Most childhood-onset MG patients have good prognosis: Study in China
Milder clinical symptoms and better prognosis than found with adult MG forms
Most people with childhood-onset myasthenia gravis (CMG) experience milder clinical symptoms and a better prognosis than those with adult forms of the disease, according to a recent study in China.
For most CMG patients, their disease could be safely controlled with prednisone and other immunosuppressive agents. Researchers also found rates of conversion from ocular to the more severe generalized MG (gMG) were generally low, whereas rates of achieving disease remission were high.
“The data presented in our study confirm the distinctive characteristics of patients with CMG in China, such as prepubertal onset predominance, less frequent generalization, lack of association with thymoma [thymus tumor], and relatively benign long-term prognosis,” researchers wrote.
The study, “Clinical Features, Treatment and Prognostic Factors of Childhood-onset Myasthenia Gravis in A Large Chinese Cohort,” was published in the journal Pediatric Neurology.
CMG accounts for about 10% to 15% of all MG cases in western countries
While the onset of MG typically occurs in adulthood, the neuromuscular disease can affect people at any age, including children and adolescents.
CMG has been reported to account for about 10% to 15% of all MG cases in European and American countries, but its incidence in Asian countries may be higher, according to the researchers.
Large epidemiological studies to examine the characteristics and outcomes of CMG are currently limited. As such, the team conducted a retrospective analysis of clinical records from CMG patients seen at a hospital in China from January 1990 to May 2021.
A total of 859 patients with a disease onset at age 14 or younger were included. They were followed for a mean of 11.7 years. Of them, 377 were boys and 482 were girls, with a median age at CMG onset of 4 years for both sexes.
Patients were further subdivided based on their age at disease onset, with the prepubescent group including 711 girls up to age 9 and boys up to age 11, and the pubertal group including 148 girls ages 9-14 and boys ages 11-14.
In general, patients in the pubertal onset group had a more aggressive disease course than those in the prepubertal group, including greater incidence of gMG at disease onset, and higher rates of conversion from ocular to gMG later on.
They also had a higher MG Foundation of America (MGFA) classification, a standard measure of disease activity ranging from class I to class V, where higher class indicates more severe disease.
Those in the pubertal group were also more likely to have certain abnormalities in the thymus gland and to require a thymectomy — a surgery to remove the thymus.
The majority of patients with CMG have mild clinical symptoms and favorable outcomes.
All patients initially treated with pyridostigmine
All patients were initially treated with pyridostigmine (marketed under the brand name Mestinon), 195 (22.7%) of whom showed improvements.
Prednisone was subsequently administered to 657 of those in whom the disease was not well-controlled by pyridostigmine alone within a median of one year after their symptoms had first appeared. Still, 226 of these patients did not show satisfactory improvements and 37 experienced adverse reactions to the medication.
Statistical analyses identified risk factors for prednisone resistance, including thymic hyperplasia (thymus gland enlargement), MGFA classification higher than class I, and a disease duration longer than about 1.7 years before starting on prednisone. Conversely, undergoing thymectomy prior to starting prednisone was linked to a lower risk of treatment-resistance.
Of the patients who did not respond to or had side effects with prednisone, 188 were then given non-steroidal immunosuppressants, with 117 subsequently improving.
A total of 70 patients underwent a thymectomy, for reasons that included a lack of improvement on other medications or a suspected thymoma, a tumor in the thymus gland. Overall, 52 of these patients experienced an improvement after surgery.
Rates of thymus gland involvement, particularly thymoma, were notably lower among these CMG patients than in adult patients.
As of their last clinic visit, 121 of the 840 (14.4%) patients with ocular MG at disease onset had developed gMG after a median of 10 years. For most of these patients (86%), gMG severity was classified as mild (MGFA class II). This rate of conversion was lower than in previous reports of juvenile and adult-onset disease, and the time to conversion was also longer, the researchers noted.
Risk factors for conversion included older age at disease onset and having an enlarged thymus gland, whereas early treatment with immunosuppressants was protective.
21.6% of CMG patients achieved complete stable remission
Overall, 186 CMG patients (21.6%) achieved complete stable remission, defined as having no symptoms or signs of MG for at least a year without medications. This was more common in people with ocular MG than in those with gMG (25.2% vs. 4.5%).
Various factors were predictive of achieving remission, including an earlier age at MG onset (earlier than age 5.7 years), disease duration shorter than 8.4 years, and more mild disease classification.
Patients given prednisone and/or immunosuppressants were less likely to achieve disease remission.
The team noted that some of their findings in CMG patients were distinct from previous studies in other regions, including a lower proportion of female patients and an earlier age of disease onset.
Nevertheless, the data indicate that “the majority of patients with CMG have mild clinical symptoms and favorable outcomes,” the researchers wrote.