Severe myasthenia gravis: diagnosis and aggressive treatment

2021-08-01 11:04 PM

Myasthenia gravis can be effectively treated, with therapies including anticholinesterases, rapid immunomodulatory therapy, immunosuppressants, and thymectomy

Myasthenia gravis is the most common disorder of neuromuscular transmission. It is one of the most well-known and well-understood autoimmune disorders. The hallmarks of the disorder are fluctuating degrees and variable combinations of weakness in the eyes, tongue, pharynx, larynx, extremities, and respiratory muscles. Weakness results from an antibody-based, T-cell-dependent immune attack that targets proteins in the postsynaptic membrane of the neuromuscular junction (acetylcholine receptors or receptor-associated proteins). The diagnosis of myasthenia gravis can be established clinically and serologically. 

The diagnostic approach to myasthenia gravis focuses on confirming the clinical diagnosis established by history and typical examination findings.

Edrophonium tests are very sensitive, but they have major limitations due to concerns about excessive false-positive results. Therefore, they are not confirmatory tests.

The most reliable testing methods that support confirmation are autoantibody serology and electrophysiological studies (repeated nerve stimulation studies and single-fiber electromyography).

Myasthenia gravis can be effectively treated with therapies including anticholinesterase drugs, rapid immunomodulatory therapy, immunosuppressants, and thymectomy. Treatment is individualized and depends on the age of the patient, severity of the disease.

In patients with myasthenia gravis (usual patients with thymoma), the body produces antibodies against the acetylcholine receptor, reducing the function of the acetylcholine receptor in the postsynaptic array, leading to a gradual weakening of skeletal muscle movement, more motor muscles may be impaired. The tendency to rapidly weaken especially the respiratory muscles leads to severe respiratory failure requiring artificial ventilation, and the weakness is likely to recur if the cause of the thymoma is not eliminated.

Aggressive therapeutic measures to reduce the number of autoimmune antibodies in the blood to improve the clinical condition include the use of immunosuppressive drugs to reduce antibody production, plasma filtration to remove autoantibodies. free from the body.

Definite diagnosis

Clinical

The patient has intermittent muscle weakness, which increases with exercise, recovers with rest.

Often there is drooping eyelids, there may be double vision.

Weakness of pharyngeal muscles: difficulty swallowing, difficulty speaking.

Respiratory muscle weakness: rapid, shallow breathing, cyanosis of the lips and extremities.

Exercise tests showed marked muscle weakness.

Subclinical

Test prostigmin (+)

+ Intravenous prostigmin 0.5mg + atropine 0.25mg IV.

+ After 5-10 minutes of injection, weak muscles are recovered quickly.

Electromyographic stimulation test: rapid decrease in muscle activity intensity under continuous stimulation.

Arterial blood gases: increased PaC02 due to decreased alveolar ventilation; Blood Pa02 may decrease.

Chest X-ray: there may be aspiration pneumonia, atelectasis due to alveolar hypoventilation.

CT scan of the chest: can identify thymoma.

Severe signs

Difficulty swallowing, choking.

Respiratory failure: hypoxemia, slurred speech, tachypnea, paradoxical abdominal breathing. 2

Differential diagnosis

Polyarthritis and neuritis.

Disabled.

Scorpion snake bite.

Hypokalemia.

Porphyrin urine.

Myelitis spreads.

Diagnose the cause

Usually due to tumor or enlargement of the thymus in adults. The thymus may be in the correct position behind the thymus or out of place. A chest CT scan or thymogram is required for diagnosis.

Worsening of myasthenia gravis is usually due to:

+ An episode of respiratory infection.

+ Using drugs in insufficient doses, skipping drugs or overdosing on drugs.

+ Some drugs that increase myasthenia gravis: aminoglycosides, erythromycin, azithromycin, beta-blockers, procainamide, quinidine, magnesium, ...

Treatment

General resuscitation

Respiration: give oxygen, if not, switch to non-invasive mechanical ventilation, if the respiratory condition is still unsuccessful, invasive mechanical ventilation with high Vt (12ml/kg) combined with PEEP 5cm of water to avoid atelectasis due to decreased alveolar ventilation.

Circulation: ensure enough translation.

Correction of electrolyte disturbances.

Ensure nutrition: eat through a nasogastric tube.

Exercise therapy: anti-arthritic, anti-ulcer pressure.

Prophylaxis against gastric - duodenal ulcers: secretory drugs, proton pump inhibitors.

Prophylaxis against deep vein thrombosis due to prolonged lying: low molecular weight heparin.

Treat the cause

The goal is to reduce the amount of anti-Ach receptor antibodies in the blood.

Anticholinesterase agents for synaptic acetylcholine maintenance.

Mestinon 60mg x 4 to 6 tablets/day. The patient's response should be monitored:

+ Slow muscle recovery: need to increase drug dose.

+ Muscle movement is weak, there is a phenomenon of muscle: drug overdose needs to reduce the dose.

Combination of atropine 0.5mg x 4 to 6 tablets/day (taken with Mestinon reduces the side effects of Mestinon).

Corticoid:

Has the effect of reducing the immune response. However, the effect is not much.

Dose of methylprednisolone 120-160mg/day x 5 days, then gradually reduce the dose.

Measures to remove anti-myelin antibodies:

Plasma exchange: remove plasma containing autoimmune antibodies, then replace the discarded plasma with fresh frozen plasma or 5% albumin in a corresponding volume (30-40ml/kg).

Plasma filtration: However, the cost is still high, so it has not been widely applied.

+ Double filter: using two filters with different membrane pore sizes to remove autoimmune antibody components, very little replacement fluid.

+ Adsorption filter: use filter with filter membrane capable of absorbing the particles to be removed, no need for a replacement solution.

Attention:

Filter time as soon as possible: good resilience.

A number of filtrations and intervals: daily or every other day, 3-6 times depending on patient response.

There is a risk of allergy or anaphylaxis, coagulopathy, electrolyte disturbance, local infection, or bacteremia, etc.

Immune globulin: very expensive treatment.

+ Dosage: 0.4g/kg/day X 5 days.

+ Contraindications: renal failure, drug allergy.

Thymic surgery if a thymic tumor is present.

Prevention

Use the right dose, get regular check-ups.

Avoid bacterial infections, especially respiratory infections.

Avoid medications that increase muscle weakness.

Thymus surgery if a thymic tumor is found.