B6-058 CBCL Trouble at the Junction Flashcards by Felicia Jones

list the anatomic possibilities for a lesion causing weakness from proximal to distal

motor cortex
internal capsule
brainstem
corticospinal tract (in spinal cord)
anterior horn cell
nerve roots
spinal nerves
plexus
peripheral nerves
neuromuscular junction
skeletal muscle

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protein that plays a role in the coordination of clustering acetylcholine receptors on the postsynaptic side

MuSK

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what is the key function of MuSK?

clustering acetycholine receptors on the motor end plate

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what is the sensitivity of repetitive nerve stimulation for generalized MG?

75-80%

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what is the sensitivity of repetitive nerve stimulation for occular MG?

15-45%

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what percentage of patients with generalized MG have AChR Ab?

80-90%

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what percentage of patients with generalized MG have anti-MuSK antibodies?

4-5%

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rapid acting therapies used to control MG during a myasthenic crisis [2]

IVIG
plasma exchange

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first line treatment for MG patients that do not adequately respond to pyridostigmine

prednisone

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cholinesterase inhibitor used for symptomatic management of MG

pyridostigmine

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drug that is particularly effective in MuSK MG patients who did not respond to pyridostigmine and prednisone

rituximab

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MG patients that receive […] have less severe disease symptoms and require less prednisone

thymectomy

**regardless of whether thymoma is present

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in LEMS, loss of voltage gated calcium channels results in…

decreased release of acetylcholine containing vesicles

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nerve conduction shows low amplitude motor potentials and >100% increase in amplitude after 10s of exercise

LEMS

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rapid repetitive nerve stimulation at 10-50 Hz frequently shows increment of >100%

LEMS

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sensory nerve conduction should be […] in LEMS patients

unaffected

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85-95% of LEMS patients have autoantibodies to

voltage gated calcium channels

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associated with autonomic features

LEMS

**dry mouth, ED, sluggish pupillary response

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dry mouth
erectile dysfunction
sluggish pupillary response

LEMS

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associated with small cell lung cancer

LEMS

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associated with thymoma

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postsynaptic NMJ disorder

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presynaptic NMJ disorder

LEMS

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associated with ocular and bulbar symptoms

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associated with proximal weakness in lower extremities

LEMS

describe the first steps of management of LEMS patients [3]

1. screen for/treat SCLC 2. amifampridine 3. immunomodulatory therapy

cause hydrolytic cleavage of SNARE proteins essential for presynaptic calcium mediated vesicle exocytosis

botulinum toxin

binding and accelerated internalization of the postsynaptic acetylcholine receptor

binding and accelerated internalization of the presynaptic voltage-gated calcium channel

LEMS

what part of the nervous system is not affected by botulinum toxin

CNS

would you expect to see seizures in a patient with botulism?

no, spares the CNS

presynaptic toxin mediated disease

botulism

presynaptic immune mediated disease

LEMS

postsynaptic immune mediated disease

hereditary disorders of neuromuscular transmission that can affect presynaptic, synaptic, or post synaptic NMJ

congenital mysathenic syndrome

proximal to distal anatomic sequence of the motor unit

anterior horn cell motor axon motor axon twig branches NMJ muscle fibers

have a specialized synapse with muscle fibers

lower motor neurons

relay excitatory electrical signals down through the motor axon

lower motor neurons

decussate in the brainstem at the level of the medulla

upper motor neurons

originate in the frontal lobe cortex

upper motor neurons

upper motor neurons synapse with lower motor neurons at the

anterior horn of the spinal cord

cardinal manifestations of lower motor neuron weakness

muscle atrophy hypotonia diminished/absent reflexes

cardinal manifestations of upper motor neuron weakness

preserved muscle bulk spastic muscle tone hyperreflexive

positive Babinski reflex in adults indicates damage to

upper motor neuron

sequence of event during neuromuscular transmission:

1. motor axon depolarization 2. voltage gated calcium channel activation 3. influx of calcium on motor axon 4. vesicle fusion with presynaptic membrane 5. ACh release into the NMJ 6. activation of the ligand gated AChR on the muscle membrane 7. sodium ion influx into the muscle sarcolemma 8. calcium release from endoplasmic reticulum 9. activation of actin-myosin contraction

bind and block ACh receptors on postsynaptic membrane

ACh-R Ab

reduced end plate potentials below the minimum necessary to activate muscle contraction

interfere with NMJ development and maintenance leading to endplate degradation and blocking of NMJ

MuSK Ab

protein that directs aggregation of AChR on the muscle during development

agrin

for [....] studies, a peripheral nerve is stimulated with an electrical pulse and the evoked potential is recorded over a distal muscle innervated by the stimulated one

motor nerve conduction studies

for [....] studies, a peripheral nerve is stimulated with an electrical pulse and the evoked potential is recorded over a proximal or distal sensory fibers innervated by the stimulated one

sensory nerve conduction studies

key bioelectric potential characteristics analyzed during nerve conduction studies [3]

distal latency amplitude conduction velocity

[...] greatly influences the accuracy of nerve conduction studies

technical factors **produces false positive/negative

what percentage of patients with ocular MG have AChR Ab?

40-50%

what degree of decrement is expected on RNS studies in patients with MG?

>10% **must be reproducible

thymectomy is an evidence based treatment strategy for patients with what type of MG?

AChR Ab MG

when should thymectomy be performed in an eligible patient?

after disease is in control **if not controlled, there is increased risk of myasthenic crises

autoantibodies found to be pathogenic in MG patients [3]

AChR Ab MuSK LRP4 Ab

CMAP decrement >10% is associated with

CMAP increment is associated with

LEMS

organized protein secreted from the motor nerve terminal

agrin

agrin binds to [...] which forms a receptor complex with [...]

LRP4 MuSK

agrin signal is transmitted through [...], Dok-7, and rapsyn to promote the accumulation, organization, and clustering of AChR

MuSK

all patients diagnosed with MG should have chest imaging to evaluate for

thymoma

MOA of pyridostigmine

inhibition of the hydrolysis of ACh within the synapse **enhances availability for binding

the AChR has a central pore that can open and allow [...] entry to the sarcolemma

sodium

the AChR has [...] binding sites

opening of the AChR creates the endplate potential to initiate

muscle fiber action potential

hyperreflexia spasticity plantar extensor sign

upper motor neuron dysfunction

fatiguable weakness with sustained upward gaze is associated with

slurred speech swallowing difficulty are associated with

what is the correct path of electrical and chemical activation along a motor unit?

anterior horn cell motor axon axon twigs NMJ muscle fibers

assesses for evidence of impairment of neuromuscular transmission from motor nerve endings to skeletal muscle tissue

RNS (repetitive nerve stimulation)

commonly used prednisone sparing agent

azathioprine

first line immunosuppressant used for MG

prednisone

drug frequently used for symptom management of MG

pyridostigmine

side effects of azathioprine [2]

hepatotoxicity bone marrow suppression

side effects of prednisone

weight gain fluid retention hyperglycemia osteoporosis

most common side effect of rituximab

injection site reaction

proximal weakness autonomic dysfunction diminished relexes

LEMS

most common malignancy associated with LEMS

SCLC

low motor amplitude but normal sensory amplitude would suggest..

LEMS

EMG shows active denervation

ALS

associated with voltage gated calcium channel antibodies

LEMS

post exercise increased of CMAP amplitudes

LEMS

fasciculations are associated with

ALS

slows acetylcholine breakdown in the synaptic cleft and reduces myasthenic symptoms

pyridostigmine

reversible cholinesterase inhibitor

pyridostigmine

what is the MOA of the botulinum toxin?

hydrolytic cleavage of different SNARE proteins

gram positive, rod shaped anaerobe

C. botulinum

C. botulinum has the ability to differentiate into [...] in stressful environmental conditions

inert endospores

why can home canning put you at risk of foodborne botulism?

C. botulinum spores are heat resistant

C. botulinum spores can be destroyed at [...] C for 5 min

120 degrees C

most common NMJ disorder

autoantibodies to postsynaptic ACh receptor

in MG, bulbar muscle weakness causes [2]

dysphagia difficulty chewing

in MG, respiratory muscle weakness causes [1]

dyspnea

in MG, fatiguable weakness causes [3]

ptosis diplopia proximal weakness

in MG, the reflexes are

spared

in LEMS, the reflexes are

hyporeflexive

[MG or LEMS] worsens with muscle use

[MG or LEMS] better with muscle use

LEMS

associated with thymoma/thymic hyperplasia

associated with SCLC

LEMS

potassium channel blocker that blocks K+ from exiting the motor axon, prolonging depolarization

amifampridine

amifamprine is used for symptom management of

LEMS

flaccid limb weakness fasiculations atrophy hyperreflexia

ALS

terminal complement inhibitors [2]

eculizumab raulizumab

selective B cell depleting agent that suppresses humoral immunity

rituximab

neonatal Fc receptor inhibitor used in MG treatment

Efgartgimod

subacute proximal limb weakness is associated with

LEMS

B6-058 CBCL Trouble at the Junction Flashcards

(112 cards)