Cognitive impairment in multiple sclerosis is associated to different patterns of gray matter atrophy according to clinical phenotype

Abstract

Objective: To investigate whether cognitive impairment in multiple sclerosis (MS) patients is associated to different patterns of gray matter (GM) atrophy and T2-visible lesion distribution according to the clinical phenotype.

Experimental design: Twenty-two relapsing remitting (RR), 29 secondary progressive (SP), and 22 primary progressive (PP) MS patients, and 39 healthy controls underwent high-field structural magnetic resonance imaging and an extensive neuropsychological battery. Voxel-wise distribution of GM damage and T2-lesions was compared between cognitively impaired (CI) and cognitively preserved (CP) patients according to their clinical phenotype.

Principal observations: Thirty-nine MS patients were CI. In all MS groups, regional GM loss was correlated with cognitive impairment. Different patterns of regional distribution of GM atrophy and T2-visible lesions were found between CI vs. CP MS patients, according to their clinical phenotype. No areas were significantly more atrophied in CI SPMS vs. CI RRMS patients. Conversely, compared with CI PPMS, CI SPMS patients had a significant GM loss in several regions of the fronto-temporal lobes, the left hypothalamus and thalami. While in RRMS and SPMS patients there was a correspondence between presence of T2 visible lesions and GM atrophy in several areas, this was not the case in PPMS patients.

Conclusion: Distinct patterns of regional distribution of GM damage and T2-visible lesions are associated with cognitive impairment in MS patients with different clinical phenotypes. The correspondence between lesion formation and GM atrophy distribution varies in the different forms of MS.

Figure 1

Statistical parametric mapping (SPM) regions of gray matter (GM) loss superimposed on the customized GM template, contrasting cognitively preserved (CP) multiple sclerosis (MS) patients, cognitively impaired (CI) MS patients, and healthy controls (HC) at a threshold of P < 0.05, family wise error corrected. a–d: Regions with significant reduced GM volume in CP MS patients compared with HC. e–h: Regions with reduced GM volume in CI MS patients compared with HC. i–n: Regions more atrophied in CI SM patients compared with CP MS patients. Images are in neurological convention. See text for further details.

Figure 2

Distribution of regions of significant gray matter atrophy (P < 0.05, family wise error corrected) (blue) and T2‐visible lesions (red) in cognitive impaired (CI) vs. cognitive preserved (CP) multiple sclerosis (MS) patients according to the clinical phenotype. Top row: relapsing remitting MS; middle row: secondary progressive MS; bottom row: primary progressive MS. Orange circles identify regions with a correspondence between presence of T2 visible lesions and GM atrophy. Images are in neurological convention. See text for further details.

Figure 3

Statistical parametric mapping (SPM) regions of gray matter (GM) loss superimposed on the customized GM template (P < 0.05, family wise error corrected) showing regions with significant reduced GM volume in: a: Cognitive impaired (CI) patients with secondary progressive multiple sclerosis (MS) compared to CI patients with primary progressive (PP) MS; b: CI patients with relapsing remitting MS compared with CI patients with PPMS. Images are in neurological convention. See text for further details.