Paediatrics chapters
Myasthenia gravis in children
The autoimmune disease of the neuromuscular junction that causes fatigable weakness: juvenile, transient neonatal and congenital forms, how to confirm it, and how to treat it and its crises.
- Myasthenia gravis is an autoimmune disease in which antibodies block or destroy acetylcholine receptors at the neuromuscular junction, giving fatigable weakness of eye, face, bulbar and limb muscles that is worse later in the day.
- Diagnosis: anti-AChR antibodies (most), anti-MuSK in some of the rest, edrophonium or neostigmine test, and a decremental response to slow repetitive nerve stimulation; CK and ECG are normal.
- Treatment: pyridostigmine, steroids and other immunosuppressants, thymectomy, IVIG or plasma exchange; recognise myasthenic vs cholinergic crisis and avoid aminoglycosides and neuromuscular blockers.
On this page
Overview
Myasthenia gravis (MG) is a chronic autoimmune disease of the neuromuscular junction. The hallmark is rapid fatigue of skeletal (striated) muscle: strength falls with repeated use and recovers with rest. The eyelid and eye muscles and the muscles of chewing and swallowing are most often affected. It occurs at any age and in both sexes, but girls are affected more often than boys; occasionally more than one family member is affected. In children there are three forms: juvenile, transient neonatal and congenital.
Pathophysiology
- At the neuromuscular junction, the nerve ending releases acetylcholine (ACh), which crosses the gap and binds receptors on the muscle fibre; enough bound receptors trigger contraction.
- In MG, IgG antibodies bind the acetylcholine receptor (AChR), blocking it and speeding its destruction faster than the body can replace it; receptor numbers may fall by up to about 80%.
- With fewer receptors, each nerve impulse activates fewer fibres, and repeated firing (as ACh stores fall) leads to progressive weakness: this is fatigability.
- Some patients without AChR antibodies have antibodies to muscle-specific tyrosine kinase (MuSK) or other junction proteins.
- The thymus is often abnormal: enlarged, and a thymoma is found in a minority (Akbar: 10 to 15%).
MG is an antibody-mediated disease of the postsynaptic receptor; botulism, by contrast, blocks presynaptic ACh release.
Types in childhood
| Feature | Juvenile MG | Transient neonatal MG | Congenital myasthenic syndromes |
|---|---|---|---|
| Cause | Autoimmune, child's own AChR antibodies | Maternal AChR antibodies cross the placenta | Gene mutations in junction proteins; not autoimmune |
| Mother | Usually normal | Has myasthenia gravis | Rarely has MG |
| Onset | Late infancy and childhood | First hours to days after birth | At birth or early infancy |
| Frequency | - | About 10 to 20% of babies of myasthenic mothers (Akbar: 12 to 19%) | Rare |
| Course | Chronic, relapsing; remissions possible | Recovers in days to weeks when antibodies clear | Permanent, static; no spontaneous remission |
| Antibodies | Usually present | Usually found in mother's blood | Rarely raised |
| Crises | Can occur | - | Do not have myasthenic crises |
| Response to treatment | Good | Good | Variable, often poor; some respond to pyridostigmine |
Transient neonatal myasthenia
- Weak suck and inability to suck or swallow, poor feeding, generalised hypotonia, weak cry, ptosis, weak face, breathing difficulty.
- Some need tube (gavage) feeding and ventilation for a time.
- Treated with cholinesterase inhibitors and support until the weakness goes.
- These babies are not at increased risk of MG later in childhood.
Congenital myasthenic syndromes
- Present at birth or in infancy with hypotonia, ptosis, external ophthalmoplegia, facial weakness, weak cry, dysphagia and breathing problems.
- Often reduced fetal movements; CK normal.
- Lifelong disability is usual.
Clinical features of juvenile MG
- Ptosis, often asymmetric and variable; it increases on sustained upward gaze (Akbar: over 30 to 90 seconds).
- Diplopia, blurred vision, ophthalmoplegia.
- Facial weakness (an expressionless or "sad" face), slurred or nasal speech.
- Difficulty chewing and swallowing; risk of aspiration.
- Poor head control: lying supine the child can lift the head against gravity for only a few seconds.
- Limb weakness and chronic fatigue; breathing difficulty in severe disease.
- Symptoms worsen through the day and with repeated activity, improve with rest.
- Reflexes and sensation are normal; no wasting early.
- Ocular myasthenia: in some children the disease stays limited to ptosis and eye movement weakness; others progress to generalised disease.
The child is typically better in the morning and worse in the evening. A history of ptosis appearing after school or reading is a strong clue.
"Tired eyes by tea time": ptosis and double vision that grow through the day.
Diagnostic approach
| Test | Finding |
|---|---|
| Anti-AChR antibodies | Positive in most (Akbar: about 85%); a positive result confirms the diagnosis |
| Anti-MuSK antibodies | Positive in a proportion of seronegative patients (Akbar: 40 to 70% of them) |
| Edrophonium (Tensilon) test | Short-acting anticholinesterase; ptosis and eye movements improve within seconds and fatigue lessens; used in older children |
| Neostigmine test | Preferred in newborns and young infants (longer acting, easier to judge) |
| Repetitive nerve stimulation | At slow rates (3 per second): progressive fall (decrement) in muscle action potential amplitude |
| EMG | More specific for MG than a muscle biopsy |
| Serum CK | Normal |
| ECG | Normal; the heart is not involved |
| Chest X-ray / CT | May show an enlarged thymus or thymoma |
Differential diagnosis
- Guillain-Barré syndrome (areflexia, ascending weakness, raised CSF protein).
- Bulbar poliomyelitis (fever, asymmetric paralysis).
- Botulism (descending paralysis, dilated pupils, constipation).
- Myopathies and myotonic dystrophy (constant, not fatigable, weakness).
Management
There is no cure, but treatment allows most children to lead normal lives.
Anticholinesterase drugs (first line)
- These keep ACh at the junction longer so more receptors are activated.
- Pyridostigmine by mouth: dose is adjusted to each child; Akbar gives a starting dose of 1 mg/kg per dose every 6 hours.
- Neostigmine: shorter acting; can be given by injection; the drug of choice in newborns; causes gut hypermotility and diarrhoea. Akbar notes that 15 mg of neostigmine is roughly equal to 60 mg of pyridostigmine.
- Atropine may be added to control muscarinic side effects: excess secretions, abdominal cramps, nausea and vomiting.
Immune treatment
- Corticosteroids (prednisone); other immunosuppressants such as azathioprine and mycophenolate mofetil.
- IVIG: alters antibody production or action; useful in crises and severe disease.
- Plasma exchange (plasmapheresis): removes antibodies; improvement can be striking but is short-lived because antibody production continues; may need repeating.
- Thymectomy: removal of the thymus; often reduces severity after some months and may lead to remission; a thymoma is always removed because of the risk of malignancy.
Myasthenic vs cholinergic crisis
| Feature | Myasthenic crisis | Cholinergic crisis |
|---|---|---|
| Cause | Disease worsening, often after infection, surgery or emotional stress | Overdose of anticholinesterase drugs |
| Picture | Sudden worsening of swallowing and breathing | Weakness with cholinergic (muscarinic) features: excess secretions, cramps, diarrhoea, vomiting |
| Edrophonium | Brief dramatic improvement (Akbar) | Not the test to use; stop the drug that caused it |
| Treatment | Airway care, suction, ventilation; IV cholinesterase inhibitor, IVIG or plasma exchange; tube feeding | Stop the anticholinesterase; atropine; airway support, tracheostomy if needed |
Both need suction, airway protection, ventilatory support and fluid and electrolyte care.
Drugs and situations to avoid
- Neuromuscular blocking drugs (succinylcholine, pancuronium): a single dose during anaesthesia may cause paralysis for weeks.
- Aminoglycoside antibiotics (gentamicin and others) worsen weakness and should be avoided.
In a child with known MG who becomes weaker, an infection treated with gentamicin can tip them into crisis. Choose a different antibiotic.
Prognosis and long-term outcomes
- Untreated, MG is usually progressive and can be life-threatening through respiratory failure and aspiration.
- With current treatment the outlook is good; most children improve substantially.
- Spontaneous improvement or remission can occur, sometimes for long periods without treatment.
- Some children remain with ocular myasthenia only.
- Transient neonatal MG recovers fully; congenital forms cause lifelong but static disability.
Expect: autoimmune antibodies against postsynaptic acetylcholine receptors; fatigable ptosis and diplopia worse in the evening; normal reflexes, sensation, CK and ECG; anti-AChR antibodies in most, anti-MuSK in some seronegatives; edrophonium test in older children and neostigmine in newborns; decrement on 3 per second repetitive stimulation; pyridostigmine as first-line drug, neostigmine in neonates; steroids, azathioprine, IVIG, plasma exchange and thymectomy; myasthenic vs cholinergic crisis; avoidance of aminoglycosides and neuromuscular blockers; transient neonatal MG in babies of myasthenic mothers; congenital MG as a non-autoimmune genetic disorder.
Quick revision
- Autoimmune, AChR antibodies, receptor loss; girls more.
- Fatigable ptosis, diplopia, bulbar and limb weakness; worse in evening.
- Reflexes, sensation, CK and ECG normal; thymus may be enlarged.
- Anti-AChR in most; anti-MuSK in some of the rest.
- Edrophonium test (older child); neostigmine test (newborn).
- Slow repetitive stimulation: decrement.
- Pyridostigmine first; neostigmine in newborns; atropine for side effects.
- Steroids, azathioprine, IVIG, plasma exchange, thymectomy.
- Crisis: myasthenic improves with edrophonium; cholinergic from overdose needs atropine.
- Avoid aminoglycosides, succinylcholine, pancuronium.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why is the weakness in myasthenia worse at the end of the day?
Fewer working receptors mean each repeated nerve signal activates fewer muscle fibres, so strength falls with use and recovers with rest.
Will a baby with transient neonatal myasthenia develop myasthenia later?
No. The weakness comes from the mother's antibodies and disappears as they are cleared, and the child is not at increased risk later.
Which test is preferred in a newborn with suspected myasthenia?
The neostigmine test, which lasts longer than edrophonium and is easier to interpret in a small baby.
Why is gentamicin dangerous in myasthenia?
Aminoglycosides impair neuromuscular transmission and can worsen weakness or precipitate a crisis, so another antibiotic should be chosen.