Supranuclear Disorders: Myasthenia Gravis (MG)

Question 1

Describe myasthenia gravis (MG)?

Answer 1

Myasthenia – Greek for weak muscle  Gravis – Latin for heavy/severe
Muscle may start off working but more ask the eyes to move, the more the muscles fatigues
IT IS NOT A PALSY
The nerve is functioning normally
MG is a myogenic disorder – disorder of muscles (specifically the muscle end-plates)
Can simulate other conditions – list this as differential diagnosis for any EOM issue

Question 2

What is the aetiology of myasthenia gravis (MG)?

Answer 2

• Autoimmune disorder – can more than 1 autoimmune disorder (e.g. DM)
  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
  o This maintains the striated muscle contracture until the stores are drained
   This then shows the classic early muscle fatigue
  Acetylcholine is being picked up & is binding to receptor sites, being absorbed, muscle is contracting, eyes are able to move freely
• 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 3

What are the types of myasthenia gravis?

Answer 3

• 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

Question 4

What are the features of myasthenia gravis?

Answer 4

• 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 5

What are the symptoms of myasthenia gravis?

Answer 5

• Generally, symptoms of MG ↑ 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 6

What are the 3 ocular symptoms of myasthenia gravis?

Answer 6

• Ptosis – can 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
• Diplopia – may not have it in morning – may be after using eyes all day
  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

Question 7

Describe ptosis in ocular myasthenia gravis?

Answer 7

• 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
   Sign of Cogan’s Lid Twitch
  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

Question 8

Describe diplopia in ocular myasthenia gravis?

Answer 8

• Will vary – depends which muscle is most fatigued at the time
• Can be horizontal/vertical/both & will vary throughout the day
• MG may cause any type of muscle palsy
• Limited elevation is most common
• 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
• 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 & then examiner tries to open them, whilst they keep them shut

Question 9

What are the systemic signs of myasthenia gravis?

Answer 9

• 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)
  o Breathlessness (Respiratory Muscles)
  o Fatigue climbing stairs or holding arms up high – shows a weakness of the limb girdle muscle
  o Lack of facial expression (Facial Muscles)

Question 10

What is the classification of myasthenia gravis?

Answer 10

• Children:
  o Neonatal – rare
  o Congenital – infants may be affected w/ both ocular & systemic MG
  o Juvenile – from birth to puberty 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
  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
  o Late Severe MG – can develop in ocular or mild group, 2 years after onset

Question 11

What are the investigations into myasthenia gravis?

Answer 11

• Ice pack test – 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 MG
  Blood Test
• Electromyography is carried out to record the electrical activity of the skeletal muscles
• Single or multiple muscle fibres may be tested
• Nerve supply to muscles are electronically stimulated & muscle activity is then recorded

Question 12

Describe the blood test result in myasthenia gravis?

Answer 12

• Serum blood testing for acetylcholine receptor site antibodies
• 80-90% seen in General MG
• 40-50% seen in Ocular MG
• Do exclude MG if -ve blood result

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 remove
   Thus eliminating the B-cells that can produce the acetylcholine receptor antibody
  MG is very difficult to diagnose

Question 14

What is the ocular mangement of myasthenia gravis?

Answer 14

• Fresnel prisms – 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