Myasthenia gravis and neuromuscular junction disorders: Case

Summary and immediate impression

This girl presents a textbook case of autoimmune myasthenia gravis with a threatened crisis. The tempo is subacute over weeks, with fluctuating, fatigable weakness of the ocular, bulbar, and proximal muscles that worsens through the day and recovers with rest, preserved reflexes and pupils, and a positive ice pack test. The falling forced vital capacity and the 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]

The first 24 hours — resuscitation, monitoring, and intensive care

I would treat this as probable myasthenia gravis with a threatened crisis and escalate immediately to intensive care. 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. I would secure the airway, preoxygenate, and arrange a rapid sequence induction with the intensive care team, choosing sedation that avoids prolonged neuromuscular blockade, because the weak respiratory muscles and the aspiration risk make this a high-risk airway. I would place cardiac and respiratory monitoring and continue the bedside spirometry every two to six hours. [7]

The workup runs in parallel. I 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 that a negative result never excludes a typical picture. I request repetitive nerve stimulation at three hertz, looking for a decremental response of greater than ten percent, and single-fibre electromyography for its sensitivity if available. I obtain a contrast computed tomography or magnetic resonance imaging of the chest to exclude a thymoma, which mandates resection, and a thyroid function test to exclude an associated thyroid disease. [11]

I 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. I 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 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 I plan an early steroid-sparing agent. I search for and reverse a precipitant such as an infection or a worsening drug. [5]

Intensive care, immunotherapy, and the thymectomy decision

The intensive care course is dominated by the management of the threatened ventilatory and bulbar failure. She is likely to need a brief period of ventilation, and weaning is guided by the rising forced vital capacity, the recovery of bulbar function, and the absence of fatigue on the weaning trials. The precipitant is treated, the fever and the infection are controlled, and the drugs that worsen the junction, including aminoglycosides, fluoroquinolones, macrolides, beta-blockers, and magnesium, are avoided. As the acute phase settles, the prednisolone is titrated upward to around one to one and a half milligrams per kilogram and then tapered to the lowest effective dose, with a steroid-sparing agent such as azathioprine introduced early after the thiopurine methyltransferase check. [2]

The thymectomy decision is framed for this adolescent with generalised acetylcholine receptor antibody disease. The MGTX trial showed that extended transsternal thymectomy plus prednisone improved the clinical status of adults with non-thymomatous generalised disease over three years, so it is a rational option to reduce the long-term immunosuppression, while it is not helpful in muscle-specific kinase disease or the congenital syndromes. For refractory disease, eculizumab is reserved after the REGAIN trial with meningococcal vaccination and vigilance, and rituximab has a particular role in muscle-specific kinase disease. [2]

Prognosis, counselling, and follow-up

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 around fifteen to twenty percent of children will have a crisis commonest in the first year, and that the corticosteroids carry the growth, weight, and bone side effects that need monitoring. I would give the family a written school and crisis plan with a safety-net for a falling forced vital capacity or a weak cough, and I would arrange paediatric neurology follow-up, a bone-density and growth baseline, and a structured transition to adult care. 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. [7]

Marking domains

• Diagnosis and reasoning: recognises the fatigable, fluctuating weakness with preserved reflexes and pupils and a positive ice pack test, and confirms on the antibody panel and neurophysiology. [1]
• Management — resuscitation: escalates to intensive care on the spirometry numbers, secures the airway with a rapid sequence induction, and monitors the forced vital capacity. [7]
• Management — definitive: starts pyridostigmine, begins prednisolone low and titrates with early steroid-sparing, and gives intravenous immunoglobulin 2 g per kg or plasma exchange for the crisis. [5]
• Communication: counsels the family honestly on the chronic relapsing course, the medication side effects, the thymectomy decision, and the transition plan. [2]