Myasthenia Gravis

Question 1

What is myasthenia gravis?

Answer 1

AI disease affecting the neuromuscular junction producing weakness in skeletal muscles

Question 2

Describe the aetiology of MG

Answer 2

Autoantibodies against the nicotinic ACh receptor/ receptor associated proteins

Question 3

Describe the epidemiology of MG

Answer 3

F > M 2:1
Equal gender distribution in middle age

Question 4

What is the key feature of MG?

Answer 4

Muscle fatiguability
Muscles become progressively weaker during periods of activity + slowly improve after periods of rest

Question 5

What are the 2 types of MG?

Answer 5

Ocular myasthenia (only extra ocular +/- eyelid muscles)

Generalised: all skeletal muscles, esp. ocular, bulbar, limb + resp

Question 6

Give 4 types of symptoms of MG

Answer 6

Ocular: Diplopia

Bulbar: Dysphagia, Facial weakness, hypernasal speech, difficulty smiling, chewing or swallowing

Proximal muscles: difficulty standing from chair, brushing hair

Resp muscles: dyspnoea, resp failure

Question 7

What pattern of weakness is seen in MG?

Answer 7

Muscle fatiguability- muscles become progressively weaker during period of activity/ end of day + improve after periods of rest

Question 8

List 4 signs seen in the eyes in MG

Answer 8

Limb weakness (typically symmetrical)

Bilateral ptosis (may be asymmetrical)

Complex ophthalmoplegia

Check for ocular fatigue by asking pt to sustain an upward gaze for 1 min + watch the progressive ptosis that develops

Question 9

What test involving the eyes may be performed in MG?

Answer 9

Ice on Eyes Test

Placing ice packs on closed eyelids for 2 mins can improve neuromuscular transmission + reduce ptosis

+ve when ptosis improves by >2mm

Question 10

List 5 factors that may worsen symptoms or precipitate a myasthenic crisis

Answer 10

Infection
Surgery + anaesthesia
Pregnancy
Medications
Stress/ heat

Question 11

List 4 classes of drugs that can exacerbate MG

Answer 11

Abx: fluoroquinolone, aminoglycosides, macrolides
Cardio: procainamide, b-blockers
Psych: chlorpromazine, risperidone, lithium
Glucocorticoids

Question 12

What bloods should be investigated in MG?

Answer 12

Serum ACh receptor antibodies (+ve in ~85-90%)
CK: normal r/o myopathies
Anti muscle-specific tyrosine kinase antibodies (+ve in ~40%)
Anti-voltage gated Ca2+ channel antibodies (Lambert-Eaton syndrome)

Question 13

What imaging should be performed in MG? Why?

Answer 13

CT Thorax: exclude thymoma in the mediastinum

Question 14

What specialist investigations should be performed in MG?

Answer 14

Single fibre EMG: Jitter (variability in latency from stimulus to muscle potential). high sensitivity (92-100%).

NCS: Repetitive stimulation shows decrements of muscle action potential.

Question 15

Which investigation is no longer performed in MG?

Answer 15

Tensolin test: IV edrophonium reduces muscle weakness temporarily,
risk of cardiac arrhythmias

Question 16

What investigations should be performed in suspected myasthenic crisis/ pre-crisis?

Answer 16

Serial pulmonary function tests
FVC + negative inspiratory force (NIF)
In crisis, low FVC + low NIF

Question 17

How can signs of MG be classified?

Answer 17

Generalised (affecting many muscle groups)
Bulbar (affecting bulbar muscles)
Ocular

Question 18

What is myasthenia gravis associated with?

Answer 18

Other AI conditions (e.g. pernicious anaemia, thyroid disorders, RhA, SLE)
Thymomas (breakdown of immune tolerance occurs in thymus)
Thymic hyperplasia in 50-70%

Question 19

What bulbar signs may be elicited in MG?

Answer 19

Reading aloud may cause dysarthria or nasal speech

Question 20

What signs should you look for in the limbs in MG?

Answer 20

Test the power of a muscle before + after repeated use of the muscle

Question 21

What occurs in the Tensilon Test in MG?

Answer 21

Short-acting anti cholinesterase (edrophonium) increases ACh levels + causes a rapid + transient improvement in clinical features
Risk of bradycardia: so generally avoided

Question 22

What is Lambert-Eaton myasthenic syndrome?

Answer 22

AI disorder of NMJ
May occur as a paraneoplastic disorder a/w cancer (small cell carcinoma of the lung), or without cancer, as part of a general AI state
Antibodies against VGCC; impairs neuromuscular transmission by inhibiting inward Ca2+ current + subsequent release of ACh into the synaptic cleft.

Question 23

Why are signs referred to as “bulbar”?

Answer 23

bulbar = relating to the medulla oblongata (CN 9, 10, 11 +12 have their nuclei in the medulla)

Question 24

What is the first line drug used in MG?

Answer 24

Pyridostigmine (long acting acetylcholinesterase inhibitor)

Question 25

What further management may eventually be required in MG, in addition to Pyridostigmine?

Answer 25

1. Prednisolone
2. Azathioprine/ Cyclosporine/ Mycophenolate mofetil
3. Thymectomy

Question 26

Describe management of myasthenic crisis

Answer 26

Intubate early
High dose prednisolone
plasmapheresis or intravenous immunoglobulins