Participants
We prospectively enrolled patients with NMOSD, who visited our clinic from June 2021 to Sep 2022. NMOSD was diagnosed according to the 2015 International Panel for Neuromyelitis Optica diagnosis (IPND) criteria (1). The exclusion criteria were as follows: (1) history of drug or alcohol abuse or other major clinical or psychiatric conditions, including Sjogren's syndrome; (2) receiving acute immunoregulatory treatment; (3) with cerebral lesions or severe visual impairments; (4) taking medications such as antihypertensives, anticholinergics, and antiarrhythmics, which may influence autonomic function; and (5) inability to complete all questionnaires with the assistance of neurologists. Demographic data and disease features were collected including gender, age, body mass index (BMI), the presence of AQP4-Ab in serum, the number of clinical attacks, disease duration, the segments of spinal cord lesions (cervical, thoracic, and total), degree of disability, clinical phenotype, and current preventive therapy. The presence of AQP4-Ab in serum was tested with a transfected cell-based assay(15). The degree of disability was evaluated by two neurologists according to the Expanded Disability Status Scale (EDSS) score (16). Severe visual impairment was referred to as a visual function subscore of 6 according to the EDSS score. The segments of spinal cord lesions were acquired from 3T spine magnetic resonance images.
Healthy controls (HCs) were recruited among individuals who attended the hospital for annual health check-ups, with no major clinical or psychiatric conditions. Demographic data and BMI regarding the HCs were collected. The study was approved by the Ethics Committee of Sichuan Provincial People’s Hospital. Recruited participants provided written informed consent before enrolling in the study.
Composite Autonomic Symptom Score 31
All participants were requested to complete the COMPASS 31 questionnaire independently according to the actual situation. COMPASS-31 comprises 6 domains with 31 items (orthostatic intolerance 4 items, vasomotor 3 items, secretomotor 4 items, gastrointestinal 12 items, bladder 3 items, and pupillomotor 5 items) and provides the minimal weighted total score equals 0 and the maximum weighted total score equals 100 (17). The higher the score, the more severe the dysautonomic symptoms.
Clinical Composite Evaluation Of Living Status In Nmosd Patients
All enrolled NMOSD patients were requested to fulfill a composite evaluation of living status, including anxiety, depression, sleep quality, and fatigue. The Hospital Anxiety and Depression Scale (HADS) used in this study was developed to identify cases of anxiety disorders and depression among patients in nonpsychiatric hospital clinics (18). It is divided into an anxiety subscale (HADS-A) and a depression subscale (HADS-D), both containing seven intermingled items. The scores of the HADS-A and HADS-D both range from 0 to 21, and higher scores indicate more severe anxiety/depression. The sleep quality of patients was assessed through the Pittsburgh Sleep Quality Index (PSQI) (19). The global PSQI score ranges from 0 to 21, with higher scores indicating worse sleep quality. Fatigue was evaluated with the Fatigue Severity Scale (FSS), which was a self-report instrument to evaluate patients' perceptions of the functional limitations caused by fatigue within the last week (20). Possible global scores range from 7 to 63, where higher scores indicate more severe fatigue.
Quality Of Life Evaluation Of Nmosd Patients
All NMOSD patients completed the evaluation of their quality of life via the 36-item short-form health survey (SF-36). SF-36 evaluates 8 dimensions: physical functioning (10 items), physical role fulfillment (4 items), bodily pain (2 items), general health (5 items), vitality (4 items), social functioning (2 items), emotional role fulfillment (3 items), and mental health (5 items) (21). The scale’s total possible score is 145, with a higher score reflecting better quality of life.
All the scales used in the present study have been utilized in previous NMOSD studies (13, 14, 22–24). All the Chinese versions of these scales have been validated previously (25–29). A psychologist administered the HADS questionnaires; the other questionnaires were completed by the participants themselves in the presence of a neurologist, who assisted the participants in reading and understanding the items.
Statistical analysis
All statistical analyses were carried out using the statistical software GraphPad Prism (version 8, San Diego, CA).
To compare the demographic characteristics between the NMOSD and HC groups, Fisher’s exact test was used in the gender ratio analysis, and the Mann-Whitney U test was used in the comparisons of age, BMI, COMPASS-31 score, and its subscores.
To analyze the related factors of dysautonomic symptoms in NMOSD, Mann-Whitney and Kruskal-Wallis tests were used to determine whether COMPASS-31 scores/subscores differed among groups defined by gender, serum AQP4 antibody, clinical phenotype, and current preventive therapy. Spearman’s ranked correlation analysis was used to explore the relationships between the COMPASS-31 score/subscores and the independent variables, including age, BMI, number of attacks, disease duration, EDSS, segments of spinal cord lesions (cervical, thoracic, total separately), HADS-A, HADS-D, PSQI, and FSS score. Multiple linear regression was used to further assess the independent factor of the COMPASS-31 score/subscore (checking the normality of residuals). Age, gender, BMI, clinical phenotype, number of attacks, disease duration, current therapy, EDSS, segments of total spinal cord lesions, HADS, PSQI, and FSS score were included as possible independent variables for the multiple linear regression model. P < 0.05 was considered statistically significant.
To analyze the influence of dysautonomic symptom burden on patients’ quality of life, another multiple linear regression model was established to assess the independent contributor of different domains of SF-36 score in NMOSD patients (checking the normality of residuals). Age, gender, BMI, clinical phenotype, number of attacks, disease duration, current therapy, EDSS, COMPASS-31, HADS, PSQI, and FSS score were included as possible independent variables for this multiple linear regression model. P < 0.05 was considered statistically significant.