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Sources: Confavreux C, et al. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000;343: 1430-1438; Whitaker JN, et al. Relationship of urinary myelin basic protein-like material with cranial MRI in advanced multiple sclerosis. Arch Neurol 2001;58:49-54.
The European database for multiple sclerosis reviewed 1844 patients with multiple sclerosis (MS) for a mean of 11 years, determining the initial course (relapsing-remitting (RR) or progressive) and subsequent course RR, secondary-progressive (SP), or primary-progressive (PP), the times of relapses, and the onset and progression of irreversible disability. Confavreux and colleagues examined landmarks of moderate to severe disability: Expanded Disability Status Scale (EDSS) score of 4 (able to walk > 500 m), EDSS of 6 (limited walking ability with unilateral support to 100 m), EDSS of 7 (ability to walk no more than 10 m with support). Of 1562 patients with a RR onset, the EDSS scores of 4, 6, and 7 were met at 11.4, 23.1, and 33.1 years after onset. The 282 patients with a progressive onset met their landmarks twice as rapidly at 0.0, 7.1, and 13.4 years (P < 0.001). In contrast, both groups evolved from EDSS 4 to 6 at similar times of 5.4 and 5.7 years (P = 0.74).
Whitaker et al measured urinary myelin basic protein (MBP)-like material in 86 RR MS patients, 259 SP MS patients without continued attacks, and 317 SP MS patients with continued attacks. Higher levels of urinary MBP had weakly significant correlations with progressive disease causing higher disability (EDSS > 5), and the volume of black hole lesions on brain MRI.
A growing understanding of the contributors to neurological disability in MS has emerged in recent years. On brain MRI and histologically, the presence of black hole formation, atrophy, and axonal loss appears to correlate with irreversible disability. The study by Confavreux et al demonstrates that more advanced, permanent neurological disability occurs with patients that have a progressive course from the onset, possibly reflecting the more destructive brain pathology occurring in this group. Thus, an early progressive course was a worse prognostic indicator than relapses. The study by Whittaker et al also supports the concept that more destructive brain injury and consequent increase in urinary MBP are seen in more advanced, progressive patterns of disease. —Brian R. Apatoff