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NEUROLOGY 2009;72:1330-1336
© 2009 American Academy of Neurology

Cortical lesions in primary progressive multiple sclerosis

A 2-year longitudinal MR study

M. Calabrese, MD, M. A. Rocca, MD, M. Atzori, MD, I. Mattisi, MD, V. Bernardi, MD, A. Favaretto, MD, L. Barachino, RT, C. Romualdi, PhD, L. Rinaldi, PhD, P. Perini, MD, P. Gallo, MD, PhD and M. Filippi, MD

From The Multiple Sclerosis Centre of Veneto Region–First Neurology Clinic (M.C., M.A., I.M., V.B., A.F., L.R., P.P., P.G.), Department of Neurosciences, University Hospital of Padua; Neuroimaging Research Unit (M.A.R., M.F.), Department of Neurology, San Raffaele Scientific Institute and University, Milan; Neuroradiology Unit (L.B.), Euganea Medica, Albignasego, Padua; and CRIBI–Biotechnology Centre and Department of Biology (C.R.), University of Padua, Italy.

Address correspondence and reprint requests to Dr. Massimo Filippi, Neuroimaging Research Unit, Department of Neurology, San Raffaele Scientific Institute and University, Via Olgettina 60, 20132 Milan, Italy filippi.massimo{at}hsr.it

Background: In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery (DIR) sequences have improved MRI sensitivity in the detection of cortical lesions (CLs) in patients with relapsing-onset MS.

Objective: This 2-year longitudinal study was designed to assess the frequency, extent, and rate of formation of CLs in PPMS and their relationship with T2 lesion volume (LV), gray matter (GM) atrophy, and disability.

Methods: Forty-eight patients with PPMS underwent clinical and magnetic resonance examinations at baseline and after 2 years. The number and volume of CLs, WM T2 LV, and GM fraction (GMf) were assessed at baseline and at follow-up.

Results: At baseline, CLs were detected in 81.2% of patients with PPMS. At least one new CL was found in 28 patients during the follow-up. In patients with PPMS, CL and T2 WM LVs increased over the follow-up. At baseline, CL number and volumes were significantly correlated with T2 WM LV, GMf, disease duration, and Expanded Disability Status Scale score, as well as with increasing GM atrophy and disability during the follow-up. A multivariate analysis showed that CL volume at baseline was an independent predictor of percentage GM volume change and disability accumulation during the subsequent 2-year period.

Conclusions: Cortical lesions are a frequent finding in primary progressive multiple sclerosis. The extent of such abnormalities is associated with the extent of cortical atrophy and clinical disability, and is able to predict their changes over a medium time period.

Abbreviations: CIS = clinically isolated syndrome; CL = cortical lesion; DIR = double-inversion recovery; EDSS = Expanded Disability Status Scale; ETL = echo train length; FFE = fast-field echo; FOV = field of view; FLAIR = fluid-attenuated inversion recovery; GM = gray matter; GMf = gray matter fraction; HV = healthy volunteers; LV = lesion volume; MS = multiple sclerosis; NAWM = normal-appearing white matter; PGVC = percentage of GM volume change; PPMS = primary progressive; RR = relapsing-remitting; SP = secondary progressive; T2 WM LV = T2 hyperintense white matter lesion volume; TE = echo time; TI = inversion time; TIV = total intracranial volume; TR = repetition time; WM = white matter.

Supplemental data at www.neurology.org

*These authors contributed equally.

Disclosure: The authors report no disclosures.

Medications and Devices: Achieva (Philips Medical Systems; Best, The Netherlands); mitoxantrone (Novantrone; Wyeth, Madison, NJ); cyclophosphamide (Endoxan; Baxter, Deerfield, IL).

Received November 10, 2008. Accepted in final form January 30, 2009.






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