Contributions
Abstract: EP1553
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Overall intracranial volume (ICV), which in part reflects maximal lifetime brain growth (MLBG), has been reported to be decreased in pediatric multiple sclerosis (MS) patients in comparison to age- and sex-matched healthy controls (HCs), suggesting that the pediatric-onset MS may affect primary brain and skull development. In adults, MS clinical symptom-onset typically occurs between the ages of 20-30; however, the majority of patients already have evidence of brain atrophy on MRI at diagnosis, suggesting that biological disease onset started at an earlier timepoint. We previously demonstrated that head circumference (as a surrogate of ICV) was decreased in adult-onset MS patients vs. HCs. To our knowledge, ICV, as an assessment of MLBG, has not been compared between adult-onset MS patients and HCs.
Objective: To compare ICV (as an assessment of MLBG) in MS patients with disease onset in adulthood vs. HCs.
Methods: MRI measures, including ICV and brain parenchymal fraction (BPF), were assessed in 106 MS patients and 112 HCs balanced for age and sex using Voxel-based Morphometry 8 (VBM8) toolbox for SPM8. Student's t-tests compared ICV in MS vs. HCs. Multivariable linear regression was performed to compare ICV in MS vs. HCs while controlling for potentially confounding covariates of age and sex.
Results: MS patients were a mean age of 43 years, 69% female, and had a mean age at clinical diagnosis of 32 years. HCs were a mean age of 45 years, and 63% female. Mean ICV was lower in MS (1395.66±14.67 mm3) vs. HCs (1426.52±14.98 mm3); but this result did not reach statistical significance (p=0.14). In MS patients with earlier clinical disease onset (≤ 40 years; n=79), mean ICV (1387.33±16.73 mm3) was even lower, with a trend towards significance (p= 0.08), particularly when controlling for potentially confounding variates of age and sex (p=0.05). As expected, there was also clear evidence of brain atrophy in MS vs. HCs as measured by BPF (0.816±0.002 vs. 0.834±0.001; p< 0.001).
Conclusion: MS patients with clinical disease-onset in adulthood show trends towards having smaller ICVs in comparison to HCs, particularly when clinical symptom onset is before the age of 40. If confirmed in larger cohorts, these findings suggest that even when MS clinically manifests in adulthood, pathologic processes affecting MLBG may begin during periods of brain and skull growth in childhood or early adolescence, which is substantially earlier than expected.
Disclosure:
Dr. Suradech Suthiiphosuwan has received fellowship funding from Sanofi-Genzyme.
Ikreet Cheema has nothing to disclose.
Dr. Courtney Casserly has received fellowship educational support from Biogen-Idec, and personal compensation for consulting from EMD-Serono, Genzyme, and Novartis.
Stephanie Sankar has nothing to disclose.
Dr. General Leung received research support from Canadian institute of health research, the national science and engineering research council, the St Michael´s Hospital Foundation and is an equity holder in Innovere Medical and MIMOSA Diagnostics Inc.
Dr. Aditya Bharatha has received personal compensation for speaking or consulting from EMD-Serono, Genzyme, and Novartis.
Dr. Amit Bar-Or has declared receipt of honoraria or consultation fees from Amplimmune, Bayhill Therapeutics, Berlex.Bayer, Biogen Idec, Diogenix, Eli-Lilly, Genentech, GlaxoSmithKlein, Guthy-Jackson/GGF, Merck/EMD Serono, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi-Genzyme, Teva Neuroscience, Wyeth.
Dr. Jiwon Oh has received grant funding from the MS Society of Canada, the National MS Society, Sanofi-Genzyme, and Biogen-Idec and has received personal compensation for consulting or speaking from Biogen-Idec, EMD-Serono, Sanofi-Genzyme, Novartis, Roche, and Teva.
Abstract: EP1553
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Overall intracranial volume (ICV), which in part reflects maximal lifetime brain growth (MLBG), has been reported to be decreased in pediatric multiple sclerosis (MS) patients in comparison to age- and sex-matched healthy controls (HCs), suggesting that the pediatric-onset MS may affect primary brain and skull development. In adults, MS clinical symptom-onset typically occurs between the ages of 20-30; however, the majority of patients already have evidence of brain atrophy on MRI at diagnosis, suggesting that biological disease onset started at an earlier timepoint. We previously demonstrated that head circumference (as a surrogate of ICV) was decreased in adult-onset MS patients vs. HCs. To our knowledge, ICV, as an assessment of MLBG, has not been compared between adult-onset MS patients and HCs.
Objective: To compare ICV (as an assessment of MLBG) in MS patients with disease onset in adulthood vs. HCs.
Methods: MRI measures, including ICV and brain parenchymal fraction (BPF), were assessed in 106 MS patients and 112 HCs balanced for age and sex using Voxel-based Morphometry 8 (VBM8) toolbox for SPM8. Student's t-tests compared ICV in MS vs. HCs. Multivariable linear regression was performed to compare ICV in MS vs. HCs while controlling for potentially confounding covariates of age and sex.
Results: MS patients were a mean age of 43 years, 69% female, and had a mean age at clinical diagnosis of 32 years. HCs were a mean age of 45 years, and 63% female. Mean ICV was lower in MS (1395.66±14.67 mm3) vs. HCs (1426.52±14.98 mm3); but this result did not reach statistical significance (p=0.14). In MS patients with earlier clinical disease onset (≤ 40 years; n=79), mean ICV (1387.33±16.73 mm3) was even lower, with a trend towards significance (p= 0.08), particularly when controlling for potentially confounding variates of age and sex (p=0.05). As expected, there was also clear evidence of brain atrophy in MS vs. HCs as measured by BPF (0.816±0.002 vs. 0.834±0.001; p< 0.001).
Conclusion: MS patients with clinical disease-onset in adulthood show trends towards having smaller ICVs in comparison to HCs, particularly when clinical symptom onset is before the age of 40. If confirmed in larger cohorts, these findings suggest that even when MS clinically manifests in adulthood, pathologic processes affecting MLBG may begin during periods of brain and skull growth in childhood or early adolescence, which is substantially earlier than expected.
Disclosure:
Dr. Suradech Suthiiphosuwan has received fellowship funding from Sanofi-Genzyme.
Ikreet Cheema has nothing to disclose.
Dr. Courtney Casserly has received fellowship educational support from Biogen-Idec, and personal compensation for consulting from EMD-Serono, Genzyme, and Novartis.
Stephanie Sankar has nothing to disclose.
Dr. General Leung received research support from Canadian institute of health research, the national science and engineering research council, the St Michael´s Hospital Foundation and is an equity holder in Innovere Medical and MIMOSA Diagnostics Inc.
Dr. Aditya Bharatha has received personal compensation for speaking or consulting from EMD-Serono, Genzyme, and Novartis.
Dr. Amit Bar-Or has declared receipt of honoraria or consultation fees from Amplimmune, Bayhill Therapeutics, Berlex.Bayer, Biogen Idec, Diogenix, Eli-Lilly, Genentech, GlaxoSmithKlein, Guthy-Jackson/GGF, Merck/EMD Serono, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi-Genzyme, Teva Neuroscience, Wyeth.
Dr. Jiwon Oh has received grant funding from the MS Society of Canada, the National MS Society, Sanofi-Genzyme, and Biogen-Idec and has received personal compensation for consulting or speaking from Biogen-Idec, EMD-Serono, Sanofi-Genzyme, Novartis, Roche, and Teva.