Clinical correlates of grey matter pathology in multiple sclerosis
Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
22397707
PubMed Central
PMC3311149
DOI
10.1186/1471-2377-12-10
PII: 1471-2377-12-10
Knihovny.cz E-zdroje
- MeSH
- atrofie MeSH
- kognitivní poruchy * patologie patofyziologie MeSH
- lidé MeSH
- mozek * patologie patofyziologie MeSH
- mozková kůra patologie patofyziologie MeSH
- progrese nemoci MeSH
- roztroušená skleróza * patologie patofyziologie MeSH
- zánět * patologie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect.
Zobrazit více v PubMed
Weiner HL. The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease? Ann Neurol. 2009;65(3):239–248. PubMed
Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–1517. PubMed
Derfuss T, Parikh K, Velhin S, Braun M, Mathey E, Krumbholz M, Kumpfel T, Moldenhauer A, Rader C, Sonderegger P. et al.Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci USA. 2009;106(20):8302–8307. PubMed PMC
Lassmann H, van Horssen J. The molecular basis of neurodegeneration in multiple sclerosis. FEBS letters. 2011. PubMed
Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009;132(Pt 5):1175–1189. PubMed PMC
IMSGC. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–219. PubMed PMC
Rio J, Comabella M, Montalban X. Predicting responders to therapies for multiple sclerosis. Nat Rev Neurol. 2009;5(10):553–560. PubMed
Sormani MP, Bonzano L, Roccatagliata L, De Stefano N. Magnetic resonance imaging as surrogate for clinical endpoints in multiple sclerosis: data on novel oral drugs. Mult Scler. 2011;17(5):630–633. PubMed
Havrdova E, Galetta S, Stefoski D, Comi G. Freedom from disease activity in multiple sclerosis. Neurology. 2010;74(Suppl 3):S3–7. PubMed
Hartung HP, Montalban X, Sorensen PS, Vermersch P, Olsson T. Principles of a new treatment algorithm in multiple sclerosis. Expert Rev Neurother. 2011;11(3):351–362. PubMed
Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando K, Plant GT, Thompson AJ, Miller DH. Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain. 2004;127(Pt 5):1101–1107. PubMed
Fisher E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008;64(3):255–265. PubMed
Chard DT, Griffin CM, Parker GJ, Kapoor R, Thompson AJ, Miller DH. Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain. 2002;125(Pt 2):327–337. PubMed
Ge Y, Grossman RI, Udupa JK, Babb JS, Nyul LG, Kolson DL. Brain atrophy in relapsing-remitting multiple sclerosis: fractional volumetric analysis of gray matter and white matter. Radiology. 2001;220(3):606–610. PubMed
Sastre-Garriga J, Ingle GT, Chard DT, Ramio-Torrenta L, Miller DH, Thompson AJ. Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis. Neuroimage. 2004;22(1):353–359. PubMed
Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002;15(3):239–245. PubMed
Comi G, Filippi M, Martinelli V, Sirabian G, Visciani A, Campi A, Mammi S, Rovaris M, Canal N. Brain magnetic resonance imaging correlates of cognitive impairment in multiple sclerosis. J Neurol Sci. 1993;115(Suppl):S66–73. PubMed
Thorpe JW, Kidd D, Moseley IF, Kenndall BE, Thompson AJ, MacManus DG, McDonald WI, Miller DH. Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis. Neurology. 1996;46(2):373–378. PubMed
Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE. et al.A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG) Neurology. 1999;53(1):139–148. PubMed
Fox NC, Jenkins R, Leary SM, Stevenson VL, Losseff NA, Crum WR, Harvey RJ, Rossor MN, Miller DH, Thompson AJ. Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI. Neurology. 2000;54(4):807–812. PubMed
Zivadinov R, Stosic M, Cox JL, Ramasamy DP, Dwyer MG. The place of conventional MRI and newly emerging MRI techniques in monitoring different aspects of treatment outcome. J Neurol. 2008;255(Suppl 1):61–74. PubMed
Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology. 1999;53(8):1698–1704. PubMed
Bagnato F, Butman JA, Gupta S, Calabrese M, Pezawas L, Ohayon JM, Tovar-Moll F, Riva M, Cao MM, Talagala SL. et al.In vivo detection of cortical plaques by MR imaging in patients with multiple sclerosis. AJNR Am J Neuroradiol. 2006;27(10):2161–2167. PubMed PMC
Geurts JJ, Blezer EL, Vrenken H, van der Toorn A, Castelijns JA, Polman CH, Pouwels PJ, Bo L, Barkhof F. Does high-field MR imaging improve cortical lesion detection in multiple sclerosis? J Neurol. 2008;255(2):183–191. PubMed
Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology. 2005;236(1):254–260. PubMed
Kangarlu A, Bourekas EC, Ray-Chaudhury A, Rammohan KW. Cerebral cortical lesions in multiple sclerosis detected by MR imaging at 8 Tesla. AJNR Am J Neuroradiol. 2007;28(2):262–266. PubMed PMC
Nelson F, Poonawalla AH, Hou P, Huang F, Wolinsky JS, Narayana PA. Improved identification of intracortical lesions in multiple sclerosis with phase-sensitive inversion recovery in combination with fast double inversion recovery MR imaging. AJNR Am J Neuroradiol. 2007;28(9):1645–1649. PubMed PMC
Pouwels PJ, Kuijer JP, Mugler JP, Guttmann CR, Barkhof F. Human gray matter: feasibility of single-slab 3D double inversion-recovery high-spatial-resolution MR imaging. Radiology. 2006;241(3):873–879. PubMed
Brownell B, Hughes JT. The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1962;25:315–320. PubMed PMC
Calabrese M, Rocca MA, Atzori M, Mattisi I, Bernardi V, Favaretto A, Barachino L, Romualdi C, Rinaldi L, Perini P. et al.Cortical lesions in primary progressive multiple sclerosis: a 2-year longitudinal MR study. Neurology. 2009;72(15):1330–1336. PubMed
Calabrese M, Rocca MA, Atzori M, Mattisi I, Favaretto A, Perini P, Gallo P, Filippi M. A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis. Ann Neurol. 2010;67(3):376–383. PubMed
Geurts JJ, Bo L, Pouwels PJ, Castelijns JA, Polman CH, Barkhof F. Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol. 2005;26(3):572–577. PubMed PMC
De Stefano N, Matthews PM, Filippi M, Agosta F, De Luca M, Bartolozzi ML, Guidi L, Ghezzi A, Montanari E, Cifelli A. et al.Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology. 2003;60(7):1157–1162. PubMed
Horakova D, Cox JL, Havrdova E, Hussein S, Dolezal O, Cookfair D, Dwyer MG, Seidl Z, Bergsland N, Vaneckova M. et al.Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case-control study. J Neurol Neurosurg Psychiatry. 2008;79(4):407–414. PubMed
Pirko I, Lucchinetti CF, Sriram S, Bakshi R. Gray matter involvement in multiple sclerosis. Neurology. 2007;68(9):634–642. PubMed
Fisniku LK, Chard DT, Jackson JS, Anderson VM, Altmann DR, Miszkiel KA, Thompson AJ, Miller DH. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64(3):247–254. PubMed
Calabrese M, Agosta F, Rinaldi F, Mattisi I, Grossi P, Favaretto A, Atzori M, Bernardi V, Barachino L, Rinaldi L. et al.Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol. 2009;66(9):1144–1150. PubMed
Chard DT, Griffin CM, Rashid W, Davies GR, Altmann DR, Kapoor R, Barker GJ, Thompson AJ, Miller DH. Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler. 2004;10(4):387–391. PubMed
Chen JT, Narayanan S, Collins DL, Smith SM, Matthews PM, Arnold DL. Relating neocortical pathology to disability progression in multiple sclerosis using MRI. Neuroimage. 2004;23(3):1168–1175. PubMed
Amato MP, Bartolozzi ML, Zipoli V, Portaccio E, Mortilla M, Guidi L, Siracusa G, Sorbi S, Federico A, De Stefano N. Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology. 2004;63(1):89–93. PubMed
Sastre-Garriga J, Ingle GT, Chard DT, Cercignani M, Ramio-Torrenta L, Miller DH, Thompson AJ. Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. Brain. 2005;128(Pt 6):1454–1460. PubMed
Valsasina P, Benedetti B, Rovaris M, Sormani MP, Comi G, Filippi M. Evidence for progressive gray matter loss in patients with relapsing-remitting MS. Neurology. 2005;65(7):1126–1128. PubMed
Tjoa CW, Benedict RH, Weinstock-Guttman B, Fabiano AJ, Bakshi R. MRI T2 hypointensity of the dentate nucleus is related to ambulatory impairment in multiple sclerosis. J Neurol Sci. 2005;234(1-2):17–24. PubMed
Tiberio M, Chard DT, Altmann DR, Davies G, Griffin CM, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH. Gray and white matter volume changes in early RRMS: a 2-year longitudinal study. Neurology. 2005;64(6):1001–1007. PubMed
Smith SM, Zhang Y, Jenkinson M, Chen J, Matthews PM, Federico A, De Stefano N. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage. 2002;17(1):479–489. PubMed
Zivadinov R, Grop A, Sharma J, Bratina A, Tjoa CW, Dwyer M, Zorzon M. Reproducibility and accuracy of quantitative magnetic resonance imaging techniques of whole-brain atrophy measurement in multiple sclerosis. J Neuroimaging. 2005;15(1):27–36. PubMed
Simon JH, Schiffer RB, Rudick RA, Herndon RM. Quantitative determination of MS-induced corpus callosum atrophy in vivo using MR imaging. AJNR Am J Neuroradiol. 1987;8(4):599–604. PubMed PMC
Tedeschi G, Lavorgna L, Russo P, Prinster A, Dinacci D, Savettieri G, Quattrone A, Livrea P, Messina C, Reggio A. et al.Brain atrophy and lesion load in a large population of patients with multiple sclerosis. Neurology. 2005;65(2):280–285. PubMed
Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T. Cortical lesions in multiple sclerosis. Brain. 1999;122(Pt 1):17–26. PubMed
Kutzelnigg A, Lassmann H. Cortical lesions and brain atrophy in MS. J Neurol Sci. 2005;233(1-2):55–59. PubMed
Peterson JW, Bo L, Mork S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001;50(3):389–400. PubMed
Wegner C, Esiri MM, Chance SA, Palace J, Matthews PM. Neocortical neuronal, synaptic, and glial loss in multiple sclerosis. Neurology. 2006;67(6):960–967. PubMed
Chard D, Miller D. Grey matter pathology in clinically early multiple sclerosis: evidence from magnetic resonance imaging. J Neurol Sci. 2009;282(1-2):5–11. PubMed
Wylezinska M, Cifelli A, Jezzard P, Palace J, Alecci M, Matthews PM. Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology. 2003;60(12):1949–1954. PubMed
Roosendaal SD, Bendfeldt K, Vrenken H, Polman CH, Borgwardt S, Radue EW, Kappos L, Pelletier D, Hauser SL, Matthews PM. et al.Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability. Mult Scler. 2011;17(9):1098–1106. PubMed
Sormani M, Stromillo ML, Battaglini M, Signori A, De Stefano N. Modelling the distribution of cortical lesions in multiple sclerosis. Mult Scler. 2011. PubMed
Khaleeli Z, Cercignani M, Audoin B, Ciccarelli O, Miller DH, Thompson AJ. Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability. Neuroimage. 2007;37(1):253–261. PubMed
Sepulcre J, Sastre-Garriga J, Cercignani M, Ingle GT, Miller DH, Thompson AJ. Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study. Arch Neurol. 2006;63(8):1175–1180. PubMed
Audoin B, Davies G, Rashid W, Fisniku L, Thompson AJ, Miller DH. Voxel-based analysis of grey matter magnetization transfer ratio maps in early relapsing remitting multiple sclerosis. Mult Scler. 2007;13(4):483–489. PubMed
Quarantelli M, Ciarmiello A, Morra VB, Orefice G, Larobina M, Lanzillo R, Schiavone V, Salvatore E, Alfano B, Brunetti A. Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load. Neuroimage. 2003;18(2):360–366. PubMed
Pomeroy IM, Jordan EK, Frank JA, Matthews PM, Esiri MM. Diffuse cortical atrophy in a marmoset model of multiple sclerosis. Neurosci Lett. 2008;437(2):121–124. PubMed PMC
Geurts JJ, Stys PK, Minagar A, Amor S, Zivadinov R. Gray matter pathology in (chronic) MS: modern views on an early observation. J Neurol Sci. 2009;282(1-2):12–20. PubMed
Zivadinov R, Uxa L, Bratina A, Bosco A, Srinivasaraghavan B, Minagar A, Ukmar M, Benedetto S, Zorzon M. HLA-DRB1*1501, -DQB1*0301, -DQB1*0302, -DQB1*0602, and -DQB1*0603 alleles are associated with more severe disease outcome on MRI in patients with multiple sclerosis. International review of neurobiology. 2007;79:521–535. PubMed
Zivadinov R, Uxa L, Zacchi T, Nasuelli D, Ukmar M, Furlan C, Pozzi-Mucelli R, Tommasi MA, Locatelli L, Ulivi S. et al.HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis. J Neurol. 2003;250(9):1099–1106. PubMed
Benedict RH, Zivadinov R, Carone DA, Weinstock-Guttman B, Gaines J, Maggiore C, Sharma J, Tomassi MA, Bakshi R. Regional lobar atrophy predicts memory impairment in multiple sclerosis. AJNR Am J Neuroradiol. 2005;26(7):1824–1831. PubMed PMC
Prinster A, Quarantelli M, Orefice G, Lanzillo R, Brunetti A, Mollica C, Salvatore E, Morra VB, Coppola G, Vacca G. et al.Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study. Neuroimage. 2006;29(3):859–867. PubMed
Sailer M, Fischl B, Salat D, Tempelmann C, Schonfeld MA, Busa E, Bodammer N, Heinze HJ, Dale A. Focal thinning of the cerebral cortex in multiple sclerosis. Brain. 2003;126(Pt 8):1734–1744. PubMed
Tekok-Kilic A, Benedict RH, Weinstock-Guttman B, Dwyer MG, Carone D, Srinivasaraghavan B, Yella V, Abdelrahman N, Munschauer F, Bakshi R. et al.Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis. Neuroimage. 2007;36(4):1294–1300. PubMed
Riccitelli G, Rocca MA, Forn C, Colombo B, Comi G, Filippi M. Voxelwise assessment of the regional distribution of damage in the brains of patients with multiple sclerosis and fatigue. AJNR Am J Neuroradiol. 2011;32(5):874–879. PubMed PMC
Morgen K, Sammer G, Courtney SM, Wolters T, Melchior H, Blecker CR, Oschmann P, Kaps M, Vaitl D. Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS. Neuroimage. 2006;30(3):891–898. PubMed
Bermel RA, Innus MD, Tjoa CW, Bakshi R. Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study. Neuroreport. 2003;14(3):335–339. PubMed
Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J, Matthews PM. Thalamic neurodegeneration in multiple sclerosis. Ann Neurol. 2002;52(5):650–653. PubMed
Ciccarelli O, Werring DJ, Wheeler-Kingshott CA, Barker GJ, Parker GJ, Thompson AJ, Miller DH. Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations. Neurology. 2001;56(7):926–933. PubMed
Calabrese M, De Stefano N, Atzori M, Bernardi V, Mattisi I, Barachino L, Morra A, Rinaldi L, Romualdi C, Perini P. et al.Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis. Arch Neurol. 2007;64(10):1416–1422. PubMed
Calabrese M, Battaglini M, Giorgio A, Atzori M, Bernardi V, Mattisi I, Gallo P, De Stefano N. Imaging distribution and frequency of cortical lesions in patients with multiple sclerosis. Neurology. 2010;75(14):1234–1240. PubMed
Geurts JJ, Bo L, Roosendaal SD, Hazes T, Daniels R, Barkhof F, Witter MP, Huitinga I, van der Valk P. Extensive hippocampal demyelination in multiple sclerosis. J Neuropathol Exp Neurol. 2007;66(9):819–827. PubMed
Gilmore CP, Bo L, Owens T, Lowe J, Esiri MM, Evangelou N. Spinal cord gray matter demyelination in multiple sclerosis-a novel pattern of residual plaque morphology. Brain Pathol. 2006;16(3):202–208. PubMed PMC
Huitinga I, De Groot CJ, Van der Valk P, Kamphorst W, Tilders FJ, Swaab DF. Hypothalamic lesions in multiple sclerosis. J Neuropathol Exp Neurol. 2001;60(12):1208–1218. PubMed
Vercellino M, Plano F, Votta B, Mutani R, Giordana MT, Cavalla P. Grey matter pathology in multiple sclerosis. J Neuropathol Exp Neurol. 2005;64(12):1101–1107. PubMed
Calabrese M, Mattisi I, Rinaldi F, Favaretto A, Atzori M, Bernardi V, Barachino L, Romualdi C, Rinaldi L, Perini P. et al.Magnetic resonance evidence of cerebellar cortical pathology in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2010;81(4):401–404. PubMed
van Horssen J, Brink BP, de Vries HE, van der Valk P, Bo L. The blood-brain barrier in cortical multiple sclerosis lesions. J Neuropathol Exp Neurol. 2007;66(4):321–328. PubMed
Dolezal O, Dwyer MG, Horakova D, Havrdova E, Minagar A, Balachandran S, Bergsland N, Seidl Z, Vaneckova M, Fritz D. et al.Detection of cortical lesions is dependent on choice of slice thickness in patients with multiple sclerosis. International review of neurobiology. 2007;79:475–489. PubMed
Rinaldi F, Calabrese M, Grossi P, Puthenparampil M, Perini P, Gallo P. Cortical lesions and cognitive impairment in multiple sclerosis. Neurol Sci. 2010;31(Suppl 2):S235–237. PubMed
Davies GR, Altmann DR, Hadjiprocopis A, Rashid W, Chard DT, Griffin CM, Tofts PS, Barker GJ, Kapoor R, Thompson AJ. et al.Increasing normal-appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing-remitting multiple sclerosis. J Neurol. 2005;252(9):1037–1044. PubMed
Oreja-Guevara C, Rovaris M, Iannucci G, Valsasina P, Caputo D, Cavarretta R, Sormani MP, Ferrante P, Comi G, Filippi M. Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study. Arch Neurol. 2005;62(4):578–584. PubMed
Versijpt J, Debruyne JC, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J. et al.Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult Scler. 2005;11(2):127–134. PubMed
Rashid W, Parkes LM, Ingle GT, Chard DT, Toosy AT, Altmann DR, Symms MR, Tofts PS, Thompson AJ, Miller DH. Abnormalities of cerebral perfusion in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2004;75(9):1288–1293. PubMed PMC
Rocca MA, Pagani E, Ghezzi A, Falini A, Zaffaroni M, Colombo B, Scotti G, Comi G, Filippi M. Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain. Neuroimage. 2003;19(3):826–836. PubMed
Geurts JJ, Roosendaal SD, Calabrese M, Ciccarelli O, Agosta F, Chard DT, Gass A, Huerga E, Moraal B, Pareto D. et al.Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI. Neurology. 2011;76(5):418–424. PubMed
Audoin B, Zaaraoui W, Reuter F, Rico A, Malikova I, Confort-Gouny S, Cozzone PJ, Pelletier J, Ranjeva JP. Atrophy mainly affects the limbic system and the deep grey matter at the first stage of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2010;81(6):690–695. PubMed
Calabrese M, Atzori M, Bernardi V, Morra A, Romualdi C, Rinaldi L, McAuliffe MJ, Barachino L, Perini P, Fischl B. et al.Cortical atrophy is relevant in multiple sclerosis at clinical onset. J Neurol. 2007;254(9):1212–1220. PubMed
Fisniku LK, Altmann DR, Cercignani M, Tozer DJ, Chard DT, Jackson JS, Miszkiel KA, Schmierer K, Thompson AJ, Miller DH. Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis. Mult Scler. 2009;15(6):668–677. PubMed PMC
Henry RG, Shieh M, Amirbekian B, Chung S, Okuda DT, Pelletier D. Connecting white matter injury and thalamic atrophy in clinically isolated syndromes. J Neurol Sci. 2009;282(1-2):61–66. PubMed
Henry RG, Shieh M, Okuda DT, Evangelista A, Gorno-Tempini ML, Pelletier D. Regional grey matter atrophy in clinically isolated syndromes at presentation. J Neurol Neurosurg Psychiatry. 2008;79(11):1236–1244. PubMed PMC
Roosendaal SD, Bendfeldt K, Vrenken H, Polman CH, Borgwardt S, Radue EW, Kappos L, Pelletier D, Hauser SL, Matthews PM, Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability. Mult Scler. 2011. PubMed
Calabrese M, Rinaldi F, Mattisi I, Bernardi V, Favaretto A, Perini P, Gallo P. The predictive value of gray matter atrophy in clinically isolated syndromes. Neurology. 2011;77(3):257–263. PubMed
Raz E, Cercignani M, Sbardella E, Totaro P, Pozzilli C, Bozzali M, Pantano P. Gray- and white-matter changes 1 year after first clinical episode of multiple sclerosis: MR imaging. Radiology. 2010;257(2):448–454. PubMed
Rocca MA, Agosta F, Sormani MP, Fernando K, Tintore M, Korteweg T, Tortorella P, Miller DH, Thompson A, Rovira A. et al.A three-year, multi-parametric MRI study in patients at presentation with CIS. J Neurol. 2008;255(5):683–691. PubMed
Bakshi R, Benedict RH, Bermel RA, Jacobs L. Regional brain atrophy is associated with physical disability in multiple sclerosis: semiquantitative magnetic resonance imaging and relationship to clinical findings. J Neuroimaging. 2001;11(2):129–136. PubMed
Sanfilipo MP, Benedict RH, Sharma J, Weinstock-Guttman B, Bakshi R. The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction. Neuroimage. 2005;26(4):1068–1077. PubMed
Amato MP, Portaccio E, Goretti B, Zipoli V, Battaglini M, Bartolozzi ML, Stromillo ML, Guidi L, Siracusa G, Sorbi S. et al.Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis. Arch Neurol. 2007;64(8):1157–1161. PubMed
Horakova D, Dwyer MG, Havrdova E, Cox JL, Dolezal O, Bergsland N, Rimes B, Seidl Z, Vaneckova M, Zivadinov R. Gray matter atrophy and disability progression in patients with early relapsing-remitting multiple sclerosis: a 5-year longitudinal study. J Neurol Sci. 2009;282(1-2):112–119. PubMed
Bonati U, Fisniku LK, Altmann DR, Yiannakas MC, Furby J, Thompson AJ, Miller DH, Chard DT. Cervical cord and brain grey matter atrophy independently associate with long-term MS disability. J Neurol Neurosurg Psychiatry. 2011;82(4):471–472. PubMed
Hayton T, Furby J, Smith KJ, Altmann DR, Brenner R, Chataway J, Hughes RA, Hunter K, Tozer DJ, Miller DH. et al.Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis. J Neurol. 2009;256(3):427–435. PubMed
Rovaris M, Judica E, Sastre-Garriga J, Rovira A, Sormani MP, Benedetti B, Korteweg T, De Stefano N, Khaleeli Z, Montalban X. et al.Large-scale, multicentre, quantitative MRI study of brain and cord damage in primary progressive multiple sclerosis. Mult Scler. 2008;14(4):455–464. PubMed
Calabrese M, Filippi M, Rovaris M, Bernardi V, Atzori M, Mattisi I, Favaretto A, Grossi P, Barachino L, Rinaldi L. et al.Evidence for relative cortical sparing in benign multiple sclerosis: a longitudinal magnetic resonance imaging study. Mult Scler. 2009;15(1):36–41. PubMed
Drayer B, Burger P, Hurwitz B, Dawson D, Cain J. Reduced signal intensity on MR images of thalamus and putamen in multiple sclerosis: increased iron content? AJR American journal of roentgenology. 1987;149(2):357–363. PubMed
Bakshi R, Dmochowski J, Shaikh ZA, Jacobs L. Gray matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients. J Neurol Sci. 2001;185(1):19–26. PubMed
Bakshi R, Shaikh ZA, Janardhan V. MRI T2 shortening ('black T2') in multiple sclerosis: frequency, location, and clinical correlation. Neuroreport. 2000;11(1):15–21. PubMed
Neema M, Stankiewicz J, Arora A, Dandamudi VS, Batt CE, Guss ZD, Al-Sabbagh A, Bakshi R. T1- and T2-based MRI measures of diffuse gray matter and white matter damage in patients with multiple sclerosis. J Neuroimaging. 2007;17(Suppl 1):16S–21S. PubMed
Neema M, Arora A, Healy BC, Guss ZD, Brass SD, Duan Y, Buckle GJ, Glanz BI, Stazzone L, Khoury SJ. et al.Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis. J Neuroimaging. 2009;19(1):3–8. PubMed PMC
Brass SD, Benedict RH, Weinstock-Guttman B, Munschauer F, Bakshi R. Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis. Mult Scler. 2006;12(4):437–444. PubMed
Bermel RA, Puli SR, Rudick RA, Weinstock-Guttman B, Fisher E, Munschauer FE, Bakshi R. Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity. Arch Neurol. 2005;62(9):1371–1376. PubMed PMC
Tovar-Moll F, Evangelou IE, Chiu AW, Richert ND, Ostuni JL, Ohayon JM, Auh S, Ehrmantraut M, Talagala SL, McFarland HF. et al.Thalamic involvement and its impact on clinical disability in patients with multiple sclerosis: a diffusion tensor imaging study at 3T. AJNR Am J Neuroradiol. 2009;30(7):1380–1386. PubMed PMC
Niepel G, Tench Ch R, Morgan PS, Evangelou N, Auer DP, Constantinescu CS. Deep gray matter and fatigue in MS: a T1 relaxation time study. J Neurol. 2006;253(7):896–902. PubMed
Filippi M, Rocca MA, Colombo B, Falini A, Codella M, Scotti G, Comi G. Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage. 2002;15(3):559–567. PubMed
Calabrese M, Rinaldi F, Grossi P, Mattisi I, Bernardi V, Favaretto A, Perini P, Gallo P. Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing-remitting multiple sclerosis. Mult Scler. 2010;16(10):1220–1228. PubMed
Poonawalla AH, Datta S, Juneja V, Nelson F, Wolinsky JS, Cutter G, Narayana PA. Composite MRI scores improve correlation with EDSS in multiple sclerosis. Mult Scler. 2010;16(9):1117–1125. PubMed PMC
Sepulcre J, Masdeu JC, Goni J, Arrondo G, Velez de Mendizabal N, Bejarano B, Villoslada P. Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways. Mult Scler. 2009;15(3):337–344. PubMed
Manconi M, Rocca MA, Ferini-Strambi L, Tortorella P, Agosta F, Comi G, Filippi M. Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage. Mult Scler. 2008;14(1):86–93. PubMed
Calabrese M, De Stefano N, Atzori M, Bernardi V, Mattisi I, Barachino L, Rinaldi L, Morra A, McAuliffe MM, Perini P. et al.Extensive cortical inflammation is associated with epilepsy in multiple sclerosis. J Neurol. 2008;255(4):581–586. PubMed
Poser CM, Brinar VV. Epilepsy and multiple sclerosis. Epilepsy Behav. 2003;4(1):6–12. PubMed
Moreau T, Sochurkova D, Lemesle M, Madinier G, Billiar T, Giroud M, Dumas R. Epilepsy in patients with multiple sclerosis: radiological-clinical correlations. Epilepsia. 1998;39(8):893–896. PubMed
Sokic DV, Stojsavljevic N, Drulovic J, Dujmovic I, Mesaros S, Ercegovac M, Peric V, Dragutinovic G, Levic Z. Seizures in multiple sclerosis. Epilepsia. 2001;42(1):72–79. PubMed
Meier DS, Weiner HL, Guttmann CR. Time-series modeling of multiple sclerosis disease activity: a promising window on disease progression and repair potential? Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. 2007;4(3):485–498. PubMed PMC
Filippi M, Rocca MA, Falini A, Caputo D, Ghezzi A, Colombo B, Scotti G, Comi G. Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage. 2002;15(3):537–546. PubMed
Lee M, Reddy H, Johansen-Berg H, Pendlebury S, Jenkinson M, Smith S, Palace J, Matthews PM. The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis. Ann Neurol. 2000;47(5):606–613. PubMed
Reddy H, Narayanan S, Arnoutelis R, Jenkinson M, Antel J, Matthews PM, Arnold DL. Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. Brain. 2000;123(Pt 11):2314–2320. PubMed
Valsasina P, Rocca MA, Absinta M, Sormani MP, Mancini L, De Stefano N, Rovira A, Gass A, Enzinger C, Barkhof F. et al.A multicentre study of motor functional connectivity changes in patients with multiple sclerosis. Eur J Neurosci. 2011;33(7):1256–1263. PubMed
Rico A, Zaaraoui W, Franques J, Attarian S, Reuter F, Malikova I, Confort-Gouny S, Soulier E, Pouget J, Cozzone PJ. et al.Motor cortical reorganization is present after a single attack of multiple sclerosis devoid of cortico-spinal dysfunction. MAGMA. 2011;24(2):77–84. PubMed
Cader S, Cifelli A, Abu-Omar Y, Palace J, Matthews PM. Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis. Brain. 2006;129(Pt 2):527–537. PubMed
Parry AM, Scott RB, Palace J, Smith S, Matthews PM. Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine. Brain. 2003;126(Pt 12):2750–2760. PubMed
Audoin B, Ibarrola D, Ranjeva JP, Confort-Gouny S, Malikova I, Ali-Cherif A, Pelletier J, Cozzone P. Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp. 2003;20(2):51–58. PubMed PMC
Giorgio A, Portaccio E, Stromillo ML, Marino S, Zipoli V, Battaglini M, Blandino A, Bartolozzi ML, Siracusa G, Amato MP. et al.Cortical functional reorganization and its relationship with brain structural damage in patients with benign multiple sclerosis. Mult Scler. 2010;16(11):1326–1334. PubMed
Agosta F, Valsasina P, Rocca MA, Caputo D, Sala S, Judica E, Stroman PW, Filippi M. Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis. Magn Reson Med. 2008;59(5):1035–1042. PubMed
Goldman MD, Motl RW, Rudick RA. Possible clinical outcome measures for clinical trials in patients with multiple sclerosis. Ther Adv Neurol Disord. 2010;3(4):229–239. PubMed PMC
Hobart J, Freeman J, Thompson A. Kurtzke scales revisited: the application of psychometric methods to clinical intuition. Brain. 2000;123(Pt 5):1027–1040. PubMed
Polman CH, Rudick RA. The multiple sclerosis functional composite: a clinically meaningful measure of disability. Neurology. 2010;74(Suppl 3):S8–15. PubMed
Rudick RA, Lee JC, Nakamura K, Fisher E. Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS. J Neurol Sci. 2009;282(1-2):106–111. PubMed PMC
Patti F. Cognitive impairment in multiple sclerosis. Mult Scler. 2009;15(1):2–8. PubMed
Rao SM. Neuropsychology of multiple sclerosis. Curr Opin Neurol. 1995;8(3):216–220. PubMed
Tur C, Penny S, Khaleeli Z, Altmann D, Cipolotti L, Ron M, Thompson A, Ciccarelli O. Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis. Mult Scler. 2011. PubMed
Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008;7(12):1139–1151. PubMed
Till C, Ghassemi R, Aubert-Broche B, Kerbrat A, Collins DL, Narayanan S, Arnold DL, Desrocher M, Sled JG, Banwell BL. MRI correlates of cognitive impairment in childhood-onset multiple sclerosis. Neuropsychology. 2011;25(3):319–332. PubMed
Amato MP, Goretti B, Ghezzi A, Lori S, Zipoli V, Moiola L, Falautano M, De Caro MF, Viterbo R, Patti F. et al.Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up. Neurology. 2010;75(13):1134–1140. PubMed
Benedict RH, Zivadinov R. Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol. 2011;7(6):332–342. PubMed
Amato MP, Zipoli V, Portaccio E. Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies. J Neurol Sci. 2006;245(1-2):41–46. PubMed
Calabrese M, Rinaldi F, Grossi P, Gallo P. Cortical pathology and cognitive impairment in multiple sclerosis. Expert Rev Neurother. 2011;11(3):425–432. PubMed
Calabrese M, Rinaldi F, Mattisi I, Grossi P, Favaretto A, Atzori M, Bernardi V, Barachino L, Romualdi C, Rinaldi L. et al.Widespread cortical thinning characterizes patients with MS with mild cognitive impairment. Neurology. 2010;74(4):321–328. PubMed
Blinkenberg M, Rune K, Jensen CV, Ravnborg M, Kyllingsbaek S, Holm S, Paulson OB, Sorensen PS. Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS. Neurology. 2000;54(3):558–564. PubMed
Filippi M, Alberoni M, Martinelli V, Sirabian G, Bressi S, Canal N, Comi G. Influence of clinical variables on neuropsychological performance in multiple sclerosis. Eur Neurol. 1994;34(6):324–328. PubMed
Benedict RH, Carone DA, Bakshi R. Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis. J Neuroimaging. 2004;14(3 Suppl):36S–45S. PubMed
Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R. Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology. 2006;66(5):685–692. PubMed
Benedict RH, Bruce JM, Dwyer MG, Abdelrahman N, Hussein S, Weinstock-Guttman B, Garg N, Munschauer F, Zivadinov R. Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol. 2006;63(9):1301–1306. PubMed
Zarei M. Clinical characteristics of cortical multiple sclerosis. J Neurol Sci. 2006;245(1-2):53–58. PubMed
Zarei M, Chandran S, Compston A, Hodges J. Cognitive presentation of multiple sclerosis: evidence for a cortical variant. J Neurol Neurosurg Psychiatry. 2003;74(7):872–877. PubMed PMC
Batista S, Zivadinov R, Hoogs M, Bergsland N, Heininen-Brown M, Dwyer MG, Weinstock-Guttman B, Benedict RH. Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis. J Neurol. 2011. PubMed
Benedict RH, Hussein S, Englert J, Dwyer MG, Abdelrahman N, Cox JL, Munschauer FE, Weinstock-Guttman B, Zivadinov R. Cortical atrophy and personality in multiple sclerosis. Neuropsychology. 2008;22(4):432–441. PubMed
Benedict RH, Ramasamy D, Munschauer F, Weinstock-Guttman B, Zivadinov R. Memory impairment in multiple sclerosis: correlation with deep grey matter and mesial temporal atrophy. J Neurol Neurosurg Psychiatry. 2009;80(2):201–206. PubMed
Anderson VM, Fisniku LK, Khaleeli Z, Summers MM, Penny SA, Altmann DR, Thompson AJ, Ron MA, Miller DH. Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study. Mult Scler. 2010;16(9):1083–1090. PubMed
Houtchens MK, Benedict RH, Killiany R, Sharma J, Jaisani Z, Singh B, Weinstock-Guttman B, Guttmann CR, Bakshi R. Thalamic atrophy and cognition in multiple sclerosis. Neurology. 2007;69(12):1213–1223. PubMed
Hildebrandt H, Hahn HK, Kraus JA, Schulte-Herbruggen A, Schwarze B, Schwendemann G. Memory performance in multiple sclerosis patients correlates with central brain atrophy. Mult Scler. 2006;12(4):428–436. PubMed
Roosendaal SD, Moraal B, Pouwels PJ, Vrenken H, Castelijns JA, Barkhof F, Geurts JJ. Accumulation of cortical lesions in MS: relation with cognitive impairment. Mult Scler. 2009;15(6):708–714. PubMed
Bagnato F, Salman Z, Kane R, Auh S, Cantor FK, Ehrmantraut M, Gallo A, Ikonomidou VN, Ohayon J, Pellicano C. et al.T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis. Mult Scler. 2010;16(10):1203–1212. PubMed
Calabrese P, Penner IK. Cognitive dysfunctions in multiple sclerosis--a "multiple disconnection syndrome"? J Neurol. 2007;254(Suppl 2):II18–21. PubMed
Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009;5(5):256–266. PubMed
Tintore M, Rovira A, Rio J, Nos C, Grive E, Tellez N, Pelayo R, Comabella M, Sastre-Garriga J, Montalban X. Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology. 2006;67(6):968–972. PubMed
Daumer M, Neuhaus A, Herbert J, Ebers G. Prognosis of the individual course of disease: the elements of time, heterogeneity and precision. J Neurol Sci. 2009;287(Suppl 1):S50–55. PubMed
Rio J, Castillo J, Rovira A, Tintore M, Sastre-Garriga J, Horga A, Nos C, Comabella M, Aymerich X, Montalban X. Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler. 2009;15(7):848–853. PubMed
Li DK, Held U, Petkau J, Daumer M, Barkhof F, Fazekas F, Frank JA, Kappos L, Miller DH, Simon JH. et al.MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability. Neurology. 2006;66(9):1384–1389. PubMed
Zivadinov R, Leist TP. Clinical-magnetic resonance imaging correlations in multiple sclerosis. J Neuroimaging. 2005;15(4 Suppl):10S–21S. PubMed
Zivadinov R, Reder AT, Filippi M, Minagar A, Stuve O, Lassmann H, Racke MK, Dwyer MG, Frohman EM, Khan O. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology. 2008;71(2):136–144. PubMed
Kelemen A, Dwyer MG, Horakova D, Vaneckova M, Havrdova E, Zivadinov R. Measurement of gray matter volume is less susceptible to pseudoatrophy effect than that of white matter or whole brain volume in patients with multiple sclerosis. Results from Avonex-Steroids-Azathioprine combination study. Mult Scler. 2008;14(280):S11.
Rovaris M, Gallo A, Valsasina P, Benedetti B, Caputo D, Ghezzi A, Montanari E, Sormani MP, Bertolotto A, Mancardi G. et al.Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI. Neuroimage. 2005;24(4):1139–1146. PubMed
Filippi M, Rocca MA, Calabrese M, Sormani MP, Rinaldi F, Perini P, Comi G, Gallo P. Intracortical lesions: relevance for new MRI diagnostic criteria for multiple sclerosis. Neurology. 2010;75(22):1988–1994. PubMed
Brex PA, Jenkins R, Fox NC, Crum WR, O'Riordan JI, Plant GT, Miller DH. Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology. 2000;54(8):1689–1691. PubMed
Agosta F, Rovaris M, Pagani E, Sormani MP, Comi G, Filippi M. Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis. Brain. 2006;129(Pt 10):2620–2627. PubMed
Bo L, Vedeler CA, Nyland H, Trapp BD, Mork SJ. Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler. 2003;9(4):323–331. PubMed
Brink BP, Veerhuis R, Breij EC, van der Valk P, Dijkstra CD, Bo L. The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol. 2005;64(2):147–155. PubMed
Geurts JJ, Barkhof F. Grey matter pathology in multiple sclerosis. Lancet Neurol. 2008;7(9):841–851. PubMed
Calabrese M, Bernardi V, Atzori M, Mattisi I, Favaretto A, Rinaldi F, Perini P, Gallo P. Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing-remitting multiple sclerosis. Mult Scler. 2011. PubMed
Zivadinov R, Locatelli L, Cookfair D, Srinivasaraghavan B, Bertolotto A, Ukmar M, Bratina A, Maggiore C, Bosco A, Grop A. et al.Interferon beta-1a slows progression of brain atrophy in relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy. Mult Scler. 2007;13(4):490–501. PubMed
Tur C, Khaleeli Z, Ciccarelli O, Altmann DR, Cercignani M, Miller DH, Thompson AJ. Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS. J Neurol Neurosurg Psychiatry. 2011;82(4):423–428. PubMed