The association between retinal nerve fibre layer thickness and N-acetyl aspartate levels in multiple sclerosis brain normal-appearing white matter: a longitudinal study using magnetic resonance spectroscopy and optical coherence tomography.

Background and purpose N-acetyl aspartate ( NAA) assessed using proton magnetic resonance spectroscopy (¹H MRS) has a high pathological specificity for axonal density. Retinal nerve fibre layer thickness ( RNFLT) measured by using optical coherence tomography is increasingly used as a surrogate marker of neurodegeneration in multiple sclerosis ( MS). Our aim was to investigate the relation between RNFLT and NAA/creatine in brain normal-appearing white matter ( NAWM), their dynamics over time and the association with clinical outcome measures in relapsing MS. T2 WM lesions served as control tissue. Methods Forty-three MS patients underwent standardized neurological examination including the Expanded Disability Status Scale ( EDSS), Multiple Sclerosis Functional Composite ( MSFC) score, optical coherence tomography and magnetic resonance imaging including ¹H MRS at baseline and after 1 year. Results At baseline, NAA/creatine level was lower in T2 WM lesions than in NAWM (1.64 ± 0.16 vs. 1.88 ± 0.24, P < 0.001). Lowest levels were found in secondary progressive MS ( SPMS). Mean RNFLT was higher in clinically isolated syndrome than in the combined group of relapsing−remitting MS and SPMS (99.8 ± 12.3 μm vs. 92.4 ± 12.8 μm, P = 0.038). In all patients, mean RNFLT decreased by 1.4% during follow-up. At baseline, MSFC z-scores correlated with NAA/creatine levels both in NAWM ( r = 0.42; P = 0.008) and T2 WM lesions ( r = 0.52, P = 0.004). NAWM NAA/creatine variation correlated with the RNFLT change over 1 year ( ρ = 0.43, P = 0.046). Conclusions N-acetyl aspartate/creatine level reduction correlated with RNFLT thinning over 1 year in an EDSS stable MS cohort suggesting that these techniques might be sensitive to detect subclinical disease progression. [ABSTRACT FROM AUTHOR]