Demographic, onset and disease course clinical features among groups in AQP4-IgG NMOSD with paediatric onset
| Total cohort | Sex | Age at onset | Race | ||||||||
| N=49 | Female n=43 | Male n=6 | P value | <12 years n=19 | 12–18 years n=30 | P value | Black* n=20 | Asian n=10 | White n=19 | P value | |
| Demography | |||||||||||
| F, n (%) | 43 (87.7) | – | – | – | 16 (84.2) | 27 (90) | ns | 15 (75) | 9 (90) | 17 (89.5) | ns |
| F:M | 7:01:00 | – | – | – | 5:01:00 | 9:01:00 | – | 7.5:1 | 9:01:00 | 8.5:1 | – |
| Mean onset age years±SD | 12.0±4.1 | 12±4 | 11±5.5 | ns | – | – | – | 13.5±3.74 | 12.7±3.74 | 9.8±4.11 | 0.014 |
| Median age at AQP4-IgG diagnosis (years) (range) | 14 (3–45) | 14 (3–45) | 15.5 (3–31) | ns | – | – | ns | 13 (3–34) | 19 (9–45) | 12 (3–32) | ns |
| Median time from onset to AQP4-IgG detection (years) (range) | 1 (0–32) | 1 (0–32) | 1 (0–17) | ns | 0 (0–22) | 1 (0–32) | ns | 0 (0–17) | 7 (0–32) | 0 (0–22) | 0.022 |
| Median disease duration (months) (range) | 79 (2–401) | 78 (2–401) | 100 (2–219) | ns | 90 (6–367) | 72 (2–401) | ns | 51 (5–273) | 155 (2–401) | 79 (2–367) | ns |
| Median current age (years) (range) | 21 (7–54) | 21 (7–54) | 22 (15–33) | ns | 19 (7–43) | 24 (16–54) | ns | 18 (16–43) | 28 (16–54) | 21 (7–43) | ns |
| Race, n (%) | |||||||||||
| Black | 17 (34.7) | 15 (34.9) | 2 (33.3) | ns | 3 (15.8) | 14 (46.7) | 0.025 | – | – | – | – |
| Asian | 10 (20.4) | 9 (21) | 1 (16.7) | ns | 3 (15.8) | 7 (23.3) | ns | ||||
| White | 19 (38.8) | 17 (39.5) | 2 (33.3) | ns | 12 (63.1) | 7 (23.3) | 0.008 | ||||
| Mixed | 3 (6.1) | 2 (4.6) | 1 (16.7) | ns | 1 (5.3) | 2 (6.7) | ns | ||||
| Coexisistent autoimmune diseases, n (%) | 7 (14) | 4 (9.3) | 3 (50) | 0.019 | 4 (21) | 3 (10) | ns | 3 (15) | 1 (10) | 3 (15.8) | ns |
| Prodromal symptoms, n (%) | 14 (28.6) | 13 (30.2) | 1 (16.7) | ns | 7 (36.8) | 7 (23.2) | ns | 8 (40) | 1 (10) | 5 (26.2) | ns |
| Onset syndromes, n (%) | |||||||||||
| ON | 23 (47) | 19 (44.2) | 4 (66.7) | ns | 10 (52.6) | 13 (43.3) | ns | 8 (40) | 6 (60) | 9 (47.4) | ns |
| BS | 24 (48.9) | 23 (53.5) | 1 (16.7) | ns | 6 (31.6) | 18 (54) | ns | 10 (50) | 5 (50) | 9 (47.4) | ns |
| TM | 12 (24.5) | 12 (28) | 0 | ns | 5 (26.3) | 7 (23.3) | ns | 6 (30) | 2 (20) | 4 (21) | ns |
| CS | 14 (28.6) | 12 (28) | 2 (33.3) | ns | 5 (26.3) | 9 (30) | ns | 6 (30) | 2 (20) | 6 (31.6) | ns |
| ON+TM | 4 (8.2) | 4 (9.3) | 0 | ns | 1 (5.3) | 3 (10) | ns | 2 (10) | 2 (20) | 0 | ns |
| Monofocal | 36 (73.5) | 31 (72) | 5 (83.3) | ns | 14 (73.7) | 22 (73.3) | ns | 15 (75) | 7 (70) | 14 (73.8) | ns |
| Multifocal | 13 (26.5) | 12 (28) | 1 (16.7) | ns | 5 (26.3) | 8 (26.7) | ns | 5 (25) | 3 (30) | 5 (26.2) | ns |
| Onset syndromes, n (%) | |||||||||||
| ON | 23 (47) | 20 (46.5) | 4 (66.7) | ns | 10 (52.6) | 14 (46.7) | ns | 9 (45) | 6 (60) | 9 (47.4) | ns |
| BS | 24 (48.9) | 22 (51.2) | 1 (16.7) | ns | 6 (31.6) | 17 (56.7) | ns | 9 (45) | 5 (50) | 9 (47.4) | ns |
| TM | 12 (24.5) | 12 (28) | 0 | ns | 5 (26.3) | 7 (23.3) | ns | 6 (30) | 2 (20) | 4 (21) | ns |
| CS | 14 (28.6) | 11 (25.6) | 2 (33.3) | ns | 5 (26.3) | 8 (26.7) | ns | 5 (25) | 2 (20) | 6 (31.6) | ns |
| ON+TM | 4 (8.2) | 3 (7.0) | 0 | ns | 1 (5.3) | 2 (6.7) | ns | 2 (10) | 1 (10) | 0 | ns |
| Monofocal | 36 (73.5) | 34 (79.1) | 5 (83.3) | ns | 15 (79) | 24 (80) | ns | 15 (75) | 7 (70) | 14 (73.8) | ns |
| Multifocal | 13 (26.5) | 9 (21) | 1 (16.7) | ns | 4 (21) | 6 (20) | ns | 5 (25) | 3 (30) | 5 (26.2) | ns |
| Severe onset attack, n (%) | 37 (75.5) | 33 (76.7) | 4 (66.7) | ns | 13 (68.4) | 24 (80) | ns | 17 (85) | 8 (80) | 12 (63.1) | ns |
| Onset acute therapy, n (%) | |||||||||||
| IVMP | 22 (45) | 20 (46.5) | 2 (33.3) | ns | 9 (47.4) | 13 (43.3) | ns | 5 (25) | 7 (70) | 10 (52.6) | ns |
| IVMP+PLEX+IVIG | 10 (20.4) | 9 (20.9) | 1 (16.7) | ns | 2 (10.5) | 8 (26.7) | ns | 8 (40) | 1 (10) | 1 (5.3) | 0.018 |
| Unknown | 1 (4.1) | 1 (2.3) | 0 | – | 1 (5.3) | 0 | – | 1 (5.3) | 0 | 0 | – |
| No therapy | 16 (30.6) | 13 (30.2) | 3 (50) | ns | 8 (42.1) | 8 (26.7) | ns | 6 (30) | 2 (20) | 8 (42.1) | ns |
| Clinical course, n (%) | |||||||||||
| MON | 8 (16.3) | 7 (16.3) | 1 (16.7) | ns | 2 (10.5) | 6 (20) | ns | 5 (25) | 1 (10) | 2 (10.5) | ns |
| R | 41 (83.7) | 36 (83.7) | 5 (83.3) | ns | 17 (89.5) | 24 (80) | ns | 15 (75) | 9 (90) | 17 (89.5) | ns |
| Median disease duration, MON (months) (range) | 8 (2–79) | 9 (2–79) | NA | – | 43 (6–79) | 8 (2–48) | ns | 9 (6–48) | NA | 41 (2–79) | – |
| Median time to IS, MON (months) (range) | 4.5 (0–20) | 4.5 (0–20) | NA | – | NA | 2 (0–20) | – | 4.5 (1–20) | NA | NA | – |
| Median disease duration, R (years) (range) | 96 (21–401) | 96 (21–401) | 138 (45–219) | ns | 96 (33–367) | 97 (21–401) | ns | 71 (21–273) | 200 (38–401) | 78 (21–367) | ns |
| Median time to IS, R (months) (range) | 11 (0–400) | 11 (0–400) | 21 (2–209) | ns | 10 (3–216) | 19 (0–400) | ns | 6 (0–209) | 48 (2–400) | 10 (0–216) | ns |
| Mean annualised relapse rate (ARR) | 0.80±0.47 | 0.87±0.44 | 0.88±0.7 | ns | 1.03±0.33 | 0.75±0.49 | ns | 0.80±0.54 | 0.75±0.30 | 0.97±0.60 | ns |
| First long-term immunosuppressant therapy, n (%) | |||||||||||
| AZA | 30 (61.2) | 28 (65.1) | 2 (33.3) | ns | 14 (73.6) | 16 (53.3) | ns | 9 (45) | 9 (90) | 12 (63.2) | ns |
| MMF | 7 (14.3) | 5 (11.6) | 2 (33.3) | ns | 3 (15.8) | 4 (13.3) | ns | 3 (15) | 1 (10) | 3 (15.8) | ns |
| RTX | 6 (12.2) | 5 (11.6) | 1 (16.7) | ns | 1 (5.3) | 5 (16.7) | ns | 4 (20) | 0 | 2 (10.5) | ns |
| Methotrexate | 2 (4.1) | 1 (2.3) | 1 (16.7) | ns | 0 | 2 (6.7) | – | 2 (10) | 0 | 0 | – |
| Cyclophosphamide | 2 (4.1) | 2 (4.7) | 0 | ns | 1 (5.3) | 1 (3.3) | ns | 1 (5) | 0 | 1 (5.3) | ns |
| Others† | 2 (4.1) | 2 (4.7) | 0 | ns | 0 | 2 (6.7) | – | 1 (5) | 0 | 1 (5.3) | ns |
| Failure of first-line therapy, n (%) | |||||||||||
| AZA | 13 (43.3) | 11 (39.2) | 2 (100) | ns | 8 (57.1) | 5 (31.2) | ns | 4 (44.4) | 1 (11.1) | 8 (66.7) | ns |
| MMF | 6 (85.7) | 4 (80) | 2 (100) | ns | 3 (100) | 3 (75) | ns | 2 (66.7) | 1 (100) | 3 (75) | ns |
| RTX | 1 (16.7) | 1 (20) | 0 | ns | 0 | 1 (20) | ns | 1 (25) | – | 0 | – |
| Methotrexate | 1 (50) | 1 (50) | – | – | – | 1 (50) | – | 1 (50) | – | – | – |
| Cyclophosphamide | 2 (100) | 2 (100) | – | – | 1 (100) | 1 (100) | ns | 1 (100) | – | 1 (100) | – |
| Median time to therapy (months) | 10.5 (4–46) | 10 (4–38) | 6.5 (4.2–9) | ns | 10 (5–20) | 11 (2–60) | ns | 6 (2–20) | 41 (18–201) | 10 (5–27) | 0.03 |
| Mean number of relapses before therapy±SD | 2.93±2.28 | 2.9±2.22 | 3.4±1.81 | ns | 3.11±1.45 | 2.82±2.55 | ns | 2.33±1.81 | 4.2±3.29 | 2.83±1.46 | 0.036 |
| ARR before starting long-term therapy±SD | 1.39±0.75 | 1.31±1.20 | 1.91±2.68 | ns | 1.94±1.81 | 1.18±1.23 | ns | 0.85±0.50 | 1.33±1.39 | 1.94±1.890 | ns |
| ARR during long-term therapy±SD | 0.31±0.05 | 0.31±0.34 | 0.3±0.41 | ns | 0.32±0.41 | 0.29±0.29 | ns | 0.35±0.32 | 0.21±0.21 | 0 .32±0.41 | ns |
| Disability after onset attack, n (%) | |||||||||||
| Visual disability | 6 (12.2) | 5 (11.6) | 1 (16.7) | ns | 4 (21.1) | 2 (6.7) | ns | 0 | 1 (10) | 5 (26.3) | 0.033 |
| Cognitive impairment | 2 (4.1) | 1 (2.3) | 1 (16.7) | ns | 1 (5.3) | 1 (3.3) | ns | 1 (5) | 0 | 1 (5.3) | ns |
| EDSS score 4 | 1 (2) | 1 (2.3) | 0 | ns | 0 | 1 (3.3) | ns | 0 | 0 | 1 (5.3) | ns |
| EDSS score 6 | 2 (4.1) | 2 (4.7) | 0 | ns | 0 | 2 (6.7) | ns | 1 (5) | 0 | 1 (5.3) | ns |
| EDSS score 8 | 1 (2) | 1 (2.3) | 0 | ns | 0 | 1 (3.3) | ns | 1 (5) | 0 | 0 | ns |
| Dead | 0 | 0 | 0 | – | 0 | 0 | – | 0 | 0 | 0 | – |
P value is estimated using Fisher’s exact test for proportion comparisons; t-test (sex and age at onset) and analysis of variance (race) for mean comparisons; Mann-Whitney U test (sex and age at onset) and Kruskal-Wallis test (race) for median comparisons.
CS includes acute disseminated encephalomyelitis and diencephalic syndromes.
ON includes monolater and bilateral ONs.
BS includes area postrema syndrome or other BSs.
*Patients with mixed black ancestry were included in the black ancestry group as they showed similarities in demographic and clinical features.
†Multiple sclerosis disease-modifying drugs.
AQP4-IgG, aquaporin-4 antibody; ARR, annualised relapse rate; AZA, azathioprine; BS, brainstem syndrome; CS, cerebral syndrome; EDSS, Expanded Disability Status Scale; F, female; IS, immunosuppression; IVIG, intravenous immunoglobulin; IVMP, intravenous methylprednisolone; M, male; MMF, mycophenolate mofetil; MON, monophasic; NMOSD, neuromyelitis optica spectrum disorder; ns, not significant; ON, optic neuritis; PLEX, plasma exchange; R, relapsing; RTX, rituximab; TM, transverse myelitis.