David, Melissa D.

BSN3Y2-2
Inflammatory Cortical Demyelination in Early Multiple Sclerosis
Summary:
Cortical disease has emerged as a critical aspect of the pathogenesis of multiple
sclerosis, being associated with disease progression and cognitive impairment. Most
studies of cortical lesions have focused on autopsy findings in patients with longstanding, chronic, progressive multiple sclerosis, and the noninflammatory nature of
these lesions has been emphasized. Magnetic resonance imaging studies indicate that
cortical damage occurs early in the disease
Cortical demyelination was present in 53 patients (38%) (104 lesions and 222
tissue blocks) and was absent in 85 patients (121 tissue blocks). Twenty-five patients
with cortical demyelination had definite multiple sclerosis (81% of 31 patients who
underwent long-term follow-up), as did 33 patients without cortical demyelination (72%
of 46 patients who underwent long-term follow-up). In representative tissues, 58 of 71
lesions (82%) showed CD3+ T-cell infiltrates, and 32 of 78 lesions (41%) showed
macrophage-associated demyelination. Meningeal inflammation was topographically
associated with cortical demyelination in patients who had sufficient meningeal tissue
for study.
In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating
lesions were frequent, inflammatory, and strongly associated with meningeal
inflammation. (Funded by the National Multiple Sclerosis Society and the National
Institutes of Health.)

Reaction:
Patients with early-stage multiple sclerosis (MS) show cortical demyelinating
lesions that are numerous, inflammatory, and strongly linked with meningeal
inflammation, according to a study published in the December 8, 2011, New England
Journal of Medicine.
Prior research into cortical lesions has centered on autopsies of patients with a
long history of chronic, progressive MS and has supported the hypothesis that these
lesions are not inflammatory. However, the new study, examined biopsies of cortical
tissues obtained from white-matter lesions in patients with early-stage MS, all
diagnosed within days or weeks of presentation.
They found that cortical demyelination is common early in MS, and our
characterization of the lesion underscored its inflammatory character. Cortical
demyelination that occurs close to the onset of MS differs substantially from that seen in
chronic

MS.

These

findings

do

not

support

primary

(non-inflammatory)

neurodegenerative process during early-stage MS.

The results enhance the understanding of MS as an inflammatory disease, which
might allow researchers to explore different treatment approaches.
Other studies have led to the concept that the underlying substrate of permanent
disability in MS is not inflammation or demyelination, both of which are potentially
reversible, but rather neuroaxonal disease. The study suggests that cortical neuronal
loss is directly associated with inflammatory demyelination, and therefore early
therapeutic efforts to suppress inflammation may be neuroprotective in both gray-matter
and white-matter compartments.