RESUMO
Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.
Assuntos
Biomarcadores , Proteína Glial Fibrilar Ácida , Proteínas de Neurofilamentos , Humanos , Adulto , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/sangue , Feminino , Masculino , Proteína Glial Fibrilar Ácida/sangue , Idoso , Adolescente , Biomarcadores/sangue , Adulto Jovem , Estudos Transversais , Voluntários Saudáveis , Fatores Etários , Valores de ReferênciaRESUMO
Vitamin D is an environmental factor related to multiple sclerosis that plays a significant role in immune regulation. TGF-ß is a superfamily of cytokines with an important dual effect on the immune system. TGF-ß inhibits the Th1 response while facilitating the preservation of regulatory T cells (FOXP3+) in an immunoregulatory capacity. However, when IL-6 is present, it stimulates the Th17 response. Our aim was to analyze the regulatory effect of vitamin D on the in vivo TGF-ß signaling pathway in patients with relapsing-remitting multiple sclerosis (RRMS). A total of 21 patients with vitamin D levels < 30 ng/mL were recruited and supplemented with oral vitamin D. All patients were receiving disease-modifying therapy, with the majority being on natalizumab. Expression of SMAD7, ERK1, ZMIZ1, BMP2, BMPRII, BMP4, and BMP5 was measured in CD4+ lymphocytes isolated from peripheral blood at baseline and one and six months after supplementation. SMAD7 was overexpressed at six months with respect to baseline and month one. ERK1 was overexpressed at six months with respect to month one of treatment. No significant differences in expression were observed for the remaining genes. No direct correlation was found with serum vitamin D levels. BMPRII expression changed differentially in non-natalizumab- versus natalizumab-treated patients. Changes were observed in the expression of ERK1, BMP2, and BMP5 based on disease activity measured using the Rio-Score, BMP2 in patients who had relapses, and BMP5 in those whose EDSS worsened. Our results suggest indirect regulation of vitamin D in TGF-ß pathway genes in patients with RRMS.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Vitamina D/metabolismo , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/genética , Natalizumab , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Fator de Crescimento Transformador beta/genéticaRESUMO
BACKGROUND AND PURPOSE: Short-chain fatty acids (SCFAs) can have pro- or anti-inflammatory properties, but their relationship with multiple sclerosis (MS) relapses during pregnancy remains unknown. This study aimed to explore SCFA profiles in MS patients during pregnancy and to assess their association with the appearance of relapses during pregnancy and postpartum. METHODS: We prospectively included 53 pregnant MS patients and 21 healthy control women. Patients were evaluated during pregnancy and puerperium. SCFAs were measured by liquid chromatography-mass spectrometry. RESULTS: Sixteen patients (32%) had relapses during pregnancy or puerperium, and 37 (68%) did not. All MS patients showed significant increases in acetate levels during pregnancy and the postpartum period compared to non-MS women. However, propionate and butyrate values were associated with disease activity. Their values were higher in nonrelapsing patients and remained similar to the control group in relapsing patients. The variable that best identified active patients was the propionate/acetate ratio. Ratios of <0.36 during the first trimester were associated with higher inflammatory activity (odds ratio = 165, 95% confidence interval = 10.2-239.4, p < 0.01). Most nonrelapsing patients showed values of >0.36, which were similar to those in healthy pregnant women. CONCLUSIONS: Low propionate/acetate ratio values during the first trimester of gestation identified MS patients at risk of relapses during pregnancy and the postpartum period.
Assuntos
Esclerose Múltipla , Ácidos Graxos Voláteis , Feminino , Humanos , Razão de Chances , Gravidez , Estudos Prospectivos , RecidivaRESUMO
Introduction: Spasticity is a common symptom in multiple sclerosis (MS) and it is often associated with other symptoms such as spasms/cramps and pain. The concept of Spasticity-Plus syndrome takes into account that spasticity is accompanied by one or more symptoms (spasms/cramps, pain, bladder dysfunction, sleep disorders, fatigue and/or tremor). As these symptoms share a common cannabinoid control, therapy acting on cannabinoid receptors may be useful. The main study objectives were to determine the number of MS patients who met Spasticity-Plus syndrome criteria and to identify the most common symptoms. Methods: Clinical records of MS patients treated with nabiximols in a tertiary hospital from 2002 to 2022 were reviewed retrospectively. Results: Of the 73 patients included in the study, 53.4% were women, and most had secondary progressive MS (64.4%). All patients met the criteria for Spasticity-Plus syndrome: 100% had spasticity and at least another symptom. Pain was the second most common symptom (91.8%), followed by spasms/cramps (79.4%), and fatigue (76.7%). Sleep disturbances (p < 0.0001) and tremor (p < 0.027) were more frequent in patients with relapsing-remitting MS than in patients with progressive MS. No statistically significant differences were found for spasticity, pain, spasms/cramps, and fatigue between MS phenotypes. Regarding symptoms clusters, 94.4% of the patients had three or more symptoms. Spasticity was more frequently associated with pain (91.8%) and spasms/cramps (79.4%). Conclusion: Spasticity-Plus syndrome was present in all the study population of patients with different MS phenotypes, and treated with nabiximols.
RESUMO
BACKGROUND: Sick leave is a common problem among healthcare professionals. Nurses play a critical role in the multidisciplinary management of multiple sclerosis (MS). However, limited information is available on the phenomenon of sick leave among MS nurses. OBJECTIVE: The aim of this study was to assess the presence of sick leave among nurses caring for patients with MS and to identify associated factors. METHODS: We conducted a multicenter, non-interventional, cross-sectional, web-based study. Nurses involved in MS care from across Spain answered a survey composed of demographic characteristics, professional background, questions about their standard practice, and a behavioral battery including the Maslach Burnout Inventory - Human Services Survey (MBI-HSS). A multivariable logistic regression analysis was conducted to determine the association between nurses' characteristics and sick leave. RESULTS: Ninety-six nurses were included in the study. Mean age (SD) was 44.6 (9.8) years, and 91.7% were female. Participants had a median of 6 (IQR 3.0, 11.0) years of expertise in MS managing a median of 15 (5.0, 35.0) patients per week. Sixteen participants (16.7%) had been on sick leave in the last 6 months, with a median absence of 14.5 days (7.0, 30.0). Sixteen nurses (16.7%) reported severe burnout. Participants on sick leave had higher levels of emotional exhaustion (mean MBI-HSS scores of 22.3 and 16.0, p=0.01) and inadequate interactions with their colleagues (mean Practice Environment Scale - Nursing Work Index scores of 11.8 and 13.1, p=0.01) than their counterparts. Burnout was associated with higher risk of sick leave in the multivariable analysis (OR=1.06 [95% CI 1.00, 1.13], p=0.04) after adjustment for confounders. CONCLUSIONS: Occupational burnout is associated with increased risk of sick leave among nurses managing patients with MS. Identifying burnout may be critical for implementing specific intervention strategies to maintain an adequate functioning of MS care units.
Assuntos
Esgotamento Profissional , Esclerose Múltipla , Enfermeiras e Enfermeiros , Adulto , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Masculino , Assistência ao Paciente , Licença Médica , Inquéritos e QuestionáriosRESUMO
ABSTRACT: BACKGROUND: Nurses play an essential role in coordinating the care of patients with multiple sclerosis (MS) throughout their disease trajectory in a complex treatment landscape. The aim of this study was to assess nurses' preferences toward different disease-modifying therapy attributes. METHODS: We conducted a multicenter, noninterventional, cross-sectional study in collaboration with the Sociedad Española de Enfermería Neurológica. Nurses actively involved in MS care were invited to participate in the study. Prevention of disability progression, preservation of cognitive function, side effect profile and safety monitoring, and method of administration were the treatment attributes tested. Conjoint analysis was used to assess preferences in 8 simulated treatment options and rank them from most to least preferred. RESULTS: A total of 98 nurses were included in the study. The mean (SD) age was 44.7 (9.8) years, and 91.8% were female with a mean (SD) time of experience in MS care of 7.5 (5.4) years. Participants prioritized preservation of cognition (38.6%), followed by preventing disability progression (35.2%) and side effect risk and safety monitoring (13.5%). Route and frequency of administration were the least preferred attributes (7.4% and 5.3%, respectively). Estimated utilities were consistent across the sample according to sociodemographic and professional practice characteristics. CONCLUSIONS: Nurses' preferences toward treatments were mainly driven by efficacy attributes. This information may support the role of nurses in the multidisciplinary management of MS facilitating shared decision making.
Assuntos
Esclerose Múltipla , Adulto , Estudos Transversais , Tomada de Decisões , Feminino , Humanos , Masculino , Esclerose Múltipla/tratamento farmacológicoRESUMO
Epstein-Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls-P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.
Assuntos
Herpesvirus Cercopitecino 1/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 6/imunologia , Esclerose Múltipla , Viroses/diagnóstico , Adulto , Anticorpos Antivirais/sangue , Biomarcadores , Retrovirus Endógenos/isolamento & purificação , Retrovirus Endógenos/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpes Zoster , Humanos , Imunoglobulina M/sangue , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/etiologia , Esclerose Múltipla/virologia , Gravidez , RNA Mensageiro/sangue , RNA Viral/sangue , Proteínas do Envelope Viral/sangue , Proteínas do Envelope Viral/genética , Viroses/complicações , Viroses/imunologiaRESUMO
OBJECTIVE: To explore the serum cytokine profile associated with disease activity during pregnancy and postpartum in MS, and to assess any potential biomarkers predicting the occurrence of relapses during this period. METHODS: We included 53 MS pregnant women recruited between 2007 and 2018. Interferon-gamma, Tumor necrosis factor-alpha, interleukin-17, granulocyte/macrophage-colony stimulating factor, Activin-A, interleukin-10, and programmed-death-ligand-1 (PD-L1) were measured quarterly in serum by ELISA. RESULTS: Seventeen patients (32%) experienced relapses during pregnancy or puerperium and 37(68%) did not. We did not found differences in clinical characteristics or treatment status between the two groups. However, relapsing patients showed at the first trimester of pregnancy considerably lower levels of serum Activin-A (336.4 pg/dl [289.6-491.7], median [IQR] vs. 760.0 pg/dl [493.2-1108.0],p = .003), which correlated positively with serum PD-L1 (r = 0.53,p = .0005) and IL-10 (r = 0.43,p = .004) values. Activin-A levels lower than 515 pg/ml at the first trimester identified patients with high probability of relapsing during pregnancy and postpartum (OR = 13.75, CI: 2.5-76.8, p = .001). CONCLUSIONS: MS patients with no relapses during pregnancy and puerperium showed an early triggering of a tolerogenic innate immune response evidenced by high serum Activin-A concentrations during the first trimester of pregnancy. Thus, serum Activin-A can be a useful biomarker to predict clinical activity during this period.