Abstract

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at −80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography–mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function.

Highlights

  • Migraine is an invalidating disorder of neurovascular origin, which causes remain partly unknown

  • The first route for NAA clearance is its transfer from neurons to oligodendrocytes, where the enzyme Asparto-Acylase cleaves the acetate moiety for use in fatty acid and steroid synthesis

  • Serum NAA levels in migraine patients were significantly lower than in tension-type headache and healthy controls. This result seems to confirm previous findings by Sarchielli et al [2], who described reduced brain NAA signal in migraine with aura examining 1Hmagnetic resonance spectroscopy (MRS) during cortical activation induced by photic stimulation

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Summary

Introduction

Migraine is an invalidating disorder of neurovascular origin, which causes remain partly unknown. Neurons are the only source of N-acetyl-aspartate (NAA). This molecule, which assesses neuronal integrity, leaves central nervous system (CNS) through astrocytes and it is reversed into circulation and excreted by kidney in urine samples [3,4,5]. The NAA is considered, in particular, a marker of axonal integrity. It is synthesized and located prevalently in neural mitochondria [3,4,5], and it has been taken as a marker of mitochondrial functioning [6].

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