ABSTRACT
Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.
ABSTRACT
A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.
ABSTRACT
BACKGROUND: Diroximel fumarate (DRF) is approved for adults with relapsing-remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF. OBJECTIVE: To report final outcomes from EVOLVE-MS-1. METHODS: EVOLVE-MS-1 was an open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in patients with RRMS. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory. RESULTS: Overall, 75.7% (800/1057) of patients completed the study; median exposure was 1.8 (range: 0.0-2.0) years. AEs occurred in 938 (88.7%) patients, mostly of mild (28.9%) or moderate (50.3%) severity. DRF was discontinued due to AEs in 85 (8.0%) patients, with < 2% discontinuing due to GI or flushing/flushing-related AEs. At Week 96, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (72.7%; p < 0.0001); adjusted annualized relapse rate was 0.13 (95% confidence interval: 0.11-0.15). CONCLUSION: DRF was generally well tolerated over 2 years, with few discontinuations due to AEs; radiological measures indicated decreased disease activity from baseline. These outcomes support DRF as a treatment option in patients with RRMS.
Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adult , Humans , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Immunosuppressive Agents/adverse effects , Multiple Sclerosis/drug therapy , Dimethyl Fumarate/adverse effects , RecurrenceABSTRACT
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Previous studies have shown that cerebrospinal fluid (CSF) kappa free light chains (K-FLCs) may have a role in MS diagnosis. In this regard, the kappa index (K-Index) has demonstrated higher sensitivity, and slightly lower specificity than oligoclonal bands (OCBs), the gold standard for the detection of intrathecal immunoglobulin synthesis, a feature of MS. Here, we evaluated the performance of the K-Index (K-Index = CSF/serum K-FLC divided by CSF/serum albumin) for the differential diagnosis of MS in a cohort of patients with suspected MS. K-FLCs were quantitatively measured in parallel serum and CSF samples by turbidimetry (Freelite Mx reagent on an Optilite system, The Binding Site Group Ltd). From 160 (63.4%) of a total of 252 patients who had K-FLC in CSF <0.03 mg/dl, below the sensitivity limit of the technique, only one had a diagnosis of MS. However, the absence of OCB in this same patient suggested no synthesis of intrathecal immunoglobulin. Globally, MS patients presented significantly higher K-Index levels than patients without an MS diagnosis (66.96 vs. 0.025, respectively; p < 0.0001). In agreement, patients with positive OCB testing also exhibited higher K-Index levels than patients negative for OCB (65.02 vs. 0.024, respectively; p < 0.0001). An optimal K-Index cutoff of 3.045 was defined by receiver operating characteristic (ROC) analysis for screening suspected MS, achieving a higher diagnostic sensitivity and slightly lower specificity than OCB (Sens. 0.9778 and Spec. 0.8629 vs. Sens. 0.8889 and Spec. 0.9086, respectively). A previously reported K-Index cutoff of 6.6 also showed good diagnostic performance (Sens. 0.9333; Spec. 0.8731), validating its power as a diagnostic biomarker for MS. Finally, a time- and cost-effective algorithm for MS screening is proposed that would offer an initial rapid evaluation of the intrathecal immunoglobulin synthesis through the K-FLC in CSF and K-Index analysis, followed by reflexing OCB testing that may be ordered more selectively.
ABSTRACT
Crucial elements for achieving optimal long-term outcomes in multiple sclerosis (MS) are patient confidence and effective physician-patient communication. Patient-reported instruments may provide the means to fill the gap in currently available clinician-rated measures. The SymptoMScreen (SMSS) is a brief self-assessment tool for measuring symptom severity in 12 neurologic domains commonly affected by MS. We conducted a non-interventional study to assess the dimensional structure and item characteristics of the SMSS. A total of 218 patients with relapsing-remitting MS and mild disability (median Expanded Disability Status Scale score 2.0) were studied. Symptom severity was low (SMSS score 13.5, interquartile range 4.2-27), fatigue being the domain with the highest impact. A non-parametric item response theory, i.e., Mokken analysis, found that the SMSS is a robust one-dimensional scale (overall scalability index H 0.60) with high reliability (Cronbach's alpha 0.94). The confirmatory factor analysis model confirmed the unidimensional structure (comparative fit index 1.0, root-mean-square error of approximation 0.001). Samejima's model fitted well an unconstrained model with different item difficulties. The SMSS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement addition to measure the symptom severity in clinical practice.
ABSTRACT
Cognitive impairment has been reported at all phases and all subtypes of multiple sclerosis. It remains a major cause of neurological disability in young and middle-aged adults suffering from the disease. The severity and type of cognitive impairment varies considerably among individuals and can be observed both in early and in later stages. The areas which have commonly shown more deficits are: information processing speed, complex attention, memory, and executive function. Even though an alteration in both the white matter and in the gray matter has been found in patients with multiple sclerosis and cognitive impairment, the underlying process still remains unknown. Standardized neurological examinations fail to detect emerging cognitive deficits and self-reported cognitive complaints by the patients can be confounded by other subjective symptoms. This review is a comprehensive and short update of the literature on cognitive dysfunctions, the possible confounders and the impact of quality of life in patients with multiple sclerosis.
ABSTRACT
Introducción. La ansiedad y la depresión son trastornos psiquiátricos vinculados a la Esclerosis Múltiple (EM). Sin embargo, la ansiedad no ha sido prácticamente estudiada. Objetivos. Examinar la asociación de ambos trastornos con el deterioro neuropsicológico y su contribución a la autopercepción de deterioro cognitivo. Sujetos y métodos. Se estudiaron 33 pacientes con EM Remitente-Recidivante y niveles de discapacidad mínima-leve. Instrumentos: Hospital Anxiety and Depression Scale (HADS); Multiple Sclerosis Neuropsychological Screening Questionnaire; Brief Repeatable Battery of Neuropsychological Tests. El examen neuropsicológico se aplicó a 67 controles. Resultados. La ansiedad y la depresión no están relacionadas con el deterioro neuropsicológico. La gravedad de la sintomatología ansiosa está especialmente asociada a una menor duración de la EM. Ansiedad y depresión están altamente correlacionadas y ambas predicen la percepción subjetiva de deterioro. La capacidad predictiva del HADS-total sobre la percepción subjetiva de deterioro fue similar a la obtenida por las subescalas de ansiedad y depresión por separado. Conclusiones. La autopercepción de deterioro cognitivo en la EMRR con discapacidad mínima podría estar relacionada con un factor de malestar psicológico general compartido por la ansiedad y la depresión. Nuestros resultados resaltan la importancia de detectar y tratar la sintomatología ansiosa en fases iniciales de la EM.
Introduction. Anxiety and depression are common psychiatric symptoms among multiple sclerosis (MS) patients. However, anxiety is relatively under-studied. Aims. To examine the associations of anxiety and depression with cognitive functioning and to evaluate their contribution to subjective cognitive impairment, after accounting for neuropsychological impairment. Subjects and methods. 33 patients with relapsing-remitting MS and minimal levels of disability were evaluated. Assessment measures: Hospital Anxiety and Depression Scale (HADS); Multiple Sclerosis Neuropsychological Screening Questionnaire-self report (MSNQ-S); Brief Repeatable Battery of Neuropsychological Tests (BRB). We also assessed a group of 67 controls with the BRB. Results. Neuropsychological impairment was not significantly correlated to anxiety or depression. Increased severity of anxiety symptoms was remarkably related with low disease duration. Hierarchical regression analysis showed that anxiety and depression predicted MSNQ-S. Anxiety and depression were highly correlated. HADS total score predicted a similar amount of variance to subjective cognitive impairment, compared with independent anxiety and depression measures. Conclusions. In RR MS patients with minimal levels of neurological disability, cognitive complaints could be related with a component of general psychological distress common to anxiety and depression. Despite this overlap, our study highlights the importance of assessing and treating anxiety symptoms in the first years since onset.
Subject(s)
Humans , Male , Female , Adult , Anxiety/psychology , Depression/psychology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Multiple Sclerosis, Relapsing-Remitting/psychology , Neuropsychological Tests , Psychiatric Status Rating Scales , Self Concept , Surveys and QuestionnairesABSTRACT
Our aim was to study cognitive performance in the early phase of MS. In addition, we studied whether depression, demographic and clinical variables differentiate cognitively impaired patients from non-impaired patients. A group of 52 MS-RR patients with mild level of neurological disability and 51 healthy controls were administered a comprehensive neuropsychological battery. The MS group performed significantly worse on several measures of attention and processing speed and visuoperceptive/visuoconstructive tasks. Verbal memory is characterized by working memory deficits, whereas the visual memory impairment is attributable to deficits in acquisition and consolidation/recuperation. Results shows that cognitive impairment is evident even in MS patients in the early course of their disease. Depression scores were higher in cognitively impaired patients as compared with unimpaired patients. The effect of educational level suggests that higher education delays the onset of cognitive decline.
Subject(s)
Affect , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Multiple Sclerosis/diagnosis , Multiple Sclerosis/epidemiology , Adult , Demography , Female , Humans , Male , Neuropsychological Tests , Severity of Illness IndexABSTRACT
El objetivo de la presente investigación es determinar la afectación cognitiva de pacientes con esclerosis múltiple (EM) en estadios iniciales de la enfermedad y estudiar si el estado de ánimo y las variables demográficas y clínicas diferencian a los pacientes con alteraciones cognitivas de los pacientes preservados. Participaron 52 pacientes con EM remitente-recurrente y leve disfunción neurológica y un grupo control de 51 sujetos. Se aplicó una amplia batería neuropsicológica. Los pacientes presentaron un rendimiento inferior en diversas tareas atencionales y de velocidad de procesamiento, así como en tareas visoperceptivas y visoconstructivas. Las alteraciones en memoria verbal se producen en memoria de trabajo, mientras que en memoria espacial está afectada la adquisición y la reproducción demorada. Estos resultados demuestran que la afectación cognitiva en la EM está presente incluso en fases iniciales. Los pacientes con alteraciones cognitivas presentan mayores niveles de depresión. Además, los resultados sugieren que un mayor nivel educativo podría retrasar el comienzo del declive cognitivo
Our aim was to study cognitive performance in the early phase of MS. In addition, we studied whether depression, demographic and clinical variables differentiate cognitively impaired patients from non-impaired patients. A group of 52 MS-RR patients with mild level of neurological disability and 51 healthy controls were administered a comprehensive neuropsychological battery. The MS group performed significantly worse on several measures of attention and processing speed and visuoperceptive/visuoconstructive tasks. Verbal memory is characterized by working memory deficits, whereas the visual memory impairment is attributable to deficits in acquisition and consolidation/recuperation. Results shows that cognitive impairment is evident even in MS patients in the early course of their disease. Depression scores were higher in cognitively impaired patients as compared with unimpaired patients. The effect of educational level suggests that higher education delays the onset of cognitive decline
