4A. Myasthenia gravis

Myasthenia gravis (MG) is the most common autoimmune disorder of the neuromuscular junction. Fluctuating weakness increasing with repeated activity and improving after a period of rest is the hallmark feature. It’s caused by antibodies directed against postsynaptic nicotinic acetylcholine receptors.

Prevalence is 1–2 per 10,000 persons.

Etiology

• Idiopathic
• Thymoma (paraneoplastic)

In about 15%, the disease can be classified as paraneoplastic, usually associated with a thymoma.

Pathomechanism

Autoantibodies against the acetylcholine receptor (AChR) causes competitive inhibition of acetylcholine at the neuromuscular junction. This decreases receptor density, causing weakness and fatigue. It also activates the complement system, causing muscle cell lysis.

Clinical features

The hallmark of the condition is fluctuating weakness and fatiguability increasing with repeated activity and improving after a period of rest. The symptoms are usually worse in the evening. Many drugs can worsen the symptoms as well, like antibiotics, beta blockers, and muscle relaxants. The condition progresses very slowly, developing over months or years.

Any muscle can be affected, but the smaller muscles are usually affected first, followed by larger and larger muscles. Most commonly symptoms initially affect the eye muscles, causing ptosis and diplopia. The patient may report having difficulty chewing or swallowing. Ocular MG is a subtype where only the eye muscles are affected.

Patients may develop myasthenic crises if exposed to certain drugs, infections, surgeries, etc. This leads to a life-threatening exacerbation of the symptoms which lead to respiratory failure.

Diagnosis and evaluation

Most patients with MG have anti-AChR antibodies in their serum. Some have anti-MuSK antibodies instead. On EMG decrement of the action potential after repeated stimulation is present. The Tensilon (edrophonium) test involves giving the patient an IV dose of edrophonium. If the patient’s symptoms is caused by MG, the symptoms should rapidly improve following the administration.

Thymoma should be excluded by imaging.

Treatment

In many cases, symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine is sufficient. If insufficient, immunosuppressants (prednisolone ± azathioprine) should be added.

If thymoma is present, thymectomy should be performed. Thymectomy may also be indicated in younger patients even in absence of thymus pathology, to improve prognosis.

The treatment for myasthenic crisis is ICU admission and IVIG/plasma exchange.

Other types

There are some other “types” of myasthenia gravis, like Lambert Eaton myasthenic syndrome. It is associated with lung cancer and usually begins in the proximal lower limbs rather than the eyes.