Abstract
Fatigue is a prevalent symptom and major burden in neuroimmunological diseases. In neuromyelitis optica spectrum disorder (NMOSD), a severe autoimmune central nervous system (CNS) inflammatory disease with autoantibodies reactive to aquaporin-4, there are few reports about fatigue and quality of life (QOL). We aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMOSD. We prospectively studied patients with NMOSD who were in remission and seropositive for anti-aquaporin-4 antibody, and they were divided into 2 groups based on the presence of fatigue assessed using the Functional Assessment of Chronic Illness Therapy-fatigue score. Sleep quality, depression, pain, and QOL were also evaluated. A total of 35 patients were enrolled (mean age, 46.5 ± 14.1 years; female: male = 29:6), and the median Expanded Disability Status Scale (EDSS) score was 2.0 (range, 0 to 8.0). The patients with fatigue (N = 25, 71.4%) had poorer sleep quality and more severe depression than those without fatigue (p = 0.009 and p = 0.001). Both the physical and mental QOL scores were lower in patients with fatigue than in those without fatigue (p = 0.033 and p = 0.004). Multiple linear regression analyses showed that the degree of fatigue with EDSS score and pain were independent predictors of physical aspects of QOL (B = 0.382, p = 0.001), whereas depression was the only predictor of the mental components of QOL (B = -0.845, p = <0.001). Fatigue is a common symptom and an important predictor of QOL in patients with NMOSD.
Introduction
Neuromyelitis optica (NMO) is an autoimmune relapsing inflammatory disorder of the central nervous system (CNS) characterized by optic neuritis, myelitis, and distinctive brain lesions.[1] An antibody against the main water channel protein in CNS, aquaporin-4 (anti-AQP4), is thought to be pathogenic and detected in 60–80% of patients with NMO.[2] NMO is distinguished from multiple sclerosis (MS) by its pathogenesis and clinical features;[1, 2] generally, it is regarded that patients with NMO have more severe attacks than relapsing-remitting MS.[1] There has been many studies on the impairment of quality of life (QOL) in MS in which fatigue, depression, and sleep disorder were considerable predictors of low QOL scores.[3–5] Particularly, fatigue was reported as one of the most frequent and disabling symptom in MS, and the improvement of fatigue is being considered as an important treatment target in patients with MS.[6, 7] In NMO, a recent study showed that the disease had a strong negative impact on health-related QOL in patients;[8] however, there are only a few reports on the relationship of fatigue and QOL in NMO. To date, the immunosuppressive therapy to reduce the number of relapses was the only apparent treatment goal of NMO,[9] although the impairment of QOL, severe fatigue, depression, and pain can be a major part of the burden of this disorder. In this study, we aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMO spectrum disorder (NMOSD).
Materials and methods
Patients
We prospectively studied consecutive NMO or NMOSD patients who were registered in the CNS Inflammatory Disease Registry at the Samsung Medical Center from June 2014 to May 2015. Patients were enrolled if they met the revised criteria for NMO or the suggestion of NMOSD with positive anti-AQP4,[1, 10] which is in agreement with the diagnosis of NMOSD with anti-AQP4 based on the International Consensus Diagnostic Criteria,[11] and they were during remission for at least 6 months. Patients who were excluded from the study are as follows: (a) anti-AQP4 status was either negative or not assessed using the cell-based indirect immunofluorescence assay as described previously,[12] (b) patients who refused to participate in the study, (c) patients who had medical disorders that could alter the status of fatigue including thyroid disease and adrenal insufficiency. The demographic and clinical characteristics were collected, including age, gender, disease duration, disability assessed by Expanded Disability Status Scale (EDSS) scores, current treatments such as immunosuppressants or oral prednisolone, and coexisting autoimmune diseases. All enrolled patients completed the self-report questionnaires for the assessment of fatigue, sleep quality, depression, pain, and QOL. The study was approved by the local ethics committees in Samsung Medical Center, and all participants provided written informed consent prior to the study.
Instruments
The severity of fatigue was assessed with a Korean version of the Functional Assessment of Chronic Illness Therapy-fatigue scale (FACIT-fatigue), which is a 13-item questionnaire that assesses self-reported fatigue and difficulty of daily activities due to fatigue; its final scores range from 0 to 52, and higher scores indicate less fatigue.[13] This questionnaire was originally developed for the assessment of fatigue in patients with cancer; however, it has been validated and used in patients with autoimmune disease including Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, and Sjogren’s syndrome.[14, 15] Considering relationship between NMOSD and systemic rheumatologic autoimmune diseases, using the FACIT-fatigue scale could be reasonable because the fatigue questionnaire specifically for the patients with NMOSD has not been settled yet.
The median score of FACIT-fatigue from a general population study in the United States with 1075 subjects was 43.[16] The patients were divided into 2 groups based on the FACIT-fatigue score: NMOSD without fatigue group (FACIT-fatigue score above 43) and NMOSD with fatigue group (FACIT-fatigue score of 43 or less).
Depression was evaluated by the Beck Depression Inventory score-II (BDI), which is composed of 21 items, and ranges from 0 to 63; higher scores indicate more severe depression. The Brief Pain Inventory (BPI), used for the assessment of pain has questions regarding 2 categories: pain severity and pain-related interference in daily life (each category ranges from 0 to 10); pain severity index score was evaluated by the average score of pain severity questions. The Pittsburgh Sleep Quality Index score (PSQI), which is composed of 7 items, and ranges from 0 to 21, was used for measuring the sleep quality. Higher scores of PSQI indicate poor sleep quality, and a poor sleeper was defined as a patient with PSQI score above 5. QOL was assessed via the Short Form 36 Health Survey (SF-36) with scores from 0 to 100, where higher scores indicate better QOL. Two summary scores of SF-36 were used for analysis: Physical component summary (PCS) and Mental component summary (MCS).