Myasthenia gravis is an acquired autoimmune neuromuscular disorder. Auto-antibodies are produced against nicotinic acetylcholine receptors in the neuromuscular junction of the skeletal muscles. This leads to skeletal muscle weakness, mostly affecting the muscles of the eyes, oro-pharynx and proximal skeletal muscles. The symptoms include drooping of eyelids, double vision, difficulty in chewing and swallowing, slurred speech, breathing problems, and respiratory distress. In addition, patients have difficulty walking, sitting, climbing stairs and rising from a chair. The symptoms of weakness are more profound in the evening and as the day ends. It is exaggerated with activity and alleviated with rest. The disease is fluctuating with relapses and remissions and lasts lifetime, although in very few cases the disease may spontaneously resolve.
Does Thymectomy Cure Myasthenia Gravis?
Conservative treatment with acetylcholine esterase inhibitors (pyridostigmine and neostigmine) and immunosuppressants (corticosteroid, azathioprine, mycophenolate mofetil, rituximab, cyclophosphamide, and cyclosporine) form the backbone of myasthenia gravis therapy. PLEX and IVIg are other immune therapies.(1)
Myasthenia gravis patients have increased tendency to develop thymic abnormalities and thymus has been known to play a role in the pathogenesis of myasthenia gravis. 85% patients with generalized myasthenia gravis have thymic hyperplasia and 10-15% has thymoma. These patients are positive for anti-AChR antibody. Studies have shown that resident cells of thymus produce AChR.
Thymectomy is the surgical removal of thymus gland. It has emerged as the first line therapy for patients with generalized myasthenia gravis. It is indicated in all patients with thymoma, in addition to patients in the age group of 10-55 years with generalized myasthenia gravis without thymoma. It is important to remove thymoma to prevent systemic metastasis and local proliferation. However, in patients with late onset myasthenia gravis and thymoma, thymectomy does not improve the disease course. It can also be indicated in patients with generalized myasthenia gravis who are negative for AChR antibodies and fail to respond to conservative therapy or in those patients in whom side-effects of immunotherapy are to be avoided or minimized.
Thymectomy is contraindicated in patients who have antibodies to muscle specific kinase, LRP4 or agrin antibodies. It is also not considered in patients with ocular myasthenia gravis and should be done when the patients progresses to generalized myasthenia gravis. It is still not clear whether thymectomy should be performed in prepubescent and patients >55 years of age, although studies suggest to consider thymectomy in patients >55 years of age.
After thymectomy, patients may experience exacerbation in symptoms for a brief period of time; however, the improvement occurs in months to years. It is critical to remove thymic tissue completely to prevent recurrence of the disease, as even a small amount of tissue left behind can lead to recurrence.
Thymectomy has been known to cause remission in some patients. Remission is mostly achieved in patients who are young with shorter duration of the disease, and have severe symptoms, high antibody titer, or hyperplastic thymus rather than thymoma. Generally, the rate of remission increases with time, such as after 7-10 years of surgery, nearly 40-60% patients undergo remission, except those with thymoma. There is improvement in 85% of cases along with 35% patients having drug free remission, in patients who do not have thymoma.
Thymectomy can be performed via various approaches, including transcervical thymectomy (T-1), videoscopic thymectomy (T-2), transsternal thymectomy (T-3) and transcervical and transsternal thymectomy (T-4). Randomized clinical trials of thymectomy done via transsternal approach have proved effective in management of the disease and even lead to remission or improve the disease in such a way that there is less requirement of immunosuppressant therapy.
Non-randomized clinical trials have shown that thymectomy is superior to conservative therapy in the management of myasthenia gravis, but still some authors doubt the role of thymectomy in the treatment of myasthenia gravis. Thymectomy may lead to remission of myasthenia gravis in certain group of patients as mentioned above, but not in all the patients.