Short-term brain volume change in relapsing-remitting multiple sclerosis: Effect of glatiramer acetate and implications

Marco Rovaris; Giancarlo Comi; Maria A. Rocca; Jerry S. Wolinsky; Massimo Filippi; D. Guillaume; J. B. D'Harcour; C. J.M. Sindic; T. P.J. Duprez; L. Truyen; G. Nagels; P. M. Parizel; E. A.C.M. Sanders; R. J. Versteylen; G. Rice; K. Kennedy; L. Metz; D. Patry; M. Yeung; A. Davis; S. Curtis; G. Francis; D. L. Arnold; G. Leroux; O. Lyon-Caen; A. Tourbah; M. Bataillard; I. R. Kraehenbuhl; E. A. Cabanis; S. Bracard; M. Debouverie; R. Anxionnat; B. Storch-Hagenlocher; K. Sartor; W. Gehlen; A. Schmidt; C. Weiller; W. Behrendt; M. Zaffaroni; C. Fieschi; S. Bastianello; R. Capra; R. Gasparotti; G. L. Mancardi; M. Inglese; F. Sardanelli; V. Cosi; C. Uggetti; F. Zappoli; C. P. Hawkins; N. Haq; D. Barnes; A. Clifton; D. Bates; A. Coulthard; G. Perkin; I. Colquhoun; C. A. Young; T. Nixon; D. Francis; D. Yates; D. Neary; A. Jackson; L. D. Blumhardt; T. Jaspan; R. Brenner; A. Valentine; I. Pye; G. Cherryman

doi:10.1093/brain/124.9.1803

Short-term brain volume change in relapsing-remitting multiple sclerosis: Effect of glatiramer acetate and implications

Marco Rovaris, Giancarlo Comi, Maria A. Rocca, Jerry S. Wolinsky, Massimo Filippi, D. Guillaume, J. B. D'Harcour, C. J.M. Sindic, T. P.J. Duprez, L. Truyen, G. Nagels, P. M. Parizel, E. A.C.M. Sanders, R. J. Versteylen, G. Rice, K. Kennedy, L. Metz, D. Patry, M. Yeung, A. DavisS. Curtis, G. Francis, D. L. Arnold, G. Leroux, O. Lyon-Caen, A. Tourbah, M. Bataillard, I. R. Kraehenbuhl, E. A. Cabanis, S. Bracard, M. Debouverie, R. Anxionnat, B. Storch-Hagenlocher, K. Sartor, W. Gehlen, A. Schmidt, C. Weiller, W. Behrendt, M. Zaffaroni, C. Fieschi, S. Bastianello, R. Capra, R. Gasparotti, G. L. Mancardi, M. Inglese, F. Sardanelli, V. Cosi, C. Uggetti, F. Zappoli, C. P. Hawkins, N. Haq, D. Barnes, A. Clifton, D. Bates, A. Coulthard, G. Perkin, I. Colquhoun, C. A. Young, T. Nixon, D. Francis, D. Yates, D. Neary, A. Jackson, L. D. Blumhardt, T. Jaspan, R. Brenner, A. Valentine, I. Pye, G. Cherryman

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Abstract

The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsing-remitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image sets from 113 out of 119 patients randomized to GA, and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume was significantly correlated with patients' disability at each time-point. No significant differences between placebo- and GA-treated patients were found for baseline brain volume and rate of brain volume change over the study, even though a possible late trend for treatment with GA to retard the loss of brain volume was observed. There was a significant, but modest, correlation between MRI activity during the double-blind phase, and brain volume change over the entire study among patients originally treated with placebo. The modest correlation between enhancement frequency and brain atrophy loss indicates that the suppression of inflammatory activity in RR multiple sclerosis patients is not fully and rapidly associated with a similar effect on the global neurodegenerative processes. This study also suggests that any effect of GA in preventing brain volume decrease is not evident early following institution of treatment.

Original language	English
Pages (from-to)	1803-1812
Number of pages	10
Journal	Brain
Volume	124
Issue number	9
DOIs	https://doi.org/10.1093/brain/124.9.1803
State	Published - 1 Jan 2001

Keywords

Brain volume
Clinical trial
Glatiramer acetate
MRI
Multiple sclerosis

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Rovaris, M., Comi, G., Rocca, M. A., Wolinsky, J. S., Filippi, M., Guillaume, D., D'Harcour, J. B., Sindic, C. J. M., Duprez, T. P. J., Truyen, L., Nagels, G., Parizel, P. M., Sanders, E. A. C. M., Versteylen, R. J., Rice, G., Kennedy, K., Metz, L., Patry, D., Yeung, M., ... Cherryman, G. (2001). Short-term brain volume change in relapsing-remitting multiple sclerosis: Effect of glatiramer acetate and implications. Brain, 124(9), 1803-1812. https://doi.org/10.1093/brain/124.9.1803

@article{e0547bfd23fc4c32b6c2d4556ba24400,

title = "Short-term brain volume change in relapsing-remitting multiple sclerosis: Effect of glatiramer acetate and implications",

abstract = "The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsing-remitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image sets from 113 out of 119 patients randomized to GA, and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume was significantly correlated with patients' disability at each time-point. No significant differences between placebo- and GA-treated patients were found for baseline brain volume and rate of brain volume change over the study, even though a possible late trend for treatment with GA to retard the loss of brain volume was observed. There was a significant, but modest, correlation between MRI activity during the double-blind phase, and brain volume change over the entire study among patients originally treated with placebo. The modest correlation between enhancement frequency and brain atrophy loss indicates that the suppression of inflammatory activity in RR multiple sclerosis patients is not fully and rapidly associated with a similar effect on the global neurodegenerative processes. This study also suggests that any effect of GA in preventing brain volume decrease is not evident early following institution of treatment.",

keywords = "Brain volume, Clinical trial, Glatiramer acetate, MRI, Multiple sclerosis",

author = "Marco Rovaris and Giancarlo Comi and Rocca, {Maria A.} and Wolinsky, {Jerry S.} and Massimo Filippi and D. Guillaume and D'Harcour, {J. B.} and Sindic, {C. J.M.} and Duprez, {T. P.J.} and L. Truyen and G. Nagels and Parizel, {P. M.} and Sanders, {E. A.C.M.} and Versteylen, {R. J.} and G. Rice and K. Kennedy and L. Metz and D. Patry and M. Yeung and A. Davis and S. Curtis and G. Francis and Arnold, {D. L.} and G. Leroux and O. Lyon-Caen and A. Tourbah and M. Bataillard and Kraehenbuhl, {I. R.} and Cabanis, {E. A.} and S. Bracard and M. Debouverie and R. Anxionnat and B. Storch-Hagenlocher and K. Sartor and W. Gehlen and A. Schmidt and C. Weiller and W. Behrendt and M. Zaffaroni and C. Fieschi and S. Bastianello and R. Capra and R. Gasparotti and Mancardi, {G. L.} and M. Inglese and F. Sardanelli and V. Cosi and C. Uggetti and F. Zappoli and Hawkins, {C. P.} and N. Haq and D. Barnes and A. Clifton and D. Bates and A. Coulthard and G. Perkin and I. Colquhoun and Young, {C. A.} and T. Nixon and D. Francis and D. Yates and D. Neary and A. Jackson and Blumhardt, {L. D.} and T. Jaspan and R. Brenner and A. Valentine and I. Pye and G. Cherryman",

year = "2001",

month = jan,

day = "1",

doi = "10.1093/brain/124.9.1803",

language = "English",

volume = "124",

pages = "1803--1812",

journal = "Brain",

issn = "0006-8950",

publisher = "Oxford University Press",

number = "9",

}

Rovaris, M, Comi, G, Rocca, MA, Wolinsky, JS, Filippi, M, Guillaume, D, D'Harcour, JB, Sindic, CJM, Duprez, TPJ, Truyen, L, Nagels, G, Parizel, PM, Sanders, EACM, Versteylen, RJ, Rice, G, Kennedy, K, Metz, L, Patry, D, Yeung, M, Davis, A, Curtis, S, Francis, G, Arnold, DL, Leroux, G, Lyon-Caen, O, Tourbah, A, Bataillard, M, Kraehenbuhl, IR, Cabanis, EA, Bracard, S, Debouverie, M, Anxionnat, R, Storch-Hagenlocher, B, Sartor, K, Gehlen, W, Schmidt, A, Weiller, C, Behrendt, W, Zaffaroni, M, Fieschi, C, Bastianello, S, Capra, R, Gasparotti, R, Mancardi, GL, Inglese, M, Sardanelli, F, Cosi, V, Uggetti, C, Zappoli, F, Hawkins, CP, Haq, N, Barnes, D, Clifton, A, Bates, D, Coulthard, A, Perkin, G, Colquhoun, I, Young, CA, Nixon, T, Francis, D, Yates, D, Neary, D, Jackson, A, Blumhardt, LD, Jaspan, T, Brenner, R, Valentine, A, Pye, I & Cherryman, G 2001, 'Short-term brain volume change in relapsing-remitting multiple sclerosis: Effect of glatiramer acetate and implications', Brain, vol. 124, no. 9, pp. 1803-1812. https://doi.org/10.1093/brain/124.9.1803

TY - JOUR

T1 - Short-term brain volume change in relapsing-remitting multiple sclerosis

T2 - Effect of glatiramer acetate and implications

AU - Rovaris, Marco

AU - Comi, Giancarlo

AU - Rocca, Maria A.

AU - Wolinsky, Jerry S.

AU - Filippi, Massimo

AU - Guillaume, D.

AU - D'Harcour, J. B.

AU - Sindic, C. J.M.

AU - Duprez, T. P.J.

AU - Truyen, L.

AU - Nagels, G.

AU - Parizel, P. M.

AU - Sanders, E. A.C.M.

AU - Versteylen, R. J.

AU - Rice, G.

AU - Kennedy, K.

AU - Metz, L.

AU - Patry, D.

AU - Yeung, M.

AU - Davis, A.

AU - Curtis, S.

AU - Francis, G.

AU - Arnold, D. L.

AU - Leroux, G.

AU - Lyon-Caen, O.

AU - Tourbah, A.

AU - Bataillard, M.

AU - Kraehenbuhl, I. R.

AU - Cabanis, E. A.

AU - Bracard, S.

AU - Debouverie, M.

AU - Anxionnat, R.

AU - Storch-Hagenlocher, B.

AU - Sartor, K.

AU - Gehlen, W.

AU - Schmidt, A.

AU - Weiller, C.

AU - Behrendt, W.

AU - Zaffaroni, M.

AU - Fieschi, C.

AU - Bastianello, S.

AU - Capra, R.

AU - Gasparotti, R.

AU - Mancardi, G. L.

AU - Inglese, M.

AU - Sardanelli, F.

AU - Cosi, V.

AU - Uggetti, C.

AU - Zappoli, F.

AU - Hawkins, C. P.

AU - Haq, N.

AU - Barnes, D.

AU - Clifton, A.

AU - Bates, D.

AU - Coulthard, A.

AU - Perkin, G.

AU - Colquhoun, I.

AU - Young, C. A.

AU - Nixon, T.

AU - Francis, D.

AU - Yates, D.

AU - Neary, D.

AU - Jackson, A.

AU - Blumhardt, L. D.

AU - Jaspan, T.

AU - Brenner, R.

AU - Valentine, A.

AU - Pye, I.

AU - Cherryman, G.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsing-remitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image sets from 113 out of 119 patients randomized to GA, and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume was significantly correlated with patients' disability at each time-point. No significant differences between placebo- and GA-treated patients were found for baseline brain volume and rate of brain volume change over the study, even though a possible late trend for treatment with GA to retard the loss of brain volume was observed. There was a significant, but modest, correlation between MRI activity during the double-blind phase, and brain volume change over the entire study among patients originally treated with placebo. The modest correlation between enhancement frequency and brain atrophy loss indicates that the suppression of inflammatory activity in RR multiple sclerosis patients is not fully and rapidly associated with a similar effect on the global neurodegenerative processes. This study also suggests that any effect of GA in preventing brain volume decrease is not evident early following institution of treatment.

AB - The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsing-remitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image sets from 113 out of 119 patients randomized to GA, and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume was significantly correlated with patients' disability at each time-point. No significant differences between placebo- and GA-treated patients were found for baseline brain volume and rate of brain volume change over the study, even though a possible late trend for treatment with GA to retard the loss of brain volume was observed. There was a significant, but modest, correlation between MRI activity during the double-blind phase, and brain volume change over the entire study among patients originally treated with placebo. The modest correlation between enhancement frequency and brain atrophy loss indicates that the suppression of inflammatory activity in RR multiple sclerosis patients is not fully and rapidly associated with a similar effect on the global neurodegenerative processes. This study also suggests that any effect of GA in preventing brain volume decrease is not evident early following institution of treatment.

KW - Brain volume

KW - Clinical trial

KW - Glatiramer acetate

KW - MRI

KW - Multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=0034853968&partnerID=8YFLogxK

U2 - 10.1093/brain/124.9.1803

DO - 10.1093/brain/124.9.1803

M3 - Article

C2 - 11522582

AN - SCOPUS:0034853968

SN - 0006-8950

VL - 124

SP - 1803

EP - 1812

JO - Brain

JF - Brain

IS - 9

ER -

Short-term brain volume change in relapsing-remitting multiple sclerosis: Effect of glatiramer acetate and implications

Abstract

Keywords

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