RESUMO
Background: Cladribine shows efficacy in multiple sclerosis (MS), but Latin American (LATAM) real-world data is limited, despite potential sociodemographic variations. Objective: Investigate baseline characteristics and clinical response in highly active MS patients in Mexico, identifying predictors of early treatment response. Method: A multicenter cohort study analyzed retrospective data from individuals with "highly active" MS in the Cladribine Patient Support Program across 11 Mexican clinics. Criteria included one-year prior treatment with another disease-modifying treatment and recent relapse with specific MRI findings. Primary outcomes focused on achieving NEDA-3 status after 12 months. Results: In the follow-up, 67.5% maintained NEDA-3 status. Baseline EDSS scores decreased significantly from 1.50 to 1.00 (p = 0.011), with no confirmed disability worsening. No significant differences were observed between NEDA-3 achievers and non-achievers in demographic and clinical variables. No severe adverse events were reported. Conclusion: Cladribine showed early and effective control of active MS in Mexican patients, demonstrating a secure profile with minimal adverse events. This study provides valuable real-world evidence in the LATAM context.
RESUMO
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by autoimmune destruction of the myelin sheath, leading to irreversible and progressive functional deficits in patients. Pre-clinical studies involving the use of neural stem cells (NSCs) have already demonstrated their potential in neuronal regeneration and remyelination. However, the exclusive application of cell therapy has not proved sufficient to achieve satisfactory therapeutic levels. Recognizing these limitations, there is a need to combine cell therapy with other adjuvant protocols. In this context, extracellular vesicles (EVs) can contribute to intercellular communication, stimulating the production of proteins and lipids associated with remyelination and providing trophic support to axons. This study aimed to evaluate the therapeutic efficacy of the combination of NSCs and EVs derived from oligodendrocyte precursor cells (OPCs) in an animal model of multiple sclerosis. OPCs were differentiated from NSCs and had their identity confirmed by gene expression analysis and immunocytochemistry. Exosomes were isolated by differential ultracentrifugation and characterized by Western, transmission electron microscopy and nanoparticle tracking analysis. Experimental therapy of C57BL/6 mice induced with experimental autoimmune encephalomyelitis (EAE) were grouped in control, treated with NSCs, treated with OPC-derived EVs and treated with a combination of both. The treatments were evaluated clinically using scores and body weight, microscopically using immunohistochemistry and immunological profile by flow cytometry. The animals showed significant clinical improvement and weight gain with the treatments. However, only the treatments involving EVs led to immune modulation, changing the profile from Th1 to Th2 lymphocytes. Fifteen days after treatment revealed a reduction in reactive microgliosis and astrogliosis in the groups treated with EVs. However, there was no reduction in demyelination. The results indicate the potential therapeutic use of OPC-derived EVs to attenuate inflammation and promote recovery in EAE, especially when combined with cell therapy.
RESUMO
Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.
Assuntos
Plaquetas , Diferenciação Celular , Células Precursoras de Oligodendrócitos , Remielinização , Animais , Células Precursoras de Oligodendrócitos/fisiologia , Remielinização/fisiologia , Camundongos , Plaquetas/fisiologia , Encefalomielite Autoimune Experimental/patologia , Camundongos Endogâmicos C57BL , Esclerose Múltipla/patologia , Modelos Animais de Doenças , Oligodendroglia/fisiologia , FemininoRESUMO
Objective. This study was conducted with the aim of the effect of team members teaching design (TMTD) vs. regular Lectures method on the self-efficacy of the multiple sclerosis patients. Methods. This research is a randomized controlled trial study. In this study, 48 multiple sclerosis persons of members of Jahrom MS Society participated. The persons were selected by simple random sampling and then divided into three groups of: TMTD (n=16), regular lecture method (n=16), and control (n=16), by random allocation method. In the intervention groups, six training sessions were held twice a week; control group did not receive education. Data was collected by the MS self-efficacy questionnaire of Rigby et al. in the before, immediately and one month after the intervention. Results. Patients in three intervention and control groups were similar in terms of demographic variables. The results of the repeated measurement test before, immediately and one month after the intervention showed that the mean of the all dimensions of self-efficacy in two intervention groups had increased significantly (p<0.05). While these changes were not significant in the control group (p ≥ 0.05). Also, there was a significant difference in the mean of the all dimensions of self-efficacy between the intervention groups of TMTD and regular lectures. Conclusion. Based on the findings, TMTD compared to regular lectures method had a more significant effect on improving the self-efficacy of multiple sclerosis patients. Therefore, it is recommended that nursing use this educational approach to increase patients' self-efficacy.
Objetivo. Determinar el efecto del diseño de la enseñanza colaborativa de los miembros del equipo (En inglés: Team Members Teaching Design -TMTD) frente al método de las clases regulares sobre la autoeficacia de los pacientes con esclerosis múltiple (EM).Métodos. Ensayo controlado aleatorizado realizado con la participación de 48 personas con esclerosis múltiple afiliados a la Sociedad de Esclerosis Múltiple de Jahrom (Iran), que fueron seleccionados por muestreo aleatorio simple y luego asignados en forma randomizada en tres grupos, dos de intervención: TMTD (n=16) y método de clases regulares (n=16), y un grupo control (n=16). En los grupos de intervención se impartieron seis sesiones educativas (dos por semana); mientras que el grupo control no recibió educación. Se empleó el cuestionario de autoeficacia en EM de Rigby et al. en los momentos: antes, inmediatamente después de terminada la intervención y un mes de finalizada la misma.Resultados. Los pacientes de los tres grupos de intervención y control eran similares en cuanto a variables demográficas. Los resultados de la prueba de medidas repetidas antes, inmediatamente y un mes después de la intervención mostraron que la media de todas las dimensiones de autoeficacia en los dos grupos de intervención había aumentado significativamente (p<0.05). Mientras que estos cambios no fueron significativos en el grupo de control (p ≥ 0.05). Además, hubo una diferencia significativa en la media de todas las dimensiones de autoeficacia entre los grupos de intervención de TMTD y clases regulares, siendo mayor en TMTD. Conclusión. El TMTD comparado con el método de clases regulares, tuvo un mejor efecto en el aumento de la autoeficacia de los pacientes con EM. Por lo tanto, se sugiere a enfermería utilizar este enfoque educativo para aumentar la autoeficacia de los pacientes.
Objetivo. Determinar o efeito do desenho de ensino colaborativo dos membros da equipe (em inglês: Team Members Teaching Design -TMTD) comparado ao método de aulas regulares na autoeficácia de pacientes com esclerose múltipla (EM). Métodos. Ensaio controlado randomizado realizado com a participação de 48 pessoas com esclerose múltipla afiliadas à Sociedade de Esclerose Múltipla de Jahrom (Irã), que foram selecionadas por amostragem aleatória simples e depois distribuídas aleatoriamente em três grupos, dois grupos de intervenção: TMTD (n=16 ) e método de aula regular (n=16), e um grupo controle (n=16). Foram ministradas seis sessões educativas nos grupos de intervenção (duas por semana); enquanto o grupo de controle não recebeu educação. Foi utilizado o questionário de autoeficácia em SM de Rigby et al. nos momentos: antes, imediatamente após o término da intervenção e um mês após seu término. Resultados. Os pacientes dos três grupos intervenção e controle foram semelhantes em termos de variáveis demográficas. Os resultados do teste de medidas repetidas antes, imediatamente e um mês após a intervenção mostraram que a média de todas as dimensões da autoeficácia nos dois grupos de intervenção aumentou significativamente (p<0.05). Embora essas alterações não tenham sido significativas no grupo controle (p ≥ 0.05). Além disso, houve diferença significativa na média de todas as dimensões de autoeficácia entre os grupos de intervenção TMTD e aulas regulares, sendo maior no TMTD. Conclusão. O TMTD comparado ao método de aula regular teve melhor efeito no aumento da autoeficácia dos pacientes com EM. Portanto, sugere-se que a enfermagem utilize essa abordagem educativa para aumentar a autoeficácia dos pacientes.
Assuntos
Humanos , Masculino , Feminino , Leitura , Autoeficácia , Esclerose Múltipla , Autocuidado , Educação , ExtremidadesRESUMO
BACKGROUND: Multiple sclerosis (MS) is an irreversible progressive CNS pathology characterized by the loss of myelin (i.e. demyelination). The lack of myelin is followed by a progressive neurodegeneration triggering symptoms as diverse as fatigue, motor, locomotor and sensory impairments and/or bladder, cardiac and respiratory dysfunction. Even though there are more than fourteen approved treatments for reducing MS progression, there are still no cure for the disease. Thus, MS research is a very active field and therefore we count with different experimental animal models for studying mechanisms of demyelination and myelin repair, however, we still lack a preclinical MS model assembling demyelination mechanisms with relevant clinical-like signs. RESULTS: Here, by inducing the simultaneous demyelination of both callosal and cerebellar white matter fibers by the double-site injection of lysolecithin (LPC), we were able to reproduce CNS demyelination, astrocyte recruitment and increases levels of proinflammatory cytokines levels along with motor, locomotor and urinary impairment, as well as cardiac and respiratory dysfunction, in the same animal model. Single site LPC-injections either in corpus callosum or cerebellum only, fails in to reproduce such a complete range of MS-like signs. CONCLUSION: We here report that the double-site LPC injections treatment evoke a complex MS-like mice model. We hope that this experimental approach will help to deepen our knowledge about the mechanisms of demyelinated diseases such as MS.
Assuntos
Cerebelo , Corpo Caloso , Doenças Desmielinizantes , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Esclerose Múltipla , Animais , Esclerose Múltipla/patologia , Corpo Caloso/patologia , Cerebelo/patologia , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/induzido quimicamente , Camundongos , Masculino , Lisofosfatidilcolinas , Citocinas/metabolismo , Bainha de Mielina/patologiaRESUMO
Multiple sclerosis (MS) is the most common acquired inflammatory and demyelinating disease in adults. The conventional diagnostic of MS and the follow-up of inflammatory activity is based on the detection of hyperintense foci in T2 and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and lesions with brain-blood barrier (BBB) disruption in the central nervous system (CNS) parenchyma. However, T2/FLAIR hyperintense lesions are not specific to MS and the MS pathology and inflammatory processes go far beyond focal lesions and can be independent of BBB disruption. MRI techniques based on the magnetic susceptibility properties of the tissue, such as T2*, susceptibility-weighted images (SWI), and quantitative susceptibility mapping (QSM) offer tools for advanced MS diagnostic, follow-up, and the assessment of more detailed features of MS dynamic pathology. Susceptibility-weighted techniques are sensitive to the paramagnetic components of biological tissues, such as deoxyhemoglobin. This capability enables the visualization of brain parenchymal veins. Consequently, it presents an opportunity to identify veins within the core of multiple sclerosis (MS) lesions, thereby affirming their venocentric characteristics. This advancement significantly enhances the accuracy of the differential diagnostic process. Another important paramagnetic component in biological tissues is iron. In MS, the dynamic trafficking of iron between different cells, such as oligodendrocytes, astrocytes, and microglia, enables the study of different stages of demyelination and remyelination. Furthermore, the accumulation of iron in activated microglia serves as an indicator of latent inflammatory activity in chronic MS lesions, termed paramagnetic rim lesions (PRLs). PRLs have been correlated with disease progression and degenerative processes, underscoring their significance in MS pathology. This review will elucidate the underlying physical principles of magnetic susceptibility and their implications for the formation and interpretation of T2*, SWI, and QSM sequences. Additionally, it will explore their applications in multiple sclerosis (MS), particularly in detecting the central vein sign (CVS) and PRLs, and assessing iron metabolism. Furthermore, the review will discuss their role in advancing early and precise MS diagnosis and prognostic evaluation, as well as their utility in studying chronic active inflammation and degenerative processes.
RESUMO
This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.
Assuntos
Encefalomielite Autoimune Experimental , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Esclerose Múltipla , Animais , Encefalomielite Autoimune Experimental/terapia , Encefalomielite Autoimune Experimental/patologia , Ratos , Esclerose Múltipla/terapia , Esclerose Múltipla/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Humanos , Feminino , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células-Tronco Neurais , Modelos Animais de Doenças , Geleia de Wharton/citologiaRESUMO
Objective: This study was conducted with the aim of the effect of team members teaching design (TMTD) vs. regular Lectures method on the self-efficacy of the multiple sclerosis patients. Methods: This research is a randomized controlled trial study. In this study, 48 multiple sclerosis persons of members of Jahrom MS Society participated. The persons were selected by simple random sampling and then divided into three groups of: TMTD (n=16), regular lecture method (n=16), and control (n=16), by random allocation method. In the intervention groups, six training sessions were held twice a week; control group did not receive education. Data was collected by the MS self-efficacy questionnaire of Rigby et al. in the before, immediately and one month after the intervention. Results: Patients in three intervention and control groups were similar in terms of demographic variables. The results of the repeated measurement test before, immediately and one month after the intervention showed that the mean of the all dimensions of self-efficacy in two intervention groups had increased significantly (p<0.05). While these changes were not significant in the control group (p ≥ 0.05). Also, there was a significant difference in the mean of the all dimensions of self-efficacy between the intervention groups of TMTD and regular lectures. Conclusion: Based on the findings, TMTD compared to regular lectures method had a more significant effect on improving the self-efficacy of multiple sclerosis patients. Therefore, it is recommended that nursing use this educational approach to increase patients' self-efficacy.
Assuntos
Esclerose Múltipla , Autoeficácia , Ensino , Humanos , Esclerose Múltipla/psicologia , Irã (Geográfico) , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Educação de Pacientes como Assunto/métodos , Adulto JovemRESUMO
Background: Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population. Methods and results: Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS national registries (Aruba, Dominican Republic, Honduras, and Panama), data on prevalence, phenotypes and demographics. Expanded Disability Status Scale (EDSS), and therapeutic schemes were included. ENHANCE data from 758 patients disclosed 79.8% of Mestizo ethnicity; 72.4% female; median age at onset 31.0 years and 33.2 at diagnosis. The highest incidence rate was from Aruba, 2.3-3.5 × 100,000 inhabitants, and the lowest, 0.07-0.15 × 100,000, from Honduras. Crude prevalence rates per 100,000 inhabitants fluctuated from 27.3 (Aruba) to 1.0 (Honduras). Relapsing MS accounted for 87.4% of cases; EDSS <3.0 determined in 66.6% (mean disease duration: 9.1 years, SD ± 5.0); CSF oligoclonal bands 85.7%, and 87% of subjects hydroxyvitamin D deficient. Common initial therapies were interferon and fingolimod. Switching from interferon to fingolimod was the most common escalation step. The COVID-19 pandemic affected follow-up aspects of these studies. Conclusion: This is the first study providing data on frequencies and clinical characteristics from 8 countries from the Central American and Caribbean region, addressing MS as an emergent epidemiologic disorder. More studies from these areas are encouraged.
RESUMO
BACKGROUND: We assessed the effectiveness, safety and patient-reported outcomes (PROs) of dimethyl fumarate (DMF) in real-world clinical practice in patients with multiple sclerosis (PwMS) from Argentina. METHODS: We conducted a multicenter ambispective cohort study in Argentina between September 2020 and March 2023. Changes in annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, magnetic resonance imaging (MRI), no evidence of disease activity (NEDA), PROs (depression, anxiety, fatigue, burden of treatment and quality of life), and safety data were collected at clinical visits performed every 6 months for at least 24 months. RESULTS: We included 161 PwMS (64% female). DMF treatment was associated with a significant reduction in ARR from baseline after 24 months of treatment (from 0.87 to 0.23, p < 0.001). Disability progression was observed in 27.9% vs. 9.3% pre- and post-DMF, and disability improvement was found in 13% of patients from baseline to month 24. MRI activity was significantly reduced compared with baseline. Fatigue, depression, and quality of life scores were significantly improved from baseline to 24 months. Flushing was the most frequent adverse event reported in 19.2%. No significant reduction was observed in the hospitalization rate pre- and post-DMF (19.8% vs. 5.6%, p = 0.32). During follow-up, 135 (83%) patients were relapse-free, 110 (68.3%) were MRI free activity (Gad + lesion) and 108 (67%) reached NEDA. CONCLUSIONS: DMF significantly reduced disease activity in PwMS from Argentina with a good safety profile in real-world settings. A significant impact on the quality of life during follow-up was found.
RESUMO
The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.
Assuntos
Astrócitos , Doenças Neurodegenerativas , Astrócitos/metabolismo , Astrócitos/patologia , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Animais , FenótipoRESUMO
Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.
Assuntos
Biologia Computacional , Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Feminino , Gravidez , Biologia Computacional/métodos , Redes Reguladoras de Genes , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Perfilação da Expressão Gênica , Transdução de Sinais/genética , Regulação da Expressão GênicaRESUMO
Objective: Multiple sclerosis (MS) may include not only severe neurological signs and symptoms, but also cognitive and psychiatric disturbances. When psychiatric symptoms precede or are comorbid with MS, it poses a clinical challenge, because it may lead to a mistaken diagnosis of MS as a psychiatric disorder, delaying proper treatment. We describe the neuropsychological profile of a female patient with MS whose diagnosis was delayed due to neuropsychiatric symptoms. Method: A comprehensive analysis of the medical history and the results of a teleneuropsychological assessment of a 36-year-old Mexican woman with a diagnosis of relapsing--remitting MS (RRMS) was performed. Results: The patient indicates a long history of psychotic, anxious, and depressive features years before the first neurological symptom that led to MS going unnoticed for several years. Language, attentional, perceptual, motor, and learning skills were found to be preserved. Short-term memory and spatial orientation problems were identified, with decreased processing speed and executive dysfunction, including working memory and planning deficits. Conclusions: The patient has a non-typical presentation of neuropsychological alterations with cognitive and behavioral symptoms that resemble dorsolateral frontal lobe syndrome. This case study highlights the importance of considering MS in differential diagnosis of patients with psychiatric symptoms, even in the absence of obvious neurological signs.
RESUMO
The aging of populations is a global phenomenon that follows a possible increase in the incidence of neurodegenerative diseases. Alzheimer's, Parkinson's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Huntington's diseases are some neurodegenerative disorders that aging could initiate or aggravate. Recent research has indicated that intestinal microbiota dysbiosis can trigger metabolism and brain functioning, contributing to the etiopathogenesis of those neurodegenerative diseases. The intestinal microbiota and its metabolites show significant functions in various aspects, such as the immune system modulation (development and maturation), the maintenance of the intestinal barrier integrity, the modulation of neuromuscular functions in the intestine, and the facilitation of essential metabolic processes for both the microbiota and humans. The primary evidence supporting the connection between intestinal microbiota and its metabolites with neurodegenerative diseases are epidemiological observations and animal models experimentation. This paper reviews up-to-date evidence on the correlation between the microbiota-gut-brain axis and neurodegenerative diseases, with a specially focus on gut metabolites. Dysbiosis can increase inflammatory cytokines and bacterial metabolites, altering intestinal and blood-brain barrier permeability and causing neuroinflammation, thus facilitating the pathogenesis of neurodegenerative diseases. Clinical data supporting this evidence still needs to be improved. Most of the works found are descriptive and associated with the presence of phyla or species of bacteria with neurodegenerative diseases. Despite the limitations of recent research, the potential for elucidating clinical questions that have thus far eluded clarification within prevailing pathophysiological frameworks of health and disease is promising through investigation of the interplay between the host and microbiota.
Assuntos
Eixo Encéfalo-Intestino , Disbiose , Microbioma Gastrointestinal , Doenças Neurodegenerativas , Humanos , Microbioma Gastrointestinal/fisiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/microbiologia , Disbiose/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismoRESUMO
BACKGROUND: Fatigue is a common symptom in patients with multiple sclerosis and it can lead to activity limitations. Thus, it is important to analyze the relationship between fatigue and activity outcomes, such as walking speed and mobility. OBJECTIVES: To investigate the relationship between fatigue and walking speed and mobility in individuals with multiple sclerosis. METHODS: A cross-sectional study was performed. Adults with multiple sclerosis, without cognitive impairments and who were able to walk were recruited. Fatigue was assessed with the Modified Fatigue Impact Scale (MFIS). Walking speed, usual and fast, was assessed with the 10-meter Walk Test (10MWT), and mobility with the Timed Up and Go Test (TUG). Pearson correlation analysis was performed. A significance level of 5 % was used. RESULTS: Thirty participants were included, most of the relapsing-remitting multiple sclerosis (n = 24, 80 %). A mean age of 41 (11) years and the median Expanded Disability Status Scale (EDSS) score was 2.65 (2.18) points. Mean MFIS score was 41.87 ± 19.42 points, mean usual walking speed was 1.02 ± 0.28 m/s, mean fast walking speed was 1.55 ± 0.48 m/s, and the mean total time in the TUG was 10.07 ± 3.05 s. A significant negative correlation of moderate magnitude was found between fatigue and usual walking speed (r=â0.51, p < 0.05). A significant negative correlation of moderate magnitude was found between fatigue and fast walking speed (r=â0.54, p < 0.05). A significant, positive correlation of moderate magnitude was found between fatigue and mobility (r = 0.54, p < 0.05). CONCLUSION: There was a correlation between fatigue and walking speed and mobility in individuals with multiple sclerosis. These results highlight the need to assess fatigue in individuals with multiple sclerosis, since the presence of fatigue is associated with reduced walking speed and mobility.
Assuntos
Fadiga , Esclerose Múltipla , Velocidade de Caminhada , Humanos , Feminino , Masculino , Fadiga/etiologia , Fadiga/fisiopatologia , Adulto , Estudos Transversais , Velocidade de Caminhada/fisiologia , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Limitação da MobilidadeRESUMO
Introduction: Multiple sclerosis significantly affects the quality of life of those suffering from this specific condition. Objective: To assess the quality of life of people with multiple sclerosis and analyse the correlation between the disease and its associated effects and different sociodemographic, clinical, and functional variables. Materials and Methods: An observational, cross-sectional, descriptive-correlational and quantitative study conducted using a non-probabilistic convenience sample composed of 70 patients suffering from multiple sclerosis registered with the Multiple Sclerosis Association of the Central Region of Portugal. The data collection protocol included sociodemographic and clinical questions, the Family Apgar Scale, and the Barthel Index. Descriptive and inferential statistics were used to process the data. Data collection took place between April and July 2021. Results: The majority of participants reported a moderate overall quality of life (M=51,78 ± 24,09). Higher scores were observed in the social relationships and environmental health domains, while lower scores were recorded for the physical domain. Better quality of life was found to be positively associated with being under 45 years old, having higher educational qualifications, living in functional families, and experiencing greater functional independence in activities of daily living. Discussion: The variables with the strongest association were those capable of influencing the physical and social domains. Those variables explained 59.00% and 53.00% of the variability. Conclusions: These results indicate that people with multiple sclerosis have a compromised quality of life, highlighting the need for new strategies focusing on early diagnosis and effective preventive interventions meant to improve quality of life across all its domains.
Assuntos
Pacientes , Qualidade de Vida , Doenças Desmielinizantes , Estimulantes do Sistema Nervoso Central , Esclerose MúltiplaRESUMO
Cumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-ß or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-ß and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b+ myeloid cells expressing TGF-ß-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b+ cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4+ T cells mediated by secretion of TGF-ß. Remarkably, adoptive transfer of splenic CD11b+ cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism whereby IFN-γ promotes beneficial effects in EAE by endowing splenic CD11b+ myeloid cells with tolerogenic and therapeutic activities.
Assuntos
Antígeno CD11b , Encefalomielite Autoimune Experimental , Interferon gama , Camundongos Endogâmicos C57BL , Células Mieloides , Baço , Animais , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Camundongos , Interferon gama/metabolismo , Células Mieloides/efeitos dos fármacos , Células Mieloides/imunologia , Células Mieloides/metabolismo , Baço/imunologia , Antígeno CD11b/metabolismo , Feminino , Glicoproteína Mielina-Oligodendrócito/toxicidade , Glicoproteína Mielina-Oligodendrócito/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Fragmentos de Peptídeos/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Fatores de Transcrição Forkhead/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: Fatigue is one of the most common symptoms reported by individuals with multiple sclerosis and it contributes to the reduction of the functionality. Therefore, it is important to assess the impact of fatigue on daily living of individuals with multiple sclerosis. The Modified Fatigue Impact Scale (MFIS) is an instrument to assess the perception of the impact of fatigue. However, there have been no investigations about the measurement properties of this instrument administered over the telephone for individuals with multiple sclerosis. OBJECTIVES: To verify the concurrent validity, the test-retest reliability, the standard error of measurement (SEM) and the minimal detectable change (MDC) of the MFIS applied over the telephone to assess the perception of the impact of fatigue of individuals with multiple sclerosis. METHODS: The MFIS, composed of 21 items covering three domains: physical, cognitive and psychosocial, was applied at three different moments with an interval of 5-7 days. To establish the concurrent criterion validity, the face-to-face application and the first evaluation by telephone were used. The two telephone assessments were used to assess the test-retest reliability The intraclass correlation coefficient (ICC) with 95 % confidence interval (CI) and the Bland-Altman method were used. The standard error of measurement (SEM) and the MDC was calculated according to reliability results. RESULTS: Thirty individuals (40.83 ± 10.61, 60 % female) were included. The median score on the Expanded Disability Status Scale was 2.00 (±4.00). The majority of participants experienced fatigue (n = 17; 56.67 %). A significant and high magnitude correlation (0.70 ≤ ICC ≤ 0.87, p < 0.001) was found in the investigation of concurrent criterion validity. The Bland-Altman method showed a mean difference between 0.70 to 2.17 points between face-to-face and telephone-based application of the MFIS. For test-retest reliability, a significant and very high magnitude correlation (0.91 ≤ ICC ≤ 0.97, p < 0.001) was found. The Bland-Altman method showed a mean difference between -0.03 and -0.77 points between two telephone-based applications. The SEM and the MDC were 0.71 and 1.97 points. CONCLUSION: The telephone-based application of the MFIS to assess the perceived impact of fatigue in individuals with multiple sclerosis demonstrated adequate measurement properties, and may be a valuable tool to assess patients in clinical practice.
Assuntos
Fadiga , Esclerose Múltipla , Telefone , Humanos , Fadiga/etiologia , Fadiga/diagnóstico , Feminino , Reprodutibilidade dos Testes , Masculino , Esclerose Múltipla/complicações , Adulto , Pessoa de Meia-Idade , Psicometria/normas , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Knowledge of the safety and efficacy of disease-modifying therapies (DMTs) in older patients with Multiple Sclerosis (pwMS) is limited due to their exclusion from clinical trials. Our purpose is to evaluate the choice of DMTs in pwMS older than 50 years old in a real-world setting. METHODS: Cross-sectional study of pwMS from the Argentine MS and NMOSD Registry. We included patients under 35 and above 50 years old prescribed DMTs. Disease activity was categorized as highly active (HA) or not highly active (NHA), and DMTs were classified as low efficacy therapies (LET) or high efficacy therapies (HET). RESULTS: 1460 patients (65% females) were enrolled. The HA group comprised 241 patients, 198 young (82.2%) and 43 older (17.8%). The NHA group included 1219 patients, 893 young (73%) and 326 older (27%). In the NHA group, older patients received LET more frequently than younger patients (66% versus 44%; p < 0.01). In the HA group, older patients received LET in 61% of cases, whereas younger patients received HET in 71% (p = 0.01). CONCLUSION: The study shows the preference of LET in older patients regardless of disease activity. However it does not demonstrate a difference in disability in older patients based on low vs high efficacy DMTs used, probably due to the design of the study. Further longitudinal studies are warranted to address this issue.
Assuntos
Esclerose Múltipla , Sistema de Registros , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Adulto , Fatores Etários , Argentina/epidemiologia , Idoso , Fatores Imunológicos/uso terapêuticoRESUMO
BACKGROUND: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. OBJECTIVES: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. METHODS: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. RESULTS: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. CONCLUSIONS: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.