Contributions
Abstract: EP1514
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Alterations in reward mechanisms have been associated with fatigue in patients with multiple sclerosis (MS). However structural integrity of the mesocorticolimbic reward pathway has not been investigated.
Objectives: To investigate the association of fatigue with diffusion abnormalities of the superolateral medial forebrain bundle (slMFB) in MS patients.
Methods: Patient stratification: 1. Sustained Fatigue (SF): latest two Modified Fatigue Impact Scale (MFIS)≥38; 2. Reversible Fatigue (RF): latest MFIS< 38, and at least one previous MFIS≥38; 3. Never Fatigued (NF): MFIS always< 38 (5 assessments minimum). We selected from the CLIMB Study cohort 93 MS patients with relapsing-remitting (82) or secondary-progressive (9) disease type (26SF/25RF/42NF). Disability and depression were assessed using the Expanded Disability Status Scale (EDSS) and Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Cross-sectional 3T diffusion tensor (DT) brain MRI was used to compare fractional anisotropy (FA), axial (AD), mean (MD) and radial diffusivity (RD) of the slMFB between the groups controlling for age+sex+disease duration+EDSS±CES-D. In post-hoc analyses, we (1) investigated the association of DT metrics with CES-D in each group and (2) compared DT metrics between SF patients with high (SFhd, ≥16) versus low (SFld, < 16) depression scores.
Results: CES-D was significantly higher in SF versus RF (p< 0.001) or NF (p< 0.001) patients. No difference was found in slMFB DT metrics between the SF, RF and NF patients. Left slMFB FA (p=0.039), MD (p=0.012) and RD (p=0.013) showed positive correlation with CES-D in SF, but not in RF or NF patients. SFhd (N=14) versus SFld (N=12) patients showed significantly higher MD (p=0.027) and RD (p=0.044) in the left slMFB.
Conclusion: Our results suggest that microstructural changes to the mesocorticolimbic reward pathway may play a role in the comorbid development of fatigue and depression in MS.
Disclosure: Dr. Palotai reports no disclosures.
Ms. Small reports no disclosures.
Dr. Makris reports no disclosures.
Mr. Somes reports no disclosures.
Dr. Morales Pinzon reports no disclosures.
Dr. Healy was on the Biogen Worldwide Medical Biostatistics Multiple Sclerosis Advisory Board and received grant support from Genzyme, Merck Serono, Novartis, and Verily Life Sciences.
Dr. Glanz received research support from Merck Serono and Verily Life Sciences.
Dr. Weiner reports grants from National Institutes of Health, National Multiple Sclerosis Society, Verily Life Sciences, Genentech, Inc., Google Life Sciences, EMD Serono, Inc., Biogen, Teva Pharmaceuticals, and Novartis; grants and consulting from Sanofi US Services, Inc.; consulting and advising from Tilos Therapeutics; consulting and advising from Tiziana Life Sciences; consulting and advising from IM Therapeutics; personal fees, consulting and advising from vTv Therapeutics; personal fees, consulting and advising from MedDay Pharmaceuticals.
Dr. Chitnis has served on the advisory boards for clinical trials sponsored by Novartis and Sanofi-Genzyme, and has received consulting/advisory fees from Bayer, Biogen, Celgene, Genentech-Roche, Novartis and Sanofi-Genzyme. She has received research grant support from Biogen, Octave, Serono and Verily.
Dr. Guttmann has nothing to disclose that could constitute a conflict of interest for this work. Dr. Guttmann has received research funding from Sanofi, the National Multiple Sclerosis Society, and the International Progressive Multiple Sclerosis Alliance.
Abstract: EP1514
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Alterations in reward mechanisms have been associated with fatigue in patients with multiple sclerosis (MS). However structural integrity of the mesocorticolimbic reward pathway has not been investigated.
Objectives: To investigate the association of fatigue with diffusion abnormalities of the superolateral medial forebrain bundle (slMFB) in MS patients.
Methods: Patient stratification: 1. Sustained Fatigue (SF): latest two Modified Fatigue Impact Scale (MFIS)≥38; 2. Reversible Fatigue (RF): latest MFIS< 38, and at least one previous MFIS≥38; 3. Never Fatigued (NF): MFIS always< 38 (5 assessments minimum). We selected from the CLIMB Study cohort 93 MS patients with relapsing-remitting (82) or secondary-progressive (9) disease type (26SF/25RF/42NF). Disability and depression were assessed using the Expanded Disability Status Scale (EDSS) and Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Cross-sectional 3T diffusion tensor (DT) brain MRI was used to compare fractional anisotropy (FA), axial (AD), mean (MD) and radial diffusivity (RD) of the slMFB between the groups controlling for age+sex+disease duration+EDSS±CES-D. In post-hoc analyses, we (1) investigated the association of DT metrics with CES-D in each group and (2) compared DT metrics between SF patients with high (SFhd, ≥16) versus low (SFld, < 16) depression scores.
Results: CES-D was significantly higher in SF versus RF (p< 0.001) or NF (p< 0.001) patients. No difference was found in slMFB DT metrics between the SF, RF and NF patients. Left slMFB FA (p=0.039), MD (p=0.012) and RD (p=0.013) showed positive correlation with CES-D in SF, but not in RF or NF patients. SFhd (N=14) versus SFld (N=12) patients showed significantly higher MD (p=0.027) and RD (p=0.044) in the left slMFB.
Conclusion: Our results suggest that microstructural changes to the mesocorticolimbic reward pathway may play a role in the comorbid development of fatigue and depression in MS.
Disclosure: Dr. Palotai reports no disclosures.
Ms. Small reports no disclosures.
Dr. Makris reports no disclosures.
Mr. Somes reports no disclosures.
Dr. Morales Pinzon reports no disclosures.
Dr. Healy was on the Biogen Worldwide Medical Biostatistics Multiple Sclerosis Advisory Board and received grant support from Genzyme, Merck Serono, Novartis, and Verily Life Sciences.
Dr. Glanz received research support from Merck Serono and Verily Life Sciences.
Dr. Weiner reports grants from National Institutes of Health, National Multiple Sclerosis Society, Verily Life Sciences, Genentech, Inc., Google Life Sciences, EMD Serono, Inc., Biogen, Teva Pharmaceuticals, and Novartis; grants and consulting from Sanofi US Services, Inc.; consulting and advising from Tilos Therapeutics; consulting and advising from Tiziana Life Sciences; consulting and advising from IM Therapeutics; personal fees, consulting and advising from vTv Therapeutics; personal fees, consulting and advising from MedDay Pharmaceuticals.
Dr. Chitnis has served on the advisory boards for clinical trials sponsored by Novartis and Sanofi-Genzyme, and has received consulting/advisory fees from Bayer, Biogen, Celgene, Genentech-Roche, Novartis and Sanofi-Genzyme. She has received research grant support from Biogen, Octave, Serono and Verily.
Dr. Guttmann has nothing to disclose that could constitute a conflict of interest for this work. Dr. Guttmann has received research funding from Sanofi, the National Multiple Sclerosis Society, and the International Progressive Multiple Sclerosis Alliance.