Neuromuscular Junction Disorders Flashcards
How does the NMJ normally work
- –AP depolarizes motor nerve terminal, Ca influx facilitates release of ACh, ACh binds at specific sarcolemmal nicotinic AChR
- –If enough AChR is bound, end plate depolarizes (EPP), and EPP exceeds threshold for single muscle fiber to contract
- –Co-activation of many muscle fibers causes muscle to contract
what limits the action of ACh
AChE
what is the safety factor
—Slight decrease in ACh release with exercise is insignificant, since more than enough ACh is normally released (“safety factor”)
what is an example of a postsynaptic NMJ disorder
Myasthenia gravis
what are 3 presynaptic NMJ disorders
Lambert-Eaton myasthenic syndrome
Botulism
Congenital myasthenia (rare disorders of the NMJ)
what is the immune target in Myasthenia gravis
nAChR
what is the immune target in Lambert-Eaton
voltage-gated Ca channel (leads to decreased release of ACh)
what type of drugs can be used to improve myasthenia gravis?
AChE inhibitors - to increase the amplitude and duration of the EPP
How does botulism cause a NMJ disorder
exotoxin inhibits ACh release
What changes to the NMJ can be seen in Myasthenia gravis with an electron microscope
loss of normal architecture, AChRs and folding of the postsynaptic NMJ
what are symptoms of generalized MG
ptosis, diplopia, dysarthria, dysphagia; respiratory, facial, neck and limb weakness.
severity ranges from person to person, fatigue may occur with some activities.
preserved sensation and reflexes
what are symptoms of ocular MG
ptosis, diplopia only symptoms after 2-3 years
doesn’t progress
what changes occur to sensation and reflexes in MG
none -the function is preserved
which muscles are most commonly affected by MG
eye and mouth muscles
describe the process of developing MG
APCs take up AChR and present it to T-cells which recognoize the AChR and interact with B cells stimulating them to produce antibodies to AChR
Normally how does exercise affect the amount of ACh released
it decreases slightly but is still well above threshold (safety factor)
In MG how does exercise affected the amount of ACh released
EPP is reduced narrowing the safety factor. The amount of ACh released decreases until it is below threshold.
how is MG diagnosed
typical clinical features + Positive Tensilon (edrophonium) test
or EMG showing abnormal NMJ transmission
or elevated serum Ab titre to AChR (most specific)
what is the most specific way to diagnose MG
Elevated serum Ab titre to AChR (80-90% in generalized and 50% in ocular)
what is the Tensilon test
IV injection of short-acting AChE inhibitor show an objective decrease in weakness. i.e. speech or ptosis may improve
3 treatment options for MG
- Anticholinesterase drugs
- Thymectomy
- immunosuppressant drugs
how do anticholinesterase drugs work in MG
inhibit AChE and enhance the effect of released ACh, imporves symptoms
how does a thymectomy help in MG
- contains AChR-like material, where autoimmune response initiated?
- hyperplastic thymus or thymoma (rarer) occur in MG
what tumor is associated with MG
thymoma
what “quick fixes” can be used in acute exasterbations of MG
plasmapheresis or IVIG
how does immunosuppressive therapy affect the NMJ
immunosuppressive therapy may shift the balance closer to the normal state by allowing more time for ACh receptors to undergo resynthesis and repair
what are the clinical symptoms of Lamber-eaton myasthenic syndrome (LEMS)
- fatigable weakness of proximal limbs, trunk—mimics a myopathy (often begins with shoulder and hips)
- exertion briefly improves power and hyporeflexia
- autonomic symptoms (dry mouth, orthostasis, ED)
what cancer is often linked to lambert-eaton
small cell carcinoma
how is lambert-eaton diagnosed
nerve stimulation tests, EMG, occasional detection of specific antibodies
what happens when a pt with lambert-eatons begins to exercise
they temporarily gain strength
treatment for lambert-eaton syndrome
- look for and treat underlying cancer (will improve neurological symptoms)
- drugs to enhance ACh release (guanidine, 3,4-diaminopyridine)
- immunosuppressive therapy (suboptimal success)
hows does MG affect the thymus
usually glandular enlargement or hyperplasia, less commonly a thymic tumor or thymoma
at what age does MG present
any age
does MS cause pain, sensory, or cognitive impairment?
no
what is a myasthenic crisis
profound weakness may cause quadriplegia with the patient unable to speak, swallow or breath
neurologic emergency
sensation and reflexes remain normal - may help differentiate from other causes
what can trigger a myasthenic crisis
serious infection or systemic illness in a myasthenic patient or may unpredictable develop over days in someone with severe MG
