ECTRIMS eLearning

Metabolites in the posterior cingulate cortex are correlated to clinical symptoms in relapsing remitting multiple sclerosis
ECTRIMS Learn. Ribbons K. 10/27/17; 200681; P1026
Karen A. Ribbons
Karen A. Ribbons
Contributions
Abstract

Abstract: P1026

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - 21 Imaging

Background and aims: Using two dimensional localised correlation spectroscopy (2D L-COSY) we have previously identified metabolic changes occurring in the posterior cingulate cortex (PCC) in MS. In the current study we investigated the association between chemical entities in the PCC with clinical symptoms including cognitive deficits, mood disorders and fatigue.
Methods: 85 relapsing remitting multiple sclerosis (RRMS) patients aged between 18 and 65, on therapy for a minimum of 6 months with no new clinical symptoms or change in their disability status in the last 6 months, were included in the study. MRI and 2D L-COSY scanning procedures were undertaken on a 3T MRI (Magnetom Prisma, Siemens Health Healthineers), equipped with 64 Channel brain coil, with data acquired from a PCC 3x3x3 cm3 voxel, employing TEinitial of 30ms. Voxel segmentation was undertaken using FSL software and spectral data was analysed using Felix 2007 (Accelrys, San Diego, CA), using total creatine as an internal reference. Cognitive function was evaluated using the Audio Recorded Cognitive Screen (ARCS). Fatigue status was determined by applying the Modified Fatigue Impact Scale and mood status was derived using the Depression Anxiety and Stress. Spearman's rho was used to describe correlations between metabolite levels and clinical symptom scores.
Results: RRMS patients had an average disease duration of 8.2±0.6years, mean MSSS of 2.9±0.2, and were 77% female with a mean age of 44±1.04years and were undergoing treatment for the last 3.2±0.3years with Fingolimod (n=43), Interferon or Glatiramer Acetate (n=42). The PCC voxel was comprised of 36.2±0.4% white matter, 50.3±0.4% gray matter and 13.4±0.5% CSF. Higher myo-inositol levels were associated with total ARCS (r=-0.34, P=0.001) and all cognitive domain scores
(r≥0.23, p≤0.01). Glucose levels were negatively correlated with attention (r=-0.30, p=0.007), while language function was positively correlated with tyrosine(r=0.32, p=0.003). Anxiety was associated with N-acetylaspartate (NAA)-amide (r=0.30, p=0.006), tyrosine (r=0.30, p=0.006) and reduced total lipids (r=-0.26, p=0.018). Higher physical fatigue was correlated with reductions in NAA (r≥-0.22, p≤ 0.05) and lipid (r≥-0.23, p< 0.05).
Conclusions: Metabolic changes in the PCC in MS, in particular levels of myo-inositol, glucose, tyrosine, and lipids in addition to NAA, may be linked to pathological processes resulting in disabling symptoms common to MS.
Disclosure:
Karen Ribbons: Funding for this study was supported by an Investigator-Initiated Grant provided by Novartis.
Jameen Arm: Nothing to disclose.
Rod Lea: Nothing to disclose.
Saadallah Ramadan: Nothing to disclose.
Oun Al-iedani: 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: P1026

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - 21 Imaging

Background and aims: Using two dimensional localised correlation spectroscopy (2D L-COSY) we have previously identified metabolic changes occurring in the posterior cingulate cortex (PCC) in MS. In the current study we investigated the association between chemical entities in the PCC with clinical symptoms including cognitive deficits, mood disorders and fatigue.
Methods: 85 relapsing remitting multiple sclerosis (RRMS) patients aged between 18 and 65, on therapy for a minimum of 6 months with no new clinical symptoms or change in their disability status in the last 6 months, were included in the study. MRI and 2D L-COSY scanning procedures were undertaken on a 3T MRI (Magnetom Prisma, Siemens Health Healthineers), equipped with 64 Channel brain coil, with data acquired from a PCC 3x3x3 cm3 voxel, employing TEinitial of 30ms. Voxel segmentation was undertaken using FSL software and spectral data was analysed using Felix 2007 (Accelrys, San Diego, CA), using total creatine as an internal reference. Cognitive function was evaluated using the Audio Recorded Cognitive Screen (ARCS). Fatigue status was determined by applying the Modified Fatigue Impact Scale and mood status was derived using the Depression Anxiety and Stress. Spearman's rho was used to describe correlations between metabolite levels and clinical symptom scores.
Results: RRMS patients had an average disease duration of 8.2±0.6years, mean MSSS of 2.9±0.2, and were 77% female with a mean age of 44±1.04years and were undergoing treatment for the last 3.2±0.3years with Fingolimod (n=43), Interferon or Glatiramer Acetate (n=42). The PCC voxel was comprised of 36.2±0.4% white matter, 50.3±0.4% gray matter and 13.4±0.5% CSF. Higher myo-inositol levels were associated with total ARCS (r=-0.34, P=0.001) and all cognitive domain scores
(r≥0.23, p≤0.01). Glucose levels were negatively correlated with attention (r=-0.30, p=0.007), while language function was positively correlated with tyrosine(r=0.32, p=0.003). Anxiety was associated with N-acetylaspartate (NAA)-amide (r=0.30, p=0.006), tyrosine (r=0.30, p=0.006) and reduced total lipids (r=-0.26, p=0.018). Higher physical fatigue was correlated with reductions in NAA (r≥-0.22, p≤ 0.05) and lipid (r≥-0.23, p< 0.05).
Conclusions: Metabolic changes in the PCC in MS, in particular levels of myo-inositol, glucose, tyrosine, and lipids in addition to NAA, may be linked to pathological processes resulting in disabling symptoms common to MS.
Disclosure:
Karen Ribbons: Funding for this study was supported by an Investigator-Initiated Grant provided by Novartis.
Jameen Arm: Nothing to disclose.
Rod Lea: Nothing to disclose.
Saadallah Ramadan: Nothing to disclose.
Oun Al-iedani: 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.

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