MYASTHENIA GRAVIS: causes, symptoms and therapy

Myasthenia gravis

What is minasthenia gravis

There myasthenia gravis, also referred to as myasthenia gravis or simply myasthenia, it is one autoimmune disease clinically characterized by eye symptoms, fatigue abnormal and a progressive one weakness gods muscles volunteers, whose ability to contract is quickly exhausted following the completion of repeated activities. Only after an adequate period of rest, the patient is able to contract the voluntary muscles again.

Causes of myasthenia

What is the cause triggering myasthenia? This disease has an autoimmune origin: it is in fact caused by the presence of altered mature antibodies which, instead of being directed against elements extraneous to our organism, bind and neutralize specific elements of the organism, thus being called "autoantibodies". In this case, these autoantibodies affect the neuromuscular junction, which is the anatomical point where the nerve stimulus transforms into the muscle contractile stimulus. When the nerve stimulus for muscle contraction arrives, our body uses a molecule, called acetylcholine, which, once bound to its receptors present in the muscle fibers, triggers a series of reactions that will lead to contraction muscular. In myasthenia gravis, autoantibodies bind to these receptors (antibodies to acetylcholine or anti-AchR), not allowing the link with theacetylcholine and, consequently, muscle contraction.

A receptor similar to AchR is frequently found in a cell colony present in the thymus, a lymphoid organ present in the thoracic level that is responsible for selecting the T lymphocytes that react only against elements external to our body. Autoantibodies bind to this receptor, inducing hyperplasia and dysplasia of the thymic cells, leading to the formation of a thymic tumor, called thymoma.

It is a fairly rare disease, which mainly affects women between the ages of 20 and 45 and men between 60 and 70. It rarely affects children and babies.

Symptoms of myasthenia

The symptomatology of the myasthenia gravis it essentially depends on the voluntary muscles affected by the disease: it is a peculiar characteristic that the symptoms are found mainly in the evening and that they are practically absent upon awakening. In the early stages, the rest period necessary for the muscles to recharge the batteries is a few minutes; over time and with the progression of the disease, the recovery time lengthens until it becomes an almost continuous paresis. There is a possibility of a transient worsening of symptoms during menstrual periods.

The disease begins with eye symptoms such as fatigue and increased tiredness of the eye muscles. The initial symptoms encountered are the presence of one drooping eyelid, otherwise known as "eyelid ptosis", strabismus is diplopia, that is, the patient's feeling of seeing double. To try to counteract the reduction of the visual field linked to eyelid ptosis, the patient hyperextends the head to be able to see better from the portion of the eye that is left open.

The disease can remain localized in the eye muscles (in 10% of cases), or it can gradually develop into a generalized form, which can affect any other muscle in the body:

  • If it affects the muscles of the limbs and trunk, it may be difficult to keep the head raised from the pillow even for a few seconds, fatigue even for the simplest movements, such as combing one's hair, taking a few steps on a ladder;
  • If it affects the facial muscles, the patient may complain of amimia, ie inability to change facial expression, chewing and swallowing disorders;
  • If it affects the respiratory and speech muscles, we will have a picture of difficulty in speech and breathing, up to a frank respiratory insufficiency.
Myasthenia-gravis

Eyelid ptosis in a patient with myasthenia gravis, in a vintage photo.

Prognosis and complications of myasthenia

Until 1895, the disease was fatal in over 90% of cases (which is why it is called "gravis"). In the following 120 years, through a better knowledge of the damage mechanisms related to the disease and the study of increasingly targeted and powerful drugs, mortality was reduced to today's 2 - 3 %, with a slow course and characterized by temporary remissions alternating with acute crises, in which the symptoms, mainly respiratory, worsen drastically and suddenly. These crises are called "myasthenic crises" and can be caused by taking drugs (such as mainly barbiturates, benzodiazepines and some antibiotics), by the presence of infectious diseases, such as flu or bronchitis / bronchopneumonia, or by general anesthesia. Death can occur from acute respiratory muscle failure or pneumonia. The incidence of death caused by the disease is highest during the first year of the disease, however it remains high within five years of the onset of the disease, and then decreases significantly in the following years.

Myasthenia Diagnosis

The diagnosis is made following several specific diagnostic criteria for myasthenia gravis:

  • Clinical criterion. A clinical history of disease consistent with myasthenia lasting at least six months should be reported. To this, some tests can be associated to evaluate increased muscle fatigue, such as opening and closing the fists rhythmically or climbing a flight of stairs. In both cases, there is progressively a reduction in the energy with which these movements are performed;
  • Electromyographic criterion. An electromyography is performed (EMG) through a precise method of electrical muscle stimulation at pre-established frequencies, which will make it possible to visualize a progressive decrease in muscle function.
  • Pharmacological criterion. The rapid improvement of muscle fatigue following the administration of an anti-myasthenia drug, such as anticholinesterases, is often decisive in formulating the diagnosis of the disease: drugs such as edrophonium chloride or prostigmine are used for this purpose;
  • Immunological criterion. The search for the anti-acetylcholine autoantibody (anti-AchR) is useful in doubtful cases, as its presence allows the diagnosis of myasthenia to be made with certainty. In cases where such antibodies are not present, ie in the so-called "seronegative" myasthenia, we can look for another autoantibody, the anti-MuSK antibody (anti muscle specific tyrosine kinase), which will be positive in 70% of seronegative myasthenia cases. If this antibody is also negative, autoantibodies found less frequently in the disease will be looked for. Also useful is the measurement of antibodies directed against calcium channels (to exclude the myastheniform syndrome of Lambert Eaton).

Myasthenia therapy

There is one care for myasthenia? Today, the treatment of myasthenia allows a control of the disease in the vast majority of cases. There are different modes of action, to be used on the basis of the type of disease we are facing:

  • Anticholinesterase drugs. They are the first drugs that are administered to the myasthenic patient, as they are very effective in the early stages of the disease, but progressively less useful as permanent damage related to the disease is established; these drugs are also not very useful in localized forms. The drug mainly used is pyridostigmine bromide, administered orally five or six times a day, as it has a very short duration of action. Side effects related to the drug are frequent (such as increased salivation, muscle fasciculations, diarrhea and abdominal cramps), therefore the dose must gradually increase over time;
  • Surgical therapy: removal of the thyme, to block the production of circulating autoantibodies. The best surgical technique used to date is the transternal one, which is associated with a greater possibility for the surgeon to remove all the thymic tissue and the adipose tissue that surrounds this organ. The results of the surgery are better if it is performed within 12 months of symptom onset, in patients with generalized myasthenia and under the age of 50. The effectiveness of the intervention is very good, as it leads to an improvement of symptoms in 75% of cases, with complete and permanent remission of the disease in 20 - 40% of patients. If the presence of thymoma is found, the percentage of remission is much lower (around 10%). On the other hand, the removal of the thymus is useless in cases of seronegative disease, especially if the patient should be positive for anti-MuSK antibodies;
  • Corticosteroid drugs. Prednisone is mainly used and are the first choice immunosuppressive drugs to use if anticholinesterases and thymectomy have not provided an improvement in symptoms. It is a therapy that is administered for a long time (at least for a year) and, therefore, not free from serious side effects, such as osteoporosis, cataracts, obesity, diabetes etc ...
  • Immunosuppressive drugs, such as azathioprine and methotrexate, to be used in case of important contraindications to the use of corticosteroids. They are drugs that have different side effects than prednisone, but their effects are more delayed and sometimes less effective;
  • Other immunosuppressants. Other drugs used to block the presence of autoantibodies in the circulation are cyclophosphamide and cyclosporine A, but which are used in rare cases as they have numerous and serious side effects;
  • Plasma exchange and haemofiltration: in cases in which the disease has a rapid course, a technique of replacement and "washing" of the patient's plasma from circulating autoantibodies, called "plasmapheresis", can be associated with the immunosuppressant. It is an invasive and annoying technique for the patient and therefore not routinely used, but associated with excellent results in a very short time. Often this method is combined in cases of thymectomy, in order to obtain the best possible result;
  • Infusion of immunoglobulin G (IgG) injecting in high doses. In cases of rapid-course disease in which plasmapheresis cannot be performed, high-dose IgG can be used instead, which disturbs the binding of autoantibodies to their target. Compared to plasmapheresis, they are less powerful and more expensive.

Myasthenic crisis

In cases of myasthenic crisis, urgent hospitalization of the patient in intensive care is indicated: assisted breathing is carried out after intubation, suspending the anticholinesterase drugs for one or two days, allowing the body to rest. Subsequently, these drugs are resumed intravenously, gradually increasing with the dose, in order to avoid side effects related to an accumulation of the drug in the body. If this happens, an antidote is available that resolves the complication in just a few minutes, atropine sulfate, administered intramuscularly.

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