Myasthenia Gravis

Description

In myasthenia gravis, destruction of postsynaptic acetylcholine receptors at neuromuscular junctions impairs the conduction of nerve impulses to muscles, causing fluctuating muscle fatigue and weakness. An autoimmune process is implicated, with acetylcholine-receptor antibodies detected in most patients, and an increased incidence of other autoimmune disease. Three-quarters of patients have abnormalities of the thymus gland (hyperplasia or thymoma).

Myasthenia gravis often presents initially with extraocular muscle involvement. The levator muscle is usually the first muscle involved. In 20 percent of patients, signs and symptoms are confined to the eye muscles throughout the disease; these cases are classified as ocular myasthenia gravis. Involvement beyond the ocular muscles is described as generalized disease. A hallmark of the disease is variability and fatigability.

Symptoms

Patients experience exacerbations and remissions, especially in the early stages. Ocular symptoms often appear first, and include eyelid droop and diplopia. Generalised symptoms include limb or facial muscle weakness, and difficulty with swallowing, breathing or speech. Symptoms are usually worse with sustained effort and towards the end of the day.

Signs

Ocular myasthenia may mimic other diseases, such as cranial nerve palsies. General inspection may reveal reduced facial expression or ptosis. Ptosis often worsens when the patient is asked to sustain upgaze for 1 minute. Diplopia may also occur with continued eye movements. Pupillary function is never affected. In generalized myasthenia, proximal limb muscle strength is often reduced, while reflexes and sensation are unaffected.

Prevalence

Rare (approximately 1/20,000).

Significance

Myasthenia often presents initially with ocular signs. The condition must be considered in any patient with acquired ptosis or ocular motility disturbance. Treatment of ocular myasthenia with immunotherapy may reduce the likelihood of progression to generalized disease. If involvement of the muscles of respiration and swallowing is not managed appropriately, death can potentially result from respiratory complications.

Differential Diagnosis

Chronic Progressive External Ophthalmoplegia, Internuclear ophthalmoplegia, Cranial nerve palsies, Ptosis and Pseudoptosis

Management

Urgent

Patients with difficulty swallowing or breathing are admitted to hospital immediately. If the patient is not acutely unwell, specialist review is best arranged within a few days. In general, patients with isolated ocular myasthenic symptoms may safely be delayed up to a few weeks.

Additional tests

Two office procedures are useful in diagnosis when ptosis is a presenting feature. The sleep test (or rest test) entails measuring the patient’s degree of ptosis, then repeating the measurement immediately after closing the eyes for 20 minutes. Improvement of ptosis is highly suggestive of myasthenia gravis. The ice pack test involves placing an ice pack over the ptotic eye for 2 minutes. The ptosis improves in 90 percent of patients with myasthenia.

Blood tests

Acetylcholine-receptor antibody assay is positive in up to 90 percent of patients with generalized myasthenia, and 70 percent of patients with ocular disease.  Thyroid function testing and autoimmune screening is usually appropriate. Expert assessment may also be required to exclude various clinical syndromes with similar presentations to myasthenia gravis, including the possibility of a medication adverse-reaction. Computed tomography (CT) or magnetic resonance imaging (MRI) of the chest are performed to identify lesions of the thymus gland.

Oral medications

Medical treatment is not always required in ocular or mild generalized myasthenia. In moderate or severe disease, the principal medications are oral anticholinesterase drugs (e.g., pyridostigmine) and immunosuppressive agents (e.g., prednisolone). Response is variable; side-effects can be significant; and some patients become refractory to these medications after prolonged use. Immunosuppresive medications achieve disease remission in some patients.

Surgery

Thymectomy is considered in all patients with generalized myasthenia, since it confers an excellent chance of remission. Controversy surrounds the utility of thymectomy in pure ocular myasthenia. Strabismus surgery is occasionally beneficial, and is best performed when symptoms are stable and medical treatment optimized.

Advice & Review

Patients treated for generalized myasthenia are monitored closely until improvement is demonstrated. When ocular myasthenia has been present for 2 years, progression to generalized disease is very unlikely.