Myasthenic disorders Flashcards
Myasthenia gravis definition
autoimmune disorder of the neuromuscular junction with impairment of the signal transmission
What 2 autoantibodies could be present in MG?
acetylcholine receptor (AChR)
muscle specific kinase (MuSK)
seronegative MG
AChR MG epidemiology
bimodal distribution
peaks young and old
earlier onset more common in women
MuSK MG epidemiology
one peak later in life
geographical distribution according to distance from the equator (most prevalent in mediterranean countries)
MG clinical features
fluctuating weakness and fatigability of the skeletal muscles:
- ocular
- generalised
- generalised + bulbar
limb weakness usually symmetric and more proximal
bulbar = dysphagia, dysarthria, dysphonia, dyspnoea
What is a life-threatening complication of MG?
myasthenic crisis - acute restrictive respiratory failure
Clinical subtypes of AChR MG?
early-onset: <40-50y, female predominance, associated with thymic hyperplasia
late-onset: >50y, male predominance, thymic pathology rare
thymoma-associated: paraneoplastic subtype, no gender predominance
What subtype are the autoantibodies in AChR-MG? How does this block receptor function
IgG1, 2 and 3
- strong interchain bonds between the 2 Fc parts of the IgG
- divalent binding of the antibody to their antigen
- internalisation of the antigen
- complement activation
- block of the receptor function
What subtype are the autoantibodies in MuSK-MG? How does this block receptor function
Mainly IgG4 subclass
- monovalent binding to the antigen
- no complement activation
- no internalisation of the target molecule
- direct blocking effect on MuSK function
Thymus normal function
promotes normal development of T lymphocytes
- T cells undergo positive and negative selection according to their ability to react to the antigen presenting cells
What happens to the thymus in myasthenia gravis?
lymphofollicular hyperplasia of the thymus can be detected in early-onset MG:
- increased number of germinal centres and lymphoid follicles
- MHC class 2 expressing thymic epithelial cells present the unfolded AChR subunits and activate auto-reactive CD4+ T cells
Where does muscle weakness start and spread to in Lambert Eaton Myasthenic syndrome?
usually starts on pelvic girdle, then spreads to upper limbs and finally to oculobulbar muscles
What lung cancer is Lambert Eaton Myasthenic syndrome associated with?
small cell lung cancer
Which antibodies are present in Lambert Eaton myasthenic syndrome?
antibodies against the pre-synaptic voltage-gated calcium channel
Lambert Eaton myasthenic syndrome treatment
3,4-Diaminopyridine
