Optimizing the association between disability and biological markers in MS

Objective: Axonal damage is an important feature of MS pathology and the li kely substrate of development of progressive disability. Brain volume measu rement 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 th e MS Functional Composite (MSFC) in an attempt to improve the clinico-radio logic 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 les ion load, and two brain volume measurements: 1) the parenchymal fraction (P F): whole brain parenchyma/intracranial volume; and 2) the ventricular frac tion (VF): ventricular volume/whole brain parenchyma. Results: The median P F was smaller and the median VF larger in the patient group (0.81 for PF an d 0.029 for VF) than in the control group (0.87 for PF, p < 0.001; and 0.01 3 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 fo r VF). Patients with short disease duration showed a correlation of MSFC wi th both brain and lesion volume measurements on MRI, whereas patients with long disease duration only showed a correlation with brain volume measureme nts. Conclusion: Brain volume measurements are correlated with disability a s assessed by the MSFC. Although in the early phase of the disease the amou nt of focal demyelination is important, the residual brain volume seems to be more relevant in determining disability in later phases of the disease.