Myasthenia Gravis (MG) is a chronic autoimmune disorder affecting the neuromuscular junction. Autoantibodies—most commonly against the acetylcholine receptor (AChR), less frequently MuSK, LRP4, or others—disrupt communication between nerves and muscles, leading to muscle weakness that increases with activity and improves with rest.
Causes & Pathophysiology
MG arises when the immune system generates antibodies that bind to key proteins at the neuromuscular junction. Most often, this targets AChR; in other cases, the antibodies affect MuSK, LRP4, or agrin. These antibodies impair nerve signal transmission, causing fatigue and weakness.click here
Epidemiology
MG is more common in women under 40 and men over 60, and affects approximately 15 to 200 per million people globally. Ocular symptoms often precede generalized weakness, with respiratory crises occurring in 15–20% of patients.
Symptoms & Clinical Presentation
Key signs include drooping eyelids (ptosis), double vision (diplopia), difficulty speaking, swallowing, walking, and shortness of breath. These symptoms typically worsen during the day or after exertion.
Diagnosis
Diagnosis combines clinical evaluation with:Myasthenia Gravis
-
Blood tests for antibodies (AChR, MuSK, LRP4)
-
Electrophysiological tests like repetitive nerve stimulation or single-fiber EMG
-
Chest CT to assess thymus abnormalities or thymoma
Treatment & Management
1. Symptomatic Treatment
-
Acetylcholinesterase inhibitors (e.g., pyridostigmine) boost neuromuscular transmission
2. Immunosuppressive Therapies
-
First-line: Corticosteroids (prednisone/prednisolone) and azathioprine
-
Additional agents may include tacrolimus, mycophenolate mofetil, or cyclosporine
3. Emergency & Rescue Therapies
-
In crises: Intravenous immunoglobulin (IVIg) or plasmapheresis provide rapid relief
4. Thymectomy
-
Recommended for AChR-positive generalized MG, especially with thymoma. Studies support its effectiveness in reducing symptoms and steroid needs.
5. New & Emerging Treatments
-
Eculizumab, Ravulizumab – complement inhibitors
-
Efgartigimod (Vyvgart) – an FcRn blocker promoting antibody clearance
-
Zilucoplan, Rozanolixizumab (Rystiggo) – FcRn/complement pathway targets
-
Rituximab – especially for MuSK-positive or refractory casesNCBIPMC
-
Gefurulimab – a promising new C5 inhibitor showing positive results in late-stage trials, potentially administered weekly subcutaneously.
6. Future Prospects
-
CAR T–based therapies targeting B cells or MuSK are experimental but show early promise.PMC
Prognosis
With modern treatments, most MG patients enjoy a normal lifespan with good quality of life. Fatality rates have declined from ~70% in the early 1900s to around 3–5% today. Myasthenic crises remain a serious risk in the first two years of disease.
Conclusion
MG is a complex but increasingly manageable autoimmune disorder. Thanks to evolving therapeutic options—from symptomatic medications to advanced biologics—many patients experience notable symptom control and improved daily functioning. Innovations like Vyvgart and gefurulimab, alongside future CAR T therapies, promise even greater hope ahead.
Frequently Asked Questions (FAQ)
Q1: Can Myasthenia Gravis be cured?
Currently, there’s no cure. However, treatments such as thymectomy, immunosuppressants, and biologics can achieve long-term remission or substantial symptom improvement.
Q2: What is a myasthenic crisis?
A sudden and severe exacerbation causing respiratory failure, often requiring mechanical ventilation, and treated emergently with IVIg or plasmapheresis.
Q3: Are there medications that can worsen MG?
Yes. Certain antibiotics (e.g. fluoroquinolones), beta-blockers, and other medications may exacerbate symptoms. Always consult your doctor before starting new medications.
Q4: What advantage does Vyvgart offer?
Vyvgart (efgartigimod) is a first-in-class FcRn blocker that speeds up the clearance of pathogenic IgG antibodies—including those against AChR—offering a novel, targeted mechanism beyond traditional immunosuppression.