Contributions
Abstract: P551
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - OCT
Background: In multiple sclerosis (MS) patients, retinal nerve fibre layer (RNFL) thinning as measured by optical coherence tomography (OCT) has been shown to reflect global brain atrophy on MRI, as well as grey matter and white matter volume changes. We previously reported the first cohort of relapsing-remitting MS (RRMS) patients to demonstrate a measurable improvement in RNFL thickness over 2-years during alemtuzumab treatment. Further analyses were undertaken to investigate the hypothesis that the neuroprotective effects seen on OCT will also be present on MRI.
Objectives: To measure the correlations between changes in RNFL thickness over 2 years with whole brain volume, cortical thickness and total N-acetylaspartate (tNAA) in RRMS patients treated with alemtuzumab.
Methods: 26 RRMS subjects at a single centre were treated with 2 courses of alemtuzumab in a prospective open-label study. The Heidelberg Spectralis SD-OCT was used to obtain the RNFL thickness at baseline and 6-monthly intervals to 2 years. Subjects were imaged with 1mm isotropic 3D T1-weighted spoiled gradient echo (SPGR) sequence and magnetic resonance spectroscopy (MRS) annually. Normalised brain volume (brain parenchymal fraction, BPF) and percentage brain volume change (PBVC) were measured with in-house segmentation-based and registration-based methods, respectively. Other MRI measurements included cortical thickness and concentrations of tNAA measured in a single large (~53ml) voxel of predominantly normal-appearing white matter (NAWM) placed above the ventricles. Spearman rank correlations assessed the association between change in RNFL over 2 years with month 24 MRI values, as well as change in RNFL with change in MRI measurements over 2 years.
Results: There were significant positive correlations between change in RNFL over 2 years with BPF at month 24 (r=0.457, p=0.033); and between change in RNFL with PBVC over 2 years (r=0.520, p=0.016). No significant correlations were seen between change in RNFL and cortical thickness.
A strong positive correlation was seen between change in RNFL and tNAA at month 24
(r=0.684, p< 0.001).
Conclusions: Associations were found between RNFL and two different measures of whole brain volume in our RRMS cohort treated with alemtuzumab over a 2-year period. In addition, the strong correlation between RNFL and tNAA but not cortical thickness may reflect a preferential effect on white matter over grey matter post alemtuzumab.
Disclosure:
AN: grant support from Novartis for fellowship; consulting for EMD Serono.
SHK: personal compensation for advisory board participation from Genzyme, Roche, Vertex Pharmaceuticals; research support from Genzyme, Roche.
APL: nothing to disclose.
RT: nothing to disclose.
AR: nothing to disclose.
IMV: nothing to disclose.
RW: nothing to disclose.
RC: speaking fees for unbranded lectures from Biogen, Genzyme, Novartis, Teva; consulting for EMD Serono, Genzyme; PI on clinical trials with MedImmune, Seattle Genetics, Guthy Jackson.
ALM: consulting for Vertex Pharmaceuticals.
DKBL: research funding from Canadian Institute of Health Research and MS Society of Canada; consulting for Vertex Pharmaceuticals; served on Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Novartis and Roche; given lectures supported by non-restricted education grants from Novartis and Biogen; Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis; the UBC MS/MRI Research Group has received grant support from Genzyme, EMD Serono, Novartis and Roche.
AJ: employee of Genzyme.
AT: consulting for Novartis, Genzyme, Roche; PI on clinical trials with Biogen, Genzyme, Roche, Chugai.
Source of funding: Sanofi Genzyme.
Abstract: P551
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - OCT
Background: In multiple sclerosis (MS) patients, retinal nerve fibre layer (RNFL) thinning as measured by optical coherence tomography (OCT) has been shown to reflect global brain atrophy on MRI, as well as grey matter and white matter volume changes. We previously reported the first cohort of relapsing-remitting MS (RRMS) patients to demonstrate a measurable improvement in RNFL thickness over 2-years during alemtuzumab treatment. Further analyses were undertaken to investigate the hypothesis that the neuroprotective effects seen on OCT will also be present on MRI.
Objectives: To measure the correlations between changes in RNFL thickness over 2 years with whole brain volume, cortical thickness and total N-acetylaspartate (tNAA) in RRMS patients treated with alemtuzumab.
Methods: 26 RRMS subjects at a single centre were treated with 2 courses of alemtuzumab in a prospective open-label study. The Heidelberg Spectralis SD-OCT was used to obtain the RNFL thickness at baseline and 6-monthly intervals to 2 years. Subjects were imaged with 1mm isotropic 3D T1-weighted spoiled gradient echo (SPGR) sequence and magnetic resonance spectroscopy (MRS) annually. Normalised brain volume (brain parenchymal fraction, BPF) and percentage brain volume change (PBVC) were measured with in-house segmentation-based and registration-based methods, respectively. Other MRI measurements included cortical thickness and concentrations of tNAA measured in a single large (~53ml) voxel of predominantly normal-appearing white matter (NAWM) placed above the ventricles. Spearman rank correlations assessed the association between change in RNFL over 2 years with month 24 MRI values, as well as change in RNFL with change in MRI measurements over 2 years.
Results: There were significant positive correlations between change in RNFL over 2 years with BPF at month 24 (r=0.457, p=0.033); and between change in RNFL with PBVC over 2 years (r=0.520, p=0.016). No significant correlations were seen between change in RNFL and cortical thickness.
A strong positive correlation was seen between change in RNFL and tNAA at month 24
(r=0.684, p< 0.001).
Conclusions: Associations were found between RNFL and two different measures of whole brain volume in our RRMS cohort treated with alemtuzumab over a 2-year period. In addition, the strong correlation between RNFL and tNAA but not cortical thickness may reflect a preferential effect on white matter over grey matter post alemtuzumab.
Disclosure:
AN: grant support from Novartis for fellowship; consulting for EMD Serono.
SHK: personal compensation for advisory board participation from Genzyme, Roche, Vertex Pharmaceuticals; research support from Genzyme, Roche.
APL: nothing to disclose.
RT: nothing to disclose.
AR: nothing to disclose.
IMV: nothing to disclose.
RW: nothing to disclose.
RC: speaking fees for unbranded lectures from Biogen, Genzyme, Novartis, Teva; consulting for EMD Serono, Genzyme; PI on clinical trials with MedImmune, Seattle Genetics, Guthy Jackson.
ALM: consulting for Vertex Pharmaceuticals.
DKBL: research funding from Canadian Institute of Health Research and MS Society of Canada; consulting for Vertex Pharmaceuticals; served on Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Novartis and Roche; given lectures supported by non-restricted education grants from Novartis and Biogen; Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis; the UBC MS/MRI Research Group has received grant support from Genzyme, EMD Serono, Novartis and Roche.
AJ: employee of Genzyme.
AT: consulting for Novartis, Genzyme, Roche; PI on clinical trials with Biogen, Genzyme, Roche, Chugai.
Source of funding: Sanofi Genzyme.