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Current Neuropharmacology 2018Cognitive impairment is one of the most important clinical features of neurodegenerative disorders including multiple sclerosis (MS). Conducted research shows that up to... (Review)
Review
BACKGROUND
Cognitive impairment is one of the most important clinical features of neurodegenerative disorders including multiple sclerosis (MS). Conducted research shows that up to 65 percent of MS patients have cognitive deficits such as episodic memory, sustained attention, reduced verbal fluency; however, the cognitive MS domain is information processing speed. It is the first syndrome of cognitive dysfunction and the most widely affected in MS. Occasionally these impairments occur even before the appearance of physical symptoms.
METHODS
Therefore, this review focused on the current status of our knowledge about possible methods of treatment cognitive impairment in MS patients including novel strategies. Research and online content was performed using Medline and EMBASE databases.
RESULTS
The most recent research suggests that cognitive impairment is correlated with brain lesion volume and brain atrophy. The examination of the cognitive impairment is usually based on particular neuropsychological batteries. However, it can be not enough to make a precise diagnosis. This creates a demand to find markers that might be useful for identifying patients with risk of cognitive impairment at an early stage of the disease. Currently the most promising methods consist of neuroimaging indicators, such as diffusion tensor imaging, the magnetization transfer ratio, and N-acetyl aspartate levels. Diagnosis problems are strictly connected with treatment procedures. There are two main cognitive therapies: pharmacological (disease modifying drugs (DMD), symptomatic treatments) and non-pharmacological interventions that are focused on psychological and physical rehabilitation. Some trials have shown a positive association between physical activity and the cognitive function.
CONCLUSION
This article is an overview of the current state of knowledge related to cognition impairment treatment in MS. Additionally, novel strategies for cognitive impairments such as cryostimulation and other complementary methods are presented.
Topics: Animals; Cognitive Dysfunction; Humans; Multiple Sclerosis; Psychotropic Drugs
PubMed: 29119933
DOI: 10.2174/1570159X15666171109132650 -
Cells Nov 2021Although the detailed pathogenesis of multiple sclerosis (MS) is not completely understood, a broad range of disease-modifying therapies (DMTs) are available. A common... (Review)
Review
Although the detailed pathogenesis of multiple sclerosis (MS) is not completely understood, a broad range of disease-modifying therapies (DMTs) are available. A common side effect of nearly every MS therapeutic agent is lymphopenia, which can be both beneficial and, in some cases, treatment-limiting. A sound knowledge of the underlying mechanism of action of the selected agent is required in order to understand treatment-associated changes in white blood cell counts, as well as monitoring consequences. This review is a comprehensive summary of the currently available DMTs with regard to their effects on lymphocyte count. In the first part, we describe important general information about the role of lymphocytes in the course of MS and the essentials of lymphopenic states. In the second part, we introduce the different DMTs according to their underlying mechanism of action, summarizing recommendations for lymphocyte monitoring and definitions of lymphocyte thresholds for different therapeutic regimens.
Topics: Animals; Autoimmunity; Clinical Trials as Topic; Drug Monitoring; Humans; Lymphocyte Count; Multiple Sclerosis
PubMed: 34831400
DOI: 10.3390/cells10113177 -
Journal of Neurology Oct 2020Recent changes in the understanding and management of multiple sclerosis (MS) have increased the role of MRI in supporting diagnosis and disease monitoring. However,...
BACKGROUND
Recent changes in the understanding and management of multiple sclerosis (MS) have increased the role of MRI in supporting diagnosis and disease monitoring. However, published guidelines on the use of MRI in MS do not translate easily into different clinical settings and considerable variation in practice remains. Here, informed by published guidelines for the use of MRI in MS, we identified a clinically informative MRI protocol applicable in a variety of clinical settings, from district general hospitals to tertiary centres.
METHODS
MS specialists geographically representing the UK National Health Service and with expertise in MRI examined existing guidelines on the use of MRI in MS and identification of challenges in their applications in various clinical settings informed the formulation of a feasible MRI protocol.
RESULTS
We identified a minimum set of MRI information, based on clinical relevance, as well as on applicability to various clinical settings. This informed the selection of MRI acquisitions for scanning protocols, differentiated on the basis of their purpose and stage of the disease, and indication of timing for scans. Advice on standardisation of MRI requests and reporting, and proposed timing and frequency of MRI scans were generated.
CONCLUSIONS
The proposed MRI protocol can adapt to a range of clinical settings, aiding the impetus towards standardisation of practice and offering an example of research-informed service improvement to support optimisation of resources. Other neurological conditions, where a gap still exists between published guidelines and their clinical implementation, may benefit from this same approach.
Topics: Humans; Magnetic Resonance Imaging; Multiple Sclerosis; State Medicine
PubMed: 32472179
DOI: 10.1007/s00415-020-09930-0 -
International Journal of Molecular... Jul 2021Multiple Sclerosis (MS) is a demyelinating disease of the human central nervous system having an unconfirmed pathoetiology. Although animal models are used to mimic the... (Review)
Review
Multiple Sclerosis (MS) is a demyelinating disease of the human central nervous system having an unconfirmed pathoetiology. Although animal models are used to mimic the pathology and clinical symptoms, no single model successfully replicates the full complexity of MS from its initial clinical identification through disease progression. Most importantly, a lack of preclinical biomarkers is hampering the earliest possible diagnosis and treatment. Notably, the development of rationally targeted therapeutics enabling pre-emptive treatment to halt the disease is also delayed without such biomarkers. Using literature mining and bioinformatic analyses, this review assessed the available proteomic studies of MS patients and animal models to discern (1) whether the models effectively mimic MS; and (2) whether reasonable biomarker candidates have been identified. The implication and necessity of assessing proteoforms and the critical importance of this to identifying rational biomarkers are discussed. Moreover, the challenges of using different proteomic analytical approaches and biological samples are also addressed.
Topics: Animals; Biomarkers; Computational Biology; Female; Humans; Male; Mass Spectrometry; Multiple Sclerosis; Protein Processing, Post-Translational; Proteome; Proteomics
PubMed: 34298997
DOI: 10.3390/ijms22147377 -
The Lancet. Neurology Feb 2013Clinical neurologists and scientists who study multiple sclerosis face open questions regarding the integration of epidemiological data with genome-wide association... (Review)
Review
Clinical neurologists and scientists who study multiple sclerosis face open questions regarding the integration of epidemiological data with genome-wide association studies and clinical management of patients. It is becoming evident that the interplay of environmental influences and individual genetic susceptibility modulates disease presentation and therapeutic responsiveness. The molecular mechanisms through which environmental signals are translated into changes in gene expression include DNA methylation, post-translational modification of nucleosomal histones, and non-coding RNAs. These mechanisms are regulated by families of specialised enzymes that are tissue selective and cell-type specific. A model of multiple sclerosis pathogenesis should integrate underlying risk related to genetic susceptibility with cell-type specific epigenetic changes occurring in the immune system and in the brain in response to ageing and environmental stimuli.
Topics: Epigenesis, Genetic; Gene Expression Regulation; Genome-Wide Association Study; Humans; Models, Molecular; Multiple Sclerosis
PubMed: 23332363
DOI: 10.1016/S1474-4422(12)70309-5 -
British Medical Journal Feb 1977
Topics: Demyelinating Diseases; Humans; Multiple Sclerosis
PubMed: 843788
DOI: No ID Found -
Multiple Sclerosis and Related Disorders Aug 2023Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented...
Demographics and baseline disease characteristics of Black and Hispanic patients with multiple sclerosis in the open-label, single-arm, multicenter, phase IV CHIMES trial.
BACKGROUND
Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population.
METHODS
CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and HpwMS aged 18-65 years with relapsing MS and an Expanded Disability Status Score (EDSS) of ≤5.5, was developed in collaboration with patients with MS, national advocacy groups and clinical researchers. Patients were enrolled at study centers across the US, including Puerto Rico, and 1 site in Kenya.
RESULTS
A total of 182 patients enrolled in CHIMES: 113 (62.1%) were BpwMS, and 69 (37.9%) were HpwMS; the mean (SD) baseline EDSS score was 2.4 (1.4), and 62.6% of patients were treatment naive. Using the pooled non-BpwMS/HpwMS group in the OPERA ocrelizumab trials as a reference population, patients enrolled in CHIMES were younger, had a higher mean body mass and had a greater T2 lesion volume but similar T2 lesion number on MRI.
CONCLUSION
BpwMS and HpwMS have been consistently underrepresented in clinical trials, limiting the understanding of disease biology and response to treatment in this population. Data from the CHIMES study revealed differences in demographics and some baseline disease characteristics and disease burden between BpwMS and HpwMS vs WpwMS. These differences could have an impact when assessing clinical outcomes in BpwMS and HpwMS.
GOV IDENTIFIER
NCT04377555.
Topics: Humans; Black or African American; Demography; Hispanic or Latino; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Adolescent; Young Adult; Adult; Middle Aged; Aged
PubMed: 37356256
DOI: 10.1016/j.msard.2023.104794 -
American Family Physician Nov 2004Multiple sclerosis, an idiopathic inflammatory disease of the central nervous system, is characterized pathologically by demyelination and subsequent axonal... (Review)
Review
Multiple sclerosis, an idiopathic inflammatory disease of the central nervous system, is characterized pathologically by demyelination and subsequent axonal degeneration. The disease commonly presents in young adults and affects twice as many women as men. Common presenting symptoms include numbness, weakness, visual impairment, loss of balance, dizziness, urinary bladder urgency, fatigue, and depression. The diagnosis of multiple sclerosis should be made by a physician with experience in identifying the disease. Diagnosis should be based on objective evidence of two or more neurologic signs that are localized to the brain or spinal cord and are disseminated in time and space (i.e., occur in different parts of the central nervous system at least three months apart). Magnetic resonance imaging with gadolinium contrast, especially during or following a first attack, can be helpful in providing evidence of lesions in other parts of the brain and spinal cord. A second magnetic resonance scan may be useful at least three months after the initial attack to identify new lesions and provide evidence of dissemination over time. It is critical to exclude other diseases that can mimic multiple sclerosis, including vascular disease, spinal cord compression, vitamin B12 deficiency, central nervous system infection (e.g., Lyme disease, syphilis), and other inflammatory conditions (e.g., sarcoidosis, systemic lupus erythematosus, Sjögren's syndrome). Symptom-specific drugs can relieve spasticity, bladder dysfunction, depression, and fatigue. Five disease-modifying treatments for multiple sclerosis have been approved by the U.S. Food and Drug Administration. These treatments are partially effective in reducing exacerbations and may slow progression of disability.
Topics: Adjuvants, Immunologic; Antineoplastic Agents; Diagnosis, Differential; Diagnostic Imaging; Humans; Multiple Sclerosis
PubMed: 15571060
DOI: No ID Found -
Seminars in Immunology Dec 2009Multiple sclerosis (MS) is an idiopathic autoimmune neurodegenerative disease. Like many common diseases, MS has a genetic component; however, as with most complex... (Review)
Review
Multiple sclerosis (MS) is an idiopathic autoimmune neurodegenerative disease. Like many common diseases, MS has a genetic component; however, as with most complex diseases, the genetic architecture may be influenced by heterogeneity, incomplete penetrance, polygenic inheritance, and environmental factors. This clinically complex disease has provided great challenges for geneticists over the years. Although the first consistent genetic association to MS (with HLA-DR*1501) was discovered more than 30 years ago, lack of consistently replicated genetic results has plagued the scientific community. New study design methods (particularly genome-wide associations studies [GWAS]) along with genome project data and larger datasets have allowed several additional MS genes to be identified and consistently replicated. Thus, after many years of frustration, the strong genetic component associated with MS is finally beginning to be characterized.
Topics: Animals; Genome-Wide Association Study; Humans; Multiple Sclerosis
PubMed: 19775910
DOI: 10.1016/j.smim.2009.08.003 -
Gaceta Sanitaria 2019To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects...
OBJECTIVE
To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects the perception of these needs.
METHOD
Interpretative-phenomenological qualitative study.
LOCATION
Granada (Spain). Year: 2014. Intentional sample: 30 patients and 20 family caregivers. Data were gathered from 26 interviews and 4 focus groups. The data were coded and analysed with the NVivo programme.
RESULTS
The multiple sclerosis patients and family caregivers had different perceptions of the loss of capacity to undertake activities of daily living. Being able to self care was considered the last vestige of autonomy. The women with multiple sclerosis tried to take on the responsibility of housework, but the male caregivers became gradually involved in these tasks. Gender roles were redefined with respect to housekeeping. The multiple sclerosis patients showed a need for emotional support. Some of the men had abandoned the stereotype of the strong male as a result of the decline in their health. Adaptations in the home took place without planning them in advance. The use of mobility devices started on an occasional basis. A fear of stigma was an obstacle for regular use of assistive technology.
CONCLUSIONS
Health care for people with multiple sclerosis should include family caregivers. Gender influences the perception that caregivers and patients have of the assistance they require to maximise their quality of life. This flags up several intervention areas for the follow-up and long-term care of these patients by the healthcare system.
Topics: Adult; Aged; Attitude to Health; Caregivers; Female; Health Services Needs and Demand; Humans; Male; Middle Aged; Multiple Sclerosis; Qualitative Research; Sex Factors; Young Adult
PubMed: 29203325
DOI: 10.1016/j.gaceta.2017.09.010