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Chapter 7: Disorders of muscle and neuromuscular junction 333

Aetiology/pathophysiology Serum acetylcholine receptor antibodies are present
80–90% of cases have an autoantibody directed at the in 90% and are specific.
acetylcholine receptor. The thymus appears to be in- Nervestimulation shows characteristic decrement in
volved in the pathogenesis, with 25% of cases having evoked muscle action potentials following repetitive
athymoma and a further 70% have thymic hyperplasia. stimulation of the motor nerve.
There also appear to be genetic factors, such as an Scanning for thymic masses.

association with HLA-B8, DRw3 and it is associated Screening for associated disease such as hyperthy-
with other autoimmune conditions including thyroid roidism, SLE and rheumatoid arthritis is useful.
disease, rheumatoid arthritis, systemic lupus erythe-
matosus (SLE) and pernicious anaemia. Management
Myasthenic syndromes can be caused by d- Oral anticholinesterases such as pyridostigmine treat the

Penicillamine, lithium and propranolol. weaknessbutdonotaffectthecourseofthedisease.Over-
At the neuromuscular junction, immune complexes are dosage can cause weakness, probably due to excessive de-
deposited at the postsynaptic membrane causing inter- polarization of the ACh receptor or desensitisation. Care
ference with and later destruction of the acetylcholine should be taken when prescribing other medications as
receptor. they may exacerbate the disease.
Thymectomy improves symptoms and prognosis in

Clinical features those under the age of 60. Complete removal of the
Fatiguability is the single most characteristic feature. Ex- thymus is important. Thymectomy in older patients
ercise increases the degree of muscle weakness, and rest with hyperplasia alone is more controversial, tumours
allows recovery of power. Acute exacerbations are trig- should however be removed. Increased weakness may
gered by stress including surgery, and by drugs. occur acutely post-operatively, which can be managed
Itaffectstheextraocularmuscles,causingvariablepto- by plasmapheresis.

sis (typically worse at the end of the day) and unusual Corticosteroids can be used with good results in 70%
abnormalities of eye movements. This causes diplopia despite risk of an initial relapse.
and blurred vision. The pupils are spared. In steroid resistant cases, azathioprine or ciclosporin
The muscles of mastication, speech and facial expres- may be added.

sion are affected. This can cause difficulty with swal- Plasmapheresis and intravenous immunoglobulin are
lowing and eating – the chin may need support whilst usually reserved for severe acute exacerbations.
chewing, and a ‘myasthenic snarl’ when smiling.
The proximal limb muscles show fatiguability on re- Prognosis

peated use. The respiratory muscles may be affected in Severity fluctuates but most have a protracted course,
amyasthenic crisis requiring ventilatory support. Ini- exacerbations are unpredictable but may be brought on
tially the reflexes are preserved but may be fatiguable, by infections or drugs.
muscle wasting is a sign of late disease.
Eaton–Lambert syndrome
Complications
Transplacental passage of ACh-R antibodies can cause Definition
neonatal myasthenia gravis in 10–20% of neonates, Arare paraneoplastic syndrome usually associated with
which manifests with flaccidity, poor feeding and res- small-call carcinoma (SCC) of the bronchus, causing
piratory difficulties within the first 48 hours. It can last muscle weakness.
up to 3 weeks.
Aetiology/pathophysiology
Investigations Antibodies directed against the presynaptic voltage-
Edrophonium (anticholinesterase) – Tensilon test – gated calcium channels have been detected. Around 70%

injected i.v. as a test dose provides improvement have an underlying tumour, almost always SCC of the
within seconds lasting for 2–3 minutes. lung.