NMJ and muscle disorders Flashcards
What is Lambert Eaton Myasthenic syndrome LEMS
Autoimmune condition with Ab forming against presynaptic Ca channels
Characteristics of LEMS
Proximal muscle weakness
autonomic features
absent deep tendon reflexes
Diagnosis and treatment of LEMS
Anti-VGCC Ab - Dx
diaminopyridien - Mx
What is myasthenia gravis MG
Autoimmune condition affecting the postsynaptic ACh receptors
Features of MG
Thymoma
Ptosis, diplopia, internuclear ophthalmoplegia
Fatiguability - especially after exercise
jaw, facial, phayngeal and respiratory muscles affected
Myasthenia crisis = weakness of respiratory muscles
bulbar palsy
proximal limb muscle weakness
Drugs that can exacerbate MG
Gentamicin B blockers Verapamil Phenytoin Lithium Penicillamine chloroquine
Investigations and management of MG
Ix - anti-AChR, anti-MUSK, TFT, CT thymus
Mx - Pyridostigmine, thymectomy
Management of myasthenic crisis
plasmapharesis and IVIG
Features of myotonic dystrophy
Myotonia = impaired muscle relaxation following use Distal muscle weakness Ptosis Cataracts Cardiac defects Frontal balding
features of LMN disorders
weakness
hypotonia
fasciculations
features of UMN disorders
hypertonia
spasticity
stiffness
what is a motor unit
aMN and all the skeletal muscle fibres it innervates
what is a motor end plate
synapse formed between the motor neuron and muscle
describe the presynaptic part of neurotransmission
AP moves along the nerve causing depolarisation
voltage gated Ca channels open causing Ca influx
ACh released from vesicles into synaptic cleft
describe the postsynaptic part of neurotransmission
ACh diffuses across synaptic cleft
AChR open meaning membrane is permeable to Na and K ions
this causes depolarisation at the motor end plate
which enzyme breaks down ACh at the synaptic cleft
acetylcholinesterase
why is curare dangerous
occupies same position on AChR but does not open ion channel therefore no muscle contraction –> respiratory muscle paralysis and failure
curare is only toxic when administered PO, true or false
FALSE
toxic when IV/IM
list PRE synaptic disorders
botulism
LEMS
which microorganism causes botulism and where is it found
clostridium botulinum
soil
how does botulinum toxin work molecularly
cleaves presynaptic proteins involved in vesicle formation
features of botulism
rapid onset weakness with no sensory loss
what is LEMS associated with
SCLC
Myasthenia gravis MG is a pre/post synaptic disorder
POST synaptic disorder
what is the most common NMJ disorder
MG
there is flattening of endplate folds in MG, true or false
true
in MG, even with normal amount of ACh, transmission is effective, true or false
false, because there are not enough AChR
when do symptoms of MG start
when AChR reduce by 30%
which antibodies are associated with MG
ACh antibodies
what else is important to look for in patient with MG
thymoma
which cranial nerves are affected in bulbar palsy
CN IX, X, XI, XII LMN
what is pyridostigmine
acetylcholinesterase inhibitor
allows persistence of ACh in synaptic cleft
which antibiotic must be avoided in those with MG and why
gentamicin
causes myasthenic crisis and respiratory failure
sarcomeres are present in smooth muscle, true or false
false
NO sarcomeres
only in skeletal and cardiac muscle
describe type 1 muscle fibres
slow oxidative
high resistance to fatigue
describe type 2a muscle fibres
fast oxidative
describe type 2b muscle fibres
fast glycolytic
low resistance to fatigue
what are fasciculations and why do they occur
visible fast fine spontaneous twitch
occur in denervated muscle which becomes hyperexcitable
what are fasciculations a sign of
disease of motor neuron
what is myotonia
failure of muscle relaxation after use
what is myotonia a disorder of
Cl- channel disorder
usually hereditary
what is dystonia
uncontrolled muscle cramps and spasms
list autoimmune muscle diseases
polymyositis
dermatomyositis
what is polymyositis and its treatment
symmetrical progressive proximal weakness developing over weeks-months
steroids
how high in CK in polymyositis
very high
>1000
how does dermatomyositis differ from polymyositis
heliotrope rash
underlying malignancy
what is inclusion body myositis
slowly progressive weakness in 60s
what is characteristic about inclusion body myositis
thumb sparing
inclusion body myositis is responsive to steroids, true or false
FALSE
no steroid response
what is the commonest muscular dystrophy
myotonic dystrophy
inheritance pattern of myotonic dystrophy and what the genetic defect is
AD
trinucleotide repeat disorder with anticipation
infective causes of muscle disease
coxsackie
trypansomiasis
cistercercosis
borrelia
toxic causes of muscle disease
drugs - statins, steroids, hydroxychloroquine, amiodarone, OCP, diuretics, IFNa
venom
what is rhabdomyolysis
skeletal msucle damage resulting in leaking of large quantities of toxic intracellular contents into plasma
causes of rhabdomyolysis
crush / trauma
seizures
statins
extreme exercise
triad of rhabdomyolysis
myalgia
muscle weakness
myoglobinuria
which scale is used to test muscle power
MRC muscle power grading
describe the MRC scale
0 - no movement at all
1 - flicker of movement when attempting to contract muscle
2 - some muscle movement with gravity removed
3 - movement against gravity but not resistance
4 - movement against resistance but not full strength
5 - normal strength
What is McArdles disease and what condition are patients at risk of
autosomal recessive condition with myophosphorylase deficiency resulting in impaired glucose release from glycogen in muscles
Rhabdomyolysis
appearance of Charcot Marie Tooth on histology
onion bulb appearance
