Myasthenia Gravis ✅

🔗 Related Subjects: | 💪 Myasthenia Gravis | ⚡ Lambert-Eaton syndrome (LEMS) |Motor Neuron Disease (MND-ALS) |Miller-Fisher syndrome |Guillain Barre Syndrome |Multifocal Motor Neuropathy with Conduction block |Multiple Sclerosis (MS) Demyelination

😴 Myasthenia gravis (MG) causes fluctuating, fatigable weakness of ocular, bulbar, respiratory, neck and limb muscles. 🧠 Sensation and reflexes are usually normal. Symptoms often worsen with repeated use and improve with rest.

🚑 Myasthenic Crisis — Practical Treatment

• Admit to ICU/HDU if respiratory, bulbar or rapidly progressive weakness.
• Monitor FVC, respiratory effort, cough strength, swallowing and secretion control.
• Treat infection, aspiration, electrolyte disturbance and medication triggers.
• Use IVIg or plasma exchange urgently for significant crisis.
• Consider temporarily withholding pyridostigmine if intubated or if secretions are problematic; restart with neurology advice.
• Avoid sedatives, magnesium and neuromuscular blockers unless essential and specialist-supervised.

📖 About

• 🧬 MG is an autoimmune disorder of the neuromuscular junction.
• Autoantibodies reduce effective neuromuscular transmission, most commonly by targeting the acetylcholine receptor.
• The hallmark is fatigable weakness: repeated activity worsens power, while rest may improve it.
• Weakness commonly affects ocular, facial, bulbar, neck flexor, proximal limb and respiratory muscles.
• Pupils, sensation and tendon reflexes are usually normal.

🧪 Aetiology / Antibodies

🧨 Pathophysiology

• Anti-AChR antibodies cause complement-mediated damage to the postsynaptic membrane.
• There are fewer functioning acetylcholine receptors and simplified postsynaptic folds.
• The “safety margin” for neuromuscular transmission falls.
• With repeated stimulation, acetylcholine release normally declines slightly; in MG this produces transmission failure and fatigable weakness.

🔗 Clinical Associations

• 🦋 Autoimmune disease: thyroid disease, rheumatoid arthritis, SLE, Sjögren’s disease.
• 🩸 Pernicious anaemia.
• 🧬 Thymic hyperplasia or thymoma.
• 🧩 Other autoimmune conditions may coexist, but thyroid disease is especially important to check.

🧩 Clinical Features

🧾 Differential Diagnosis

• ⚡ Lambert-Eaton myasthenic syndrome — proximal weakness, autonomic symptoms, reflexes improve after exercise; associated with small-cell lung cancer.
• ☠️ Botulism — pupils often affected, autonomic features, descending paralysis.
• 💊 Drug-induced worsening — aminoglycosides, fluoroquinolones, magnesium, beta-blockers and others.
• 🧿 Chronic progressive external ophthalmoplegia.
• 🧠 Brainstem stroke, multiple sclerosis, motor neurone disease or mitochondrial disease depending on presentation.
• 🦋 Thyroid eye disease if ocular symptoms predominate.

🔎 Investigations

• 🧪 Anti-AChR antibody first-line.
• 🧪 Anti-MuSK antibody if AChR negative and suspicion remains.
• 🧪 Consider LRP4 or specialist antibody testing if AChR/MuSK negative.
• ⚡ Neurophysiology: repetitive nerve stimulation shows decrement; single-fibre EMG is highly sensitive.
• 🧊 Ice-pack test may support ocular MG with ptosis.
• 🫁 Respiratory function: FVC and negative inspiratory force in suspected crisis.
• 🫀 CT or MRI chest to assess thymus / thymoma once MG is confirmed or strongly suspected.
• 🦋 TFTs to check for thyroid disease.
• 🚫 Edrophonium/Tensilon test is historical and not routinely used in modern UK practice.

⚡ Neurophysiology in Myasthenia Gravis

📌 Learning tip: In MG, repetitive nerve stimulation shows decrement; single-fibre EMG shows increased jitter. SFEMG is very sensitive, but not perfectly specific, so results must be interpreted with the clinical picture and antibody testing.

❓ Key Diagnostic Questions

• Is this ocular MG or generalised MG?
• Are there bulbar or respiratory symptoms suggesting impending crisis?
• Is the patient AChR-positive, MuSK-positive, LRP4-positive or seronegative?
• Is there thymoma or thymic hyperplasia?
• Could this be Lambert-Eaton, botulism, thyroid eye disease or a brainstem disorder?
• Is a medication or infection worsening the weakness?

🚫 Drugs That May Worsen MG

🛠️ Management

🚨 Myasthenic Crisis — Initial Management

💊 Medications in MG

📚 References

• Association of British Neurologists: autoimmune myasthenia gravis management guidelines, 2025 update
• NICE TA1155: Rozanolixizumab for treating antibody-positive generalised myasthenia gravis
• International Consensus Guidance for Management of Myasthenia Gravis, 2021 update
• Myasthenia Gravis Foundation of America: cautionary drugs

Cases - Myasthenia Gravis (MG)

• Case 1 - Ocular Myasthenia 👁️: A 28-year-old woman reports drooping of her right eyelid that worsens by evening and double vision after prolonged reading. Examination shows fatigable ptosis and ophthalmoparesis, with normal pupils, sensation and reflexes.
  Diagnosis: Ocular myasthenia gravis.
  Management: Anti-AChR antibodies, consider MuSK if negative, neurophysiology if needed, pyridostigmine for symptoms, and monitor for progression to generalised MG.
• Case 2 - Generalised MG with Bulbar Symptoms 🗣️: A 45-year-old man presents with fluctuating limb weakness, nasal speech and difficulty swallowing, especially late in the day. Examination shows fatigable proximal weakness, weak neck flexion and reduced palatal movement.
  Diagnosis: Generalised MG with bulbar involvement.
  Management: Neurology review, pyridostigmine, immunosuppression, swallowing assessment, screen for thymoma with CT chest and safety-net for respiratory deterioration.
• Case 3 - Myasthenic Crisis in ICU ⚠️: A 52-year-old woman with known MG develops pneumonia and acute worsening weakness, now with difficulty speaking and shallow breathing. Examination shows weak cough and reduced vital capacity.
  Diagnosis: Myasthenic crisis precipitated by infection.
  Management: ICU/anaesthetic review, ventilatory support if required, IVIg or plasma exchange, treat pneumonia, avoid MG-worsening drugs and optimise long-term immunotherapy.

Teaching Commentary 🧠

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction, usually due to antibodies against AChR or MuSK. The clinical hallmark is fluctuating, fatigable weakness, especially ocular, bulbar, neck, proximal limb and respiratory weakness, with normal sensation and reflexes. AChR antibodies are the first-line test, but negative antibodies do not exclude MG; MuSK, LRP4 and neurophysiology may be needed. The dangerous presentation is myasthenic crisis, where bulbar and respiratory weakness can progress to ventilatory failure even before oxygen saturations fall. Treatment includes pyridostigmine for symptoms, immunotherapy for disease control, IVIg or plasma exchange for crisis, and thymectomy for thymoma or selected AChR-positive generalised disease.