Overview
Myasthenia gravis (MG) is an autoimmune condition affecting the neuromuscular junction characterised by painless fatigable muscle weakness. It is due to autoantibodies against proteins in the neuromuscular junction, usually the acetylcholine receptor (AChR) or the muscle-specific tyrosine kinase (MuSK)
The fatigable muscle weakness is worse with exercise and improves with rest. This is because as activity continues, more AChRs are blocked.
Myasthenic crisis
Myasthenic crisis is a complication of MG that is characterised by impaired respiratory muscle function leading to respiratory failure. It requires intubation and ventilation.
Associations
- Thymoma:
- 15% of patients with MG have a thymoma
- 30-50% of patients with thymoma have MG
- Other autoimmune diseases
- Family history
Epidemiology
- Peak incidence is in the 20s in women and 50s-60s in men
- Incidence is higher in women than in men
Risk Factors
- Thymoma
- Family history of MG and other autoimmune diseases
Presentation
The main feature that patients have is muscle fatiguability:
- Muscles fatigue readily after exercise
- Extraocular muscle weakness – diplopia
- Ptosis
- Dysphagia – weakness in oropharyngeal muscles
- Patients may have difficulties chewing or swallowing
- Dysarthria – weakness in oropharyngeal muscles
- The patient’s voice may get quieter and quieter as they speak more
- Muscle weakness – usually proximal
- Patients often have difficulty getting out of chairs or walking up the stairs
- There is no muscle wasting and both reflexes and sensation are intact
Differential Diagnoses
Lambert-Eaton myasthenic syndrome
- Proximal limb weakness with diminished reflexes that both improve with exercise
- In MG weakness is worse with exercise, and reflexes are normal
- There may be an associated small cell lung cancer in the majority of patients
- Antibodies against voltage-gated calcium channels are present in most patients
Investigations
- Serum acetylcholine receptor antibodies (anti-AChR):
- Usually positive
- Muscle-specific tyrosine kinase antibodies (anti-MuSK):
- Single-fibre EMG
- CT chest in all new patients:
- To detect thymoma
- Pulmonary function tests – measure FVC in acute myasthenic crisis:
- FVC is low
Management
Acute myasthenic crisis
- 1st-line: intubation and ventilation if FVC reduced + plasmapheresis or IV immunoglobulins (IVIG)
Chronic myasthenia gravis
- 1st-line: long-acting acetylcholinesterase inhibitors (e.g. pyridostigmine)
- Consider corticosteroids/immunosuppressants (azathioprine, tacrolimus, or ciclosporin)
- Consider thymectomy
Aggravating Drugs
The following drugs should be avoided where possible in MG as they can aggravate the condition:
- Antibiotics:
- Aminoglycosides
- Ciprofloxacin
- Macrolides
- Tetracycline
- Clindamycin
- Ampicillin
- Beta-blockers
- Verapamil
- Lithium
Monitoring and Patient Advice
Monitoring
- Patients are generally followed up every 3-12 months and assessed regarding their response to treatment and resolution or emergence of signs and symptoms
Patient Advice
- Patients should avoid exacerbating drugs where possible and let people in their care know about their MG
- Patients should seek help if new symptoms/signs emerge and/or if breathlessness arises
Complications and Prognosis
Complications
- Acute respiratory failure in an acute myasthenic crisis
- Aspiration pneumonia secondary to throat muscle weakness
- Impaired ability to carry out activities of daily living
Prognosis
- Newer treatments have allowed for a better quality of life and reduced mortality rates
- Treatment of MG may fail to treat symptoms and problems secondary to immunosuppression can arise
