Cognitive Fatigue Predicts Cognitive Failure in Multiple Sclerosis Patients and Healthy Controls: A Case-Control Study

Abstract Objective Fatigue and cognitive deficits are frequent symptoms of multiple sclerosis (MS). However, the exact nature of their co-occurrence is not fully understood. We sought to determine the impact of cognitive and physical fatigue on subjective cognitive deficits in MS patients and healthy controls. Methods Self-reports of fatigue (FSMC), depression (CES-D), cognitive deficits (CFQ), and personality traits (NEO-FFI, ANPS) among 30 MS inpatients and 30 healthy controls were analyzed using hierarchical regression models. The frequency of cognitive mistakes was used as the dependent variable and the extent of cognitive and physical fatigue as the independent variable. Results Cognitive fatigue was the only unique and significant predictor of cognitive mistakes in both groups, explaining 13.3% of additional variance in the MS group after correcting for age, mood, and physical fatigue. Physical fatigue had no significant impact on cognitive mistakes. While age had an impact on cognitive mistakes and depression in healthy controls, this association was not significant in MS patients. Depression was significantly correlated with cognitive mistakes and cognitive fatigue in MS patients. Conclusions The interplay of cognitive fatigue and subjective cognitive impairment can be generalized, with the exception of the variables of age and depression, which were shown to have differing impacts on cognitive mistakes in MS patients and healthy controls, respectively. Cognitive fatigue was linked to cognitive mistakes even after correcting for overlapping items in MS patients only. Future research should further investigate the link between cognitive fatigue and attention lapses in daily life by using various objective assessments.

Download Full-text

ASSESSMENT OF FATIGUE ACROSS SEASONS OVER YEAR IN MULTIPLE SCLEROSIS PATIENTS AND HEALTHY CONTROLS

10.26226/morressier.5ab4d4eed462b80296ca4dac ◽

2018 ◽

Author(s):

Daphne Bakalidou

Keyword(s):

Multiple Sclerosis ◽

Healthy Controls ◽

Multiple Sclerosis Patients

Download Full-text

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.

Download Full-text

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.

Download Full-text

TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls

Immunological Investigations ◽

10.3109/08820139.2015.1059851 ◽

2015 ◽

Vol 44 (6) ◽

pp. 590-601 ◽

Cited By ~ 9

Author(s):

Mehrdad Farrokhi ◽

Masoud Etemadifar ◽

Maryam Sadat Jafary Alavi ◽

Sayyed Hamid Zarkesh-Esfahani ◽

Mohaddeseh Behjati ◽

...

Keyword(s):

Multiple Sclerosis ◽

Peripheral Blood ◽

Tnf Alpha ◽

Healthy Controls ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Alpha Production ◽

Multiple Sclerosis Patients

Download Full-text

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458513489853 ◽

2013 ◽

Vol 19 (14) ◽

pp. 1867-1877 ◽

Cited By ~ 10

Author(s):

Que Lan Quach ◽

Luanne M Metz ◽

Jenna C Thomas ◽

Jonathan B Rothbard ◽

Lawrence Steinman ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cytokine Production ◽

Clinical Signs ◽

Healthy Controls ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

Download Full-text

Cerebellar Dysfunction in Multiple Sclerosis: Considerations for Research and Rehabilitation Therapy

Neurorehabilitation and Neural Repair ◽

10.1177/15459683211065442 ◽

2021 ◽

pp. 154596832110654

Author(s):

Erin M. Edwards ◽

Nora E. Fritz ◽

Amanda S. Therrien

Keyword(s):

Multiple Sclerosis ◽

Motor Control ◽

Motor Impairment ◽

Future Research ◽

Disability Progression ◽

Cerebellar Dysfunction ◽

Motor Disability ◽

Rehabilitation Outcomes ◽

Critical Knowledge ◽

The Impact

Introduction. Cerebellar pathology is common among persons with multiple sclerosis (PwMS). The cerebellum is well recognized for its role in motor control and motor learning and cerebellar pathology in multiple sclerosis is associated with enhanced motor impairment and disability progression. The Problem. To mitigate motor disability progression, PwMS are commonly prescribed exercise and task-specific rehabilitation training. Yet, whether cerebellar dysfunction differentially affects rehabilitation outcomes in this population remains unknown. Furthermore, we lack rehabilitation interventions targeting cerebellar dysfunction. The Solution. Here, we summarize the current understanding of the impact of cerebellar dysfunction on motor control, motor training, and rehabilitation in persons with multiple sclerosis. Recommendations. Additionally, we highlight critical knowledge gaps and propose that these guide future research studying cerebellar dysfunction in persons with multiple sclerosis.

Download Full-text

Characterization of Th17 cells in multiple sclerosis patients and healthy controls

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2014.08.377 ◽

2014 ◽

Vol 275 (1-2) ◽

pp. 140-141

Author(s):

Ulrike Bühler ◽

René Gollan ◽

Patrick Belikan ◽

Frauke Zipp ◽

Volker Siffrin

Keyword(s):

Multiple Sclerosis ◽

Th17 Cells ◽

Healthy Controls ◽

Multiple Sclerosis Patients

Download Full-text

Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318815513 ◽

2018 ◽

Vol 4 (4) ◽

pp. 205521731881551 ◽

Cited By ~ 3

Author(s):

L De Meijer ◽

D Merlo ◽

O Skibina ◽

EJ Grobbee ◽

J Gale ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Change ◽

Progressive Multiple Sclerosis ◽

Healthy Controls ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Serial Addition ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

Download Full-text