Myasthenia gravis

What it is

Myasthenia gravis is an autoimmune neuromuscular disease characterized by generalized muscle weakness, with autoantibodies directed against postsynaptic acetylcholine receptors (AchR). It is the most common NMJ disorder. 80–90% of patients with generalized MG have antibodies, and 100% of patients with thymoma have antibodies.

Causes and risk

There is an association with other autoimmune diseases, including SLE, Hashimoto thyroiditis, rheumatoid arthritis and sarcoidosis. The associated conditions are thymoma and thymic hyperplasia, and every patient must have a CT to screen.

How it presents

Eye muscle weakness is the most common initial symptom: ptosis, diplopia and blurred vision, worse at the end of the day. There is bulbar muscle weakness or slurred speech, difficulty chewing and/or swallowing, proximal limb weakness on rising from a chair, climbing stairs and brushing hair, and respiratory muscle weakness which causes dyspnea. Muscle fatigue worsens throughout the day and with increased activity, and the most important feature is the fatigability. Deep tendon reflexes are not affected, which separates it from GBS. Against Lambert-Eaton myasthenic syndrome: myasthenia gravis is associated with thymoma, starts with weakness of the extraocular muscles, worsens with exercise and throughout the day, reflexes are normal, repetitive nerve stimulation gives a decremental response, and there is no autonomic dysfunction. Lambert-Eaton myasthenic syndrome is uncommon, is associated with small-cell lung cancer, has autoantibodies to the presynaptic Ca channel with decreased ACh release, starts with weakness of proximal limb muscles, improves with exercise and throughout the day, has reduced or absent reflexes, gives an incremental response on repetitive nerve stimulation, and has autonomic dysfunction, which is common in it, with symptoms such as dry mouth and impotence. Botulism is the third member of that same table and it parts from both. Its toxin inhibits ACh release at the presynaptic end, the paralysis is descending, the pupils are dilated and fixed where they are normal in the other two, and there is dry mouth. Infant botulism follows honey ingestion, with constipation and hypotonia. Read the three side by side: weakness worsens with use in myasthenia gravis, improves with use in Lambert-Eaton, and is descending in botulism; reflexes are normal in myasthenia gravis and reduced or absent in the other two; the cancer is thymoma in myasthenia gravis, SCLC in Lambert-Eaton and none in botulism.