Epidemiology
Myasthenia Gravis is believed to occur in approximately 1 in 20,000 persons with 10% occurring in pediatric patients. The incidence of new cases is approximately 4 to 6 per million each year. In persons under 40 years, females are more likely to develop myasthenia gravis.
We don’t know why people develop Myasthenia Gravis, but it does appear to be autoimmune. That means, the body doesn’t recognize itself, and causes an immune attack. Specifically, it is caused by an antibody-mediated, cell-dependent immunologic attack on the postsynaptic membrane of the neuromuscular junction. This is a complicated way of saying the body is attaching itself at the junction of the muscle and the nerve that controls it.
Clinical Presentation
How do patients with Myasthenia Gravis present to their doctors? Typical symptoms include a fluctuating, fatigable, painless weakness. Eye findings are common including ocular weakness with binocular diplopia (double vision that goes away when one eye is shut). Patients may have difficulty watching television, reading or driving. Their upward gauze is easily fatigued.
Other symptoms include:
Jaw muscle weakness (more problems with closing than opening)
Difficulty chewing (especially candies, meats, etc)
Muscle weakness in chewing
Difficulty swallowing
Difficulty whistling or using straws.
Inability to blow up balloons
Slurred speech
Neck weakness
Respiratory weakness
Shortness of breath with heavy breathing
Limb weakness
Difficulty performing overhead tasks
Difficulty climbing stairs
Exam Findings
Asymmetrical weakness of multiple extraocular muscles
Pupils function normally
Ptosis (drooping eyelids) may be elicited during sustained up gaze – “Myasthenia Fatigue Test”
Diagnosis
Complete evaluation by a neurologist is recommended.
Edrophonium testing
RNS (repetitive nerve stimulation) studies
SFEMG (single fiber electromyography)
AChR antibody serology
Anti-striated muscle antibody serology
MuSK antibody serology
Thymoma
Thymoma is an uncommon, slow-growing tumor that originates from thymic epithelial cells The lymphocytic component is histologically benign. Thymomas comprises approximately 20-30% of mediastinal masses in adults, but only ~1% in pediatric patients. This tumor may present with mass-associated respiratory symptoms, Superior vena cava obstruction (SVC syndrome), or paraneoplastic syndrome (such as Myasthenia Gravis) caused by production of antibodies by the tumor itself. In children less than 10 years of age, girls are 6 times more likely to have a Thymoma than boys and are more likely to have an advanced tumor stage
Treatment Options
• Acetylcholinesterase Inhibitors
• Corticosteroids
• Azathioprine
• Cyclosporine
• Mycophenolate mofetil
• Plasma Exchange
• Intravenous Immunoglobulins (IVIG)
• Thymectomy
• rituximab (limited to pediatric case report)
Surgical Management
For patients with non-thymomatous autoimmune myasthenia gravis, thymectomy is recommended as an option to increase the probability of remission or improve symptoms over time. Currently, the recommendation for patients with myasthenia is to perform thymectomy in patients <65 years old within first 3 years of diagnosis. Thymectomy is almost always recommended in patients with Thymoma, but these only account for about 10% of patients with Myasthenia Gravis.
Sternotomy (open) versus minimally invasive (thoracoscopic thymectomy)
Thoracoscopic and open approaches to thymectomy in patients with myasthenia gravis are both effective treatments. One pediatric series reported more than 80% of patients in both groups (open and thoracoscopic) with remission or with improvement. The pediatric series, however, was small with only 14 patients over the 12 year reporting period in that series.
The general consensus is that thoracoscopic thymectomy produces equivalent post-op complete remission rates with superior results compared to median sternotomy in terms of hospital stay, operative blood loss, need for post-operative medications, and patient satisfaction and appearance. One metaanalysis reported 33% complete remission for thoracoscopic and 44.7% for open procedures, but these where statistically non-significant based on the small sample size. Other series have reported higher results.
DeFilippi classification of remission
Class 1
Complete remission; no medication requirements
Class 2
Asymptomatic; decreased medication requirements
Class 3
Improvement in symptoms; decreased medication requirements
Class 4
No change in symptoms or medication requirements
Class 5
Worsening symptoms
References
Wagner AJ, Cortes RA, Strober J, Grethel EJ, Clifton MS, Harrison MR, Farmer DL, Nobuhara KK, Lee H. Long-term follow-up after thymectomy for myasthenia gravis: thoracoscopic vs open. J Pediatr Surg. 2006 Jan;41(1):50-4; discussion 50-4. http://www.ncbi.nlm.nih.gov/pubmed/16410107
Kumar, V., Kaminski, HJ. Treatment of Myasthenia Gravis. Curr Neurol Neurosci
Rep. Oct 7 2010
Zahid, Imran et. al. Video-Assisted Thoracoscopic Surgery or Transsternal
Thymectomy in the Treatment of Myasthenia Gravis? 2010 Article in Press
Evoli, Amelia. Acquired Myasthenia Gravis in Childhood. Current Opinion in
Neurology. 2010, 23:536-540
Juel, V., Massey, J. Myasthenia Gravis. Orphanet Journal of Rare Diseases 2007,
2:44
Dhall, G. et. Al. Thymoma in Children. Report of Two Cases and Review of Literature.
J Pediatr Hematol Oncol 2004;26:681-685
Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune
myasthenia gravis (an evidence-based review): report of the Quality Standards
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12;55(1):7-15
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refractory myasthenia gravis using rituximab: a pediatric case report. J Pediatr.
2003 Nov;143(5):674-7
V.J. DeFilippi, D.P. Richman and M.K. Ferguson, Transcervical thymectomy for myasthenia gravis, Ann Thorac Surg 57 (1994), pp. 194–197.