scholarly journals Lower total cerebral arterial flow contributes to cognitive performance in multiple sclerosis patients

2019 ◽  
Vol 26 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Dejan Jakimovski ◽  
Ralph HB Benedict ◽  
Karen Marr ◽  
Sirin Gandhi ◽  
Niels Bergsland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Performance ◽  
Cognitive Aging ◽  
Verbal Learning ◽  
Analysis Of Covariance ◽  
Arterial Blood Flow ◽  
Cognitively Impaired ◽  
Lesion Volume ◽  
Arterial Blood ◽  
Multiple Sclerosis Patients

Background: The cognitive performance in multiple sclerosis (MS) patients declines with aging, longer disease duration, and possibly cardiovascular comorbidities. Objectives: We investigated whether lower total cerebral arterial blood flow (CABF) measured at the level of the carotid and vertebral arteries may contribute to worse cognitive performance in 132 MS patients and 47 healthy controls. Methods: Total CABF was evaluated with extracranial Doppler, whereas structural T2-lesion volume (LV) and gray matter volume (GMV) were measured on 3T MRI. The cognitive performance was assessed by Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test—Revised (BVMT-R), and California Verbal Learning Test—Second Edition (CVLT-II). Analysis of covariance, partial correlation, and regression models were used to test the differences between study groups and cognition/CABF correlations. False discovery rate (FDR)-corrected (Benjamini–Hochberg) p-values (i.e. q-values) less than 0.05 were considered significant. Results: Association between lower total CABF and the lower cognitive performance was observed only in MS patients ( r = 0.318, q < 0.001 and r = 0.244, q = 0.012 for SDMT and BVMT-R, respectively). Lower GMV, higher T2-LV, and CABF were significantly associated with poorer performance on the processing speed measure of SDMT (adjusted R2 = 0.295, t-statistics = 2.538, standardized β = 0.203, and q = 0.020), but not with memory tests. Cognitively impaired MS patients had lower total CABF compared to cognitively preserved (884.5 vs 1020.2 mL/min, q = 0.008). Conclusion: Cognitively impaired MS patients presented with lower total CABF. Altered CABF may be a result of reduced metabolic rate and might contribute to abnormal cognitive aging in MS.

T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis

2010 ◽  
Vol 16 (10) ◽  
pp. 1203-1212 ◽  
Author(s):  
Francesca Bagnato ◽  
Zeena Salman ◽  
Robert Kane ◽  
Sungyoung Auh ◽  
Fredric K Cantor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Statistical Significance ◽  
Verbal Learning ◽  
Lesion Volume ◽  
Cognitive Disability ◽  
3.0 Tesla ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: Neocortical lesions (NLs) largely contribute to the pathology of multiple sclerosis (MS), although their relevance in patients’ disability remains unknown. Objective: To assess the incidence of T1 hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment. Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm3 three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T1- and T2-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated. Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed. Conclusions: Although T 1 hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease.

Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients

2012 ◽  
Vol 19 (5) ◽  
pp. 631-638 ◽  
Author(s):  
M Mäurer ◽  
S Ortler ◽  
M Baier ◽  
M Meergans ◽  
P Scherer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Deficits ◽  
Memory Function ◽  
Recall Score ◽  
Analysis Of Covariance ◽  
Controlled Study ◽  
Cognitively Impaired ◽  
Total Recall ◽  
Double Blind ◽  
Multiple Sclerosis Patients

Background: Cognitive decline has been recognised as a frequent symptom in multiple sclerosis (MS). Cholinesterase inhibitors (ChEIs) are employed for the treatment of Alzheimer’s disease, but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits, particularly deficits of memory function. Objective: The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test (SRT) after 16 weeks of treatment. Methods: Efficacy and safety of rivastigmine were analysed in a 16-week, multicentre, double-blind, randomised, placebo-controlled study, followed by an optional one-year open-label treatment phase. Effects of rivastigmine and placebo were compared by an analysis of covariance. Results: In total, 86 patients were enrolled. Patients who received rivastigmine ( n = 43) showed a non-significant increase in total recall score (sum of all words immediately recalled over all six trials) over placebo ( n = 38) after 16 weeks of treatment ( p = 0.2576). Other outcome measures provided no evidence supporting benefits of rivastigmine. Treatment with rivastigmine was well tolerated. Conclusions: With the results of this study, the need for an effective therapy in cognitively impaired MS patients is still required. Thus, intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients.

scholarly journals Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1712
Author(s):  
Roberta Magliozzi ◽  
Francesco Pezzini ◽  
Mairi Pucci ◽  
Stefania Rossi ◽  
Francesco Facchiano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Protein Pattern ◽  
Fold Change ◽  
Cortical Lesion ◽  
Control Group ◽  
Lesion Volume ◽  
Mri Features ◽  
Csf Levels ◽  
Multiple Sclerosis Patients

An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.

A prolonged antibiotic protocol to treat persistent Chlamydophila pneumoniae infection improves the extracranial venous circulation in multiple sclerosis

2017 ◽  
Vol 33 (6) ◽  
pp. 397-406 ◽  
Author(s):  
Paul Thibault ◽  
John Attia ◽  
Chris Oldmeadow
Keyword(s):  
Multiple Sclerosis ◽  
Blood Flow ◽  
Chlamydophila Pneumoniae ◽  
Post Treatment ◽  
Mean Difference ◽  
Arterial Blood Flow ◽  
Volume Data ◽  
Mean Flow ◽  
Arterial Blood ◽  
Affected Side

Objective Chronic cerebrospinal venous insufficiency (CCSVI) is a condition associated with multiple sclerosis (MS). One mechanism that has been proposed is that the venous obstructions found in MS are due to a chronic persistent venulitis caused by the intra-cellular bacterial parasite, Chlamydophila pneumoniae (Cpn). The objective of the current study is to determine the effect of a combined antibiotic protocol (CAP) on the venous flow in MS patients as measured by a quantitative duplex ultrasound examination (QDUS). Method A non-randomised before-after cohort study was conducted to investigate differences in blood flow volumes pre and 6-months post antibiotic treatment for Cpn infection. Flow volume data were measured by QDUS across affected and unaffected sides from multiple veins segments, including internal jugular vein (IJV) segments J2 and J3, and vertebral vein (VV), as well as global arterial blood flow (GABF). Results 91 patients were included in the study. 64 (70%) were found to have positive Cpn serology. There was a statistically significant post-treatment difference seen for the affected side of Cpn infected patients (mean difference = 56 mL/min, p = 0.02). There was a non-significant increase seen for the affected side of uninfected patients (mean difference = 23 mL/min, p = 0.2). The difference in these effects (34 mL/min) was not statistically significant ( p = 0.3). The mean flow rate decreased in the unaffected side for both infected (−27 mL/min, p = 0.5) and uninfected patients (−69 mL/min, p = 0.01). There was a statistically significant post-treatment increase in GABF for the infected patients (mean difference = 90 mL/min, p = 0.02) and a difference of 76 mL/min for non-infected patients ( p = 0.01). Conclusion A CAP appears to improve the extra-cranial circulation in patients diagnosed with MS. This effect is statistically significant in patients with positive Cpn serology, although patients with negative Cpn serology also show some benefit, betraying a lack of specificity of this effect.

Executive functioning affects verbal learning process in multiple sclerosis patients: Behavioural and imaging results

2019 ◽  
Vol 14 (3) ◽  
pp. 384-398
Author(s):  
Marco Pitteri ◽  
Caterina Dapor ◽  
Anna Isabella Pisani ◽  
Marco Castellaro ◽  
John DeLuca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Executive Functioning ◽  
Learning Process ◽  
Verbal Learning ◽  
Imaging Results ◽  
Multiple Sclerosis Patients

scholarly journals Human Leukocyte Antigen Genotype as a Marker of Multiple Sclerosis Prognosis

2019 ◽  
Vol 47 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Andreas P. Lysandropoulos ◽  
Gaetano Perrotta ◽  
Thibo Billiet ◽  
Annemie Ribbens ◽  
Renaud Du Pasquier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Visual Memory ◽  
Verbal Learning ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Lesion Volume ◽  
Leukocyte Antigen ◽  
Hla Genotype

ABSTRACT:Objective:In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.Methods:Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.Results:Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.Conclusion:In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.

Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis

2007 ◽  
Vol 13 (3) ◽  
pp. 376-385 ◽  
Author(s):  
J. Lovera ◽  
B. Bagert ◽  
K. Smoot ◽  
C.D. Morris ◽  
R. Frank ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Performance ◽  
Ginkgo Biloba ◽  
Color Word ◽  
Word Association ◽  
Controlled Trial ◽  
Verbal Learning ◽  
Stroop Test ◽  
Interference Condition ◽  
Double Blind

Objectives To determine if Ginkgo biloba (GB) improves the cognitive performance of subjects with multiple sclerosis (MS). Methods Randomized, double-blind, placebo-controlled trial of GB, 120 mg twice a day or placebo for 12 weeks. The primary outcomes were: the long delay free recall from the California Verbal Learning Test-II; the Paced Auditory Serial Addition Test; the Controlled Oral Word Association Test; the Symbol Digit Modalities Test; Useful Field of View Test; and the color-word interference condition from the Stroop Color and Word Test. Results On completion, the GB group (n=20) was 4.5 seconds (95% confidence interval (CI) (7.6, 0.9), P=0.015) faster than the placebo group (n=18) on the color-word interference condition of the Stroop test. Subjects who were more impaired at baseline experienced more improvement with GB (treatment*baseline interaction, F=8.10, P=0.008). We found no differences on the other neuropsychological tests. Subjects on GB reported fewer cognitive difficulties in the Retrospective Memory Scale of the Perceived Deficits Questionnaire than subjects on placebo (1.5 points, 95% CI (2.6, 0.3), P=0.016). No serious drug related side-effects occurred and GB did not alter platelet function assays. Conclusion Overall, GB did not show a statistically significant improvement in cognitive function. A treatment effect trend, limited to the Stroop test, suggests that GB may have an effect on cognitive domains assessed by this test, such as susceptibility to interference and mental flexibility. Multiple Sclerosis 2007; 13: 376-385. http://msj.sagepub.com

scholarly journals Axonal Damage in Multiple Sclerosis Patients with High versus Low Expanded Disability Status Scale Score

2004 ◽  
Vol 31 (2) ◽  
pp. 225-228 ◽  
Author(s):  
Steven D. Brass ◽  
Sridar Narayanan ◽  
Jack P. Antel ◽  
Yves Lapierre ◽  
Louis Collins ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Disease Process ◽  
Resonance Spectroscopy ◽  
Lesion Volume ◽  
Spinal Cord Atrophy ◽  
Neuronal Marker ◽  
Multiple Sclerosis Patients

AbstractBackground:The pathophysiological basis for differences in disability in patients with multiple sclerosis is unclear.Methods:We used magnetic resonance imaging to examine whether differences in disability in cohorts of multiple sclerosis patients with similar T2-weighted lesion volume and disease duration were associated with a more destructive disease process in the more disabled patients.Results:The benign and severely disabled groups had similar brain atrophy metrics and similar decreases of the neuronal marker, N-acetylaspartate, in the normal appearing white matter of the cerebrum on magnetic resonance spectroscopy examination in vivo. The severely disabled cohort had more spinal cord atrophy.Conclusion:The dissociation of spinal cord atrophy and cerebral atrophy between these two groups suggests that the difference between the more benign and more disabled groups cannot be explained by a more aggressive pathological process that is affecting the entire neuroaxis in a homogeneous fashion.

scholarly journals The Neurocognitive Study for the Aging: Longitudinal Analysis on the Contribution of Sex, Age, Education and APOE ɛ4 on Cognitive Performance

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreas Chadjikyprianou ◽  
Marilena Hadjivassiliou ◽  
Savvas Papacostas ◽  
Fofi Constantinidou
Keyword(s):  
Cognitive Performance ◽  
Sex Education ◽  
Cognitive Aging ◽  
Repeated Measures ◽  
Analysis Of Covariance ◽  
Significant Interaction Effect ◽  
Prospective Longitudinal Study ◽  
Mini Mental Status Examination ◽  
Subject Factor ◽  
Prospective Longitudinal

Objective: The effects of normal cognitive aging on executive functions (EF), Verbal Episodic Memory (VEM) and the contribution of age, sex, education, and APOΕ ε4 in a group of old Greek Cypriots across a five-year period were investigated.Design: NEUROAGE, the first project on cognitive aging in Cyprus, is a prospective longitudinal study with a rolling admission process. Participants are assessed at baseline and retested every 24–30 months.Subjects: 170 participants completed all three testing cycles; 86 men and 84 women with ages ranging between 60 and 88 years (mean = 73.21, SD = 5.84); education, 2–20 years (mean = 9.07, SD = 4.27).Results: Α Repeated Measures Multivariate Analysis of Covariance was conducted with one between-subject factor: sex; two covariates: age and education, while Time (time 1, time 2, time 3) served as a within – subject factor. Time did not have an effect on mini mental status examination in Greek (MMSE), EF or VEM. Also, sex had no effect on MMSE, EF and VEM. There was no time by sex interaction. Age and Education significantly predicted the EF performance, F(1, 168) = 11.23, p &lt; 0.05; F(1, 158) = 90.03, p &lt; 0.001 and VEM performance, F(1, 171) = 17.22, p &lt; 0.001; F(1, 171) = 61.25, p &lt; 0.001. Furthermore, there was a significant interaction effect between time and education, for EF, F(2, 167) = 7.02, p &lt; 0.001. Performance of the APOE ε4 carriers did not differ on any of the above measures as compared to performance of non-carriers in this older adult group.Conclusion: Cognitively healthy adults maintained overall cognitive performance across the five-year period. Male and female participants performed similarly and the pattern of change over time was similar across the two sexes. Education was predictive of VEM and EF performance across time. Furthermore, those with higher education maintained higher levels of EF performance. APOE results did not differentiate performance at baseline. Implications of findings are discussed.

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