Myasthenia gravis - Diagnosis

Diagnosis of myasthenia gravis

Pharmacological tests based on the administration of agents that block the enzyme acetylcholinesterase (AChE), which catalyzes the breakdown of acetylcholine, are of great importance for the diagnosis of myasthenia. These agents can reduce the severity of myasthenia symptoms. Edrophonium (Tensilon) is a short-acting acetylcholinesterase inhibitor that, when administered intravenously, increases the strength of muscles that have been previously weakened by the load during the examination (for example, the muscle that raises the upper eyelid, the deltoid or iliopsoas muscles). Initially, 2 mg of edrophonium is administered and muscle strength is checked after 1 minute. If there is no improvement, the drug can be additionally administered in a dose of 3 mg, then 5 mg. In some patients who are hypersensitive to small doses of edrophonium, the drug can provoke a respiratory crisis. In this regard, when performing the test, a breathing apparatus should be nearby in case of an emergency. The positive effect of edrophonium usually lasts only a few minutes. Positive test results support the diagnosis of myasthenia gravis, although they are not specific for this disease, as they are possible in patients with peripheral neuropathies, brainstem lesions, amyotrophic lateral sclerosis and poliomyelitis.

Electromyography also has a certain diagnostic value in myasthenia. In most patients with generalized myasthenia, rhythmic stimulation at a frequency of 3 Hz causes a decrease (decrement) in the amplitude of the M-response by more than 10%. This fading reaction is a consequence of the narrowing of the safe range of neuromuscular transmission and is explained by a decrease in the number of AChR on the muscle membrane, expansion of the synaptic cleft, and a decrease in the amount of acetylcholine released after the first 5-10 low-frequency stimuli. When examining two or more distal muscles and two or more proximal muscles, 95% of patients with myasthenia reveal a specific reaction in at least one muscle. However, if only one muscle is examined, the probability of detecting a decrement of the M-response is only 50%. When examining proximal muscles, the probability of detecting this reaction is higher than when examining distal muscles. In patients with ocular myasthenia, a significant decrement of the M-response is found in less than half of the cases. Recording of electromyography of individual fibers can also be useful in identifying pathology of neuromuscular transmission. In myasthenia, the average interval between the potentials of two fibers is prolonged. This sign is not specific for myasthenia, but may indicate pathology of the neuromuscular junction, which is important in cases where the diagnosis is in doubt.

In 80% of patients with acquired autoimmune myasthenia, antibodies to acetylcholinesterase are detected in the serum, but they are absent in more than half of patients with the ocular form of myasthenia. In generalized myasthenia, the antibody titer is usually higher than in the ocular form. Antibodies to acetylcholinesterase can bind to various sites on the receptor, but most are directed against a region of the alpha subunit, called the major immunogenic region and located outside the receptor binding zone with acetylcholine. Although the functional properties of antibodies to the major immunogenic region of acetylcholinesterase are well studied, none of the antibody characteristics correlates with the clinical status or duration of the disease. As a rule, the titer of antibodies to acetylcholinesterase also correlates poorly with the severity of myasthenia. However, against the background of the improvement of the patient's condition after immunosuppressive therapy, a persistent decrease in the titer of antibodies to acetylcholinesterase is noted. In myasthenia, antibodies are also detected that bind directly to striated muscles, especially in patients with thymoma. One study showed that such antibodies are detected in 84% of patients with thymoma.

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