title: Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis.
abstract: OBJECTIVE
  To assess the relationship between the spectroscopically measured axonal damage in the normal-appearing white matter of the brainstem, the total brain T2-hyperintense lesion volume (T2LV), and disability in patients with early relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Forty-three RRMS patients and 10 sex- and age-matched healthy controls were prospectively studied for 2 years. T2-weighted magnetic resonance (MR) images and proton MR spectroscopy were acquired at the time of recruitment and at year 2. Brainstem was considered, where large tracts join together, as a suitable region to detect early axonal damage. The T2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) resonances areas were integrated with the jMRUI program, and the ratios were calculated for the sum of the volume elements represented at brainstem.
  
  
  RESULTS
  The basal NAA/Cho ratio was significantly decreased in patients compared with controls. After 2-year follow-up, there was a decrease in the NAA/Cho (-9%; p = 0.002) and NAA/Cr (-13%; p = 0.001) ratios, and an increase in the T2LV (19%; p = 0.043) in multiple sclerosis patients, whereas control subjects had no significant metabolic changes. Significant NAA/Cr ratio decreases were observed in both patients, with and without relapses, whereas T2LV only increased in patients with relapses. The final Expanded Disability Status Scale (EDSS) score correlated with T2LV at baseline, but no significant correlations were found between metabolic values, T2LV change, or EDSS score over the study period.
  
  
  CONCLUSIONS
  Our data reveal an early and progressive axonal damage in relapsing-remitting multiple sclerosis. Axonal loss and T2 lesion volume seem to be at least partly dissociated processes in early stages of the disease.
authors.affiliation: Department of Neurology, Hospital Universitario La Fe, Avda. Campanar 21, at Valencia. E. 46009, Valencia, Spain. med004201@saludalia.com
authors.forename: A M
authors.initials: AM
authors.lastname: Pascual
authors.forename: M C
authors.initials: MC
authors.lastname: Martínez-Bisbal
authors.forename: I
authors.initials: I
authors.lastname: Boscá
authors.forename: C
authors.initials: C
authors.lastname: Valero
authors.forename: F
authors.initials: F
authors.lastname: Coret
authors.forename: B
authors.initials: B
authors.lastname: Martínez-Granados
authors.forename: L
authors.initials: L
authors.lastname: Marti-Bonmati
authors.forename: A
authors.initials: A
authors.lastname: Mir
authors.forename: B
authors.initials: B
authors.lastname: Celda
authors.forename: B
authors.initials: B
authors.lastname: Casanova
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001369:Axons / Q000473:pathology*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002794:Choline / Q000032:analysis; D003401:Creatine / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline