Therapeutic Response and Possible Biomarkers in Acute Attacks of Neuromyelitis Optica Spectrum Disorders: A Prospective Observational Study

Abstract

Objective: To explore the outcomes of NMOSD attacks and investigate serum biomarkers for prognosis and severity.

Method: Patients with NMOSD attacks were prospectively and observationally enrolled from January 2019 to December 2020 at four hospitals in Guangzhou, southern China. Data were collected at attack, discharge and 1/3/6 months after acute treatment. Serum cytokine/chemokine and neurofilament light chain (NfL) levels were examined at the onset stage.

Results: One hundred patients with NMOSD attacks were included. The treatment comprised intravenous methylprednisolone pulse therapy alone (IVMP, 71%), IVMP combined with apheresis (8%), IVMP combined with intravenous immunoglobulin (18%) and other therapies (3%). EDSS scores decreased significantly from a medium of 4 (interquartile range 3.0-5.5) at attack to 3.5 (3.0-4.5) at discharge, 3.5 (2.0-4.0) at the 1-month visit and 3.0 (2.0-4.0) at the 3-month visit (p<0.01 in all comparisons). The remission rate was 38.0% at discharge and 63.3% at the 1-month visit. Notably, relapse occurred in 12.2% of 74 patients by the 6-month follow-up. Higher levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-10, IL-13, and IL-1 receptor antagonist, predicted remission at the 1-month visit (OR=9.33, p=0.04). Serum NfL levels correlated positively with onset EDSS scores in acute-phase NMOSD (p<0.001, R² = 0.487).

Conclusions: Outcomes of NMOSD attacks were generally moderate. A high level of serum Th2-related cytokines predicted remission at the 1-month visit, and serum NfL may serve as a biomarker of disease severity at attack.

Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04101058, identifier NCT04101058.

Keywords: acute attack; biomarkers; expanded disability status scale; neuromyelitis optica spectrum disorders; prognosis.

Figure 1

Enrollment and Follow-up. *one follow-up is counted as long as the time-point is correct regardless of whether the previous follow-up was completed or not.

Figure 2

Demyelinating phenotypes (A) and therapeutic patterns (B) in the cohort. EDSS, Expanded Disability Status Scale; IVMP, intravenous methylprednisolone pulse therapy; IVMP+PE, IVMP combined with plasma exchange; IVMP+IVIg, IVMP combined with intravenous immunoglobulin; others in (A) included 9 patients with a brainstem syndrome, 5 with a cerebral syndrome, 6 with a diencephalic syndrome, 4 with a area postrema syndrome with or without ON or MY; others in (B) were 3 patients treated with oral glucocorticoid. Fisher’s exact test was used for statistical analysis.

Figure 3

The outcome of attacks of NMOSD patients. Changes in expanded disability status scale (EDSS) scores and visual acuities in NMOSD patients from acute attacks to 6-month follow-up. (A) EDSS scores were compared in all matched patients corresponding to 4 time points in the whole cohort. (B) The values of visual acuities of the affected eyes were recorded as Snellen charts and transformed to logMAR values in patients with optic neuritis attacks. Paired Wilcoxon signed rank test was used for statistical analysis; and remission rates categorized by clinical manifestations and therapeutic methods in the cohort. (C) Remission status at discharge (n = 100) and (D) at the 1-month visit (n = 79) in isolated myelitis (MY), isolated optic neuritis (ON), simultaneous MY plus ON (MY+ON) and other subtypes. (E) Remission rates at discharge (n = 100, E) and at the 1-month visit (n = 79, F) with treatment with intravenous methylprednisolone pulse therapy (IVMP), IVMP combined with plasma exchange (IVMP+PE) IVMP combined with intravenous immunoglobulin (IVMP+IVIg) and other drugs. Fisher’s exact test was used for statistical analysis. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 4

Principal component analysis (PCA) based on 19 multiple cytokines and chemokines. (A) PCA plot for principal component (PC)1 composed of interleukin(IL)-4, IL-10, IL-13 and IL-1 receptor atagonist; (B) PCA plot for 15 other cytokines and chemokines including rotated components (RC)1, RC2 and RC3. Comparisons were between patients with remission and those without remission from NMOSD attacks at 1-month visit.

Figure 5

The serum NFL (sNFL) levels were positively related with the expanded disability status scale (EDSS) scores at attack in NMOSD patients. R2, determination coefficient.