Structural differences observed on magnetic resonance imaging (MRI) could help distinguish cognitive function impairment between primary progressive multiple sclerosis (MS) and secondary progressive MS, according to a study recently published in the European Journal of Neurology.

“Although there were no significant differences in the pattern of structural MRI alterations between [primary progressive MS] and [secondary progressive MS], subtle variations in the location or extent of damage could account for the differences in MRI predictors of global cognition,” the authors wrote.

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This observational study included 183 patients previously diagnosed with MS. The majority (67.21%) had secondary progressive MS, while the remaining 38.78% had primary progressive MS. The control group comprised 75 age- and sex-matched healthy individuals. All participants underwent MRI and completed the Expanded Disability Status Scale (EDSS).

Neuropsychological performance was similar in all cognitive domains among patients with MS, regardless of the subtype. Interestingly, suboptimal cognitive function was further associated with lower fractional anisotropy in different areas of the brain according to the MS subtype.

In primary progressive MS, the medial lemniscus showcased decreased fractional anisotropy, while the gray matter volume was also lower. Conversely, patients with secondary progressive MS had markedly diminished fractional anisotropy of the fornix and lower normalized white matter volumes.

These results correlate with clinical findings previously reported in the literature. Specifically, lower normalized white matter columns correlate with cognitive impairment and declining mental processing speed. In addition, temporary storage and usage of new information require constant communication between multiple brain structures, which is achieved through white matter tracts. These seemingly minimal variations regarding the location and extent of the affected areas may determine global cognition.

“Our findings indicate that the different disease courses of [primary progressive MS] and [secondary progressive MS] do not seem to affect cognitive function in a detectably distinct manner; however, different structural substrates contribute to explain cognitive dysfunction in these clinical phenotypes of MS,” the authors concluded.


Mistri D, Cacciaguerra L, Valsasina P, Pagani E, Filippi M, Rocca MA. Cognitive function in primary and secondary progressive multiple sclerosis: a multiparametric magnetic resonance imaging study. Eur J Neurol. Published online May 29, 2023. doi:10.1111/ene.15900