Myasthenia gravis Flashcards
what is myasthenia gravis
Thomas Willis first described MG in 1683. The term Myasthenia is derived from Greek and means ‘Weak muscle’.
Acquired auto-immune disorder affecting neuromuscular transmission (similar to MS)
Excessive fatigue of striated muscle
Longer term permanent denervation and muscle weakness
what is the incidence of myasthenia gravis
incidence= 5/7 per 100, 000
more commonly affects woman but men are increasingly more affected
very variable- complete remisiion in 18% of patients
can be 40 years between first signs and next epsidode
what is the aetiology of myasthenia
Auto-immune disease
Antibodies to nicotinic ACh receptors reduce post synaptic receptors by:
- degrading receptor protein
- directly blocking receptor sites
- destroying receptor sites
What proteins aren’t found in MG
Muscle specific KINASE
MuSK protein (not found in ocular MG)- can also lead to neuro-transmission problems at the neuro-muscular junction
LIPOPROTEIN RECEPTOR RELATED PROTEIN 4 (LRP4)
can be found in MG and ocular MG
why do you get muscle fatigue in ach
ACh continues to be released from pre-synaptic membrane until supplies diminished, resulting in muscle fatigue
Blood findings in MG patients
85% of MG patients have nicotinic ACh receptorantibodies circulating in blood
Post synaptic membrane of neuromuscular junction is less folded in MG patients and synaptic space is wider
Enlarged thymus gland - antigen antibody reaction between endplate protein and thymus epithelial cells
What is the function of the thymus glans
Major role in babies and children up to puberty, then shrinks in size
programmes abcs into attacking and invading foreign cells such as viruses
important in normal development. response development
What is the role of the thymus gland in MG
Thymus gland enlarged in approx 75% of cases (thymomas in some patients, especially over 40 years of age)
Thymus removal cures 35% and improves a further 33% of MG patients
Thymectomy even effective in cases of non-thymomatous MG, with remission rate higher than for non-surgical treatment (Cataneo et al. 2018)
Removal advocated in MG patients between 10 - 40 years of age within 3 years of disease onset
Classifying MG
classified by paediatric populations and adult populations
Paediatric - neonatal, congenital and juvenile
Adult - ocular
- mild/moderate
- acute fulminating
- late severe
Grades of MG
Grade I
- restricted to EOM only
Grade IIa
- mild general disease
Grade IIb
- moderate general disease
Grade III
- severe general disease
Grade 5
- myasthenia crisis
Drugs related to mg
Following D-penicillamine for rheumatoid arthritis
Some antibiotics, cardiovascular agents, anti-depressants, sedatives, anaesthetics can induce or aggravate the condition
What muscle groups are affected
EOM - diplopia and ptosis are the presenting features in 50% of cases and will be present in 90% of patients
Bulbar muscles - innervated by V,VII, IX,X,XI cranial nerves
Limb/trunk muscles - 15-20% start with arm or leg weakness- weakness of intercostal muscles causes breathing problems
Natural history of MG
Variable disease, affecting individuals very differently (sometimes mimics other disease)
If onset initially in EOM prognosis better than if in limbs
Disease may peak 2-5 years from onset then improve
Periods of remission quite common
MG 50 times more common in Grave’s disease patients
Myasthenia crisis
Classed as a Medical Emergency
It is when intercostal muscles are affected and MG patient is unable to breathe without a ventilator
15-20% of generalised MG patients will have at least one myasthenic crisis
50% no known cause, others triggered by stress, infection, surgery or drug sensitivity
EOMs affected in MG
EOM highly innervated with densely concentrated receptors. Small reduction in ACh receptors and ACh levels quickly results in fatigue
Increased sensitivity of EOM neuromuscular junctions
Specific antibodies directed at specific sites on EOM
