Neuromuscular Junction And Associated Pathologies Flashcards
Myasthenia Gravis
Autoimmune disease against ACh receptors on the post-synaptic neuron
- the presynaptic neuron can still fire and release ACh, but the post synaptic receptors cant bind them as well
- results in reduced stimulation and affects of ACh
Same amount of ACh release, less binding
History components:
- females (20-30) and men (50-60) most common
- weakness in the neck extensors
- fluctuating fatigue that worsens with repeated activity
- might have thymus disorders and other autoimmune responses
Physcial exam
- cranial muscle weakness
- diploid/ptosis/dysarthria/dysphagia/dyspnea
- reflexes and sensations are intact still
- muscle strength grades in neck and extremities should be lowered
How to diagnosis myasthenia gravis
Anti-AChR/ MuSK antibodies are high
Exclude intracranial lesions by CT/MRI
Rule out Thomas with CT
Thyroid panel and RA factor will show decreases and increases respectively
Endrophonium (tensilon) test is sensitive to myasthenia gravis
- administer ACh inhibitor, (+) = shows normal results for a minute amount of time
Treatment of myasthenia gravis
Acetylcholinesterase inhibitors (1st line) (AChE-I) - pyridostigmine/neostigmine
Thymectomy (subacute only and 2nd line)
Immunosuppressive drugs
- steroid
- immunosuppressants
IVIG & plasmapheresis (only in crisis)
Durgs that exacerbate Myasthenia gravis patients
Antibiotic groups as follows
- Aminoglycosides
- macrolides
- fluroquinolones
D-tubocurine
BBs
Local anesthetic (specifically procaine and xylocaine)
Quinine derivatives
Drugs that are absolutely contraindicated in patients with MG
Botulinum
D-peniclliamine
A-interferon therapies
Telithromycin
Difference between myasthenia crisis and cholinergic crisis
Myasthenia crisis
- too little/no ACh
- causes are infection, severe MG, surgery, OD on meds
- symptoms are respiratory distress and severe widespread weakness.
- improves after tensilon test
- treatments = IVIG/plasmaphoresis and immunosuppressants
Cholinergic crisis
- too much ACh
- causes are high does of ACh inhibitors and organophosphate poisoning
- symptoms = respiratory distress, weakness, fasciculations, SLUD
- worsens after tensilon test
- treatment = stop any pro-cholinergic medications (the body will fix itself its 99% of cases)
Lambert-Eaton Myasthenic syndrome (LEMS)
Autoimmune dysfunction that targets the calcium gated voltage channels on the presynaptic neurons
- results in decreases Ca2+ influx and lowered release in ACh
- not complete halting of the release however.
History/physical associated results
- men and women equally likely and usually 40s
- 50% associated with SCLC
- weakness improves with activity
- weakness is prominent in large muscles and affects legs > arms
- diminished reflexes
- sensation is normal
Symptoms/signs
- autonomic features (Anti-SLUD)
- has difficulties getting out of chairs
What’s the Cardinal sign difference between LEMS and MG?
LEMS
- patients get better and reduced symptoms with muscle movements
MG
- patients get worse and exaggerated symptoms with muscle movements
Diagnosis of LEMS
Voltage gated calcium channel antibodies
EMG/NCS
Edrophonium test
- no effect but rules out MG
Rule out underlying malignancy vis PET/CT
- ALWAYS check for malignancy
Treatment of LEMS
- Based on what cases it*
1) treat underlying causes
2) 3/4 DAP and guanidine are 1st ;one pharmacological
3) immunosuppression
Botulism toxicity
Destroys SNARE proteins which halts release of ACh vesicles in presynaptic neuron
- complete stop of ACh release
- paralyzes neurons and muscles
History
- almost always infants/children
- history of eating foos improperly or consumed honey as a child
- constipation in children
Symptoms/signs
- Anti-SLUD
- flaccid paralysis (cant flex at neck)
- respiratory compromise
- cranial nerve defects
- diminished flexes
Diagnosis of botulism toxicity
EMG/NCS
- no activity will be noted
Toxin in serum bioassay comes back (+)
If possible, check food sample
Flaccid paralysis with inability to flex neck as a child
- almost 100% confirmed if this is true
