Contributions
Abstract: EP1368
Type: ePoster
Abstract Category: Clinical aspects of MS - 7 MS symptoms
Background and aims: Fatigue is one of the most debilitating symptoms for MS patients. However, the role of neurotransmitters such as Gamma aminobutyric acid (GABA) and Glutamate in the pathology of fatigue is poorly understood. In this study, we utilized two-dimensional localised correlation spectroscopy (2D L-COSY) to determine if there was any association between GABA and Glutamate+Glutamine (Glx), in the posterior cingulate cortex, with clinical fatigue in relapsing remitting MS (RRMS).
Methods: 58 adult RRMS patients and 44 age and sex matched healthy subjects (HC) were recruited to the study. All patients were undergoing treatment with Fingolimod or Interferon or Glatiramer Acetate therapy. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). All participants were scanned on a Siemens Prisma 3T MR system with 64 channel head coil and 2D L-COSY was acquired from a 3x3x3 cm3 voxel in the normal appearing posterior cingulate cortex (PCC) with TEinitial=30ms and 96 increments. Spectral analysis was undertaken using Felix software with all peaks normalised to total creatine (tCr) as an internal reference. To evaluate the differences in fatigue status between MS and control groups, independent student t-tests were used. Correlation (Spearman's rho) assessed the association between fatigue scores with GABA and Glx levels.
Results: Total MFIS, physical fatigue and cognitive fatigue were significantly increased by 54.35%, 59.6% and 49.12%, respectively, in RRMS compared to HCs (p≤ 0.05). The levels of PCC GABA/tCr and Glx/tCr in RRMS were significantly reduced by 3.22% and 4.52% (p≤0.05), respectively, compared to those in HCs. In RRMS, we saw a positive association between GABA and Glx (r=0.28, p≤0.05). However, there was no significant correlation between either Glx/tCr or GABA/tCr PCC levels with fatigue levels in RRMS.
Conclusions: The reduced levels of GABA and Glx in this study may reflect pathological alterations in RRMS patients with fatigue. The close link between GABA and Glx, primarily glutamate, production in the GABAergic pathway could explain the positive association. Although we could not find a correlation with fatigue levels, this study is the first to investigate changes in these neurotransmitters using 2D L-COSY in MS fatigued subjects.
Disclosure:
Jameen Arm: Nothing to disclose.
Karen Ribbons: Funding for this study was supported by an Investigator-Initiated Grant provided by Novartis.
Rod Lea: Nothing to disclose.
Saadallah Ramadan: Nothing to disclose.
Jeannette Lechner-Scott: Accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis, Teva and Roche, has been involved in clinical trials with Biogen, Novartis and Teva.
Abstract: EP1368
Type: ePoster
Abstract Category: Clinical aspects of MS - 7 MS symptoms
Background and aims: Fatigue is one of the most debilitating symptoms for MS patients. However, the role of neurotransmitters such as Gamma aminobutyric acid (GABA) and Glutamate in the pathology of fatigue is poorly understood. In this study, we utilized two-dimensional localised correlation spectroscopy (2D L-COSY) to determine if there was any association between GABA and Glutamate+Glutamine (Glx), in the posterior cingulate cortex, with clinical fatigue in relapsing remitting MS (RRMS).
Methods: 58 adult RRMS patients and 44 age and sex matched healthy subjects (HC) were recruited to the study. All patients were undergoing treatment with Fingolimod or Interferon or Glatiramer Acetate therapy. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). All participants were scanned on a Siemens Prisma 3T MR system with 64 channel head coil and 2D L-COSY was acquired from a 3x3x3 cm3 voxel in the normal appearing posterior cingulate cortex (PCC) with TEinitial=30ms and 96 increments. Spectral analysis was undertaken using Felix software with all peaks normalised to total creatine (tCr) as an internal reference. To evaluate the differences in fatigue status between MS and control groups, independent student t-tests were used. Correlation (Spearman's rho) assessed the association between fatigue scores with GABA and Glx levels.
Results: Total MFIS, physical fatigue and cognitive fatigue were significantly increased by 54.35%, 59.6% and 49.12%, respectively, in RRMS compared to HCs (p≤ 0.05). The levels of PCC GABA/tCr and Glx/tCr in RRMS were significantly reduced by 3.22% and 4.52% (p≤0.05), respectively, compared to those in HCs. In RRMS, we saw a positive association between GABA and Glx (r=0.28, p≤0.05). However, there was no significant correlation between either Glx/tCr or GABA/tCr PCC levels with fatigue levels in RRMS.
Conclusions: The reduced levels of GABA and Glx in this study may reflect pathological alterations in RRMS patients with fatigue. The close link between GABA and Glx, primarily glutamate, production in the GABAergic pathway could explain the positive association. Although we could not find a correlation with fatigue levels, this study is the first to investigate changes in these neurotransmitters using 2D L-COSY in MS fatigued subjects.
Disclosure:
Jameen Arm: Nothing to disclose.
Karen Ribbons: Funding for this study was supported by an Investigator-Initiated Grant provided by Novartis.
Rod Lea: Nothing to disclose.
Saadallah Ramadan: Nothing to disclose.
Jeannette Lechner-Scott: Accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis, Teva and Roche, has been involved in clinical trials with Biogen, Novartis and Teva.