Neuromuscular Disorders B&B Flashcards
fill in the blank regarding the neuromuscular junction:
1. ___ ions rush into the neuron
2. ____ NT is released…
3. and binds ______ receptors
- calcium ions rush into the neuron
- acetylcholine NT is released…
- and binds nicotinic receptors
what causes myasthenia gravis?
autoimmune (Type II hypersensitivity) - antibodies block nicotinic ACh receptors in neuromuscular junction (competing with ACh) —> muscle weakness
therefore, can diagnose by detecting ACh receptor antibodies
what are the classic clinical features of myasthenia gravis? why do these occur? (3)
auto-antibodies block ACh nicotinic receptors in NMJs
- muscle fatigability because repeated nerve stimulation causes decrease in ACh release, and when some receptors are blocked this has pronounced effect
- diplopia/ ptosis because eye muscles are very vulnerable to small amount of receptor blockage
- bulbar symptoms (speech, chewing, swallowing problems) because cranial nerves are also vulnerable (innervate small muscles)
what is the mainstay of treatment for myasthenia gravis?
auto-antibodies block ACh nicotinic receptors in NMJs
treat with acetylcholine esterase inhibitors (pyridostigmine, neostigmine, edrophonium) + immunosuppressants
what are the 2 potential causes of an exacerbation in myasthenia gravis patients? how can you differentiate the cause?
- insufficient dose of AChE inhibitor
- cholinergic crisis (too much medication, muscle refractory to ACh)
Tensilon test: administer edrophonium (short acting AChE inhibitor) - if muscle function improves, the dose must be raised (if not, the dose must be lowered)
what is the potential adverse effect of administering the Tensilon test to patients with myasthenia gravis?
auto-antibodies block ACh nicotinic receptors in NMJs
Tensilon (edrophonium) test is giving short-acting AChE inhibitor.. if symptoms improve, medication dose must be raised
however, can cause diffusely increased ACh levels —> activation of parasympathetic system (salivation, abdominal cramping, asthma/bronchoconstriction, bradycardia)
which gland is often abnormal in patients with myasthenia gravis?
auto-antibodies block ACh nicotinic receptors in NMJs
most patients have abnormal thymus (85% hyperplasia, 15% thymoma) —> MG often resolves with thymectomy!!
patients with new onset MG should have imaging done of mediastinum (CT or MRI)
what occurs in Lambert-Eaton Myasthenic Syndrome (LENS)?
rare NMJ disorder due to antibodies against pre-synaptic Ca2+ channels, preventing ACh release
therefore, can diagnose via detection of VGCC antibodies (voltage gated calcium channels)
paraneoplastic syndrome of small cell lung cancer
Lambert-Eaton Myasthenic syndrome (LEMS) is a paraneoplastic syndrome classically of which cancer?
rare NMJ disorder due to antibodies against pre-synaptic Ca2+ channels, preventing ACh release
paraneoplastic syndrome classically of small cell lung cancer
rare NMJ disorder due to antibodies against pre-synaptic Ca2+ channels, preventing ACh release
Lambert-Eaton Myasthenic Syndrome (LEMS)
autoimmune condition in which auto-antibodies block ACh nicotinic receptors in NMJs
myasthenia gravis
myasthenia gravis vs Lambert-Eaton Myasthenic Syndrome (LEMS)
MG: auto-antibodies block post-synaptic ACh nicotinic receptors in NMJs
LEMS: rare NMJ disorder due to antibodies against pre-synaptic Ca2+ channels, preventing ACh release
what is the typical presentation of Lambert-Eaton Myasthenic Syndrome (LEMS)?
slow onset symmetric proximal muscle weakness (difficulty walking, rising from chair, combing hair) which improves with use
normal CK levels and no muscle pain/myalgia because this is purely a nerve problem
autonomic dysfunction due to blocked Ca2+ (dry mouth, electively dysfunction, constipation)
[antibodies against pre-synaptic Ca2+ channels]
Pt presents with gradually worsening muscle weakness which has made walking and rising from chairs difficult. With use, however, the muscle weakness improves. CK levels are normal and there is no myalgia. Pt also complains of dry mouth and constipation. What is going on, and what underlying condition should be located?
Lambert-Eaton Myasthenia syndrome (LENS): rare NMJ disorder due to antibodies against pre-synaptic Ca2+ channels, preventing ACh release
paraneoplastic syndrome of small cell lung cancer
[CK normal because this is purely a nerve problem]
does muscle weakness worsen or improve with use in patients with Lambert-Eaton Myasthenic Syndrome (LENS)? explain why
antibodies against pre-synaptic Ca2+ channels
muscle use —> improved symptoms because more depolarization causes more ACh release (overcoming some of the depolarization blocked by antibodies)
administering Tensilon test (short acting AChE inhibitor) will cause mild increase in muscle function
how can guanidine be used to treat Lambert-Eaton Myasthenic Syndrome (LENS)?
antibodies against pre-synaptic Ca2+ channels —> muscle weakness
guanidine: inhibits K+ channels —> increased ACh release
contrast the following in myasthenia gravis and Lambert-Eaton (LENS):
a. cause
b. symptom severity with increased muscle use
c. which causes eye symptoms?
d. which affects proximal muscles?
e. which causes autonomic symptoms?
f. response to Tensilon test
a. cause: MG = ACh nicotinic receptor Abs, LENS = Ca2+ channel Abs
b. symptom severity with increased muscle use: worsens with MG, improves with LENS
c. causes eye symptoms: MG (ptosis, diplopia)
d. affects proximal muscles: LENS
e. causes autonomic symptoms: LENS (dry mouth, constipation)
f. response to Tensilon test (short acting AChE inhibitor): symptom reversal with MG, mild improvement with LENS
how does myasthenia gravis progress?
repeated exacerbations and remissions - less severe in the morning, worsens as day progresses or with exertion
spreads from ocular —> facial —> bulbar muscles then to trunk/limbs —> respiratory involvement = crisis
note deep tendon reflexes and sensation are unaffected
what is the DOC for myasthenia gravis?
pyridostigmine: oral acetylcholinesterase (AChE) inhibitor
which medications should be avoided in patients with myasthenia gravis? (4)
[auto-antibodies against ACh receptors at NMJ]
- aminoglycosides - only if absolutely necessary
- macrolides
- fluoroquinolone
- magnesium sulfate
what are the 2 etiologies of Lambert-Eaton Myasthenic Syndrome (LEMS)?
60% paraneoplastic of small cell lung cancer - presents FIRST, most patients smoke
40% non-tumor associated
what are 3 criteria for diagnosing LEMS?
Lambert-Eaton Myasthenic Syndrome, auto-antibodies against pre-synaptic Ca2+ channels
- proximal muscle weakness WITH reduced deep tendon reflexes
- autonomic symptoms (dry mouth/eyes, orthostatic hypotension, ED, sweating, etc)
- VGCC antibodies (voltage gated calcium channel)
what is the DOC for patients with LEMS (Lambert-Eaton Myasthenic Syndrome) and severe muscle weakness?
1 search for small cell lung cancer (paraneoplastic)
[auto-antibodies against pre-synaptic Ca2+ voltage gated channels, VGCCs]
rx: diaminopyridines (amifampridine)
compare between myasthenia gravis and LEMS:
a. pattern of spread
b. medical association
c. deep tendon reflexes
d. repetitive movements
MG (Abs against AChR) is uneven muscle weakness spreading distally, associated with thymoma/thymic hyperplasia, normal DTR, symptoms worsen with repetitive movements
LEMS (Abs against VGCC) is even/spreading lower to upper body, associated with small cell lung cancer, diminished DTR, symptoms improve with repetitive movements
how does botulism poisoning present?
symmetric neurological defects (double vision, difficulty swallowing) + descending flaccid paralysis
persevered cognition, NO fever, NO sensory deficits
4 D’s: Diplopia, Dysarthria, Dysphagia, Dyspnea
____ should be considered in any patient with acute onset of unexplained cranial nerve weakness
botulism
