RESUMO
Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p<0.028 for TBX21) and demonstrate longitudinal stability (p<10(-4)) and high heritability (h(2)=0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were under-represented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.
Assuntos
Esclerose Múltipla/genética , Proteínas com Domínio T/genética , Adulto , Idoso , Antígeno CD56 , Estudos de Casos e Controles , Movimento Celular , Fumarato de Dimetilo/uso terapêutico , Antígenos Nucleares do Vírus Epstein-Barr/sangue , Feminino , Cloridrato de Fingolimode/uso terapêutico , Regulação da Expressão Gênica , Predisposição Genética para Doença , Acetato de Glatiramer/uso terapêutico , Cadeias HLA-DRB1/genética , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Interferon beta/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Natalizumab/uso terapêutico , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
BACKGROUND: Self-concept change may impact psychological wellbeing and functioning in people with MS (pwMS). However, the extent and nature of change in self-concept that pwMS experience is poorly understood, owing to the lack of quantitative measures available to assess this construct. OBJECTIVE: To examine the factor structure, validity, and internal consistency of the newly developed Multiple Sclerosis Self-Concept Change Scale (MSSCCS). METHODS: Items measuring self-concept change were created, reviewed by a panel of experts and pre-tested in a sample of 135 pwMS. A revised list of 51 items were then administered to 1307 pwMS (80.3% female; Age M = 59.21 years, SD = 11.40), together with measures of disease impact and psychosocial functioning. RESULTS: Exploratory factor analysis using principal axis factor extraction in 643 randomly selected participants yielded 23-items measuring 5 latent factors for the final MSSCCS. Confirmatory factor analysis involving the remaining participants supported the 5-factor model, as well as a 2nd order model of "global change". Internal consistency of the total scale was good (α = 0.89). The MSSCCS also demonstrated evidence of concurrent and construct validity. CONCLUSION: The MSSCCS is a reliable and valid assessment, which may assist in enhancing understanding of self-concept change in pwMS.
Assuntos
Esclerose Múltipla , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/psicologia , Reprodutibilidade dos Testes , Inquéritos e Questionários , PsicometriaRESUMO
BACKGROUND: Gray matter atrophy has been implicated in the development of secondary progressive multiple sclerosis (SPMS). Cortical function may be assessed by transcranial magnetic stimulation (TMS). Determining whether cortical dysfunction was a feature of SPMS could be of pathophysiological significance. OBJECTIVES: Consequently, novel paired-pulse threshold tracking TMS techniques were used to assess whether cortical dysfunction was a feature of SPMS. METHODS: Cortical excitability studies were undertaken in 15 SPMS, 25 relapsing-remitting MS patients (RRMS) and 66 controls. RESULTS: Short interval intracortical inhibition (SPMS 3.0 ± 2.1%; RRMS 12.8 ± 1.7%, p < 0.01; controls 10.5 ± 0.7%, p < 0.01) and motor evoked potential (MEP) amplitude (SPMS 11.5 ± 2.2%; RRMS 26.3 ± 3.6%, p <0.05; controls 24.7 ± 1.8%, p < 0.01) were reduced in SPMS, while intracortical facilitation (SPMS -5.2 ± 1.9%; RRMS -2.0 ± 1.4, p < 0.05; controls -0.9 ± 0.7, p < 0.01) and resting motor threshold were increased (SPMS 67.5 ± 4.5%; RRMS 56.0 ± 1.5%, p < 0.01; controls 59.0 ± 1.1%, p < 0.001). Further, central motor conduction time was prolonged in SPMS (9.1 ± 1.2 ms, p < 0.001) and RRMS (7.0 ± 0.9 ms, p < 0.05) patients compared with controls (5.5 ± 0.2 ms). The observed changes in cortical function correlated with the Expanded Disability Status Scale. CONCLUSION: Together, these findings suggest that cortical dysfunction is associated with disability in MS, and documentation of such cortical dysfunction may serve to quantify disease severity in MS.
Assuntos
Potencial Evocado Motor , Córtex Motor/patologia , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Idoso , Atrofia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Condução Nervosa , Inibição Neural/fisiologia , Estimulação Magnética TranscranianaRESUMO
BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative disease with symptoms that are varied and unpredictable, and although there are effective medications to treat some forms of MS, there is no cure. For many, an MS diagnosis means decades living with a chronic illness and disability. OBJECTIVE: Providing medical and support care to people with MS can be a long and complex partnership between the patient and the general practitioner (GP). The aim of this article is to provide knowledge of the lived experience of MS and the factors leading to a reduced quality of life. DISCUSSION: Often alongside the considerable threats to physical health and neurological function that MS poses, there are also significant mental health burdens. This article uses lived experience to outline some of the crucial trigger points where support from the GP, and the wider general practice team, can have a significant impact on a positive path forward for the patient.
Assuntos
Pessoas com Deficiência , Clínicos Gerais , Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Esclerose Múltipla/psicologia , Esclerose Múltipla/terapia , Qualidade de Vida/psicologiaRESUMO
BACKGROUND AND PURPOSE: The aim of this study was to gain insights and understanding into the lived experience of relapsing remitting multiple sclerosis (RRMS) in order to better inform patient-centerd nursing and healthcare. METHODS: This qualitative study used life history methodology, a form of focused ethnography, to explore the life history of 13 study participants living with RRMS. Semi-structured interviews were transcribed and analysed using thematic analysis. FINDINGS: A total of eight key themes emerged, explaining the journey of living with RRMS. Commencing with "Piecing Together the Puzzle" of symptoms at the beginning of the RRMS journey, followed by "(Re)defining ME now that I have RRMS," "Battling the Demons," the experiences of "Surplus Suffering," negotiating "High Invisibility," gaining control by "Taming the Beast," learning "The DMT Dance," and ultimately "Holding Hands with Hope," expressing hope and practising purposeful positivity. IMPLICATIONS FOR PRACTICE: The eight key themes of living with RRMS were reflective of the ebbs and flows of life. By gaining these insights into the world of people living with RRMS, it is anticipated that clinical nursing care and quality of life for people living with this chronic neurological disease may be improved.
Assuntos
Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/enfermagem , Assistência Centrada no Paciente , Pesquisa Qualitativa , Qualidade de VidaRESUMO
Allergic rhinoconjunctivitis is a common condition with a peak incidence in the age range of the majority of elite athletes. The condition has been shown to have a significant impact on the quality of life of those affected and poses particular challenges when present in the elite athlete. When an athlete is looking for exceptional performance at events such as the Olympic Games, any factor which affects quality of life by interfering with sleep, decreasing the ability to concentrate, or reducing peak physical fitness, may have a significant impact on the ability to perform at one's best. Optimal management begins with correct diagnosis and identification of triggering factors. There are a number of therapeutic options available to the treating physician. When formulating a management plan for the elite athlete, the physician must consider "doping" rules and the possible effect of medication on athletic performance. Medication choices include the newer, non-sedating antihistamines, used either orally or topically, and the prophylactic use of intranasal corticosteroids. When allergic conjunctivitis is the principal problem, the newer, topical antihistamines are highly effective and have a rapid onset of action. Since avoidance strategies are rarely practical for the athlete, consideration should be given to strategies such as immunotherapy, where long-term benefit is possible.
Assuntos
Conjuntivite Alérgica/tratamento farmacológico , Qualidade de Vida , Rinite Alérgica Perene/tratamento farmacológico , Medicina Esportiva/métodos , Análise e Desempenho de Tarefas , Doença Aguda , Administração Intranasal , Corticosteroides/administração & dosagem , Antiasmáticos/uso terapêutico , Doença Crônica , Conjuntivite Alérgica/complicações , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Imunoterapia/métodos , Ipratrópio/uso terapêutico , Descongestionantes Nasais/uso terapêutico , Rinite Alérgica Perene/complicaçõesRESUMO
The ability to predict disability development in multiple sclerosis (MS) is limited. While abnormalities of evoked potentials (EP) have been associated with disability, the prognosticating utility of EP in MS remains to be fully elucidated. The present study assessed the utility of multimodal EP as a prognostic biomarker of disability in a cohort of clinically heterogeneous MS patients. Median and tibial nerve somatosensory, visual, and brainstem auditory EP were performed at initial assessment on 63 MS patients (53 relapsing-remitting and 10 secondary progressive) who were followed for an average of 2 years. A combined EP score (CEPS) was calculated consisting of the total number of abnormal EP tests, and was correlated with the Expanded Disability Status Scale (EDSS) at baseline and follow-up. There was a significant correlation between multimodal EP and baseline and follow-up EDSS. Specifically, tibial nerve P37 latencies correlated with EDSS (R(BASELINE)=0.49, p<0.01; R(FOLLOW-UP)=0.47, p<0.01), as did the median nerve N13 (R(BASELINE)=0.40, p<0.01; R(FOLLOW-UP)=0.35, p<0.05) and N20 latencies (R(BASELINE)=0.43, p<0.01; R(FOLLOW-UP)=0.47, p<0.01), and P100 full-field (R(BASELINE)=0.50, p<0.001; R(FOLLOW-UP)=0.45, p<0.001) and central field latencies (R(BASELINE)=0.60, p<0.001; R(FOLLOW-UP)=0.50, p<0.001). In addition, there was a significant correlation between the CEPS with baseline (R=0.65, p<0.001) and follow-up (R=0.57, p<0.01) EDSS. In contrast, white matter disease burden, as measured by T2 lesion load, exhibited a weaker correlation with EDSS (R(BASELINE)=0.28, p<0.05). In conclusion, these findings suggest that abnormalities of EP, as quantified by the novel CEPS, may be a useful biomarker for prognosticating clinical disability in MS, and may aid in the quantification of MS disease severity and in guiding therapeutic decisions.
Assuntos
Potenciais Evocados/fisiologia , Esclerose Múltipla/fisiopatologia , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is an important adjunct to the diagnosis of multiple sclerosis (MS) and clinically isolated syndromes (CIS). OCBs are considered present if two or more extra IgG bands are present in CSF in comparison to a simultaneously collected serum sample. However, using isoelectric focusing and immunofixation with anti-IgG, we observed two distinct banding patterns, one in which the bands were numerous and prominent (which we termed 'delta') and a much more subtle pattern, with fewer, more indistinct bands ('theta'). AIM: To perform a prospective study to determine the diagnostic implications of the two OCB patterns for multiple sclerosis. METHODS: Over a 2-year period, 56 consecutive CSF samples with OCBs were identified. Clinical information and radiological data were collected and correlated with the two banding patterns. RESULTS: : Of the 56 positive CSF samples, 46 (82%) demonstrated a delta pattern, and 10 (18%), a theta pattern. The delta pattern was associated with MS/CIS in 34 of 46 (74%) samples, compared with zero of the 10 theta samples (0%, pâ<â0.001). Exclusion of the theta pattern samples increased the positive predictive value of OCB testing from 61% to 74% for MS/CIS. CONCLUSION: The diagnostic significance of oligoclonal bands in CSF for MS/CIS can be improved by restricting interpretation to the delta banding pattern alone.
Assuntos
Líquido Cefalorraquidiano/química , Doenças Desmielinizantes/diagnóstico , Imunoglobulina G/líquido cefalorraquidiano , Focalização Isoelétrica/métodos , Esclerose Múltipla/diagnóstico , Bandas Oligoclonais/líquido cefalorraquidiano , Adulto , Doenças Desmielinizantes/líquido cefalorraquidiano , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidianoRESUMO
A greater understanding of the pathogenesis of multiple sclerosis (MS) and the need for treatments with increased efficacy, safety, and tolerability have led to the ongoing development of new treatments. The evolution of treatments for MS is expected to have a dramatic impact on the entire health-care team, especially MS nurses, who build strong collaborative partnerships with their patients. MS nurses help patients better understand their disease and treatment options, facilitate the initiation and management of treatment, and encourage adherence. With new oral therapies entering the market, the potential for increased efficacy, tolerability, adherence, and convenience for patients is evident. However, the resulting change in the treatment paradigm means that the skill set required of an MS nurse will inevitably expand. There will be a growing need for professional training and development to ensure that nurses are familiar with the wider range of treatments and their specific modes of action, dosing schedules, and benefit/risk profiles. In addition, the MS nurse's role will expand to include management of the complex monitoring needs specific to each therapy. This article explores how the role of the MS nurse is evolving with the development of new MS therapies, including novel oral therapies.
Assuntos
Esclerose Múltipla/diagnóstico , Esclerose Múltipla/enfermagem , Austrália/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Papel do Profissional de Enfermagem , Guias de Prática Clínica como Assunto , PrevalênciaRESUMO
BACKGROUND: There is increasing interest in the daily pollen count, with pollen-sensitive individuals using it to determine medication use and researchers relying on it for commencing clinical drug trials and assessing drug efficacy according to allergen exposure. Counts are often expressed qualitatively as low, medium, and high, and often only 1 pollen trap is used for an entire region. OBJECTIVES: To examine the spatial variability in the pollen count in Sydney, Australia, and to compare discrepancies among low-, medium-, and high-count days at 3 sites separated by a maximum of 30 km. METHODS: Three sites in western Sydney were sampled using Burkard traps. Data from the 3 sites were used to compare vegetation differences, possible effects of some meteorological parameters, and discrepancies among sites in low-, medium-, and high-count days. RESULTS: Total pollen counts during the spring months were 14,382 grains/m3 at Homebush, 11,584 grains/m3 at Eastern Creek, and 9,269 grains/m3 at Nepean. The only significant correlation between differences in meteorological parameters and differences in pollen counts was the Homebush-Nepean differences in rainfall and pollen counts. Comparison between low- and high-count days among the 3 sites revealed a discordance rate of 8% to 17%. CONCLUSIONS: For informing the public about pollen counts, the count from 1 trap is a reasonable estimation in a 30-km region; however, the discrepancies among 3 trap sites would have a significant impact on the performance of a clinical trial where enrollment was determined by a low or high count. Therefore, for clinical studies, data collection must be local and applicable to the study population.
Assuntos
Pólen , Poluentes Atmosféricos/análise , Austrália/epidemiologia , Monitoramento Ambiental , Monitoramento Epidemiológico , Humanos , Conceitos Meteorológicos , Variações Dependentes do Observador , Estações do Ano , Estatística como Assunto , TemperaturaRESUMO
OBJECTIVE: To assess change in symptoms, quality of life (QOL), and performance ability before, during, and after treatment with budesonide in a group of Olympic and Paralympic athletes with seasonal allergic rhinoconjunctivitis (SAR/C). DESIGN: Because budesonide has already been proven to be an effective and well-tolerated treatment of SAR/C(1), an open-label treatment format was used. SETTING: The study was community-based with participating athletes preparing for Olympic competition. PARTICIPANTS: Olympic and Paralympic athletes were screened for the presence of SAR/C using history and positive skin test results for pollen allergens. INTERVENTIONS: All were offered treatment with intranasal budesonide, applied to each nostril, once daily for eight weeks. OUTCOME MEASUREMENTS: Symptom and medication diaries were completed before treatment and after 4 and 8 weeks of treatment. Similarly, Quality of Life (QOL) was measured with the Rhinoconjunctivitis Quality of Life Questionnaire. As a secondary outcome measure, the ability to train and compete was assessed using a performance diary. RESULTS: Of the 236 athletes eligible for the study, 145 (61%) agreed to participate. Forty-six percent of the athletes who were dispensed treatment did not return questionnaires. For those returning questionnaires, scores between baseline (week 0) and weeks 4 and 8 were calculated for total symptoms, QOL, and performance scores. There were statistically significant improvements in symptoms, QOL, and performance scores in athletes who used intranasal budesonide. CONCLUSION: SAR/C is a common condition and has demonstrable negative effects on athletes. Better education of coaches and athletes is necessary to ensure that the condition is correctly diagnosed and treated, with safe, effective, permitted medication.