Height and Bone Age in Treated Juvenile Myasthenia Gravis
Abstract & Commentary
By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: In young children with myasthenia gravis, height and bone age are negatively impacted by chronic corticosteroid usage, but not by thymectomy.
Source: Wang H, et al. The effect of steroid treatment and thymectomy on bone age and height development in juvenile myasthenia gravis. Neurol Sci 2013;34:2173-2180.
Treatment of juvenile myasthenia gravis (mg) mirrors that of adult-onset disease, with first-line agents, all of temporary benefit, encompassing anticholinesterase medication, plasmapheresis, and intravenous immune globulin. Thymectomy, widely accepted for both seropositive and seronegative patients, both peri- or post-pubertal, remains controversial in the pre-pubertal child, and glucocorticoids, though problematic for chronic use, are administered for severe disease. Thymectomy is not beneficial for MuSK antibody-positive adult or juvenile MG, but azathioprine, mycophenolate mofetil, cyclosporine, and cyclophosphamide, despite risks of infertility and delayed malignancy, are beneficial. What are the risks to bone age and height development in such treated children?
Among 76 consecutive juvenile MG patients treated between July 2011 and August 2012 in the outpatient clinic of the First Affiliated Hospital of Sun Yatsen University, China, and enrolled into this cross-sectional study, 52 had undergone thymectomy and 71 had received prednisone. All satisfied diagnostic criteria for juvenile MG, including age < 18 years, muscle fatigability which improved with rest, and one of either abnormal jitter on single-fiber electromyography, decrement of 10% on repetitive nerve stimulation, or positive response to anticholinesterase. Exclusionary criteria included bulbar MG, other autoimmune disease, congenital or neonatal MG, thymoma, or any disease that might impair growth or metabolism. Statistical analysis encompassed t tests and variance analyses, and Chi square and Rank sum tests, with P < 0.05 considered statistically significant.
Among 76 juvenile MG patients, 45 female and 31 male, median age was 10.3 years, median onset age was 4.8 years, and 62 (82%) were purely ocular with 18% generalized. Treatment was not significantly different between the sexes. Among the 52 thymectomized children, bone age was not delayed, and bone growth and height were not impacted, by the duration or presence of thymectomy. Height retardation was related to past cumulative prednisone intake, as was delayed bone age, which was also impacted by age of onset, with delayed bone age more pronounced the earlier the age of onset. Bone age and height are negatively affected by prednisone but not by thymectomy, and monitoring of these parameters should be routine in juvenile MG, with intervention, particularly the use of steroid-sparing agents, undertaken when appropriate.
Commentary
Recently, a coincidence of two rare diseases, seropositive MG and aquaporin-4 antibody-mediated neuromyelitis optica spectrum disorder (NMOSD), has been described in 16 patients, an occurrence 70 times more frequent than would be expected by chance.1 Most were female (15/16), and Caucasian (11/16), with MG onset prior to NMOSD onset (14/16), the former of which was usually mild, and mostly developing within the first 3 decades of life (12/16) of which 11/12 were female, with many in remission or having only minimal manifestations (11/16). Of those with MG onset prior to neuromyelitis optica onset (14/16), 10/11 had undergone thymectomy prior to NMOSD onset. NMOSD appears to develop almost exclusively in females with juvenile or early-onset MG, and prior thymectomy may be a risk factor in its development.
Reference
- Leite MI, et al. Myasthenia gravis and neuromyelitis optica spectrum disorder: A multicenter study of 16 patients. Neurology 2012;78:1601-1607.
