The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients

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.

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Astrocyte metabolism in multiple sclerosis investigated by 1-C-11 acetate PET

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20911469 ◽

2020 ◽

pp. 0271678X2091146 ◽

Cited By ~ 1

Author(s):

Hiroki Kato ◽

Tatsusada Okuno ◽

Kayako Isohashi ◽

Toru Koda ◽

Mikito Shimizu ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Fractional Anisotropy ◽

Normal Control ◽

Gray Matter ◽

Control Subjects ◽

Quantitative Pet ◽

Fiber Tracts ◽

Positron Emission ◽

Multiple Sclerosis Patients

This study was aimed at evaluating the metabolism of reactive astrocytes in the brains of patients with multiple sclerosis by quantitative 1-C-11 acetate positron emission tomography (PET). Magnetic resonance imaging and 1-C-11 quantitative PET were performed in eight patients with multiple sclerosis and 10 normal control subjects. The efflux rate (k2) of 1-C-11 acetate, which reportedly reflects the metabolic rate of 1-C-11 acetate, was calculated based on the one-tissue compartmental model. Fractional anisotropy was also determined to evaluate the integrity of the neuronal tracts. The values of k2 in the patients with multiple sclerosis were significantly higher than those in the normal control subjects, in both the white matter ( p = 0.003) and the gray matter ( p = 0.02). In addition, the white matter/gray matter ratio of k2 was significantly higher in the multiple sclerosis patients than in the normal control subjects ( p = 0.02). Voxel-based statistical analysis revealed most prominent increase in k2 in the neuronal fiber tracts, as well as decrease in fractional anisotropy in them in the multiple sclerosis patients. The present study clarified that the pathological changes associated with astrocytic reactivation in multiple sclerosis patients could be visualized by quantitative 1-C-11 acetate PET.

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Atrophy in white matter fiber tracts in multiple sclerosis is not dependent on tract length or local white matter lesions

Multiple Sclerosis Journal ◽

10.1177/1352458507088106 ◽

2008 ◽

Vol 14 (6) ◽

pp. 779-785 ◽

Cited By ~ 13

Author(s):

IB Kezele ◽

DL Arnold ◽

DL Collins

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Tissue Injury ◽

White Matter Lesions ◽

Volume Loss ◽

Focal Lesions ◽

Lesion Load ◽

Tract Length ◽

Fiber Tracts ◽

White Matter Fiber Tracts

The pathogenesis of tissue injury outside the white matter (WM) plaques of multiple sclerosis (MS) has not yet been clearly defined. To better understand the pathogenesis of this injury and the associated atrophy, we investigated volume loss over time in 20 WM fiber tracts. We defined two main aims: (1) to examine whether certain fiber tracts were more prone to atrophy, and to test the possible relation of tract atrophy to tract length and selected MS-specific variables; and (2) to investigate the possible relation of atrophy to lesion load (whole brain and in the specific tract). Local volume change was assessed between two distant time points for each MS patient studied. Fiber tracts were segmented automatically using a tractography-based atlas. Results demonstrate volume loss in all fiber tracts. The uncinate fasciculus and anterior-thalamic radiation had the greatest yearly percentage atrophy. Disease type, duration, median expanded disability status scale, total lesion load, and gender exhibited significant effects on atrophy in at least one tract. Together, these data are more consistent with a pathogenesis for the degeneration related to diffuse inflammation rather than the secondary effects of focal lesions.

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A Sensitive and Automatic White Matter Fiber Tracts Model for Longitudinal Analysis of Diffusion Tensor Images in Multiple Sclerosis

PLoS ONE ◽

10.1371/journal.pone.0156405 ◽

2016 ◽

Vol 11 (5) ◽

pp. e0156405 ◽

Cited By ~ 12

Author(s):

Claudio Stamile ◽

Gabriel Kocevar ◽

François Cotton ◽

Françoise Durand-Dubief ◽

Salem Hannoun ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Longitudinal Analysis ◽

Diffusion Tensor ◽

Fiber Tracts ◽

Diffusion Tensor Images ◽

White Matter Fiber Tracts

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JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

Journal of Clinical Medicine ◽

10.3390/jcm10091998 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1998

Author(s):

Robert Bonek ◽

Wojciech Guenter ◽

Robert Jałowiński ◽

Anna Karbicka ◽

Anna Litwin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Jc Virus ◽

Dimethyl Fumarate ◽

Risk Category ◽

Seroprevalence Rate ◽

Immunomodulatory Drugs ◽

Cross Sectional ◽

Treatment Type ◽

Multiple Sclerosis Patients ◽

The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

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Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

Journal of Personalized Medicine ◽

10.3390/jpm11080721 ◽

2021 ◽

Vol 11 (8) ◽

pp. 721

Author(s):

Afshin Derakhshani ◽

Zahra Asadzadeh ◽

Hossein Safarpour ◽

Patrizia Leone ◽

Mahdi Abdoli Shadbad ◽

...

Keyword(s):

Multiple Sclerosis ◽

Mononuclear Cells ◽

Demyelinating Disease ◽

Immune Checkpoints ◽

Peripheral Blood Mononuclear ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

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