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1.
Epidemiol Psychiatr Sci ; 29: e84, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31915099

RESUMO

AIMS: Although immune-mediated inflammatory diseases (IMID) are associated with multiple mental health conditions, there is a paucity of literature assessing personality disorders (PDs) in these populations. We aimed to estimate and compare the incidence of any PD in IMID and matched cohorts over time, and identify sociodemographic characteristics associated with the incidence of PD. METHODS: We used population-based administrative data from Manitoba, Canada to identify persons with incident inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) using validated case definitions. Unaffected controls were matched 5:1 on sex, age and region of residence. PDs were identified using hospitalisation or physician claims. We used unadjusted and covariate-adjusted negative binomial regression to compare the incidence of PDs between the IMID and matched cohorts. RESULTS: We identified 19 572 incident cases of IMID (IBD n = 6,119, MS n = 3,514, RA n = 10 206) and 97 727 matches overall. After covariate adjustment, the IMID cohort had an increased incidence of PDs (incidence rate ratio [IRR] 1.72; 95%CI: 1.47-2.01) as compared to the matched cohort, which remained consistent over time. The incidence of PDs was similarly elevated in IBD (IRR 2.19; 95%CI: 1.69-2.84), MS (IRR 1.79; 95%CI: 1.29-2.50) and RA (IRR 1.61; 95%CI: 1.29-1.99). Lower socioeconomic status and urban residence were associated with an increased incidence of PDs, whereas mid to older adulthood (age 45-64) was associated with overall decreased incidence. In a restricted sample with 5 years of data before and after IMID diagnosis, the incidence of PDs was also elevated before IMID diagnosis among all IMID groups relative to matched controls. CONCLUSIONS: IMID are associated with an increased incidence of PDs both before and after an IMID diagnosis. These results support the relevance of shared risk factors in the co-occurrence of PDs and IMID conditions.


Assuntos
Artrite Reumatoide/epidemiologia , Doenças do Sistema Imunitário/complicações , Inflamação/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Esclerose Múltipla/epidemiologia , Transtornos da Personalidade/epidemiologia , Adolescente , Adulto , Canadá/epidemiologia , Estudos de Coortes , Comorbidade/tendências , Feminino , Humanos , Doenças do Sistema Imunitário/epidemiologia , Incidência , Inflamação/epidemiologia , Masculino , Manitoba/epidemiologia , Pessoa de Meia-Idade , Transtornos da Personalidade/psicologia , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
2.
J Comput Assist Tomogr ; 44(1): 47-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939881

RESUMO

PURPOSE: The discrimination between neuromyelitis optica (NMO)- and multiple sclerosis (MS)-related acute optic neuritis (ON) after the first presentation is difficult in clinical practice. Through a comparison with diffusion-weighted imaging using readout-segmented echo-planar imaging (RESOLVE-DWI), our aim was to determine the feasibility of diffusional kurtosis imaging (DKI) for differential diagnosis. MATERIALS AND METHODS: Orbital DKI and RESOLVE-DWI in a 3.0-T scanner were performed on 37 patients with acute ON (15 NMO-related and 22 MS-related). The mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) were calculated for quantitative analyses, and receiver operating characteristic curve analyses were also performed to determine their abilities to differentiate the 2 conditions. RESULTS: The intraclass correlation coefficients among observers were 0.842, 0.885, 0.828, 0.871, and 0.942 for MK, RK, AK, MD, and ADC, respectively, in the affected nerve group and 0.890, 0.840, 0.832, 0.934, and 0.941 in the unaffected nerve group. Regarding the comparisons of the DKI and RESOLVE-DWI parameters among the groups, the mean MK, RK, AK, MD, and ADC values were significantly lower in the affected groups (all, P < 0.001). Furthermore, the MK, RK, MD, and ADC values were significantly lower in the NMO-ON group than in the MS-ON group (P = 0.001, 0.002, 0.013, and <0.001, respectively), and no significant differences were found in the AK values (P = 0.064). In addition, establishing MK ≤ 0.843 as the diagnostic criterion for NMO-related acute ON provided the highest sensitivity (90.5%), whereas the highest specificity (91.3%) was obtained using RK ≤ 0.784 as the diagnostic criterion. CONCLUSIONS: Diffusional kurtosis imaging is helpful for differentiating NMO-related acute ON from MS-related acute ON, and it can achieve more agreeable sensitivity and specificity than RESOLVE-DWI in differential diagnosis.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Esclerose Múltipla/diagnóstico por imagem , Neuromielite Óptica/diagnóstico por imagem , Neurite Óptica/etiologia , Adolescente , Adulto , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Masculino , Esclerose Múltipla/complicações , Neuromielite Óptica/complicações , Neurite Óptica/diagnóstico por imagem , Adulto Jovem
3.
Immunity ; 52(1): 11-13, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31951547

RESUMO

Multiple sclerosis is a chronic inflammatory disease characterized by demyelination in the central nervous system. In this issue of Immunity, Werneberg et al. report a striking loss of synapses driven by excessive microglial pruning early in demyelinating disease, which can be rescued by inhibiting the complement component C3.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Sistema Nervoso Central , Humanos , Microglia , Sinapses
4.
Brain Nerve ; 72(1): 45-60, 2020 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-31907332

RESUMO

Treatments for multiple sclerosis have improved dramatically over the last 20 years. These treatments help to reduce relapses and prevent progression of neurodegeneration and physical disability. Other clinical trials on remyelination therapies for multiple sclerosis are ongoing. Various treatments for multiple sclerosis have been developed and are expected to enter the treatment arena soon.


Assuntos
Esclerose Múltipla , Progressão da Doença , Humanos , Recidiva
5.
Brain Nerve ; 72(1): 61-68, 2020 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-31907333

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is a disease related to anti-aquaporin-4 antibody. Since NMOSD was once considered a phenotype of multiple sclerosis, no approved drugs are available for its treatment. In Japan, the current standard treatment for preventing relapses in patients with NMOSD is low-dose prednisolone and/or oral immuno-suppressants. There is a critical unmet need for non-steroid treatments for patients with NMOSD. Four monoclonal antibodies have completed their clinical trials in Japan and are pending approval. In this review, we summarize the results of each of these clinical trials.


Assuntos
Esclerose Múltipla , Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Humanos , Japão
6.
Medicine (Baltimore) ; 99(4): e18866, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977888

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease, affecting both the sensorimotor and cognitive systems. The typical pattern of cognitive impairment includes reduced speed of information processing, decreased phonological and semantic speech fluency, deficits in verbal and visual episodic memory, as well as attention and executive dysfunctions. We aimed to investigate the influence of the neurologic music therapy (NMT) on mood, motivation, emotion status, and cognitive functions in patients with MS. METHODS: Thirty patients with MS were randomly divided in 2 groups: the control group (CG) undergoing conventional cognitive rehabilitation (CCR), 6 times a week for 8 weeks, and the experimental group (EG) undergoing CCR 3 times a week for 8 weeks plus NMT techniques, performed 3 times a week for 8 weeks. All the participants were submitted to the same amount of treatment. Each patient was evaluated before (baseline: T0) and immediately after the end of each training (T1). MAIN OUTCOMES MEASURES: We used as main outcome measure: the brief repeatable battery of neuropsychological test to assess various cognitive abilities; and the multiple sclerosis quality of life-54 (MSQoL-54). RESULTS: Both the groups benefit from 8 weeks of CR. In particular, the EG got better results in cognitive function, with regard to selective reminding test long term storage (P < .000), long term retrieval (P = .007), and delayed recall of the 10/36 spatial recall test (P = .001), as compared with the CG. Moreover, the improvement in emotional status, motivation, mood and quality of life (with regard to the mental component; P < .000) was more evident in the EG. CONCLUSIONS: NMT could be considered a complementary approach to enhance CCR in patients affected by MS.


Assuntos
Disfunção Cognitiva/terapia , Esclerose Múltipla/terapia , Musicoterapia/métodos , Afeto , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Projetos Piloto , Qualidade de Vida , Método Simples-Cego , Resultado do Tratamento
8.
Nat Rev Neurol ; 16(1): 56-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31649335

RESUMO

New so-called immune reconstitution therapies (IRTs) have the potential to induce long-term or even permanent drug-free remission in people with multiple sclerosis (MS). These therapies deplete components of the immune system with the aim of allowing the immune system to renew itself. Haematopoietic stem cell transplantation, the oral formulation cladribine and the monoclonal antibodies alemtuzumab, rituximab and ocrelizumab are frequently categorized as IRTs. However, the evidence that IRTs indeed renew adaptive immune cell repertoires and rebuild a healthy immune system in people with MS is variable. Instead, IRTs might foster the expansion of those cells that survive immunosuppression, and this expansion could be associated with acquisition of new functional phenotypes. Understanding immunological changes induced by IRTs and how they correlate with clinical outcomes will be instrumental in guiding the optimal use of immune reconstitution as a durable therapeutic strategy. This Perspectives article critically discusses the efficacy and potential mechanisms of IRTs in the context of immune system renewal and durable disease remission in MS.


Assuntos
Reconstituição Imune/imunologia , Imunoterapia/tendências , Esclerose Múltipla/imunologia , Esclerose Múltipla/terapia , Humanos , Imunoterapia/métodos , Indução de Remissão/métodos
9.
Immunity ; 52(1): 167-182.e7, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31883839

RESUMO

Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. While work has focused on myelin and axon loss in MS, less is known about mechanisms underlying synaptic changes. Using postmortem human MS tissue, a preclinical nonhuman primate model of MS, and two rodent models of demyelinating disease, we investigated synapse changes in the visual system. Similar to other neurodegenerative diseases, microglial synaptic engulfment and profound synapse loss were observed. In mice, synapse loss occurred independently of local demyelination and neuronal degeneration but coincided with gliosis and increased complement component C3, but not C1q, at synapses. Viral overexpression of the complement inhibitor Crry at C3-bound synapses decreased microglial engulfment of synapses and protected visual function. These results indicate that microglia eliminate synapses through the alternative complement cascade in demyelinating disease and identify a strategy to prevent synapse loss that may be broadly applicable to other neurodegenerative diseases. VIDEO ABSTRACT.


Assuntos
Complemento C3/imunologia , Encefalomielite Autoimune Experimental/patologia , Microglia/patologia , Esclerose Múltipla/patologia , Sinapses/patologia , Tálamo/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Callithrix , Linhagem Celular Tumoral , Complemento C3/antagonistas & inibidores , Modelos Animais de Doenças , Feminino , Gliose/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Receptores de Complemento 3b/metabolismo
10.
Arch Esp Urol ; 72(10): 1010-1017, 2019 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-31823849

RESUMO

OBJECTIVES: To determine the risk factors of recurrent urinary infections (rUTIs) in patients with Multiple Sclerosis (MS). METHODS: A retrospective cohort study was conducted including 114 patients with MS, 84 women (74%) and 30 men (26%), with a mean age of 49. They underwent videourodynamic study and selective sphincter electromyography due to urinary symptoms (LUTS). Clinical data (both neurological and urological) and videourodynamic data (including free flowmetry, cystomanometry and pressure flow study) were collected. In 37 patients (32%), the presence of rTUIs was demonstrated. RESULTS: Statistically significant differences were demonstrated between the patients with and without rUTIs with respect to the following clinical variables: the time of evolution of the symptoms (greater in the case of rUTIs), time from the diagnosis of MS (higher in the case of rUTIs), EDSS score (Expanded Disability Staus Scale) (higher in the case of rUTIs) and the EM type [higher frequency of rUTIs in the progressive types (primary and secondary)]. Urodynamic variables with significant differences were: maximum flow in free flowmetry (lower in patients with rUTIs), voiding volume in free flowmetry (lower in patients with rUTIs), micturition efficiency (higher percentage of residual urine in patients with rUTIs), stress urinary incontinence (SUI) (higher frequency of rUTIs in patients with SUI), detrusor pressure at maximum flow (lower in patients with rUTIs) and bladder contractility index (lower in patients with rUTI). No significant difference was demonstrated in relation to the presence and type of neurogenic lower urinary tract dysfunction (NLUTD). CONCLUSIONS: The severity and duration of MS is a risk factor for rUTIs. Urodynamic risk factors are compatible with a lower contractile capacity in patients with rUTIs, while the existence of NLUTD would not imply any specific risk factor.


Assuntos
Esclerose Múltipla , Infecções Urinárias , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/complicações , Urodinâmica
11.
Zhonghua Yi Xue Za Zhi ; 99(45): 3574-3580, 2019 Dec 03.
Artigo em Chinês | MEDLINE | ID: mdl-31826574

RESUMO

Objective: To investigate the effect of HLA-DP gene expression on the susceptibility and disease status of neuromyelitis optica spectrum disorders (NMOSD). Methods: A total of 86 NMOSD patients (52 in acute phase and 34 in remission phase), 52 multiple sclerosis (MS) patients (20 in acute phase and 32 in remission phase) diagnosed in Department of Neurology, the Third Affiliated Hospital of Sun Yat-sen University and 29 healthy controls were enrolled prospectively. Genotyping of HLA-DP was performed. The expression levels of HLA-DP molecules in peripheral blood B cells and monocytes were measured by flow cytometry. The transcription levels of HLA-DPB1 mRNA in peripheral blood mononuclear cells (PBMC) were measured by real time-PCR. The results were compared among different groups Results: There was no statistically significant difference of the distributions of HLA-DPB1*0501/HLA-DPB1*0501, HLA-DPB1*0501/X and X/X genotypes and the frequencies of allele of HLA-DPB1*0501 among NMOSD, MS patients and healthy controls (P=0.96 and 0.71, respectively). The expression levels of HLA-DP on the surface of B cells in NMOSD patients, especially in remission phase patients, were significantly higher than those in healthy controls(212±328 and 374±394 vs 55±57, P=0.049 and 0.002, respectively). The expression levels of HLA-DP on the surface of monocytes in NMOSD patients in acute phase were significantly higher than those in healthy controls(158±175 vs 65±90, P=0.025). The transcription levels of PMBC HLA-DPB1 mRNA in acute phase and remission phase of NMOSD patients were significantly higher than those in healthy controls (3.0±1.4 and 2.9±1.3 vs 1.5±1.4, P=0.000 and 0.003, respectively). The expression levels of HLA-DP molecules on the surface of peripheral blood B cells and monocytes and the transcription levels of PMBC HLA-DPB1 mRNA in MS patients at the acute and remission stages were not significantly different from those in healthy controls. The expression levels of HLA-DP molecules on the surface of B cells in patients with HLA-DPB1*0501/HLA-DPB1*0501, HLA-DPB1*0501/X and X/X genotypes were statistically different (P=0.017). Conclusion: HLA-DP gene transcription and molecular expression levels in antigen presenting cells may affect the susceptibility and disease status of NMOSD patients, while HLA-DPB1*0501 allele may affect the transcription and molecular expression levels of HLA-DP gene in antigen presenting cells.


Assuntos
Neuromielite Óptica , Alelos , Expressão Gênica , Humanos , Leucócitos Mononucleares , Esclerose Múltipla
12.
Artigo em Russo | MEDLINE | ID: mdl-31793538

RESUMO

AIM: To analyze the interaction between the localization of demyelination plaques and damage to the optic nerve in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Fifty-five patients (18 men and 37 women) with a confirmed diagnosis of MS were examined based on magnetic resonance imaging of the brain (MRI) and the conclusion of a neurologist. Four topographic zones of localization of the visual paths were identified: the orbital part of the optic nerve, periventricular white matter, areas of the right and left thalamus, and white matter of the occipital lobe of the big hemispheres. The MRI data were compared with the results of spectral optical coherence tomography (C-OCT) of the same study. RESULTS: The greatest number of demyelination plaques is described in the periventricular white matter of the lateral ventricles, and the smallest number in the white matter of the occipital lobe of the large hemispheres. In patients with optic neuritis (ON), demyelination plaques were also detected in the projection of the orbital part of ON in 18% of cases. A comparison analysis reveals no correlation between the side of optical nerve lesion and the presence of lesions in the projection of the orbital part of ON. The predictive ability of C-OCT of focal changes in the brain in interaction with C-OCT parameters in groups with ON and partial ON atrophy due to MS is not confirmed. CONCLUSION: In all patients with MS, demyelination plaques are detected in the visual analyzer (VA) projection, even with the manifestation of the disease. In the course of MS progression, their total number increases. Localization of focal demyelination processes in MS in the projection VA and the side of the lesion do not have reliably confirmed the interaction with the parameters of the optic disc in accordance with C-OCT. A lesion of the peripheral neuron VA is identified in all patients.


Assuntos
Esclerose Múltipla , Neurite Óptica , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Esclerose Múltipla/complicações , Nervo Óptico/diagnóstico por imagem , Neurite Óptica/complicações , Tomografia de Coerência Óptica
13.
Neurol Neurochir Pol ; 53(6): 458-465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31793659

RESUMO

INTRODUCTION: Prompt successful control of disease activity in multiple sclerosis (MS) patients improves outcomes. Therefore, tools to aid drug selection and detect non-responders are urgently needed. Although several biochemical markers for predicting response to treatment have been proposed, clinical markers involving relapses, imaging activity and disability progression in the initial years of therapy remain competitive and appear cost-effective in a real-life setting. The aim of this study was to evaluate the prognostic value of select clinical scores in interferon beta-1b (IFNß-1b) treated MS patients. MATERIALS AND METHODS: Eighty-eight relapsing-remitting MS (RRMS) patients initiating treatment with IFNß-1b in a Polish outpatient clinic were followed for a median of 5.5 years. Rio, modified Rio and BREMSO scores, as well as two-year no evidence of disease activity (NEDA), were assessed as predictors of disease activity during the observation. RESULTS: A Rio score of 1 had a Positive Predictive Value (PPV) of 83.3% and a Negative Predictive Value (NPV) of 71.4% for the occurrence of relapses in the first five years. A Rio and modified Rio score of 1 was associated with MRI activity after year 3. A loss of NEDA within the first two years was associated with a failure to maintain NEDA in the next three years. The BREMSO score was higher in patients with early relapse activity. Only baseline EDSS and total number of pre-treatment relapses were significantly associated with disability progression. CONCLUSIONS: Rio, modified Rio, early NEDA on treatment and BREMSO score are relatively specific, but insensitive, predictors of relapse activity in the first years of IFNß-1b treatment. Higher pre-treatment EDSS and relapse activity is associated with disability progression, but not overall NEDA, in subsequent observation. While none of the markers is sufficiently sensitive or specific to make a certain prognosis, they may aid treatment decisions in patients with continued early disease activity.


Assuntos
Esclerose Múltipla , Avaliação da Deficiência , Humanos , Interferon beta-1b , Polônia , Prognóstico
14.
S D Med ; 72(10): 472-476, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31816210
15.
Nihon Yakurigaku Zasshi ; 154(6): 340-344, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787687

RESUMO

Central nervous system (CNS) inflammation causes severe neurological dysfunction, such as motor, sensory, and cognitive impairments. One of the reasons for the developing disease depends on the damage of neuronal network, a predominant feature of many CNS diseases. Therefore, protection and/or regeneration of damaged neuronal network after injury is considered to be useful for treating neurological diseases; however, the mechanism of protection and regeneration of neuronal network is not fully elucidated. In this paper, I describe our recent findings about the mechanism that disrupt and regenerate neuronal network by using animal model of multiple sclerosis. I also introduce the key molecules which is involved in inflammation, neurovascular interaction, and systemic regulation. These findings have a potential to contribute develop the new therapies for treating neurological disease.


Assuntos
Doenças do Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Regeneração Nervosa , Animais , Humanos , Inflamação/patologia , Esclerose Múltipla , Neurônios/patologia
16.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31885862

RESUMO

Emerging data point to important contributions of both autoimmune inflammation and progressive degeneration in the pathophysiology of multiple sclerosis (MS). Unfortunately, after decades of intensive investigation, the fundamental cause remains unknown. A large body of research on the immunobiology of MS has resulted in a variety of anti-inflammatory therapies that are highly effective at reducing brain inflammation and clinical/radiological relapses. However, despite potent suppression of inflammation, benefit in the more important and disabling progressive phase is extremely limited; thus, progressive MS has emerged as the greatest challenge for the MS research and clinical communities. Data obtained over the years point to a complex interplay between environment (e.g., the near-absolute requirement of Epstein-Barr virus exposure), immunogenetics (strong associations with a large number of immune genes), and an ever more convincing role of an underlying degenerative process resulting in demyelination (in both white and grey matter regions), axonal and neuro-synaptic injury, and a persistent innate inflammatory response with a seemingly diminishing role of T cell-mediated autoimmunity as the disease progresses. Together, these observations point toward a primary degenerative process, one whose cause remains unknown but one that entrains a nearly ubiquitous secondary autoimmune response, as a likely sequence of events underpinning this disease. Here, we briefly review what is known about the potential pathophysiological mechanisms, focus on progressive MS, and discuss the two main hypotheses of MS pathogenesis that are the topic of vigorous debate in the field: whether primary autoimmunity or degeneration lies at the foundation. Unravelling this controversy will be critically important for developing effective new therapies for the most disabling later phases of this disease.


Assuntos
Doenças Desmielinizantes , Encefalite , Esclerose Múltipla , Axônios , Substância Cinzenta , Humanos
17.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(11): 133-138, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31851185

RESUMO

Endothelial dysfunction today is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and induction of apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in the pathogenesis of MS.


Assuntos
Endotélio , Hiper-Homocisteinemia , Esclerose Múltipla , Barreira Hematoencefálica , Sistema Nervoso Central , Endotélio/fisiopatologia , Humanos , Hiper-Homocisteinemia/imunologia , Hiper-Homocisteinemia/fisiopatologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/fisiopatologia , Neurônios
18.
Adv Exp Med Biol ; 1189: 233-265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31758537

RESUMO

Inflammation plays an important role in the onset and progression of many neurological diseases. As the central nervous system (CNS) constitutes a highly specialized environment where immune activation can be detrimental, it is crucial to understand mechanisms by which the immune system is regulated during neurological diseases. The system of co-signaling pathways provides the immune system with the means to fine-tune immune responses by turning on and off immune cell activation. Studies of co-signaling molecules in neurological diseases and their animal models have highlighted the complexities of immune regulation within the CNS and the intricacies of the interplay between the different cells of the immune system and how they interact with the resident cells of the CNS. This complexity poses challenges when targeting co-signaling pathway to treat neurological diseases and may explain why no drugs targeting these pathways have been successfully developed this far. Here, we will review the current literature on some important co-signaling pathways in multiple sclerosis (MS), Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and ischemic stroke to understand these pathways in mediating and controlling neuroinflammation.


Assuntos
Doenças do Sistema Nervoso , Transdução de Sinais , Doença de Alzheimer , Esclerose Amiotrófica Lateral , Animais , Isquemia Encefálica , Esclerose Múltipla , Doença de Parkinson
19.
Adv Exp Med Biol ; 1190: 217-247, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760647

RESUMO

Multiple sclerosis (MS) is an inflammatory demyelinating disorder. Although all MS patients initially show a relapsing-remitting course, 20-50% subsequently enter a chronic progressive course at 10-20 years after onset that greatly influences their activities of daily living. There are 2.5 million MS patients worldwide with large regional and racial differences. In particular, there are many MS patients among Caucasians living in Europe, while the disease is relatively rare in Asians and Africans.Although MS is regarded as an autoimmune disease, many factors such as genetic background, environmental factors, and sex are involved in its pathogenesis. While the immunological mechanisms remain to be fully elucidated, invasion of autoreactive T cells into the central nervous system (CNS) tissue is considered the first step of the disease. These T cells react with myelin antigens and initiate demyelination of the CNS by activating cytotoxic T cells, macrophages, and B cells through the release of inflammatory cytokines. As a treatment option, disease-modifying therapies have recently been developed to prevent the recurrence of MS in addition to conventional treatment with corticosteroids for acute relapse. However, there are still few effective treatments for the chronic progressive phase, and it is thus imperative to decipher the mechanism for chronic progression.


Assuntos
Esclerose Múltipla/fisiopatologia , Linfócitos T/imunologia , Atividades Cotidianas , Linfócitos B/imunologia , Sistema Nervoso Central/fisiopatologia , Citocinas/imunologia , Humanos , Macrófagos/imunologia , Esclerose Múltipla/imunologia , Bainha de Mielina/imunologia
20.
Adv Exp Med Biol ; 1190: 249-256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760648

RESUMO

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) affecting more than two million people worldwide. As the exact etiology of MS remains elusive, the diagnosis of MS is made by referring to the McDonald diagnostic criteria, which utilizes MRI as a tool to identify "demyelinated" MS lesions. In particular, hyperintense lesions on T2-weighted images (T2WI) or so-called "T2-lesions" are considered to represent demyelinated MS lesions. T2WI, however, lacks myelin specificity, and moreover, remyelination could not be depicted by the use of such modality. For the accurate diagnosis and treatment decision-making, or for the future development of remyelination therapeutics, imaging tools to visualize myelin-specific signals are mandatory. In this chapter, the current use and the limitation of imaging modalities in MS diagnosis and treatment will be reviewed, with the introduction of new imaging method, namely q-space Myelin Map (qMM), to be used for visualization of demyelination and remyelination in MS.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/terapia , Bainha de Mielina/patologia , Humanos , Imagem por Ressonância Magnética
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