Skip to main content
Top
Published in: BMC Neurology 1/2011

Open Access 01-12-2011 | Research article

Computational classifiers for predicting the short-term course of Multiple sclerosis

Authors: Bartolome Bejarano, Mariangela Bianco, Dolores Gonzalez-Moron, Jorge Sepulcre, Joaquin Goñi, Juan Arcocha, Oscar Soto, Ubaldo Del Carro, Giancarlo Comi, Letizia Leocani, Pablo Villoslada

Published in: BMC Neurology | Issue 1/2011

Login to get access

Abstract

Background

The aim of this study was to assess the diagnostic accuracy (sensitivity and specificity) of clinical, imaging and motor evoked potentials (MEP) for predicting the short-term prognosis of multiple sclerosis (MS).

Methods

We obtained clinical data, MRI and MEP from a prospective cohort of 51 patients and 20 matched controls followed for two years. Clinical end-points recorded were: 1) expanded disability status scale (EDSS), 2) disability progression, and 3) new relapses. We constructed computational classifiers (Bayesian, random decision-trees, simple logistic-linear regression-and neural networks) and calculated their accuracy by means of a 10-fold cross-validation method. We also validated our findings with a second cohort of 96 MS patients from a second center.

Results

We found that disability at baseline, grey matter volume and MEP were the variables that better correlated with clinical end-points, although their diagnostic accuracy was low. However, classifiers combining the most informative variables, namely baseline disability (EDSS), MRI lesion load and central motor conduction time (CMCT), were much more accurate in predicting future disability. Using the most informative variables (especially EDSS and CMCT) we developed a neural network (NNet) that attained a good performance for predicting the EDSS change. The predictive ability of the neural network was validated in an independent cohort obtaining similar accuracy (80%) for predicting the change in the EDSS two years later.

Conclusions

The usefulness of clinical variables for predicting the course of MS on an individual basis is limited, despite being associated with the disease course. By training a NNet with the most informative variables we achieved a good accuracy for predicting short-term disability.
Appendix
Available only for authorised users
Literature
1.
go back to reference Janssens AC, van Doorn PA, de Boer JB, van der Meche FG, Passchier J, Hintzen RQ: Perception of prognostic risk in patients with multiple sclerosis: the relationship with anxiety, depression, and disease-related distress. J Clin Epidemiol. 2004, 57 (2): 180-186. 10.1016/S0895-4356(03)00260-9.CrossRefPubMed Janssens AC, van Doorn PA, de Boer JB, van der Meche FG, Passchier J, Hintzen RQ: Perception of prognostic risk in patients with multiple sclerosis: the relationship with anxiety, depression, and disease-related distress. J Clin Epidemiol. 2004, 57 (2): 180-186. 10.1016/S0895-4356(03)00260-9.CrossRefPubMed
2.
go back to reference Bielekova B, Martin R: Development of biomarkers in multiple sclerosis. Brain. 2004, 127 (Pt 7): 1463-1478.CrossRefPubMed Bielekova B, Martin R: Development of biomarkers in multiple sclerosis. Brain. 2004, 127 (Pt 7): 1463-1478.CrossRefPubMed
3.
go back to reference Confavreux C, Vukusic S: Natural history of multiple sclerosis: a unifying concept. Brain. 2006, 129 (Pt 3): 606-616.CrossRefPubMed Confavreux C, Vukusic S: Natural history of multiple sclerosis: a unifying concept. Brain. 2006, 129 (Pt 3): 606-616.CrossRefPubMed
4.
go back to reference Daumer M, Neuhaus A, Lederer C, Scholz M, Wolinsky JS, Heiderhoff M: Prognosis of the individual course of disease--steps in developing a decision support tool for Multiple Sclerosis. BMC Med Inform Decis Mak. 2007, 7: 11-10.1186/1472-6947-7-11.CrossRefPubMedPubMedCentral Daumer M, Neuhaus A, Lederer C, Scholz M, Wolinsky JS, Heiderhoff M: Prognosis of the individual course of disease--steps in developing a decision support tool for Multiple Sclerosis. BMC Med Inform Decis Mak. 2007, 7: 11-10.1186/1472-6947-7-11.CrossRefPubMedPubMedCentral
5.
go back to reference Bergamaschi R, Berzuini C, Romani A, Cosi V: Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis. J Neurol Sci. 2001, 189 (1-2): 13-21. 10.1016/S0022-510X(01)00572-X.CrossRefPubMed Bergamaschi R, Berzuini C, Romani A, Cosi V: Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis. J Neurol Sci. 2001, 189 (1-2): 13-21. 10.1016/S0022-510X(01)00572-X.CrossRefPubMed
6.
go back to reference Gauthier SA, Mandel M, Guttmann CR, Glanz BI, Khoury SJ, Betensky RA, Weiner HL: Predicting short-term disability in multiple sclerosis. Neurology. 2007, 68 (24): 2059-2065. 10.1212/01.wnl.0000264890.97479.b1.CrossRefPubMed Gauthier SA, Mandel M, Guttmann CR, Glanz BI, Khoury SJ, Betensky RA, Weiner HL: Predicting short-term disability in multiple sclerosis. Neurology. 2007, 68 (24): 2059-2065. 10.1212/01.wnl.0000264890.97479.b1.CrossRefPubMed
7.
go back to reference Minneboo A, Jasperse B, Barkhof F, Uitdehaag BM, Knol DL, de Groot V, Polman CH, Castelijns JA: Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters. J Neurol Neurosurg Psychiatry. 2008, 79 (8): 917-923. 10.1136/jnnp.2007.124123.CrossRefPubMed Minneboo A, Jasperse B, Barkhof F, Uitdehaag BM, Knol DL, de Groot V, Polman CH, Castelijns JA: Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters. J Neurol Neurosurg Psychiatry. 2008, 79 (8): 917-923. 10.1136/jnnp.2007.124123.CrossRefPubMed
8.
go back to reference Sormani MP, Rovaris M, Comi G, Filippi M: A composite score to predict short-term disease activity in patients with relapsing-remitting MS. Neurology. 2007, 69 (12): 1230-1235. 10.1212/01.wnl.0000276940.90309.15.CrossRefPubMed Sormani MP, Rovaris M, Comi G, Filippi M: A composite score to predict short-term disease activity in patients with relapsing-remitting MS. Neurology. 2007, 69 (12): 1230-1235. 10.1212/01.wnl.0000276940.90309.15.CrossRefPubMed
9.
go back to reference Sepulcre J, Murie-Fernandez M, Salinas-Alaman A, Garcia-Layana A, Bejarano B, Villoslada P: Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology. 2007, 68 (18): 1488-1494. 10.1212/01.wnl.0000260612.51849.ed.CrossRefPubMed Sepulcre J, Murie-Fernandez M, Salinas-Alaman A, Garcia-Layana A, Bejarano B, Villoslada P: Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology. 2007, 68 (18): 1488-1494. 10.1212/01.wnl.0000260612.51849.ed.CrossRefPubMed
10.
go back to reference Villar LM, Sadaba MC, Roldan E, Masjuan J, Gonzalez-Porque P, Villarrubia N, Espino M, Garcia-Trujillo JA, Bootello A, Alvarez-Cermeno JC: Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J Clin Invest. 2005, 115 (1): 187-194.CrossRefPubMedPubMedCentral Villar LM, Sadaba MC, Roldan E, Masjuan J, Gonzalez-Porque P, Villarrubia N, Espino M, Garcia-Trujillo JA, Bootello A, Alvarez-Cermeno JC: Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J Clin Invest. 2005, 115 (1): 187-194.CrossRefPubMedPubMedCentral
11.
go back to reference Schurink CA, Lucas PJ, Hoepelman IM, Bonten MJ: Computer-assisted decision support for the diagnosis and treatment of infectious diseases in intensive care units. Lancet Infect Dis. 2005, 5 (5): 305-312. 10.1016/S1473-3099(05)70115-8.CrossRefPubMed Schurink CA, Lucas PJ, Hoepelman IM, Bonten MJ: Computer-assisted decision support for the diagnosis and treatment of infectious diseases in intensive care units. Lancet Infect Dis. 2005, 5 (5): 305-312. 10.1016/S1473-3099(05)70115-8.CrossRefPubMed
12.
go back to reference Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS: Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005, 58 (6): 840-846. 10.1002/ana.20703.CrossRefPubMed Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS: Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005, 58 (6): 840-846. 10.1002/ana.20703.CrossRefPubMed
13.
go back to reference Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983, 33 (11): 1444-1452.CrossRefPubMed Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983, 33 (11): 1444-1452.CrossRefPubMed
14.
go back to reference Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, et al: Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005, 64 (7): 1144-1151.CrossRefPubMed Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, et al: Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005, 64 (7): 1144-1151.CrossRefPubMed
15.
go back to reference Fischer JS, Rudick RA, Cutter GR, Reingold SC: The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler. 1999, 5 (4): 244-250.CrossRefPubMed Fischer JS, Rudick RA, Cutter GR, Reingold SC: The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler. 1999, 5 (4): 244-250.CrossRefPubMed
16.
go back to reference Rio J, Nos C, Tintore M, Tellez N, Galan I, Pelayo R, Comabella M, Montalban X: Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients. AnnNeurol. 2006, 59 (2): 344-352. Rio J, Nos C, Tintore M, Tellez N, Galan I, Pelayo R, Comabella M, Montalban X: Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients. AnnNeurol. 2006, 59 (2): 344-352.
17.
go back to reference Leocani L, Rovaris M, Boneschi FM, Medaglini S, Rossi P, Martinelli V, Amadio S, Comi G: Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study. J Neurol Neurosurg Psychiatry. 2006, 77 (9): 1030-1035. 10.1136/jnnp.2005.086280.CrossRefPubMedPubMedCentral Leocani L, Rovaris M, Boneschi FM, Medaglini S, Rossi P, Martinelli V, Amadio S, Comi G: Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study. J Neurol Neurosurg Psychiatry. 2006, 77 (9): 1030-1035. 10.1136/jnnp.2005.086280.CrossRefPubMedPubMedCentral
18.
go back to reference Kimura J: Electrodiagnosis in diseases of nerve and muscles: principles and practice. Volume Osford University Press New York. 2001, 3 Kimura J: Electrodiagnosis in diseases of nerve and muscles: principles and practice. Volume Osford University Press New York. 2001, 3
19.
go back to reference Esteban FJ, Sepulcre J, de Mendizabal NV, Goni J, Navas J, de Miras JR, Bejarano B, Masdeu JC, Villoslada P: Fractal dimension and white matter changes in multiple sclerosis. Neuroimage. 2007, 36 (3): 543-549. 10.1016/j.neuroimage.2007.03.057.CrossRefPubMed Esteban FJ, Sepulcre J, de Mendizabal NV, Goni J, Navas J, de Miras JR, Bejarano B, Masdeu JC, Villoslada P: Fractal dimension and white matter changes in multiple sclerosis. Neuroimage. 2007, 36 (3): 543-549. 10.1016/j.neuroimage.2007.03.057.CrossRefPubMed
20.
go back to reference Sepulcre J, Masdeu JC, Sastre-Garriga J, Goñi J, Velez N, Duque B, Pastor M, Bejarano B, Villoslada P: Mapping the brain pathways of declarative verbal memory: Evidence from white matter lesions in the living human brain. Neuroimage. 2008, 42 (3): 1237-1243. 10.1016/j.neuroimage.2008.05.038.CrossRefPubMed Sepulcre J, Masdeu JC, Sastre-Garriga J, Goñi J, Velez N, Duque B, Pastor M, Bejarano B, Villoslada P: Mapping the brain pathways of declarative verbal memory: Evidence from white matter lesions in the living human brain. Neuroimage. 2008, 42 (3): 1237-1243. 10.1016/j.neuroimage.2008.05.038.CrossRefPubMed
21.
go back to reference Bottaci L, Drew PJ, Hartley JE, Hadfield MB, Farouk R, Lee PW, Macintyre IM, Duthie GS, Monson JR: Artificial neural networks applied to outcome prediction for colorectal cancer patients in separate institutions. Lancet. 1997, 350 (9076): 469-472. 10.1016/S0140-6736(96)11196-X.CrossRefPubMed Bottaci L, Drew PJ, Hartley JE, Hadfield MB, Farouk R, Lee PW, Macintyre IM, Duthie GS, Monson JR: Artificial neural networks applied to outcome prediction for colorectal cancer patients in separate institutions. Lancet. 1997, 350 (9076): 469-472. 10.1016/S0140-6736(96)11196-X.CrossRefPubMed
22.
go back to reference Altmann A, Rosen-Zvi M, Prosperi M, Aharoni E, Neuvirth H, Schulter E, Buch J, Struck D, Peres Y, Incardona F, Sonnerborg A, Kaiser R, Zazzi M, Lengauer T: Comparison of classifier fusion methods for predicting response to anti HIV-1 therapy. PLoS ONE. 2008, 3 (10): e3470.-CrossRefPubMedPubMedCentral Altmann A, Rosen-Zvi M, Prosperi M, Aharoni E, Neuvirth H, Schulter E, Buch J, Struck D, Peres Y, Incardona F, Sonnerborg A, Kaiser R, Zazzi M, Lengauer T: Comparison of classifier fusion methods for predicting response to anti HIV-1 therapy. PLoS ONE. 2008, 3 (10): e3470.-CrossRefPubMedPubMedCentral
23.
go back to reference Witten I, Frank E: Data Mining: Practical machine learning tools and techniques. 2005, London: Elsevier Witten I, Frank E: Data Mining: Practical machine learning tools and techniques. 2005, London: Elsevier
24.
go back to reference Kohavi R, John G: Wrappers for feature subset selection. Artif Intell. 1997, 97 (1-2): 273-324. 10.1016/S0004-3702(97)00043-X.CrossRef Kohavi R, John G: Wrappers for feature subset selection. Artif Intell. 1997, 97 (1-2): 273-324. 10.1016/S0004-3702(97)00043-X.CrossRef
25.
go back to reference Inza I, Larrañaga P, Blanco R, Cerrolaza A: Filter versus wrapper gene selection approaches in DNA microarray domains. Artif Intell Med. 2004, 31 (2): 91-103. 10.1016/j.artmed.2004.01.007.CrossRefPubMed Inza I, Larrañaga P, Blanco R, Cerrolaza A: Filter versus wrapper gene selection approaches in DNA microarray domains. Artif Intell Med. 2004, 31 (2): 91-103. 10.1016/j.artmed.2004.01.007.CrossRefPubMed
26.
go back to reference Kohavi R: A study of cross-validation and bootstrap for accuracy estimation and model selection. Proceedings of the International Joint Conference on Artificial Intelligence. 1995, 1137-1145. Kohavi R: A study of cross-validation and bootstrap for accuracy estimation and model selection. Proceedings of the International Joint Conference on Artificial Intelligence. 1995, 1137-1145.
27.
go back to reference Weigend A: On overfitting and the effective number of hidden units. Proceedings of the 1993 Connectionist Models Summer School. 1994, 335-342. Weigend A: On overfitting and the effective number of hidden units. Proceedings of the 1993 Connectionist Models Summer School. 1994, 335-342.
28.
go back to reference Smith M: Neural Networks for Statistical Modeling. 1996, Boston: International Thomson Computer Press Smith M: Neural Networks for Statistical Modeling. 1996, Boston: International Thomson Computer Press
29.
go back to reference Leray P, Gallinari P: Feature selection with Neural Networks. Behaviormetrika. 1998, 26: 6-16. Leray P, Gallinari P: Feature selection with Neural Networks. Behaviormetrika. 1998, 26: 6-16.
30.
go back to reference Fisher E, Lee JC, Nakamura K, Rudick RA: Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008, 64 (3): 255-265. 10.1002/ana.21436.CrossRefPubMed Fisher E, Lee JC, Nakamura K, Rudick RA: Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008, 64 (3): 255-265. 10.1002/ana.21436.CrossRefPubMed
31.
go back to reference Mastaglia FL: Can abnormal evoked potentials predict future clinical disability in patients with multiple sclerosis?. Nat Clin Pract Neurol. 2006, 2 (6): 304-305.CrossRefPubMed Mastaglia FL: Can abnormal evoked potentials predict future clinical disability in patients with multiple sclerosis?. Nat Clin Pract Neurol. 2006, 2 (6): 304-305.CrossRefPubMed
32.
go back to reference Villoslada P, Oksenberg J: Neuroinformatics in clinical practice: are computers going to help neurological patients and their physicians?. Future Neurology. 2006, 1 (2): 1-12.CrossRef Villoslada P, Oksenberg J: Neuroinformatics in clinical practice: are computers going to help neurological patients and their physicians?. Future Neurology. 2006, 1 (2): 1-12.CrossRef
33.
go back to reference Bates DW, Gawande AA: Improving safety with information technology. N Engl J Med. 2003, 348 (25): 2526-2534. 10.1056/NEJMsa020847.CrossRefPubMed Bates DW, Gawande AA: Improving safety with information technology. N Engl J Med. 2003, 348 (25): 2526-2534. 10.1056/NEJMsa020847.CrossRefPubMed
Metadata
Title
Computational classifiers for predicting the short-term course of Multiple sclerosis
Authors
Bartolome Bejarano
Mariangela Bianco
Dolores Gonzalez-Moron
Jorge Sepulcre
Joaquin Goñi
Juan Arcocha
Oscar Soto
Ubaldo Del Carro
Giancarlo Comi
Letizia Leocani
Pablo Villoslada
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2011
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-11-67

Other articles of this Issue 1/2011

BMC Neurology 1/2011 Go to the issue