Neuromuscular junction disorders
Acquired disorder of the neuromuscular junction characterised by muscle fatiguability, ptosis & dysphagia.
4 in 100,000.
Peaks in women aged 20–40 and in men over age 60.
2F : 1M
80–90% of cases have an autoantibody directed at the acetylcholine receptor. The thymus appears to be involved in the pathogenesis, with 25% of cases having a thymoma and a further 70% have thymic hyperplasia.
· There also appear to be genetic factors, such as an association with HLA-B8, DRw3 and it is associated with other autoimmune conditions including thyroid disease, rheumatoid arthritis, systemic lupus erythematosus (SLE) and pernicious anaemia.
· Myasthenic syndromes can be caused by D-Penicillamine, lithium and propranolol.
At the neuromuscular junction, immune complexes are deposited at the postsynaptic membrane causing interference with and later destruction of the acetylcholine receptor.
Fatiguability is the single most characteristic feature. Exercise increases the degree of muscle weakness, and rest allows recovery of power. Acute exacerbations are triggered by stress including surgery, and by drugs.
· It affects the extraocular muscles, causing variable ptosis (typically worse at the end of the day) and unusual abnormalities of eye movements. This causes diplopia and blurred vision. The pupils are spared.
· The muscles of mastication, speech and facial expression are affected. This can cause difficulty with swallowing and eating – the chin may need support whilst chewing, and a ‘myasthenic snarl’ when smiling.
· The proximal limb muscles show fatiguability on repeated use. The respiratory muscles may be affected in a myasthenic crisis requiring ventilatory support. Initially the reflexes are preserved but may be fatiguable, muscle wasting is a sign of late disease.
Transplacental passage of ACh-R antibodies can cause neonatal myasthenia gravis in 10–20% of neonates, which manifests with flaccidity, poor feeding and respiratory difficulties within the first 48 hours. It can last up to 3 weeks.
Edrophonium (anticholinesterase) – Tensilon test – injected i.v. as a test dose provides improvement within seconds lasting for 2–3 minutes.
Serum acetylcholine receptor antibodies are present in 90% and are specific.
Nerve stimulation shows characteristic decrement in evoked muscle action potentials following repetitive stimulation of the motor nerve.
Scanning for thymic masses.
Screening for associated disease such as hyperthyroidism, SLE and rheumatoid arthritis is useful.
Oral anticholinesterases such as pyridostigmine treat the weakness but do not affect the course of the disease. Over-dosage can cause weakness, probably due to excessive depolarization of the ACh receptor or desensitisation. Care should be taken when prescribing other medications as they may exacerbate the disease.
· Thymectomy improves symptoms and prognosis in those under the age of 60. Complete removal of the thymus is important. Thymectomy in older patients with hyperplasia alone is more controversial, tumours should however be removed. Increased weakness may occur acutely post-operatively, which can be managed by plasmapheresis.
· Corticosteroids can be used with good results in 70% despite risk of an initial relapse.
· In steroid resistant cases, azathioprine or ciclosporin may be added.
· Plasmapheresis and intravenous immunoglobulin are usually reserved for severe acute exacerbations.
Severity fluctuates but most have a protracted course, exacerbations are unpredictable but may be brought on by infections or drugs.