NMJ and muscle pathologies Flashcards
Symptoms of LMN disorders?
Weak
Low tone
Fasciculations
What innervated skeletal muscle fibres?
Motor neurones whose cell bodies arise in the ventral horn of the spinal cord
What is the motor end plate?
Synapses formed between motor neurons and the muscle
What is a motor unit?
A single motor neurone and all of the muscle fibres it innervates
What occurs when an action potential reaches the nerve?
Ca 2+ channels open
Vesicles of ACh are released into the synaptic cleft
ACh receptor opens and renders the membrane permeable to Na/K+ ions
Depolarisation starts an action potential at the motor end plate
What is the action of acetylcholinesterase?
Breaks up ACh into acetate and choline
What happens to choline in the synaptic cleft?
Sequestered into presynaptic vesicles
How does botulism affect the presynaptic membrane?
Cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with the presynaptic membrane
What are the symptoms of botulism toxin?
Rapid onset weakness WITHOUT sensory loss
What is the pathogenesis of Lambert Eaton Myasthenic Syndrome?
Antibodies to presynaptic calcium channels leading to vesicle release
Strong assoc with small cell lung carcinoma
What is the treatment for LEMS?
3-4 diaminopyridine
What is the pathogenesis of myasthenia gravis?
Autoimmune antibodies to AChR resulting a reduced number of functioning receptors leading to muscle weakness and fatigability
Flattening of endplate folds
Even with normal ACh; transmission becomes inefficient
What is the role of the thymus in myasthenia?
75% have hyperplasia or thymoma
What is the epidemiology of myasthenia gravis?
Occurs at any age; 2 peaks of incidence
Females in 3rd decade
Males in 6/7th decade
Female:male ration 3:2
What are the clinical features of myasthenia?
Fluctuating weakness throughout the day; tends to be best in the morning
Extraocular weakness
Facial and bulbar weakness
Limb weakness is proximal
What is the treatment for myasthenia?
Acetylcholinesterase inhibitor; pyridostigmine
IVIg in acute emergencies
Thymectomy
What immune modulating drugs are used in myasthenia?
Steroids
Azathioprine
Mycophenolate
Emergency; plasma exchange or immunoglobulin
What drug should be avoided in myasthenia?
GENTAMICIN
Lots of antibiotics CI, lots of anaesthetic drugs are CI
What do most people with myasthenia die from?
Resp failure
Aspiration pneumonia
Immunosuppression SE in the elderly
Co-morbid
What are the different types of muscle fibres?
Type 1; slow oxidative; resist fatigue, myoglobin, RED
Type 2a; fast oxidative; aerobic metabolism
Type 2b; fast glycolytic, easily fatigued
What is a fasciculation?
Visible, fast, fine, spontaneous twitch
Why do fasciculations occur?
Healthy muscle; stress, caffeine, fatigue
Denervated muscle which becomes hyperexcitable
What are fasciculations a sign of?
MND
What is myotonia?
Failure of muscle relaxation after use
Chloride channel issues
What are the Si/Sy of muscle disease?
Myalgia
Muscle weakness
Wasting
Hyporeflexia
What can cause a head drop?
Myopathy
Myositis
MND
What muscles are commonly weak in muscle disease?
Proximal leg
Shoulder girdle
Neck weakness
What are immune mediated muscle weaknesses?
Dermatomyositis
Polymyoisitis
What are inherited muscle disorders?
Muscular dystrophies
Limb girdle muscular dystrophies
Myotonic dystrophy
What are congenital muscle disorders?
Congenital myasthenic syndromes
Congenital myopathies
What is the pattern of muscle disease in polymyositis?
Symmetrical
Progressive proximal weakness developing over weeks to months
What test will help in the diagnosis of polymyositis?
Raised CK
Muscle biopsy
EMG
Difference between polymyositis and dermatomyositis?
Dermatomyositis will show cutaneous features such as heliotrope rash and shawl sign
Also has a 50% recurrence with an underlying malignancy
What is the presentation of inclusion body myositis?
Slowly progressive weakness in the 6th decade with characteristic thumb sparing
What is the inheritance of myotonic dystrophy?
AD of trinucleotide repeat disorder with anticipation
What is the presentation of myotonic dystrophy?
Myotonic Weakness Cataracts Ptosis Frontal balding Cardiac defects
What are the inherited muscular dystrophies?
Duchenne and Becker
What infective causes can result in muscle disease?
Viral; coxsackie
Trypanosomiasis
Cisticercosis
Borrelia
What are some common drugs that cause myopathy?
Necrotising myopathies; stating, fibrates
Corticosteroid myopathy
Lysosomal storage myopathy; hydroxychloroquine, amiodarone
Hypokalemic myopathy; diuretics, OCP
What is rhabdomyolysis?
Damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into the plasma such as myoglobin
What can cause rhabdomyolysis?
Crush injuries
Toxins
Post-convulsions
Extreme exercise
What is the triad of rhabdo?
Myalgia
Muscle weakness
Myoglobinuria
What are common complications of rhabdo?
AKI
DIC
What should be tested in examination of muscles?
Inspection; thin, wasted, fasciculations Palpation Strenth Neck strength Core strength Fatiguability
What does 0 on the MRC muscle power grading mean?
No movement at all
What does 1 on the MRC muscle power grading mean?
Flicker of movement when attempting to contract the muscle
What does 2 on the MRC muscle power grading mean?
Some muscle movement if gravity removed but none against gravity
What does 3 on the MRC muscle power grading mean?
Movement against gravity but not against resistance
What does 4 on the MRC muscle power grading mean?
Movement against resistance but not full strength
What does 5on the MRC muscle power grading mean?
Normal strength
Is 4 on the MRC muscle power grading split up?
Yes; can be 4+ or 4-
