Contributions
Abstract: P993
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Natural course
Background: Brain atrophy is a well accepted marker of disease severity with association to clinical disability in multiple sclerosis (MS). It is unclear to which extent physiological effects, i.e. an association with age, may outweigh disease-related effects on functional performance, especially in patients with mild disability.
Objective: To explore how functional performance in gait, upper extremities and cognition is associated with brain atrophy in patients with expanded disability status scale (EDSS) score ≤3, controlling for effects of age and sex.
Methods: We analyzed 86 patients with clinically isolated syndrome or MS (CIS/MS) with an EDSS ≤3 and 63 healthy controls (HC). 3T MRI were analyzed for T2 lesion count (T2C), volume (T2V) and overall and substructure brain volumes (FSL SIENAX and FIRST normalized brain volume (NBV), grey matter volume (NGMV), white matter volume (NWMV), thalamic volume (NThalV)). Functional performance was measured with short distance maximum walking speed (SMSW speed), 9-hole peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models were created for functional variables with stepwise inclusion of age, sex and MR imaging markers.
Results: CIS/MS differed from HC in NThalV (t=-2.2, p=0.03, 2.74% difference), T2C and T2V, but not in other substructure brain volumes. A strong association with age was seen in various volumetric measures in CIS/MS and HC: NBV (r=-0.6, p< 0.0001; r=-0.5, p< 0.0001), NGMV (r=-0.7, p< 0.0001; r=-0.6, p< 0.0001), NThalV (r=-0.5, p< 0.0001; r=-0.3, p=0.02). No effect of age was seen on NWMV. Correlations of functional performance with age in CIS/MS were seen for SMSW speed (r=-0.24, p=0.03), 9HPT (r=-0.42, p< 0.0001) and SDMT (r=-0.25, p=0.02). Regression analyses yielded significant models only for 9HPT. These included NBV, NGMV, NThalV, Age and sex as predictors. In one model predicting 9HPT (R2=0.30, p< 1e-04), NThalV had a standardized beta of 0.36, which was higher than for age and sex taken together.
Conclusion: Thalamic atrophy was a stronger predictor of hand function (9HPT) in CIS/MS patients with EDSS ≤3, than age and sex taken together. This underlines the clinical relevance of thalamic atrophy and the relevance of hand function as a clinical marker even in mildly disabled patients. In contrast, when using other compartmental brain atrophy as predictor of performance in gait, hand and cognitive function, age and sex effects outweighed disease-related effects.
Disclosure: Ludwig Rasche: nothing to disclose. Michael Scheel: nothing to disclose. Karen Otte is a shareholder of Motognosis and named as inventor on patent applications describing perceptive visual computing for tracking of motor dysfunction. Patrik Althoff: nothing to disclose. Annemieke Van Vuuren: nothing to disclose. Rene M. Gieß: nothing to disclose. Judith Bellmann-Strobl received speaking fees and travel grants from Bayer Healthcare, sanofi-aventis/Genzyme, Biogen and Teva Pharmaceuticals, unrelated to the present scientific work. Klemens Ruprecht was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis. Friedemann Paul reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to this work. Alexander U. Brandt is founder and holds shares of Motognosis and nocturne - oct. He is named as inventor on several patent applications describing serum biomarkers for MS, perceptive visual computing for tracking of motor dysfunction and OCT image analysis. Tanja Schmitz-Hübsch received research grants from Ipsen Pharma and speaker honoraria from Rölke pharma, all unrelated to this work.
Abstract: P993
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Natural course
Background: Brain atrophy is a well accepted marker of disease severity with association to clinical disability in multiple sclerosis (MS). It is unclear to which extent physiological effects, i.e. an association with age, may outweigh disease-related effects on functional performance, especially in patients with mild disability.
Objective: To explore how functional performance in gait, upper extremities and cognition is associated with brain atrophy in patients with expanded disability status scale (EDSS) score ≤3, controlling for effects of age and sex.
Methods: We analyzed 86 patients with clinically isolated syndrome or MS (CIS/MS) with an EDSS ≤3 and 63 healthy controls (HC). 3T MRI were analyzed for T2 lesion count (T2C), volume (T2V) and overall and substructure brain volumes (FSL SIENAX and FIRST normalized brain volume (NBV), grey matter volume (NGMV), white matter volume (NWMV), thalamic volume (NThalV)). Functional performance was measured with short distance maximum walking speed (SMSW speed), 9-hole peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models were created for functional variables with stepwise inclusion of age, sex and MR imaging markers.
Results: CIS/MS differed from HC in NThalV (t=-2.2, p=0.03, 2.74% difference), T2C and T2V, but not in other substructure brain volumes. A strong association with age was seen in various volumetric measures in CIS/MS and HC: NBV (r=-0.6, p< 0.0001; r=-0.5, p< 0.0001), NGMV (r=-0.7, p< 0.0001; r=-0.6, p< 0.0001), NThalV (r=-0.5, p< 0.0001; r=-0.3, p=0.02). No effect of age was seen on NWMV. Correlations of functional performance with age in CIS/MS were seen for SMSW speed (r=-0.24, p=0.03), 9HPT (r=-0.42, p< 0.0001) and SDMT (r=-0.25, p=0.02). Regression analyses yielded significant models only for 9HPT. These included NBV, NGMV, NThalV, Age and sex as predictors. In one model predicting 9HPT (R2=0.30, p< 1e-04), NThalV had a standardized beta of 0.36, which was higher than for age and sex taken together.
Conclusion: Thalamic atrophy was a stronger predictor of hand function (9HPT) in CIS/MS patients with EDSS ≤3, than age and sex taken together. This underlines the clinical relevance of thalamic atrophy and the relevance of hand function as a clinical marker even in mildly disabled patients. In contrast, when using other compartmental brain atrophy as predictor of performance in gait, hand and cognitive function, age and sex effects outweighed disease-related effects.
Disclosure: Ludwig Rasche: nothing to disclose. Michael Scheel: nothing to disclose. Karen Otte is a shareholder of Motognosis and named as inventor on patent applications describing perceptive visual computing for tracking of motor dysfunction. Patrik Althoff: nothing to disclose. Annemieke Van Vuuren: nothing to disclose. Rene M. Gieß: nothing to disclose. Judith Bellmann-Strobl received speaking fees and travel grants from Bayer Healthcare, sanofi-aventis/Genzyme, Biogen and Teva Pharmaceuticals, unrelated to the present scientific work. Klemens Ruprecht was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis. Friedemann Paul reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to this work. Alexander U. Brandt is founder and holds shares of Motognosis and nocturne - oct. He is named as inventor on several patent applications describing serum biomarkers for MS, perceptive visual computing for tracking of motor dysfunction and OCT image analysis. Tanja Schmitz-Hübsch received research grants from Ipsen Pharma and speaker honoraria from Rölke pharma, all unrelated to this work.