NMJ and Muscle disorders Flashcards
what distinguishes a LMN lesion from a UMN one
weakness
low tone
fasiculations
what part of spinal cord to motor neurones arise from
ventral horn
what do the terminal projections of motor neurones do
give rise to very fine projections that run along the muscle cell
synapse at motor end plate
how many motor neurones can a muscle respond to
only one
what is between the motor neurone and muscle
synaptic cleft/ gutter
describe transmission at the NMJ
Action potential moves along the nerve
Voltage gated calcium channels open allowing influx of calcium
Vesicles of acetyl choline released into synaptic cleft
Acetyl choline diffuses across the synaptic cleft
The acetylcholine receptor opens and renders the membrane permeable to Na / K ions
The depolarisation starts an action potential at the motor end plate
what does acetylcholinesterase do
converts acetyl choline in acetate and choline
what happens to choline
is sequestered back into presynaptic vesicles
what are the main presynaptic NMJ disorders
botulism
lambert eaton myasthenic syndrome
abnormality of calcium/ sodium/ magnesium
what causes botulism
clostridium botulinum (organism present in soil- food and wounds can become infected)
what does botulinum toxin do
cleaves presynaptic proteins involved in vesicle (acetylcholine) formation and blocks vesicle docking with the presynaptic membrane
what are the features of botulism
rapid onset weakness without sensory loss
overwhelming paralysis
what causes lambert eaton myasthenic syndrome (LEMS)
antibodies to presynaptic calcium channels leads to reduced vesicle release of ACh
what is LEMS strongly associated with
underlying small cell carcinoma
50% paraneoplastic syndrome, 50% autoimmune
what is the treatment for LEMS
3-4 diaminopyridine
what is the treatment for botulism
self limiting condition
supportive- ventilation
what is the main post synaptic MNJ disorder
myasthenia gravis
what causes myasthenia gravis
autoimmune disorder- antibodies against acetyl choline receptors
= reduced number of functioning receptors leads to muscle weakness and fatiguability
=flattening of end plate folds
even with normal amounts of ACh, transmission becomes insufficient when receptors drop by 30%
where do you get weakness in MG
strange presentations
- around eyes (ptosis)
- paraveterbal muscles
- facial muscles (square smile, flat facial expression)
- resp muscles (resp arrest)
what do the antibodies do in MG
block the binding of ACh and also trigger inflammatory response that damages the folds of postsynaptic membranes
what organ is particular involved in MG
thymus- 75% have hyperplasia/ thymoma
who gets MG
females in 3rd decade
males in 6/7th decade
what are the clinical features of MG
weakness typically fluctuating - worse at end of day
most commonly extraocular weakness, facial and bulbar weakness
limb weakness is typically proximal
(hard to keep eyes open watching TV,get tired eating meals)
what is the acute treatment for MG
- acetylcholinesterase inhibitor - pyridostigmine (allows persistence of ACh in the synaptic cleft)
- IV immunoglobulin
thymectomy (controversial)
what is the long term treatment for MG
-acetylcholinesterase inhibitor - pyridostigmine (allows persistence of ACh in the synaptic cleft)
(immunomodulation)
-steroids (high doses of prednisolone)
then
-steroid sparing agents (azathioprine/ mycophenolate)
emergency treatment with plasma exchange or immunoglobulin
what drug should you always avoid in MG
gentamicin - can cause MG crisis
what is the prognosis for MG
3-4%
from resp failure and aspiration pneumonia/ immunosuppression in the elderly
what is the smallest contractile unit in skeletal muscle
muscle fibre - sarcomere
what is a sarcomere
from one z line to the next, is the basic functional unit of the muscle
what are the features of LEMS
gradual onset of leg and arm weakness
what surrounds each muscle fibre
endomysium
what forms a fascicle
20-80 muscle fibres
what wraps round a fascile
perimysium
what wraps around skeletal msucle
epimysium (extends from tendon)
what are the features of smooth muscles
not striated
single central nucleus
gap junction between cells
no sarcomeres
what are the different types of muscle fibres
type 1- slow oxidative (dense capillary network, myoglobin, resist fatigue)
type IIa - fast oxidative (aerobic metabolism)
type IIb- fast glycolytic (easily fatigued)
what are fasciculations
visible fast, fine, spontaneous twitch
can fasciculations be normal
yes in healthy muscles (large) can be caused by stress, caffeine, fatigue
when are fasciulations abnormal
occur in denervated muscle which becomes hyperexcitable - usually a sign of disease in the motor neurone not the muscle
(abnormal in small muscles)
what is myotonia
failure of muscle relaxation after use
due to chloride channel disorder (usually hereditary)
what are the symptoms/ signs of muscle disease
myalgia
muscle weakness
wasting
hyporeflexia
what are the causes of neck weakness with drop
motor disease
muscle disorders
myositis
myopathy
what are the immune mediated muscle diseases
dermatomyositis
polymyositis
what are the inherited muscle diseases
muscular dystrophies
dystrophinopathies
limb girls muscular dystrophies
myogenic dystrophy
what are the congenital muscles diseases
congential myasthenic syndromes
congenital myopathies
what are the symptoms/ signs of polymyositis
symmetrical, progressive proximal weakness developing over weeks to months Raised CK (in 1000s)- responds to steroid
what are the symptoms/ signs of dermatimyositis
clinically similar but associated with skin lesions ‘heliotrope rash’
50% have underlying malignancy
what is inclusion body myositis
slowly progressive weakness in 6th decade of life with characteristic thumb sparing
what is myotonic dystrophy
commonest muscular dystrophy
AD
what are the features of myotonic dystrophy
myotonia weakness cataracts ptosis frontal balding cardiac defects
what are the features of muscular dystrophies
inherited
noninflammatory
progressive
no central/ peripheral nerve abnormality
duchenne and becker most common
what are the common infective muscle diseases
viral- coxsacchie
trypanosomiasis
cistercosis - uncooked pork
borrelia
what are the toxic causes of muscle disease
drugs
venoms
what are the congenital muscle diseases
congenital myasthenic syndromes
congenital myopathies
what drugs cause myopathies
statins- myalgia, myopathy, persistent myositis
steroids
duiretics
what is rhabdomyolosis
dissolution of muscle
damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma
what can cause rhabdomyolsis
crush injuries
toxins
post convulsions
extreme exercise
what are the features of rhabdomyolsis
myalgia
muscle weakness
myoglobinuria
complications = acute renal failure and DIC
what are the MRC muscle power grades
0 – no movement at all
1 - flicker of movement when attempting to contract muscle
2 – some muscle movement if gravity removed but none against gravity
3 - movement against gravity but not against resistance
4 – movement against resistance but not full strength
4- not alright but they are managing
4+ almost normal but not quite
5 – normal strength
