Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors

Myasthenia gravis- .19
Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases*. Myasthenia is more common in women (2:1)

The key feature is muscle fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest:
• extraocular muscle weakness: diplopia
• proximal muscle weakness: face, neck, limb girdle
• ptosis
• dysphagia

Associations- 1.09
• thymomas in 15%
• autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE
• thymic hyperplasia in 50-70%

• single fibre electromyography: high sensitivity (92-100%)
• CT thorax to exclude thymoma
• CK normal
• autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodies
• Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used anymore due to the risk of cardiac arrhythmia

Management- 2.16
• long-acting anticholinesterase e.g. pyridostigmine
• immunosuppression: prednisolone initially
• thymectomy

Management of myasthenic crisis- 2.29
• plasmapheresis
• intravenous immunoglobulins
*antibodies are less commonly seen in disease limited to the ocular muscles

Myasthenia gravis: exacerbating factors-2.53
The most common exacerbating factor is exertion resulting in fatigability, which is the hallmark feature of myasthenia gravis . Symptoms become more marked during the day

The following drugs may exacerbate myasthenia:
• penicillamine
• quinidine, procainamide
• beta-blockers
• lithium
• phenytoin
• gentamicin

Lambert-Eaton syndrome- 3.35
Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer, and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous system

Features- 4.29
• repeated muscle contractions lead to increased muscle strength* (in contrast to myasthenia gravis)
• limb girdle weakness (affects lower limbs first)
• hyporeflexia
• autonomic symptoms: dry mouth, impotence, difficultly micturating
• ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)

EMG- 4.54
• incremental response to repetitive electrical stimulation
• Management
• treatment of underlying cancer
• immunosuppression, for example with prednisolone and/or azathioprine
• 3,4-diaminopyridine is currently being trialled**
• intravenous immunoglobulin therapy and plasma exchange may be beneficial
*in reality this is seen in only 50% of patients and following prolonged muscle use muscle strength will eventually decrease
**works by blocking potassium channel efflux in the nerve terminal so that the action potential duration is increased. Calcium channels can then be open for a longer time and allow greater acetylcholine release to the stimulate muscle at the end plate