From the 2006 Archives: Multiple Immune-mediated Diseases in a 2 year old FS Old English Sheepdog with Progressive Weakness
Contributed by Drs. Roger Pettigrew and Fillipo Adamo
University of Wisconsin, Madison, WI

Clinical History
A 2 year old female spayed Old English Sheepdog presented for a 1 month history of progressive weakness. The owner first noticed that the dog was lethargic and was not following her around the house as she normally would. About the same time as the onset of initial clinical signs, Panda developed diarrhea and was treated with a 7 day course of Metronidazole (unknown dosage) by the referring veterinarian. Fecal analysis performed at that time was negative for parasites and a cryptosporidium/giardia antigen titer was also negative. Over the 10 days prior to presentation, Panda progressed from weakly ambulatory paraparesis to non-ambulatory tetraparesis, and the owner noted a change in bark.

Physical and Neurological Examination
Routine physical examination was unremarkable other than dry mucous membranes.  Mentation was within normal limits.  The dog was non-ambulatory tetraparetic.  Cranial nerve examination was within normal limits.  Proprioception was absent in the pelvic limbs bilaterally.  Spinal reflexes were within normal limits other than reduced withdrawal reflexes in the pelvic limbs bilaterally and in the right thoracic limb.  The neuroanatomic localization was consistent with neuromuscular disease. 

Diagnostic Testing
CBC- Plasma Protein 10.9 g/dL (6-7.5), PCV- 35%  (37-55)
Serum chemistry profile - 
Calcium- 12.2 mg/dL (8.7-11.2)
Total Protein- 9.1 g/dL (5-8.3)
Albumin- 4.3 g/dL  (2.8-4.3)
Cholesterol- 653 mg/dL (98-300)
Ionized Calcium-1.48 mmol/L (1.15-1.32)

PTH  1.10 pmol/L  (3.00-17.00)
Ionized Calcium 1.36 mmol/L (1.25-1.45)
PTHrp 0.0 pmol (0.0-1.0)

ACTH Stimulation Pre – 6.6 ug/dL  (1-5)
ACTH Stimulation Post- 13.3 ug/dL (10-20)

Acetylcholine receptor antibody - 0.05 nmol/L  (canine reference <0.6 nmol/L)

Neospora caninum- negative
Toxoplasma gondii- negative

Thyroid Profile-
Total Thyroxine (TT4) >156 nmol/L (15-67)
Total Triidothyronine  (TT3) 0.2 nmol/L  (1.0-2.5)
Free Thyroxine (FT4) 3 pmol/L  (8-26)
Free Triiodothyronine (FT3) 3.3 pmol/L (4.5-12.0)
Thyroid Stimulating Hormone 61 mU/L (0-37)
Thyroglobulin Autoantibody 180 %  (0-35)
Interpretation- The combination of low T3, F(T4), F(T3) concentrations and elevation of thyroid stimulating hormone supports a diagnosis of primary hypothyroidism.  The positive thyroglobulin autoantibody result indicates that lymphocytic thyroiditis is the cause.  The elevated T4 concentration was repeatable, and may be due to interference from T4 autoantibodies.

Thoracic radiographs-within normal limits

Abdominal ultrasound-within normal limits

Electromyography- fibrillation potentials and positive sharp waves were identified in the thoracic and pelvic limb musculature along with the temporalis and epaxial musculature.

Nerve Conduction Velocity- reduced in peroneal and tibial nerves

CSF Analysis- elevated protein 105 mg/dL (< 25)

Nerve Biopsy – A biopsy from the peroneal nerve was normal

Muscle Biopsy – Biopsies were submitted from the quadriceps, triceps, and cranial tibial muscles.  Although atrophy was not a prominent finding, there was a type 1 fiber predominance and numerous myofibers contained nemaline rods, evident on the modified Gomori trichrome stain.

H & E Stain

Trichrome Stain

Based on the clinical findings of neuromuscular disease, the muscle and nerve histopathology and the presence of thyroglobulin autoantibodies, a presumptive diagnosis of hypothyroid myopathy was made.  The elevated CSF protein also supported a concurrent polyradiculoneuritis.

Clinical Outcome
Approximately 3-4 weeks after initial diagnosis, the dog was returned to the clinic for acute weakness and inappetance. The mucous membranes were pale with evident petechia.  The PCV was 9 %, platelet count 6000 X 103/mm3, and a Coombs test was positive. A diagnosis of autoimmune hemolytic anemia and thrombocytopenia was made.  The dog died 1 week after this clinical presentation.  It is of interest that this dog had multiple immune-mediated diseases that manifested at different time points over this short period of time.
















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