Neuromuscular Disease Flashcards
How does curare affect cholinergic transmission and muscle contraction?
Competes for and blocks ACh receptor so no muscle stimulation occurs
Curare is only toxic when administered how?
Intravenous
Intramuscular
How does Botox affect cholinergic transmission and muscle contraction?
Cleaves proteins involved in ACh vesicle formation and blocks vesicle docking to prevent exocytosis
What happens molecularly in Lambert Eaton myasthenic syndrome?
Antibodies attack presynaptic Ca channels resulting in less NT release
Which cancer is associated with Lambert Eaton syndrome?
Small cell carcinoma (typically of the lung)
Which disease is the most common neuromuscular junction disorder?
Myasthenia gravis
Autoantibodies attack what in myasthenia gravis? What does this cause?
ACh receptors (MUSK receptors) Triggers inflammatory cascades that damage the folds of the postsynaptic membrane
When do symptoms start in myasthenia gravis?
When ACh receptors reduced to 30% of normal
A patient must have Autoantibodies to suggest myasthenia gravis. True/False?
False
Patient with fatigue and weakness without antibodies may still have it
Which organ must be screened/assessed in people with myasthenia gravis? What other investigations can be performed?
Thymus (arrange CT chest to check for thymoma or hyperplasia) Ice test to reduce ptosis Autoantibody screen Electromyography Muscle biopsy
Females are more affected than males by myasthenia gravis. True/False? What age group is most commonly affected?
True
20-30s
List clinical features of myasthenia gravis
Fluctuating weakness (typically proximal limbs)
Tiredness at end of the day
Extraocular weakness (ptosis, diplopia, ophthalmaplegia) - DIFFICULTY READING
Facial and bulbar weakness - DIFFICULTY CHEWING
What is the acute treatment for myasthenia gravis?
Acetylcholinesterase inhibitor (pyridosigmine) IV immunoglobulin/ plasma exchange Thymectomy
What are muscle fasciculations?
Visible fine fast spontaneous twitches that occur in denervated muscle that become excited
Indicates problem in motor neurone
What is myotonia? It occurs due to a problem in what ion channel?
Failure of muscle relaxation after use
Chlorine channel
What is the commonest muscular dystrophy?
Myotonic dystrophy
List clinical features of myotonic dystrophy
Myotonia
Weakness
Cataracts ('christmas tree')
Ptosis
Frontal balding
Cardiac defectsWhat is the synapse between a motor neurone and muscle called?
Motor end plate
What ion channel is responsible for the release of acetylcholine into the synaptic cleft?
Ca voltage-gated channel
What is the outcome of acetylcholine binding to the post-synaptic receptor?
Renders the membrane potential permeable to sodium and potassium ions and depolarisation starts an action potential at motor end plate
What drug is used to manage Lambert Eaton myasthenic syndrome?
3-4 diaminopyridine
Name two pre-synaptic disorders affecting the NMJ
Botulinism
Lambert Eaton myasthenic syndrome
Which part of the NMJ does myasthenia gravis affect?
Post-synaptic membrane
What is the long term management for myasthenia gravis?
Immunomodulators
Steroids
Steroid sparing agents (azathioprine, mycophenolate)
Which drug should be avoided in myasthenia gravis?
Gentamicin
What are the three main types of muscle found within the body?
Skeletal
Smooth
Cardiac
What are the three main types of muscle FIBRES found within the body?
- Slow oxidative
2a. Fast oxidative
2b. Fast glycotic
Outline the process of muscle contraction
- ATP is hydrolysed into ADP and Pi which binds to the mysosin head forming a crossbridge
- Crossbridge attaches to actin
- Myosin head pivots and bends as it pulls on actin, sliding towards the M line (ADP + Pi are released)
- New ATP attaches to myosin head and crossbridge detaches
- ATP splits into ADP + Pi and myosin head cocks
What are the four main clinical signs of muscle disease?
Myalgia
Muscle weakness
Wasting
Hyporeflexia
Name the two main causes of immune-mediated muscle disorder
Polymyositis
Dermatomyositis
List the main causes of muscle disorders
Immune Inherited Congenital Infective Toxic (drugs, venoms)
What is the characteristic clinical picture suggesting inclusion body myositis?
Slowly progressive weakness occuring in 60s with thumb sparing
Little response to steroid
What is the mechanism behind muscular dystrophy?
Abnormality in protein causing movement of muscle
Which micro-organisms most commonly cause muscle disorders?
Viral (coxsachie, trypanosomiasis)
Cistercosis (uncooked pork)
Borellia
What class of drug, in particular, can cause myopathy as a common side effect?
Statins
What is rhabdomyolysis?
Damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma
What is the potential aetiology of rhabdomyolysis?
Crush injury
Toxin
Post convulsion
Extreme exercise
List the clinical features of rhabdomyolysis
Triad of myalgia, weakness, myoglobinuria
List potential complications of rhabdomyolysis
Acute renal failure
Disseminated intravascular coagulation
What is the genetic mechanism behind myotonic dystrophy?
Chromosome 19 trinucleotide expansion
What is the broad presenting picture in NMJ disease?
Fatiguable motor symptoms with no sensory symptoms
What is the first and second line investigation in myasthenia gravis?
- AChR antibodies
2. MUSK antibodies
