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1.
Phys Med Rehabil Clin N Am ; 32(2): 239-251, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33814055

RESUMEN

Amyotrophic lateral sclerosis and multiple sclerosis are neurodegenerative diseases requiring interdisciplinary rehabilitation services to maximize function, manage symptoms, prevent complications, and promote higher quality of life. Distance and disability may pose barriers to access of subspecialized care. Telehealth is one solution to facilitate access and was rapidly expanded during the COVID-19 pandemic. This article details the utility of telehealth services across the disease spectrum-including to establish a diagnosis, monitor progression for ongoing management, and identify and manage symptoms and provide therapy interventions. The challenges and promise of telehealth services for clinical care and research will be explored.


Asunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/terapia , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/terapia , Telemedicina/métodos , /epidemiología , Accesibilidad a los Servicios de Salud , Humanos , Pandemias , Grupo de Atención al Paciente , Examen Físico
2.
Nat Commun ; 12(1): 2078, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33824310

RESUMEN

Multiple sclerosis (MS) can be divided into four phenotypes based on clinical evolution. The pathophysiological boundaries of these phenotypes are unclear, limiting treatment stratification. Machine learning can identify groups with similar features using multidimensional data. Here, to classify MS subtypes based on pathological features, we apply unsupervised machine learning to brain MRI scans acquired in previously published studies. We use a training dataset from 6322 MS patients to define MRI-based subtypes and an independent cohort of 3068 patients for validation. Based on the earliest abnormalities, we define MS subtypes as cortex-led, normal-appearing white matter-led, and lesion-led. People with the lesion-led subtype have the highest risk of confirmed disability progression (CDP) and the highest relapse rate. People with the lesion-led MS subtype show positive treatment response in selected clinical trials. Our findings suggest that MRI-based subtypes predict MS disability progression and response to treatment and may be used to define groups of patients in interventional trials.


Asunto(s)
Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico , Aprendizaje Automático no Supervisado , Adulto , Bases de Datos como Asunto , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Placebos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Reproducibilidad de los Resultados
3.
Artículo en Ruso | MEDLINE | ID: mdl-33901380

RESUMEN

The article considers issues of pharmacoeconomics of applying gadolinium-containing contrast medium in diagnostic of multiple sclerosis in patients. MATERIALS AND METHODS: The MS Excel calculator was applied to estimate costs and analyze impact on the budget under treatment of multiple sclerosis exacerbations, that were diagnosed using various gadolinium-containing contrast mediums. The direct medical costs for diagnostics with gadolinium-containing contrast medium and hospitalization due to exacerbation in accordance with mandatory medical insurance system were taken into account. THE RESULTS: At the expense of reducing number of multiple sclerosis exacerbations due to the use of single-molar gadolinium-containing contrast medium (gadobutrol) as compared with semi-polar gadolinium-containing contrast medium (gadodiamide, gadoteric acid and gadoteridol) in 1000 patients it is possible to reduce financial expenses from 1,968,642 to 7,175,520 RUB. CONCLUSION: The cost of magnetic resonance imaging diagnostics with contrast enhancement and treatment of multiple sclerosis exacerbations increases in the series: gadobutrol < gadodiamide (Jodas Expoim) < gadodiamide (GE Health Care) < gadoteridol < gadoteric acid.


Asunto(s)
Gadolinio , Esclerosis Múltiple , Medios de Contraste , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico
4.
Wiad Lek ; 74(3 cz 1): 512-516, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33813460

RESUMEN

OBJECTIVE: The aim: To study the peculiarities of demyelination by detection of changes in the levels of myelin basic protein (MBP) in CSF of patients with acute herpesviral meningitis (M) and meningoencephalitis (ME). PATIENTS AND METHODS: Materials and methods: A total of 136 CSF samples from 68 patients with herpesviral M and ME were collected. The control group consisted of patients with acute respiratory infection and meningismus. MBP level in CSF was identified at the admission and after 10-12 days of treatment. Analysis of MBP concentrations in CSF was performed using an enzyme immunoassay. RESULTS: Results: Examination of patients on the first day of hospitalization showed the presence of a significant increase of MBP in the CSF in all patients with viral M/ME compared with the indicators of the comparison group (р<0.01). In all groups of patients with ME, the level of MBP in CSF was significantly higher than the indicators of comparison group and M groups of the suitable etiology of the disease (p<0.01). In patients with lethal outcome, the MBP level was significantly higher (p<0.01) than in all meningitis groups, but we did not find a significant difference with the patients with ME (p>0.05). CONCLUSION: Conclusions: The increase of MBP level identified in patients with acute M/ME confirms the presence of the demyelinating process that occurs in all patients, but it is more pronounced in patients with ME.


Asunto(s)
Meningoencefalitis , Esclerosis Múltiple , Humanos , Proteína Básica de Mielina
5.
Wiad Lek ; 74(2): 257-262, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33813482

RESUMEN

OBJECTIVE: The aim: Our study aimed at evaluating the relationships between sleep disorders (SD), cognitive impairment (CI), anxiety and depression in patients with relapsing-remitting multiple sclerosis (RRMS). PATIENTS AND METHODS: Materials and methods: One hundred and five patients with RRMS (80 females and 25 males) aged from 22 to 67 years (mean age: 41,8±10,7; EDSS:3,5±1,6; disease duration (DD): 10,3±8,5 years) were enrolled into the study. All participants completed questionnaires on sleep (the Pittsburgh Sleep Quality Index /PSQI), cognitive functions (The Montreal Cognitive Assessment /MoCA), anxiety (Hamilton Anxiety Rating Scale /HAM-A), depression (Beck Depression Inventory/ BDI). RESULTS: Results: According to PSQI score the patients were divided into two groups: with (n=42) and without SD (n=63). The patients with SD were older (45,36±1,66 vs 39,41±1,27, p=0.005), had higher EDSS score (3,98±0,26 vs 3,14±0,19, p=0,008), BDI (13,79±1,14 vs 8,96±0,86, p=0,0009) and HAM-A (24,52±1,42 vs 16,56±0,99, p<0,0001) scales compared with patients without SD. The frequency of anxiety (p=0,0034) and depression (p=0,038) was significantly higher in RRMS patients with compared to those without SD. No significant difference was found in gender, DD and MoCA score. In patients with SD significant negative correlation between MoCA and BDI score (r = -0,42, p<0,005) was found. In the group of patients without SD significant negative correlation between MoCA and EDSS (r = -0,27, p=0,03), MoCA and BDI (r = -0,26, p=0,043),) MoCA and HAM-A (r = -0,25, p=0,041) score was detected. CONCLUSION: Conclusions: Insomnia type SD in RRMS patients were associated with older age, higher EDSS score and presence of anxiety and depression.


Asunto(s)
Disfunción Cognitiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Trastornos del Sueño-Vigilia , Adulto , Anciano , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Escalas de Valoración Psiquiátrica , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/etiología
6.
Wiad Lek ; 74(2): 367-370, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33813502

RESUMEN

The aim was to analyze the contemporary scientific literature on Devic's opticomyelitis and to present a case report from our clinical practice. Based on the patient's complaints, case history and features of clinical course, objective neurological status, clinical laboratory and additional examination methods, characteristic MR-patterns, consultations of related specialists and differential diagnostics, we made the clinical diagnosis according to ICD-10: G36.0 Devic's opticomyelitis, exacerbation, with a sustained bilateral lesion of the optic nerves in the form of retrobulbar neuritis with the development of partial atrophy of the optic nerves in both eyes, spinal cord lesions with common cystic, cicatrical and atrophic alterations at C1-Th8 level with moderate lower paraparesis, expressed by sensory ataxia, sensory disturbances by the descending conductive type from Th10, impaired function of pelvic organs by the type of acute urinary retention, asthenic and neurotic syndrome. Widespread cases of demyelinating pathology in medical practice and complexity of differential diagnostics determine the need for a specific diagnostic algorithm. This algorithm should consider anamnestic data along with the course of the disease, clinical, laboratory and instrumental examination, including neuroimaging, analysis of CSF for oligoclonal bands, analysis for IgG antibodies to AQP4, which will allow to carry out diagnostics and to decide on tactics for further management of patients of this cohort. Further research is needed to conduct additional studies for optimization of tactics for dynamics monitoring and improvement of diagnostic, treatment and rehabilitation measures in patients with Devic's opticomyelitis, including appropriate immunological control, given the complexity of differential diagnostics and the affinity of this pathology to multiple sclerosis.


Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Atrofia , Diagnóstico Diferencial , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Neuromielitis Óptica/diagnóstico
7.
Biol Res ; 54(1): 12, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795012

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is a central nervous system disease with a high disability rate. Modern molecular biology techniques have identified a number of key genes and diagnostic markers to MS, but the etiology and pathogenesis of MS remain unknown. RESULTS: In this study, the integration of three peripheral blood mononuclear cell (PBMC) microarray datasets and one peripheral blood T cells microarray dataset allowed comprehensive network and pathway analyses of the biological functions of MS-related genes. Differential expression analysis identified 78 significantly aberrantly expressed genes in MS, and further functional enrichment analysis showed that these genes were associated with innate immune response-activating signal transduction (p = 0.0017), neutrophil mediated immunity (p = 0.002), positive regulation of innate immune response (p = 0.004), IL-17 signaling pathway (p < 0.035) and other immune-related signaling pathways. In addition, a network of MS-specific protein-protein interactions (PPI) was constructed based on differential genes. Subsequent analysis of network topology properties identified the up-regulated CXCR4, ITGAM, ACTB, RHOA, RPS27A, UBA52, and RPL8 genes as the hub genes of the network, and they were also potential biomarkers of MS through Rap1 signaling pathway or leukocyte transendothelial migration. RT-qPCR results demonstrated that CXCR4 was obviously up-regulated, while ACTB, RHOA, and ITGAM were down-regulated in MS patient PBMC in comparison with normal samples. Finally, support vector machine was employed to establish a diagnostic model of MS with a high prediction performance in internal and external datasets (mean AUC = 0.97) and in different chip platform datasets (AUC = (0.93). CONCLUSION: This study provides new understanding for the etiology/pathogenesis of MS, facilitating an early identification and prediction of MS.


Asunto(s)
Biomarcadores , Perfilación de la Expresión Génica , Leucocitos Mononucleares , Esclerosis Múltiple , Biología Computacional , Redes Reguladoras de Genes , Humanos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/genética , Análisis de Secuencia por Matrices de Oligonucleótidos
8.
Bratisl Lek Listy ; 122(5): 357-361, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33848187

RESUMEN

BACKGROUND: In this study, we aimed to determine whether neutrophil / lymphocyte ratio (NLR), obtained by dividing the number of neutrophils by the number of lymphocytes, and uric acid (UA) levels in multiple sclerosis (MS) patients vary compared with healthy controls and to establish correlations among these changes themselves as well as between such changes and MS subtypes, immunomodulatory drug use, the duration of the disease and prognosis. METHODS: 150 patients who presented to our hospital and were diagnosed with MS and 150 healthy volunteers were retrospectively included in our study. EDSS score (Expanded Disability Status Scale) was used to assess the disability of the patients. RESULTS: Compared to healthy volunteers, MS patients had lower UA levels (p < 0.001) and higher NLR values (p = 0.02). In addition, UA levels were higher in patients with a low EDSS score or those on immunomodulating drugs (p < 0.001, p = 0.04, respectively). NLR value was lower in patients with a low EDSS score (p < 0.001). There was a negative correlation between NLR value and UA (r = ‒0.23, p = 0.003). Similarly, UA level decreased with increasing EDSS score and duration of disease (r = ‒0.38, p < 0.001; r = ‒0.17, p = 0.02, respectively). CONCLUSION: Evaluating the NLR value, recognized as a new marker for inflammation in MS, together with the UA value, thought to be protective in MS, might be more effective than evaluating these parameters alone in demonstrating disability in patients (Tab. 4, Ref. 28). Text in PDF www.elis.sk Keywords: neutrophil/lymphocyte ratio, uric acid, multiple sclerosis, inflammation, Expanded Disability Status Scale.


Asunto(s)
Esclerosis Múltiple , Neutrófilos , Humanos , Linfocitos , Estudios Retrospectivos , Ácido Úrico
9.
Artículo en Ruso | MEDLINE | ID: mdl-33834732

RESUMEN

The relevance of the study of demyelinating diseases is due to their increasing frequency in children, clarification of the role of infectious agents in their genesis, as well as the possibility of transformation of disseminated encephalomyelitis into multiple sclerosis. The literature review presents the currently available information on the causes of the development of demyelinating diseases, biomarkers of disseminated encephalomyelitis and multiple sclerosis, the causes of an unfavorable course and possible laboratory parameters indicating the transition from one disease to another, which can be used as prognostic factors. The authors also noted the experience of the authors on the importance of adequate etiopathogenetic therapy in changing the nature of the course of the disease, in particular, when confirming the relationship between the frequency of exacerbations of ADEM and MS with the activation of herpesvirus infections, courses of specific antiviral therapy are effective, as well as pathogenetic therapy aimed at correcting endothelial dysfunction using the drug cytoflavin.


Asunto(s)
Encefalomielitis Aguda Diseminada , Encefalomielitis , Herpesviridae , Esclerosis Múltiple , Biomarcadores , Niño , Encefalomielitis Aguda Diseminada/diagnóstico , Encefalomielitis Aguda Diseminada/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/tratamiento farmacológico
10.
Artículo en Inglés | MEDLINE | ID: mdl-33811158

RESUMEN

OBJECTIVE: Vaccine hesitancy is a complex public health issue referring to concerns about safety, efficacy, or need for vaccination. Using pneumococcal vaccination, which is recommend in anti-CD20-treated multiple sclerosis (MS) patients, as a model, we assessed vaccination behavior in patients with MS to prepare for the upcoming SARS-CoV-2 vaccination challenge. METHODS: By a medical chart review, we retrospectively identified patients with MS treated with ocrelizumab at the University Hospital Bern in 2018-2020. Pneumococcal vaccination was discussed with the patients during clinical visits and highlighted in the after-visit summary addressed to the general practitioner before ocrelizumab initiation as part of our clinical standard of care. RESULTS: Pneumococcal vaccination was performed in 71/121 (58.7%) of patients, and 50/121 (41.3%) patients were not vaccinated. Patients who did not get a pneumococcal vaccination were younger (no vaccination vs vaccination; mean [95% CI] 40.1 [36.1-44.1] vs 45.4 [41.9-48.8], p = 0.028) and had more frequently a relapsing remitting disease course (no vaccination vs vaccination, n [%]; 43/50 [86.0%] vs 49/71 [69.0%], p = 0.031). Furthermore, patients who did not get vaccination had more frequently a history of comorbid psychiatric disorder (no vaccination vs vaccination, n (%); 12/50 [24.0] vs 7/71 [9.8], p = 0.035). CONCLUSION: Our study demonstrated that in our single-center cohort, 41.3% of patients with MS do not get the recommended pneumococcal vaccination. Future research should focus on vaccine hesitancy in the vulnerable cohort of patients with MS to improve the safety of MS immunotherapies.


Asunto(s)
/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Esclerosis Múltiple , Vacunación , Adulto , Comorbilidad , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Estudios Retrospectivos , Vacunación/psicología , Vacunación/estadística & datos numéricos
11.
Sensors (Basel) ; 21(9)2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33925075

RESUMEN

BACKGROUND: Walking disorders represent the most disabling condition in persons with Multiple Sclerosis (PwMS). Several studies showed good reliability of the 6-min walk test (6MWT) (i.e., especially distance traveled), but little is known about the reliability of the Spatio-temporal (ST) variables in the 6MWT. OBJECTIVE: To evaluate the test-retest reliability of ST variables and perceived exertion during the 6MWT in PwMS and comparable healthy persons. METHODS: We explored three 1-min intervals (initial: 0'-1', middle: 2'30″-3'30″, end: 5'-6') of the 6MWT. Six ST variables and perceived exertion were measured (respectively, using the GAITRite system and the Borg Scale). These measurements were performed twice, 1 week apart. The test-retest effects were assessed using the intraclass correlation coefficient (ICC) or the weighted kappa. RESULTS: Forty-five PwMS and 24 healthy persons were included. The test-retest reliability of ST variables values was good-to-excellent for PwMS (ICC range: 0.858-0.919) and moderate-to-excellent for healthy persons (ICC range: 0.569-0.946). The test-retest reliability values of perceived exertion were fair for PwMS (weighted kappa range: 0.279-0.376) and substantial for healthy persons (weighted kappa range: 0.734-0.788). CONCLUSION: The measurement of ST variables during these 6MWT intervals is reliable and applicable in clinical practice and research to adapt rehabilitation care in PwMS.


Asunto(s)
Personas con Discapacidad , Esclerosis Múltiple , Prueba de Esfuerzo , Humanos , Esclerosis Múltiple/diagnóstico , Reproducibilidad de los Resultados , Prueba de Paso , Caminata
12.
Neurol Neurochir Pol ; 55(2): 212-222, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33856686

RESUMEN

INTRODUCTION: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. MATERIALS AND METHODS: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. RESULTS: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. CONCLUSIONS AND CLINICAL IMPLICATIONS: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Femenino , Humanos , Factores Inmunológicos , Inmunosupresores , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Polonia/epidemiología
13.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33810144

RESUMEN

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus. RT-PCR analysis revealed glial fibrillary acidic protein (GFAP), proteolipid protein (PLP), and myelin basic protein (MBP) expression, but an absence of myelin oligodendrocyte glycoprotein (MOG) in the murine esophagus. Selected immunohistochemistry for GFAP, PLP, and MBP including transgenic mice with cell-type specific expression of PLP and GFAP supported these results by detection of (1) GFAP, PLP, and MBP in Schwann cells in skeletal muscle and esophagus; (2) GFAP, PLP, but no MBP in perisynaptic Schwann cells of skeletal and esophageal motor endplates; (3) GFAP and PLP, but no MBP in glial cells surrounding esophageal myenteric neurons; and (4) PLP, but no GFAP and MBP in enteric glial cells forming a network in the esophagus. Our results pave the way for further investigations regarding the involvement of esophageal glial cells in the pathogenesis of dysphagia in MS.


Asunto(s)
Biomarcadores , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/metabolismo , Esófago/metabolismo , Expresión Génica , Neuroglía/inmunología , Neuroglía/metabolismo , Animales , Sistema Nervioso Central/patología , Femenino , Técnica del Anticuerpo Fluorescente , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Esclerosis Múltiple/etiología , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Proteína Básica de Mielina/genética , Proteína Básica de Mielina/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
14.
Artículo en Inglés | MEDLINE | ID: mdl-33802599

RESUMEN

(1) Background: Complex genetic relationships, including gene-gene (G × G; epistasis), gene(n), and gene-environment (G × E) interactions, explain a substantial portion of the heritability in multiple sclerosis (MS). Machine learning and data mining methods are promising approaches for uncovering higher order genetic relationships, but their use in MS have been limited. (2) Methods: Association rule mining (ARM), a combinatorial rule-based machine learning algorithm, was applied to genetic data for non-Latinx MS cases (n = 207) and controls (n = 179). The objective was to identify patterns (rules) amongst the known MS risk variants, including HLA-DRB1*15:01 presence, HLA-A*02:01 absence, and 194 of the 200 common autosomal variants. Probabilistic measures (confidence and support) were used to mine rules. (3) Results: 114 rules met minimum requirements of 80% confidence and 5% support. The top ranking rule by confidence consisted of HLA-DRB1*15:01, SLC30A7-rs56678847 and AC093277.1-rs6880809; carriers of these variants had a significantly greater risk for MS (odds ratio = 20.2, 95% CI: 8.5, 37.5; p = 4 × 10-9). Several variants were shared across rules, the most common was INTS8-rs78727559, which was in 32.5% of rules. (4) Conclusions: In summary, we demonstrate evidence that specific combinations of MS risk variants disproportionately confer elevated risk by applying a robust analytical framework to a modestly sized study population.


Asunto(s)
Esclerosis Múltiple , Alelos , Predisposición Genética a la Enfermedad , Cadenas HLA-DRB1/genética , Humanos , Esclerosis Múltiple/genética , Oportunidad Relativa , Polimorfismo de Nucleótido Simple
15.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33804243

RESUMEN

A growing body of preclinical evidence indicates that certain cannabinoids, including cannabidiol (CBD) and synthetic derivatives, may play a role in the myelinating processes and are promising small molecules to be developed as drug candidates for management of demyelinating diseases such as multiple sclerosis (MS), stroke and traumatic brain injury (TBI), which are three of the most prevalent demyelinating disorders. Thanks to the properties described for CBD and its interesting profile in humans, both the phytocannabinoid and derivatives could be considered as potential candidates for clinical use. In this review we will summarize current advances in the use of CBD and other cannabinoids as future potential treatments. While new research is accelerating the process for the generation of novel drug candidates and identification of druggable targets, the collaboration of key players such as basic researchers, clinicians and pharmaceutical companies is required to bring novel therapies to the patients.


Asunto(s)
Cannabidiol/uso terapéutico , Cannabinoides/uso terapéutico , Cannabis/química , Enfermedades Desmielinizantes/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/patología , Enfermedades Desmielinizantes/patología , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/patología
16.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805762

RESUMEN

Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX's effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (µMT) mice. Without PTX treatment, disease severity was equivalent between WT and µMT mice. In contrast, with PTX treatment, the µMT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis.


Asunto(s)
Linfocitos B/patología , Encefalomielitis Autoinmune Experimental/patología , Toxina del Pertussis/administración & dosificación , Células Th17/patología , Traslado Adoptivo/métodos , Animales , Linfocitos B/inmunología , Movimiento Celular/inmunología , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Glicoproteína Mielina-Oligodendrócito/administración & dosificación , Índice de Severidad de la Enfermedad , Células Th17/inmunología , Células Th17/trasplante
17.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805769

RESUMEN

Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein-Barr virus (EBV) infection may contribute to the development of MS. Here, we aimed to identify the potential contribution of EBV-encoded and host cellular miRNAs to MS pathogenesis. We identified differentially expressed host miRNAs in EBV infected B cells (LCLs) and putative host/EBV miRNA interactions with MS risk loci. We estimated the genotype effect of MS risk loci on the identified putative miRNA:mRNA interactions in silico. We found that the protective allele of MS risk SNP rs4808760 reduces the expression of hsa-mir-3188-3p. In addition, our analysis suggests that hsa-let-7b-5p may interact with ZC3HAV1 differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases ZC3HAV1 expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased IFN response via ZC3HAV1 and so decreased immune evasion by EBV. Taken together, this provides evidence that EBV infection dysregulates the B cell miRNA machinery, including MS risk miRNAs, which may contribute to MS pathogenesis via interaction with MS risk genes either directly or indirectly.


Asunto(s)
Linfocitos B/virología , Sitios Genéticos , Interacciones Huésped-Patógeno/genética , MicroARNs/genética , ARN Mensajero/genética , Proteínas de Unión al ARN/genética , Alelos , Linfocitos B/inmunología , Secuencia de Bases , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/inmunología , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , MicroARNs/inmunología , Modelos Biológicos , Esclerosis Múltiple/genética , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Esclerosis Múltiple/virología , Polimorfismo de Nucleótido Simple , Cultivo Primario de Células , ARN Mensajero/inmunología , Proteínas de Unión al ARN/inmunología , Transducción de Señal
18.
Artículo en Inglés | MEDLINE | ID: mdl-33807004

RESUMEN

Multiple sclerosis (MS) is an immune-mediated, demyelinating disease of the central nervous system. In this study, an MS cohort and healthy controls were stratified into Caucasian and African American groups. Patient hematological profiles-composed of complete blood count (CBC) and complete metabolic panel (CMP) test values-were analyzed to identify differences between MS cases and controls and between patients with different MS subtypes. Additionally, random forest models were used to determine the aggregate utility of common hematological tests in determining MS disease status and subtype. The most significant and relevant results were increased bilirubin and creatinine in MS cases. The random forest models achieved some success in differentiating between MS cases and controls (AUC values: 0.725 and 0.710, respectively) but were not successful in differentiating between subtypes. However, larger samples that adjust for possible confounding variables, such as treatment status, may reveal the value of these tests in differentiating between MS subtypes.


Asunto(s)
Esclerosis Múltiple , Sistema Nervioso Central , Estudios de Cohortes , Humanos , Esclerosis Múltiple/diagnóstico
19.
BMC Med Inform Decis Mak ; 21(1): 123, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836742

RESUMEN

BACKGROUND: Since decision making about treatment with disease-modifying drugs (DMDs) for multiple sclerosis (MS) is preference sensitive, shared decision making between patient and healthcare professional should take place. Patient decision aids could support this shared decision making process by providing information about the disease and the treatment options, to elicit the patient's preference and to support patients and healthcare professionals in discussing these preferences and matching them with a treatment. Therefore, a prototype of a patient decision aid for MS patients in the Netherlands-based on the principles of multi-criteria decision analysis (MCDA) -was developed, following the recommendations of the International Patient Decision Aid Standards. MCDA was chosen as it might reduce cognitive burden of considering treatment options and matching patient preferences with the treatment options. RESULTS: After determining the scope to include DMDs labelled for relapsing-remitting MS and clinically isolated syndrome, users' informational needs were assessed using focus groups (N = 19 patients) and best-worst scaling surveys with patients (N = 185), neurologists and nurses (N = 60) to determine which information about DMDs should be included in the patient decision aid. Next, an online format and computer-based delivery of the patient decision aid was chosen to enable embedding of MCDA. A literature review was conducting to collect evidence on the effectiveness and burden of use of the DMDs. A prototype was developed next, and alpha testing to evaluate its comprehensibility and usability with in total thirteen patients and four healthcare professionals identified several issues regarding content and framing, methods for weighting importance of criteria in the MCDA structure, and the presentation of the conclusions of the patient decision aid ranking the treatment options according to the patient's preferences. Adaptations were made accordingly, but verification of the rankings provided, validation of the patient decision aid, evaluation of the feasibility of implementation and assessing its value for supporting shared decision making should be addressed in further development of the patient decision aid. CONCLUSION: This paper aimed to provide more transparency regarding the developmental process of an MCDA-based patient decision aid for treatment decisions for MS and the challenges faced during this process. Issues identified in the prototype were resolved as much as possible, though some issues remain. Further development is needed to overcome these issues before beta pilot testing with patients and healthcare professionals at the point of clinical decision-making can take place to ultimately enable making conclusions about the value of the MCDA-based patient decision aid for MS patients, healthcare professionals and the quality of care.


Asunto(s)
Esclerosis Múltiple , Preparaciones Farmacéuticas , Toma de Decisiones , Técnicas de Apoyo para la Decisión , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Países Bajos , Prioridad del Paciente
20.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33802122

RESUMEN

Autoantibodies-abzymes hydrolyzing DNA, myelin basic protein, and oligosaccharides have been revealed in the sera of patients with multiple sclerosis (MS). In MS, specific microRNAs are found in blood and cerebrospinal fluid, which are characterized by increased expression. Autoantibodies, specifically hydrolyzing four different miRNAs, were first detected in the blood of schizophrenia patients. Here, we present the first evidence that 23 IgG antibodies of MS patients effectively recognize and hydrolyze four neuroregulatory miRNAs (miR-137, miR-9-5p, miR-219-2-3p, and miR-219-5p) and four immunoregulatory miRNAs (miR-21-3p, miR-146a-3p, miR-155-5p, and miR-326). Several known criteria were checked to show that the recognition and hydrolysis of miRNAs is an intrinsic property of MS IgGs. The hydrolysis of all miRNAs is mostly site-specific. The major and moderate sites of the hydrolysis of each miRNA for most of the IgG preparations coincided; however, some of them showed other specific sites of splitting. Several individual IgGs hydrolyzed some miRNAs almost nonspecifically at nearly all internucleoside bonds or demonstrated a combination of site-specific and nonspecific splitting. Maximum average relative activity (RA) was observed in the hydrolysis of miR-155-5p for IgGs of patients of two types of MS-clinically isolated syndrome and relapsing-remitting MS-but was also high for patients with primary progressive and secondary progressive MS. Differences between RAs of IgGs of four groups of MS patients and healthy donors were statistically significant (p < 0.015). There was a tendency of decreasing efficiency of hydrolysis of all eight miRNAs during remission compared with the exacerbation of the disease.


Asunto(s)
Anticuerpos Catalíticos/sangre , Autoanticuerpos/sangre , Inmunoglobulina G/sangre , MicroARNs/metabolismo , Esclerosis Múltiple/sangre , Adulto , Femenino , Humanos , Hidrólisis , Masculino , Persona de Mediana Edad
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