4A. Myasthenia gravis

Definition and epidemiology

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. 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, over months or years.

Patients usually either have ocular MG, where only the eye muscles are affected, or more rarely generalised MG, where all muscles are affected. In ocular MG, the patient experiences ptosis, diplopia, and blurred vision. In generalised MG, the smaller muscles are usually affected first, followed by larger and larger muscles. The patient may report having difficulty chewing or swallowing.

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

Diagnosis is based on serology for anti-AChR antibodies and EMG findings. On EMG we see decrement of the action potential after repeated stimulation.

Thymoma should be excluded by imaging.

Treatment

Treatment usually includes an acetylcholinesterase inhibitor like pyridostigmine, as well as immunosuppressants, usually steroid + azathioprine. If the thymus is abnormal it should be surgically removed.

The treatment for myasthenic crisis is plasma exchange.

Other types

There are some other “types” of myasthenia gravis, like Myasthenia Gravis associated with muscle-specific kinase antibodies (MuSK) and Lambert Eaton myasthenic syndrome.

MuSK-positive MG is more severe than normal MG. Lambert Eaton myasthenic syndrome is associated with lung cancer and usually begins in the proximal lower limbs rather than the eyes.


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