Cognitive functions in multiple sclerosis: impact of gray matter integrity

2013 ◽  
Vol 20 (4) ◽  
pp. 424-432 ◽  
Author(s):  
Sara Llufriu ◽  
Eloy Martinez-Heras ◽  
Juan Fortea ◽  
Yolanda Blanco ◽  
Joan Berenguer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Performance ◽  
Gray Matter ◽  
Cognitive Functions ◽  
Diffusion Tensor ◽  
Lesion Volume ◽  
Memory And Attention ◽  
Diffusion Tensor Images ◽  
Explained Variance ◽  
The Impact

Objectives: Our aim was to investigate the impact of gray matter (GM) integrity on cognitive performance in multiple sclerosis (MS), and its relationship with white matter (WM) integrity and presence of lesions. Methods: Sixty-seven patients with MS and 26 healthy controls underwent voxel-based analysis of diffusion tensor images (DTI) in GM and tract-based spatial statistics (TBSS) from WM to identify the regional correlations between cognitive functions and integrity. Lesion probability mapping (LPM) was generated for correlation analysis with cognition. Multiple linear regression analyses were used to identify the imaging measures associated with cognitive scores. Results: Compared with controls, patients showed abnormal DTI indices in several GM regions and in most WM tracts. Impairment in DTI indices in specific GM regions was associated with worse performance of distinct cognitive functions. Those regions showed anatomical correspondence with cognitively relevant tracts in TBSS and LPM. The combination of regional GM and WM DTI and lesion volume accounted for 36–51% of the variance of memory and attention scores. Regional GM DTI explained less than 5% of that variance. Conclusion: GM and WM integrity of specific networks influences cognitive performance in MS. However, GM damage assessed by DTI only adds a small increment to the explained variance by WM in predicting cognitive functioning.

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

2015 ◽  
Vol 22 (5) ◽  
pp. 620-627 ◽  
Author(s):  
MA Rocca ◽  
M Sonkin ◽  
M Copetti ◽  
E Pagani ◽  
DL Arnold ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Structural Integrity ◽  
Linear Models ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Lesion Volume ◽  
Resonance Imaging ◽  
The Impact

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

T2 hypointensity in the deep gray matter of patients with benign multiple sclerosis

2009 ◽  
Vol 15 (6) ◽  
pp. 678-686 ◽  
Author(s):  
A Ceccarelli ◽  
M Filippi ◽  
M Neema ◽  
A Arora ◽  
P Valsasina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Diffusion Tensor ◽  
Iron Deposition ◽  
Lesion Volume ◽  
Hyperintense Lesion ◽  
Benign Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Putative Marker ◽  
And Diffusion

Background Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, commonly occurs in multiple sclerosis (MS). However, GM T2 hypointensity in benign MS (BMS) has not yet been characterized. Objective To determine the presence of deep GM T2 hypointensity in BMS, compare it to secondary progressive (SP) MS and assess its association with clinical and diffusion tensor (DT) MRI measures. Methods Thirty-five cognitively unimpaired BMS, 26 SPMS patients, and 25 healthy controls were analyzed for normalized T2-intensity in the basal ganglia and thalamus, global T2 hyperintense lesion volume, global atrophy, and white matter and GM DT metrics. Results BMS and SPMS patients showed deep GM T2 hypointensity compared with controls. T2 hypointensity was similar in both MS subgroups and moderately correlated ( r = −0.45 to 0.42) with DT MRI metrics. GM T2 hypointensity in BMS showed a weak to moderate correlation ( r = −0.44 to −0.35) with disability. Conclusions GM in BMS is not spared from structural change including iron deposition. However, while T2 hypointensity is related to global tissue disruption reflected in DT MRI, the expression of benign versus non-benign MS is likely related to other factors.

High-intensity interval exercise improves cognitive performance and reduces matrix metalloproteinases-2 serum levels in persons with multiple sclerosis: A randomized controlled trial

2017 ◽  
Vol 24 (12) ◽  
pp. 1635-1644 ◽  
Author(s):  
Philipp Zimmer ◽  
Wilhelm Bloch ◽  
Alexander Schenk ◽  
Max Oberste ◽  
Stefan Riedel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Matrix Metalloproteinases ◽  
Aerobic Exercise ◽  
Cognitive Performance ◽  
Verbal Memory ◽  
High Intensity ◽  
Controlled Trial ◽  
Exercise Programme ◽  
Healthy Elderly ◽  
The Impact

Background: Aerobic exercise can improve cognitive performance in healthy elderly people. Objective: The aim of this study was to investigate the influence of a 3-week high-intensity aerobic exercise programme (high-intensity training group (HIT)) on cognitive performance in persons with multiple sclerosis (MS) compared with a standard exercise programme (control training (CT)). Methods: A total of 60 persons with MS (Expanded Disability Status Scale (EDSS): 1.0–6.5) were randomized to a HIT group (3×/week for 20 minutes, including five 3-minute exercise intervals at 80% of peak oxygen uptake (VO2-peak)) or a CT group (continuously 5×/week for 30 minutes/session at 65% of VO2-peak). Cognitive performance was assessed using the Brief International Cognitive Assessment for MS at entry ( t0) and discharge ( t1). Furthermore, VO2-peak, brain-derived neurotrophic factor, serotonin and matrix metalloproteinases (MMP)-2 and -9 were measured. Results: Compared to CT, HIT significantly improved verbal memory. Significant improvements over time in executive functions were found in both groups. Secondary outcomes indicated significant improvements in VO2-peak and a significant reduction in MMP-2 in the HIT group only. Conclusion: HIT represents a promising strategy to improve verbal memory and physical fitness in persons with MS. Further research is needed to determine the impact of exercise on biomarkers in MS.

Cognitive reserve moderates the impact of subcortical gray matter atrophy on neuropsychological status in multiple sclerosis

2015 ◽  
Vol 22 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Claire M Modica ◽  
Niels Bergsland ◽  
Michael G Dwyer ◽  
Deepa P Ramasamy ◽  
Ellen Carl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Decline ◽  
Cognitive Processing ◽  
Gray Matter ◽  
Cognitive Reserve ◽  
Cognitive Outcome ◽  
Brain Reserve ◽  
The Impact ◽  
Normal Controls

Background: Cognitive decline is characterized in multiple sclerosis (MS), but the rate and severity vary. The reserve hypothesis proposes that baseline neurological differences impact cognitive outcome in neurodegenerative disease. Objective: To elucidate how brain reserve and cognitive reserve influence subcortical gray matter (SCGM) atrophy and cognitive decline in MS over 3 years. Methods: Seventy-one MS patients and 23 normal controls underwent magnetic resonance imaging and cognitive assessment at baseline and 3-year follow-up. The influence of reserve on cognitive processing speed (CPS) and memory was examined. Results: SCGM volume and cognitive scores were lower in MS than normal controls ( P⩽0.001). Accounting for baseline, comparison of follow-up means yielded a difference between groups in SCGM volume ( P<0.001) but not cognition (NS). Cognitive reserve ( P=0.005), but not brain reserve, contributed to CPS, with only low cognitive reserve MS subjects showing decline in CPS ( P=0.029). SCGM change predicted CPS outcome in MS with low cognitive reserve ( P=0.002) but not high cognitive reserve. There were no effects in the domain of memory. Conclusions: SCGM atrophy occurs in normal controls, but significantly more so in MS. While CPS did not change in normal controls, low cognitive reserve was associated with CPS decline in MS. High cognitive reserve protect MS patients from cognitive decline related to SCGM atrophy.

The Impact of MRI T1 Hypointense Brain Lesions on Cerebral Deep Gray Matter Volume Measures in Multiple Sclerosis

2019 ◽  
Author(s):  
Korhan Buyukturkoglu ◽  
Enricomaria Mormina ◽  
Philip L. Jager ◽  
Claire S. Riley ◽  
Victoria M. Leavitt
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Gray Matter Volume ◽  
Brain Lesions ◽  
Matter Volume ◽  
Deep Gray Matter ◽  
The Impact

Gray matter trophism, cognitive impairment, and depression in patients with multiple sclerosis

2017 ◽  
Vol 23 (14) ◽  
pp. 1864-1874 ◽  
Author(s):  
Emanuele Pravatà ◽  
Maria A Rocca ◽  
Paola Valsasina ◽  
Gianna C Riccitelli ◽  
Claudio Gobbi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Gray Matter ◽  
Rating Scale ◽  
Three Dimensional ◽  
Emotional Behavior ◽  
Cortical Atrophy ◽  
Lesion Volume ◽  
Cortical Thinning ◽  
C Statistic

Background: Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. Objectives: To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. Methods: Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls. Cognitive impairment was assessed using the Brief Repeatable Battery of Neuropsychological Tests and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). Using FreeSurfer and FIRST software, we assessed cortical thickness (CTh) and deep GM volumetry. Magnetic resonance imaging (MRI) variables explaining depression and cognitive impairment were investigated using factorial and classification analysis. Multivariate regression models correlated GM abnormalities with symptoms severity. Results: Compared with controls, MS patients exhibited widespread bilateral cortical thinning involving all brain lobes. Depressed MS showed selective CTh decrease in fronto-temporal regions, whereas cognitive impairment MS exhibited widespread fronto-parietal cortical and subcortical GM atrophy. Frontal cortical thinning was the best predictor of depression ( C-statistic = 0.7), whereas thinning of the right precuneus and high T2 lesion volume best predicted cognitive impairment ( C-statistic = 0.8). MADRS severity correlated with right entorhinal cortex thinning, whereas cognitive impairment severity correlated with left entorhinal and thalamus atrophy. Conclusion: MS-related depression is linked to circumscribed CTh changes in areas deputed to emotional behavior, whereas cognitive impairment is correlated with cortical and subcortical GM atrophy of circuits involved in cognition.

scholarly journals Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

2019 ◽  
Vol 5 (2) ◽  
pp. 205521731985603 ◽  
Author(s):  
Jenny Feng ◽  
Erik Offerman ◽  
Jian Lin ◽  
Elizabeth Fisher ◽  
Sarah M Planchon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Tensor ◽  
Phase 1 ◽  
Lesion Volume ◽  
Open Label ◽  
Mesenchymal Stem Cell Transplantation ◽  
Post Transplant ◽  
Normal Appearing White Matter ◽  
Motor Tracts ◽  
Clinical Measures

Background Mesenchymal stem cells (MSC) have immunomodulatory and neuro-protective properties and are being studied for treatment of multiple sclerosis (MS). Tractography-based diffusion tensor imaging (DTI), cortical thickness (Cth) and T2 lesion volume (T2LV) can provide insight into treatment effects. Objective The objective of this study was to analyse the effects of MSC transplantation in MS on exploratory MRI measures. Methods MRIs were obtained from 24 MS patients from a phase 1 open-label study of autologous MSC transplantation. DTI metrics were obtained in lesions and normal-appearing white matter motor tracts (NAWM). T2LV and Cth were derived. Longitudinal evolution of MRI outcomes were modelled using linear mixed effects. Pearson’s correlation was calculated between MRI and clinical measures. Results Lesional radial diffusivity (RD) and axial diffusivity (AD) decreased pre-transplant and showed no changes post-transplant. There were mixed trends in NAWM RD and AD pre/post-transplant. Transplantation stabilized T2LV growth. NAWM RD and AD correlated with Cth, T2LV and with leg and arm function but not with cognition. Lesional DTI demonstrated similar but less robust correlations. Conclusions Microstructural tissue integrity is altered in MS. DTI changes pre-transplant may be influenced by concomitant lesion accrual. Contributor to DTI stabilization post-transplant is multifactorial. DTI of major motor tracts correlated well with clinical measures, highlighting its sensitivity to clinically meaningful changes.

scholarly journals Word-finding difficulty is a prevalent disease-related deficit in early multiple sclerosis

2019 ◽  
Vol 26 (13) ◽  
pp. 1752-1764 ◽  
Author(s):  
Rachel Brandstadter ◽  
Michelle Fabian ◽  
Victoria M Leavitt ◽  
Stephen Krieger ◽  
Anusha Yeshokumar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Objective Assessment ◽  
Lesion Volume ◽  
Healthy Controls ◽  
Patient Report ◽  
Word Finding ◽  
Cognitive Complaint ◽  
Two Samples ◽  
Patient Reported

Background: Persons with multiple sclerosis (MS) commonly report word-finding difficulty clinically, yet this language deficit remains underexplored. Objective: To investigate the prevalence and nature of word-finding difficulty in persons with early MS on three levels: patient report, cognitive substrates, and neuroimaging. Methods: Two samples of early MS patients ( n = 185 and n = 55; ⩽5 years diagnosed) and healthy controls ( n = 50) reported frequency/severity of cognitive deficits and underwent objective assessment with tasks of rapid automatized naming (RAN), measuring lexical access speed, memory, word generation, and cognitive efficiency. High-resolution brain magnetic resonance imaging (MRI) derived measurements of regional cortical thickness, global and deep gray matter volume, and T2 lesion volume. Relationships among patient-reported word-finding difficulty, cognitive performance, and neural correlates were examined. Results: Word-finding difficulty was the most common cognitive complaint of MS patients and the only complaint reported more by patients than healthy controls. Only RAN performance discriminated MS patients with subjective word-finding deficits from those without subjective complaints and from healthy controls. Thinner left parietal cortical gray matter independently predicted impaired RAN performance, driven primarily by the left precuneus. Conclusion: Three levels of evidence (patient-report, objective behavior, regional gray matter) support word-finding difficulty as a prevalent, measurable, disease-related deficit in early MS linked to left parietal cortical thinning.

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