Myasthenia Gravis

Introduction
o Myasthenia gravis (MG) is a chronic autoimmune disease of the neuromuscular junction in skeletal muscle.
o This is commonly due to circulating antibodies to acetycholine receptor protein (anti-AChR antibodies).
o Other antibodies such as muscle-specific receptor tyrosine kinase (anti-MuSK antibodies) can also be present.
o Relatively rare condition with an estimated worldwide prevalence of 100-200 cases per million.
o MG can present in all age groups
o It is more common in women (normally present at childbearing age)
Presentation
o Muscle fatigability – worsen with activity and improves on rest.
o Ptosis – Cooling of eyelid with ice pack improves ptosis in more than 95% of patients.
o Diplopia – commonly occurs
o Dysphagia – after prolonged chewing/eating
o Dysarthria – characteristic nasal speech
o Facial paresis – characteristic flattened or transverse smile
o Proximal limb weakness – difficulty getting out of chairs or climbing stairs
o Shortness of breath – if severe enough that the patient needs mechanical ventilation then the patient is said to be in MG crisis.
History
o Family history of autoimmune disorders.
o Family history of MG.
o History of thymus cancer symptoms – cough, chest pain, trouble swallowing, loss of appetite and weight loss.
Examination
o Full neurological examination (same signs seen as presentation).
• Evidence of muscle weakness
• Ptosis
• Laboratory investigations
o Serum anti-acetylcholine receptor (AChR) antibody testing – first line in non-urgent cases.
o Thyroid function tests
o Serum anti-muscle-specific kinase (MuSK) – for all AChR antibody negative patients.
• Radiological investigations
o MRI brain – useful in patients that are seronegative and have negative findings on neurophysiology or symptoms suggestive of ocular myasthenia (structural brain disease).
o Thymus scanning (CT or MRI) – for all patients to exclude thymus cancer.
• Other investigations
o Neurophysiology – useful in seronegative patients. Initial test is repetitive nerve stimulation, if negative consider single-fibre electromyography.
o Edrophonium/Tensilon test
Generalised MG Management
o Pyridostigmine – lowest effective dose
• Initially 30mg q.d.s for 2–4 days.
• Then 60 mg q.d.s for 5 days.
• Then increase to 90 mg four times daily over 1 week if required. If pyridostigmine does not control symptoms within a few weeks, start prednisolone.
• Management of side effects: Propantheline or mebeverine can help cholinergic side effects.
• Withdrawal:
• If asymptomatic following introduction of prednisolone only, withdraw slowly at 30–60 mg per week, until either withdrawn, or use the lowest effective dose.
o Prednisolone
• Start 10mg on alternate days for three doses and increase by 10mg every three doses until symptoms improve.
• Maximum dose is 100mg alternate days or 1.5mg/kg for generalized myasthenia gravis.
• Remission is defined as the absence of symptoms after pyridostigmine withdrawal.
• If not in remission after 3 months of corticosteroid treatment, refer for expert opinion.
o Immunosuppression with azathioprine (maintenance dose 2.5mg/kg) in patients with contraindication to long–term corticosteroid use or unresponsive to corticosteroids.
MG Inpatient Management
o MG patients should be admitted to hospital if there is:
• Significant bulbar symptoms
• Low vital capacity
• Respiratory symptoms
• Progressive deterioration
o Assessment of swallowing by a speech and language therapist is mandatory.
o Regular assessment of vital capacity is required.
o Intravenous (IV) immunoglobulin use for severe bulbar or respiratory symptoms.
• 1-2g/kg is the total dose (given as 0.5g/day for 2 days or 0.4g/day for 5 days).
o Plasma exchange is required if IV immunoglobulin is contraindicated or ineffective.
o Prednisolone (as per outpatient dosing)
MG Intensive care management
o Required to monitor respiratory function.
o For ventilated patients:
• Start prednisolone at 100mg on alternate days.
• Start IV immunoglobulins immediately
• Avoid inappropriate IV magnesium use.
• Consider avoiding pyridostigmine/neostigmine due to increased secretions.
o For non-ventilated patients:
• Initiate prednisolone following standard protocol for general myasthenia gravis.
• Initiate IV immunoglobulin immediately.
• Avoid using pyridostigmine/neostigmine.
Complications
o The timescale complications of MG are variable depending on each individual’s patient’s circumstances.
o Respiratory failure
o Impaired swallowing
o Acute aspiration
o Secondary pneumonia
o Plasma exchange-induced adverse reactions
o IVIG-induced adverse reactions

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