Disorders of the NMJ and Skeletal Muscle Flashcards
In general terms, describe how the NMJ works.
- depolarization of the nerve terminal leads to activation of the VG calcium channels, leading to an influex of calcium into the presynaptic bouton
- this triggers a release of ACh via exocytosis
- the ACh diffuses across the cleft and binds to the ACh receptors
- triggers an inward sodium current leading to depolarization of the muscle endplate
- triggers the activation of voltage-dependent sodium channels in the troughs of the endplate folds
- results in muscle contraction
What are the antibodies in myasthenia gravis directed against?
post-synaptic nicotinic acetylcholine receptors
but also Muscle Specific Kinase and Lipoprotein-related protein 4
Describe the bimodal distribution of MG incidence.
there’s a peak in the 20s-30s and a second peak in the 70s-80s
Early-onset MG is more often associated with what? Late-onset MG?
Early-onset more associated with thymic hyperplasia
Late-onset more associated with thymoma
Describe the typical presentation of MG.
fatigable muscle weakness
ocular involvement is the most common, manifesting as ptosis and diplopia
bulbar weakness manifests as dysarthria and dysphagia
limb weakness is usually proximal and symmetric
What does myasthenic crisis entail?
MG affecting the diaphragm
Describe the Edorphonium/Tensilon test for MG.
Tension is an anti-acetylcholinesterase agent - you give it IV and observe the patient for improvement in muscle strength
What will repetitive nerve stimulation show in MG?
decremental response (compound muscle action potential response amplitude that falls with successive nerve stimulation)
What is the most sensitive clinical test for MG and what’s the characteristic result?
single-fiber electomyograpy with increased jitter (a measure of the variability of NMJ transmission)
How is MG treated?
acetylcholinesterase inhibitors, especially pyridostigmine
steroids
immunosuppressive therapy
thymectomy if there’s a thymoma
What is the antibody against in Lambert-Eaton?
presynaptic P/Q type- voltage gated calcium channel
LE is usually associated with what cancer?
Small-cell lung cancer
Describe the typical presentation of LE.
fatigable proximal weakness (bulbar and ocular symptoms are rare) with autonomic complaints like dry eyes, dry mouth and impotence
the characteristic finding is muscle facilitation: with brief intense exercise, muscle strength increases, but fatigue develops with sustained activity
What will LE show on slow repetitive nerve stimulation? How about with fast repetitive nerve stimulation?
with slow: a decremental response
with fast: an incremental response
What medication is the most effective for improving muscle strength in patients with LE?
3,4-diaminopyridine (and may be more effective if used in conjunction with pyridostigmine)
What is the mutation in Duchenne musclaar dystrophy and Becker muscular dystrophy?
mutations of the dystrophin gene on the X-chromosome
How do Duchenne’s and Becker’s present?
proximal weakness in young boys
Positive Gowers’ sign, pseudohypertrophy of the calf muscles
usually wheel-chair bound by age 12 in Duchenne’s, death usually around 20 2/2 respiratory insufficiency and aspiration
Is the CK level normal or elevated in Duchenne’s?
elevated - if it’s normal, Duchenne’s is likely not the diagnosis
What is the treatment for Duchenne’s and Becker’s?
glucocorticoids are recommended for all
What characterizes the limb-girdle muscular dystrophies?
shoulder and hip girdle weakness with relative sparing of the extraocular, pharyngeal and facial muscles
Myotonic Dystrophy is the most common inherited skeletal muscle disorder affecting adults. What are the two mutations?
autosomal dominant
either an unstable CTG expansion in the CMPK gene or a CCTG expansion in the XNF9 gene
(pathophysiology results from disordered RNA processing)
Describe the typical presentation of myotonic dystrophy.
Usually weakness and stiffness of DISTAL muscles
action and percussion myotonia are present
proximal weakness develops later in the disease
What are some of the systemic findings in myotonic dystrophy?
cataracts, ptosis, arrhythmias, dysphagia, insulin resistance, testicular atrophy and frontal balding
changes in affect, personality and motivation in addition to cognitive dysfunction are also commonly observed
Is the CK normal or elevated in myotonic dystrophy?
usually normal, but may be mildly elevated