Contributions
Abstract: P507
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background and goals: In multiple sclerosis (MS), tissue abnormality - as assessed using magnetisation transfer ratio (MTR) - increases close to the lateral ventricles. We aimed to determine whether or not they:
i) are present from the earliest clinical stages of MS;
ii) occur independently of white matter lesions;
iii) are associated with conversion to clinically definite MS and disability following a clinically isolated syndrome.
Methods: Seventy-one people had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (ON, 49 females, mean age 33.5 years) and were followed up clinically two and five years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter (NAWM), MTR gradients were measured 1-5mm and 6-10mm from the lateral ventricles.
Results: The MTR gradient over 1-5mm differed significantly between the ON and control groups (+0.059 percentage units/mm (pu/mm) vs -0.033 pu/mm, p=0.010). The MTR gradient was not significantly affected by the presence of brain lesions (T2 lesions (p=0.918), periventricular T2 lesions (p=0.580) or gadolinium-enhancing T1 lesions (p=0.724)). It was significantly steeper in those developing clinically definite MS within two years compared to those who did not (0.132 pu/mm vs 0.016 pu/mm, p=0.020). In multivariate binary logistic regression the MTR gradient was independently associated with the development of clinically definite MS within two years (MTR gradient odds ratio (OR) 61.708, p=0.023; presence of T2 lesions OR 8.500, p=0.071). At five years, lesional measures overtook MTR gradients as significant predictors of conversion to MS. The MTR gradient also correlated with Expanded Disability Status Scale (EDSS) score five years later (Spearman r=0.313, p=0.027).
Conclusions: A gradient in periventricular MTR abnormality occurs early in MS, is at least partly independent of lesion formation, and is associated with the development of MS and disability following a clinically isolated syndrome.
Disclosure:
Funding: The Queen Square MS centre is supported by the MS Society of Great Britain and Northern Ireland. J.W.L.B is funded through a Next Generation Fellowship funded by the Grant Charity of the Freemason"s. M.P. is supported by the non-profit Karol Wojtila Association (Lavagna, Italy).
Potential conflicts of interest:
J.W.L.B is in funded through a Next Generation Fellowship funded by the
Grant Charity of the Freemason"s and has received travel expenses from Novartis, Sanofi-Genzyme and Biogen-Idec. M.P. is supported by the non-profit Karol
Wojtila Association (Lavagna, Italy) and has received research support from
Novartis. R.S. has nothing to disclose. C.G.W-K. was on the advisory board for
BG12 (Biogen) and is editor of Functional Neurology. D.H.M has received
honoraria from Biogen Idec, Novartis, GlaxoSmithKline, and Bayer Schering,
and research grant support for undertaking MRI analysis in multiple sclerosis
trials sponsored by GlaxoSmithKline, Biogen Idec and Novartis. D.T.C. has
received honoraria (paid to his employer) from Ismar Healthcare NV, Swiss
MS Society, Excemed (previously Serono Symposia International
Foundation), Merck, Bayer and Teva for faculty-led education work; Teva for
advisory board work; meeting expenses from Merck, Teva, Novartis, the MS
Trust and National MS Society; and has previously held stock in
GlaxoSmithKline.
Abstract: P507
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background and goals: In multiple sclerosis (MS), tissue abnormality - as assessed using magnetisation transfer ratio (MTR) - increases close to the lateral ventricles. We aimed to determine whether or not they:
i) are present from the earliest clinical stages of MS;
ii) occur independently of white matter lesions;
iii) are associated with conversion to clinically definite MS and disability following a clinically isolated syndrome.
Methods: Seventy-one people had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (ON, 49 females, mean age 33.5 years) and were followed up clinically two and five years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter (NAWM), MTR gradients were measured 1-5mm and 6-10mm from the lateral ventricles.
Results: The MTR gradient over 1-5mm differed significantly between the ON and control groups (+0.059 percentage units/mm (pu/mm) vs -0.033 pu/mm, p=0.010). The MTR gradient was not significantly affected by the presence of brain lesions (T2 lesions (p=0.918), periventricular T2 lesions (p=0.580) or gadolinium-enhancing T1 lesions (p=0.724)). It was significantly steeper in those developing clinically definite MS within two years compared to those who did not (0.132 pu/mm vs 0.016 pu/mm, p=0.020). In multivariate binary logistic regression the MTR gradient was independently associated with the development of clinically definite MS within two years (MTR gradient odds ratio (OR) 61.708, p=0.023; presence of T2 lesions OR 8.500, p=0.071). At five years, lesional measures overtook MTR gradients as significant predictors of conversion to MS. The MTR gradient also correlated with Expanded Disability Status Scale (EDSS) score five years later (Spearman r=0.313, p=0.027).
Conclusions: A gradient in periventricular MTR abnormality occurs early in MS, is at least partly independent of lesion formation, and is associated with the development of MS and disability following a clinically isolated syndrome.
Disclosure:
Funding: The Queen Square MS centre is supported by the MS Society of Great Britain and Northern Ireland. J.W.L.B is funded through a Next Generation Fellowship funded by the Grant Charity of the Freemason"s. M.P. is supported by the non-profit Karol Wojtila Association (Lavagna, Italy).
Potential conflicts of interest:
J.W.L.B is in funded through a Next Generation Fellowship funded by the
Grant Charity of the Freemason"s and has received travel expenses from Novartis, Sanofi-Genzyme and Biogen-Idec. M.P. is supported by the non-profit Karol
Wojtila Association (Lavagna, Italy) and has received research support from
Novartis. R.S. has nothing to disclose. C.G.W-K. was on the advisory board for
BG12 (Biogen) and is editor of Functional Neurology. D.H.M has received
honoraria from Biogen Idec, Novartis, GlaxoSmithKline, and Bayer Schering,
and research grant support for undertaking MRI analysis in multiple sclerosis
trials sponsored by GlaxoSmithKline, Biogen Idec and Novartis. D.T.C. has
received honoraria (paid to his employer) from Ismar Healthcare NV, Swiss
MS Society, Excemed (previously Serono Symposia International
Foundation), Merck, Bayer and Teva for faculty-led education work; Teva for
advisory board work; meeting expenses from Merck, Teva, Novartis, the MS
Trust and National MS Society; and has previously held stock in
GlaxoSmithKline.