Neuromyelitis optica spectrum disorders with unevenly clustered attack occurrence

Abstract

Objective: The aim of this study was to elucidate the characteristics of clinical attacks in neuromyelitis optica spectrum disorders (NMOSDs) with positive serum anti-aquaporin-4 antibody. Both the timing and sequential pattern of clinical types were analyzed.

Methods: A total of 69 patients with NMOSD were enrolled in this study, all of whom were treated at a single university hospital. All data regarding the clinical attacks (including types and date) together with other clinical information were collected.

Results: Analysis of clinical attacks from the enrolled patients showed that there were 2 distributional patterns of attack occurrence in each patient: (1) "clustered" occurrences, which occurred within 12 months from the previous attack, and (2) "nonclustered" intermittent occurrences, which occurred ≥12 months after the previous attack. These occurrences were regardless of the duration from the onset. During the "clustered" period, clinical attacks were more likely to show a similar clinical manifestation, such as optic neuritis or myelitis. After entering the "nonclustered" intermittent period, the relapses were of random clinical type, regardless of the previous clinical manifestation.

Conclusions: Patients with NMOSD showed mixed periods of "clustered" occurrence with frequent attacks presenting with similar manifestations and "nonclustered" intermittent periods with sparse relapses. Approximately half of the relapses occurred during the "clustered" period within 12 months of the last clinical attack. Clinicians should pay special attention to whether the patients are presently in the "clustered" or "nonclustered" period to decide optimal relapse-preventive strategies.

Figure 1. The number of patients with ≥2 attacks based on the rate of attacks with optic neuritis (ON)

ON = optic neuritis

Figure 2. Clinical course and relapses in each of the patients with ≥3 attacks (n = 43)

The presented clinical courses imply a clustered occurrence of attacks, irrespective of the duration from clinical onset.

Figure 3. Tendency of clustered attacks in NMOSD, irrespective of treatments

(A) Histograms of the months between 2 tandem attacks (black bars) and the months of relapse-free period by June 2019 (white bars) in all 69 enrolled patients. The center of the gray-colored diamond is the average and its width is the standard error (SE). (B) Histogram of the months between 2 tandem attacks during the medication-free period. (C) Histogram of the months between 2 tandem attacks during the treatment period with oral relapse-preventive therapy. NMOSD = neuromyelitis optica spectrum disorder.

Figure 4. Kaplan-Meier survival analysis comparing relapse-free periods without medications between 0 and 24 months from onset and later

The analysis compared the relapse-free period without relapse-preventive therapies between 0 and 24 months from the onset (36 patients with no relapse-preventive therapy) and 24–48 months from the onset (14 patients without relapses in the first 24 months). The latter group represents the “nonclustered” intermittent period status. The former group showed a shorter relapse-free period and a higher relapse rate than the latter group (p = 0.0206, generalized Wilcoxon test).