Cerebral atrophy in MS attributed to inflammatory lesions

MS therapy that does not reduce contrast enhancing lesion (CEL) activity may increase the risk of cerebral atrophy, suggest investigators demonstrating a temporal association between the two events. The investigators point out that the current model of MS proposes two distinct phases of disease: early inflammation during the relapsing remitting stage and neurodegeneration in the secondary progressive stage. They say this model "predicts a temporal dissociation between inflammatory lesion activity and subsequent cerebral atrophy," which makes it difficult to demonstrate a correlation between the two events. Therefore, they investigated whether there is a temporal relationship between monthly CEL activity and whole brain atrophy in patients with relapsing remitting MS followed for an average of four years.The data showed that the extent of cerebral atrophy paralleled CEL activity (measured as cumulative CELs). Furthermore, patients who responded to IFN therapy with a 70-90% reduction in CELs had cerebral atrophy rates similar to those in healthy controls; in contrast, those who had ongoing CEL accumulation, despite therapy, had high rates of cerebral atrophy, and the atrophy correlated with cumulative CELs.One of the 19 patients in the trial was shown to have a dramatic reduction in cerebral atrophy (from 1.68% per year to 0.36% per year) when new CELs were reduced by 98% upon the initiation of combination therapy. The authors note that similar reductions in cerebral atrophy in response to a reduction in enhancing lesion activity with IFN have previously been reported, and that these observations provide further evidence that the rate of cerebral atrophy is driven at least in part by CELs.Analysis suggested that 50 to 79% of cerebral atrophy could be attributed to inflammatory lesion activity. The authors say, "These data would argue that enhancing lesions are not epiphenomena but rather the cause of permanent tissue damage." They add, "?our observations suggest that therapies that fail to reduce CEL activity, also fail to reduce the rate of brain atrophy."Reference...