To report the characteristics of juvenile-onset (<20 years) myasthenia gravis (MG) in Africa.
Six South African centres collected data which included acetylcholine receptor-antibody (AChR-ab) status, delay before diagnosis, MG Foundation of America grade at onset, maximum severity and severity at last visit, therapies, outcomes and complications.
We report on 190 individuals with a 4-year median follow-up (interquartile range (IQR) 1 - 8). The median age at symptom onset was 7 years (IQR 4 - 14). Ocular MG (26%) occurred among younger children (mean 5.1 years), compared with those developing generalised MG (74%) (mean 10.2 years) (p=0.0004). Remissions were obtained in 45% of generalised and 50% of ocular MG patients, of whom the majority received immunosuppressive treatment, mainly prednisone. Children with post-pubertal onset had more severe MG, but deaths were infrequent. Thymectomies were performed in 43% of those with generalised MG who suffered greater maximum disease severity (p=0.002); there was a trend towards more remissions in the thymectomy group compared with the non-thymectomy group (p=0.057). There was no racial variation with respect to AChR-ab status, maximum severity, or use of immunosuppression. However, 23% of children of African genetic ancestry developed partial or complete ophthalmoplegia as a complication of generalised MG (p=0.002).
Younger children developed ocular MG and older children generalised MG. Persistent ophthalmoplegia developing as a MG complication is not uncommon among juveniles of African genetic ancestry. A successful approach to the management of this complication that causes significant morbidity is, as yet, unclear.
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"These observations support the postulate that during active MG, patients with severe EOM damage may have inadequate DAF upregulation and therefore less protection against complement-mediated damage. Since some of the patients developed the ophthalmoplegic-MG complication whilst on prednisone, with or without a steroid-sparing agent  , we were interested in the effect of these drugs on DAF expression. "
[Show abstract][Hide abstract] ABSTRACT: Decay accelerating factor (DAF) expression at the muscle endplate is an important defence against complement-mediated damage in myasthenia gravis. Previously we implicated the c.-198C>G DAF polymorphism with the development of treatment-resistant myasthenia-associated ophthalmoplegia by showing that the C>G DAF polymorphism prevented lipopolysaccharide-induced upregulation of lymphoblast DAF. We postulated that drugs used in myasthenia gravis may increase the susceptibility of extraocular muscles to complement-mediated damage and studied their effects on endogenous DAF using patient-derived lymphoblasts as well as mouse myotubes. We show that prednisone repressed C>G DAF expression in lymphoblasts and increased their susceptibility to cytotoxicity. Methotrexate, but not azathioprine or cyclosporine, increased DAF in C>G lymphoblasts. In mouse myotubes expressing wild-type Daf, prednisone also repressed Daf expression. Although cyclosporine, azathioprine, and methotrexate increased muscle Daf levels when used alone, upon co-treatment with prednisone only azathioprine maintained myotube Daf levels close to basal. Therefore, prednisone negatively influences DAF expression in C>G lymphoblasts and in myotubes expressing wild-type Daf. We speculate that myasthenic individuals at risk of developing the ophthalmoplegic complication, such as those with C>G DAF, may have inadequate endogenous levels of complement regulatory protein protection in their extraocular muscle in response to prednisone, increasing their susceptibility to complement-mediated damage.
Full-text · Article · Jun 2014 · Neuromuscular Disorders
[Show abstract][Hide abstract] ABSTRACT: Introduction: A variety of tests have been devised for the diagnosis of myasthenia gravis (MG). The best known of these (Tensilon test, using intravenous edrophonium chloride) may cause serious complications (bradycardia and syncope) dictating cardiac monitoring during the procedure. Ocular neostigmine drops, a simple procedure, may significantly reduce the risk of diagnostic testing for possible MG.
Method: To investigate its efficacy, the miotic effect of neostigmine was explored using 30 rabbits. One drop of sterile neostigmine solution (2.5 mg/ml) was instilled into the right eye (RE) of each rabbit using the left eye (LE), which received sterile normal saline, as control. Serial assessments of pupillary size were done. One drop of neostimine was instilled daily for 7 days to investigate its safety. Six patients (aged 4.5–55y, median=42y, mean=36.4y) with MG had the same test and were observed for increase of the palpebral fissure height (documented by photography).
Results: At baseline there was no significant difference in the mean [SD] pupillary size of the rabbits between the RE (7 mm [1.07]) and LE (7 mm [1.07]), p=0.63). Significant miotic effect was observed in the RE compared to the LE at 30, 60 and 90 minutes (respectively, 4.8 mm [1.86] vs 7.0 mm [1.09], p=0.0001; 4.8 mm [1.86] vs 7.0 mm [1.09], p=0.0001; and 3.2 [0.76] vs 7.0 [0.0], p=0.013). Administration of one drop of neostimine daily for 7 days caused no ocular inflammation. All six patients with MG had an observable increase of the palpebral fissure height (documented by photography) of at least 2 mm, 30 minutes after neostigmine instillation. The response was dramatic in the three patients with no prior treatment for MG.
Conclusion: Ocular neostigmine drops is a safe, simple and efficient diagnostic test for MG.
[Show abstract][Hide abstract] ABSTRACT: Background:
The role of surgical treatment for juvenile myasthenia gravis (MG) remains unclear. Here, we performed a retrospective study to evaluate the predictors of clinical outcome of juvenile MG treated with extended transsternal thymectomy.
A total of 141 consecutive juvenile MG patients underwent extended transsternal thymectomy at an academic hospital over a 20-year period were reviewed. Thymectomy was performed in patients resistant to pyridostigmine therapy, with generalized symptoms or ocular MG with partial response to pyridostigmine for more than 2 years. Variables potentially affecting responses to extended transsternal thymectomy were evaluated using Kaplan-Meier analysis and Cox regression modeling. Complete stable remission (CSR) is defined as asymptomatic without medication for more than 12 months.
There were 96 patients with ocular MG and 45 generalized MG, the median age at disease onset was 6 years and that at operation was 12 years. Among 135 patients with complete postoperative follow-up, 34 (25.2%) achieved CSR, 28 (20.7%) experienced pharmacologic remission, 61 (45.2%) improved, 5 (3.7%) remained stable, and 7 (5.2%) deteriorated. The results indicated the disease-onset age greater than 6 years and age at operation greater than 12 years were both positively associated with CSR responses. Postoperative steroid treatments in ocular MG and preoperative disease duration in generalized MG (>12 months) were negatively associated with CSR responses.
Extended transsternal thymectomy for Chinese juvenile MG patients has an efficacy comparable with reports from other ethnicities. Juvenile patients with disease-onset age greater than 6 years, age at operation greater than 12 years, and shorter disease duration of generalized MG are associated with favorable clinical outcomes.
No preview · Article · Jan 2013 · The Annals of thoracic surgery