L42 Diseases of the NMJ and Motor Unit Flashcards
what describes muscle weakness that originates in the nervous pathway (motor neuron, axon or NMJ)?
neurogenic
what describes muscle weakness that originates in the muscle itself?
myogenic/myopathic
what are the sites of lesions in the motor units?
soma axon schwann cell nerve ending synaptic cleft end plate muscle fiber
what can cause nerve cell lesions in the soma or axon?
diseases
toxins
drugs
trauma
what are the sx/sx of lesions of the nerve cell in soma or axon?
- atrophy/weakness
- fibrillations and fasciculations
- muscle fiber replaced by fibrous CT
what are examples of diseases that can occur in the soma or axon?
Lou Gehrig’s disease (ALS)
poliomyelitis
what does poliomyelitis affect?
muscles and nerves - particularly motor neuron of the spinal cord ventral horn
how is poliomyelitis transmitted?
direct person to person contact through oral, nasal and anal secretions
where does poliomyelitis enter, proliferate and spread?
mouth and nose
throat and intestinal tract
vascular and lymph system
how effective is the polio vaccine?
90% effective
what can cause lesions of Schwann cells?
autoimmune disease
toxins
what are the sx/sx of lesions of Schwann cells?
demyelination
conduction slowing or block
what are toxins and diseases can effect the NMJ?
botulism alpha-latrotoxin beta-bungarotoxin curare Lambert Eaton syndrome
what happens in botulism?
toxic protease of anerobic bacteria inhibits ACh exocytosis = paralysis of all muscles
what are the 3 ways that botulism is spread
eating food that contains botulism toxin
infection of a wound with clostridium botulinum
consuming spores of clostridium botulinum
what happens with alpha-latrotoxin
black widow spider makes a neurotoxic venom
which causes a huge release of ACh
venom acts at nerve endings = tetanus and eventual paralysis
the venom reaches blood and lymph
what happens with beta-bungarotoxin?
snake venom toxin inhibits ACh exocytosis
what happens with curare (tubocurarin)?
arrowhead poison found in plants
non-depolarizing muscle relaxant
blocks ACh receptors at NMJ = temporary paralysis
what is Lambert Eaton syndrome (at the cellular level)
autoimmune disease against voltage-gated Ca2+ channels in motor neuron terminal which causes insufficient release of ACh at the synaptic cleft
in Lambert eaton syndrome, continued contractions will cause an _____ in the [ACh] in the cleft until it reaches a concentration sufficient to elicit a proper contraction
increase
strength increases with repeats muscular contraction
what is lambert eaton syndrome associated with?
oat cell carcinoma of the lung
in lambert eaton syndrome, what are the physiological changes seen at the end plate?
- reduced amplitude of EPP
- many EPPs do NOT attain threshold in muscle fibers
- amplitude of minEPP is unchanged
what are signs of Lambert eaton syndrome?
strength increase with activity
decreased reflexes
waxing on EMG (little to big)
what are possible treatment options for Lambert eaton syndrome?
- remove tumor + immunosuppresents
- do plasma exchange
- calcium gloconate (enhance Ca2+ influx into nerve terminal)
- 4-aminopyridine (block K+ channels, prolong presyn AP and improve NT release)
what are examples of synaptic cleft impairments?
congenital myesthenias
myesthenia gravis
myotonia congenita
what are the types of congenital myasthenias?
- AChE deficiency
- slow channel syndrome
- other
what happens in AChE deficiency (congenital myasthenias)?
EPP is large and long
single stimuli delivered at low freq = single motor twitch
high freq. motor stimuli = temporal summation of EPPs + depolarization block of muscle
what happens in slow channel syndrome (congenital myasthenias)?
binding of ACh to nAChR = prolonged opening of ACh receptor channel
if the channel is open too long = prolonged depolarization = depolarization block
muscle weakness, rapid fatigue, progressive atrophy
what are the other forms of congenital myasthenias?
abnormal binding of ACh to nAChR
very brief opening times of ACh-gated channels
what happens with myasthenia gravis?
autoimmune antibodies bind to alpha subunits of nAChR which block ACh ability to bind to receptor
most commonly affects young women and older men
antibodies do not compete with ACh
weakness NOT associated with denervation
serum from pts with MG causes disease symptoms in animals…
what are the structural changes that occur at the end plate due to myasthenia gravis?
fewer nAChR
wider cleft
smaller/shallow junctional folds
what is myasthenia gravis sometimes associated with?
thymus tumors
what are the symptoms of MG?
weakness of voluntary muscle which improves with rest and worsens with activity
difficulty swallowing(choking?)
diplopia (double vision)
ptosis
late day paralysis
myasthenic crisis - difficulty breathing = may be life threatening
what are the signs associated with dx of MG?
EMG waning pattern Tensilon test (AChE) test +
what are possible treatment options for MG?
neostigmine/pyridostigmine (AChE inhibitor)
prednisone (cortisone)
axathioprine/cyclosporine (immunosuppresents)
plasma exchange (temporary improvement)
thymectomy (remission?)
describe myotonia congenita?
autosomal dominant
Cl- channels are decreased in number which causes slower muscle relaxation
Cl- channels usually reset Vm after an AP, thus without the proper amount will increase excitability (unopposed K+ = soon depo) and decrease relaxation
pt suffer from muscle stiffness and hypertrophy
describe Duchenne’s MD?
x linked recessive
absense of Dystrophin
onset in early childhood
die of respiratory and/or cardiac failure
what is LMN syndrome?
second order neurons are lost
where are the possible lesions sites for LMN syndrome?
motor axon or soma in the spinal cord or brainstem (CNs)
what are the causes of LMN syndrome?
viral infections - poliomyelitis
trauma
neurodegeneration
what are the sx/sx of LMN syndrome?
weakness/paralysis loss of reflex fasciculations fibrillations atrophy
describe poliomyelitis
most cases affects the motor neurons in the ventral horn (but can affect the whole entire body)
severe cases cause permanent paralysis or death
how is poliomyelitis transmitted?
person to person contact (nose, mouth, fecal)
how is polio prevented?
vaccine
