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Massimiliano Calabrese, MD; Nicola De Stefano, MD, PhD; Matteo Atzori, MD; Valentina Bernardi, MD; Irene Mattisi, MD; Luigi Barachino, PhD; Aldo Morra, MD; Luciano Rinaldi, MD, PhD; Chiara Romualdi, PhD; Paola Perini, MD; Leontino Battistin, MD; Paolo Gallo, MD, PhD

Arch Neurol. 2007;64(10):1416-1422.

Background  A significant inflammatory pathologic disorder in the cortex of patients with multiple sclerosis (MS) has been demonstrated by ex vivo studies.

Objective  To determine the frequency, time of appearance, and clinical relevance of intracortical lesions (ICLs) in MS in vivo.

Design  Double inversion recovery sequence study.

Setting  Multiple Sclerosis Centre of the Veneto Region.

Patients  We enrolled 380 patients (116 with clinically isolated syndrome [CIS], 163 with relapsing-remitting MS [RRMS], and 101 with secondary progressive MS [SPMS]) and 40 age- and sex-matched healthy volunteers between May 1, 2005, and December 31, 2006.

Main Outcome Measures  We assessed the frequency and number of ICLs and brain parenchyma fraction, white matter T2 lesion volume, and clinical disability.

Results  Although never observed in healthy volunteers, ICLs were detected in 58% of patients (36% of patients with CIS, 64% of patients with RRMS, and 73% of patients with SPMS). The number of ICLs was higher in patients with SPMS than in those with CIS or RRMS (P <.001), and patients with ICLs had a higher Expanded Disability Status Scale score (P = .004), a higher white matter T2 lesion volume (P = .008), a lower brain parenchyma fraction (P = .009), and a higher frequency of IgG oligoclonal bands (IgGOBs) (P <.001) than patients without ICLs. Patients positive for IgGOBs had more ICLs than patients negative for IgGOBs (P = .02). The number of ICLs correlated with the Expanded Disability Status Scale score (r = 0.48, P <.001), white matter T2 lesion volume (r = 0.38, P = .001), and brain parenchyma fraction (r = –0.47, P = .001). A significant association between ICLs and male sex was observed.

Conclusions  Although more frequent in patients with SPMS, ICLs were observed from the early disease stages. The ICLs were more frequently detected in patients with IgGOBs and were associated with a higher clinical disability score and male sex. The ICLs may help to define MS clinical heterogeneity and prognosis in clinical settings.

Author Affiliations: The Multiple Sclerosis Centre of the Veneto Region–First Neurology Clinic, Department of Neurosciences, University Hospital of Padova (Drs Calabrese, Atzori, Bernardi, Mattisi, Rinaldi, Perini, Battistin, and Gallo), Neuroradiology Unit, Euganea Medica (Drs Barachino, Morra, and Battistin), and CRIBI–Biotechnology Centre and Department of Biology, University of Padova (Drs Romualdi and Battistin), Padova; Quantitative Neuroimaging Laboratory, Department of Neurological and Behavioral Sciences, University of Siena, Siena (Drs De Stefano and Battistin); and IRCCS Hospital San Camillo, Venezia (Dr Battistin), Italy.

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