title: Optimizing the association between disability and biological markers in MS.
abstract: OBJECTIVE
  Axonal damage is an important feature of MS pathology and the likely substrate of development of progressive disability. Brain volume measurement on MRI can be used as an overall marker of tissue damage and axonal loss. The authors studied the relation of brain volume measurements with the MS Functional Composite (MSFC) in an attempt to improve the clinico-radiologic association.
  
  
  METHODS
  In 137 patients with MS (80 relapsing-remitting [RR], 36 secondary progressive [SP], and 21 primary progressive [PP]) and 12 healthy controls, a brain MRI scan was obtained. Patients also underwent MSFC and Expanded Disability Status Scale (EDSS) assessments. MRI analysis included determination of hypointense T1- and hyperintense T2-weighted lesion load, and two brain volume measurements: 1) the parenchymal fraction (PF): whole brain parenchyma/intracranial volume; and 2) the ventricular fraction (VF): ventricular volume/whole brain parenchyma.
  
  
  RESULTS
  The median PF was smaller and the median VF larger in the patient group (0.81 for PF and 0.029 for VF) than in the control group (0.87 for PF, p < 0.001; and 0.013 for VF, p < 0.01). For the patient population, moderate correlations were found between brain volume measurements and MSFC (0.36 for PF and -0.40 for VF). Patients with short disease duration showed a correlation of MSFC with both brain and lesion volume measurements on MRI, whereas patients with long disease duration only showed a correlation with brain volume measurements.
  
  
  CONCLUSIONS
  Brain volume measurements are correlated with disability as assessed by the MSFC. Although in the early phase of the disease the amount of focal demyelination is important, the residual brain volume seems to be more relevant in determining disability in later phases of the disease.
authors.affiliation: MS-MRI Center, VU Medical Center, Amsterdam, the Netherlands. nf.kalkers@azvu.nl
authors.forename: N F
authors.initials: NF
authors.lastname: Kalkers
authors.forename: E
authors.initials: E
authors.lastname: Bergers
authors.forename: J A
authors.initials: JA
authors.lastname: Castelijns
authors.forename: M A
authors.initials: MA
authors.lastname: van Walderveen
authors.forename: J C
authors.initials: JC
authors.lastname: Bot
authors.forename: H J
authors.initials: HJ
authors.lastname: Adèr
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers