* M.L. Stromillo, *A. Giorgio, *F. Rossi, *M. Battaglini, # B. Hakiki,, # E. Portaccio, * A. Federico, # M.P. Amato and * N. De Stefano *Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy; # Department of Neurology, University of Florence, Florence, Italy Imaging Cortical Lesions in Radiologically Isolated Syndrome A B Quantitative Neuroimaging Lab MR data analysis Cortical Lesions. All CLs were identified on DIR images. CLs were defined as those focal hyperintensities entirely or partly located in the cortical GM, in accordance to recently published consensus recommendations 7 . Lesion Volumes. T2 hyperintense white matter (WM) lesions were identified on PD/T 2 -W images, employing a segmentation technique based on user-supervised local thresholding. Brain Volumes. Normalized volumes of brain (NBV) and cortex (NCV) were measured on T 1 -W images by using the software SIENAX, part of FSL. Statistical analysis Comparisons between RIS subjects with and without CLs were performed with Mann-Whitney test. Correlations of CLs with MRI features were done through Spearman coefficient. A p-value <0.05 was considered for statistical significance. DISCLOSURE MLS, AG, FR, BH, AF have nothing to declare; EP receives research support from Merck Serono, Biogen-Idec, Bayer Schering and Sanofi Aventis; MPA serves on a scientific advisory board for Biogen-Idec and Sanofi-Aventis, receives research support and honoraria for speaking from Biogen-Idec, Merck Serono, Bayer Schering and Sanofi Aventis; NDS has received honoraria from Schering, Biogen Idec, Teva and Merck-Serono for consulting services, speaking and travel support and serves on advisory boards for Merck Serono. Discussion We assessed here for the first time the presence of CLs in subjects with RIS. They were found in the 40% of our asymptomatic subjects, mainly located in the frontal and temporal lobes. These data suggest that CLs are relevant in subjects with RIS and their presence can help in a better characterization of this asymptomatic condition. Whether the occurrence of CLs in RIS can be interpreted as an indicator of possible clinical evolution in MS cannot be established here. Moreover, it is noteworthy that all 6 RIS subjects with CLs were classified in a previous study as having a very high probability of being relapsing-remitting (RR) MS on a logistic regression analysis based on quantitative MRI indices 3 . Our study demonstrates that CLs similar to those found in MS patients can be found in a subgroup of RIS subjects. This may contribute to a better identification of presymptomatic MS among RIS, improving the management of subjects with this new pre-clinical condition. Materials and methods Fifteen asymptomatic subjects fulfilling criteria for RIS 1 were included in the study. Table 1 reports their clinical-demographic features. They were all part of a previously studied RIS cohort 3 . The study included an MR examination (without injection of contrast agent), a full neurological examination to further exclude signs of CNS dysfunction and neuropsychological testing through the Rao Brief Repeatable Battery (BRB) (with failure of at least 2 tests defining cognitive impairment [CI]). The brain MRI examination included conventional proton density (PD), T 2 -weighted (T 2 -W) and T 1 -weighted (T 1 -W) sequences (50 slices, 3mm thickness) as well as a DIR sequence. Images were acquired at the MR center of the University of Siena using a 1.5T scanner (Philips Medical Systems, Best, The Netherlands). P 836 Table 1. Demographic and clinical characteristics of subjects with RIS Subjects Sex Age Family history of MS Age at first brain MRI Reason for first brain MRI Spinal cord MRI ^ DIT at brain MRI CSF* CI index score $ 1 M 46 No 44 Depression - - - 16 $$ 2 F 44 No 43 Anxiety n.p. - + 8 3 F 53 No 50 Cervical trauma + + + 16 $$ 4 M 38 No 35 Dermatitis - - - 0 5 M 45 Yes 42 Neuropathic pain - + - 9 6 F 42 No 40 Dizziness (<2 mins) - - - 1 7 F 49 Yes 40 MS family history + - n.p. 3 8 F 26 No 21 Pituitary adenoma + + + 2 9 M 33 Yes 29 Headache - + - n.p. 10 F 40 No 31 Migraine with aura - + + 5 11 F 24 No 22 Migraine without aura + + + 4 12 F 35 No 34 Neck pain + + + 6 13 M 48 No 45 Headache n.p. - n.p. 1 14 F 20 No 19 Headache + + + 3 15 F 32 No 28 Obesity - + + 6 DIT= dissemination in time CSF= cerebrospinal fluid CI=cognitive impairment n.p.= not performed ^ +: presence of cervical spine lesion; -: absence of signal abnormalities *+: presence of oligoclonal bands and/or abnormal IgG Index; -: normal pattern $ The CI index score is obtained, as previously described 19 , by a grading system applied to each subject’s score on every cognitive test of the BRB, dependent on the number of standard deviations from the mean normative values $$ subjects with CI Table 2. MRI features of subjects with RIS Subjects CL number CL volume* T2-WM lesion number T2 -WM LV* NBV* NCV* 1 0 0 15 1.9 1557 530 2 0 0 22 4.3 1390 520 3 11 0.8 23 30.4 1252 440 4 0 0 29 4.3 1418 526 5 0 0 14 3.4 1477 521 6 0 0 25 3.6 1436 551 7 0 0 12 1.8 1478 540 8 8 0.5 41 7.8 1557 604 9 0 0 15 10.9 1479 551 10 0 0 22 3.3 1400 496 11 0 0 12 1.8 1487 580 12 6 0.5 22 13.7 1530 604 13 3 0.2 10 2.7 1518 570 14 2 0.5 27 10.8 1462 578 15 4 0.1 34 3.7 1448 552 Mean±SD 2.3±3.5 0.17±0.27 21.5±8.8 7±7.5 1460±77 544±42 INTRODUCTION Due to the increasing use of magnetic resonance imaging (MRI) nowadays, a new condition named as radiologically isolated syndrome (RIS) has recently emerged 1 . This condition refers to those subjects who show unanticipated brain spatial dissemination of MRI lesions highly suggestive of multiple sclerosis (MS) in the absence of a clinical scenario. Two very recent studies have provided important clues to this relevant issue 2, 3 , showing that lesion anatomic location and its relative tissue damage could help in discriminating RIS subjects with high likelihood to develop MS. In recent years, histopathology studies have shown extensive focal demyelination in the cortical gray matter (GM) of MS patients 4 . A substantial number of these cortical lesions (CLs) can be imaged in vivo using advanced MRI techniques such as double inversion recovery (DIR) 4 or multisequence- imaging protocols 5 . Thus, several studies have shown that CLs are a prominent feature of MS patients from the earliest disease stages 4 , leading to the conclusion that this is an aspect that needs to be considered in the diagnostic workup of patients with clinically isolated syndrome (CIS) suggestive of MS 6 . Against this background, we used DIR MRI acquisition to assess whether CLs could be detected in subjects with RIS. If CLs could be found, this could help to better classify RIS. Results A total of 34 round/ovoid CLs was identified in 6/15 subjects with RIS. CL type was leucocortical (i.e., mixed GM-WM) (n=15) and intracortical (n=19). They were distributed predominantly in the frontal (n=14) and temporal (n=9) lobes, were less frequent in the parietal lobe (n=6) and were sporadically found in the occipital lobe (n=3) and cerebellar cortex (n=2). The presence of CLs was frequent in RIS subjects with IgG oligoclonal bands on cerebrospinal fluid (CSF) (5/5 of those who performed CSF analysis), cervical cord lesions (4/5 of those who performed spinal imaging) and dissemination in time (DIT) at brain MRI (5/6). Moreover, CLs were found in one of the 2 RIS (subjects 1 and 3) with CI (Tables 1 and 2). There were no differences in age, sex, CI index score, NBV, NCV, and T2-WM lesion number (p>0.10 for all) between RIS subjects with and without CLs. See text for abbreviations Figure 1. Arrows identify cortical lesions (CLs) on double inversion recovery (DIR) images in subjects with radiologically isolated syndrome (RIS). REFERENCES 1.Okuda DT. Unanticipated demyelinating pathology of the CNS. Nat Rev Neurol. 2009;5:591-597 2. Okuda DT, Mowry EM, Cree BA et al. Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome. Neurology. 2011;76:686-692 3. De Stefano N, Stromillo ML, Rossi F et al. Improving the characterization of radiologically isolated syndrome suggestive of multiple sclerosis. PLos One. 2011 4. Calabrese M, Filippi M, Gallo P. Cortical lesions in multiple sclerosis. Nat Rev Neurol. 2010;6:438-444 5. Bagnato F, Yao B, Cantor F et al. Multisequence-imaging protocols to detect cortical lesions of patients with multiple sclerosis: observations from a post-mortem 3 Tesla imaging study. Journal of the neurological sciences. 2009;282:80-85 6. Filippi M, Rocca MA, Calabrese M et al. Intracortical lesions: relevance for new MRI diagnostic criteria for multiple sclerosis. Neurology. 2010;75:1988-1994 7. Geurts JJ, Roosendaal SD, Calabrese M et al. Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI. Neurology. 2011;76:418-424 However, WM lesion volume (LV) was higher in subjects with CLs than in those without CLs (11.5±10.1 cm3 versus 3.9±2.8 cm3, p=0.04). Indeed, CL number and volume correlated with WM-LV (r=0.57, p=0.03 and r=0.61, p=0.01 respectively) whereas correlation of CL number with WM lesion number was r=0.42, p=0.12. s. Copyright protected. F F1000 Posters. Copyright protected. F1000 Posters cted. F1000 Posters. Copyright protected. F1000 Posters. Copyright pr osters. Copyright protected. F1000 Posters. Copyright protected. F ght protected. F1000 Posters. Copyrigh . F1000 Post