NMJ Disorders Flashcards
Describe the firing of action potentials during normal muscle contraction at LMNs.
AP reaches the motor neuron terminal -> Ca2+ influx facilitates presynaptic ACh release from vesicles -> ACh binds at nicotinic receptors in the end plate of the post-synaptoc muscle membrane -> activates ion channels and creates an end plate potential (EPP) -> contraction
What limits the effect of ACh and EPP?
Synaptic acetylcholinesterase, which breaks down ACh
What happens in MG?
AChR degraded or blocked, less ACh is able to bind, produces EPPs which are either initially below the threshold for generating APs or which become too low during repeated contractions; occurs at the post-synaptic NMJ
What occurs in LEMS?
Voltage-gated calcium channel at the pre-synaptic membrane is targeted
Presentation of MG?
Any age (childhood to late adult life)
Only motor symptoms -> weakness and fatigue of skeletal muscles during non-strenuous activity (chewing, climb stairs, etc.)
Most commonly: ptosis, diplopia, dysarthria, dysphagia, some with fatiguability
What is ocular myasthenia?
Patients who have only visual symptoms (ptosis, diplopia)
What is neonatal myasthenia?
Healthy newborns of mothers with MG who have symptoms for a few days before maternal antibodies “wash out”
What is a myasthenic crisis?
Profound weakness that may cause quadriplegia and an inability to speak, walk, or breath; may be triggered by a serious infection or other systemic illness; may be unpredictable
DDx - acute paralysis of speech, chewing, swallowing, limb, and respiratory muscles, as in MG
Extensive brain stem infarction (hyperreflexia, MRI confirms)
GBS (areflexia and sensory impairment with weakness, EMG confirms, expect elevated CSF protein)
Spinal cord lesion (spares CNs, localizing sensory level, may have neck or back pain, MRI)
Dx MG?
Edrophonium test (AChE inhibitor) -> marked improvement of weakness
EMG -> repeated nerve stimulation shows NMJ abnormalities
Most specific test: presence of serum AChR Ab
Rx MG?
Oral anticholinesterase drugs (pryidostigmine)
Some may need immunosupression (steroids, azathioprine, MMF, cyclosporine)
Thymectomy in some
Myasthetnic crisis - IVIg or plasmapheresis
Presentation of LEMS?
Proximal muscle fatigue and weakness (shoulders, hips, trunk)
Do not typically involve the eyes, swallowing, or speech
Possible decreased reflexes that improve after a brief period of isometric exercise
May have autonomic symptoms (dry mouth, orthostatic hypotension, ED)
Common cause of LEMS?
Small cell carcinoma
Dx LEMS?
EMG -> pre-synaptic NMJ abnormalities
Ab to the voltage-gated Ca2+ channel
Search for small cell carcinoma
Rx LEMS?
Search for small cell lung cancer and treat
Guanidine or 3,4-diaminopyridine (enhance ACh release)
