Neurology/Neurosurgery - Myasthenia Gravis (Core Clinical Problems - Generalised weakness/squint)

Question 1

What is the pathology behind myasthenia gravis?

Answer 1

Autoimmune disease

- Antibodies to acetylcholine receptor at post-synaptic membrane of the NMJ

Question 2

Why should you get a CXR in a patient with myasthenia gravis?

Answer 2

in 15% of patients there will be a thymus pathology - either hypertrophy or neoplasm; seen as mediastinal widening

Question 3

How would you see a thymoma or thymus hypertrophy on CXR?

Answer 3

Mediastinal widening
Anterior mediastinal
Still visible lung markings as not lung pathology

Question 4

What is the incidence of MG?

Answer 4

0.4/100,000

Question 5

What is the prevalence?

Answer 5

10/100,000

Question 6

Looking at the incidence and prevalence is long term survival good or bad?

Answer 6

Good; 25x the number of people living with it than diagnosed with it yearly

Question 7

What age groups does MG typically affect?

Answer 7

all age groups (trick question sorry)

Question 8

What are the classical muscular symptoms of MG?

Answer 8

1) Fatigue of muscles that gets worse throughout the day
2) Ptosis - worsening throughout the day
3) Diplopia with limited eye movements
4) may include facial weakness (myasthenia snarl)
5) weakness of eye closure

Question 9

What bulbar symptoms may occur in MG?

Answer 9

1) Dysphasia with nasal regurgitation of liquids

2) dysarthria with nasal qualities

Question 10

Acute involvement of bulbar or respiratory symptoms is worrying; why?

Answer 10

Neurological emergency; myasthenia crisis, respiratory failure usually involving mechanical ventilation

Question 11

Which muscles are most commonly affected in MG? What is the pattern?

Answer 11

Proximal pectoral and pelvic girdle, neck and face, >distal musculature.
Usually worse at the end of the day and better at start

Question 12

Diagnostic factors include:

Answer 12

1) Muscle fatiguability
2) Ptosis
3) Diplopia
4) Dysphagia
5) Dysarthria (with nasal speech)
6) Facial paresis
7) proximal limb weakness
8) SOB - less common

Question 13

What investigations do you want to do?

Answer 13

1) ACh receptor autoantibodies - 15% false negative rate
2) Tensilon test - transient, rapid improvement when edrophonium is given
3) EMG - including single fibre studies
4) TFTs - to assess for associated thyrotoxicosis
5) Striated muscle antibody - positive un most patients with thymoma
6) CT of anterior mediastinum for thymus enlargement

Question 14

What is the first line treatment for MG?

Answer 14

Anti-cholinesterases such as pyridostigmine/rivastigmine

Question 15

How do anti-cholinesterases help?

Answer 15

Symptom control; increases ACh in the cleft and therefore allows more transmission

Question 16

What are some of the common side effects of anti-cholinesterase?

Answer 16

if requiring increases doses may cause:

• diarrhoea
• abdo pain
• vomiting
• increased salivation
• bradycardia
• extrapyramidal signs
• insomnia

Question 17

In extreme cases what is the worst thing an anti-cholinesterase might do?

Answer 17

Might make the weakness worse - cholinergic crisis

Question 18

Prednisolone may be used for MG - when?

Answer 18

When the disease is moderately severe and poorly/unresponsive to treatments

Question 19

When should a patient be admitted before starting steroids?

Answer 19

When the symptoms are not purely ocular

Question 20

Why should a patient be admitted before starting steroids?

Answer 20

Can make the disease worse initially - start low go slow.

Question 21

When should an immunosuppressant be used for MG?

Answer 21

Azathioprine may be used for moderately to severe disease in conjunction with steroids

Question 22

Thymectomy is useful in all patients but especially which category and why?

Answer 22

Younger patients, early in course, may reduce requirement for subsequent therapy and in rare cases cause complete remission

Question 23

Plasma exchange or IVIG should be given to which patients?

Answer 23

• in preparation for thymectomy

- severe disease

Question 24

List some complications of plasma exchange

Answer 24

Coagulopathy
Thrombocytopenia
Electrolyte disturbances 
arrythmia
hypotension
Bleeding
Pneumothorax 
venous thrombosis
line infection 
Sepsis 
(Monitor coagulation, FBC and U+E daily)

Question 25

List complications of IVIG

Answer 25

Headache
Aseptic meningitis
Migraine headache
Back Pain
Fever 
Chills
Hives
Anaphylactoid reaction (rarely) 
Anaemia/reduced WBC/thrombocytopenia
Renal Failure
Stroke 
MI

Question 26

Renal failure, stroke and MI are more likely to occur in IVIG with what type of patients?

Answer 26

Older patients with pre-existing risk factors for renal and cardiovascular disease

Question 27

How might we reduce risk of headache, back pain, renal failure, stroke or MI with IVIG?

Answer 27

Slower infusion

Question 28

Prophylactic paracetamol or NSAIDS may prevent which side effects of IVIG?

Answer 28

Fever
Chills
Headache
Back pain

Question 29

Prophylactic dexamethasone IV may be useful in patients on IVIG, especially those suffering worsening migraine - true/false

Answer 29

True

Question 30

Which class of antibiotics should be avoided in myasthenia gravis? Why?

Answer 30

Aminoglycosides

Blocks ACh receptor at NMJ and thus can worsen symptoms

Question 31

Define myasthenia crisis

Answer 31

• Respiratory failure
• Caused by MG exacerbation
• often requiring hospitalisation and mechanical ventilations

Question 32

What percentage of patients will experience a myasthenic crisis? What is the usual timeframe?

Answer 32

15-20% will experience one

Most commonly within the first 2 years. May recur

Question 33

What might provoke myasthenic crisis?

Answer 33

infection 
aspiration
medicines (especially high dose steroid) 
malignancy
Surgery
Failure of medication concordance 
trauma

Question 34

what do you do in a myasthenic crisis?

Answer 34

• serial FVC; <15ml/Kg and inspiratory pressure <20cmH2O, consider mechanical ventilation
• do not await ABG result; unlikely abnormal except very late in decompensation

Question 35

What complications are likely due to dysphagia?

Answer 35

• Aspiration pneumonia
• Myasthenic crisis
• rarely requires PEG tube for feeding

Question 36

What is a mimic of MG?

Answer 36

Lambert eaton myasthenic syndrome (LEMS)

Question 37

What is the difference between MG and LEMS?

Answer 37

1) LEMS is paraneoplastic
2) does not affect ACh receptors post synaptically; affects pre-synaptic voltage gated calcium channels
3) does no exhibit repeated fatiguability

Question 38

What is the commonest cause of LEMS?

Answer 38

Small cell lung cancer