myasthenia gravis

Question 1

What is the definition of Myasthenia Gravis?

Answer 1

Myasthenia gravis is a chronic autoimmune disorder of the postsynaptic membrane at the neuromuscular junction of skeletal muscle.

Question 2

Epidemiology of MG

Answer 2

• Myasthenia gravis is a rare disease with an estimated worldwide prevalence of 200 people per million
• Symptoms peak in women during their 20s or 30s, and in men in their 50s or 60s

Question 3

What are the Risk Factors for MG?

Answer 3

• Female gender: twice as common in women
• Familyhistory
• Autoimmunity: either a personal or family history of autoimmune disorders such as rheumatoid arthritis and SLE
• Thymoma or thymic hyperplasia: 10-15% of patients have a thymoma, whilst up to 70% have thymic hyperplasia

Question 4

Physiology of MG

Answer 4

Ach antibodies bind to the receptors on the post synaptic membrane ,
thus Achieving cant bind and thus causes muscle weakness over time

Question 5

What does MG occur due to?

Answer 5

• circulating autoantibodies against thenicotinic acetylcholine receptor(AChR)
• this causes fewer available binding sites for acetylcholine (Ach) at the postsynaptic membrane, resulting in weakness.

Question 6

What happens as the receptors are used more during muscle activity

Answer 6

more of them become blocked up. This leads to less effective stimulation of the muscle with increased activity.

Question 7

What do the antibodies of MG activate

Answer 7

activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane. This further worsens the symptoms.

Question 8

What do a small proportion of MG patients have?

Answer 8

have antibodies against muscle-specific kinase(MuSK) and antibodies against low-density lipoprotein receptor-related protein 4 (LRP4).

Question 9

What is MuSK and LRP4 important proteins for?

Answer 9

the creation and organisation of the acetylcholine receptor. Destruction of these proteins by autoantibodies leads to inadequate acetylcholine receptors.

Question 10

What can MG present as in very rare cases?

Answer 10

paraneoplastic syndrome - an underlying cancer like bronchogenic carcinoma or thymoma generates an immune response which results in generation of autoantibodies.

Question 11

Signs of MG

Answer 11

• Proximal muscle weakness with fatigability: often affecting the face and neck
• Ptosis (drooping eyelid) exacerbated on upward gaze: may be bilateral or unilateral
• Complex ophthalmoplegia: cannot be isolated to one cranial nerve
• Head drop: a rare sign due to weakness of cervical extensor muscles
• Myasthenic snarl: a ‘snarling’ expression when attempting to smile

Question 12

Symptoms of MG

Answer 12

• Lethargy
• Muscle weakness: worsens throughout the day, can improve with rest
• Diplopia: double vision due to effects on eye muscles
• Slurred speech
• Dysphagia: difficulty swallowing
• Fatigue in jaw when chewing
• Shortness of breath: may suggest a myasthenic crisis
• Ptosis

Question 13

Primary investigations for MG

Answer 13

• Antibodies:AchR antibodies are first-line, whilst anti-MuSK and anti-LRP4 can also be tested in patients who are AchR antibodynegative
• Electrophysiological studies:repetitive nerve stimulation shows a decremental muscle response
• CT thorax:all patients should have a CT chest to exclude a thymoma; MRI is an alternative
• Thyroid function:all patients require thyroid function tests, as there is a higher prevalence of autoimmune thyroiditis

Question 14

Other investigations to consider for MG

Answer 14

• Tensilon test:edrophonium is administered and improves muscle weakness; this is now rarely performed due to the risk of inducing heart block and asystole
• Serial pulmonary function tests:carried out if respiratory compromise is suspected, for example in patients with shortness of breath and suspected myasthenic crisis

Question 15

DDs for MG

Answer 15

• Lambert-eaton myasthenic syndrome
• Botulism
• Penicillamine-induced myasthenia gravis
• Primary myopathies
• Management

Question 16

What is the management of a stable patient with MG

Answer 16

• First-line: pyridostigmine; an acetylcholinesterase inhibitor
• Second-line: prednisolone(to dampen down immune system) on alternate days is offered if - given first acutely THIS IS FIRST LINE symptomatic despite pyridostigmine
• Third-line: azathioprineis offered if symptoms are not controlled on prednisolone
• Other: if symptoms remain uncontrolled, consider alternatives such as methotrexate orrituximab
• Thymectomy:indicated if a thymoma is present on imaging,orin patients aged < 45 years old with positive serology; thymectomy may help to induce remissio

Question 17

Management of myasthenic crisis

Answer 17

• IV immunoglobulin or plasmapheresis
• Intubation:**if severe respiratory compromise
• Corticosteroidsmay be used as an adjunct

Question 18

What are the complications of myasthenia gravis

Answer 18

• Myasthenic crisis: weakening of the respiratory muscles and is often provoked by infections or medications. Patients present with increasing shortness of breath, which can deteriorate into respiratory failure.
• Respiratory failure
• Aspiration pneumonia: dysphagia increases the risk of aspiration

Question 19

Prognosis of MG

Answer 19

The goal of therapy is to induce clinical remission. Myasthenia gravis is associated with a reasonably good prognosis and patients who undergo thymectomy tend to have a better prognosis.

However, it is estimated that as many as 10 to 20% of patients may experience at least one myasthenic crisis, and the annual risk of a myasthenic crisis is approximately 2 to 3%.

Question 20

Medications to avoid in MG

Answer 20

penicillamine
quinidine, procainamide
beta-blockers
lithium
phenytoin
antibiotics: gentamicin, macrolides, quinolones, tetracyclines

Question 21

What percentage of people are anti Ach-r

Answer 21

85%

Question 22

What percent of people are Anti Musk

Answer 22

15%