Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis

Objective-The association between brain atrophy and permanent functional de ficits in multiple sclerosis and the temporal relation between atrophy and the clinical disease course have seldom been investigated. This study aims to determine the amount of infratentorial and supratentorial atrophy in pat ients by comparison with healthy controls, to establish the relation betwee n atrophy and disability, and to derive the rates of volume loss in individ ual patients from their estimated disease durations. Methods-Three dimensional acquired MRI was performed on 20 relapsing-remitt ing and 20 secondary progressive multiple sclerosis patients and 10 control subjects. Volume data on infratentorial and supratentorial structures were obtained using the Cavalieri method of modern design stereology in combina tion with point counting. Corpus callosal sectional area and "T2 lesion loa d" were also determined. Results-Significantly reduced infratentorial and cerebral white matter volu mes and corpus callosal sectional areas occurred in all patients compared w ith controls (p=0.0001-0.004). Mean estimates of volume loss in the cohort were -21%,-19%,-46%, and -12% for the brain stem, cerebellum, upper cervica l cord and white matter, respectively, and -21% for the corpus callosal sec tional area. Analysis of the amount of atrophy (volume differences between patients and controls) showed that upper cervical cord and cerebral white m atter atrophy correlated with the expanded disability status scale (r=-0.37 and -0.37, p=0.018-0.023) and the Scripps neurologic rating scale scores ( r=+0.49 and +0.43, p=0.002-0.007), There was no relation between estimated volume loss in the supratentorial and infratentorial compartments. The "T2 lesion load" was associated with ventricular enlargement and corpus callosa l atrophy (r=+0.50 and -0.55, p=0.0003-0.0012). Infratentorial atrophy rate s correlated with baseline exacerbation rates (r=-0.50 to -0.48, p=0.0016-0 .0021) and were higher in relapsing-remitting than secondary progressive pa tients (p=0.009-0.02). Conclusions-Significant cerebral and spinal cord volume reductions occurred in both patient subgroups compared with controls. Functional correlates we re found with estimated volume loss in the upper cervical cord and cerebral white matter. Particularly for infratentorial structures, estimated rates of atrophy were higher in relapsing-remitting than secondary progressive pa tients, suggesting that atrophy, perhaps mainly due to tract degeneration, begins early in multiple sclerosis and may relate predominantly to acute in flammatory events, with or without other gradual non-inflammatory processes later in the disease course.