Volume 3, Issue 3, May 2015, Page: 40-49
Brain atrophy in Multiple Sclerosis
Rugilo Carlos, Department of Neurology, British Hospital, Buenos Aires, Argentina
Seifer Gustavo, Department of Neurology, José María Ramos Mejía Hospital, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina; Department of Medicine, Novartis Argentina
Kuperman Gaston, Department of Medicine, Novartis Argentina
Villa Andrés María, Department of Neurology, José María Ramos Mejía Hospital, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina
Received: Feb. 25, 2015;       Accepted: Mar. 9, 2015;       Published: Mar. 31, 2015
DOI: 10.11648/j.ajpn.20150303.11      View  3126      Downloads  231
Abstract
Multiple sclerosis (MS) has traditionally been considered to be primarily an inflammatory demyelinating disorder affecting the white matter. Nowadays it is recognized as both an inflammatory and a neurodegenerative condition involving the white and grey matter. Grey matter atrophy occurs in the earliest stages of MS, progresses faster than in healthy individuals, and shows significant correlations with cognitive function and physical disability; indeed, brain atrophy is the best predictor of subsequent disability and can be measured using magnetic resonance imaging (MRI). There are a number of MRI methods for measuring global or regional brain volume, including cross-sectional and longitudinal techniques. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article summarizes the knowledge on brain volume in MS.
Keywords
Multiple Sclerosis, Brain Atrophy, Brain Volume Loss
To cite this article
Rugilo Carlos, Seifer Gustavo, Kuperman Gaston, Villa Andrés María, Brain atrophy in Multiple Sclerosis, American Journal of Psychiatry and Neuroscience. Vol. 3, No. 3, 2015, pp. 40-49. doi: 10.11648/j.ajpn.20150303.11
Reference
[1]
A. Compston, and A. Coles, "Multiple sclerosis," Lancet, vol. 359, no. 9313, pp. 1221-31, 2002.
[2]
D. Miller, F. Barkhof, X. Montalban, A. Thompson, and M. Filippi, "Clinically isolated syndromes suggestive of multiple sclerosis, part 2: non-conventional MRI, recovery processes, and management," Lancet Neurol, vol. 4, no. 6, pp. 341-8, 2005.
[3]
D. Miller, F. Barkhof, X. Montalban, A. Thompson, and M. Filippi, "Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis," Lancet Neurol, vol. 4, no. 5, pp. 281-8, 2005.
[4]
J. H. Noseworthy, C. Lucchinetti, M. Rodriguez, and B. G. Weinshenker, "Multiple sclerosis," N Engl J Med, vol. 343, no. 13, pp. 938-52, 2000.
[5]
J. H. Simon, "Brain and spinal cord atrophy in multiple sclerosis: role as a surrogate measure of disease progression," CNS Drugs, vol. 15, no. 6, pp. 427-36, 2001.
[6]
E. Fisher, R. A. Rudick, J. H. Simon, G. Cutter, M. Baier, J. C. Lee, D. Miller, B. Weinstock-Guttman, M. K. Mass, D. S. Dougherty, and N. A. Simonian, "Eight-year follow-up study of brain atrophy in patients with MS," Neurology, vol. 59, no. 9, pp. 1412-20, 2002.
[7]
D. H. Miller, F. Barkhof, J. A. Frank, G. J. Parker, and A. J. Thompson, "Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance," Brain, vol. 125, no. Pt 8, pp. 1676-95, 2002.
[8]
H. Vrenken, M. Jenkinson, M. A. Horsfield, M. Battaglini, R. A. van Schijndel, E. Rostrup, J. J. Geurts, E. Fisher, A. Zijdenbos, J. Ashburner, D. H. Miller, M. Filippi, F. Fazekas, M. Rovaris, A. Rovira, F. Barkhof, and N. de Stefano, "Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis," J Neurol, 2012.
[9]
N. C. Fox, R. Jenkins, S. M. Leary, V. L. Stevenson, N. A. Losseff, W. R. Crum, R. J. Harvey, M. N. Rossor, D. H. Miller, and A. J. Thompson, "Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI," Neurology, vol. 54, no. 4, pp. 807-12, 2000.
[10]
M. Wylezinska, A. Cifelli, P. Jezzard, J. Palace, M. Alecci, and P. M. Matthews, "Thalamic neurodegeneration in relapsing-remitting multiple sclerosis," Neurology, vol. 60, no. 12, pp. 1949-54, 2003.
[11]
A. Cifelli, M. Arridge, P. Jezzard, M. M. Esiri, J. Palace, and P. M. Matthews, "Thalamic neurodegeneration in multiple sclerosis," Ann Neurol, vol. 52, no. 5, pp. 650-3, 2002.
[12]
N. De Stefano, P. M. Matthews, M. Filippi, F. Agosta, M. De Luca, M. L. Bartolozzi, L. Guidi, A. Ghezzi, E. Montanari, A. Cifelli, A. Federico, and S. M. Smith, "Evidence of early cortical atrophy in MS: relevance to white matter changes and disability," Neurology, vol. 60, no. 7, pp. 1157-62, 2003.
[13]
J. H. Simon, "Brain atrophy in multiple sclerosis: what we know and would like to know," Mult Scler, vol. 12, no. 6, pp. 679-87, 2006.
[14]
C. F. Lucchinetti, W. Bruck, M. Rodriguez, and H. Lassmann, "Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis," Brain Pathol, vol. 6, no. 3, pp. 259-74, 1996.
[15]
M. Filippi, M. A. Rocca, F. Barkhof, W. Bruck, J. T. Chen, G. Comi, G. DeLuca, N. De Stefano, B. J. Erickson, N. Evangelou, F. Fazekas, J. J. Geurts, C. Lucchinetti, D. H. Miller, D. Pelletier, B. F. Popescu, and H. Lassmann, "Association between pathological and MRI findings in multiple sclerosis," Lancet Neurol, vol. 11, no. 4, pp. 349-60, 2012.
[16]
N. Evangelou, G. C. DeLuca, T. Owens, and M. M. Esiri, "Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions," Brain, vol. 128, no. Pt 1, pp. 29-34, 2005.
[17]
G. C. DeLuca, G. C. Ebers, and M. M. Esiri, "Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts," Brain, vol. 127, no. Pt 5, pp. 1009-18, 2004.
[18]
M. Rovaris, G. Comi, M. A. Rocca, J. S. Wolinsky, M. Filippi, and G. European/Canadian Glatiramer Acetate Study, "Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications," Brain, vol. 124, no. Pt 9, pp. 1803-12, 2001.
[19]
A. Vidal-Jordana, J. Sastre-Garriga, F. Perez-Miralles, C. Tur, M. Tintore, A. Horga, C. Auger, J. Rio, C. Nos, M. C. Edo, M. J. Arevalo, J. Castillo, A. Rovira, and X. Montalban, "Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes," Mult Scler, vol. 19, no. 9, pp. 1175-81, 2013.
[20]
M. P. Coleman, and V. H. Perry, "Axon pathology in neurological disease: a neglected therapeutic target," Trends Neurosci, vol. 25, no. 10, pp. 532-7, 2002.
[21]
C. Bjartmar, and B. D. Trapp, "Axonal degeneration and progressive neurologic disability in multiple sclerosis," Neurotox Res, vol. 5, no. 1-2, pp. 157-64, 2003.
[22]
J. H. Caldwell, K. L. Schaller, R. S. Lasher, E. Peles, and S. R. Levinson, "Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses," Proc Natl Acad Sci U S A, vol. 97, no. 10, pp. 5616-20, 2000.
[23]
M. J. Craner, J. Newcombe, J. A. Black, C. Hartle, M. L. Cuzner, and S. G. Waxman, "Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger," Proc Natl Acad Sci U S A, vol. 101, no. 21, pp. 8168-73, 2004.
[24]
M. J. Craner, T. G. Damarjian, S. Liu, B. C. Hains, A. C. Lo, J. A. Black, J. Newcombe, M. L. Cuzner, and S. G. Waxman, "Sodium channels contribute to microglia/macrophage activation and function in EAE and MS," Glia, vol. 49, no. 2, pp. 220-9, 2005.
[25]
K. J. Smith, and H. Lassmann, "The role of nitric oxide in multiple sclerosis," Lancet Neurol, vol. 1, no. 4, pp. 232-41, 2002.
[26]
R. Dutta, J. McDonough, X. Yin, J. Peterson, A. Chang, T. Torres, T. Gudz, W. B. Macklin, D. A. Lewis, R. J. Fox, R. Rudick, K. Mirnics, and B. D. Trapp, "Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients," Ann Neurol, vol. 59, no. 3, pp. 478-89, 2006.
[27]
S. G. Waxman, "Axonal conduction and injury in multiple sclerosis: the role of sodium channels," Nat Rev Neurosci, vol. 7, no. 12, pp. 932-41, 2006.
[28]
A. Giorgio, M. Battaglini, S. M. Smith, and N. De Stefano, "Brain atrophy assessment in multiple sclerosis: importance and limitations," Neuroimaging Clin N Am, vol. 18, no. 4, pp. 675-86, xi, 2008.
[29]
R. A. Rudick, E. Fisher, J. C. Lee, J. Simon, and L. Jacobs, "Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group," Neurology, vol. 53, no. 8, pp. 1698-704, 1999.
[30]
J. H. Simon, L. D. Jacobs, M. K. Campion, R. A. Rudick, D. L. Cookfair, R. M. Herndon, J. R. Richert, A. M. Salazar, J. S. Fischer, D. E. Goodkin, N. Simonian, M. Lajaunie, D. E. Miller, K. Wende, A. Martens-Davidson, R. P. Kinkel, F. E. Munschauer, 3rd, and C. M. Brownscheidle, "A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG)," Neurology, vol. 53, no. 1, pp. 139-48, 1999.
[31]
S. M. Smith, Y. Zhang, M. Jenkinson, J. Chen, P. M. Matthews, A. Federico, and N. De Stefano, "Accurate, robust, and automated longitudinal and cross-sectional brain change analysis," Neuroimage, vol. 17, no. 1, pp. 479-89, 2002.
[32]
J. Ashburner, and K. J. Friston, "Voxel-based morphometry--the methods," Neuroimage, vol. 11, no. 6 Pt 1, pp. 805-21, 2000.
[33]
C. D. Good, I. S. Johnsrude, J. Ashburner, R. N. Henson, K. J. Friston, and R. S. Frackowiak, "A voxel-based morphometric study of ageing in 465 normal adult human brains," Neuroimage, vol. 14, no. 1 Pt 1, pp. 21-36, 2001.
[34]
F. Barkhof, P. A. Calabresi, D. H. Miller, and S. C. Reingold, "Imaging outcomes for neuroprotection and repair in multiple sclerosis trials," Nat Rev Neurol, vol. 5, no. 5, pp. 256-66, 2009.
[35]
F. Barkhof, and M. Filippi, "MRI--the perfect surrogate marker for multiple sclerosis?," Nat Rev Neurol, vol. 5, no. 4, pp. 182-3, 2009.
[36]
R. A. Bermel, and R. Bakshi, "The measurement and clinical relevance of brain atrophy in multiple sclerosis," Lancet Neurol, vol. 5, no. 2, pp. 158-70, 2006.
[37]
A. F. Fotenos, M. A. Mintun, A. Z. Snyder, J. C. Morris, and R. L. Buckner, "Brain volume decline in aging: evidence for a relation between socioeconomic status, preclinical Alzheimer disease, and reserve," Arch Neurol, vol. 65, no. 1, pp. 113-20, 2008.
[38]
E. Pagani, M. A. Rocca, A. Gallo, M. Rovaris, V. Martinelli, G. Comi, and M. Filippi, "Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype," AJNR Am J Neuroradiol, vol. 26, no. 2, pp. 341-6, 2005.
[39]
N. De Stefano, A. Giorgio, M. Battaglini, M. Rovaris, M. P. Sormani, F. Barkhof, T. Korteweg, C. Enzinger, F. Fazekas, M. Calabrese, D. Dinacci, G. Tedeschi, A. Gass, X. Montalban, A. Rovira, A. Thompson, G. Comi, D. H. Miller, and M. Filippi, "Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes," Neurology, vol. 74, no. 23, pp. 1868-76, 2010.
[40]
M. Filippi, M. Bozzali, M. Rovaris, O. Gonen, C. Kesavadas, A. Ghezzi, V. Martinelli, R. I. Grossman, G. Scotti, G. Comi, and A. Falini, "Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis," Brain, vol. 126, no. Pt 2, pp. 433-7, 2003.
[41]
N. F. Kalkers, N. Ameziane, J. C. Bot, A. Minneboo, C. H. Polman, and F. Barkhof, "Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of the disease subtype," Arch Neurol, vol. 59, no. 10, pp. 1572-6, 2002.
[42]
R. Zivadinov, J. Sepcic, D. Nasuelli, R. De Masi, L. M. Bragadin, M. A. Tommasi, S. Zambito-Marsala, R. Moretti, A. Bratina, M. Ukmar, R. S. Pozzi-Mucelli, A. Grop, G. Cazzato, and M. Zorzon, "A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis," J Neurol Neurosurg Psychiatry, vol. 70, no. 6, pp. 773-80, 2001.
[43]
R. M. Vigeveno, O. T. Wiebenga, M. P. Wattjes, J. J. Geurts, and F. Barkhof, "Shifting imaging targets in multiple sclerosis: from inflammation to neurodegeneration," J Magn Reson Imaging, vol. 36, no. 1, pp. 1-19, 2012.
[44]
O. Fernandez, J. C. Alvarez-Cermeno, R. Arroyo-Gonzalez, L. Brieva, M. C. Calles-Hernandez, B. Casanova-Estruch, M. Comabella, V. de las Heras, J. A. Garcia-Merino, M. A. Hernandez-Perez, G. Izquierdo, J. E. Meca-Lallana, D. Munoz-Garcia, J. Olascoaga, C. Oreja-Guevara, J. M. Prieto, L. Ramio-Torrenta, A. Rodriguez-Antiguedad, L. Romero-Pinel, F. Sanchez, N. Tellez, M. Tintore, X. Montalban, and E. g. Post, "Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I)," Rev Neurol, vol. 54, no. 11, pp. 677-91, 2012.
[45]
M. Rovaris, G. Comi, M. A. Rocca, M. Cercignani, B. Colombo, G. Santuccio, and M. Filippi, "Relevance of hypointense lesions on fast fluid-attenuated inversion recovery MR images as a marker of disease severity in cases of multiple sclerosis," AJNR Am J Neuroradiol, vol. 20, no. 5, pp. 813-20, 1999.
[46]
M. Rovaris, F. Agosta, M. P. Sormani, M. Inglese, V. Martinelli, G. Comi, and M. Filippi, "Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study," Brain, vol. 126, no. Pt 10, pp. 2323-32, 2003.
[47]
M. P. Amato, E. Portaccio, B. Goretti, V. Zipoli, M. Battaglini, M. L. Bartolozzi, M. L. Stromillo, L. Guidi, G. Siracusa, S. Sorbi, A. Federico, and N. De Stefano, "Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis," Arch Neurol, vol. 64, no. 8, pp. 1157-61, 2007.
[48]
M. P. Amato, L. Razzolini, B. Goretti, M. L. Stromillo, F. Rossi, A. Giorgio, B. Hakiki, M. Giannini, L. Pasto, E. Portaccio, and N. De Stefano, "Cognitive reserve and cortical atrophy in multiple sclerosis: a longitudinal study," Neurology, vol. 80, no. 19, pp. 1728-33, 2013.
[49]
J. I. Rojas, L. Patrucco, C. Besada, L. Bengolea, and E. Cristiano, "[Brain atrophy in clinically isolated syndrome]," Neurologia, vol. 25, no. 7, pp. 430-4, 2010.
[50]
M. Di Filippo, V. M. Anderson, D. R. Altmann, J. K. Swanton, G. T. Plant, A. J. Thompson, and D. H. Miller, "Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes," J Neurol Neurosurg Psychiatry, vol. 81, no. 2, pp. 204-8, 2010.
[51]
M. Tiberio, D. T. Chard, D. R. Altmann, G. Davies, C. M. Griffin, W. Rashid, J. Sastre-Garriga, A. J. Thompson, and D. H. Miller, "Gray and white matter volume changes in early RRMS: a 2-year longitudinal study," Neurology, vol. 64, no. 6, pp. 1001-7, 2005.
[52]
H. Lassmann, "Brain damage when multiple sclerosis is diagnosed clinically," Lancet, vol. 361, no. 9366, pp. 1317-8, 2003.
[53]
C. M. Dalton, P. A. Brex, R. Jenkins, N. C. Fox, K. A. Miszkiel, W. R. Crum, J. I. O'Riordan, G. T. Plant, A. J. Thompson, and D. H. Miller, "Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis," J Neurol Neurosurg Psychiatry, vol. 73, no. 2, pp. 141-7, 2002.
[54]
C. M. Dalton, D. T. Chard, G. R. Davies, K. A. Miszkiel, D. R. Altmann, K. Fernando, G. T. Plant, A. J. Thompson, and D. H. Miller, "Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes," Brain, vol. 127, no. Pt 5, pp. 1101-7, 2004.
[55]
K. T. Fernando, M. A. McLean, D. T. Chard, D. G. MacManus, C. M. Dalton, K. A. Miszkiel, R. M. Gordon, G. T. Plant, A. J. Thompson, and D. H. Miller, "Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis," Brain, vol. 127, no. Pt 6, pp. 1361-9, 2004.
[56]
M. Filippi, M. Rovaris, M. Inglese, F. Barkhof, N. De Stefano, S. Smith, and G. Comi, "Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial," Lancet, vol. 364, no. 9444, pp. 1489-96, 2004.
[57]
F. Perez-Miralles, J. Sastre-Garriga, M. Tintore, G. Arrambide, C. Nos, H. Perkal, J. Rio, M. Edo, A. Horga, J. Castillo, C. Auger, E. Huerga, A. Rovira, and X. Montalban, "Clinical impact of early brain atrophy in clinically isolated syndromes," Mult Scler, 2013.
[58]
M. Quarantelli, A. Ciarmiello, V. B. Morra, G. Orefice, M. Larobina, R. Lanzillo, V. Schiavone, E. Salvatore, B. Alfano, and A. Brunetti, "Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load," Neuroimage, vol. 18, no. 2, pp. 360-6, 2003.
[59]
D. T. Chard, C. M. Griffin, G. J. Parker, R. Kapoor, A. J. Thompson, and D. H. Miller, "Brain atrophy in clinically early relapsing-remitting multiple sclerosis," Brain, vol. 125, no. Pt 2, pp. 327-37, 2002.
[60]
J. Sastre-Garriga, G. T. Ingle, D. T. Chard, L. Ramio-Torrenta, D. H. Miller, and A. J. Thompson, "Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis," Neuroimage, vol. 22, no. 1, pp. 353-9, 2004.
[61]
M. Sailer, B. Fischl, D. Salat, C. Tempelmann, M. A. Schonfeld, E. Busa, N. Bodammer, H. J. Heinze, and A. Dale, "Focal thinning of the cerebral cortex in multiple sclerosis," Brain, vol. 126, no. Pt 8, pp. 1734-44, 2003.
[62]
D. T. Chard, C. M. Griffin, W. Rashid, G. R. Davies, D. R. Altmann, R. Kapoor, G. J. Barker, A. J. Thompson, and D. H. Miller, "Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis," Mult Scler, vol. 10, no. 4, pp. 387-91, 2004.
[63]
D. Kidd, F. Barkhof, R. McConnell, P. R. Algra, I. V. Allen, and T. Revesz, "Cortical lesions in multiple sclerosis," Brain, vol. 122 ( Pt 1), pp. 17-26, 1999.
[64]
L. Bo, C. A. Vedeler, H. I. Nyland, B. D. Trapp, and S. J. Mork, "Subpial demyelination in the cerebral cortex of multiple sclerosis patients," J Neuropathol Exp Neurol, vol. 62, no. 7, pp. 723-32, 2003.
[65]
A. Charil, A. Dagher, J. P. Lerch, A. P. Zijdenbos, K. J. Worsley, and A. C. Evans, "Focal cortical atrophy in multiple sclerosis: relation to lesion load and disability," Neuroimage, vol. 34, no. 2, pp. 509-17, 2007.
[66]
D. H. Salat, R. L. Buckner, A. Z. Snyder, D. N. Greve, R. S. Desikan, E. Busa, J. C. Morris, A. M. Dale, and B. Fischl, "Thinning of the cerebral cortex in aging," Cereb Cortex, vol. 14, no. 7, pp. 721-30, 2004.
[67]
N. A. Losseff, S. L. Webb, J. I. O'Riordan, R. Page, L. Wang, G. J. Barker, P. S. Tofts, W. I. McDonald, D. H. Miller, and A. J. Thompson, "Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression," Brain, vol. 119 ( Pt 3), pp. 701-8, 1996.
[68]
A. Minneboo, B. Jasperse, F. Barkhof, B. M. Uitdehaag, D. L. Knol, V. de Groot, C. H. Polman, and J. A. Castelijns, "Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters," J Neurol Neurosurg Psychiatry, vol. 79, no. 8, pp. 917-23, 2008.
[69]
H. Kearney, M. Rocca, P. Valsasina, L. Balk, J. Sastre-Garriga, J. Reinhardt, S. Ruggieri, A. Rovira, C. Stippich, L. Kappos, T. Sprenger, P. Tortorella, M. Rovaris, C. Gasperini, X. Montalban, J. Geurts, C. Polman, F. Barkhof, M. Filippi, D. Altmann, O. Ciccarelli, D. Miller, and D. Chard, "Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration," Mult Scler, 2013.
[70]
L. Hofstetter, Y. Naegelin, L. Filli, P. Kuster, S. Traud, R. Smieskova, N. Mueller-Lenke, L. Kappos, A. Gass, T. Sprenger, I. K. Penner, T. E. Nichols, H. Vrenken, F. Barkhof, C. Polman, E. W. Radue, S. J. Borgwardt, and K. Bendfeldt, "Progression in disability and regional grey matter atrophy in relapsing-remitting multiple sclerosis," Mult Scler, 2013.
[71]
M. Muller, R. Esser, K. Kotter, J. Voss, A. Muller, and P. Stellmes, "Third ventricular enlargement in early stages of multiple sclerosis is a predictor of motor and neuropsychological deficits: a cross-sectional study," BMJ Open, vol. 3, no. 9, pp. e003582, 2013.
[72]
N. A. Losseff, L. Wang, H. M. Lai, D. S. Yoo, M. L. Gawne-Cain, W. I. McDonald, D. H. Miller, and A. J. Thompson, "Progressive cerebral atrophy in multiple sclerosis. A serial MRI study," Brain, vol. 119 ( Pt 6), pp. 2009-19, 1996.
[73]
I. T. Redmond, S. Barbosa, L. D. Blumhardt, and N. Roberts, "Short-term ventricular volume changes on serial MRI in multiple sclerosis," Acta Neurol Scand, vol. 102, no. 2, pp. 99-105, 2000.
[74]
M. Calabrese, F. Rinaldi, P. Grossi, and P. Gallo, "Cortical pathology and cognitive impairment in multiple sclerosis," Expert Rev Neurother, vol. 11, no. 3, pp. 425-32, 2011.
[75]
D. Horakova, T. Kalincik, J. B. Dusankova, and O. Dolezal, "Clinical correlates of grey matter pathology in multiple sclerosis," BMC Neurol, vol. 12, pp. 10, 2012.
[76]
M. Calabrese, D. Seppi, C. Romualdi, F. Rinaldi, S. Alessio, P. Perini, and P. Gallo, "Gray matter pathology in MS: a 3-year longitudinal study in a pediatric population," AJNR Am J Neuroradiol, vol. 33, no. 8, pp. 1507-11, 2012.
[77]
N. D. Chiaravalloti, and J. DeLuca, "Cognitive impairment in multiple sclerosis," Lancet Neurol, vol. 7, no. 12, pp. 1139-51, 2008.
[78]
M. P. Sanfilipo, R. H. Benedict, B. Weinstock-Guttman, and R. Bakshi, "Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis," Neurology, vol. 66, no. 5, pp. 685-92, 2006.
[79]
M. P. Amato, B. Hakiki, B. Goretti, F. Rossi, M. L. Stromillo, A. Giorgio, M. Roscio, A. Ghezzi, L. Guidi, M. L. Bartolozzi, E. Portaccio, N. De Stefano, and R. I. S. M. S. S. G. Italian, "Association of MRI metrics and cognitive impairment in radiologically isolated syndromes," Neurology, vol. 78, no. 5, pp. 309-14, 2012.
[80]
L. K. Fisniku, D. T. Chard, J. S. Jackson, V. M. Anderson, D. R. Altmann, K. A. Miszkiel, A. J. Thompson, and D. H. Miller, "Gray matter atrophy is related to long-term disability in multiple sclerosis," Ann Neurol, vol. 64, no. 3, pp. 247-54, 2008.
[81]
O. Yaldizli, I. K. Penner, K. Frontzek, Y. Naegelin, M. Amann, A. Papadopoulou, T. Sprenger, J. Kuhle, P. Calabrese, E. W. Radu, L. Kappos, and A. Gass, "The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients," Mult Scler, 2013.
[82]
K. Morgen, G. Sammer, S. M. Courtney, T. Wolters, H. Melchior, C. R. Blecker, P. Oschmann, M. Kaps, and D. Vaitl, "Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS," Neuroimage, vol. 30, no. 3, pp. 891-8, 2006.
[83]
S. D. Roosendaal, K. Bendfeldt, H. Vrenken, C. H. Polman, S. Borgwardt, E. W. Radue, L. Kappos, D. Pelletier, S. L. Hauser, P. M. Matthews, F. Barkhof, and J. J. Geurts, "Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability," Mult Scler, vol. 17, no. 9, pp. 1098-106, 2011.
[84]
D. P. Ramasamy, R. H. Benedict, J. L. Cox, D. Fritz, N. Abdelrahman, S. Hussein, A. Minagar, M. G. Dwyer, and R. Zivadinov, "Extent of cerebellum, subcortical and cortical atrophy in patients with MS: a case-control study," J Neurol Sci, vol. 282, no. 1-2, pp. 47-54, 2009.
[85]
R. A. Rudick, J. C. Lee, K. Nakamura, and E. Fisher, "Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS," J Neurol Sci, vol. 282, no. 1-2, pp. 106-11, 2009.
[86]
M. P. Amato, G. Ponziani, G. Siracusa, and S. Sorbi, "Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years," Arch Neurol, vol. 58, no. 10, pp. 1602-6, 2001.
[87]
S. M. Rao, G. J. Leo, L. Bernardin, and F. Unverzagt, "Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction," Neurology, vol. 41, no. 5, pp. 685-91, 1991.
[88]
B. I. Glanz, C. M. Holland, S. A. Gauthier, E. L. Amunwa, Z. Liptak, M. K. Houtchens, R. A. Sperling, S. J. Khoury, C. R. Guttmann, and H. L. Weiner, "Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis," Mult Scler, vol. 13, no. 8, pp. 1004-10, 2007.
[89]
M. Calabrese, F. Agosta, F. Rinaldi, I. Mattisi, P. Grossi, A. Favaretto, M. Atzori, V. Bernardi, L. Barachino, L. Rinaldi, P. Perini, P. Gallo, and M. Filippi, "Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis," Arch Neurol, vol. 66, no. 9, pp. 1144-50, 2009.
[90]
M. Calabrese, F. Rinaldi, I. Mattisi, P. Grossi, A. Favaretto, M. Atzori, V. Bernardi, L. Barachino, C. Romualdi, L. Rinaldi, P. Perini, and P. Gallo, "Widespread cortical thinning characterizes patients with MS with mild cognitive impairment," Neurology, vol. 74, no. 4, pp. 321-8, 2010.
[91]
M. K. Houtchens, R. H. Benedict, R. Killiany, J. Sharma, Z. Jaisani, B. Singh, B. Weinstock-Guttman, C. R. Guttmann, and R. Bakshi, "Thalamic atrophy and cognition in multiple sclerosis," Neurology, vol. 69, no. 12, pp. 1213-23, 2007.
[92]
S. Batista, R. Zivadinov, M. Hoogs, N. Bergsland, M. Heininen-Brown, M. G. Dwyer, B. Weinstock-Guttman, and R. H. Benedict, "Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis," J Neurol, vol. 259, no. 1, pp. 139-46, 2012.
[93]
M. Calabrese, F. Rinaldi, P. Grossi, I. Mattisi, V. Bernardi, A. Favaretto, P. Perini, and P. Gallo, "Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing-remitting multiple sclerosis," Mult Scler, vol. 16, no. 10, pp. 1220-8, 2010.
[94]
M. Calabrese, F. Rinaldi, I. Mattisi, V. Bernardi, A. Favaretto, P. Perini, and P. Gallo, "The predictive value of gray matter atrophy in clinically isolated syndromes," Neurology, vol. 77, no. 3, pp. 257-63, 2011.
[95]
M. A. Rocca, S. Mesaros, E. Pagani, M. P. Sormani, G. Comi, and M. Filippi, "Thalamic damage and long-term progression of disability in multiple sclerosis," Radiology, vol. 257, no. 2, pp. 463-9, 2010.
[96]
R. Zivadinov, R. A. Rudick, R. De Masi, D. Nasuelli, M. Ukmar, R. S. Pozzi-Mucelli, A. Grop, G. Cazzato, and M. Zorzon, "Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS," Neurology, vol. 57, no. 7, pp. 1239-47, 2001.
[97]
D. W. Paty, D. K. Li, U. M. M. S. Group, and I. M. S. S. Group, "Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. 1993 [classical article]," Neurology, vol. 57, no. 12 Suppl 5, pp. S10-5, 2001.
[98]
P. O'Connor, J. S. Wolinsky, C. Confavreux, G. Comi, L. Kappos, T. P. Olsson, H. Benzerdjeb, P. Truffinet, L. Wang, A. Miller, M. S. Freedman, and T. T. Group, "Randomized trial of oral teriflunomide for relapsing multiple sclerosis," N Engl J Med, vol. 365, no. 14, pp. 1293-303, 2011.
[99]
R. J. Fox, D. H. Miller, J. T. Phillips, M. Hutchinson, E. Havrdova, M. Kita, M. Yang, K. Raghupathi, M. Novas, M. T. Sweetser, V. Viglietta, K. T. Dawson, and C. S. Investigators, "Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis," N Engl J Med, vol. 367, no. 12, pp. 1087-97, 2012.
[100]
R. Gold, L. Kappos, D. L. Arnold, A. Bar-Or, G. Giovannoni, K. Selmaj, C. Tornatore, M. T. Sweetser, M. Yang, S. I. Sheikh, K. T. Dawson, and D. S. Investigators, "Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis," N Engl J Med, vol. 367, no. 12, pp. 1098-107, 2012.
[101]
G. Comi, D. Jeffery, L. Kappos, X. Montalban, A. Boyko, M. A. Rocca, M. Filippi, and A. S. Group, "Placebo-controlled trial of oral laquinimod for multiple sclerosis," N Engl J Med, vol. 366, no. 11, pp. 1000-9, 2012.
[102]
L. Kappos, E. W. Radue, P. O'Connor, C. Polman, R. Hohlfeld, P. Calabresi, K. Selmaj, C. Agoropoulou, M. Leyk, L. Zhang-Auberson, P. Burtin, and F. S. Group, "A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis," N Engl J Med, vol. 362, no. 5, pp. 387-401, 2010.
[103]
P. A. Calabresi, E. W. Radue, D. Goodin, D. Jeffery, K. W. Rammohan, A. T. Reder, T. Vollmer, M. A. Agius, L. Kappos, T. Stites, B. Li, L. Cappiello, P. von Rosenstiel, and F. D. Lublin, "Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial," Lancet Neurol, vol. 13, no. 6, pp. 545-56, 2014.
[104]
J. A. Cohen, F. Barkhof, G. Comi, H. P. Hartung, B. O. Khatri, X. Montalban, J. Pelletier, R. Capra, P. Gallo, G. Izquierdo, K. Tiel-Wilck, A. de Vera, J. Jin, T. Stites, S. Wu, S. Aradhye, L. Kappos, and T. S. Group, "Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis," N Engl J Med, vol. 362, no. 5, pp. 402-15, 2010.
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