A cholinergic crisis is not accompanied by an overdose of proserin. Treatment of myasthenic crisis. Familial periodic paralysis

The cause of a myasthenic crisis is usually a sudden worsening of a pre-existing myasthenia gravis due to a medication error or an intercurrent illness, most often an infection. Only in rare cases is myasthenic crisis the debut manifestation of myasthenia gravis. There is an acute crisis with respiratory failure and sudden cessation of breathing, heart failure due to severe cardiac arrhythmias caused by myocarditis, and a subacute crisis with decompensation of the functionality of acetylcholine receptors and weakness of the respiratory and/or bulbar muscles.

Symptoms and signs of myasthenic crisis

Ptosis and diplopia may be observed. Reflexes and sensitivity are not impaired.

Dyspnea. At first glance, there is no impression that the patient's condition is serious. The combination of facial expression and weakness of the respiratory muscles creates a false impression of the patient’s satisfactory condition.

Boulevard violations carry the potential danger of disrupting the protective function of the upper respiratory tract and the development of aspiration pneumonia.

Fatigue and respiratory failure lead to the development of coma.

Taking penicillamine (can cause the development of a syndrome identical to idiopathic myasthenia gravis).

Common predisposing factors for myasthenic crisis

Infection, surgery, medications. Note! Glucocorticoids used to treat myasthenia gravis may initially lead to exacerbation.

Severity rating

The most important indicator of the severity of the crisis is the vital capacity of the lungs. Arterial blood gases are not a sensitive criterion; their determination makes it possible to detect hypercapnia at a late stage.

Tabloid violations. Cholinergic crisis.

Sometimes it is not possible to differentiate between myasthenia gravis and the excessive effect of anticholinesterase therapy (which leads to muscle weakness as a result of depolarization blockade) on the basis of clinical data alone. The issue of discontinuing anticholinesterase drugs is decided only after consultation with a neurologist. It should be remembered that cholinergic crisis is much less common than myasthenic crisis.

Treatment of myasthenic crisis

Stabilize the patient's condition. You should make sure that there are no electrolyte disturbances (decreased potassium and calcium concentrations, increased magnesium concentrations), and that the patient is not taking medications that aggravate muscle weakness.

Treatment is aimed at maintaining vital functions, which includes intubation and connection to a ventilator. Measures of symptomatic therapy, as well as differential diagnosis with cholinergic crisis, include the introduction of a short-acting anticholinesterase agent - edrophonium chloride. If the condition improves, treatment is continued with longer-acting anticholinesterase agents administered parenterally or orally (for example, pyridostigmine (kalimine)).

When switching from oral to intravenous administration, it is necessary to remember that the ratio of equivalent doses administered intravenously and orally is 1:30!

At the same time, additional measures are carried out: the prescription of anticholinergic drugs (atropine) in the presence of a large amount of mucus, adequate replenishment of potassium deficiency (plasma concentration should be at the upper limit of normal), treatment of concomitant diseases. After recovery from the acute condition, immunomodulatory therapy is prescribed.

The issue of conducting a test with edrophonium (tensilone test) is decided. Anticholinesterase therapy is effective provided that a cholinesterase crisis is excluded. If there is no effect after administration of edrophonium, the correctness of the diagnosis is assessed. All anticholinesterase drugs are discontinued for 72 hours. The edrophonium test can be repeated after some time.

Immunosuppressive therapy should be carried out under the supervision of a neurologist: prescribing prednisolone according to an alternating regimen leads to improvement. However, such treatment must be carried out with caution, since muscle weakness may occur at the beginning of glucocorticoid treatment. High doses of glucocorticoids are prescribed until remission is achieved. Azathioprine is also used for maintenance therapy, but the effect is achieved only after several months of taking it.

Plasmapheresis removes circulating antibodies from the bloodstream. Usually a replacement of 50 ml/(kg/day) is carried out over several days.

Long-term therapy with cholinesterase inhibitors is prescribed by a neurologist. The choice of drug determines the patient's response to therapy, but treatment should always begin with pyridostigmine at a dose of 60 mg every 4 hours. The drug can be administered through a tube or, if intramuscular administration is necessary, replace it with neostigmine (at the rate of 1 mg neostigmine per 60 mg pyridostigmine).

Relative contraindications are bronchial asthma and arrhythmias. Atropine should be administered before the test, since the administration of edrophonium (belongs to the group of cholinesterase inhibitors) may be accompanied by a severe cholinergic reaction, such as symptomatic bradycardia.

Prepare and label two 1 ml syringes: one with saline and the other with 10 mg edrophonium.

Select a muscle to be monitored and ask colleagues to evaluate the strength of the muscle being tested before testing.

The contents of both syringes are injected, and neither the patient nor the doctor should know in what sequence they were injected. Ask the observer to reassess muscle strength after injecting the contents of each syringe.

Initially, edrophonium 2 mg (0.2 ml) is administered as a bolus and the patient is assessed for adverse cholinergic effects. If the patient has tolerated this dose, the remaining 0.8 mg (0.8 ml) of the drug is administered after 1 minute.

An increase in muscle strength after administration of edrophonium-3 indicates the presence of a myasthenic rather than a cholinergic crisis in the patient.

The most dangerous, life-threatening condition with myasthenia gravis are crises - myasthenic And cholinergic.

Myasthenic crisis in myasthenia gravis usually associated with impairment of neuromuscular transmission. This may be due to a change in the functional state of the synaptic apparatus under the influence of various factors: malaise, fever, menstruation, fatigue, etc. or a decrease in the dose of ACEP for one reason or another. The main danger is deterioration of bulbar functions, up to aphagia, as well as weakness of the respiratory muscles with increasing respiratory failure. At the prehospital stage, immediate subcutaneous or even intravenous administration of a 0.05% proserine solution is necessary; after 30 minutes, proserin is re-injected subcutaneously; intravenous administration of methylprednisolone is mandatory - up to 1.5-2 g or prednisolone 1.5-2 mg/kg.

Patients with complications of myasthenia gravis are hospitalized in centers of neuromuscular pathology or resuscitation, neurointensive care units, or intensive care units, where they usually undergo plasmapheresis, and, if necessary and possible (the drug is very expensive!), immunoglobulin G is administered intravenously - 0.4 mg/kg, according to indications mechanical ventilation is used.

Cholinergic crisis in myasthenia gravis is associated with an overdose of anticholinesterase drugs, resulting in symptoms of muscarinic and nicotinic intoxication: muscle fasciculations, ptosis, hypersecretion of saliva, sweating, pallor, bradycardia, abdominal pain, diarrhea. AHEP are immediately temporarily cancelled. In a threatening situation, 0.5-1.0 ml of a 0.1% atropine solution is slowly injected intravenously. Patients are taken to the above departments, where, according to indications, they are prescribed mechanical ventilation and plasmapheresis is performed.

Myasthenia gravis is a fairly rare pathology of an autoimmune nature. Officially registered cases of this violation are about 0.01%.

Typically, the disease occurs in people aged 15 to 45 years, but the greatest number of cases of its development occurs at the age of 20-30 years, and the smallest in childhood.

With the gradual development of the pathological condition, the transmission of nerve impulses to muscle tissue is blocked, which leads to their dystrophic changes.

There are 2 forms of myasthenia gravis – ocular and generalized. In the first option, the muscles of the eyeball suffer more from the disease, and in the second, the disease affects the entire body equally.

The worst type of pathology development is myasthenic crisis, which requires urgent intervention by specialists.

There is currently no proven information about the origin of such a disease as myasthenia gravis.

The vast majority of experts are inclined to the hereditary theory of the origin of the pathology, since many of the patients with myasthenia gravis indicated that there were already cases of such a disease in the family.

The etiology of the process lies in the disruption of immune processes, that is, pathological changes in the thymus () - the body begins to produce antibodies that block the receptors of the postsynaptic membrane with its subsequent destruction.

When considering myasthenia gravis as an independent disease, there are a number of reasons that can provoke the body to produce antibodies:

• frequent stressful situations;
• depressive states;
• infectious effects;
• immune pathologies.

When myasthenia gravis is one of a set of diseases, it is considered as a syndrome. Typically associated diseases are:

• thymic hyperplasia;
• amyotrophic syndrome (lateral);
• malignant neoplasms (usually lung, testicle, mammary glands);
• systemic pathologies of connective tissues.

There are no separate changes specific to myasthenia gravis in the central nervous system. With the gradual development of pathology, there are risks of muscle fibers weakening to the point of disability or the occurrence of myasthenic crisis.

Myasthenic crisis

Myasthenic crisis is the most severe manifestation of the pathology.

There is a severe blocking of the conduction of neuromuscular impulses at the heart of the respiratory system, with the development of apnea and bulbar disorders. With myasthenia gravis, a crisis can be triggered by the following reasons:

• active development of pathology;
• exacerbation of a secondary disease;
• infectious damage to the body;
• stress exposure;
• skipping medications;
• over or under dosage;
• use of contraindicated drugs.

At the initial stage of myasthenic crisis, the patient’s condition is expressed as follows:

The latter occurs due to significant relaxation of the sphincters in the patient’s body. If the heart muscle is damaged, acute heart failure occurs.

Symptomatic signs increase over 20-30 minutes; in the process, disturbances in the central blood supply to the brain may occur with the onset of hypoxia, which can lead to loss of consciousness and death of the patient.

Diagnosis of myasthenia gravis

Diagnosing myasthenia gravis has some difficulties, due to the uncertainty of the origin of the pathological condition at the time of detection of symptomatic signs.

The best diagnostic option is to identify the following changes:

• lymphocytosis;
• decrease in biopotentials (electrical excitability of muscle tissue);
• enlargement of the thymus shadow.

One of the most accurate research techniques is pneumomediastinotomography, but the technique requires invasive intervention.

Today, experts have abandoned this practice in favor of the use of computed tomography, which has a sufficient number of advantages:

• expanded information content;
• safety for the patient;
• high reliability.

The number of reliable results when examining the thymus gland on CT is about 92%, with small sizes of thymus enlargement.

In the case of advanced development of the pathological condition, diagnosis is simplified.

In the process of making a diagnosis, a proserine test is used.

Some experts claim that when using this research technique, certain patients experienced a weakening of the symptoms inherent in myasthenia gravis and after surgical treatment (in this case, removal of the thymus gland), all symptomatic manifestations of the disease disappeared.

In the absence of changes, complete disappearance of signs of the disease is not observed.

In some cases, the pathological condition progresses in the absence of secondary pathologies and unchanged thymus parameters.

This variant of the pathological disorder is a persistent thymus, and it requires surgical intervention, excluding the presence of direct contraindications.

Also, there is a need to further differentiate the diagnosis from myasthenic syndrome, which has a different origin, but is characterized by a similar symptomatic picture.

This syndrome occurs in patients suffering from:

• encephalitis;
• amyotrophic lateral sclerosis;
• multiple sclerosis;
• certain types of hormone-producing tumors.

In cases where myasthenia gravis is a consequence of development, an immunohistochemical study of the spectrum of proteins plays an important role in diagnosing the pathological condition.

Thanks to this analysis, it becomes possible to determine the type of tumor process, the presence of metastases and its effect on the body.

Treatment

Conservative treatment of myasthenia gravis is not always possible.

Relief of a pathological disorder with medications is allowed only for mild cases of the disease in localized forms. As part of therapeutic treatment, the following are used:

1. Anticholinesterase drugs, among which the most widespread are: Galantamine, Oxazil, Kalimin, Proserin. In addition to them, potassium salts are used (they give an enhancing effect).
2. “Pulse therapy” is the use of Prednisolone in increased dosages. Start using the drug with 1-2 thousand mg with a gradual decrease.
3. Immunosuppressants (pharmacological agents for artificially weakening the immune system) - Cyclophosphamide, Azothioprine, Cyclosporine.
4. In case of severe myasthenia gravis and the impossibility of surgical treatment, an individually selected version of HRT and cytostatics (drugs that inhibit the development of tumors) are used.

With generalized myasthenia, there is a need for thymectomy, since all types of disease have a direct relationship with the thymus.

Thymectomy, as a treatment method for myasthenia gravis, was first used in 1939 and has been recognized as the main treatment method since approximately the 50s of the 20th century.

The absolute indications for surgery to remove the thymus are the following:

1. True myasthenia. First of all, the generalized form of the disease, as well as musculoskeletal and pharyngeal-facial in moderate and severe types.
2. Myasthenia gravis against the background of a developing tumor in the thymus gland. Both malignant and benign tumors are considered.
3. In cases where the pathology leads to a gradual impairment of the functions of swallowing and breathing, as it carries increased risks to the patient’s life and causes particular discomfort.
4. Active progression of myasthenia gravis, regardless of treatment with HRT and other pharmacological agents.

The relative indications are:

• alleviated course of the disease;
• local forms of myasthenia;
• illness duration over 5 years.

Among the contraindications to surgery of the thymus gland are:

• myasthenic syndrome;
• inoperability of the tumor process;
• patient age over 65 years;
• severe secondary pathologies (usually cardiovascular).

In any case, the decision on the possibility of surgical treatment of the disease requires a completely individual approach.

This is due to the multiplicity of factors influencing the course of the disease. Sometimes, for mild forms of myasthenia gravis, surgery may be prescribed, for example:

1. The diagnosis corresponds to an uncomplicated localized form of myasthenia gravis and does not pose a serious danger to the patient.
2. Anticholinesterase therapy was prescribed to correct the condition and relieve the main symptoms of the pathology.
3. For a long time, the prescribed therapy does not help, and the symptoms of the disease begin to progress and myasthenia gravis becomes a generalized form.
4. The doctor decides to operate on the thymus, since the disease poses an increased threat to the health and life of the patient.

In any case, there is no direct dependence on the presence of tumors or myasthenia gravis as a disease.

Therefore, each individual case requires careful diagnosis and multiple tests to determine the patient’s condition.

To reduce the risks for the patient, in the event of a possible myasthenic crisis, constant accompaniment by a loved one is recommended, as emergency assistance may be required.

If anticholinesterase drugs are ineffective, the patient’s condition worsens - myasthenic crisis, in case of an overdose of these drugs - cholinergic crisis. Muscle weakness increases sharply, severe bulbar phenomena develop, sharply complicating breathing, both due to weakness of the muscles of the chest, diaphragm, and due to obstruction of the upper respiratory tract (accumulation of tracheobronchial secretions).

Myasthenic crisis: wide pupils, tachycardia, normal or low blood pressure .

Cholinergic crisis: narrow pupils, bradycardia, rapidly developing hypotension, pronounced muscle fasciculations, hypersecretion of saliva and bronchial mucus, abdominal pain, diarrhea, vomiting due to rapid intestinal motility.

Emergency care for patients with myasthenia gravis

should be aimed at correcting breathing - intubation and transfer to mechanical ventilation.

With myasthenic crisis immediately inject 1 ml of 0.05% proserin solution intravenously and after 15 minutes 1 ml of proserin subcutaneously. The patient is hospitalized in the intensive care unit of the hospital. In addition to prozerin, you can use oxazil in suppositories and orally (0.01 g) or mestinon (0.06) orally. The administration of prednisolone 90 - 120 mg per day is indicated. The best results in myasthenic crisis are achieved by plasmapheresis or intravenous administration of immunoglobulins.

At cholinergic crisis anticholinesterase drugs are discontinued and 0.5 - 1 ml of 0.1% atropine solution is administered intravenously at intervals of 1 - 1.5 hours until the pupils dilate and dry mouth appears. Administration of the cholinesterase reactivator dipyroxime subcutaneously or intramuscularly (1 ml of 15% solution) is indicated. Patients are fed through a nasal tube.

Myasthenic crisis is a sudden, life-threatening deterioration in a patient with myasthenia gravis, characterized by disruption of vital functions. During some periods of the disease, such a critical condition may acutely arise when the chances of survival directly depend on the speed of medical care in intensive care conditions. Statistics show that myasthenic crisis occurs in every 10th patient.

Why does it occur?

Any crisis during the course of the disease indicates a worsening of the process. With myasthenia gravis, this can be due to two types of reasons:

1. Deterioration of the condition due to exposure to unfavorable factors (infection, exacerbation of concomitant pathology, severe stress, etc.). The result is not only a more massive attack of autoimmune complexes on neuromuscular impulse transmission receptors, but also qualitative changes in the composition of ion channels and remaining receptors. That is, negative changes occur in the very nature of the disease.
2. Acute progression of the disease due to iatrogenic causes (omission of medications, use of inadequate dosages, use of drugs contraindicated for myasthenia gravis).

How does it manifest?

Symptoms of myasthenic crisis are usually associated with increasing respiratory failure, which appears against the background of rapidly progressing generalized weakness of all muscle groups. Breathing disorders can be a consequence of damage to different muscle groups:

1. damage to the swallowing muscles, the muscles of the tongue, and the occurrence of asphyxia (suffocation) due to mucus or food entering the respiratory tract;
2. damage to the muscles of the larynx;
3. The intercostal muscles involved in the act of breathing, providing inspiration, and the muscles of the diaphragm.

Respiratory failure appears suddenly and progresses over several minutes. A person experiences a feeling of lack of air, anxiety, and agitation. First, breathing quickens due to the superficial muscles, the face becomes red, the pressure rises to 200 mm Hg, the pulse quickens to 160 beats per minute.

Then breathing becomes increasingly rare and superficial until it stops completely. With increasing hypoxia, cyanosis of the skin appears, blood pressure drops to 80 mmHg, the pulse becomes rare and can barely be felt. There is first confusion and then loss of consciousness.

Autonomic disorders occur: cold sticky sweat appears, saliva flows from the corner of the mouth, involuntary urination and defecation occur.

If the heart muscle is damaged, there can be death due to acute heart failure.

Diagnosis of the condition

Typically, diagnosing the condition does not cause difficulties. If the patient has an accompanying person (someone who can talk about the causes of the disease and the therapy used), diagnostic and therapeutic procedures will be more successful.

Clinically similar to myasthenic crisis is the deterioration of the condition of patients with myasthenia gravis associated with an overdose of ACEP drugs. It is called a cholinergic crisis. It is more characterized by vomiting, diarrhea, abdominal pain, and general trembling.

These crises require differential diagnosis, since the treatment is different. For this purpose, a proserine test is carried out: with a myasthenic crisis, compensation of symptoms is observed, but with a cholinergic crisis, there is no compensation.

However, a mixed crisis often occurs, the diagnosis and treatment of which is also carried out in the intensive care unit and requires special attention.

Crisis treatment

Emergency care consists of checking the airway and restoring breathing through a ventilator. The difficulties of synchronizing the patient’s spontaneous breathing and the operation of the device require highly qualified medical personnel.

Intravenous administration of proserin allows you to quickly stop an attack. However, in a mixed crisis, the use of ACEP for the duration of mechanical ventilation is completely canceled. The proserine test is used no earlier than 24 hours later if the symptoms of cholinergic crisis stop.

The most effective method that quickly improves the condition of a patient with myasthenic crisis is plasmapheresis or hemosorption - methods of purifying the blood from pathological autoimmune complexes. The number and frequency of courses is determined by doctors.

It is important that a loved one is always with a patient with myasthenia gravis. If signs of acute respiratory failure appear, emergency hospitalization is required - the chances of survival decrease every minute. Diagnosis of myasthenic crisis and treatment is carried out in intensive care.