Myasthenia Gravis

Key Points

·         Myasthenia Gravis is an acquired, autoimmune condition.

·         Antibodies attack the Acetylcholine receptor.

·         This gives weakness in muscles, particularly the ocular, bulbar and proximal skeletal.

·         Fatigability is a key symptom!

·          Disease has a fluctuating pattern of ‘crises’ and remittances.

·         Treatment is usually with Acetylcholinesterase inhibitors and immunosupression, however in crises other treatments may be needed.

·         Despite this it is easily treated and patients have a good life expectancy.

Epidemiology

                The prevalence of Myasthenia Gravis is about 1 in 200,000. Although anyone is susceptible to it, there are two main subgroups, young women (20-35) and older men (60-75).

Aetiology

                The exact cause is unknown, however as with most autoimmune disorders, there does seem to be a genetic link.

Pathophysiology

                B and T cell mediated IgG autoantibodies are created which attack the postsynaptic acetylcholine receptors at the neuromuscular junction. This causes the physical symptoms of weakness and fatigability.

                There is a very strong association with disorders of the THYMUS. In 75% of patients with Myasthenia Gravis there is hyperplasia of the thymus, and in 10% this becomes a thymoma.

Signs and Symptoms

                Although some symptoms are more predominant than others, Myasthenia Gravis generally has a course which has periods of remission, interrupted by ‘Crises’. Some patients can predict when they are ‘due a crisis’, and others find there is no pattern whatsoever.

Due to the destruction of the synapse there is decreased conduction at the neuromuscular junctions, leading to muscle fatigue and weakness. There are four sets of muscles that are particularly affected

1-      Ocular- Ptosis and Diplobia

2-      Bulbar-Dysphagia, Dysphonia, Dysarthria and weak/droopy face

3-      Proximal muscles- Shoulders and Thighs

4-      Axial – Neck and trunk, but also muscles involved in Respiration

The fatigability of muscles can be demonstrated by getting the patient to do a repetitive movement (e.g flap their arm’s) for 30-60 seconds. They also report that their symptoms get worse as the day wears on, and that their best times are in the morning, or after a sleep.

Limb reflexes are usually normal or brisk, and there are no sensory abnormalities.

Muscle wasting is usually not present, unless there is severe disease, or the patient has had the condition for a long time.

Investigations

                The traditional test for Myasthenia Gravis is the TENSILON test, in which patients are given two drugs, Edrophionium, which prevents breakdown of acetylcholine, and atropine to prevent cardiac side effects associated with Edrophionium. If the patient has myasthenia gravis, then within seconds there is a dramatic symptomatic improvement, however this goes after a couple of minutes.

                Blood tests for serum acetylcholine receptor antibodies are positive in over 85% of patients with Myasthenia gravis, and there may also be other autoantibodies present, usually against muscle, joints or the thyroid.

                Electromyography is used to measure how fatigable a muscle is. Electricity is used to repeatedly stimulate a muscle, fatigue can be seen. Single fibre electromyography is usually preferred, as stimulating a single motor unit (remember those, a motor neurone and the muscle fibres it supplies), a variability called a ‘jitter’ can be found.

                CT/ MRI scans are used to image the thymus, looking in particular for hyperplasia.

                Spirometry is important as it gives an indication as to how badly affected the respiratory muscles are. In some crises respiratory function is compromised, and urgent medical attention is needed.

Management

                As already mentioned the disease course is very fluctuating, with remitting periods and crises. There is no cure; however several cases of permanent remission have been reported post thymectomy or heavy immunosupression.

                Oral acetylcholinesterase inhibitors are used to prevent destruction of acetylcholine in the synaptic space. The doses of these are patient determined, as an overdose can cause a cholinergic crisis, but you don’t want to undertreat the condition. A commonly used one is Pyridostigmine, which has a very short half life, and lasts 3-5h.

                Immunosupression is often given in conjunction with acetylcholinesterase inhibitors. Corticosteroids (mainly Prednisolone) are the mainstay here and work in 70% of cases; however in some cases steroid-sparing agents such as Azathiprine may be needed. Immunosuppressive treatment should be started and increased in hospital because patients often deteriorate when starting the treatment and an improvement follows. Because of the increased falls risk, prevention of osteoporosis is vital, and so many patients are on several drugs to combat this.

                More recently immunomodulatory agents such as Methotrexate, cyclosporine and cyclophosphamide have found a place in the treatment of Myasthenia Gravis, however second or third line behind immunosupression.

                In crises, additional treatments such as the use of IV immunoglobulins or Plasmapheresis may be needed.

                The use of thymectomies is changing. Previously if a thymus was found to be hyperplasic, or a thymoma was present, then thymectomy was performed, however some consultants now prefer to take the thymus out as early as possible, as better prognoses have been noted, and as already mentioned permanent relapse has been obtained.

Prognosis

                Although Myasthenia Gravis (as the name suggests!) used to be a life threatening condition due to respiratory failure, with treatment a normal life expectancy can be achieved. Patients do have to be aware about the association with the development of thymomas, as this can have a large impact on both morbidity and mortality.

Useful Links

                Tensilon Test – Although the Myasthenia Gravis is in a dog, this video is great as it shows the dog getting very tired, weak proximal muscles (look at the back legs) as it walks across the room. The Edrophionium is then given, and look at the response!

                Patient information video – A great example of how to explain the disease to the patient.

                Guidelines – Released by the European Federation of Neurological Societies, it describes the treatment of neuromuscular junction disorders; however there is a great section at the beginning about Myasthenia Gravis.