Clinical characteristics of ADEM children seropositive for anti-MOG antibodies
We identified 35 patients, 21 males and 14 females (male-to-female ratio of 1.5:1), with a median onset age of 69 months (range: 20-138 months), in the MOG+ group. The disease duration ranged from 1 to 30 days (median: 10 days), with a hospital stay length of 6-35 days (median: 17 days). Seasonal increases in incidence during spring or winter were seen in our cohort (13 cases in winter, 10 cases in spring, 5 cases in summer, and 7 cases in fall). Among the patients, 28.6% (10/35) had an acute upper respiratory history, while the other 71.4% of patients had no preceding or concomitant diagnosis of respiratory infection. None of our patients had a preceding vaccination history. Encephalopathy was seen in all patients, including altered consciousness in 21 patients (60%) and behavioral changes in the other 14 children (40%). Other symptoms included fever (23/35, 65.7%), headache (15/35, 42.9%), vomiting (13/35, 37.1%), limb weakness (13/35, 37.1%), meningeal irritation (11/35, 37.1%), seizures (8/35, 22.3%), optic neuritis (6/35, 17.1%), and ataxia (3/35, 8.6%) (Table 1).
The initial cranial MRI revealed typical multifocal high lesions on fluid attenuated inversion recovery and T2-weighted images in all 35 MOG-IgG-positive ADEM patients. The most commonly involved brain site was the frontal lobe (29/35, 82.9%), followed by the parietal lobe (19/35, 54.3%), temporal lobe (18/35, 51.4%), and occipital lobe (13/35, 37.1%). In addition to the white matter, the basal ganglia (17/35, 48.6%), thalamus (16/35, 45.7%), brainstem (13/35, 37.1%), cerebellum (9/35, 25.7%), and corpus callosum (5/35, 14.3%) were also involved. Lesions in the thalamus, basal ganglia, brainstem, and cerebellum were bilaterally involved in general, and corpus callosum lesions were mainly involved in the compression part (4/5, 80%). Initial spinal cord MRI showed lesions of high signal intensity on T2-weighted images in 42.9% (15/35) of the cases, in which the cervical, thoracic, lumbar, and sacral cord were invaded in 42.9% (15/35), 37.1% (13/35), 17.1% (6/35), and 5.7% (2/35) of patients, respectively (Table 2).
CSF analysis showed pleocytosis (>5/ml, range 12-352/ml, monocyte predominance) in 29 (82.9%) cases and protein elevation in 13 (37.1%) cases (>400 mg/L, range 388-972 mg/L) (Table 2). CSF glucose and chloride were normal in all patients. Oligoclonal bands in CSF were positive in five patients who showed intrathecal synthesis. There were 8 patients (22.9%) with MOG-IgG positivity in the CSF. The results of the autoimmune encephalitis antibodies, AQP 4 antibodies, and anti-myelin basic protein antibodies in the CSF and serum were negative in all children. Interictal EEGs demonstrated that 23 patients (65.7%) had abnormal background activity, and none showed epileptiform discharges. Six patients showed abnormal visual evoked potentials. All children had normal brainstem auditory evoked potentials. The median serum MOG-IgG titre was 1:20 (range 1:10-1:320).
All children received high-dose, intermittent intravenous methylprednisolone therapy (20-30 mg/kg/day, 5 days for 1 course, 1-2 courses in total) followed by tapered oral corticosteroids over 6-8 weeks, whereas 21 patients received intravenous immunoglobulin (2 mg/kg divided over 2 days) therapy, and 6 cases (17.1%) were treated with immunosuppressants. All clinical symptoms and signs were significantly improved within 1-3 weeks of the treatment. With a median follow-up of 1.6 (range, 1.2-2.3) years, 30 cases (85.7%) were diagnosed with monophasic ADEM, while the remaining 5 cases (14.3%) recurred during follow-up. Among the five recurrent cases, the final diagnoses were multiphasic disseminated encephalomyelitis (MDEM, n=3), neuromyelitis optica spectrum disorders (NMOSDs, n=1), and ADEM-ON (n=1). All recurrent episodes occurred between 4 months and 10 months after the initial event. Five patients (14.3%) suffered from neurological sequelae, including motor deficits (n=3) and secondary epilepsy (n=2). Five recurrent patients showed new MRI lesions during the follow-up period between 4 months and 10 months, and the lesions were significantly improved after subsequent retreatment. Nevertheless, MRI studies at one-year follow-up showed that the lesions in the brain and spinal cord were improved to varying degrees. Brain MRI scans showed complete T2 lesion resolution in 12 patients (34.3%) and partial reduction in the size of the T2 lesion in 23 patients (65.7%), while spinal cord MRI scans showed complete T2 lesion resolution in 31 patients (88.6%). Of the 23 patients with abnormal EEG, the recheck EEG showed that only five cases were mildly abnormal, and the remaining 18 cases recovered to a normal level at the one-year follow-up. At the last follow-up, 18 patients (51.4%) still had positive MOG-IgG in the serum.
Comparison of clinical, MRI, and laboratory features between the MOG+ and MOG− groups
To evaluate what characterizes ADEM children with positive MOG antibodies, a statistical comparison of clinical data, including the general conditions, clinical manifestations, imaging manifestations, laboratory findings, and prognosis after treatment, was performed between the MOG+ and MOG− groups (Tables 1-2). The results showed that the MOG+ group had a significantly longer disease duration (median: 10 vs. 6 days, P < 0.05), more meningeal involvement (31.4% vs. 8%, P < 0.05), and a higher recurrence rate (14.3% vs. 2%, P < 0.05) than the MOG− group (Table 2). Comparison of the initial and follow-up MRI studies between the two groups revealed that MOG-IgG-positive ADEM patients had a higher chance of frontal lobe involvement (82.8% vs. 68%, P < 0.05), in contrast to children with absent MOG antibodies. Another finding was that children with or without MOG antibodies did not differ in bilateral lesions, spinal cord involvement, infratentorial lesion involvement, or residual MRI findings. Furthermore, the serum levels of tumor necrosis factor (TNF) and interferon γ (IFN-γ) in the MOG+ group were significantly lower than those in the MOG− group (TNF: 1-12.4 pg/ml, median 1.7 vs. 1-34 pg/ml, median 2.2, P < 0.05; IFN-γ: 1-9.4 pg/ml, median 1.3 vs. 1-64 pg/ml, median 3, P < 0.05), while no significant differences in serum interleukin (IL)-2, 4, 6, 10, CSF cytokines, or serum complements were noted between the two groups (Table 2). In addition, no significant differences in age, gender, other clinical characteristics, or other laboratory findings were found between the two groups.
Analysis of factors associated with MOG-IgG-positive ADEM in children
To further study the associated factors for seropositive MOG-IgG ADEM patients, all factors with P < 0.05 in univariate analyses and other potentially related factors were included in the binary logistic regression analysis. Significant differences in the disease duration, meningeal involvement, and frontal lobe involvement were found between the two groups (P < 0.05), indicating that MOG-IgG-positive ADEM patients were predicted by longer disease duration, higher meningeal involvement, and higher frontal lobe involvement (Table 3).