Abstract
The use of non-routine MRI sequences such as DIR has highlighted the role of gray matter (GM) pathology in multiple sclerosis (MS). The aim of this study was to assess the detection and relevance of cortical lesions (CLs) using MRI in early (<5 years) MS patients. 3D DIR and 3D FLAIR images at 3T from 122 patients [93 relapsing–remitting MS (RRMS), 29 clinically isolated syndrome (CIS)] were scored for CLs by two blinded readers. Patients were divided into two groups depending on the presence or absence of CLs. For FLAIR, 51 CLs were identified, of which 13 were purely intracortical and 38 mixed CLs; for DIR, this was 60 in total and 16 and 44, respectively. In both groups, there was no difference in GM fraction. Neuropsychological testing was performed for a subgroup of 66 patients. In 22.1 % of patients CLs were identified. The number of CLs revealed an association with lower working memory scores and semantical word fluency. Overall, CLs imaged with 3D FLAIR and 3D DIR sequences are found more frequently in RRMS patients than CIS and may also be a correlate for mild neuropsychological pathology.
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Sander M (1898) Hirnrindenbefunde bei multipler Sklerose. Monatschrift Psychiatrie Neurol IV:427–436
Calabrese M, Gallo P (2009) Magnetic resonance evidence of cortical onset of multiple sclerosis. Mult Scler 15:933–941
Coebergh JA, Roosendaal SD, Polman CH, Geurts JJ, van Woerkom TC (2010) Acute severe memory impairment as a presenting symptom of multiple sclerosis: a clinical case study with 3D double inversion recovery MR imaging. Mult Scler 16:1521–1524
Popescu BF, Bunyan RF, Parisi JE, Ransohoff RM, Lucchinetti CF (2011) A case of multiple sclerosis presenting with inflammatory cortical demyelination. Neurology 76:1705–1710
Lucchinetti CF, Popescu BF, Bunyan RF, Moll NM, Roemer SF, Lassmann H, Bruck W, Parisi JE, Scheithauer BW, Giannini C, Weigand SD, Mandrekar J, Ransohoff RM (2011) Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 365:2188–2197
Bo L, Vedeler CA, Nyland H, Trapp BD, Mork SJ (2003) Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 9:323–331
Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712
Calabrese M, De Stefano N (2014) Cortical lesion counts by double inversion recovery should be part of the MRI monitoring process for all MS patients: yes. Mult Scler 20:537–538
Chard D (2014) Cortical lesion counts by double inversion recovery should be part of the MRI monitoring process for all MS patients: no. Mult Scler 20:539–540
Rovira A, Auger C (2014) Cortical lesion counts by double inversion recovery should be part of the MRI monitoring process for all MS patients: commentary. Mult Scler 20:541–542
Sethi V, Muhlert N, Ron M, Golay X, Wheeler-Kingshott CA, Miller DH, Chard DT, Yousry TA (2013) MS cortical lesions on DIR: not quite what they seem? PLoS One 8:e78879
Sethi V, Yousry TA, Muhlert N, Ron M, Golay X, Wheeler-Kingshott C, Miller DH, Chard DT (2012) Improved detection of cortical MS lesions with phase-sensitive inversion recovery MRI. J Neurol Neurosurg Psychiatry 83:877–882
Tallantyre EC, Morgan PS, Dixon JE, Al-Radaideh A, Brookes MJ, Morris PG, Evangelou N (2010) 3 Tesla and 7 Tesla MRI of multiple sclerosis cortical lesions. J Magn Reson Imaging 32:971–977
Calabrese M, Agosta F, Rinaldi F, Mattisi I, Grossi P, Favaretto A, Atzori M, Bernardi V, Barachino L, Rinaldi L, Perini P, Gallo P, Filippi M (2009) Cortical lesions and atrophy associated with cognitive impairment in relapsing–remitting multiple sclerosis. Arch Neurol 66:1144–1150
Calabrese M, Poretto V, Favaretto A, Alessio S, Bernardi V, Romualdi C, Rinaldi F, Perini P, Gallo P (2012) Cortical lesion load associates with progression of disability in multiple sclerosis. Brain 135:2952–2961
Calabrese M, Rocca MA, Atzori M, Mattisi I, Bernardi V, Favaretto A, Barachino L, Romualdi C, Rinaldi L, Perini P, Gallo P, Filippi M (2009) Cortical lesions in primary progressive multiple sclerosis: a 2-year longitudinal MR study. Neurology 72:1330–1336
Damasceno A, Damasceno BP, Cendes F (2014) The clinical impact of cerebellar grey matter pathology in multiple sclerosis. PLoS One 9:e96193
Papadopoulou A, Muller-Lenke N, Naegelin Y, Kalt G, Bendfeldt K, Kuster P, Stoecklin M, Gass A, Sprenger T, Radue EW, Kappos L, Penner IK (2013) Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler 19:1290–1296
Roosendaal SD, Moraal B, Pouwels PJ, Vrenken H, Castelijns JA, Barkhof F, Geurts JJ (2009) Accumulation of cortical lesions in MS: relation with cognitive impairment. Mult Scler 15:708–714
Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA (2005) Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 236:254–260
Geurts JJ, Roosendaal SD, Calabrese M, Ciccarelli O, Agosta F, Chard DT, Gass A, Huerga E, Moraal B, Pareto D, Rocca MA, Wattjes MP, Yousry TA, Uitdehaag BM, Barkhof F (2011) Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI. Neurology 76:418–424
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O’Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452
Chen JT, Pirko I (2011) MS cortical lesion or not? Double inversion recovery MRI reveals some answers and uncertainties. Neurology 76:412–413
Simon B, Schmidt S, Lukas C, Gieseke J, Traber F, Knol DL, Willinek WA, Geurts JJ, Schild HH, Barkhof F, Wattjes MP (2010) Improved in vivo detection of cortical lesions in multiple sclerosis using double inversion recovery MR imaging at 3 Tesla. Eur Radiol 20:1675–1683
Schmidt P, Gaser C, Arsic M, Buck D, Forschler A, Berthele A, Hoshi M, Ilg R, Schmid VJ, Zimmer C, Hemmer B, Muhlau M (2012) An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis. Neuroimage 59:3774–3783
Chard DT, Parker GJ, Griffin CM, Thompson AJ, Miller DH (2002) The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM-based segmentation methodology. J Magn Reson Imaging 15:259–267
Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing–remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 53:1698–1704
Roep BO, Buckner J, Sawcer S, Toes R, Zipp F (2012) The problems and promises of research into human immunology and autoimmune disease. Nat Med 18:48–53
Siffrin V, Vogt J, Radbruch H, Nitsch R, Zipp F (2010) Multiple sclerosis—candidate mechanisms underlying CNS atrophy. Trends Neurosci 33:202–210
Zipp F, Gold R, Wiendl H (2013) Identification of inflammatory neuronal injury and prevention of neuronal damage in multiple sclerosis: hope for novel therapies? JAMA Neurol 70:1569–1574
Calabrese M, De Stefano N, Atzori M, Bernardi V, Mattisi I, Barachino L, Morra A, Rinaldi L, Romualdi C, Perini P, Battistin L, Gallo P (2007) Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis. Arch Neurol 64:1416–1422
Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ (2003) Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 62:723–732
Kutzelnigg A, Lassmann H (2005) Cortical lesions and brain atrophy in MS. J Neurol Sci 233:55–59
Kilsdonk ID, de Graaf WL, Soriano AL, Zwanenburg JJ, Visser F, Kuijer JP, Geurts JJ, Pouwels PJ, Polman CH, Castelijns JA, Luijten PR, Barkhof F, Wattjes MP (2013) Multicontrast MR imaging at 7T in multiple sclerosis: highest lesion detection in cortical gray matter with 3D-FLAIR. Am J Neuroradiol 34:791–796
Vural G, Keklikoglu HD, Temel S, Deniz O, Ercan K (2013) Comparison of double inversion recovery and conventional magnetic resonance brain imaging in patients with multiple sclerosis and relations with disease disability. Neuroradiol J 26:133–142
Rocca MA, De Meo E, Amato MP, Copetti M, Moiola L, Ghezzi A, Veggiotti P, Capra R, Fiorino A, Pippolo L, Pera MC, Falini A, Comi G, Filippi M (2014) Cognitive impairment in paediatric multiple sclerosis patients is not related to cortical lesions. Mult Scler
Rovaris M, Filippi M, Minicucci L, Iannucci G, Santuccio G, Possa F, Comi G (2000) Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis. Am J Neuroradiol 21:402–408
Giorgio A, Stromillo ML, Rossi F, Battaglini M, Hakiki B, Portaccio E, Federico A, Amato MP, De Stefano N (2011) Cortical lesions in radiologically isolated syndrome. Neurology 77:1896–1899
Acknowledgments
F.Z. is grateful for financial support from the German Multiple Sclerosis Competence Network (KKNMS, Project B7.3) funded by the Federal Ministry for Education and Research (BMBF).
Conflicts of interest
Pierre Kolber reports no conflicts of interest and financial disclosures. Swantje Montag reports no conflicts of interest and financial disclosures. Dr. Vinzenz Fleischer reports no conflicts of interest and financial disclosures. Dr. Felix Lüssi reports no conflicts of interest and financial disclosures. Janine Wilting reports no conflicts of interest and financial disclosures. Dr. Joachim Gawehn reports no conflicts of interest and financial disclosures. Dr. Adriane Gröger reports no conflicts of interest and financial disclosures. Dr. Frauke Zipp has received research grants from Teva, Merck Serono, Novartis and Bayer as well as consultation funds from Teva, Merck Serono, Novartis, Bayer Healthcare, Biogen Idec Germany, ONO, Genzyme, Sanofi-Aventis and Octapharma. Her travel compensation has been provided for by the aforementioned companies.
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All patients gave their written informed consent to examinations before participating in this study, which was approved by the local ethics committee and adhered to institutional guidelines in accordance with the Declaration of Helsinki.
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A. Gröger and F. Zipp contributed equally.
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Kolber, P., Montag, S., Fleischer, V. et al. Identification of cortical lesions using DIR and FLAIR in early stages of multiple sclerosis. J Neurol 262, 1473–1482 (2015). https://doi.org/10.1007/s00415-015-7724-5
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DOI: https://doi.org/10.1007/s00415-015-7724-5