Myasthenia gravis and neuromuscular junction disorders: SAQ

This girl presents the classic picture of autoimmune myasthenia gravis: fluctuating, fatigable weakness of the ocular, bulbar, and proximal muscles that worsens through the day and recovers with rest, with preserved reflexes and pupils, and a positive ice pack test. Her falling forced vital capacity and bulbar weakness are the immediate threats, and they drive the decision to escalate to intensive care. The diagnosis is supported by the clinical picture and confirmed by the antibody panel and neurophysiology, and the symptomatic treatment is pyridostigmine with disease-modifying immunotherapy. [1]

Question 1 (10 marks)

Outline your immediate assessment and investigations, and your initial management over the first 24 hours. [1]

I would treat this as probable myasthenia gravis with a threatened crisis and escalate immediately to intensive care, because the forced vital capacity of 17 mL per kilogram is under the 20 mL per kilogram watch threshold and has fallen by more than thirty percent from baseline, and the weak cough signals bulbar weakness and aspiration risk. The decision to intubate is driven by the numbers, not by how the child looks, and a child who is still talking can have a falling vital capacity. I would secure the airway, preoxygenate, and arrange a rapid sequence induction with the intensive care team, choosing sedation that avoids prolonged neuromuscular blockade, and I would place cardiac and respiratory monitoring. [7]

The workup runs in parallel. I would send the acetylcholine receptor antibody as binding, blocking, and modulating assays and the muscle-specific kinase antibody, knowing that the acetylcholine receptor antibody is positive in around eighty percent of generalised disease and a positive result is essentially diagnostic. I would request repetitive nerve stimulation at three hertz, looking for a decremental response of greater than ten percent in a clinically weak muscle, and single-fibre electromyography for its sensitivity if available. I would obtain a contrast computed tomography or magnetic resonance imaging of the chest to exclude a thymoma, which is rare in children but mandates resection, and a thyroid function test to exclude an associated thyroid disease. [11]

I would start symptomatic therapy with pyridostigmine around one milligram per kilogram per dose four to five times daily, which is around 50 mg four to five times daily for this 52 kg girl, titrated to the response and limited by the cholinergic side effects. I would start crisis-specific therapy with intravenous immunoglobulin 2 g per kg over two to five days, which is 104 grams in total, or plasma exchange three to five sessions over one to two weeks, which the Cochrane review found equally effective for an exacerbation. I would begin prednisolone low at around half a milligram per kiligram per day and titrate upward over weeks, because a high starting dose can transiently worsen the disease, and add a steroid-sparing agent early. I would search for and reverse a precipitant such as infection or a worsening drug. [5]

Question 2 (10 marks)

Discuss the differential diagnosis of fatigable weakness in this child, the distinguishing features of the muscle-specific kinase antibody subtype and the congenital myasthenic syndromes, and the prognosis and follow-up plan you would discuss with the family. [1]

The differential of fatigable weakness runs across the junction, the nerve, the muscle, and the brain. This girl has the fluctuating, fatigable ocular and bulbar weakness with preserved reflexes and pupils and a positive ice pack test that fits autoimmune myasthenia gravis. Guillain-Barre syndrome would be ascending, fixed over days rather than fluctuating, and areflexic early. A congenital myopathy or muscular dystrophy would be fixed and slowly progressive with reduced reflexes in proportion to the weakness and a raised creatine kinase in the dystrophies. Thyroid ophthalmopathy would produce fixed proptosis and lid lag rather than fatigable ptosis. Lambert-Eaton myasthenic syndrome would show facilitation with repeated activity and a paraneoplastic association. [1]

The muscle-specific kinase antibody subtype behaves differently and is the one to recognise, because it presents with dominant bulbar, facial, neck flexor, and respiratory weakness, responds poorly to acetylcholinesterase inhibitors, is more refractory, and carries a higher crisis risk, and it does not benefit from thymectomy, with a particular role for rituximab. The congenital myasthenic syndromes are genetic and not antibody-mediated, present from infancy, and their treatment is subtype-specific: pyridostigmine helps acetylcholine receptor deficiency and RAPSN syndrome, but it worsens Dok7, ColQ endplate acetylcholinesterase deficiency, and the slow-channel syndrome, which are treated with ephedrine, salbutamol, quinidine, or fluoxetine. The message is to confirm the antibody or the gene before committing to long-term pyridostigmine. [9][11]

I would tell the family that children with autoimmune myasthenia gravis have a good prognosis when well managed, with many achieving pharmacological remission on low-dose immunotherapy, and that the ocular-only form often remits. I would be honest that the course is chronic and relapsing, that the corticosteroids carry the side effects of growth suppression, weight gain, and osteopenia that need monitoring, and that the immunosuppression requires live-vaccine avoidance and influenza and pneumococcal cover. I would discuss thymectomy as an option in this adolescent with generalised acetylcholine receptor antibody disease after the MGTX trial, and I would give the family a written school and crisis plan with a safety-net for a falling forced vital capacity. I would arrange paediatric neurology follow-up and a structured transition to adult care, and the predictors of a poorer outcome are a muscle-specific kinase subtype, early generalised onset, a crisis in the first year, and a poor early response. [2]