What is the natural progression of Myasthenia Gravis (MG)?

From the Guidelines

Myasthenia gravis typically progresses from localized symptoms to more generalized weakness if left untreated, with 50% of patients presenting with ocular symptoms only and 50-80% of these patients developing generalized systemic myasthenia within a few years 1. The disease often begins with ocular symptoms like ptosis (drooping eyelids) and diplopia (double vision) in about 50% of patients.

• Within a few years, approximately 50-80% of patients who initially present with ocular symptoms will develop generalized weakness affecting limb, bulbar, and respiratory muscles 1.
• The progression is usually gradual but can be punctuated by exacerbations triggered by infections, stress, surgery, or certain medications.
• Disease severity often peaks within the first few years after onset.
• About 15-20% of patients will experience at least one myasthenic crisis during their lifetime, characterized by severe respiratory muscle weakness requiring ventilatory support. The natural course includes periods of remission and exacerbation, with symptoms typically worsening with fatigue and improving with rest.
• Without treatment, most patients experience progressive disability, but with modern immunosuppressive therapies and symptomatic treatments like pyridostigmine, the disease can be well-controlled in most patients 1.
• The mortality rate has dramatically decreased from 30% historically to less than 5% today with proper management.
• Elderly patients and those with thymoma-associated myasthenia gravis may have a more severe disease course requiring more aggressive treatment. The most recent and highest quality study 1 suggests that the natural progression of myasthenia gravis is a gradual process, with most patients experiencing progressive disability if left untreated, but with modern treatments, the disease can be well-controlled in most patients.

From the Research

Natural Progression of Myasthenia Gravis

The natural progression of myasthenia gravis (MG) is a complex process that can vary significantly from patient to patient.

• MG is an autoimmune disease caused by antibodies against the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), or other AChR-related proteins in the postsynaptic muscle membrane 2.
• The disease is characterized by localized or general muscle weakness, which is induced by the antibodies 2.
• Patients are grouped according to the presence of antibodies, symptoms, age at onset, and thymus pathology 2.

Treatment and Management

Treatment of MG should be ambitious and aim for clinical remission or only mild symptoms with near-normal function and quality of life 2.

• Treatment options include:
  • Symptomatic treatment using acetylcholinesterase inhibitors, such as pyridostigmine 3
  • Thymectomy 4, 5
  • Immunotherapy, including corticosteroids, azathioprine, and other immunosuppressive agents 4, 5
  • Intravenous immunoglobulin and plasma exchange for disease exacerbations 6, 2
• Active physical training should be encouraged to improve quality of life and manage symptoms 2.

Disease Course and Prognosis

The natural course of MG has changed significantly over the past century, from a disease with poor prognosis and high mortality rate to a treatable condition with a large proportion of patients attaining good disease control 5.

• With current treatment options, many patients can achieve significant improvement in symptoms and quality of life 4, 5, 2.
• However, comorbidity is frequent, particularly in elderly patients, and requires careful management 2.