Paediatrics: Neuromuscular junction

Neuromuscular junction

Autoimmune myasthenia gravis

The hallmark of this condition is fluctuating, fatiguable weakness. At onset 50% of patients have ptosis with, eventually, more than 80% developing it. The condition is caused by autoantibodies against the nicotinic acetylcho-line (ACh) receptor, which blocks transmission at the neuromuscular junc-tion. Normally, the condition is insidious, but sometimes an acute onset of fluctuating weakness of the extra-ocular, facial, oropharyngeal, respiratory, and limb muscles may present.

Diagnosis

·  Clinical picture: fatiguability of power/reflexes, particularly upward gaze with eyelids/elevation, fluctuating weakness of the extra-ocular, facial, oropharyngeal, respiratory, and limb muscles.

·  Electrophysiological assessment of the neuromuscular junction (NMJ) in affected muscles.

·  Response to a trial of edrophonium: video recording is essential as response may be brief.

·  ACh-receptor antibodies are present in more than 50% of cases.

Management

·  Immediate assessment of respiratory status using bedside measurement of FVC.

·  Immediate assessment of bulbar function looking at swallowing.

·  First-line: cholinesterase inhibitors such as pyridostigmine with steroids.

·  Refractory cases: acute, severe cases may respond to plasmapheresis. Subsequent immunosuppression, azathioprine, ciclosporin, methotrexate, and thymectomy. Needs to be monitored by an expert.

·  Outpatient management of NMJ and muscular disorders.

Congenital myasthenia gravis (CMG)

These are mainly a group of autosomal recessive disorders. However, can rarely be caused by passive transfer of maternal antibodies, which quite often have a predeliction for the foetal NMJ. Unlike the better known acquired version, they are caused by congenital abnormalities in the release, receptors for or recycling of acetylcholine at the NMJ. Despite ‘less publicity’, they contribute a much greater part of neuromuscular practice as they are lifelong and cannot be cured completely, so require expert management.

Presentation

In some cases as neonates, with arthrogryposis +/– bulbar/respiratory insufficiency +/– facial weakness +/– limb girdle weakness. One symptom is particularly noteworthy—laryngeal palsy, as this is a rare condition, and very likely to be caused by a CMG if there are no other ENT problems.

Diagnosis

·Clinical picture, including examination of mother (passive transfer of maternal antibodies).

·Electrophysiological assessment of the NMJ in affected muscles.

·Response to a trial of edrophonium: video recording is essential as response may be brief.

·ACh-receptor antibodies are not normally present if the mother is unaffected.

Management

Outpatient management of NMJ and muscular disorders.