title: 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.
abstract: 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.
  
  
  
  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 including1H MRS at baseline and after 1 year.
  
  
  
  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).
  
  
  
  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.
authors: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoaand IRCCS S.Martino-IST, Genoa, Italy.
authors: M
authors: M
authors: Pardini
authors: Novartis AG, Basel, Switzerland.
authors: D
authors: D
authors: Botzkowski
authors: Department of Neurology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors: S
authors: S
authors: Müller
authors: Department of Neurology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors: J
authors: J
authors: Vehoff
authors: Department of Neurology, University Hospital Basel, Basel, Switzerland.|Departments of Medicine, Biomedicine and Clinical Research, Basel, Switzerland.
authors: J
authors: J
authors: Kuhle
authors: Medical Image Analysis Center, Basel, Switzerland.
authors: E
authors: E
authors: Ruberte
authors: Medical Image Analysis Center, Basel, Switzerland.
authors: J
authors: J
authors: Würfel
authors: Department of Neurology, University Hospital Mannheim, Mannheim, Germany.
authors: A
authors: A
authors: Gass
authors: Department of Ophthalmology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors: C
authors: C
authors: Valmaggia
authors: Department of Neurology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors: B
authors: B
authors: Tettenborn
authors: Novartis AG, Basel, Switzerland.
authors: N
authors: N
authors: Putzki
authors: Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors: Ö
authors: Ö
authors: Yaldizli
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D055351:Retinal Neurons / Q000378:metabolism / Q000473:pathology*; D012680:Sensitivity and Specificity; D041623:Tomography, Optical Coherence; D066127:White Matter / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: N-acetyl aspartate; magnetic resonance spectroscopy; multiple sclerosis; optical coherence tomography; retinal nerve fibre layer thickness