Myasthenia Gravis Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr Tan is a 41-year-old engineer with a 14-month history of acetylcholine-receptor-antibody-positive generalized myasthenia gravis. He presents for review two weeks after a myasthenic crisis requiring three days of intensive care and plasma exchange, triggered by a respiratory infection. His CT thorax at diagnosis demonstrated a 3-centimetre anterior mediastinal mass reported as a thymoma. He is currently on pyridostigmine 90 milligrams five times daily and prednisolone 40 milligrams daily, and over the past year he has developed steroid-induced osteoporosis with a vertebral wedge fracture. ^[1]

His main problems are:

1. AChR-positive generalized MG, recently in crisis — disease control inadequate on current therapy
2. Thymoma on CT thorax — requires thymectomy
3. Steroid-induced osteoporosis with a vertebral wedge fracture — on prednisolone 40 milligrams daily
4. Risk of recurrent myasthenic crisis — precipitant (infection) and exacerbating drugs to address
5. Occupational and driving implications — he has been off work for three months" ^[1]

Examiner probing questions and model answers

Q1: "What is the MGFA clinical classification, and where does this patient sit?" ^[1]

"The MGFA clinical classification, established in 2000, stratifies myasthenia gravis severity from Class I to Class V ^[1]. Class I is any ocular weakness only. Class II is mild weakness affecting other than ocular muscles, subdivided into IIa limb-predominant and IIb bulbar or respiratory predominant. Class III is moderate weakness, again IIIa limb and IIIb bulbar or respiratory. Class IV is severe weakness, IVa limb and IVb bulbar or respiratory. Class V is defined by the need for intubation, with or without mechanical ventilation — the operational definition of myasthenic crisis. This patient, who required intubation during his recent crisis, was at Class V at that point; he is now recovering and probably sits at Class III to IV. The classification is the common language of MG trials and clinic letters and guides the intensity of treatment."

Q2: "Why is this patient a candidate for thymectomy, and what is the evidence?" ^[1]

"He has two indications. First, 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 ^[3]. About 10 to 15 per cent of MG patients have a thymoma, and all of them undergo thymectomy. Second, even setting the thymoma aside, he is young — 41 — with AChR-positive generalized MG that is poorly controlled and recently culminated in crisis. The MGTX trial, published in the New England Journal of Medicine in 2016, randomised 126 patients with non-thymomatous AChR-positive generalized MG to extended transsternal thymectomy plus prednisone versus prednisone alone, and showed that the thymectomy group had a lower time-weighted average Quantitative Myasthenia Gravis score, required a lower average prednisone dose, and needed fewer azathioprine courses and hospitalisations over three years ^[2]. So thymectomy in this patient is both mandatory (thymoma) and beneficial (disease control and steroid reduction). I would refer him to a thoracic surgeon for an extended transsternal thymectomy once his MG is stabilised. Critically, this does not apply to MuSK-positive MG, where thymectomy is not beneficial — the thymus is not part of the pathology in MuSK disease."

Q3: "How would you optimise his immunosuppression to reduce the chance of another crisis?" ^[1]

"His disease is inadequately controlled — he has had a crisis on pyridostigmine and prednisolone alone. My plan is to add a steroid-sparing immunosuppressant so that I can taper the prednisolone and reduce both his risk of recurrence and his steroid toxicity. I would check TPMT activity and start azathioprine, titrating to 1 to 3 milligrams per kilogram per day, accepting that it takes 6 to 12 months to reach full effect. Mycophenolate mofetil is an alternative with a slightly faster onset. If he remains refractory or has another crisis despite azathioprine, I would escalate to a biological therapy. Rituximab — anti-CD20 B-cell depletion — is effective in both AChR-positive and MuSK-positive MG, with a particularly strong response in MuSK disease. Eculizumab, a monoclonal antibody against complement C5, is approved for refractory AChR-positive MG on the basis of the REGAIN trial ^[4], and its open-label extension showed that 57 per cent of patients achieved minimal-manifestation status by 130 weeks. Before eculizumab, he must be vaccinated against meningococcus at least two weeks in advance. The newer FcRn inhibitors such as efgartigimod deplete IgG including pathogenic antibodies and offer a rapid-onset option. The aim throughout is MGFA minimal-manifestations status on the lowest possible drug burden."

Q4: "He fractured a vertebra on prednisolone. How will you manage his bone health?" ^[1]

"Steroid-induced osteoporosis is a predictable and preventable complication. He already has a fragility fracture, which puts him in a high-risk category. My plan is: first, reduce the steroid exposure as fast as disease control allows, by adding the steroid-sparing agent and tapering prednisolone. Second, initiate bone-protective therapy — a bisphosphonate such as alendronate 70 milligrams weekly with calcium and vitamin D supplementation, having checked his bone densitometry, renal function, calcium and 25-hydroxyvitamin D level. A denosumab or zoledronate is an alternative if oral bisphosphonate is not tolerated. Third, screen for and manage other steroid complications — monitor fasting glucose and blood pressure, consider gastric protection, and counsel on weight, diet and smoking. I would involve a bone-health or endocrine service for the fragility fracture. The principle is that the complications of treatment are themselves a reason to minimise steroids — every effort to achieve disease control on steroid-sparing therapy protects his bones as well as his myasthenia." ^[1]

Q5: "What advice would you give him about future crises?" ^[1]

"I would give him a written action plan and a medical alert. The key messages are: recognise the early warning signs of a crisis — increasing breathlessness, a weak cough, slurred or fading speech, difficulty clearing secretions, and difficulty chewing — and seek emergency care early rather than waiting. He should carry a list of drugs to avoid: aminoglycosides such as gentamicin, fluoroquinolones, macrolides, beta-blockers, calcium channel blockers, magnesium, and immune checkpoint inhibitors. He should be up to date with influenza, pneumococcal and COVID-19 vaccination to reduce infectious precipitants. He should not stop his myasthenia medications abruptly. And he should tell any doctor, dentist or anaesthetist that he has myasthenia gravis before any procedure or prescription. I would document this conversation and give him a written summary." ^[1]