Cognitive and neuropsychiatric deficits can be the first manifestations of multiple sclerosis (MS) in a minority of patients. Based on this, some authors have proposed a variant of the disease called ‘‘cortical’’ or ‘‘cerebral-type’’ (cort-MS), which is characterized by a severe progressive cognitive impairment, focal cortical syndromes, and cortical signs, with a relative sparing of motor, sensory and cerebellar functions at disease onset. Distinctive imaging features of cort-MS have not been identified yet.
In this article, the authors investigated the patterns of regional distribution of focal lesions, white matter (WM) and gray matter (GM) atrophy in patients with cort-MS in comparison to classical MS (c-MS) patients. They applied VBM to investigate the patterns of regional distribution of focal lesions as well as WM and GM atrophy. Their working hypothesis was that a more distributed involvement of GM structures is likely to characterize patients with this rare variant of MS.
In this cross-sectional study, nine patients with cort-MS were enrolled. The main presenting symptoms were cognitive impairment (77 per cent), psychiatric manifestations (55 per cent), and seizures (22 per cent). Two control groups were selected. The first group included nine sex- and age-matched healthy controls (HC) with no previous history of neurological, psychiatric, or cardiovascular disorders, and a normal neurological exam. The second included nine patients with c-MS, matched to cort-MS patients for sex, age, disease duration and disability.
All the subjects underwent MRI scan, neurological and neuropsychological assessments. The latter included:
• Mini Mental State Examination
• Raven’s colored progressive matrices
• Token test
• Semantic fluency test
• Phonemic fluency test
• Digit span and Corsi test
• Selective Reminding Test-SRT and 10/36 Spatial Recall Test-SPART
• Montgomery–Asberg Depression Rating Scale.
Using a 1.5-T scanner, brain scans were acquired and the following analysis were performed: FLAIR-hyperintense lesions were identified and FLAIR lesion volume (LV) was quantified; T1-hypointense lesions were identified and quantified on the 3D MPRAGE images; using 3D MPRAGE images, normalized brain volumes (NBV), WM volume (WMV) and GM volume (GMV) were measured using the SIENAx software. Voxel-based morphometry (VBM) analysis was performed using SPM8.
The cort-MS patients showed a severe cognitive impairment, and a past history of seizures or psychiatric disorders. Furthermore, the cognitive domains most frequently involved in cort-MS patients compared to those with c-MS were general reasoning, memory, and language production.
The first intriguing finding of the analysis is that all measures of structural brain damage were significantly more altered in cort-MS vs c-MS patients. The more severe involvement of both brain WM and GM in cort-MS than in c-MS patients was also confirmed by the results of the VBM analysis, which showed different patterns of regional tissue loss in these two patient groups. Two of the areas which were more affected in cort-MS patients were the cingulum bundle and the cingulate cortex. In line with the functional role of the cingulum bundle and cingulate cortex, the analysis of correlation showed that tissue loss in these structures is associated with global cognitive function (as measured with the MMSE), logical-deductive intelligence (as measured with Raven test), and tests for long-term memory (as measured with SRT/DR). GM atrophy in cort-MS patients also involved the left IPL, another key region for cognitive functions. Another region involved in language functions that was found to be more atrophic in cort-MS than c-MS patients was the right middle temporal gyrus (MTG), which contributes to syllable processing and perception of figurative language.
Another intriguing finding of this study was that, compared to c-MS, cort-MS patients showed also a distributed pattern of WM atrophy involving several associative tracts, which included, in addition to the cingulum bundle, the inferior longitudinal fasciculus (ILF) and superior longitudinal fasciculus (SLF). Consistently with their functions, atrophy of these WM tracts correlated with performance at neuropsychological tests for long-term memory, global functioning and abstract reasoning. FLAIR-hyperintense and T1-hypointense lesion distribution did not differ between c-MS and cort-MS patients. VBM analysis disclosed atrophy of cortical and subcortical GM structures as well as WM tracts in both groups of MS patients vs HC. No GM/WM area was more atrophic in c-MS vs cort-MS patients.
: Parisi L, Rocca MA
: J Neurol. 2014 Jun 22. [Epub ahead of print]
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