Myasthenia gravis is an autoimmune disease that causes muscle weakness due to impaired neuromuscular transmission. Most often, the work of the muscles of the eyes, facial and masticatory muscles is disrupted, sometimes the respiratory muscles. This determines the symptoms characteristic of myasthenia gravis: drooping of the lower eyelid, nasal voice, swallowing and chewing disorders. The diagnosis is established after a proserin test and a blood test for the presence of antibodies to the receptors of the postsynaptic membrane. Specific treatment of myasthenia gravis consists in the appointment of anticholinesterase drugs, such as ambenonium chloride or pyridostigmine. These drugs restore neuromuscular transmission.
General information
Myasthenia gravis (or false / asthenic bulbar paralysis, or Erb-Goldflam disease) is a disease whose main manifestation is rapid (painfully rapid) muscle fatigue. Myasthenia gravis is an absolutely classic autoimmune disease in which cells of the immune system, for one reason or another, destroy other cells of their own body. Such a phenomenon can be considered a normal immune response, only it is directed not at foreign cells, but at its own.
Pathological muscle fatigue was described by clinicians in the middle of the XVI century. Since then, the incidence of myasthenia gravis has been growing rapidly and is detected in 6-7 people for every 100 thousand of the population. Women suffer from myasthenia gravis three times more often than men. The largest number of cases of the disease is observed in people aged 20 to 40 years, although the disease can develop at any age or be congenital.
Causes
Congenital myasthenia gravis is a consequence of a gene mutation, due to which neuromuscular synapses cannot function normally (such synapses are something like “adapters” that allow the nerve to interact with the muscle). Acquired myasthenia gravis is more common than congenital, but it is easier to treat. There are several factors that, under certain conditions, can cause the development of myasthenia gravis. Most often, pathological muscle fatigue is formed against the background of tumors and benign hyperplasia (tissue overgrowth) of the thymus gland – thymomegaly. Less often, other autoimmune pathologies become the cause of the disease, for example– dermatomyositis or scleroderma.
There are enough cases of detection of myasthenic muscle weakness in patients with oncological diseases, for example, with tumors of the genitals (ovaries, prostate gland), less often – lungs, liver, etc.
As already mentioned, myasthenia gravis is an autoimmune disease. The mechanism of development of the disease is based on the development of antibodies by the body to receptor proteins that are located on the postsynaptic membrane of synapses that carry out neuromuscular transmission.
Schematically, this can be described as follows: the neuron process has a permeable membrane through which specific substances – mediators can penetrate. They are needed to transmit an impulse from a nerve cell to a muscle cell that has receptors. The latter lose the ability to bind the mediator acetylcholine on muscle cells, neuromuscular transmission becomes much more difficult. This is exactly what happens with myasthenia gravis: antibodies destroy the receptors on the “second side” of the contact between the nerve and the muscle.
Myasthenia gravis symptoms
Myasthenia gravis is called “false bulbar paralysis” due to the fact that the symptoms of these two pathologies are really similar. Bulbar paralysis is damage to the nuclei of three cranial nerves: lingual, vagus and sublingual. All these nuclei are located in the medulla oblongata and their damage is extremely dangerous. Both with bulbar paralysis and with myasthenia gravis, there is weakness of the masticatory, pharyngeal and facial muscles. As a result, this leads to the most formidable manifestation – dysphagia, that is, a violation of swallowing. The pathological process in myasthenia gravis, as a rule, first affects the muscles of the face and eyes, then the lips, pharynx and tongue. With prolonged progression of the disease, weakness of the respiratory muscles and neck muscles develops. Depending on which groups of muscle fibers are affected, the symptoms can be combined in different ways. There are also universal signs of myasthenia gravis: a change in the severity of symptoms during the day; deterioration after prolonged muscle tension.
In the ocular form of myasthenia gravis, the disease affects only the oculomotor muscles, the circular muscle of the eye, the muscle that raises the upper eyelid. As a result, the main manifestations will be: double vision, strabismus, difficulty in focusing the gaze; inability to look at objects located very far or very close for a long time. In addition, there is almost always a characteristic symptom – ptosis or drooping of the upper eyelid. The peculiarity of this symptom in myasthenia gravis is that it appears or increases in the evening. In the morning, it may not be at all.
Pathological fatigue of the facial, chewing muscles and muscles responsible for speech leads to voice changes, difficulties with eating and speech. The voice of patients with myasthenia gravis becomes deaf, “nasal” (such speech sounds about the same as if a person just spoke with his nose pinched). At the same time, it is very difficult to talk: a short conversation can tire the patient so much that he will need several hours to recover. The same applies to the weakness of the masticatory muscles. Chewing solid food can be a physically impossible task for a person with myasthenia gravis. Patients always try to clearly plan their meal times in order to take food at the time of maximum effect of the medications taken. Even during periods of relative improvement in well-being, patients prefer to eat in the first half of the day, as symptoms worsen in the evening.
The defeat of the pharyngeal muscles is a more dangerous condition. The problem here, on the contrary, is the inability to take liquid food. When trying to drink something, patients often choke, and this is fraught with fluid entering the respiratory tract with the development of aspiration pneumonia.
All the described symptoms noticeably increase after loading on a particular muscle group. For example, a long conversation can cause even greater weakness, and chewing solid food often leads to additional deterioration of the masticatory muscles.
And finally, a few words about the most dangerous form of myasthenia gravis – generalized. It provides a stable 1% mortality rate among patients with this pathology (over the past 50 years, the mortality rate has decreased from 35% to 1%). The generalized form may be manifested by weakness of the respiratory muscles. The respiratory disorder that occurs for this reason leads to acute hypoxia and death if the patient was not treated in time.
Myasthenia gravis steadily progresses over time. The rate of deterioration may vary significantly in different patients, it is even possible to temporarily stop the progression of the disease (however, this is quite rare). Remissions are possible: as a rule, they arise spontaneously and end the same way – “by themselves”. Exacerbations of myasthenia gravis can be episodic or prolonged. The first option is called a myasthenic crisis, and the second is a myasthenic condition. With a crisis, the symptoms pass quickly and completely, that is, no residual effects are observed during remission. Myasthenic condition is a long–term exacerbation with the presence of all the symptoms, which, however, do not progress. This condition can continue for several years.
Diagnostics
The most revealing study for myasthenia gravis, which can give a neurologist a lot of information about the disease, is a proserin test. Proserin blocks the work of an enzyme that cleaves acetylcholine (mediator) in the synapse space. Thus, the amount of mediator increases. Proserin has a very powerful, but short-term effect, so this drug is almost not used for treatment, but in the process of diagnosing myasthenia proserin is necessary. With the help of the latter, several studies are carried out. First, the patient is examined to assess the condition of the muscles before the test. After that, proserin is injected subcutaneously. The next stage of the study is performed 30-40 minutes after taking the drug. The doctor re-examines the patient, thereby finding out the reaction of the body.
In addition, a similar scheme is used for electromyography – recording the electrical activity of muscles. EMG is performed twice: before the introduction of proserin and an hour after it. The study allows us to determine whether the problem really lies in a violation of neuromuscular transmission or the function of an isolated muscle or nerve is impaired. If, even after EMG, doubts remain about the nature of the disease, it may be necessary to conduct a number of studies of the nerve conduction ability (electroneurography).
It is important to study the blood test for the presence of specific antibodies in it. Their detection is a sufficient reason for the diagnosis of myasthenia gravis. If necessary, a biochemical blood test is performed (according to individual indications).
Computer tomography of mediastinal organs can provide valuable information. Due to the fact that a large percentage of cases of myasthenia gravis can be associated with volumetric processes in the thymus gland, CT of the mediastinum is performed quite often in such patients.
In the process of diagnosing myasthenia gravis, it is necessary to exclude all other variants – diseases that have similar symptoms. First of all, this is, of course, the bulbar syndrome already described above. In addition, differential diagnosis is carried out with any inflammatory diseases (encephalitis, meningitis) and tumors in the brain stem (glioma, hemangioblastoma, etc.), other neuromuscular pathology (ALS, Guillain syndrome, myopathy). In some cases, symptoms similar to myasthenia gravis can give a violation of cerebral circulation (ischemic stroke) in the vertebral artery basin.
Myasthenia gravis treatment
The purpose of treatment for myasthenia gravis is to increase the amount of acetylcholine in neuromuscular synapses. This is done not by increasing the synthesis of this substance (this is quite difficult), but by inhibiting its destruction. To do this, in practical neurology, drugs from the same group, which includes neostigmine, are used. For long-term treatment, drugs of a different type are chosen: the best option here is a remedy with a mild and long-lasting effect. The most commonly used derivatives are pyridostigmine and ambenonium.
In the case of severe course and rapid progression of the disease, drugs that inhibit the immune response are prescribed. As a rule, glucocorticoids are used, less often – classical immunosuppressants. When selecting steroids, you should always exercise maximum caution. Patients with myasthenia gravis are contraindicated with drugs containing fluoride, so the range of drugs to choose from is not very large. All patients with myasthenia gravis older than 69 years are removed from the thymus gland. Also, this method is resorted to when a volumetric process is detected in the thymus and in the case of treatment-resistant myasthenia gravis.
Preparations for symptomatic treatment are selected individually, based on the characteristics of each patient. A person with myasthenia gravis should follow certain rules in their lifestyle in order to speed up recovery or prolong remission. It is not recommended to spend too much time in the sun and endure excessive physical exertion. Before you start taking any medicine on your own, consultation with a doctor is absolutely necessary. With myasthenia gravis, some remedies are contraindicated. For example, taking certain antibiotics, diuretics, sedatives and medications containing magnesium – the latter can significantly worsen the patient’s condition.
Prognosis and prevention
The prognosis for myasthenia gravis depends on a lot of factors: on the form, time of onset, type of course, conditions, gender, age, quality or presence/absence of treatment, etc. The ocular form of myasthenia gravis is easiest, the most severe is generalized. At the moment, with strict adherence to the doctor’s recommendations, almost all patients have a favorable prognosis.
Since myasthenia gravis is a chronic disease, most often patients are forced to constantly take treatment (courses or continuously) to maintain well-being, but their quality of life does not suffer very much from this. It is very important to diagnose myasthenia gravis in a timely manner and stop its progression until irreversible changes appear.