Chloe
2023
PRESENTING COMPLAINT
Collapse
Frequent sitting
Weak on the pelvic limbs, especially with exercise
Slower to eat
Excess salivation
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 unwilling to get up
MEET CHLOE
Chloe is a four-year-old female spayed, mixed breed who presented to BVNS with frequent sitting, collapse, slower to eat, weakness, and excess salvation.
Our team performed a full neurologic exam.
NEUROLOGICAL EXAM
Mentation: Normal to slightly dull
Posture: Weak on the pelvic limbs
Gait: No ataxia, exercise intolerant
Postural Responses: Normal
Reflex: Normal
Cranial Nerves: Subtle delay in palpebral response, worse with repeated stimulation
Hyperesthesia: None / not painful
Normal orthopedic exam
GENERAL EXAM
BCS6/9
Normal orthopedic exam
No heart murmur, strong, synchronous pulses
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
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 (NC T):
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 is 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.
