NMJ and Muscle disorders

Question 1

what distinguishes a LMN lesion from a UMN one

Answer 1

weakness
low tone
fasiculations

Question 2

what part of spinal cord to motor neurones arise from

Answer 2

ventral horn

Question 3

what do the terminal projections of motor neurones do

Answer 3

give rise to very fine projections that run along the muscle cell
synapse at motor end plate

Question 4

how many motor neurones can a muscle respond to

Answer 4

only one

Question 5

what is between the motor neurone and muscle

Answer 5

synaptic cleft/ gutter

Question 6

describe transmission at the NMJ

Answer 6

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

Question 7

what does acetylcholinesterase do

Answer 7

converts acetyl choline in acetate and choline

Question 8

what happens to choline

Answer 8

is sequestered back into presynaptic vesicles

Question 9

what are the main presynaptic NMJ disorders

Answer 9

botulism
lambert eaton myasthenic syndrome
abnormality of calcium/ sodium/ magnesium

Question 10

what causes botulism

Answer 10

clostridium botulinum (organism present in soil- food and wounds can become infected)

Question 11

what does botulinum toxin do

Answer 11

cleaves presynaptic proteins involved in vesicle (acetylcholine) formation and blocks vesicle docking with the presynaptic membrane

Question 12

what are the features of botulism

Answer 12

rapid onset weakness without sensory loss

overwhelming paralysis

Question 13

what causes lambert eaton myasthenic syndrome (LEMS)

Answer 13

antibodies to presynaptic calcium channels leads to reduced vesicle release of ACh

Question 14

what is LEMS strongly associated with

Answer 14

underlying small cell carcinoma

50% paraneoplastic syndrome, 50% autoimmune

Question 15

what is the treatment for LEMS

Answer 15

3-4 diaminopyridine

Question 16

what is the treatment for botulism

Answer 16

self limiting condition

supportive- ventilation

Question 17

what is the main post synaptic MNJ disorder

Answer 17

myasthenia gravis

Question 18

what causes myasthenia gravis

Answer 18

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%

Question 19

where do you get weakness in MG

Answer 19

strange presentations

• around eyes (ptosis)
• paraveterbal muscles
• facial muscles (square smile, flat facial expression)
• resp muscles (resp arrest)

Question 20

what do the antibodies do in MG

Answer 20

block the binding of ACh and also trigger inflammatory response that damages the folds of postsynaptic membranes

Question 21

what organ is particular involved in MG

Answer 21

thymus- 75% have hyperplasia/ thymoma

Question 22

who gets MG

Answer 22

females in 3rd decade

males in 6/7th decade

Question 23

what are the clinical features of MG

Answer 23

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)

Question 24

what is the acute treatment for MG

Answer 24

• acetylcholinesterase inhibitor - pyridostigmine (allows persistence of ACh in the synaptic cleft)
• IV immunoglobulin

thymectomy (controversial)

Question 25

what is the long term treatment for MG

Answer 25

-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

Question 26

what drug should you always avoid in MG

Answer 26

gentamicin - can cause MG crisis

Question 27

what is the prognosis for MG

Answer 27

3-4% | from resp failure and aspiration pneumonia/ immunosuppression in the elderly

Question 28

what is the smallest contractile unit in skeletal muscle

Answer 28

muscle fibre - sarcomere

Question 29

what is a sarcomere

Answer 29

from one z line to the next, is the basic functional unit of the muscle

Question 30

what are the features of LEMS

Answer 30

gradual onset of leg and arm weakness

Question 31

what surrounds each muscle fibre

Answer 31

endomysium

Question 32

what forms a fascicle

Answer 32

20-80 muscle fibres

Question 33

what wraps round a fascile

Answer 33

perimysium

Question 34

what wraps around skeletal msucle

Answer 34

epimysium (extends from tendon)

Question 35

what are the features of smooth muscles

Answer 35

not striated single central nucleus gap junction between cells no sarcomeres

Question 36

what are the different types of muscle fibres

Answer 36

type 1- slow oxidative (dense capillary network, myoglobin, resist fatigue) type IIa - fast oxidative (aerobic metabolism) type IIb- fast glycolytic (easily fatigued)

Question 37

what are fasciculations

Answer 37

visible fast, fine, spontaneous twitch

Question 38

can fasciculations be normal

Answer 38

yes in healthy muscles (large) can be caused by stress, caffeine, fatigue

Question 39

when are fasciulations abnormal

Answer 39

occur in denervated muscle which becomes hyperexcitable - usually a sign of disease in the motor neurone not the muscle (abnormal in small muscles)

Question 40

what is myotonia

Answer 40

failure of muscle relaxation after use | due to chloride channel disorder (usually hereditary)

Question 41

what are the symptoms/ signs of muscle disease

Answer 41

myalgia muscle weakness wasting hyporeflexia

Question 42

what are the causes of neck weakness with drop

Answer 42

motor disease muscle disorders myositis myopathy

Question 43

what are the immune mediated muscle diseases

Answer 43

dermatomyositis | polymyositis

Question 44

what are the inherited muscle diseases

Answer 44

muscular dystrophies dystrophinopathies limb girls muscular dystrophies myogenic dystrophy

Question 45

what are the congenital muscles diseases

Answer 45

congential myasthenic syndromes | congenital myopathies

Question 46

what are the symptoms/ signs of polymyositis

Answer 46

``` symmetrical, progressive proximal weakness developing over weeks to months Raised CK (in 1000s)- responds to steroid ```

Question 47

what are the symptoms/ signs of dermatimyositis

Answer 47

clinically similar but associated with skin lesions 'heliotrope rash' 50% have underlying malignancy

Question 48

what is inclusion body myositis

Answer 48

slowly progressive weakness in 6th decade of life with characteristic thumb sparing

Question 49

what is myotonic dystrophy

Answer 49

commonest muscular dystrophy | AD

Question 50

what are the features of myotonic dystrophy

Answer 50

``` myotonia weakness cataracts ptosis frontal balding cardiac defects ```

Question 51

what are the features of muscular dystrophies

Answer 51

inherited noninflammatory progressive no central/ peripheral nerve abnormality duchenne and becker most common

Question 52

what are the common infective muscle diseases

Answer 52

viral- coxsacchie trypanosomiasis cistercosis - uncooked pork borrelia

Question 53

what are the toxic causes of muscle disease

Answer 53

drugs | venoms

Question 54

what are the congenital muscle diseases

Answer 54

congenital myasthenic syndromes | congenital myopathies

Question 55

what drugs cause myopathies

Answer 55

statins- myalgia, myopathy, persistent myositis steroids duiretics

Question 56

what is rhabdomyolosis

Answer 56

dissolution of muscle | damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma

Question 57

what can cause rhabdomyolsis

Answer 57

crush injuries toxins post convulsions extreme exercise

Question 58

what are the features of rhabdomyolsis

Answer 58

myalgia muscle weakness myoglobinuria complications = acute renal failure and DIC

Question 59

what are the MRC muscle power grades

Answer 59

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