Multiple Sclerosis

Multiple sclerosis (MS) is a nontraumatic, immune-mediated and neurodegenerative disease of the central nervous system. This chapter describes cognitive dysfunction in persons with MS. The chapter begins with a description of the disease and its prevalence and economic impact. This is followed by its diagnosis and current understanding of the mechanisms of the disease and its symptoms. The bulk of the chapter describes the cognitive impairments commonly observed in persons with MS. This includes the assessment of cognitive impairment, neuroimaging studies of how cognition is affected by brain pathology, the impact of cognitive impairment on daily life, and cognitive rehabilitation in MS. The chapter concludes with a brief discussion on future directions.

Cognitive Impairment in Multiple Sclerosis

Folia Medica ◽

10.1515/folmed-2016-0029 ◽

2016 ◽

Vol 58 (3) ◽

pp. 157-163 ◽

Cited By ~ 12

Author(s):

Anastasiya G. Trenova ◽

Georgi S. Slavov ◽

Maria G. Manova ◽

Jana B. Aksentieva ◽

Lyuba D. Miteva ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Disorders ◽

Social Burden ◽

Immune Mediated ◽

The Social ◽

Axonal Transection ◽

The Relationship

Abstract Multiple sclerosis (MS) is a socially significant immune-mediated disease, characterized by demyelination, axonal transection and oligodendropathy in the central nervous system. Inflammatory demyelination and neurodegeneration lead to brain atrophy and cognitive deficit in up to 75% of the patients. Cognitive dysfunctions impact significantly patients’ quality of life, independently from the course and phase of the disease. The relationship between pathological brain findings and cognitive impairment is a subject of intensive research. Summarizing recent data about prevalence, clinical specificity and treatment of cognitive disorders in MS, this review aims to motivate the necessity of early diagnosis and complex therapeutic approach to these disturbances in order to reduce the social burden of the disease.

Cognitive impairment in multiple sclerosis – a review of current knowledge and recent research

Reviews in the Neurosciences ◽

10.1515/revneuro-2017-0011 ◽

2017 ◽

Vol 28 (8) ◽

Cited By ~ 34

Author(s):

Tomasz Grzegorski ◽

Jacek Losy

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Rehabilitation ◽

Current Knowledge ◽

Cognitive Domains ◽

Speed Of Information Processing ◽

Chronic Progressive Disease ◽

Scientific Results ◽

Underlying Mechanisms

AbstractMultiple sclerosis (MS) is a chronic, progressive disease of the central nervous system that is characterised by inflammatory damage to the myelin sheath. Though often neglected, cognitive impairment is a common feature of MS that affects 43–70% of patients. It has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions and visual perceptual functions. In recent years there has been growing interest in neuroimaging findings with regard to cognitive impairment in MS. The possible options of managing cognitive dysfunction in MS are pharmacologic interventions, cognitive rehabilitation and exercise training; however, not enough evidence has been presented in this field. The aim of our article is to provide current knowledge on cognitive impairment in MS based on the most recent scientific results and conclusions with regard to affected cognitive domains, neuropsychological assessment, underlying mechanisms of this disturbance, neuroimaging findings and therapeutic options.

The neuropsychiatry of multiple sclerosis

BJPsych Advances ◽

10.1192/bja.2017.19 ◽

2018 ◽

Vol 24 (3) ◽

pp. 178-187 ◽

Cited By ~ 2

Author(s):

Maria A. Ron

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Psychiatric Comorbidity ◽

Psychiatric Morbidity ◽

Learning Objectives ◽

List Type ◽

Disease Modifying Therapies ◽

Immune Mediated ◽

The Uk ◽

SUMMARYMultiple sclerosis (MS), an immune-mediated demyelinating condition, is the most common neurological disease affecting young adults in the UK. It has a high psychiatric comorbidity and over half of patients have some degree of cognitive impairment that adds to the burden of disability. This article reviews the psychiatric and cognitive manifestations of MS and their detection and treatment. Recent advances in the treatment of the disease are briefly reviewed and the impact of disease-modifying therapies on psychiatric morbidity and cognitive impairment is discussed.LEARNING OBJECTIVES•Understand the psychiatric morbidity in MS and its biological counterparts•Understand the cognitive impairment and its biological counterparts•Become familiar with the detection and treatment of the psychiatric and cognitive manifestations of MSDECLARATION OF INTERESTNone.

The Impact of Cognitive Impairment in Adults with Multiple Sclerosis and Their Family Caregivers

International Journal of MS Care ◽

10.7224/1537-2073.2019-091 ◽

2020 ◽

pp. 0000-0000

Author(s):

Elizabeth J. Halstead ◽

Justin Stanley ◽

Damian Fiore ◽

Kim T. Mueser

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Daily Living ◽

Social Impact ◽

Cognitive Impairments ◽

Cognitive Symptoms ◽

Structured Interviews ◽

Cognitive Changes ◽

The Impact ◽

Cognitive Challenges

Abstract Background: Cognitive impairment is a prominent feature of multiple sclerosis. However, the impact that cognitive symptoms have on daily life, and the effect this has on persons with multiple sclerosis and their relationship with spouses/partners, remains unclear. This qualitative study sought information on the nature of cognitive impairments experienced, and the impact of cognitive impairments on the daily lives of both adults with multiple sclerosis and their partners, to gain further insights into how healthcare professionals can best support families. Methods: Fifteen persons with multiple sclerosis and their spouses/partners participated in separate telephone semi-structured interviews. Results: Six themes were identified from the data, along with several subthemes. These were: the social impact of cognitive impairments in MS, changes to daily living, relationship quality, communication, ways of coping with MS, and the desire for help in managing MS. Conclusions: Our results identified types of support that couples needed and wanted; ways that multiple sclerosis affects couples' social lives; that there are difficulties negotiating changes in roles due to cognitive challenges; that there are difficulties coping with the impact of cognitive challenges on daily living; that couples often have difficulty communicating about the impact of cognitive changes on daily living and related issues, which also contributes to relationship strain; and finally, that most participants felt that they did not understand enough about the cognitive symptoms of multiple sclerosis. We outline key areas to address these needs identified.

Validation and cross-cultural adaptation of sexual dysfunction modified scale in multiple sclerosis for Brazilian population

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20150078 ◽

2015 ◽

Vol 73 (8) ◽

pp. 681-687 ◽

Cited By ~ 6

Author(s):

Raquel Ataíde Peres da Silva ◽

Guilherme Sciascia do Olival ◽

Lívia Palma Stievano ◽

Vania Balardin Toller ◽

Sergio Semeraro Jordy ◽

...

Keyword(s):

Multiple Sclerosis ◽

Sexual Dysfunction ◽

Cultural Adaptation ◽

Chronic Inflammatory Disease ◽

Cross Cultural ◽

Brazilian Population ◽

Control Group ◽

Cross Cultural Adaptation ◽

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). These patients suffer from various comorbidities, including sexual dysfunction (SD). The lesions of MS may affect regions of the CNS along the pathway of sexual response. The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a scale that assesses sexual dysfunction. Adapt and validate the MSISQ-19 to Brazilian patients with MS. 204 individuals were evaluated, 134 patients with MS and 70 healthy persons for the control group. It was determined reproducibility, validity, internal consistency and sensitivity of the MSISQ-19-BR. Among patients with MS, 54.3% of male and 71.7% of female presented some kind of SD. In the control group the results were 12.5% and 19.5%, respectively. The MSISQ-19-BR is reproducible, reliable and valid for the Brazilian population and may be used as a tool for assessing the impact of sexual dysfunction in patients with MS.

Aerobic or strength training and flexibility activities and mild cognitive impairment: CETI cohort

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.884 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

C Dupré ◽

B Bongue ◽

L Fruteau de Laclos ◽

J Blais ◽

M-J Sirois

Keyword(s):

Physical Activity ◽

Cognitive Impairment ◽

Neurodegenerative Diseases ◽

Cognitive Impairments ◽

Cognitive Status ◽

Physical Activities ◽

Community Dwelling ◽

Different Types ◽

Initiative Program ◽

Abstract Background Previous studies have been notably criticized for not studying the different types of physical activity. The objective of this work was to examine the association between types of physical activity and cognitive decline in older people. Methods This is a sub-group analysis from the CETI cohort, a multicenter prospective study conducted by the Canadian Emergency Team Initiative Program (CETIE), between 2011 and 2016. Participants were community-dwelling seniors aged ≥ 65 years, consult emergency services for minor injuries with follow-up at 3 and 6 months. Physical activity was assessed by the RAPA (Rapid assessment of Physical activity), which describes the level of aerobic activities and the overall level of muscle strength and flexibility activities. The cognitive status was assessed with the Montreal Cognitive Assessment (MoCA) and the Telephone Interview for Cognitive Status (TICS), using their current cut-offs (MoCA <26/30 and TICS < = 35/50) for mild cognitive impairments (MCI). Logistic regression, COX models and splines were used to examine the association between the type of physical activities and the onset of cognitive impairment. Results At inclusion, 281 individuals were free of MCI, or 43.8% of the total sample, with an average age of 73 years. During follow-ups, MCI appeared in 31.7% of participants initially free of it. The risk of MCI was lower with higher muscular strength & flexibility physical activities (HR = 0.84 [0.70-0.99]), while the relationship with aerobic physical activities was not significant. Conclusions These results showed a potential link between strength & flexibility activities and cognitive impairments, but not with aerobic physical activities. Further analyses are needed to examine whether these relationships persist as a function of the adjustment variables, or statistical methods. This study contributes to the debate on the evaluation of physical activity in the elderly, and its link with neurodegenerative diseases. Key messages This study analyzed the link between types of physical activity and mild cognitive disorders. The aim is to put in place preventive policies of aging, specially in neurodegenerative diseases. The work allowed us to see the effect of the different types of physical activity and the impact of the statistical method on the results.

GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis

Science Translational Medicine ◽

10.1126/scitranslmed.aat4301 ◽

2018 ◽

Vol 10 (462) ◽

pp. eaat4301 ◽

Cited By ~ 19

Author(s):

Raquel Planas ◽

Radleigh Santos ◽

Paula Tomas-Ojer ◽

Carolina Cruciani ◽

Andreas Lutterotti ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Cell Clone ◽

Autoimmune Response ◽

Guanosine Diphosphate ◽

Immune Mediated ◽

T Cell Clone ◽

Positional Scanning ◽

The Central Nervous System

Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood. By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)–l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide. These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.

The impact of hypoxia on blood-brain, blood-CSF and CSF-brain barriers

Journal of Applied Physiology ◽

10.1152/japplphysiol.00108.2020 ◽

2021 ◽

Author(s):

Jeff F. Dunn ◽

Albert M Isaacs

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Cellular Structures ◽

Bacterial Toxin ◽

Blood Brain ◽

High Altitude Cerebral Edema ◽

Neurological Conditions ◽

The Impact ◽

Brain Barriers

The blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB) and CSF-brain barriers (CSFBB) are highly regulated barriers in the central nervous system comprising of complex multi-cellular structures that separate nerves and glia from blood and cerebrospinal fluid, respectively. Barrier damage has been implicated in the pathophysiology of diverse hypoxia-related neurological conditions including stroke, multiple sclerosis, hydrocephalus and high-altitude cerebral edema. Much is known about damage to the BBB in response to hypoxia but much less is known about the BCSFB and CSFBB. Yet it is known that these other barriers are implicated in damage after hypoxia or inflammation. In the 1950s, it was shown that the rate of radionucleated human serum albumin passage from plasma to CSF was 5-times higher during hypoxic than normoxic conditions in dogs, due to blood-CSF barrier disruption. Severe hypoxia due to administration of the bacterial toxin, lipopolysaccharide (LPS) is associated with disruption of the CSFBB. This review discusses the anatomy of the BBB, BCSFB and CSFBB, and the impact of hypoxia and associated inflammation on the regulation of those barriers.

Immune and Infectious Diseases

Mayo Clinic Essential Neurology ◽

10.1093/med/9780190206895.003.0013 ◽

2018 ◽

pp. 430-470

Author(s):

Andrea C. Adams

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Young People ◽

Connective Tissue ◽

Infectious Diseases ◽

Temporal Profile ◽

Immune Mediated ◽

The Common

Many immune-mediated diseases and infections affect the central and peripheral nervous systems. The common feature that characterizes both immune-mediated diseases and infections is a subacute temporal profile. Immune-mediated disease can affect only the nervous system or involve the nervous system as part of a systemic illness, as in vasculitis and connective tissue disease. Multiple sclerosis (MS), the most common disabling neurologic illness of young people, is the prototypical immune-mediated disease of the central nervous system (CNS).

Early detection of cognitive dysfunction in patients with multiple sclerosis: Implications on outcome

Brain Impairment ◽

10.1017/brimp.2019.26 ◽

2019 ◽

Vol 21 (2) ◽

pp. 208-216

Author(s):

Maged Abdel Naseer ◽

Shereen Fathi ◽

Dalia M. Labib ◽

Dalia H. Khalil ◽

Alshaimaa M. Aboulfotooh ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Early Detection ◽

Negative Correlation ◽

Cognitive Rehabilitation ◽

Word Association ◽

Significant Negative Correlation ◽

Fiber Layer ◽

Rnfl Thickness ◽

Increased Risk

AbstractObjective:Cognitive impairment in multiple sclerosis (MS) has a complex relationship with disease progression and neurodegeneration. The aim of this study was to shed light on the importance of early detection of cognitive impairment in MS patients.Methods:The study comprised two groups of definite MS patients, relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), each with 25 patients. Physical disability was assessed using the Expanded Disability Status Scale (EDSS), while the risk of secondary progression was assessed using the Bayesian Risk Estimate for Multiple Sclerosis (BREMS). Cognitive functions were assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and Controlled Oral Word Association Test (COWAT). Assessment of neurodegeneration was done using optical coherence tomography (OCT) via quantification of retinal nerve fiber layer (RNFL).Results:MS patients with higher RNFL thickness demonstrated a larger learning effect size than patients who had lower values in RNFL thickness regardless of MS type. RRMS patients showed significant improvement in delayed recall after giving cues than SPMS. The symbol digit modalities test was the only neuropsychological test that showed a significant negative correlation with EDSS (P = 0.009). There was a statistically significant negative correlation between BREMS scores and performance in all neuropsychological tests.Conclusion:Inclusion of neurocognitive evaluation in the periodic assessment of MS patients is mandatory to detect patients at increased risk of secondary progression. The thickness of RNFL is suggested as a method to estimate the expected benefit of cognitive rehabilitation, regardless of MS type.