myasthenia gravis Flashcards
definition of myesthenia gravis
An autoimmune disease affecting the neuromuscular junction = weakness of skeletal muscles.
aetiology of myesthenia gravis
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).
epidemiology of myesthenia gravis
Prevalence is 8–9 in 100 000
more common in females at younger age
equal gender at middle age
sx of myesthenia gravis
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
signs of myesthenia gravis
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
eyes signs of myesthenia gravis
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
bulbar signs of myesthenia gravis
Reading aloud may provoke dysarthria or nasal speech after 3 min
limbs signs of myesthenia gravis
test power of muscle before and after repeated use eg 20repititions
Ix for myesthenia gravis
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
blood results for myesthenia gravis
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)
tensilon test for myesthenia gravis
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
nerve conduction study for myesthenia gravis
repetitive stimulation demonstrating decrements of the muscle action potential
May differentiate between myasthenic gravis and Lambert–Eaton myasthenic syndrome.
EMG for myesthenia gravis
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
CT thorax and/or CXR for myesthenia gravis
visualise thymoma in mediastinum/malignancies in lung
what are myasthenia sx exacerbated by
pregnancy
low K
infection
over treatment
change of climate
emotion
exercise
gentamicin
opiates
tetracycline
quinine
B blockers
ddx for myasthenia gravis
polymyositis/other myopathies
SLE
takayasu’s arteritis (fatigability of the extremities)
botulism
associations with myasthenia gravis
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
myasthenic crisis
life threatening weakness of resp muscles during relapse
difficult to distinguish from a cholinergic crisis ie overtreatment
monitor FVC
Lambert-Eaton myasthenic syndrome
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
patholgy of MG and lambertpeaton syndrome
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
mx of myasthenia
pyridostigmine - acethylchlinesterase inhibitor
steroids and azathioprine/mycophenalate/ccyclosporin - immunosuppression
plasma exchange and IVIG - rapid short term improval
thymectomy
px factors of myasthenia gravis
age
autoab subtype
thymus hx
response to rx
mx of myasthenia crisis
- intubation and ventialtion
- plasma exchhnage / IVIG
- supportive care
