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Research ArticleADULT BRAIN
Open Access

Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline

R. Vitorino, S.-P. Hojjat, C.G. Cantrell, A. Feinstein, L. Zhang, L. Lee, P. O'Connor, T.J. Carroll and R.I. Aviv
American Journal of Neuroradiology October 2016, 37 (10) 1800-1807; DOI: https://doi.org/10.3174/ajnr.A4824
R. Vitorino
cMedical Imaging (R.V., S.-P.H., L.Z., R.I.A.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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  • ORCID record for R. Vitorino
S.-P. Hojjat
cMedical Imaging (R.V., S.-P.H., L.Z., R.I.A.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
fMedical Imaging (S.-P.H., R.I.A.), University of Toronto, Toronto, Ontario, Canada
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C.G. Cantrell
gDepartments of Biomedical Engineering (C.G.C., T.J.C)
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A. Feinstein
aFrom the Departments of Psychiatry (A.F.)
ePsychiatry (A.F.)
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L. Zhang
cMedical Imaging (R.V., S.-P.H., L.Z., R.I.A.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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L. Lee
bNeurology (L.L.)
dDepartments of Medicine (L.L., P.O.)
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P. O'Connor
dDepartments of Medicine (L.L., P.O.)
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T.J. Carroll
gDepartments of Biomedical Engineering (C.G.C., T.J.C)
hRadiology (T.J.C.), Northwestern University, Chicago, Illinois.
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R.I. Aviv
cMedical Imaging (R.V., S.-P.H., L.Z., R.I.A.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
fMedical Imaging (S.-P.H., R.I.A.), University of Toronto, Toronto, Ontario, Canada
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    FIGURE.

    Areas of significantly (Puncorrected < .001) reduced cortical perfusion in RRMS subgroups and healthy controls, with volumes for atrophied regions added as covariates. Green indicates healthy controls versus nonimpaired RRMS; red, healthy controls versus cognitively impaired RRMS; and yellow, nonimpaired RRMS versus cognitively impaired RRMS.

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    Table 1:

    Demographic, neurologic, and neuropsychological data of healthy controls and patients with RRMSa

    Healthy Controls (n = 19)Cognitively Nonimpaired RRMS (n = 19)Cognitively Impaired RRMS (n = 20)
    Demographic and clinical data
        Age (yr)49.0 ± 7.146.4 ± 7.248.1 ± 4.7
        Sex (F/M)14:515:412:8
        Education (yr)16.9 ± 2.9b16.1 ± 1.314.6 ± 1.9b
        Disease duration (yr)NA11.8 ± 5.411.6 ± 4.9
        EDSSNA1.8 ± 0.7c2.6 ± 0.7c
        HADS-Anxiety4.4 ± 4.3b,d6.37 ± 3.1d8.5 ± 3.7b
        HADS-Depression2.3 ± 2.3b3.5 ± 3.2c7.6 ± 2.9b,c
        TreatmentNA
            β-interferon4 (21%)3 (15%)
            Other immune suppressors11 (58%)12 (60%)
            None4 (21%)5 (25%)
        Presence of enhancing lesionsNA1 (5%)5 (25%)
    Volumetric data (cm3)
        GM653.37 ± 81.51618.83 ± 53.94605.09 ± 60.90
        WM458.22 ± 65.02b421.84 ± 39.29414.53 ± 71.56b
        BG19.41 ± 2.7518.68 ± 2.5218.04 ± 2.93
        Th9.83 ± 1.92b9.14 ± 1.987.91 ± 1.88b
        CL0.00 ± 0.00b0.12 ± 0.110.22 ± 0.36b
        T2H0.00 ± 0.00b9.37 ± 10.0213.47 ± 13.30b
        T1bh0.00 ± 0.00b3.21 ± 2.985.85 ± 6.77b
        CSF320.89 ± 210.43b353.22 ± 131.71400.29 ± 173.78b
    Neurocognitive tests (z score)
        COWAT-FAS−0.67 ± 0.83−0.26 ± 1.06c−1.16 ± 0.89c
        COWAT-Animals−0.13 ± 1.14−0.41 ± 0.95c−0.59 ± 1.18c
        BVMT-IR−0.37 ± 1.15b−0.07 ± 1.04c−1.68 ± 1.34b,c
        BVMT-DR−0.40 ± 1.14b−0.42 ± 0.77c−1.62 ± 1.48b,c
        PASAT-3−0.39 ± 0.94b−0.05 ± 0.61c−1.71 ± 0.82b,c
        PASAT-2−0.21 ± 0.89b−0.26 ± 0.66c−1.80 ± 0.57b,c
        JLO−0.98 ± 0.20−0.83 ± 0.56−0.40 ± 0.67
        SDMT−0.14 ± 0.92b−0.02 ± 0.75c−1.80 ± 1.17b,c
        CVLT II-IR−0.25 ± 1.05b−0.23 ± 1.04c−1.94 ± 1.36b,c
        CVLT II-DR−0.11 ± 0.66b−0.21 ± 0.92c−2.20 ± 1.61b,c
        DKEFS-ST−0.51 ± 0.73−0.26 ± 0.61−0.20 ± 1.25
    • Note:—NA indicates not applicable; EDSS, Expanded Disability Status Score; HADS, Hospital Anxiety and Depression Scale; COWAT, Controlled Oral Word Association Test; BVMT, Brief Visuospatial Test- Revised; PASAT, Paced Auditory Serial Addition Test; JLO, Judgment of Line Orientation Test; SDMT, Symbol Digit Modalities Test; CVLT II, California Verbal Learning Test-II; IR, immediate recall; DR, delayed recall; DKEFS-ST, Delis-Kaplan Executive Function System Sorting Test; BG, basal ganglia; Th, thalamus; CL, cortical lesions; T2H, T2 hyperintensities; T1bh, T1 black holes.

    • ↵a Significance at P <.017, corrected for multiple comparisons; all values are means unless specified.

    • ↵b Healthy controls vs patients with RRMS with cognitive impairment..

    • ↵c Patients with RRMS without impairment vs those with cognitive impairment.

    • ↵d Healthy controls vs patients with RRMS without impairment.

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    Table 2:

    Areas of significantly (Puncorrected < .001) reduced cortical perfusion in RRMS subgroups and healthy controls, with volumes for atrophied regions added as covariates

    qCBFqCBVAnatomic RegionsCluster SizeMNI Coordinatest Values
    xyzHC vs CIHC vs NINI vs CI
    ✓✓Left superior frontal gyrus (BAs 6, 10)a78−3250283.523.62
    ✓Right middle frontal gyrus (BA 6)a26340643.31
    ✓✓Left middle frontal gyrus (BAs 10, 11, 46)a100−2256264.794.563.21
    ✓Left inferior frontal gyrus (BA 46)21−4830203.29
    ✓Right parahippocampal gyrus (BA 28)a2724−22−124.15
    ✓✓Right lingual gyrusa10112−72−25.11
    ✓Left lingual gyrus (BA 18)72−6−6823.99
    ✓Right inferior parietal lobule (BA 40)a2248−40563.98
    ✓Right superior temporal gyrus (BA 38)382810−463.64
    ✓Left temporal fusiform gyrus (BA 20)a134−44−22−303.74
    ✓Left caudate heada36−10643.64
    ✓Right caudate body2418−20263.68
    ✓Left thalamic medial dorsal nucleia31−6−1863.63
    • Note:—CI indicates patients with RRMS with cognitive impairment; NI, patients with RRMS without impairment; ✓, anatomic region was present in VBM analysis for this map.

    • ↵a Anatomic regions remained significant from previous VBM analysis without atrophy areas added as covariates.

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R. Vitorino, S.-P. Hojjat, C.G. Cantrell, A. Feinstein, L. Zhang, L. Lee, P. O'Connor, T.J. Carroll, R.I. Aviv
Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline
American Journal of Neuroradiology Oct 2016, 37 (10) 1800-1807; DOI: 10.3174/ajnr.A4824

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Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline
R. Vitorino, S.-P. Hojjat, C.G. Cantrell, A. Feinstein, L. Zhang, L. Lee, P. O'Connor, T.J. Carroll, R.I. Aviv
American Journal of Neuroradiology Oct 2016, 37 (10) 1800-1807; DOI: 10.3174/ajnr.A4824
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