RESUMO
BACKGROUND: In this study, we hypothesized that clinically isolated syndrome-optic neuritis patients may have disturbances in neuropsychological functions related to visual processes. METHODS: Forty-two patients with optic neuritis within 3 months from onset and 13 healthy controls were assessed at baseline and 6 months with MRI (brain volumes, lesion load, and optic radiation lesion volume) and optical coherence tomography (OCT) (peripapillary retinal nerve fiber layer [RNFL], ganglion cell and inner plexiform layers [GCIPLs], and inner nuclear layer). Patients underwent the brief cognitive assessment for multiple sclerosis, high-contrast and low-contrast letter acuity, and color vision. RESULTS: At baseline, patients had impaired visual function, had GCIPL thinning in both eyes, and performed below the normative average in the visual-related tests: Symbol Digit Modalities Test and Brief Visuospatial Memory Test-Revised (BVMT-R). Over time, improvement in visual function in the affected eye was predicted by baseline GCIPL (P = 0.015), RNFL decreased, and the BVMT-R improved (P = 0.001). Improvement in BVMT-R was associated with improvement in the high-contrast letter acuity of the affected eye (P = 0.03), independently of OCT and MRI metrics. CONCLUSION: Cognitive testing, assessed binocularly, of visuospatial processing is affected after unilateral optic neuritis and improves over time with visual recovery. This is not related to structural markers of the visual or central nervous system.
Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Neurite Óptica , Cognição , Doenças Desmielinizantes/complicações , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Fibras Nervosas/patologia , Neurite Óptica/complicações , Neurite Óptica/diagnóstico , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: Fatigue is common in multiple sclerosis and is associated with reduced quality of life. This study aimed to assess the correlation between fatigue scores and data from other self-assessment questionnaires, neuropsychological tests and neuroimaging, as well as data on neuroimmunological markers in cerebrospinal fluid (CSF) and serum/plasma, in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). METHODS: Modified fatigue impact scale (MFIS) scores were determined in 38 patients with newly diagnosed CIS or RRMS at baseline and after one year in a prospective longitudinal cohort study. Non-parametric correlation analyses were used to assess associations between MFIS scores and other self-assessment questionnaire data (Hospital Anxiety and Depression scale (HAD), Multiple Sclerosis Impact Scale 29 (MSIS-29) and Short Form 36 (SF-36)), as well as with neuropsychological test performances (e.g. Auditory Consonant Trigram Test (ACTT)), clinical parameters (e.g. disease duration and expanded disability status scale (EDSS)), magnetic resonance imaging (MRI) data (number of T2 lesions in brain MRI and total brain volume) and several neurodegenerative/neuroinflammatory markers in CSF and serum/plasma (IL-1ß, IL-6, CXCL1, CXCL10, CXCL13, CCL-22 in plasma; neurofilament light chain (NFL) in serum; IL-6, CXCL1, CXCL10, CXCL13, CCL22, NFL and chitinase-3-like-1 (CHI3L1) in CSF. CSF and serum/plasma from 21 age- and sex-matched healthy controls were available for comparison. RESULTS: At both baseline and one-year follow-up, fatigue scores correlated significantly with HAD, MSIS-29 and SF-36 scores and ACTT performance (Spearman´s rho 0.45-0.78, all pâ¯≤â¯0.01) but not with the other neuropsychological test results, disease duration, EDSS ratings, number of T2 lesions, total brain volume or neurodegenerative/neuroinflammatory markers, including neurofilament light chain levels in CSF and serum. In group comparisons, MFIS scores were similar in patients fulfilling no evidence of disease activity-3 (NEDA-3) (nâ¯=â¯18) and patients not fulfilling NEDA-3 (nâ¯=â¯20) during one year of follow-up (p > 0.01). CONCLUSIONS: In this cohort of patients with newly diagnosed CIS and RRMS, fatigue scores were associated with mood, disease impact on daily life and quality of life as well as with alterations of attentive functions. Study results indicate that subjective fatigue scores are not well reflected by some commonly used and objectively measurable disease parameters like EDSS, T2 lesions and NFL levels.
Assuntos
Doenças Desmielinizantes , Autoavaliação Diagnóstica , Fadiga , Esclerose Múltipla Recidivante-Remitente , Proteínas de Neurofilamentos/metabolismo , Receptores Nicotínicos/sangue , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/fisiopatologia , Fadiga/etiologia , Fadiga/metabolismo , Fadiga/fisiopatologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/metabolismo , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND PURPOSE: As a high proportion of people with clinically isolated syndrome (pwCIS) exhibit sympathetic adrenergic and sudomotor dysfunction, the aim of this study was to investigate the evolution of autonomic nervous system (ANS) abnormalities in pwCIS over a 2-year follow-up. METHODS: This was a prospective cohort study in which 121 pwCIS were enrolled and followed for 2 years. After 2-year follow-up, data were available for 84 pwCIS. ANS symptoms were evaluated with the Composite Autonomic System Score-31 (COMPASS-31) and results of the ANS tests were expressed using the Composite Autonomic Scoring Scale (CASS) at baseline and visit at month 24. Symptomatic dysautonomia was defined if the patient had a COMPASS-31 value above the median of the whole cohort at baseline evaluation (COMPASS-31 > 6.79) and CASS score >0. RESULTS: Complete CASS data at baseline and month 24 were available for 62 patients; in 24 (38.7%) patients there was worsening, in 16 (25.8%) there was improvement and in 22 (35.5%) there was no change in CASS score. In 90% of pwCIS (72 of 80) there was no change in parasympathetic nervous system tests, whereas 47.3% (35 of 74) had either worsening or improvement in sympathetic adrenergic and 28.6% (20 of 70) had either worsening or improvement in sudomotor function. A multivariable regression model identified the total number of T2 lesions as an independent predictor for worsening of symptomatic dysautonomia. No predictors for worsening or improving of CASS score were identified. CONCLUSION: A substantial proportion of pwCIS experienced worsening of ANS abnormalities during the 2-year follow-up and magnetic resonance imaging parameters seemed to predict these abnormalities.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Doenças Desmielinizantes/fisiopatologia , Esclerose Múltipla/fisiopatologia , Adulto , Sistema Nervoso Autônomo/diagnóstico por imagem , Doenças do Sistema Nervoso Autônomo/diagnóstico por imagem , Doenças do Sistema Nervoso Autônomo/etiologia , Estudos de Coortes , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico por imagem , Progressão da Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Sistema Nervoso Parassimpático/fisiopatologia , Estudos Prospectivos , Sistema Nervoso Simpático/fisiopatologiaRESUMO
INTRODUCTION: Approximately 85% of patients with multiple sclerosis have an initial demyelinating event. Treatment with interferon beta delays the progression of multiple sclerosis for nearly two years in patients with a clinically isolated syndrome. In Colombia, interferon is very expensive when compared to other countries. OBJECTIVE: We sought to determine the cost-effectiveness of a two-year interferon beta treatment within Colombia in patients with a clinically isolated syndrome. MATERIALS AND METHODS: Based on patient and society perspectives, a cost-effectiveness analysis was conducted using a decision tree. A variety of probabilities were defined after a systematic review of the available literature. The disease costs were calculated by reviewing medical charts at the Hospital San Ignacio University and surveys completed by multiple sclerosis patients. To control for uncertainty in these data, analysis of approximately one-thousand patients was performed using Monte Carlo methods. RESULTS: The two-year treatment cost per patient exceeds Col$ 95,000,000 (US$ 50,000). Approximately 80 % of this cost corresponds to medications (US$ 40,500). The price of relapse and indirect costs totals Col$ 41,632,149 (US$ 21,744) and Col$ 11,656,389 (US$ 6,088), respectively. Treatment represents an increase of 0.06 quality-adjusted life years (QALY). The incremental cost-effectiveness ratio exceeds the threshold, regardless of the use of Monte Carlo methods for analysis. CONCLUSION: Administering interferon beta over the course of two years to high-risk patients with a clinically isolated syndrome is not cost-effective within Colombia.
Assuntos
Análise Custo-Benefício , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/economia , Interferon beta/economia , Interferon beta/uso terapêutico , Colômbia , Árvores de Decisões , Doenças Desmielinizantes/complicações , Progressão da Doença , Humanos , Esclerose Múltipla/etiologia , Esclerose Múltipla/prevenção & controle , Fatores de TempoRESUMO
Introducción. En 85 % de los pacientes con esclerosis múltiple se presenta como manifestación inicial un primer evento desmielinizante o síndrome clínico aislado. En estos casos, el tratamiento con interferón beta retrasa hasta dos años la progresión a esclerosis múltiple. Sin embargo, en Colombia este medicamento es costoso. Objetivo. Determinar si el tratamiento del síndrome clínico aislado con interferón beta es costo-efectivo al retrasar la esclerosis múltiple en dos años. Materiales y métodos. Se realizó un análisis de costo-efectividad empleando un árbol de decisiones basado en la perspectiva del paciente y la sociedad. A partir de una revisión sistemática de la literatura y de conceptos de expertos se definieron las diversas probabilidades. Los costos de la enfermedad se calcularon por medio de la revisión de historias y la aplicación de encuestas a los pacientes atendidos en el Hospital Universitario San Ignacio. Para controlar la incertidumbre se realizó un análisis de sensibilidad mediante una simulación de Monte Carlo con mil pacientes. Resultados. El costo del tratamiento con interferón sobrepasa los Col$ 95´000.000 (US$ 50.000) por paciente durante los dos años. Aproximadamente, 80 % corresponde a los costos del medicamento. El costo de la recaída se acerca a Col$ 39´139.200 (US$ 21.744), y los costos indirectos corresponden a Col$ 10´958.400 (US$ 6.088). La tasa representativa del mercado fue de Col$ 1.800. Con el tratamiento se ganan sólo 0,06 años de vida ajustados por discapacidad (AVAD) adicionales. La razón de costo-efectividad incremental´ (sic.) supera el umbral, incluso en el análisis de sensibilidad. Conclusión. La administración de interferón beta en pacientes con síndrome clínico aislado de alto riesgo en los primeros dos años no es costo-efectiva en Colombia.
Introduction: Approximately 85% of patients with multiple sclerosis have an initial demyelinating event. Treatment with interferon beta delays the progression of multiple sclerosis for nearly two years in patients with a clinically isolated syndrome. In Colombia, interferon is very expensive when compared to other countries. Objective: We sought to determine the cost-effectiveness of a two-year interferon beta treatment within Colombia in patients with a clinically isolated syndrome. Materials and methods: Based on patient and society perspectives, a cost-effectiveness analysis was conducted using a decision tree. A variety of probabilities were defined after a systematic review of the available literature. The disease costs were calculated by reviewing medical charts at the Hospital San Ignacio University and surveys completed by multiple sclerosis patients. To control for uncertainty in these data, analysis of approximately one-thousand patients was performed using Monte Carlo methods. Results: The two-year treatment cost per patient exceeds Col$ 95,000,000 (US$ 50,000). Approximately 80 % of this cost corresponds to medications (US$ 40,500). The price of relapse and indirect costs totals Col$ 41,632,149 (US$ 21,744) and Col$ 11,656,389 (US$ 6,088), respectively. Treatment represents an increase of 0.06 quality-adjusted life years (QALY). The incremental cost-effectiveness ratio exceeds the threshold, regardless of the use of Monte Carlo methods for analysis. Conclusion: Administering interferon beta over the course of two years to high-risk patients with a clinically isolated syndrome is not cost-effective within Colombia.
Assuntos
Humanos , Análise Custo-Benefício , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/economia , Interferon beta/economia , Interferon beta/uso terapêutico , Colômbia , Árvores de Decisões , Progressão da Doença , Doenças Desmielinizantes/complicações , Esclerose Múltipla/etiologia , Esclerose Múltipla/prevenção & controle , Fatores de TempoRESUMO
OBJECTIVE: To assess the cost-effectiveness of subcutaneous interferon (sc IFN) beta-1a 44 mcg 3-times weekly (tiw) vs no treatment at reducing the risk of conversion to multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS) in Sweden. METHODS: A Markov model was constructed to simulate the clinical course of patients with CIS treated with sc IFN beta-1a 44 mcg tiw or no treatment over a 40-year time horizon. Costs were estimated from a societal perspective in 2012 Swedish kronor (SEK). Treatment efficacy data were derived from the REFLEX trial; resource use and quality-of-life (QoL) data were obtained from the literature. Costs and outcomes were discounted at 3%. Sensitivity analyses explored whether results were robust to changes in input values and use of Poser criteria. RESULTS: Using McDonald criteria sc IFN beta-1a was cost-saving and more effective (i.e., dominant) vs no treatment. Gains in progression free life years (PFLYs) and quality-adjusted life-years (QALYs) were 1.63 and 0.53, respectively. Projected cost savings were 270,263 SEK. For Poser criteria cost savings of 823,459 SEK were estimated, with PFLY and QALY gains of 4.12 and 1.38, respectively. Subcutaneous IFN beta-1a remained dominant from a payer perspective. Results were insensitive to key input variation. Probabilistic sensitivity analysis estimated a 99.9% likelihood of cost-effectiveness at a willingness-to-pay threshold of 500,000 SEK/QALY. CONCLUSION: Subcutaneous IFN beta-1a is a cost-effective option for the treatment of patients at high risk of MS conversion. It is associated with lower costs, greater QALY gains, and more time free of MS. LIMITATIONS: The risk of conversion from CIS to MS was extrapolated from 2-year trial data. Treatment benefit was assumed to persist over the model duration, although long-term data to support this are unavailable. Cost and QoL data from MS patients were assumed applicable to CIS patients.
Assuntos
Adjuvantes Imunológicos/economia , Interferon beta/economia , Itraconazol/economia , Adjuvantes Imunológicos/administração & dosagem , Análise Custo-Benefício , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/tratamento farmacológico , Humanos , Infusões Subcutâneas/economia , Interferon beta-1a , Interferon beta/administração & dosagem , Itraconazol/administração & dosagem , Cadeias de Markov , Esclerose Múltipla Recidivante-Remitente/etiologia , Esclerose Múltipla Recidivante-Remitente/prevenção & controle , Suécia , Resultado do TratamentoRESUMO
We followed up 102 patients with a monofocal clinically isolated syndrome (CIS) during 8 years. Factors determining its transition to definite multiple sclerosis were singled out according to the data of anamnesis and MRI scans. Age of patients at the onset of CIS and the volume of demyelination measured by the first MRI were the most significant predictors of the transition of CIS to definite multiple sclerosis. A mathematical model based on logistic regression analysis for the estimation of the risk of this transition is suggested.
Assuntos
Encéfalo/patologia , Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla/diagnóstico , Medula Espinal/patologia , Adolescente , Adulto , Doenças Desmielinizantes/complicações , Progressão da Doença , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Síndrome , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION. Demielinating diseases are a group of heterogenic diseases in whom mieline is attacked. The optic nerve (ON) is one of the most commonly affected. SUBJECTS AND METHODS. An observational prospective case-control study with ON orbital echography was developed. The case group was formed by 31 demielinating diseases patients and the control group was formed by 24 healthy people. Mean age of cases: 48.3 ± 11.8 years old, controls 48.7 ± 9.9 years old. 46% of controls and 35% of cases were males. RESULTS. We found statistical significance differences between cases and controls regarding the diameter of right (controls 3.64 ± 0.58 mm vs patients 2.84 ± 0.56 mm; p < 0.001) and left ON (controls 3.95 ± 0.84 mm vs patients 2.74 ± 0.54 mm; p < 0.001). We found no differences between maximum systolic and median velocities regarding ophthalmic arteries in both groups, neither for previous acute optical neuritis history or visual evocated potentials. CONCLUSIONS. ON evaluation with transorbital echography is an easy, feasible, non invasive, useful and costless technique for the evaluation of the ON atrophy. As for visual evocated potentials are abnormal in a huge number of patients without previous optical neuritis evidence, the diameter of ON measured by transorbital Doppler could be a consistent paraclinic marker of these diseases.
Assuntos
Atrofia Óptica/diagnóstico por imagem , Estudos de Casos e Controles , Doenças Desmielinizantes/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Óptica/etiologia , Órbita , Projetos Piloto , Estudos Prospectivos , Método Simples-Cego , Ultrassonografia/métodosRESUMO
BACKGROUND: There is evidence that at least 5% of Multiple sclerosis (MS) cases manifest in childhood. Children with MS present with a demyelinating episode involving single or multiple symptoms prior to developing a second event (usually within two years) to then meet criteria for diagnosis. There is evidence from adult cohorts that the incidence and sex ratios of MS are changing and that children of immigrants have a higher risk for developing MS. A paediatric population should reflect the vanguard of such changes and may reflect trends yet to be observed in adult cohorts. Studying a paediatric population from the first demyelinating event will allow us to test these hypotheses, and may offer further valuable insights into the genetic and environmental interactions in the pathogenesis of MS. METHODS/DESIGN: The Paediatric UK Demyelinating Disease Longitudinal Study (PUDDLS) is a prospective longitudinal observational study which aims to determine the natural history, predictors and outcomes of childhood CNS inflammatory demyelinating diseases. PUDDLS will involve centres in the UK, and will establish a cohort of children affected with a first CNS inflammatory demyelinating event for long-term follow up by recruiting for approximately 5 years. PUDDLS will also establish a biological sample archive (CSF, serum, and DNA), allowing future hypothesis driven research. For example, the future discovery of a biomarker will allow validation within this dataset for the evaluation of novel biomarkers. Patients will also be requested to consent to be contacted in the future. A secondary aim is to collaborate internationally with the International Paediatric Multiple Sclerosis Study Group when future collaborative studies are proposed, whilst sharing a minimal anonymised dataset. PUDDLS is the second of two jointly funded studies. The first (UCID-SS) is an epidemiological surveillance study that already received ethical approvals, and started on the 1st September 2009. There is no direct patient involvement, and UCID-SS aims to determine the UK and Ireland incidence of CNS inflammatory demyelinating disorders in children under 16 years. DISCUSSION: A paediatric population should reflect the vanguard of MS epidemiological changes and may reflect trends yet to be observed in adult MS cohorts. The restricted window between clinical expression of disease and exposure to environmental factors in children offers a unique research opportunity. Studying a paediatric population from the first demyelinating event will allow us to investigate the changing epidemiology of MS, and may offer further valuable insights into the genetic and environmental interactions in the pathogenesis of MS.