NMJ Disorders Flashcards
Describe normal transmission within a neuromuscular junction
An action potential causes Ca2+ influx which triggers release of ACh into the junction. ACh bind sarcolemmal AChR, which can cause end plate potentials that sum to form a muscle fiber contraction.
What is responsible for limiting the action of ACh in NMJs?
Acetylcholinesterase (AChE)
Which NMJ disorders are presynaptic and which are postsynaptic?
Presynaptic: Lambert-Eaton myasthenic syndrome, Botulism
Postsynaptic: Myasthenia gravis
Which NMJ disorders are autoimmune disorders?
Myasthenia gravis (immune targets AChR) Lambert-Eaton myasthenic syndrome (immune targets voltage gated Ca channels)
How does myasthenia gravis typically present?
Begins at any age presents typically with ptosis, diplopia, dysarthria, dysphagia, and facial/neck/limb weakness.
Sensation and reflexes are intact.
Often fatigue with certain activities.
What is the pathogenesis of myasthenia gravis?
Antibodies to AChR block receptors and increase turnover. Weakness is due to loss of functional AChR. Progressive weakness is due to exercise/activity resulting in decreased release of ACh in an already AChR depleted setting.
How is myasthenia gravis diagnosed?
Clinical diagnosis
Positive tensilon test (edrophonium, AChE inhibitor)
EMG shows abnormal NMJ transmission
Increased serum Ab to AChR (most specific test)
How is myasthenia gravis treated?
Anticholinesterase drugs
Thymectomy
Immunosuppressant drugs (corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine)
Quick fixes: plasma exchange, IVIG
How does Lambert-Eaton Myasthenic syndrome present?
Fatigable weakness of proximal limbs, trunk
Exertion improves power and hyporeflexia
Autonomic symptoms like dry mouth and orthostasis
What disorder is often associated with LEMS?
Small cell lung cancer
What is the treatment of LEMS?
Find and treat underlying cancer
Drugs to enhance ACh release (guanidine, 34diaminopyridine)
Immunosuppressives
