Predicting a window of therapeutic opportunity in multiple sclerosis

Abstract

ARTICLE Sir, The relationship between cumulative relapses and unremitting progressive disability is highly relevant to clinical practice and to randomized controlled trial design. Neuropathological studies unmentioned by Andersen (2010) have not been able to confirm the widespread belief that severe disability accumulates as a result of successive exacerbations. DeLuca et al. (2006), examining one of the largest reported pathological cohorts of multiple sclerosis cases, demonstrated lack of correlation between plaque load and axonal loss in the corticospinal tracts throughout the length of the spinal cord where the clinical phenomena characterizing the progressive phase typically localize. Disease progression and inflammatory attacks are probably driven by different mechanisms (Trapp and Nave, 2008). This became clear in the interferon and monoclonal antibody studies which showed no impact on disease evolution following relapse suppression, and MRI studies have provided but weak or non-existent correlations between lesion load and long-term disease evolution (Fisniku et al. , 2008). Previous natural history studies have demonstrated predictive value of early disease features, including early relapse rate (Weinshenker et al ., 1989 b ; Eriksson et al. , 2003). Nevertheless, this was no longer reported to apply once permanent disability occurs (defined as 4 on the Disability Status Scale [DSS]; Confavreux et al. , 2003). Outcome appears to be largely determined during the early stage of the disease, and once progression has begun, its rate seems independent of factors preceding it (Confavreux et al. , 2003). It is unaffected by superimposed inflammatory attacks (Kremenchutzky et al. , 1999) and it is homogeneous among progressive subtypes (Kremenchutzky et al. , 2006). Number of relapses during the first 2 (Weinshenker et al. , 1989 b ) and 5 years (Kantarci et al. , 1998; Confavreux et al. , 2003) had …