Overview

Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular disorder where antibodies target acetylcholine receptors (AChR) or MuSK proteins at the post-synaptic membrane, impairing neuromuscular transmission and causing muscle weakness

Myasthenia Gravis (MG) is a rare autoimmune disorder marked by fluctuating muscle weakness that worsens with activity and improves with rest, commonly affecting the ocular (ptosis, diplopia), bulbar (dysphagia, dysarthria), and proximal limb muscles; severe cases may involve respiratory muscles, leading to myasthenic crisis. It is most prevalent in women under 40 and men over 60, with a strong association with thymic hyperplasia in about 70% of cases. Early diagnosis and treatment—such as pyridostigmine, immunosuppressants, and thymectomy—are crucial to prevent complications and improve outcomes.

Aetiology and Risk Factors

The specific aetiology of MG remains largely unclear, however some genotypes have been shown to increase the risk. These include human leukocyte antigen complex (HLA) and single nucleotide polymorphisms (SNP’s).  The presence of autoimmune diseases in family members is thought to also be a risk factor.¹

The biggest associated factor for MG is a dysregulated thymus. MG is associated with thymic hyperplasia in 70% of pateints. This is because the thymus contains a small number of “myoid” cells, which are the only known cells outside of muscle to express AChR on their surface.²

Pathophysiology

MG has two possible mechanisms that target two different antigens:

1. In MG associated with acetylcholine receptor (AChR) antibodies, the immune system attacks these receptors, resulting in dysfunction and destruction of the neuromuscular junction at the post-synaptic membrane by blocking the binding of Ach to AChR. This pathologic mechanism is present in 80-90% of MG patients.³
2. In MG associated with muscle-specific tyrosine kinase (MuSK), antibodies attack this protein which plays a role in anchoring AChR at the post-synaptic membrane. This is less common in patients with MG.⁴ 

Clinical Manifestations 

The hallmark feature of MG is skeletal muscle weakness and corresponding muscle fatigue, which worsens with exercise and is relieved upon rest. Patients often present with complaints of specific muyscle weakness and not necessarily generlised muscle fatigue. 

The muscle weakness can occur in ANY muscle, however more common thatn not it affects the ocular muscles first (in two thirds of patients) and bulbar muscle function in comparison to other groups (neck, limbs and respiratory muscles):

• Ocular function: Presents typically as ptosis (drooping of the eyelid) or diplopia (double vision)⁶
  • Note: The “ice pack” test is a part of the neurological exam that is based on the principle that neuromuscular transmission improves at lower muscle temperatures, therefore improving ptosis in MG when the eyelids are cooled. 

Figure 2: Ptosis of the left upper eyelid in MG⁷

• Bulbar function: Relates to oropharyngeal or facial muscle weakness and may present with dysphagia, dysarthria or the inability to make certain facial expressions. 
• Limb function: Limb weakness is common in patients with generalised MG but doesn’t typically show upon first presentation. The pattern of limb weakness is commonly proximal, with arms > legs⁸ 
• Respiratory function: Patients typically develop respiratory muscle weakness later down the line in MG and is the most severe manifestation, leading to respiratory failure, also termed as “myasthenic crisis”.