Treating Early MS By Targeting Inflammation?

Laurie L. Barclay, MD


February 09, 2012

Inflammatory Cortical Demyelination in Early Multiple Sclerosis

Lucchinetti CF, Popescu BF, Bunyan RF, et al
N Engl J Med. 2011;365:2188-2197

Study Summary

In multiple sclerosis (MS), cortical disease is associated with disease progression and cognitive impairment. Although MRI studies suggest that cortical lesions occur early in the disease course, most studies of cortical lesions have been autopsy studies in patients with long-standing, chronic, progressive MS. These studies suggest that cortical lesions are not associated with inflammation.

Lucchinetti and colleagues examined the prevalence and nature of demyelinating cortical lesions in patients with MS using cortical tissues obtained during stereotactic biopsy sampling of white-matter lesions. Of 563 patients screened, 138 had sufficient cortex in the biopsy sample for assessment of cortical demyelination. Immunohistochemistry allowed determination in cortical lesions of demyelinating activity, inflammatory infiltrates, meningeal inflammation, and topographic association between cortical demyelination and meningeal inflammation. A subgroup of 77 patients (56%) had confirmation of diagnoses at the last follow-up visit, at a median of 3.5 years.

Cortical demyelination was present in 38% of patients. Of 31 patients with cortical demyelination who underwent long-term follow-up, 25 (81%) had definite MS compared with 72% of patients without cortical demyelination. Characteristics of inflammatory cortical demyelination were CD3+ T-cell infiltrates in 82%, and macrophage-associated demyelination in 41%. Among patients with sufficient meningeal tissue for study, meningeal inflammation was topographically associated with cortical demyelination.


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