Disorders of Neuromuscular Junction Flashcards
3 general features of lower motor neurone disorders?
weakness
low tone
fasciculations
3 general features of UPN disorders?
stiffness
spasticity
increased tone
cell bodies of motor neurones arise where?
ventral horn of spinal cord
what is the motor end plate?
the terminal portion of motor neurones give rise to very fine projections which run along the muscle cell
synapses formed between these projections and the muscle = end plate
each muscle can only respond to one motor neurone>
true
describe what happens at the NMJ?
AP moves along nerve
voltage gated calcium channels open allowing influx of calcium
vesicles of acetyl choline released into synaptic cleft
ACh diffuses across synaptic cleft
ACh receptor opens and renders membrane permeable to Na/K ions
the depolarisation starts an AP at the motor end plate
acetylcholinesterase breaks down ACh into acetate and choline
- choline is sequestered into presynaptic vesicles
what is curare?
chemical compound which ooccupies same position on ACh receptor but doesn’t open ion channel, so no muscle contraction can take place
- causes resp arrest when given IV or IM
where can problems occur at NMJ?
presynaptic (e.g botulism, lambert eaton)
synaptic cleft
ACh receptor (e.g myasthenia gravis)
what is botulism?
aka clostridium botulinum
- organism in soil which can infect food and wounds
- common in black tar heroin
- toxin cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with the presynaptic membrane
- rapid onset weakness (6 hrs) without sensory loss
- causes paralysis
- not permanent?
what is LEMS?
lambert eaton myasthenic syndrome
- antibodies to presynaptic calcium channels leads to less vesicle release
- strong association with underlying small cell carcinoma
- treatment = 3-4 diaminomyridine
what is myasthenia gravis?
most common NMJ disorder
autoimmune - antibodies to ACh receptors
causes reduced number of functioning receptors leads to weakness and fatiguability
- often in unusual muscle groups - eyes
- can also cause resp arrest
- bilateral facial weakness (can be missed as bilateral)
pathophysiology of MG?
reduced number of ACh receptors and flattening of endplate folds causes inefficient ACh transmission, even wit normal amounts of ACh
ACh antibodies found in most patients which block binding of ACh and trigger inflammatory acscades which damage folds of posysynaptic membrane
when do MG symptoms start?
symptoms start when ACh receptors reduced to 30% normal
which organ is often involved in MG?
thymus
75% have hyperplasia or thymoma
epidemiology of MG?
peaks of incidence - females in 3rd decade and males in 60s-70s
more common in females overall
more common in thyroid disease/addisons disease
clinical features of MG?
fluctuating weakness (worse through the day)
extraocular weakness, facial and bulbar weakness
limb weakness when it occurs is usually proximal (not usually first symptom)
how is MG manages acutely?
acetylcholinesterase inhibitor (pyridostigmine)
IV Ig
thymectomy (even in the absence of thymus abnormality it helps)
long term treatment of MG?
immunomodulating
steroids (prednisolone)
steroid sparing agents (azathioprine/mycophenolate)
plasma exchange or Ig in emergency
what must be avoided in MG?
gentamicin!
- causes myasthenic crisis > resp failure
depolarizing anaesthetic agents
mortality of MG?
3-4%
what causes death in MG?
usually due to resp failure in elderly
side effects of immunosuppression in elderly can also cause problems
types of muscle?
skeletal muscle
cardiac muscle
smooth muscle
describe features of skeletal muscle
striated
highly organised
muscle fibres each surrounded by thin layer of endomysium
20-80 fibres grouped to form a fascicle encapsulated by perimysium
large number of fascicles encapsulated in epimysium = muscle
smooth muscle?
not striated single central nucleus gap junctions between cells significant connective tissue around them no sarcomeres
muscle fibre types?
type 1 = slow oxidative, dense capillaries, myoglobin, resist fatigue
type 2a = fast oxidative, aerobic metabolism
type 2b = fast glycolytic, easily fatigued
what is a faciculation?
visible fast, fine, spontaneous twitch
what causes fasciculations?
may occur in healthy muscle - precipitated by stress, caffeine and fatigue
occur in denervated muscle which become hyperexcitebale
usually sign of disease in MN, not the muscle
what is myotonia?
failure of muscle relaxation after use
due to problems in Cl channel
signs and symptoms of muscle disease?
myalgia
muscle weakness (often specific patterns of weakness - neck, shoulder and pelvic girdle)
wasting
hyporeflexia
3 groups of muscle disorders?
immune mediated
inherited
congenital
examples of immune mediated muscle disorders?
polymyositis
- symmetrical progressive proximal weakness over weeks-months
- CK in thousands
- responds well to steroids
dermatomyositis
- similar but with skin lesions (heliotrope rash etc)
- can have underlying malignancy
what is the most common inherited muscle disorder?
myotonic dystrophy (type of muscular dystrophy)
- AD
- trinucleotide repeat disorder with anticipation
other less common muscle disorder types?
toxic
infective
describe degenerative muscle disorders and what category they fit into?
used to think they were inflammatory but don’t respond to steroids
inclusion body myositis
typically presents as slowly progressing weakness in 6th decade of life with thumb sparing
features of myotonic dystrophy?
myotonia weakness cataracts ptosis frontal balding cardiac defects
what are muscular dystrophies?
inherited, non-inflammatory progressive disorders of muscle
no central or peripheral nerve abnormality
Duchenne and becker muscular dystrophies most common
examples of infective muscle disorders?
viral - coxsaccie
trypanosomiasis
cistercercosis - uncooked pork
borrelia
examples of toxic muscle disorders?
caused by drugs or venoms
examples of congenital muscle disorders?
congenital myasthenic syndromes
congenital myopathies
examples of drugs which can cause a myopathy?
statins some steroids (dexamethasone) amiodarone colchicine diuretics oral contraceptives D-penicillamine interferon alpha
what is rhabdomyolysis?
dissolution of muscle
damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma
what can cause rhabdomyolysis?
crush injury toxins post convulsions extreme exercise elderly lying on floor for long time after a fall
features of rhabdomyolysis?
triad of myalgia, muscle weakness and myoglobinuria
can cause acute renal failure and DIC
how is muscle examined?
inspection - thin? wasting? fasciculation?
palpating
strength testing across joints
neck strength (should never be able to overcome neck muscles)
core strength
fatiguability
how is muscle power graded?
MRC grading
0 = no movement
1 = flicker of movement
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
5 = normal strength
