The neuromuscular junction is vulnerable to autoimmune attack both
at the pre-synaptic nerve terminal and at the post-synaptic muscle membrane.
Antibodies directed to the nicotinic acetylcholine receptor at the muscle surface
are the cause of myasthenia gravis in the majority of cases. Myasthenia gravis is
an acquired condition, characterised by weakness and fatigability of the skeletal
muscles. The ocular muscles are commonly affected first, but the disease often
generalises. Treatment includes symptom control and immunosuppression.
The thymus gland plays an important role in the pathogenesis of myasthenia gravis
and thymectomy is indicated in certain subgroups. Lambert-Eaton myasthenic
syndrome is associated with antibodies directed to the voltage-gated calcium
channel antibodies at the pre-synaptic nerve terminal. It is an acquired condition
and, in some cases, may be paraneoplastic, often secondary to underlying small
cell lung carcinoma. Clinical presentation is distinct from myasthenia gravis, with
patients often first presenting with lower limb muscle fatigability and autonomic
symptoms. Congenital myasthenic syndromes are inherited neuromuscular
disorders due to mutations in proteins at the neuromuscular junction. Various
phenotypes exist depending on the protein mutation. Treatment is directed
towards symptom control and immunosuppression is not indicated.
