Pathology/Pathogenesis

• MG is mediated by antibodies (IgG) directed against the acetylcholine receptor (AchR) found on the postsynaptic membrane at the NMJ.
• This decreases the number of functional AchRs resulting in impaired neuromuscular transmission.

History

• Symptoms may have been present for months or years.
• Cardinal feature is variable weakness and fatigue of voluntary muscles (fatiguability) with diurnal variation, which may be evident with symptoms worsening towards the end of the day.
• Patients may report episodic double vision and droopy eyelids (ptosis) with possible weakness of eye closure, facial weakness, problems with speech and swallowing, breathing difficulties, neck weakness and proximal limb weakness (relative sparing of lower limbs).
• Patients can present with sudden myasthenic crisis.

Examination

• Usually tone, reflexes and sensation are normal.
• Weakness may be evident or power may be normal in which case clinical tests for fatiguability should be performed.

Eyes: Ask the patient to sustain upgaze for 30 s—ptosis or diplopia may be provoked.

Speech (bulbar): For example, ask the patient to count up to 50.

• Arms (proximal muscle): Ask the patient to perform repeated shoulder abduction (20–30 times) and assess shoulder abduction strength before and after.
• Examination may demonstrate ptosis, diplopia and the characteristic myasthenic snarl on smiling.
• Muscle groups involved in decreasing order of frequency are extraocular, bulbar, face, neck, proximal limbs and trunk.

Investigations

• Blood tests: AchR antibodies are present (sero-positive) in up to 90% of patients with generalised MG.
• Neurophysiology:

Decrement of compound muscle action potentials (cMAPs) on repetitive stimulation (proximal muscle).

Presence of increased jitter on single-fibre EMG.