Project description:Multiple sclerosis is the most common autoimmune disease of the central nervous system. Studying whole blood RNA from a cohort of 195 MS patients and 66 healthy controls, we identified gene expression signatures for interferon treatment and disease status by microarray analysis. Blood was collected at multiple time points (up to 3 for patients, 2 for controls). Patients were either untreated or treated with Interferon. In total, 626 Affymetrix exon arrays were analyzed, split into discovery and replication data sets. This metadata file contains information on all samples processed in the discovery data set (n=318) when we compared gene expression in untreated MS patients (n=62) to IFN treated patients (n=58). Overall design: The following comparisons were made: untreated MS vs Controls (discovery and replication), untreated vs Interferon treated MS (discovery and replication). For each comparison, respective arrays were processed (background corrected and normalized) together, but seperate from other comparisons. The two time points for controls were averaged. For the first comparison, we report differentially expressed genes at an FDR cutoff of 0.1 at any of the three tested time points in MS patients in the discovery data set. For the second comparison, the FDR cutoff was 0.001. The respective genes were validated in the replication data set when they passed a nominal p-value cutoff of 0.05 at any of the three tested time points.
Project description:Multiple sclerosis is the most common autoimmune disease of the central nervous system. Studying whole blood RNA from a cohort of 195 MS patients and 66 healthy controls, we identified gene expression signatures for interferon treatment and disease status by microarray analysis. Blood was collected at multiple time points (up to 3 for patients, 2 for controls). Patients were either untreated or treated with Interferon. In total, 626 Affymetrix exon arrays were analyzed, split into discovery and replication data sets. This metadata file contains information on all samples processed in the replication data set (n=102) when we compared gene expression in untreated MS patients (n=27) to healthy controls (n=25). The following comparisons were made: untreated MS vs Controls (discovery and replication), untreated vs Interferon treated MS (discovery and replication). For each comparison, respective arrays were processed (background corrected and normalized) together, but seperate from other comparisons. The two time points for controls were averaged. For the first comparison, we report differentially expressed genes at an FDR cutoff of 0.1 at any of the three tested time points in MS patients in the discovery data set. For the second comparison, the FDR cutoff was 0.001. The respective genes were validated in the replication data set when they passed a nominal p-value cutoff of 0.05 at any of the three tested time points.
Project description:Multiple sclerosis is the most common autoimmune disease of the central nervous system. Studying whole blood RNA from a cohort of 195 MS patients and 66 healthy controls, we identified gene expression signatures for interferon treatment and disease status by microarray analysis. Blood was collected at multiple time points (up to 3 for patients, 2 for controls). Patients were either untreated or treated with Interferon. In total, 626 Affymetrix exon arrays were analyzed, split into discovery and replication data sets. This metadata file contains information on all samples processed in the replication data set (n=183) when we compared gene expression in untreated MS patients (n=27) to IFN treated patients (n=48). The following comparisons were made: untreated MS vs Controls (discovery and replication), untreated vs Interferon treated MS (discovery and replication). For each comparison, respective arrays were processed (background corrected and normalized) together, but seperate from other comparisons. The two time points for controls were averaged. For the first comparison, we report differentially expressed genes at an FDR cutoff of 0.1 at any of the three tested time points in MS patients in the discovery data set. For the second comparison, the FDR cutoff was 0.001. The respective genes were validated in the replication data set when they passed a nominal p-value cutoff of 0.05 at any of the three tested time points.
Project description:Multiple sclerosis is the most common autoimmune disease of the central nervous system. Studying whole blood RNA from a cohort of 195 MS patients and 66 healthy controls, we identified gene expression signatures for interferon treatment and disease status by microarray analysis. Blood was collected at multiple time points (up to 3 for patients, 2 for controls). Patients were either untreated or treated with Interferon. In total, 626 Affymetrix exon arrays were analyzed, split into discovery and replication data sets. This metadata file contains information on all samples processed in the discovery data set (n=212) when we compared gene expression in untreated MS patients (n=62) to healthy controls (n=41). The following comparisons were made: untreated MS vs Controls (discovery and replication), untreated vs Interferon treated MS (discovery and replication). For each comparison, respective arrays were processed (background corrected and normalized) together, but seperate from other comparisons. The two time points for controls were averaged. For the first comparison, we report differentially expressed genes at an FDR cutoff of 0.1 at any of the three tested time points in MS patients in the discovery data set. For the second comparison, the FDR cutoff was 0.001. The respective genes were validated in the replication data set when they passed a nominal p-value cutoff of 0.05 at any of the three tested time points.
Project description:Multiple sclerosis is the most common autoimmune disease of the central nervous system. Studying whole blood RNA from a cohort of 195 MS patients and 66 healthy controls, we identified gene expression signatures for interferon treatment and disease status by microarray analysis. Blood was collected at multiple time points (up to 3 for patients, 2 for controls). Patients were either untreated or treated with Interferon. In total, 626 Affymetrix exon arrays were analyzed, split into discovery and replication data sets. This metadata file contains information on all samples processed in the discovery data set (n=318) when we compared gene expression in untreated MS patients (n=62) to IFN treated patients (n=58). The following comparisons were made: untreated MS vs Controls (discovery and replication), untreated vs Interferon treated MS (discovery and replication). For each comparison, respective arrays were processed (background corrected and normalized) together, but seperate from other comparisons. The two time points for controls were averaged. For the first comparison, we report differentially expressed genes at an FDR cutoff of 0.1 at any of the three tested time points in MS patients in the discovery data set. For the second comparison, the FDR cutoff was 0.001. The respective genes were validated in the replication data set when they passed a nominal p-value cutoff of 0.05 at any of the three tested time points.
Project description:In multiple sclerosis, pathological changes of both tissue iron and myelin occur, yet these factors have not been characterized in a longitudinal fashion using the novel iron- and myelin-sensitive quantitative susceptibility mapping (QSM) MRI technique. We investigated disease-relevant tissue changes associated with myelin loss and iron accumulation in multiple sclerosis deep gray matter (DGM) over two years. One-hundred twenty (120) multiple sclerosis patients and 40 age- and sex-matched healthy controls were included in this prospective study. Written informed consent and local IRB approval were obtained from all participants. Clinical testing and QSM were performed both at baseline and at follow-up. Brain magnetic susceptibility was measured in major DGM structures. Temporal (baseline vs. follow-up) and cross-sectional (multiple sclerosis vs. controls) differences were studied using mixed factorial ANOVA analysis and appropriate t-tests. At either time-point, multiple sclerosis patients had significantly higher susceptibility in the caudate and globus pallidus and lower susceptibility in the thalamus. Over two years, susceptibility increased significantly in the caudate of both controls and multiple sclerosis patients. Inverse thalamic findings among MS patients suggest a multi-phase pathology explained by simultaneous myelin loss and/or iron accumulation followed by iron depletion and/or calcium deposition at later stages.
Project description:Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.