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

Eur J Neurol. 2016 Dec;23(12):1769-1774. doi: 10.1111/ene.13116. Epub 2016 Sep 3.

Abstract

Background and purpose: N-acetyl aspartate (NAA) assessed using proton magnetic resonance spectroscopy (1 H 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 1 H 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.

Keywords: N-acetyl aspartate; magnetic resonance spectroscopy; multiple sclerosis; optical coherence tomography; retinal nerve fibre layer thickness.

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Axons / metabolism
  • Axons / pathology
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Brain / pathology
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Retinal Neurons / metabolism
  • Retinal Neurons / pathology*
  • Sensitivity and Specificity
  • Tomography, Optical Coherence
  • White Matter / diagnostic imaging*
  • White Matter / metabolism
  • White Matter / pathology

Substances

  • Aspartic Acid
  • N-acetylaspartate