Myasthenia gravis: diagnosis

Diagnosis of myasthenia gravis

Important for the diagnosis of myasthenia gravis are pharmacological tests based on the administration of agents that block the enzyme acetylcholinesterase (AChE) catalyzing the breakdown of acetylcholine. These drugs can reduce the severity of symptoms of myasthenia gravis. Edrophonia (tensilone) is a short-acting inhibitor of acetylcholinesterase that, when injected intravenously, increases the strength of the muscles previously weakened by the load during examination (for example, the muscles lifting the upper eyelid, deltoid or ilio-lumbar muscle). Initially, 2 mg of edrophonia is injected and the muscle strength is checked after 1 minute. In the absence of improvement, the drug can be additionally administered at a dose of 3 mg, followed by 5 mg. In some patients, hypersensitive to small doses of edrophonia, the drug may trigger a respiratory crisis. In this regard, during the test, you should have a nearby breathing apparatus in case of an emergency. The positive effect of eudrophonia usually lasts only a few minutes. Positive test results support the diagnosis of myasthenia gravis, although they are not specific for this disease, since they are possible in patients with peripheral neuropathies, brainstem lesions, amyotrophic lateral sclerosis and poliomyelitis.

A certain diagnostic value for myasthenia gravis has also an electromyography. In most patients with a generalized form of myasthenia with rhythmic stimulation at a frequency of 3 Hz, the amplitude of the M-response decreases (decrement) by more than 10%. This fading reaction is a consequence of the narrowing of the safe range of neuromuscular transmission and is explained by the decrease in the number of AXR on the muscle membrane, the expansion of the synaptic cleft, the decrease in the amount of acetylcholine released after the first 5-10 low-frequency stimuli. In the study of two or more distal muscles and two or more proximal muscles, 95% of myasthenia patients exhibit a specific reaction in at least one muscle. However, if only one muscle is examined, the probability of finding an M-response decrement is only 50%. In the study of proximal muscles, the probability of detecting this reaction is higher than in the study of distal muscles. In patients with an ocular form of myasthenia, a significant decrement of the M-response is found in less than half the cases. Registration of electromyography of individual fibers is also useful in detecting the pathology of neuromuscular transmission. In myasthenia gravis, the average interval between the potentials of the two fibers is elongated. This symptom is not specific for myasthenia gravis, but it may indicate a pathology of the neuromuscular junction, which is important when the diagnosis is questionable.

In 80% of patients with acquired autoimmune myasthenia gravis, antibodies to acetylcholinesterase are detected in the serum, but in more than half of patients with myasthenia gravis, they are absent. In the generalized form of myasthenia gravis, the antibody titer is usually higher than with the ocular form. Antibodies to acetylcholinesterase may bind to different sites of receptors, but most of them are directed against the site of the alpha subunit, designated as the main immunogenic region and located outside the receptor binding zone with acetylcholine. Although the functional properties of antibodies to the main immunogenic region of acetylcholinesterase have been well studied, none of the characteristics of antibodies correlates with the clinical status or duration of the disease. As a rule, it is poorly correlated with the severity of myasthenia and the antibody titer to acetylcholinesterase. Nevertheless, against the background of improvement in the patient's condition after immunosuppressive therapy, there is a persistent decrease in the antibody titer to acetylcholinesterase. Myasthenia gravis also reveals antibodies that bind directly to the striated muscles, especially in patients with thymoma. In one study, it was shown that similar antibodies are detected in 84% of patients with thymoma.

[1], [2], [3], [4]