Myasthenic syndromes

Which one of the following clinical features is MOST LIKELY to distinguish myasthenia

gravis from Lambert–Eaton myasthenic syndrome?

a) Aged 55 at onset of symptoms

b) An improvement of strength with the administration of intravenous edrophonium

c) Involvement of facial muscles

d) Finding of immunoglobulin G antibodies to the nicotinic acetylcholine receptor

e) Presence of deep tendon reflexes

Answer: d

Explanation

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction

involving autoantibodies to the post-synaptic acetylcholine receptor. Given the

amount of receptor redundancy at this site, receptors need to be reduced to less

than 30% of their quantity in health before the typical weakness is manifest. Most

commonly bulbar and eye muscles are affected but a fluctuating degree of generalised

muscle weakness is seen, which at its greatest extreme (Grade IV) requires

mechanical ventilation. Lambert–Eaton myasthenic syndrome (LEMS) is also an

autoimmune disorder of the neuromuscular junction involving immunoglobulin G

autoantibodies but these are to the pre-synaptic voltage-gated calcium channels,

which ultimately cause defective release of acetylcholine from the terminal button

of the motor neurone. It is associated with small cell lung cancer and the distribution

of the weakness tends to favour proximal muscles of the lower limb. However, facial

muscle weakness, diplopia and ptosis are seen with LEMS and this feature is not a

reliable distinguisher. Classically, tendon reflexes are present in MG and absent in

LEMS; however, LEMS weakness improves with exercise of the muscle at which

point tendon reflexes may return. Myasthenia gravis weakness worsens with sustained

or repeated use of the muscle – the so-called fatiguability. Edrophonium is a

cholinesterase inhibitor, which via increasing the quantity of acetylcholine at the

neuromuscular junction will cause a transient improvement of symptoms in MG.

However, it is not uncommon for edrophonium to have a similar effect in LEMS. In

LEMS, autonomic dysfunction is sometimes noted, in particular a dry mouth and, of

course, if there is an underlying malignancy the patient may be cachectic and

complain of B-symptoms. The presence of anti-acetylcholine receptor autoantibodies

would allow the confident diagnosis of MG rather than LEMS (however, it is only

identified in 90% of cases).