Myasthenia Gravis

Question 1

Describe the aetiology of myasthenia gravis?

Answer 1

• Autoimmune disorder – can have more than 1 autoimmune disorder (e.g. DM, Grave’s, Rheumatoid Arthritis)
  o Nothing is usually in isolation
• Formation of acetylcholine receptor site antibodies
  o These antibodies prevent acetylcholine from binding & reduce effectiveness of the neurotransmitter (means cannot sustain muscle movement)
• Acetylcholine continues to be released (brain still sending message to muscle to move)
  o This maintains the striated muscle contracture until the stores are drained
   This then shows the classic early muscle fatigue

Question 2

What is the aetiology of myasthenia gravis?

Answer 2

• Autoimmune – regarding the antibodies – at muscle end plate
• Other autoimmune conditions – DM, Crohn’s, arthritis
  o If have one then likely to have 2 – take detailed H&S
  o Someone else in family will have another condition
• MG can be congenital/juvenile – things changing all time
  o When things are changing consider MG as diagnosis
• Antibodies are stopping the firing of the nerve impulses – acetylcholine is not able to get though
• MG affects striate muscles
• Ocular MG is more common than general MG – EOMs are working much more
• Muscle will start moving but then cannot maintain the movement
  o Not a nerve palsy – nerve is still functioning normally
• Problem is at muscle nerve palsy – may need to CT scan thymoid gland
• General MG can be life-threatening – cannot ignore that it may be generalised MG
• Ocular MG – blood test often comes back normal – so then look for fatigue, look for fluttering of eye movements

Question 3

Describe the mechanism of myasthenia gravis?

Answer 3

Normally: Acetylcholine is being picked up & is binding to receptor sites, being absorbed, muscle is contracting, eyes are able to move freely
In myasthenia gravis: - Antibodies developed over receptor site -> they are fielding off acetylcholine
- Antibodies are stopping acetylcholine coming in & binding
- Some acetylcholine will escape in so eyes can make some movement but cannot sustain this movement because there is insufficient acetylcholine being connected to that muscle

Question 4

What are the types of myasthenia gravis?

Answer 4

• Systemic MG – eyes also affected – this type can be fatal due to difficulty of the striated muscles – e.g. px may choke on food, stop breathing etc
• Ocular MG – will not have generalised systemic problems
  o Systemic and/or ocular

Question 5

Describe the features of myasthenia gravis?

Answer 5

• Characterised by excessive fatigue-ability of striated muscle
   By time have done full eye test – px may be sitting with a ptosis
• EOM, facial, bulbar, neck, limb girdle, distal limb & trunk muscles
  o Px cannot maintain a smile, px may struggle walking up/down stairs
• 80-90% of pxs w/ general MG have receptor site antibodies in their blood serum
  o Compared to only 40-50% in ocular MG
   Hard to diagnose
• When respiratory muscles are severely affected it can be fatal
• EOM’s may be mostly affected as they have a v high concentration of receptors & an ↑sensitivity of the neuromuscular junction
• It may be associated w/ other autoimmune diseases: Diabetes, Graves’ Orbitopathy & Rheumatoid Arthritis

Question 6

What are the symptoms of myasthenia gravis?

Answer 6

• Generally, symptoms of MG ↑(get worse) as day goes on
  o Muscles have had a rest so lots of Acetylcholine going through them
  o Different from thyroid eye disease who starts day feeling dreadful
• Pxs may be symptoms free in morning & only complain of fatigue by evening
  o Ask in H&S, “is it worse in morning or evening?”

Question 7

Describe the ocular symptoms of myasthenia gravis?

Answer 7

• Ptosis – can be unilateral/bilateral/asymmetrical – can have no ptosis at start of test & it appears during the test
  o Measure their palpebral aperture before you start any tests – if you suspect MG
  o If congenital then there from birth but if newly acquired ptosis that gets worse through the day then SUSPECT MG
• Diplopia – may not have it in morning – may be after using eyes all day
  o May or may not have dip – depends on muscles that are affected & symmetry (whether one eye is affected more than other will determine if they have horizontal &/or vertical diplopia)
  o May be variable – different EOM affected day by day
  o So if px presents once with difficult moving eyes in one direction then next time you see them it is in another direction  SUSPECT MG
• Inadequate lid closure – weakness of orbicularis
  o Px unable to squeeze eyes tight – if you try to open their eyes you could
  o If you can prise open the eyelids then shows weakness of orbicularis  sign of MG

Question 8

Describe ptosis and assessment of ptosis in myasthenia gravis?

Answer 8

• Usually, 1st presenting sign of MG
• Bilateral by asymmetrical
• Ptosis increases throughout day
• Assessment of Ptosis:
  o Measure palpebral aperture by getting px to either look in distance or at near target – make sure in primary position & not looking down
   Measuring distance between upper & lower lid margin
  o Ptosis should ↑ on continued elevation or repeated up & down gaze, or in extreme cases lids may drop on continues gaze in primary position (PP)
  o +ve Cogan’s Lid Twitch
  o Pxs should look down for ~15secs, then re-fixate in PP – a twitch can bee seen in upper lid as it overshoots midline & then returns to its ptotic position
  o ‘Flutter type’ upper lid movements can be observed due to lid twitches (as acetylcholine is being absorbed)
   Sign of Cogan’s Lid Twitch
   May be a very variable eye movement
  o If you hold most affected eyelid open, the innervational drive to both upper eyelids is reduced & the ptosis on the other less affected eye ↑
  o Frontalis overaction in an attempt to raise eyelids can give rise to apparent upper lid retraction (as using frontalis muscle so severely to keep eye as wide open as possible)

Question 9

Describe diplopia in myasthenia gravis?

Answer 9

• Will vary – depends which muscle is most fatigued at the time
• Can be horizontal/vertical/both & will vary throughout the day
• MG may cause/mimic any type of muscle palsy
• Limited elevation is most common EOM defect in MG
• Pseudo INO
  o If have what looks like MR palsy
• Isolated IR palsy
  o Quite rare
• Pseudo gaze palsy where they cannot look in one direction – appears px cannot look L or R
• Pseudo 3rd, 4th, 6th nerve palsies
• MG can be a pseudo anything – can mimic any EOM condition
• Orbicularis weakness
  o Ask px to close their eyes tightly (ask them to bury their eyelashes into their eyelid) & then examiner tries to open them, whilst they keep them shut – in normal musculature you will not be able to but easily opened in MG

Question 10

Describe the systemic signs of mysathenia gravis?

Answer 10

• All dependent on which muscle groups are affected
• Ensure you ask for signs of general MG in case hx
  o Difficulty chewing/swallowing (Jaw Muscles)
  o Difficulty speaking (bulbar muscles) – do they tire when they speak? Slurring words by end of conversation?
  o Breathlessness (Respiratory Muscles) - DO NOT IGNORE
  o Fatigue climbing stairs or holding arms up high – shows a weakness of the limb girdle muscle – may start climbing well then not able to maintain the pace
   Ask them to hold their arms out to the side – normal px can hold their arms out for quite a long time but px with MG will not be able to
  o Lack of facial expression (Facial Muscles) – may look glum/sad

Question 11

What is the classification of myasthenia gravis?

Answer 11

• Children:
  o Neonatal – rare
  o Congenital – infants may be affected w/ both ocular & systemic MG
  o Juvenile –from birth to puberty (average age of px of 8-12 years) similar to adult cases
• Adults:
  o Ocular – that does not become generalised after 2 years since onset
   If it does not become generalised MG in 1st 2 years then it probably will not & will remain ocular MG (often does become generalised though)
  o Mild/Mod Generalised MG – ocular signs before disease spreads to skeletal & bulbar muscles
  o Acute Fulminating MG – rapid onset w/ early involvement of respiratory muscles (can be quite devastating for px)
  o Late Severe MG – can develop in ocular or mild group, 2 years after onset

Question 12

What are the investigations carried out in a px who may have myasthenia gravis?

Answer 12

• Ice pack test (if px has ptosis) – get ice pack and put it on eyelids – cooling everything down can allow release of acetylcholine back into muscle & eyelid can start to come up (doesn’t always work)
  o Lowering temp can improve symptoms
• Ice pack applied to eyelid can improve the ptosis
• Sleep test
  o Ask px to go out into waiting room or tx room bed & have a nap for 30 mins
   Lid position will improve if px has MG

Blood Test:
* Serum blood testing for acetylcholine receptor site antibodies – ask GP for
* 80-90% seen in General MG
* 40-50% seen in Ocular MG
* Do exclude MG if -ve blood result

EMG:
* Electromyography is carried out to record the electrical activity of the skeletal muscles
* Single or multiple muscle fibres may be tested/biopsied (invasive)
* Nerve supply to muscles are electronically stimulated & muscle activity is then recorded

Tensilon Test:
* Edrophonium (aka tensilon) is a short acting anticholinesterase
* Injected intravenously
* If +ve MG then muscle function should improve
* High risk of reaction to edrophonium – high risk of cardiac arrest – NOT USED ANY MORE
* 1st a test does of 2mg is delivered into vein & flushed through with saline
* If px becomes brachycardic due to hypersensitivity then atropine should be given to reverse effects
* If no reaction, then the further 8mg is delivered & px is assessed
* Usually performed on HESS screen
* Observation of ptosis
o Or using EMG to assess improvement in muscle function as px had tensilon injected

Question 13

What is the management of myasthenia gravis?

Answer 13

• If think it is systemic MG – MUST phone GP and say you are concerned they have this
  o Speak to them and tell them to make sure this px will be looked after – just in case they then had a problem
• If they do not have any of the systemic MG signs/symptoms then think it is ocular MG
  o Still need to refer them into the hospital but with less worry about the px – i.e. they are less likely to choke etc
  o If just ocular – they will be chewing fine, no speech difficulties, & only have a ptosis
   Urgent referral if only OCULAR MG – want them seen at hospital within next few weeks
• Ophthalmologist may trial a longer acting anticholinesterase drug e.g. pyridostigmine or mestinon
  o These have opposite effect of the antibodies & allow for acetylcholine release into the muscles
   If px has a -ve blood test but is trialled on these drugs & improves then confirms diagnosis of MG
  o These drugs can be long term  do not often have side effects
• CT scan of thymus gland – as thymus can be enlarged in MG - rarer
  o If gland is enlarged (Thymoma) it can be removed
   Thus eliminating the B-cells that can produce the acetylcholine receptor antibody
• Immunosuppression w/ systemic steroids – beginning w/ 10mg prednisolone
• Azathioprine or myophenolate can enhance the steroid action
• In severe generalised MG: Plasmapheresis – removal of plasma & antibodies & replacement w/ plasma substitute  EXTREME CASES
  MG is v difficult to diagnose

Question 14

What is the ocular management of myasthenia gravis?

Answer 14

• MG that remains confined to EOMs for >2yrs is unlikely to progress into generalised MG
  o In 158 pxs, a study found that conversion rate to generalised MG was 20.9%
• Fresnel prisms – will need to monitor these pxs frequently as may be base out one week & base in the next
• Ptosis props – allows lids to be lifted in evenings but px does not need it in morning
• Occlusion – to stop px having diplopia – especially if v variable
• Botox – less likely used – may weaken an opposing muscle
• Strabismus surgery under local anaesthesia w/ adjustables
  o This is ONLY considered when MG is stable

If have ocular MG then it is only the EOM that are affected & all the other muscles are unaffected