Chloe, four-year-old, FS, Mixed Breed
History
6 weeks ago – infrequent sitting during walks, slower with stairs.
3 weeks ago – eating less, slower to eat, occasionally salivating.
5 days ago – progressively frequent sitting while walking.
Today – collapsed on a walk and was unwilling to get up.
Presenting Complaint
- Collapse
- Frequent sitting
- Weak on the pelvic limbs, especially with exercise
- Slower to eat
- Excess salivation
Mentation (level of awareness, presence of confusion)
- Normal to slightly dull
Gait: No ataxia, exercise intolerant
Postural Reactions (ability to correct the position of a limb)
- Normal
Hyperesthesia: None/Not Painful
General Exam
- BCS 6/9
- Normal orthopedic exam
- No heart murmur, strong, synchronous pulses
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What is localization?
Nerve/Muscle based on weakness without ataxia, postural deficit, or back pain.
More specifically, normal reflex and fatigue of palpebral reflex suggest nerve-muscle junction disease.
What are the top Differentials?
Immune / infectious / metabolic disease of the muscle / nerve or junction.
What is the sequence of recommended testing?
- CBC
- Chemistry
- Creatine Phospohokinase (CPK)
- Thoracic radiographs
- Neostigmine Response Testing
- +/- Acetlycholine Antibody Testing
- +/-Thyroid and Adrenal Testing
- +/- Protozoal Testing (Toxoplamosis gondi or Neopsora caninum)
Initial diagnostic results
CBC – normal
Chemistry – normal
T4 –low normal
CPK – normal
Thoracic Radiographs – non-remarkable – no megaesophagus
Next Step – Investigate Myasthenia Gravis
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Myasthenia Gravis Testing
- In Myasthenia gravis antibodies bind to acetylcholine (ACH) receptors on the muscle endplate preventing muscle contraction.
- Acetylcholinesterase breaks down ACH. Inhibition of synaptic acetylcholinesterase, increases acetylcholine, and improves muscle contraction and strength with MG.
- Oral acetylcholinesterase inhibiton with Mestinon (Pyridostigmine) is a useful treatment for MG. IV injection of a short acting acetylcholinesterase inhibitor can test for MG
- Gold standard testing is the ACH receptor antibody test – results back in about 1 week
Safety Factor
Normally there is 3-5 times the amount of ACH needed to bind post-synaptic membrane, trigger an action potential and then muscle contraction. In MG there is an insufficient concentration of ACH.
Neostigmine Challenge Test (NCT)
- Neostigmine Dose 0.02, IV, observe for improved gait and prolonged ability to walk before becoming weak – typical response time is 2 minutes (range of 1-20 mins.
- Possible side-effects from increased ACH
- Muscarinic receptor binding can cause hypersalivation (and less commonly vomiting, diarrhea, bronchoconstriction, AV block). Atropine will block the muscarinic receptor and reduce these side effects.
- Nicotinic receptor binding can cause muscle fasiculation (and theoretically flaccid paralysis and respiratory failure). Atropine will not block nicotinic receptor and prevent respiratory failure.
- When performing neostigmine challenge test (NCT):
- Closely observe for 30 minutes
- Consider pre- or post-treatment with atropine 0.02 mg/kg, IV
- ET tube ready for intubation from respiratory failure
Chloe’s Outcome:
ACH Antibody Test Result:
ACH antibody test – 0.08 (positive is > 0.05 nmol/L)
Treatment:
- Mestinon 1 mg/kg, BID resolved clinical signs but was increased to TID because she was weak prior to next dose
- Cyclosporine 6 mg/kg, BID was NOT started because of low titer and relatively mild signs
- Prednisone contraindicated because can cause neuromuscular weakness and muscle atrophy
Prognosis:
- Among all dogs with MG about 65% survive. Chloe’s prognosis was considered good because of relatively low titer, absence of megaesophagus /regurgitation /pneumonia, and younger age.
Outcome:
- Normal at 6-month and 12-month follow-up, Mestinon was then successfully tapered and eliminated.
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