Background: The ability of conventional magnetic resonance imaging (MRI) to predict subsequent physical disability and cognitive deterioration after a clinically isolated syndrome (CIS) is weak. Objectives: We aimed to investigate whether conventional MRI changes over 1 year could predict cognitive and physical disability 5 years later in CIS. We performed analyses using a global approach (T 2 lesion load, number of T 2 lesions), but also a topographic approach. Methods: This study included 38 patients with a CIS. At inclusion, 10 out of 38 patients fulfilled the 2010 revised McDonald’s criteria for the diagnosis of multiple sclerosis. Expanded Disability Status Scale (EDSS) evaluation was performed at baseline, year 1 and year 5, and cognitive evaluation at baseline and year 5. T 2 -weighted MRI was performed at baseline and year 1. We used voxelwise analysis to analyse the predictive value of lesions location for subsequent disability. Results: Using the global approach, no correlation was found between MRI and clinical data. The occurrence or growth of new lesions in the brainstem was correlated with EDSS changes over the 5 years of follow-up. The occurrence or growth of new lesions in cerebellum, thalami, corpus callosum and frontal lobes over 1 year was correlated with cognitive impairment at 5 years. Conclusion: The assessment of lesion location at the first stage of multiple sclerosis may be of value to predict future clinical disability.
Scientific Reports 5: Article number: 17650; published online: 03 December 2015; updated: 15 February 2016 The original version of this Article contained errors in the spelling of the authors Catherine Faget-Agius, Jonathan Wirsich, Jean-Philippe Ranjeva, Raphaelle Richieri, Elisabeth Soulier, Sylviane Confort-Gouny, Pascal Auquier, Maxime Guye and Christophe Lançon which were incorrectly given as Faget-Agius Catherine, Wirsich Jonathan, Ranjeva Jean-Philippe, Richieri Raphaelle, Soulier Elisabeth, Confort-Gouny Sylviane, Auquier Pascal, Guye Maxime & Lançon Christophe respectively.
To investigate whether brain total sodium accumulation assessed by 23Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS).
Methods:
Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using 23Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and 1H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction).
Results:
The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0–4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively.
Conclusions:
This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex.
In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions.EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected).At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0-3] at Year 1 to 2.5 [range: 0-6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression.The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.
