NMJ dysfunction (Perlman) Flashcards
Neuromuscular weakness is characterized by flaccid or spastic paralysis, and depressed or exaggerated reflexes?
flaccid paralysis, depressed or absent reflexes
proteins that mediate acetylcholine vesicle docking
SNARE proteins
Which of the following statements about the NMJ safety factor is INCORRECT?
A. A motor nerve action potential (AP) results in the release of about 100 molecues of ACh into the synaptic cleft
B. Normally, end plate potential (EPP) is less than the threshhold for a muscle action potential
C. With repetitive motor nerve APs, less ACh quanta are released into the cleft
D. ACh in the neuromuscular junction is what triggers muscle membrane depolarization
B. The end plate potential is usually higher than the threshhold for an action potential, resulting in continuous stimulation of the muscle for normal muscle strength
A 15 yo female presents with facial weakness and fatigue when playing the clarinet or blowing out candles, sucking through a straw, etc for the last two months. For the last 3 days, she also has left eyelid drooping about 30 minutes after she wakes up in the morning (improves with rest). She has double vision when looking to the side and choking and coughing on food, and difficulty with chewy foods. Diagnosis?
Myasthenia gravis
- often asymmetric
- affects ocular and bulbar muscles, as well as proximal limbs
- worsens over the course of day - fatiguable
- may lead to respiratory failure
Which of the following statements about autoimmune myasthenia gravis is FALSE?
A. Most common form (85%)
B. IgG antibodies target ACh receptors
C. Results in complement-mediated damage to end plate
D. Results in loss and flattening of junctional folds
E. Fatiguability due to decreased release of ACh from presynaptic motor neuron vesicles
Fatiguability is due to decreased response of the muscle cell membrane to ACh ► loss of safety factor and inability to generate AP
How is myasthenia gravis diagnosed?
- serology (not definitive, not always very sensitive)
- icepack and tensilon testing - these inhibit acetylcholinesterase
Which of the following is the quickest management for autoimmune myasthenia gravis?
A. Corticosteroids to suppress Ab production
B. Pyridostigmine to inhibit acetylcholinesterase
C. IVIG to dilute problem antibodies
D. Thymectomy - t cells are thought to be critical in pathogenesis
B
Which of the following statements about congenital myasthenia gravis is TRUE?
A. Maternal Abs from a mom with myasthenia gravis don’t cross the placenta, so most forms are thought to be due to inherited genetic mutations and spontaneous point mutations.
B. The subtypes can be differentiated by pattern of weakness, which varies substantially
C. Results from mutations in genes encoding NMJ proteins
D. Most common subtype is a fast channel defect
C.
A is false: Maternal Abs DO cross the placenta
B is false: All types present with similar pattern of weakness in infants/neonates
D is false. Most common subtype is ACh receptor defect.
A 67 yo male presents with several months of bilateral leg weakness and difficulty getting out of chairs or climbing stairs. He has trouble lifting his arms over his head to comb his hair and sometimes feels stronger after brief exercise. He has slurred speech, occasional double vision, and 20 pound unintentional weight loss. On exam, his patellar reflexes are absent but can be obtained after brief knee extension exercises. Diagnosis?
Lambert-eaton myasthenic syndrome (LEMS)
- proximal symmetric limb weakness, LE>>UE
- ptosis + extraocular muscle and neck weakness
- dysarthria
- improved strength after exercise
- often paraneoplastic (1/2 the time, usually small cell lung carcinoma)
Which of the following statements regarding LEMS is false?
A. Mostly due to antibodies that target voltage-gated Ca++ channels
B. Voluntary maximal contraction (>10 hz firing frequency) causes a buildup of Ca++ in the axon terminal leading to ACh release
C. Diagnostic testing includes antibody titers, electrodiagnostic testing via RNS, and a thorough search for cancer
D. Management of choice is 3,4 DAP
D. Primary management is pyridostigmine. 3,4 DAP acts on K+ channels and is not FDA approved in the US. Immunomodulatory drugs (IVIG and corticosteroids) may also help.
A 4 mo male is brought into clinic with 2 days of increasing weakness in all limbs, not having poopy diapers, not passing gas. His eyelids are drooping equally and he is floppy and limp. On exam, the pupils are dilated and not reacting to light. Reflexes are diminished. He is urgently intubated and placed on a ventilator. He lives in a new house, in a new subdivision. Diagnosis?
Botulism
- Flaccid weakness, ptosis, respiratory failure, dysphagia
- GI dysfunction, constipation
- Mydriasis
- Bradycardia
- Urinary retention
Which of the following is not a usual cause of later-onset botulism infection?
A. Ingesting preformed toxin
B. Bioterrorism
C. GI colonization of spores
D. Iatrogenic
E. Wound infection
C. GI colonization of spores is indicative in botulism infections of infants <6 mo, because their normal flora is still developing. The others are associated with later onset.
There are 7 types of botulism toxin that interact with the host neuron cell. Which is not a step of action in the pathogenesis of this disease?
A. Toxin binds to receptors on the presynaptic nerve cell membrane
B. Toxin is taken up into nerve terminals via endocytosis
C. Toxin splits inside the endosome releasing its heavy chain into the cytosol to cleave SNARE protein.
D. Each toxin targets a different kind of SNARE protein, interfering with ACh exocytosis.
C. It is the light chain that is released into the cytosol and that cleaves the SNARE protein.
How is botulism diagnosed?
stool culture, electrodiagnostic testing via repeat nerve stimulation (RNS - similar to LEMS)
What are two presynaptic NMJ disorders discussed in the lecture?
botulism and lambert-eaton myasthenic syndrome (LEMS)
