Contributions
Abstract: P1109
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Neurodegeneration is an essential and devastating part of the pathophysiology of multiple sclerosis (MS), occurring already during the early stages of MS. The ability to measure and determine the degree of neurodegeneration could provide tools for diagnostics and characterization of patients.
Objective: To determine the diagnostic value of degenerative biomarkers in patients with recent onset of suspect MS and evaluate these biomarkers for characterizing phenotypes of MS.
Methods: In a prospective study at the MS Center of Sahlgrenska University Hospital, Gothenburg, Sweden, we included 276 patients with clinical features of suspect MS onset. After diagnostic investigation the patients were categorized: clinically isolated syndrome (CIS)/early relapsing MS (n=100), relapsing MS with disease duration of 2 years or more (n=80), and non-MS/symptomatic controls (SC; n=96). In addition we included healthy controls (HC; n=51) and progressive MS (PrMS; n=23) as control subjects. We used ELISA for analyzing CSF concentrations of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP). Synthetic MRI (SyMRI) was used for automatic quantification of brain parenchymal fraction (BPF), and white and grey matter volumes.
Results: All phenotypes of MS had increased NFL (CIS/early MS 92.3%, MS>2 years 85%, PrMS 72.7%) compared to HC and SC. The NFL levels were within the normal range in all HC and SC. PrMS had higher GFAP compared with HC, SC and CIS/relapsing MS (p< 0.001). There was no difference in levels of GFAP between CIS/relapsing MS, HC and SC. Reduced BPF was found in relapsing MS with longer disease duration and PrMS, compared to HC and compared to CIS/early relapsing MS. There was no difference in BPF between HC, SC, and CIS/early relapsing MS. White matter and grey matter volumes were not significantly different between the different MS phenotypes.
Conclusion: In clinically suspected MS, NFL had diagnostic value but not GFAP or BPF. NFL may therefore be included in the diagnostic work-up of MS. Increased GFAP was associated with PrMS but not with other phenotypes of MS. Lower BPF, indicating increased brain atrophy and degeneration was associated with longer disease duration. However, BPF could not distinguish between HC, SP and CIS/early MS, suggesting that neurodegeneration had not reached a significant magnitude in patients with recent clinical onset of CIS/early MS or SyMRI was unable to detect brain atrophy of low rate.
Disclosure: LN has no disclosures.
HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg and has served at advisory boards for Roche Diagnostics, Eli Lilly and Pharmasum Therapeuticss.
MA has received compensation for lectures and/or advisory boards from Biogen, Genzyme, and Novartis.
CM has received honoraria for lectures and advisory boards from Biogen and Novartis.
JL has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva.
Abstract: P1109
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Neurodegeneration is an essential and devastating part of the pathophysiology of multiple sclerosis (MS), occurring already during the early stages of MS. The ability to measure and determine the degree of neurodegeneration could provide tools for diagnostics and characterization of patients.
Objective: To determine the diagnostic value of degenerative biomarkers in patients with recent onset of suspect MS and evaluate these biomarkers for characterizing phenotypes of MS.
Methods: In a prospective study at the MS Center of Sahlgrenska University Hospital, Gothenburg, Sweden, we included 276 patients with clinical features of suspect MS onset. After diagnostic investigation the patients were categorized: clinically isolated syndrome (CIS)/early relapsing MS (n=100), relapsing MS with disease duration of 2 years or more (n=80), and non-MS/symptomatic controls (SC; n=96). In addition we included healthy controls (HC; n=51) and progressive MS (PrMS; n=23) as control subjects. We used ELISA for analyzing CSF concentrations of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP). Synthetic MRI (SyMRI) was used for automatic quantification of brain parenchymal fraction (BPF), and white and grey matter volumes.
Results: All phenotypes of MS had increased NFL (CIS/early MS 92.3%, MS>2 years 85%, PrMS 72.7%) compared to HC and SC. The NFL levels were within the normal range in all HC and SC. PrMS had higher GFAP compared with HC, SC and CIS/relapsing MS (p< 0.001). There was no difference in levels of GFAP between CIS/relapsing MS, HC and SC. Reduced BPF was found in relapsing MS with longer disease duration and PrMS, compared to HC and compared to CIS/early relapsing MS. There was no difference in BPF between HC, SC, and CIS/early relapsing MS. White matter and grey matter volumes were not significantly different between the different MS phenotypes.
Conclusion: In clinically suspected MS, NFL had diagnostic value but not GFAP or BPF. NFL may therefore be included in the diagnostic work-up of MS. Increased GFAP was associated with PrMS but not with other phenotypes of MS. Lower BPF, indicating increased brain atrophy and degeneration was associated with longer disease duration. However, BPF could not distinguish between HC, SP and CIS/early MS, suggesting that neurodegeneration had not reached a significant magnitude in patients with recent clinical onset of CIS/early MS or SyMRI was unable to detect brain atrophy of low rate.
Disclosure: LN has no disclosures.
HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg and has served at advisory boards for Roche Diagnostics, Eli Lilly and Pharmasum Therapeuticss.
MA has received compensation for lectures and/or advisory boards from Biogen, Genzyme, and Novartis.
CM has received honoraria for lectures and advisory boards from Biogen and Novartis.
JL has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva.