12th August 2024

Myasthenia gravis (MG)

Overview of MG

The most common disorder of the neuromuscular junction (NMJ) (incidence 7-23 per million), myasthenia gravis has a bimodal age distribution with peaks at 20-30 years, predominantly in females, and 60-80 years, predominantly in males.

It is caused by antibody-mediated disruption of signalling at the acetylcholine receptor (AChR), with 80-90% of patients having direct IgG antibodies to the AChR. Other antibodies that may be identified are anti-muscle-specific receptor tyrosine kinase (MuSK) and, more rarely, LRP4 antibodies. In some cases however, no antibodies are identified. Those with generalised disease are more likely to have identifiable antibodies than those with purely ocular disease, only half of whom are antibody positive.

Clinical features of MG

Patients most commonly present with ocular symptoms including ptosis or diplopia, along with muscle weakness. Symptoms typically worsen throughout the day and show fatigue. Fifteen percent present with bulbar symptoms such as difficulty chewing and weakness or fatigability of the voice. Fewer than 5% present with limb weakness alone.

Common drugs that may exacerbate MG include the following:

Abbreviations: PD-1 (Programmed cell death protein 1)

Management of MG

The mainstay of MG treatment are the acetylcholinesterase inhibitors, such as pyridostigmine. Many patients will also require additional treatments such as glucocorticoids or steroid-sparing agents (azathioprine or mycophenolate). Thymectomy is another important modality in management and may be considered in those with or without thymoma in certain cases.

Side effects of acetylcholinesterase inhibitors are largely cholinergic and can be managed by dose reduction, taking doses with food, or with the addition of propantheline or another anticholinergic.

Myasthenic crisis is a medical emergency characterised by life-threatening compromise of respiratory muscle function. All patients should be admitted and closely monitored, with vital capacity (VC) the most important modality. For those with falling VC or respiratory distress, intubation should be urgently considered. Plasma exchange and IVIG have similar efficacy in the acute treatment of MG so are both used, often in combination with steroids.