The Multiple Sclerosis Functional Composite
A clinically meaningful measure of disability
Abstract
Background: The Multiple Sclerosis Functional Composite (MSFC) provides a focused and sensitive evaluation of disability in patients with multiple sclerosis (MS) that may be more responsive to change than that provided by the Expanded Disability Status Scale.
Expert Clinical Opinion: The MSFC is a 3-part quantitative instrument that measures arm, leg, and cognitive function with the 9-Hole Peg Test (arm/hand dexterity), the Timed 25-Foot Walk (leg function), and the Paced Auditory Serial Addition Test (3-second version, PASAT3; cognition). The MSFC has excellent test-retest reliability. Construct validity was supported by expected differences in scores between patients with primary or secondary progressive MS compared with relapsing-remitting MS. Concurrent validity was demonstrated by significant correlations with the Expanded Disability Status Scale, the Sickness Impact Profile, and the Short Form-36, particularly on the physical components of the latter 2 scales. MSFC scores also correlate with MRI changes. Limitations of the MSFC include practice effects with the PASAT and to a lesser extent the 9-Hole Peg Test, variations in the reference populations used to calculate Z-scores, and the lack of an accepted definition of a clinically meaningful change.
Future Directions: Future research should be directed at adding a test that measures visual function (e.g., contrast acuity), at replacing the PASAT by a cognition test that has better measurement characteristics, and at developing methods to better understand the clinical relevance of changes in MSFC scores.
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REFERENCES
1.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–1452.
2.
Kragt JJ, Nielsen JM, van der Linden FA, Uitdehaag BM, Polman CH. How similar are commonly combined criteria for EDSS progression in multiple sclerosis? Mult Scler 2006;12:782–786.
3.
Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology 1993;43:655–661.
4.
Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995;45:1268–1276.
5.
Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996;39:285–294.
6.
Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998;352:1498–1504.
7.
Polman CH, O'Connor PW, Havrdova E, et al; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354:899–910.
8.
Rudick RA, Stuart WH, Calabresi PA, et al; SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;354:911–923.
9.
Cutter GR, Baier ML, Rudick RA, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain 1999;122(Pt 5):871–882.
10.
Rudick R, Antel J, Confavreux C, et al. Clinical outcomes assessment in multiple sclerosis. Ann Neurol 1996;40:469–479.
11.
Rudick R, Antel J, Confavreux C, et al. Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force. Ann Neurol 1997;42:379–382.
12.
Whitaker JN, McFarland HF, Rudge P, Reingold SC. Outcomes assessment in multiple sclerosis clinical trials: a critical analysis. Mult Scler 1995;1:37–47.
13.
Goodkin DE, Hertsgaard D, Seminary J. Upper extremity function in multiple sclerosis: improving assessment sensitivity with box-and-block and nine-hole peg tests. Arch Phys Med Rehabil 1988;69:850–854.
14.
Kaufman M, Moyer D, Norton J. The significant change for the Timed 25-foot Walk in the multiple sclerosis functional composite. Mult Scler 2000;6:286–290.
15.
Gronwall DM. Paced auditory serial-addition task: a measure of recovery from concussion. Percept Mot Skills 1977;44:367–373.
16.
Cohen JA, Fischer JS, Bolibrush DM, et al. Intrarater and interrater reliability of the MS functional composite outcome measure. Neurology 2000;54:802–806.
17.
Cohen JA, Cutter GR, Fischer JS, et al, for the IMPACT Investigators. Use of the multiple sclerosis functional composite as an outcome measure in a phase 3 clinical trial. Arch Neurol 2001;58:961–967.
18.
Solari A, Radice D, Manneschi L, Motti L, Montanari E. The multiple sclerosis functional composite: different practice effects in the three test components. J Neurol Sci 2005;228:71–74.
19.
Fischer JS, Rudick RA, Cutter GR, Reingold SC. The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. The National MS Society Clinical Outcomes Assessment Task Force. Mult Scler 1999;5:244–250.
20.
Fox RJ, Lee JC, Rudick RA. Optimal reference population for the multiple sclerosis functional composite. Mult Scler 2007;13:909–914.
21.
Ford HL, Gerry E, Tennant A, Whalley D, Haigh R, Johnson MH. Developing a disease-specific quality of life measure for people with multiple sclerosis. Clin Rehabil 2001;15:247–258.
22.
Kalkers NK, de Groot V, Lazeron RH, et al. MS functional composite: relation to disease phenotype and disability strata. Neurology 2000;54:1233–1239.
23.
Hoogervorst EL, Kalkers NF, Uitdehaag BM, Polman CH. A study validating changes in the multiple sclerosis functional composite. Arch Neurol 2002;59:113–116.
24.
Miller DM, Rudick RA, Cutter G, Baier M, Fischer JS. Clinical significance of the multiple sclerosis functional composite: relationship to patient-reported quality of life. Arch Neurol 2000;57:1319–1324.
25.
Kalkers NF, Bergers L, de Groot V, et al. Concurrent validity of the MS Functional Composite using MRI as a biological disease marker. Neurology 2001;56:215–219.
26.
Kalkers NF, Bergers E, Castelijns JA, et al. Optimizing the association between disability and biological markers in MS. Neurology 2001;57:1253–1258.
27.
Vrenken H, Pouwels PJ, Ropele S, et al. Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease. Mult Scler 2007;13:708–716.
28.
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;37:253–261.
29.
Khaleeli Z, Sastre-Garriga J, Ciccarelli O, Miller DH, Thompson AJ. Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 2007;78:1076–1082.
30.
Lowe MJ, Horenstein C, Hirsch JG, et al. Functional pathway-defined MRI diffusion measures reveal increased transverse diffusivity of water in multiple sclerosis. Neuroimage 2006;32:1127–1133.
31.
Rudick RA, Cutter G, Baier M, et al. Use of the Multiple Sclerosis Functional Composite to predict disability in relapsing MS. Neurology 2001;56:1324–1330.
32.
Fisher E, Rudick RA, Cutter G, et al. Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. Mult Scler 2000;6:373–377.
33.
Sastre-Garriga J, Ingle GT, Chard DT, Ramió-Torrentà L, Miller DH, Thompson AJ. Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis. Neuroimage 2004;22:353–359.
34.
Chard DT, Griffin CM, McLean MA, et al. Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis. Brain 2002;125(Pt 10):2342–2352.
35.
Jasperse B, Jakobs C, Eikelenboom MJ, et al. N- acetylaspartic acid in cerebrospinal fluid of multiple sclerosis patients determined by gas-chromatography-mass spectrometry. J Neurol 2007;254:631–637.
36.
Moldovan IR, Rudick RA, Cotleur AC, et al. Interferon gamma responses to myelin peptides in multiple sclerosis correlate with a new clinical measure of disease progression. J Neuroimmunol 2003;141:132–140.
37.
van Veen T, Nielsen J, Berkhof J, et al. CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis. J Neuroimmunol 2007;190:157–164.
38.
Fischer JS, Jak AJ, Kniker JE, Rudick RA, Cutter G. Multiple Sclerosis Functional Composite (MSFC): Administration and Scoring Manual. National Multiple Sclerosis Society: New York; 2001.
39.
Hobart J, Kalkers N, Barkhof F, Uitdehaag B, Polman C, Thompson A. Outcome measures for multiple sclerosis clinical trials: relative measurement precision of the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite. Mult Scler 2004;10:41–46.
40.
Uitdehaag BM, Adèr HJ, Roosma TJA, de Groot V, Kalkers NF, Polman CH. Multiple sclerosis functional composite: impact of reference population and interpretation of changes. Mult Scler 2002;8:366–371.
41.
Schwid SR, Goodman AD, McDermott MP, Bever CF, Cook SD. Quantitative functional measures in MS: what is a reliable change? Neurology 2002;58:1294–1296.
42.
Uitdehaag BM, Adèr HJ, Kalkers NF, Polman CH. Quantitative functional measures in MS: what is a reliable change? Neurology 2002;59:648–649.
43.
Rudick RA, Lee JC, Simon J, Fisher E. Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study. Ann Neurol 2006;60:236–242.
44.
Cohen JA, Cutter GR, Fischer JS, et al. IMPACT Investigators. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002;59:679–687.
45.
Miller DM, Cohen JA, Kooijmans M, Tsao E, Cutter G, Baier M. Change in clinician-assessed measures of multiple sclerosis and subject-reported quality of life: results from the IMPACT study. Mult Scler 2006;12:180–186.
46.
Kappos L, Freedman MS, Polman CH, et al. BENEFIT Study Group. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 2007;370:389–397.
47.
Montalban X. Overview of European pilot study of interferon beta-1b in primary progressive multiple sclerosis. Mult Scler 2004;10(suppl 1):S62–S64.
48.
Polman CH, Rudick RA, Balcer LJ, et al. Sustained disability progression using scores from the Multiple Sclerosis Functional Composite. Presented at the 59th Annual Meeting of the American Academy of Neurology; April 28–May 5, 2007; Boston.
49.
Phillips JT, Kappos L, O'Connor PW, et al; for the AFFIRM Investigators. The effects of natalizumab monotherapy on multiple sclerosis measures of disability progression in patients with multiple sclerosis. Presented at the 58th Annual Meeting of the American Academy of Neurology; April 1–8, 2006; San Diego, CA.
50.
Lublin FD, O'Connor PW, Havrdova E, et al; for the AFFIRM Investigators. The effects of natalizumab on disability progression in the AFFIRM study: correlation between changes in Multiple Sclerosis Functional Composite and Expanded Disability Status Scale scores (poster P580). Presented at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 28–October 1, 2005; Thessaloniki, Greece.
51.
Fischer JS, Priore RL, Jacobs LD, et al. Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group. Ann Neurol 2000;48:885–892.
52.
Weinstein A, Schwid SR, Schiffer RB, McDermott MP, Giang DW, Goodman AD. Neuropsychologic status in multiple sclerosis after treatment with glatiramer. Arch Neurol 1999;56:319–324.
53.
Fisher E, O'Connor PW, Havrdova E, et al; for the AFFIRM Investigators. The effects of natalizumab on brain atrophy and cognitive function: results from the AFFIRM study (poster P383). Presented at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27–30, 2006; Madrid, Spain.
54.
Kragt JJ, Thompson AJ, Montalban X, et al. Responsiveness and predictive value of EDSS and MSFC in primary progressive MS. Neurology 2008;70:1084–1091.
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Neurology®
Volume 74 • Number 17_supplement_3 • April 27, 2010
Pages: S8-S15
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Published online: April 26, 2010
Published in print: April 27, 2010
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