Myasthenia Gravis — Written Clinical Reasoning

SAQ 1 — Acute Myasthenic Crisis Management (15 marks, 20 minutes)

Prompt: Outline your immediate and acute management of this patient, addressing airway and ventilatory support, rapid immunotherapy, treatment of the precipitant, and avoidance of drugs that worsen myasthenia gravis. Justify each step with reference to physiological thresholds and guideline recommendations. [1]

Model Answer

Recognition and severity (2 marks): [1]

This patient is in myasthenic crisis with established ventilatory failure — MGFA Class V (the operational definition is the need for intubation, which she is about to require). The diagnosis is supported by the worsening bulbar and respiratory weakness on a background of known MG, a precipitating respiratory infection, a forced vital capacity of 14 mL/kg, a negative inspiratory force of 26 cmH2O, and hypercapnia (pCO2 56 mmHg) with a respiratory acidosis (pH 7.31). Hypercapnia is a late and ominous sign indicating respiratory muscle fatigue; the patient should have been escalated before this point [1].

Airway and ventilatory support (4 marks): [1]

1. The thresholds for intubation in neuromuscular respiratory failure are a forced vital capacity below 15 to 20 mL/kg or a negative inspiratory force below 30 cmH2O (the 20/30/30 rule). She has breached both (FVC 14 mL/kg, NIF 26 cmH2O) and is already hypercapnic — she requires immediate intubation and mechanical ventilation.
2. Non-invasive ventilation (BiPAP) is not appropriate here because she has excessive secretions and weak bulbar function that prevent airway protection, and she is already in type 2 respiratory failure. BiPAP may buy time in a cooperative, secretion-free patient but is contraindicated when the airway cannot be protected.
3. Rapid-sequence intubation is required. Succinylcholine and non-depolarising neuromuscular blockers must be used with extreme caution — patients with MG are exquisitely sensitive to neuromuscular blocking agents and may have prolonged paralysis. A reduced dose of a non-depolarising agent, with the team prepared for prolonged ventilation, is the approach.
4. Admit to ICU. Once intubated, continue ventilatory support and begin the search for and treatment of the precipitant. [1]

Rapid immunotherapy — IVIG or plasma exchange (4 marks): [1]

Both intravenous immunoglobulin and plasma exchange are effective for rapid short-term immunotherapy in myasthenic crisis; neither has been shown clearly superior in head-to-head trials [1][2].

• Plasma exchange (plasmapheresis): 5 exchanges over 1 to 2 weeks (typically 1.5 plasma volumes per exchange). Onset is rapid (improvement within days), and it is preferred in severe crisis and in MuSK-MG. It requires central venous access and carries risks of hypotension, line infection, bleeding from citrate, and haemodynamic instability.
• IVIG: 0.4 g/kg/day for 5 days (total 2 g/kg). Easier to administer, fewer line complications, but slower onset (1 to 2 weeks). Adverse effects include headache, aseptic meningitis, thromboembolism, volume overload, and acute kidney injury. [1]

For this patient with hypercapnic crisis, plasma exchange is reasonable given the need for the fastest possible response; if vascular access is problematic or there are contraindications, IVIG is an acceptable alternative. [1]

Treatment of the precipitant and avoidance of exacerbating drugs (3 marks): [1]

The precipitant is a respiratory infection with right basal consolidation. Treat with antibiotics — but choose agents that do not worsen MG: avoid aminoglycosides (gentamicin, tobramycin), fluoroquinolones, and macrolides. A beta-lactam (for example, ceftriaxone or amoxicillin-clavulanate guided by local guidelines and cultures) is preferred. Treat secretion clearance aggressively with physiotherapy and suction once intubated. [1]

Avoid drugs that worsen MG throughout the admission: no intravenous magnesium (it inhibits ACh release and can precipitate catastrophic weakness), no beta-blockers, no calcium channel blockers where possible, and no fluoroquinolones. Review her full medication list for interactions. [1]

Ongoing care and prevention of recurrence (2 marks): [1]

Continue her baseline pyridostigmine cautiously once the airway is secured (intravenous pyridostigmine at 1/30th of the oral dose if she is nil by mouth), and maintain her prednisolone. After the acute episode, optimise long-term immunosuppression with a steroid-sparing agent to reduce the chance of recurrence, and consider biological therapy (rituximab or eculizumab) if she is refractory. Vaccinate against influenza, pneumococcus and COVID-19 once stable. Provide a written action plan and medical alert for future crises. [1]

SAQ 2 — AChR-Positive MG with Thymoma: Integrated Management (10 marks, 15 minutes)

Prompt: A 36-year-old man presents with a 6-month history of fatigable diplopia, dysarthria and proximal limb weakness. Anti-acetylcholine receptor antibodies are positive. CT thorax demonstrates a 4 cm anterior mediastinal mass with features of a thymoma, without radiological evidence of invasion. His MGFA clinical class is IIIa (moderate limb-predominant weakness). He works as a carpenter and hopes to start a family with his partner in the next 2 years. Outline your integrated management plan. [1]

Model Answer

Problem list (2 marks): [1]

1. AChR-antibody-positive generalized MG, MGFA Class IIIa — needs disease control
2. Thymoma (4 cm, anterior mediastinum) — requires surgical resection
3. Occupational and reproductive considerations — carpentry (driving, safety), planned fatherhood
4. Risk of future myasthenic crisis and need for patient education and an action plan [1]

Symptomatic and immunosuppressive therapy (3 marks): [1]

Start pyridostigmine 30 to 60 mg four to six times daily for symptomatic control. Because he has generalized disease (Class IIIa), add immunosuppression: initiate prednisolone at a low dose (10 to 20 mg daily) and titrate up gradually over 2 to 4 weeks toward 0.75 to 1 mg/kg/day, because high-dose steroids can precipitate early worsening of MG [1]. Introduce a steroid-sparing agent early — azathioprine (after confirming TPMT activity) 1 to 3 mg/kg/day — so prednisolone can be tapered to the lowest effective dose, minimising steroid toxicity (osteoporosis, diabetes, hypertension, infertility in the longer term). The aim is MGFA post-intervention status of minimal manifestations or better.

Thymectomy (3 marks): [1]

The thymoma is an absolute indication for thymectomy — it may be malignant and must be resected en bloc with the surrounding thymic tissue for diagnosis, staging and therapy [1]. An extended transsternal thymectomy is the standard approach. He should be referred to a thoracic surgeon. Optimise his MG control pre-operatively — he may need a short course of IVIG or plasma exchange before surgery if his weakness is significant, to reduce peri-operative respiratory complications. The MGTX trial showed that even in non-thymomatous AChR-positive generalized MG, thymectomy plus prednisone was superior to prednisone alone (lower QMG score and lower prednisone dose over 3 years) [3]; here, with a thymoma, the indication is unequivocal. Thymectomy is not indicated in MuSK-MG, but this patient is AChR-positive.

Reproductive, occupational and preventive counselling (2 marks): [1]

Fatherhood is achievable; azathioprine is used in men without the teratogenicity concerns that apply in pregnancy, though discuss timing with his specialist. Discuss driving restrictions during any worsening or medication changes. Provide a written list of drugs to avoid (aminoglycosides, fluoroquinolones, magnesium, beta-blockers, immune checkpoint inhibitors), a medical alert, and a crisis action plan. Vaccinate against influenza, pneumococcus and COVID-19 once stable. Arrange long-term follow-up in a neurology-neuromuscular clinic with monitoring of MGFA post-intervention status and drug toxicity [2][4].