Brain metabolites and retinal nerve fibre layer thickness and their relation to disability in multiple sclerosis: a longitudinal high-field proton magnetic resonance spectroscopy and optical coherence tomography study
Conference Paper/Poster - Oct 7, 2015
Pardini M., Botzkowski D., Müller Stefanie, Vehoff Jochen, Kuhle Jens, Gass Andrea, Würfel Jens, Valmaggia Christophe, Tettenborn Barbara, Putzki Norman, Yaldizli Ozgür
Background: In multiple sclerosis (MS), the retinal nerve fibre layer thickness (RNFLT) has been shown to correlate with brain atrophy, T2 white matter lesion load and diffusion tensor imaging abnormalities in normal-appearing white matter (NAWM). If this is true, we might expect similar associations between RNFLT and brain metabolites in NAWM quantified using proton magnetic resonance spectroscopy (H-MRS).
Aim: To investigate associations between N-acetylaspartate (NAA) and Choline (Chol) levels relative to creatine (Crea) in T2 WM lesions, NAWM and RNFLT, their dynamics over time and associations with clinical outcome measures in clinically isolated syndrome (CIS), relapsing-remitting (RR) and secondary-progressive (SP)MS.
Methods: In total, 43 patients (mean age 40.1±9.9 years; disease duration 5.5±7.3 years; median EDSS 2.0 (range 0-6.0); 15 CIS, 21 RRMS, 7 SPMS) underwent standardised neurological examination including Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores, optical coherence tomography and 3T MRI including H-MRS at baseline and after one year.
Results: During follow-up, none of the patients changed disease modifying therapy. The median EDSS remained constant. In all patients, mean NAA/Crea was lower in T2 WM lesions than NAWM (1.64±0.16 vs. 1.89±0.26, p< 0.001). Mean NAA/Crea was marginally lower in MS than CIS both in NAWM (1.84±0.23 vs. 1.97±0.25, p=0.12) and T2 WM lesions (1.62±0.17 vs. 1.68±0.12, p=0.18). During follow-up, mean NAA/Crea decreased in T2 WM lesions (1.60±0.15 vs. 1.64±0.16, p=0.02) and by trend in NAWM (1.76±0.53 vs. 1.88±0.24, p=0.098). In NAWM, relative NAA/Crea change over time was similar in CIS and MS. Mean RNFLT was higher in CIS than MS (100.71+9.86 vs. 92.23±12.8 µm, p=0.038). In all patients, mean RNFLT decreased over one year (94.27±11.40 vs. 92.64±10.87 µm, p=0.008). At baseline, EDSS correlated with NAA/Crea in T2 WM lesions (Spearman Rho=0.39) and MSFC correlated with NAA/Crea in T2 WM lesions (Rho=0.39) and NAWM (Rho=0.38; all p< 0.05). At baseline, RNFLT correlated with NAA/Crea in NAWM (Rho=0.46) and T2 WM lesions (Rho=0.63, both p< 0.05). In NAWM, relative NAA/Crea change correlated modestly with the RNFLT change over time (Rho=0.43, p< 0.05).
Conclusions: In NAWM, relative NAA/Crea change correlated with RNFLT change over one year in a clinically stable MS population suggesting that both techniques are sensitive to detect subclinical disease progression.