Myasthenia Gravis

Question 1

what is myasthenia gravis

Answer 1

acquired auto immune disorder affecting nmj

excessive fatigue of striated muscle

longer term permenant deterieration and muscle weakness

affects nmj- multiple sclerosis = similar

longer you have myasthenia - higher risk of permeant derivation

signs and symptoms are variable and are dependent on when you are seen

Question 2

what are some of the symptoms of mystenia gravis

Answer 2

breathing difficulty

difficulty to chew or swallow

difficulty to climb stairs , lift objects

difficulty in talking

drooping position of head

change in voice

facial paralysis

fatigue

weakness of eye muscles

Question 3

what is the incidence of myasthenia gravis

Answer 3

incidence= 5/7 rare

affects women more than it affects men but they are increasingly affected over the age of 40

very variable

complete remission in 18% of patients

can be 40 yrs between firsts signs and next episodes

Question 4

what is the aetiology of mg

Answer 4

antibodies to nicotinic ach receptors reduce post synaptic receptors by degrading receptor proteins

directly blocking receptor sites

destroying receptor sites

(more difficult for ach to reach the muscle and hit it)

Question 5

what antibodies are found to other proteins in mg

Answer 5

muscle specific kinase

can lead to neurotransmission
problems at nmj

lrp4 - can be found in mg and ocular mg

Question 6

how can the nmj be affected in mg

Answer 6

surface area = degraded in mysthemia

muscle contraction is less

Question 7

how does the aetiology of mg cause muscle fatigue

Answer 7

ach continues to be released from the presynaptic membrane until supplies are diminished - resulting in muscle fatigue

common eye signs can be - proptosis and ptosis

Question 8

what is commonly found in patients with mg

Answer 8

85% of mg patients have nicotinic ach receptor antibodies circulating in the blood

post synaptic membrane of nmj is less folded in mg patients and synaptic space is wider

enlarged thymus glands - antigen antibody reaction between endplate protein and thymus epitheliel cells

Question 9

what is the function of the thymus gland

Answer 9

• in children and babies - has a major role in puberty
• programmes abc into attacking invading foreign cells such as viruses

important in normal immune response development

Question 10

what is the role of the thymus gland in mg

Answer 10

it is enlarged in approx 75% of mg cases - thymomas in some patients - especially over the age of 40

thymus removal cures 35% and improves a further 33% of patients

thymectomy even effective in cases of non thymomamtmus mg with remission rate higher than for non surgical treatment (catalo et al 2018)

removal advocated in mg patients between 10-40 years of age within the first 3 years of disease onset

Question 11

what are the classifications of mg

Answer 11

paediatric- neonatal, congenital, juvenile

adult- ocular, mild/moderate, acute fulminating , late severe

Question 12

how is the severity of mg classified

Answer 12

grade 1 = less severe - restricted to eom only

grade 4 = myasthenia crisis

Question 13

what is drug related mg

Answer 13

following d peniclliamine for rheumatoid arthritis

some antibiotics cardiovascular agents , anti-depressants , sedatives , anaesthetics, can induce or aggravate the condition

important to note this in history

Question 14

what muscle groups are affected on mg

Answer 14

eom - diplopia and ptosis are the presenting feature in 50% of cases and will be present in 90% of patients

bulbar muscles - innervated by cranial 5, 7, 9, 10,

limb/ trunk muscle - 15- 20% start with arm or leg weakness
weakness of intercostal muscles causing breathing problems

Question 15

what is the natural history of mg

Answer 15

variable disease affecting individuals very differently sometimes mimics other diseases

if onset initially in eom prognosis better than if in limbs

disease may peak 2-5 years from onset that improve

periods of remission = quite common

mg = 50 times more common in graves disease patients

Question 16

what is a myasthenia crisis

Answer 16

classed as a medical emergency

intercostal muscles are affected and mg patient is unable to breathe without ventilator

15- 20- % of generalised mg patients will have at least one myasthenia crisis

50% of known cause others triggered by stress, infection , surgery or drug sensitivity

Question 17

what is ocular mg

Answer 17

may mimic any pupil sparing painless eye movement problem

unilateral or bilateral- 3rd, 4th, 6th nerve palsy

isolated muscle palsy - gaze palsy , one and a half syndrome

gaze palsy INO, one and a half syndrome ( 3rd year)

extremely variable = may change muscles from one visit to the next - hard to diagnose

Question 18

what are common ocular presenting features on ocular mg

Answer 18

diplopia and ptosis are present in 75% of cases

10-16% of all mg is confined to the eyes

if no spread to other muscle groups within the first 2 years of onset it is unlikely to ever to do so

Question 19

why are eom particulary affected

Answer 19

eom are highly innervated with densely concentrated receptors - small reduction in ach receptors and ach levels quickly result in fatigue

increased sensitivity of eom nmj

specific antibodies direct at specific sites on eom

Question 20

what are some clinical features of ocular myasthenia

Answer 20

ptosis - unilateral or asymmetrical or bilateral

may increase on least affected side if examiner holds most affected lid

fine fluttering lid movements

patient may use brow to lift lid or adopt app (upper eyelid fold may be reduced/ absent)

Question 21

what are some lid abnormaliies seen in mg

Answer 21

afternoon ectropion
- through reduced nmj activity and your muscles not working not working the bottom lid begins to droop

Question 22

what are other lib abnormalities seen

Answer 22

cogans lid twitch - lid twitchs upwards

and overshoots before settling on moving from depression to normal

lids forced open easily - (weak obicularis)

lids separate slightly on voluntary closure

nystagmoid jerks of upper lid ( rare )

Question 23

can mg be cured

Answer 23

cannot be completely cured can go into periods of remission, autoimmune disorder

Question 24

what would be included in the orthoptic investigation

Answer 24

history- medication , fatigue , arm weakness

eyelid assessment - measure ptosis- if stable give fresel prism

Question 25

why is the diagnosis of mg hard to arrive at

Answer 25

can be difficult as weakness is a common complaint of many diseases

correct diagnosis is important so that appropriate treatment can be offered

Question 26

what tests are used in the diagnosis of mg

Answer 26

tension test - 10 mg injected intravenously (2mg initially followed by rest )

intravenous atropine if side effects occur

improvement in 1 min lasts ofr 5 mins

positive response - diagnostic but negative response cannot exclude diagnosis

because there are multiple receptors involved

blood test for ach receptor site antibodies

presence suggests mg = highly probable

absence cannot exclude disease

anti musk antibody test - present in 50% of those who don’t show ach receptor site antibodies

absence doesn’t exclude mg

Question 27

what other tests can be used in the diagnosis of mg

Answer 27

sleep test - improvement after 30 mins in darkened room - ask pt to go to sleep for 30mins and try and see them upon waking

symptoms may reappear 1-5 mins after reawakening

repeptitive nerve stimulation

saccadic velocity measurement

EMG

single fibre emg

Question 28

what other diagnostic tests may be done If mg = suspected

Answer 28

ct scans of chest to check for enlarged thymus/thyoma

chest xray

Question 29

what are the general treatment options for mg

Answer 29

long acting ach drugs

immunosuppressive agents

plasmapheresis

intravenous immunoglobins

thymectomy (not for ocular mg) appears effective in the treatment for non - thymotoamous mg ) cataneo et al 2018)

Question 30

ocular management

Answer 30

plotting course of disease / serial record

prisms or occlusion to make patient comfortable

ptosis props

botulinum toxin a injection

strabismus surgery if really stable

Question 31

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