Myasthenia Gravis in Children

What is Myasthenia Gravis in Children?

Myasthenia gravis refers to autoimmune diseases, with transient muscle weakness and pathological fatigue. Immunological disorders in myasthenia gravis have a genetic condition.

The prevalence of myasthenia gravis is 1-5 cases per 100 thousand people, there is a tendency to increase the number of patients. Children and adolescents under 17 years old make up 9-15% of patients with myasthenia gravis, girls are more often ill. The average age at the onset of the disease is 7.2 years. Clinical observations show that myasthenia gravis can begin at any age.

Causes of Myasthenia Gravis in Children

The basis of the origin of myasthenia gravis is an autoimmune reaction to acetylcholine receptors (AChR) of skeletal muscle. Antibodies to acetylcholine receptors cause neuromuscular block.

The manifestation of immunopathological reactions in patients with myasthenia is considered to be changes in the thymus, or thymus gland, (the central organ of the immune system). This is noted in most patients in whom the disease developed between the ages of 1 year to 17 years. Immunological research methods allow to determine changes in the structures of the postsynaptic membrane in patients with myasthenia.

Pathogenesis during Myasthenia Gravis in Children

In children born to mothers with myasthenia gravis, 10-20% of cases are diagnosed with myasthenia gravis, in which myasthenic syndrome is transient. Clinical manifestations include general muscle hypotension, weak cry, shortness of breath and sucking, ptosis (omission of an organ), amimia, oculomotor disturbances, swallowing disorders, and a decrease in deep reflexes are possible. It is proved that the transient myasthenic syndrome, which manifests itself in such children in the first days of life and lasts for 1-1.5 months, is due to the transfer of antibodies to the AChR from the mother through the placental barrier.

There are 6 forms of congenital myasthenia gravis with different types of inheritance, which should be considered as congenital myasthenic syndromes. Among them are:

  • autosomal recessive syndrome with generalized muscle fatigue due to end platelet deficiency of acetylcholinesterase;
  • autosomal dominant syndrome with weakness and atrophy of the scapular muscles and muscles of the forearm;
  • autosomal recessive syndrome, in which the size of synaptic vesicles containing AChR is below normal;
  • autosomal recessive syndrome caused by a decrease in the amount of AHR on the end plate;
  • autosomal recessive syndrome, manifested by generalized pathological muscle fatigue due to a reduced content of synaptic vesicles and a decrease in the release of acetylcholine;
  • autosomal dominant syndrome with bulbar and lumbar muscle weakness, aggravated by muscle tension and contact with heat.

It should be emphasized that congenital myasthenic syndromes usually occur in children whose mothers do not suffer from myasthenia gravis, myasthenic symptoms are determined at birth.

The following types of myasthenia disorders are distinguished:

  • generalized two types:
    – without respiratory failure and cardiac activity;
    – with respiratory failure and cardiac activity.
  • local:
    – pharyngeal-facial: without respiratory failure; with respiratory failure;
    – ophthalmic;
  • musculoskeletal:
    – without respiratory failure;
    – with respiratory failure.

Symptoms of Myasthenia Gravis in Children

In childhood, a juvenile form of myasthenia is more common. The first symptoms may be oculomotor disorders: ptosis, limitation of the range of movements of the eyeballs, double vision. The latter symptom is sometimes difficult to detect, as young children often cannot explain their feelings. Violations of the masticatory muscles, facial muscles, swallowing disorders, dysphonia, dysarthria are noted. Often there is pathological fatigue in the muscles of the pelvic girdle, neck, and upper limbs. The face of a sick child may have a lifeless expression, often the upper eyelids are lowered, the gaze is fixed. There is an increase in ptosis, slurred speech, the appearance of a nasal tone of voice – at the end of a long conversation; fatigue is observed during repeated active movements. Muscle weakness and fatigue usually increase in the evening.

An increase in muscle weakness is noted after physical exertion. So, ptosis appears with repeated squats, clenched hands into a fist, with repeated horizontal movements of the eyeballs.

In children, myasthenia gravis often begins monosymptomatically, but other symptoms join very quickly; generalization of the process during the first months is characteristic. The course is usually progressive, in most children generalized forms with severe manifestations are detected. Local forms of myasthenia gravis in children occur in 12% of cases; their course is more severe than in adults.

With the pharyngeal-facial and musculoskeletal form, respiratory and cardiac disturbances quickly develop.

With a generalized form of myasthenia gravis, the muscles of the cranial section, neck, limbs, and trunk are primarily involved in the pathological process. Fatigue and muscle weakness intensify after exercise, towards the end of the day. Movement disorders are caused by the predominant damage to the muscles of the arms and legs, and the weakness of the muscles of the neck.

With an ophthalmic form, oculomotor disorders dominate in the clinical picture: ptosis, unilateral or bilateral, double vision, strabismus; the severity of symptoms is unstable, intensifying towards evening, decreasing after rest, a peculiar “nystagmus” due to weakness and fatigue of the external muscles of the eye is noted.

With the pharyngeal-facial form of myasthenia gravis, weakness of facial muscles is combined with weakness of the muscles of the larynx, soft palate and tongue, the occurrence of immobility of the tongue, palate. This is manifested by impaired speech (phonation and articulation), swallowing.

Diagnosis of Myasthenia Gravis in Children

Diagnosis of myasthenia gravis in children is a significant challenge due to the variability of clinical symptoms and the characteristics of the examination of the child.

The objective of a clinical examination is to identify the main symptom of the disease – pathological muscle fatigue. To confirm the diagnosis, a proserin test, electromyography, thymus scintigraphy, and the study of the immune status are used.

A prozerin test with an assessment of the strength and fatigue of the affected muscles is carried out before and 30 minutes after intramuscular administration of a 0.05% solution of proserin in a single age-related dose. Distinguish:

  • sharply positive proserin test, when all myasthenic symptoms disappear;
  • a positive test – only individual symptoms remain;
  • weakly positive test, in which the severity of myasthenic symptoms decreases;
  • dubious proserin test – the severity of the manifestations of myasthenia varies slightly;
  • negative proserin test – clinical symptoms do not change after administration of prozerin.

The diagnosis of myasthenia gravis can be judged by having one of the first three variants of the proserin test.

Electrophysiological studies in myasthenia gravis are performed to determine the phenomenon of “myasthenic reaction” – a progressive decrease in the strength of muscle contraction during nerve stimulation. Currently, children use global electromyography, in which after physical activity there is a significant decrease in amplitude, a decrease in the time of electroactivity, and a decrease in the frequency of action currents. To clarify the nature of the pathology of the thymus, not only the functional activity of the thymus is examined, but also tomography of the anterior mediastinum, pneumomediastinography, and computed tomography of the chest are performed. It is known that in 8–9% of patients with myasthenia gravis, a thymus tumor is diagnosed – a thymus characterized by rapid development with a predominant lesion of the muscles performing the act of swallowing, facial muscles.

Along with an assessment of the immune status, a serological analysis is done to determine antibodies to AChR, the number of which is increased in most patients. With localized forms of myasthenia gravis these indicators and electrophysiological data may not be changed, therefore, the differential diagnosis of localized forms of myasthenia gravis is rather complicated. Differential diagnosis is necessary to exclude diseases in the structure of which myasthenic syndrome occurs. These include botulism, antibiotic poisoning from the aminoglycoside group, Itsenko-Cushing’s disease, Addison’s disease, hypo- and hyperthyroidism, polymyositis.

Treatment of Myasthenia Gravis in Children

In the treatment of myasthenia gravis conservative and surgical methods are used.

The basis of conservative therapy is anticholinesterase drugs (AHEP). Use proserin (neostigmine), Kalimin (pyridostigmine bromide), oxazyl. The dose of AHEP is selected individually and depends on the age of the child, the form of the disease, the results of the proserin test, which allows to evaluate the reaction to the drug, the degree of compensation achieved, the presence or absence of side effects. When choosing ACEP, their inherent pharmacokinetics are taken into account:

Proserin, when administered subcutaneously at a dose of 1-2 ml of a 0.05% solution, acts after 15-20 minutes, the maximum effect is manifested 30-40 minutes after injection. The duration of action is 2-3 hours.

When ingested, Kalimin causes an effect after 40-90 minutes, which lasts up to 5-6 hours.

Oxazil begins to act after 45-50 minutes for 6-8 hours.

In case of swallowing disorder, a combination of AHEP is often used: 30 ml of food is injected intramuscularly with 1 ml of a 0.05% solution of proserin, and 1 hour after it, Kalimin is prescribed inside, which gives a longer effect.

In cases of severe overdose of AHEP, a cholinergic crisis may develop, which is manifested by symptoms of combined muscarinic and nicotine intoxication. Bradycardia, miosis, fibrillar twitching, increased salivation, cramping abdominal pain, vomiting, diarrhea, agitation, respiratory failure (bronchospasm, hypercapnia) occur. In severe cases, tremor develops, convulsions and death occurs. At a young age (up to 1 year), the body is more resistant to anticholinesterase drugs. Therefore, parents need to be very careful and monitor the manifestation of side effects in the child. In the case of a cholinergic crisis, immediate hospitalization of a sick child is necessary. Cholinergic crisis develops slowly over several days, it is characterized by tingling in the muscles, a feeling of spasm in the throat, signs of peripheral vascular insufficiency: pale skin, cold extremities, marbling of the skin.

Also, patients may have a myasthenic crisis, in which the aggravation of the patient’s condition is due to an insufficient dose of ACEP. In the treatment of myasthenic crisis, use proserin or kalimin in higher doses.

Some drugs aggravate myasthenia gravis: antibiotics (neomycin, streptomycin, tetracyclines), d-penicillamine, hydantoin, magnesium-containing drugs, quinine, quinidine, clonazepam, as well as muscle relaxants, polymyxin, kanamycin, gentamicin, lincomycin, fendamine, clinin lithium, tricyclic antidepressants, novopassit.

In severe myasthenia gravis, corticosteroid drugs are prescribed: prednisone 1.5 mg / kg per day or more, focusing on the clinical condition of the patient.

The method of enterosorption, in particular using polyphepan, is noteworthy. This method leads to an improvement in neuromuscular transmission. There is evidence of successful use of plasmapheresis as a component of complex therapy in children with myasthenia gravis.

In myasthenia gravis, immunoglobulins for intravenous administration (intraglobin, immunoglobulin, pentaglobin) can be used. They are administered at a dose of 400-1000 mg / kg per day for 2-5 days. Individual intolerance of immunoglobulins can be manifested by headache, nausea, dizziness, vomiting, diarrhea, tachycardia, cyanosis, shortness of breath, hyperthermia, chills, increased sweating, back pain, myalgia, etc. The listed symptoms can occur 30 minutes after the start of the infusion and during the first day.

Surgical treatment of myasthenia gravis in childhood consists of a thymectomy (removal of the thymus gland), which in case of myasthenia gravis gives a positive effect in 70-80% of cases. The main indications for thymectomy are:

  • the presence of thymoma or thymus cysts;
  • insufficient effectiveness of treatment with AChEP;
  • resistance to ongoing therapy, despite high doses of AHEP;
  • intolerance to achep.

In children, surgical treatment is indicated for severe and moderate forms of the disease. The best results are observed in patients with the shortest duration of the disease. Children who have been suffering from myasthenia gravis for less than 5 years have an improvement after surgery in 98% of cases, more than 5 years – only 71%.

After surgery, thimectomy patients are transferred to the dispensary. Treatment continues with a reduced dose of AChEP drugs, additionally prescribed B vitamins, vitamin E, ATP. Long-term follow-up of children with myasthenia undergoing thimectomy surgery shows that excellent and good results (complete recovery, significant improvement) are observed in 75-80% of patients.

Corticosteroids (prednisone, etc.) are prescribed:

  • in the preoperative period – with severe myasthenia gravis;
  • in the postoperative period – in the absence of a thimectomy effect or with a worsening of the condition in the near or distant period. There are various schemes of corticosteroid therapy, which are developed and prescribed individually, depending on the severity of the disease.

Currently, despite the successes achieved in therapy, the improvement of treatment methods for myasthenia in children continues.

Myasthenia Prophylaxis in Children

If the child is diagnosed with myasthenia gravis, he is prohibited from excessive physical exertion and long exposure to the sun. Baby food should contain low-calorie foods. In order to prevent the need to take drugs that strengthen the immune system. During treatment and prevention of myasthenia gravis there are a number of drugs that are not indicated for use, these include: antipsychotics, diuretics, tranquilizers, antibiotics of the fluoroquinolone groups. Therefore, when choosing a medicine, you should be careful.