Neurology
Question 17 of 92
A 47 year old woman is brought to the Emergency Department with worsening difficulty in breathing. She has a past medical history of myasthenia gravis and you suspect she is experiencing a myasthenic crisis. She is hypoventilating and is acidotic. She is intubated and ventilated by the critical care team. What is the next management step for this patient?
Answer:
Myasthenia crisis is a complication of myasthenia gravis and a medical emergency, defined as an exacerbation requiring mechanical ventilation. Initial therapy consists of optimised ventilatory settings to provide rest to respiratory muscles, removal of provoking factor(s) for the crisis, and acute therapy for the recovery of transmission across neuromuscular junction with either immunoglobulin (IVIG) or plasma exchange. High-dose corticosteroids may be initiated concurrently with IVIG or plasma exchange, as they reach their maximal effectiveness at the time that the effects of IVIG and plasma exchange are waning. Supportive care includes deep venous thrombosis prophylaxis and ulcer prophylaxis, adequate nutrition and hydration, and avoidance of infections and drugs that may worsen myasthenia symptoms.Myasthenia Gravis
Neurology
Last Updated: 8th September 2021
Myasthenia gravis (MG) is a chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction (NMJ) in skeletal muscle. Circulating antibodies against the nicotinic acetylcholine receptor (AChR) and associated proteins impair neuromuscular transmission. Myasthenia gravis (MG) occurs in all ethnic groups and both genders. It most commonly affects young adult women (under 40 years of age) and older men (over 60 years of age), but it can occur at any age.
Clinical features
History:
- Typical features are weakness and fatigability of skeletal muscles with a characteristic distribution.
- The disease usually presents with 1 of 3 different forms: ocular, oropharyngeal, or generalised.
- Depending on the predominant initial form, patients with MG may complain of a multitude of symptoms including ptosis, diplopia, dysarthria (speech disorder), dysphagia (difficulty swallowing), facial paresis, proximal limb weakness, and shortness of breath.
- Characteristically the limb weakness worsens with activity (fatigue) and improves on rest and the fluctuations show diurnal variation (better in morning than in the evening).
Examination:
- Ptosis and diplopia occur early in the majority of patients. Ptosis time (which is normally more than 3 minutes) is checked by asking the patient to look up and recording the time until ptosis develops. Pulling up on the upper eyelid may induce ptosis in the contralateral lid. Between 50% and 60% of those who present with purely ocular symptoms will progress to develop generalised disease, and the vast majority will do so within the first 1 to 2 years.
- When the facial and oropharyngeal muscles are affected, there may be a characteristic flattened or transverse smile, or nasal speech, and difficulty in chewing and swallowing.
- Examination of the limbs shows proximal muscle weakness with fatigue. Arm abduction time (which is normally more than 3 minutes) is checked by asking patients to hold their arms outstretched.
- There should be no evident muscle wasting and reflexes are normal. Sensations are intact and there is no autonomic dysfunction.
- In cases of myasthenic crisis there is severe respiratory involvement and/or bulbar involvement.
Investigations
MG is a clinical diagnosis supported by serological and electrophysiological tests.
- Serological testing
- AChR antibodies are detected in 80% to 90% of generalised MG patients and 50% of ocular MG patients, with 99% specificity in both cases.
- MuSK antibodies are detected in up to 70% of AChR seronegative generalised MG patients.
- Electrophysiological testing
- Repetitive nerve stimulation (RNS) at slow rate should reveal a decrement. In this procedure, electric shocks are delivered to the nerve, and action potentials are recorded from surface electrodes over the muscle. Improvement of a baseline decrement after brief exercise (post-exercise facilitation) and enhanced decrement at 2 to 3 minutes post-exercise (post-exercise exhaustion) are typical electrodiagnostic features.
- Single-fibre EMG (SFEMG) is a measure of neuromuscular junction (NMJ) transmission between 2 or more adjacent muscle fibres innervated by the same motor axon. SFEMG may show an increased variability in motor latencies (jitter) or complete failure of NMJ transmission (block) in muscle fibres.
- CT chest
- Computed tomography (CT) scan of the chest should be performed in all newly diagnosed patients to detect thymoma (which occurs in about 15% of patients with MG) or thymic hyperplasia (which occurs in 75% of MG patients).
- Tensilon test
- Edrophonium is an acetylcholinesterase inhibitor with a very short half-life. It can be used to test the clinical response to an increase in acetylcholine levels. Test performance requires some objective measurement of weakness (e.g. ptosis, ophthalmoparesis, or forced vital capacity). Clear improvement following edrophonium strongly supports a diagnosis of myasthenia gravis, but lack of a response doesn't exclude the diagnosis.
Management
- Mild disease
- Patients with mild and occasional symptoms require no treatment.
- Patients with frequent symptoms should be treated with a cholinesterase inhibitor. First-line treatment includes pyridostigmine, a cholinesterase inhibitor, for temporary relief of symptoms.
- Corticosteroids are used in patients with ocular myasthenia gravis (MG) and those with mild disease who fail pyridostigmine monotherapy. For those requiring high doses of corticosteroids, other immunosuppressants should be considered, particularly if there are comorbidities that are problematic for high-dose corticosteroids.
- Moderate disease
- Some patients with moderate disease can be managed with pyridostigmine alone, some with immunosuppressants alone, and some with a combination. Several options are available and include low-dose corticosteroids, azathioprine, mycophenolate, ciclosporin, and tacrolimus, or a combination of corticosteroids and one of these agents.
- In addition, thymectomy may be performed in patients with moderate or severe disease with or without thymoma.
- Plasma exchange and intravenous immunoglobulin (IVIG) may also prove useful in some patients when combined with corticosteroids or other immunosuppressants and both can be done as an outpatient intermittently.
- Severe disease (including those with myasthenic crisis (MC), those unable to swallow and those with impaired respiration)
- MC is a complication of MG and a medical emergency, defined as an exacerbation requiring mechanical ventilation. Risk factors for crisis include non-compliance with medications, addition of medications that can worsen neuromuscular transmission (including high-dose corticosteroids), surgery, trauma, and concomitant infections, particularly respiratory infections.
- Serial measurements of forced vital capacity (FVC) and negative inspiratory force (NIF) are taken.
- Indication for mechanical ventilation includes forced vital capacity (FVC) 15 mL/kg or less (normal ≥60 mL/kg) and negative inspiratory force (NIF) 20 cm H2O or less (normal ≥70 cm H2O).
- Physicians should not wait for abnormal arterial blood gas (ABG) as it occurs late in the course after clinical decompensation.
- Initial therapy consists of optimised ventilatory settings to provide rest to respiratory muscles, removal of provoking factor(s) for the crisis, and acute therapy for the recovery of transmission across neuromuscular junction with either immunoglobulin (IVIG) or plasma exchange. High-dose corticosteroids may be initiated concurrently with IVIG or plasma exchange, as they reach their maximal effectiveness at the time that the effects of IVIG and plasma exchange are waning. Supportive care includes deep venous thrombosis prophylaxis and ulcer prophylaxis, adequate nutrition and hydration, and avoidance of infections and drugs that may worsen myasthenia symptoms.
Report A Problem
Is there something wrong with this question? Let us know and we’ll fix it as soon as possible.
Loading Form...
- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
