myasthenia gravis

Question 1

definition of myesthenia gravis

Answer 1

An autoimmune disease affecting the neuromuscular junction = weakness of skeletal muscles.

Question 2

aetiology of myesthenia gravis

Answer 2

impairment of NMJ transmission - because of auto-Ab against nAChR on post-synaptic side of NMJ

B and T cells implicated

paraneoplastic subtype (Lambert-Eaton myasthenic syndrome) caused by auto-Ab against pre-synaptic Ca ion channels impairing ACh release

associated with other autoimmune conditions eg pernicious anaemia and thymoma development. Breakdown in immune tolerance thought to arise in thymus(75% have thymoma).

Question 3

epidemiology of myesthenia gravis

Answer 3

Prevalence is 8–9 in 100 000

more common in females at younger age

equal gender at middle age

Question 4

sx of myesthenia gravis

Answer 4

muscle weakness that worsens with repetitive use or towards the end of the day

slowly increasing or relapsing muscular fatigue

In Lambert–Eaton syndrome, the muscle weakness improves after repeated use.

muscle groups affected in order: extraocular, bulbar (swallowing, chewing), face, neck, limb girdle, trunk

ocular: drooping eyelids, diplopia

bulbar symptoms: facial weakness (myasthenic snarl), disturbed hypernasal speech, difficulty smiling chewing or swallowing - nasal regurg of fluids

Question 5

signs of myesthenia gravis

Answer 5

May be generalized (affecting many muscle groups), bulbar (affecting bulbar muscles) or ocular (affecting only the eyes).

ptosis

diplopia

myasthenic snarl on smiling

peek sign of orbicularis fatigability (eyelids begin to separate agter mannual opposition in sustained closure

on counting to 50 the voice fades - dysphonia is a rare presentation

tendon reflexes are normal

Question 6

eyes signs of myesthenia gravis

Answer 6

blateral ptosis, may be asymmetrical

complex ophthalmoplegia

ocular fatigability - ask look up for 1 min and watch for progressive ptosis

ICE on eyes test

• ice packs on closed eyes for 2mins can improve neuromuscular transmission, reducing ptosis
• +ve when ptosis improves by >-2mm from baseline

Question 7

bulbar signs of myesthenia gravis

Answer 7

Reading aloud may provoke dysarthria or nasal speech after 3 min

Question 8

limbs signs of myesthenia gravis

Answer 8

test power of muscle before and after repeated use eg 20repititions

Question 9

Ix for myesthenia gravis

Answer 9

blood

tensilon test

nerve conduction study

EMG

CT thorax and/or CXR

Ptosis improves by >2mm after ice application to the eyelid for >2min - not diagnostic

Question 10

blood results for myesthenia gravis

Answer 10

CK to exclude myopathies

serum AChR Ab - +ve in 80%

TFT - associated hyperthyroidism

anti-MUSK (muscle specific tyrosine kinase, especially in female) Ab (uncommon variant)

anti-voltage-gated-calcium-channel Ab (lambert-Eaton syndrome)

Question 11

tensilon test for myesthenia gravis

Answer 11

Short-acting anti-cholinesterase (e.g. edrophonium) increases acetylcholine levels by blocking its metabolism

= rapid and transient improvement in clinical features

avoided - risk of bradycardia (atropine and cardiac resus equipment close) and subjectivity of clinical features

Question 12

nerve conduction study for myesthenia gravis

Answer 12

repetitive stimulation demonstrating decrements of the muscle action potential

May differentiate between myasthenic gravis and Lambert–Eaton myasthenic syndrome.

Question 13

EMG for myesthenia gravis

Answer 13

Single-fibre EMG may demonstrate jitter (variability in latency from stimulus to muscle potential) indicating fluctuation in neuromuscular conduction.

Decremental muscle response to repetitive nerve stimulation

Question 14

CT thorax and/or CXR for myesthenia gravis

Answer 14

visualise thymoma in mediastinum/malignancies in lung

Question 15

what are myasthenia sx exacerbated by

Answer 15

pregnancy

low K

infection

over treatment

change of climate

emotion

exercise

gentamicin

opiates

tetracycline

quinine

B blockers

Question 16

ddx for myasthenia gravis

Answer 16

polymyositis/other myopathies

SLE

takayasu’s arteritis (fatigability of the extremities)

botulism

Question 17

associations with myasthenia gravis

Answer 17

autoimmune disease - SLE, RA

if <50yrs more common in women and associated with thymic hyperplasia

>50yrs - more common in men, associated with thymic atrophy or thymic tumour

Question 18

myasthenic crisis

Answer 18

life threatening weakness of resp muscles during relapse

difficult to distinguish from a cholinergic crisis ie overtreatment

monitor FVC

Question 19

Lambert-Eaton myasthenic syndrome

Answer 19

can be paraneoplastic (50% are associated with malignancies, in particular SCLC) or autoimmjne

AB are to voltage gated Ca channels on pre-synaptic membrane

; anti-P/Q type VGCC antibodies are +ve in 85–95%).

Sx:

• gait difficulty before eye signs
• autonomic involvement - dry mouth, constipation, impotence
• hyporeflexia and weakness, improve after exercise
• diplopia and resp muscle involvement are rare
• EMG - similar to MG except amplitude increases greatly post exercise

Question 20

patholgy of MG and lambertpeaton syndrome

Answer 20

ACh into synaptic vesicles

when AP arrives depolarisation opens VGCCs - in LE syndrome anti-P/Q type VGCC Ab disrupt this stahe

influx of Ca through VGCC triggers fusion of synaptic vesicles with pre-synaptic membrane and ACh released into synaptic cleft

ACh molecules cross the synaptic cleft by diffusion and bind to the receptors on the post-synaptic membrane = depol of post-synaptic membrane (the end plate potential)

change in post-synaptic membrane triggers muscle contraction at NMJ - in MG Ab block the post-synaptic ACh receptors - preventing the end plate potential from becoming large enough to trigger muscle contraction = muscle weakness

transmitter action is terminated by acetylcholinesterase, uptake into the pre-synaptic terminal or glial cells, or by diffusion away from the synapse

Question 21

mx of myasthenia

Answer 21

pyridostigmine - acethylchlinesterase inhibitor
steroids and azathioprine/mycophenalate/ccyclosporin - immunosuppression
plasma exchange and IVIG - rapid short term improval
thymectomy

Question 22

px factors of myasthenia gravis

Answer 22

age
autoab subtype
thymus hx
response to rx

Question 23

mx of myasthenia crisis

Answer 23

1. intubation and ventialtion
2. plasma exchhnage / IVIG
3. supportive care