Neurology- Lecture 20: Disease of the NM Junction Flashcards
Acetylcholine is a neurotransmitter in?
pg 8
what degrades it?
- all neuromuscular junctions
- preganglionic sympathetic neurons
- pre and postganglionic parasympathetic neurons
- many various areas of the cerebral cortex and basal ganglia
Its degraded by acetylcholinerase which hydrolyses it to choline and acetate.
Check out diagram on slide 12
The acetylcholine Receptor
The 2 major subdivisions of cholinergic receptors are:
- muscarinic (activated by muscarine)
- Either excitatory or inhibitory
- glands, heart and smooth muscles
Nicotinic
- Excitatory always
- postsynaptic ANS, adrenal medulla, NMJ, limbic system (most important neuromuscular junction in the limbic system)
What is Myasthenia Gravis (MG)?
what is it characterised by?
Neuromuscular disorder characterised by:
Weakness and fatigability of skeletal muscles
• Underlying cause is autoimmune attack on the AChR by
Anti-AChR antibodies
• Reduction in the number of ACh receptors (AChRs) in the neuromuscular junction (NMJ)
MG- Autoimmune attack.
What are the Multiple Mechanisms?
Dysfunction of the Ach receptors occurs in 3 distinct ways:
- Blockade of the active binding site on the receptors by the antibodies
- Damage to the postsynaptic muscle cell membrane by complement/antibody interactions- when the antigen attaches to an antibody the body sees it that something is wrong so immune system wants to get rid of it. Body destroys complex
- Accelerated turnover of receptors at the NMJ membrane by endocytosis-because the body knows the receptor isn’t working anymore it takes it into the cell and tries to make it another receptor. But takes time so doenst have enough Ach
What is the role of the Thymus in MG
Thymus may be involved
The mechanism of how the immune response is initiated and maintained in MG is not understood
• However, the thymus is abnormal in about 75% of MG
What is the pathogenesis with MG?
20
ACh is released in normal amount and structure
• Reduced numbers of ACh receptors on the muscle cell
membranes
• Postsynaptic folds are also reduced, flattened or simplified in nature
• These result in decreased efficiency of neuromuscular neurotransmission
• Reduced activation of receptors results in small endplate potential (EPP) which either fail to initiate or sustain muscle contraction
- Under normal circumstances the amount of ACh released at the NMJ decreases during repeated activity (presynaptic run-down)
- In successive nerve impulses, presynaptic run-down combined with inefficiency of neuromuscular transmission results in the activation of fewer and fewer muscle fibers causing an exaggerated weakness called myasthenic fatigue
- This also accounts for the declining response on EMG seen on repetitive stimulus
What are the clinical features of MG
24 + 25
Affects all ages and both sexes. Prevalence in Australia is 117 per one million (2009), F:M ratio is 3:2
• Peak of incidence: women in their 20s and 30s, and men in their 50s and 60s
• Weakness and fatigability of muscles
MG- Differential Dx
27
- Lambert-Eaton myasthenic syndrome (LEMS)
- Drug-induced myasthenia
- Botulism
- Thyroid disease
- MS
- ALS
- Basilar Artery Thrombosis
- Congenital myasthenic syndromes
- Mitochondrial diseases
What is the treatment of MG
28
• Anticholinesterase medications
Myasthenic Crisis and management.
• •
Is when the weakness of respiratory muscles becomes so severe as to require respiratory assistance
May be precipitated by:
What is Lambert-Eaton Myasthenic Syndrome? (LEMS)
30
• Is a rare presynaptic autoimmune disorder
• Autoantibodies against the Ca channels of the presynaptic
membranes
• Release of Ach is impaired
• Initial symptoms similar to MG:
Clinical presentation of LEMS?
31
- Clinical manifestations often precede cancer identification*
- Most patients express autonomic symptoms (dry mouth, impotence, postural hypotension)*
- DTRs are hypotonic or absent
- High frequency EMG is diagnostic
- An increase in reflex activity after a few contractions is a pathognomonic sign of LEMS
- Managed by Surgery (in case of cancer), steroids, IVIg, plasmapheresis and pyridostigmine
