–2961.

Calabrese

Rocca

Atzori

. Cortical lesions in primary progressive multiple sclerosis: A 2-year longitudinal MR study. Neurology 2009; 72: 1330–1336.

Geurts

Pouwels

. Cortical lesions in multiple sclerosis: Combined postmortem MR imaging and histopathology. Am J Neuroradiol 2005; 26: 572–577.

Amato

Portaccio

Goretti

. Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis. Arch Neurol 2007; 64: 1157–1161.

Calabrese

Gallo

Magnetic resonance evidence of cortical onset of multiple sclerosis. Mult Scler 2009; 15: 933–941.

Yao

Hametner

van Gelderen

. 7 Tesla magnetic resonance imaging to detect cortical pathology in multiple sclerosis. PLoS ONE 2014; 9: e108863.

Mainero

Louapre

Govindarajan

. A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging. Brain 2015; 138: 932–945.

Tardif

Bedell

Eskildsen

. Quantitative magnetic resonance imaging of cortical multiple sclerosis pathology. Mult Scler Int 2012; 2012: 742018.

10.

Seewann

Vrenken

Kooi

. Imaging the tip of the iceberg: Visualization of cortical lesions in multiple sclerosis. Mult Scler 2011; 17: 1202–1210.

11.

Calabrese

Rinaldi

Seppi

. Cortical diffusion-tensor imaging abnormalities in multiple sclerosis: A 3-year longitudinal study. Radiology 2011; 261: 891–898.

12.

Faiss

Dahne

Baum

. Reduced magnetisation transfer ratio in cognitively impaired patients at the very early stage of multiple sclerosis: A prospective, multicenter, cross-sectional study. BMJ Open 2014; 4: e004409.

13.

Debernard

Melzer

Van Stockum

. Reduced grey matter perfusion without volume loss in early relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2014; 85: 544–551.

14.

Aviv

Francis

Tenenbein

. Decreased frontal lobe gray matter perfusion in cognitively impaired patients with secondary-progressive multiple sclerosis detected by the bookend technique. Am J Neuroradiol 2012; 33: 1779–1785.

15.

Peruzzo

Castellaro

Calabrese

. Heterogeneity of cortical lesions in multiple sclerosis: An MRI perfusion study. J Cereb Blood Flow Metab 2013; 33: 457–463.

16.

Polman

Reingold

Banwell

. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292–302.

17.

Vakil

Lee

Mouannes-Srour

. Cerebrovascular occlusive disease: Quantitative cerebral blood flow using dynamic susceptibility contrast MR imaging correlates with quantitative h2[15o] pet. Radiology 2013; 266: 879–886.

18.

Shin

Horowitz

Ragin

. Quantitative cerebral perfusion using dynamic susceptibility contrast MRI: Evaluation of reproducibility and age- and gender-dependence with fully automatic image postprocessing algorithm. Magn Reson Med 2007; 58: 1232–1241.

19.

Ashburner

Friston

KJ.

Unified segmentation. Neuroimage 2005; 26: 839–851.

20.

Demaree

Gaudino

DeLuca

The relationship between depressive symptoms and cognitive dysfunction in multiple sclerosis. Cogn Neuropsychiatry 2003; 8: 161–171.

21.

Morrow

Rosehart

Pantazopoulos

Anxiety and depressive symptoms are associated with worse performance on objective cognitive tests in MS. J Neuropsychiatry Clin Neurosci 2015, http://www.ncbi.nlm.nih.gov/pubmed/26569152

22.

Scarpazza

Braghittoni

Casale

. Education protects against cognitive changes associated with multiple sclerosis. Restor Neurol Neurosci 2013; 31: 619–631.

23.

Papadopoulou

Muller-Lenke

Naegelin

. Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler 2013; 19: 1290–1296.

24.

Inglese

Adhya

Johnson

. Perfusion magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis. J Cereb Blood Flow Metab 2008; 28: 164–171.

25.

Inglese

Park

Johnson

. Deep gray matter perfusion in multiple sclerosis: Dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T. Arch Neurol 2007; 64: 196–202.

26.

Rashid

Parkes

Ingle

. Abnormalities of cerebral perfusion in multiple sclerosis. J Neurol Neurosurg Psychiatry 2004; 75: 1288–1293.

27.

Francis

Jakubovic

O’Connor

. Robust perfusion deficits in cognitively impaired patients with secondary-progressive multiple sclerosis. Am J Neuroradiol 2013; 34: 62–67.

28.

Politis

Giannetti

. Increased PK11195 pet binding in the cortex of patients with MS correlates with disability. Neurology 2012; 79: 523–530.

29.

Hulst

Steenwijk

Versteeg

. Cognitive impairment in MS: Impact of white matter integrity, gray matter volume, and lesions. Neurology 2013; 80: 1025–1032.

30.

Varga

Johnson

Babb

. White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis. J Neurol Sci 2009; 282: 28–33.

31.

Dutta

McDonough

Yin

. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 2006; 59: 478–489.

32.

D’Haeseleer

Cambron

Vanopdenbosch

. Vascular aspects of multiple sclerosis. Lancet Neurol 2011; 10: 657–666.

33.

De Keyser

Steen

Mostert

. Hypoperfusion of the cerebral white matter in multiple sclerosis: Possible mechanisms and pathophysiological significance. J Cereb Blood Flow Metab 2008; 28: 1645–1651.

34.

McMahon

McQuaid

Reynolds

. Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis. Mult Scler 2012; 18: 1437–1447.

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Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients

Abstract

Background:

Methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material