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Relation of vision to global and regional brain MRI in multiple sclerosis

From the Departments of Neurology (G.F.W., D.A.J., C.E.M., S.L.G., M.L.N.-S., L.J.B.), Radiology (E.D.S., T.L., A.S., S.M., L.M.D., J.K.U.), and Ophthalmology (S.L.G., L.J.B.), University of Pennsylvania School of Medicine, Philadelphia, PA; Department of Biostatistics (G.R.C.), University of Alabama, Birmingham, AL; and Department of Neurology (P.A.C.), The Johns Hopkins University School of Medicine, Baltimore, MD.

Address correspondence and reprint requests to Dr. Laura J. Balcer, 3 E. Gates–Neurology, 3400 Spruce Street, Philadelphia, PA 19104 lbalcer{at}mail.med.upenn.edu

Objective: To examine the relation between low-contrast letter acuity, an emerging visual outcome for multiple sclerosis (MS) clinical trials, and brain MRI abnormalities in an MS cohort.

Methods: T2 lesion volume and brain parenchymal fraction were determined for whole brain and within visual pathway regions of interest. Magnetization transfer ratio histograms were examined. Vision testing was performed binocularly using low-contrast letter acuity (2.5%, 1.25% contrast) and high-contrast visual acuity (VA). Linear regression, accounting for age and disease duration, was used to assess the relation between vision and MRI measures.

Results: Patients (n = 45) were aged 44 ± 11 years, with disease duration of 5 years (range <1 to 21), Expanded Disability Status Scale score of 2.0 (0 to 6.0), and binocular Snellen acuity of 20/16 (20/12.5 to 20/25). The average T2 lesion volume was 18.5 mm³. Patients with lower (worse) low-contrast letter acuity and high-contrast VA scores had greater T2 lesion volumes in whole brain (2.5% contrast: p = 0.004; 1.25%: p = 0.002; VA: p = 0.04), Area 17 white matter (2.5%: p < 0.001; 1.25%: p = 0.02; VA: p = 0.01), and optic radiations (2.5%: p = 0.001; 1.25%: p = 0.02; VA: p = 0.007). Within whole brain, a 3-mm³ increase in lesion volume corresponded, on average, to a 1-line worsening of low-contrast acuity, whereas 1-line worsening of high-contrast acuity corresponded to a 5.5-mm³ increase.

Conclusions: Low-contrast letter acuity scores correlate well with brain MRI lesion burden in multiple sclerosis (MS), supporting validity for this vision test as a candidate for clinical trials. Disease in the postgeniculate white matter is a likely contributor to visual dysfunction in MS that may be independent of acute optic neuritis history.

Abbreviations: BP = brain parenchymal; BPF = brain parenchymal fraction; DICOM = Digital Imaging and Communications in Medicine; EDSS = Expanded Disability Status Scale; ETDRS = Early Treatment Diabetic Retinopathy Study; HIPAA = Health Insurance Portability and Accountability Act; MS = multiple sclerosis; MSFC = MS Functional Composite; OCT = optical coherence tomography; PASAT = paced auditory serial addition test; ROIs = regions of interest; VA = visual acuity.

Editorial, see page 2119

e-Pub ahead of print on September 19, 2007, at www.neurology.org.

Supported by National Multiple Sclerosis Society Fellowship Grant FG 1681-A-1 (G.F.W.), National Multiple Sclerosis Society Research Grants RG 3208-A-1 and RG 3428-A/2 (L.J.B.), and National Multiple Sclerosis Society Translational Research Partnership TR 3760-A-3 (P.A.C., L.J.B.).

Disclosure: The authors report no conflicts of interest.

Received April 10, 2007. Accepted in final form June 1, 2007.

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