Term
| neuromuscular junction (NMJ) disease |
|
Definition
diffuse process; subacute time course
inflammatory
-myasthenia gravis
-LEMS
toxic
-botulism |
|
|
Term
myasthenia gravis
clinical features |
|
Definition
-initial symptoms usually ptosis/diplopia
-problems with speech, swallowing, and chewing are common early on
-limb weakness usually occurs later (proximal>distal)
*FATIGUE* is characteristic
-symptoms tend to worsen as day progresses
-any muscle in the body can be affected |
|
|
Term
myasthenia gravis
clinical course |
|
Definition
~1/4 patients have disease restricted to eye, lid, bulbar muscles (double vision common)
-some weakness in most patients (may get severe)
UNtreated-->progressive weakness, eventually with bulbar muscles leading to respiratory failure/aspiration pneumonia
treated-->good (but variable, unpredictable) prognosis |
|
|
Term
myasthenia gravis
pathology |
|
Definition
abnormal motor end plate
-reduction in the area of the nerve terminal
-simplification of post synaptic region
-widening of the primary synaptic cleft
-shallower pits, less complex, less Ach receptors
muscle fibers themselves and cell bodies and proximal axons appear normal |
|
|
Term
myasthenia gravis
pathogenesis |
|
Definition
results from an immune attack on the postsynaptic muscle membrane --> impaired neuromuscular transmission
less "safety factor"
thymus abnormalities |
|
|
Term
myasthenia gravis pathology
impaired neruomuscular transmission |
|
Definition
presynaptic function is normal: vesicles of ACH are and get released normally
postsynaptic membrane abnormal: ACh released triggers LESS depolarization, summed end-p;late potential is reduced, lowers probability of triggering an AP |
|
|
Term
myasthenia gravis pathology
less "safety factor" |
|
Definition
initial firings may exceed threshold for AP in postsynaptic cell, but sustained muscle activation (in anyone) causes decrease in ACh store and less ACh release, but usually the postsynaptic effect still exceeds threshold
in myasthenia, this causes some muscle fibers to fall below threshold for AP and the magnitude of the compound AP begins to fall |
|
|
Term
myasthenia gravis pathology
thymus abnormalities |
|
Definition
role of thymus in pathogenesis is unknown
thymus plays a role in the induction of tolerance to self-antigens and contains myoid cells that express the ACh receptor antigen
~15% of pts have thymoma, 65-70% have hyperplastic changes in thymus
thymectomy may result in clinical improvement in many patients |
|
|
Term
myasthenia gravis
diagnosis |
|
Definition
circulating ACh receptor antibodies
nerve conduction studies with repetitive stimulation
single fiber EMG
response to cholinesterase inhibitors (allows ACh to stay in the synapse longer)
CT/MRI of chest to look for thymomas |
|
|
Term
myasthenia gravis
repetitive motor nerve stimulation |
|
Definition
successive stimuli are less likely to exceed threshold, compund AP will be reduced
rapid reduction in the amplitude of the compund AP during repetitive stimulation = decremental response |
|
|
Term
myasthenia gravis
management |
|
Definition
initially treat wit the cholinesterase inhibitor, pyridostrigmine
if needed, add immunosuppression
thymectomy
(many meds, such as aminoglycosides, need to be avoided because they exacerbate symptoms) |
|
|
Term
myasthenia gravis
management for acute clinical deterioration |
|
Definition
plasma exchange, IVIg
monitor of respiratory parameters important, don't hesitate to intubate as deterioration is typically rapid |
|
|
Term
|
Definition
rare!
-neonatal myasthenia
-congenital myasthenia |
|
|
Term
|
Definition
~15% of infants born to MG mothers
hypotonia, poor feeding
self limiting process, typ <2 weeks, mostly supportive care
likely something more that simple antibody transfer since so few affected |
|
|
Term
|
Definition
secondary several rare genetic disorders affecting various aspects fo NMJ function
NOT born to MG moms |
|
|
Term
Lambert-Easton myasthenia syndrome (LEMS)
clinical features |
|
Definition
most often affects muscles of the trunck, shoulder girdle, pelvic girdle, and LEs
ocular and oropharyngeal muscle involvement is milde and occurs later
strength temporarily increases after exercise, declines with sustained activity - increased reflex on exertion
autonomic: dry mouth, impotence, postural hypotension, constipation, micturition difficulty |
|
|
Term
|
Definition
no distinct LM findings
ultrasound shows marked depletion of presynaptic active zones, disorganization of the intramembrane particles and remaining active zones |
|
|
Term
|
Definition
presynaptic abnormality pf ACh release
abnormalities of the voltage-gated calcium channels on presynaptic motor nerve terminals
mobilization of ACh is impaired, number of quanta of ACh released in response to an AP is smaller than normal |
|
|
Term
LEMS pathophysiology
better with exercise |
|
Definition
| excercise/rapid repetitive stimulation can increase ACh mobilization because the calcium that does manage to enter the presynaptic terminal does not have enough time to leave again before the next AP arrives |
|
|
Term
|
Definition
deep tendom reflexes may be reduced at rest but normal/brisk after brief exercise
most have serum antibodies to the P/Q types of voltage-gated calcium channels
nerve conduction studies |
|
|
Term
| LEMS nerve conduction studies findings |
|
Definition
low amplitude compound muscle AP at baseline
decrement at low rates of repetitive stimulation
INCREMENT at HIGH RATES or after 10 seconds of exercise - stimulation must be RAPID to show benefits |
|
|
Term
|
Definition
search for underlying cancer
myasthenia treatments may help (cholinesterase inhibitors, plasma exchange , IVIg, immunosuppression)
3,4 diaminopyridine for symptomatic treatment (blocks potassium channels to prolong AP) |
|
|
Term
botulism
clinical features |
|
Definition
12-36 hours after eating tainted food:
nausea and vomiting-->
blurred vision, diplopia-->
dysarthria, hoarseness-->
inability to phonate-->
dysphagia-->
weakness of muscles of face, neck, trunk, limbs; progressing over several days; respiratory insufficiency |
|
|
Term
|
Definition
8 immunologically distinct toxins all produced by the Clostridium botulinum bacterium
toxins are endopeptides: cleave proteins essential for the docking and fusion of synaptic vesicles to the presynaptic nerve terminal membrane
decreased number of vesicles released, but each vescile has correct amount of ACh within it (same as with LEMS) |
|
|
Term
botulism pathophysiology
modes of exposure |
|
Definition
ingestion of toxin from contaminated food
wound infection (most common form in US - localized condition in IVDA)
ingestion of bacterial spores (infants and honey; infancts aren't immune to organism like adults are)
iatrogenic (Joan Rivers) |
|
|
Term
|
Definition
detection of C. botulinum organism in stool
botulinum toxin in stool, serum, or wound
testing of suspected food for prganism and toxin
nerve conduction studies: similar to LEMS |
|
|
Term
|
Definition
intensive medical support, especially respiratory support
usually do well, though recovery can take months
antitoxin: controversial; high risk of SE, lack of consistent benefit |
|
|
