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Lilo is a seven-year and four-month-old female Maltese Chihuahua cross, who presented to Veterinary Specialist Services (VSS) in Brisbane for abnormal behaviour, circling to the right and ataxia. She had no history of toxin exposure or trauma. As a puppy she was diagnosed with an intrahepatic portosystemic shunt (PSS) via a CT scan.
One week prior, Lilo had been treated at the emergency centre for similar presentation including ataxia in the hindlimbs. Due to previously being diagnosed with a PSS, a diagnosis of hepatic encephalopathy was suspected and treated with lactulose, Royal Canin hepatic biscuits and metronidazole.
However, her clinical signs deteriorated over the week, and she re-presented to the emergency centre and was subsequently referred to the Internal Medicine department at Veterinary Specialist Services.
On physical examination Lilo was mentally appropriate with normal menace response, proprioception and gag reflex. When ambulating she would intermittently circle to the right and occasionally fall towards the right side. The withdrawal reflex was normal in all her four limbs. There was mild reaction to back and neck palpation, but this was not clearly elicited.
The differential diagnoses considered for Lilo’s case was meningitis of unknown origin (MUO), granulomatous meningoencephalomyelitis (GME), hepatoencephalopathy secondary to PSS, or an intracranial mass (e.g. meningoma or glioma). Intervertebral disc disease was also considered given the back pain elicited in palpation, however, this differential would not have explained the circling.
A CT scan was performed, and CSF sample collected from the cerebellomedullary cistern. On in-house interpretation, a preliminary diagnosis of meningoencephalitis of unknown origin (MUO) was the most likely while awaiting a full interpretation report. However, given the previous history of PSS, a resting ammonia test was sent to an external laboratory to determine if the PSS was causing any of the clinical signs presented.
Dexamethasone 0.35mg/kg IV q24hr and Amoxicillin 30mg/kg IV q8hr was administered as preliminary therapy on the first day of Lilo’s hospitalisation.
On day two of hospitalisation Lilo’s clinical signs had deteriorated, with mentation becoming markedly duller, an absent menace response, reduced gag reflex and increased ataxia. She had an intermittent lateral strabismus and when attempting to walk she would bump into objects and walk along the walls. She was also uninterested in eating.
The results for resting ammonia levels returned as normal (Plasma ammonia 52umol/L (reference interval <75umol/L)). The full CT report stated no abnormal brainstem, cerebellar, or cerebral attenuation and no mass structures were observed. A significant, unexpected finding was that there was no evidence of a PSS, or any vascular abnormalities as suggested in the 2014 CT report. Therefore, it was assumed that the previous diagnosis may have interpreted a PSS-like structure given the small size of the dog. The differential diagnosis of hepatoencephalopathy secondary to PSS was ruled out due to the CT findings and the negative ammonia results.
Intervertebral disc herniations (IVDD) were observed at L1-2 and L2-3 on CT, however as a myelogram was not performed the magnitude of spinal compression could not be evaluated. As the locations of the intervertebral disc herniations did not support the degree of clinical signs and history, it was assumed that the IVDD was not the primary disease.
The CSF analysis was interpreted as a marked lymphocytic pleocytosis, showing a nucleated cell count of 296 x106/L (reference range <6 x106/L) with 69% lymphocytes, 18% non-degenerate neutrophils and 13% monocytes and macrophages. Lymphocytes were primarily small mature cells with low numbers of medium/large reactive cells. Protein was 0.47g/L, with a reference range of <0.3g/L (cisterna magna).
There was no evidence of microorganisms and there were low numbers of erythrocytes with a red cell count of 3 x106/L. Therefore, the differential diagnoses for lymphocytic pleocytosis include non-infectious inflammatory diseases (e.g. meningitis of unknown origin or steroid responsive meningitis-arteritis (SRMA)), or less likely, infectious diseases such as of viral, fungal or protozoan origin (e.g. canine distemper, cryptococcus neoformans or Amebiasis respectively).
The findings on the CT report and CSF analysis confirmed the preliminary diagnosis of MUO. The treatment plan was revised and Lilo was to be administered maropitant 1mg/kg IV q24hr, levetiracetam 20mg/kg IV q24hr and continued dexamethasone 0.35mg/kg IV q24. Amoxycillin 30mg/kg IV q8hr was to be discontinued.
Cytosine arabinoside (Cytarabine) 200mg/m2 (20mg/ml) was administered as four subcutaneous injections in 24hrs. Cytarabine is commonly used as a chemotherapy treatment in dogs with neoplasia, such as acute myeloid leukemia, but is also used for neurological inflammatory diseases such as MUO as seen in this case.
By day three hospitalisation, and after receiving the cytarabine injections, Lilo had begun showing signs of improvement. She had become more engaged with surroundings and when being handled. She also started having an interest in food, however, Lilo did have prehension difficulties and would mouth food for a period. Levetiracetam administration was changed to levetiracetam oral solution 100mg/ml 0.7ml PO q8hr.
Lilo was able to eat slurry food well and was observed drinking by herself on the fourth day of hospitalisation. Dexamethasone 0.35mg/kg IV q24hr was discontinued and prednisolone 5mg tablet PO q12hr was commenced. Maropitant 6mg PO q24hr was used instead of injectable maropitant.
Lilo was able to be discharged on day five of hospitalisation. She still exhibited neurological signs, including ataxia and a slight circling to the right. However, given her improvement and ability to eat, the owners elected for discharge and to continue caring for Lilo at home.
Lilo required continued cytarabine treatments at 2 weeks, 5 weeks, 9 weeks, 14 weeks and 20 weeks post-first cytarabine injections, following the same protocol of 200mg/m2 over four subcutaneous injections in 24-hours. Prednisolone dosage reduced to 2.5mg PO q24hr at 9 weeks then to 1.25mg PO q24hr at 14 weeks, and levetiracetam reduced to q12hr at 5 weeks.
Lilo has been recovering well at home.
Special acknowledgement to Dr Bruce Mackay and Dr Josh King for their input into this case study report.
Dr Farrah Harris
Veterinary Intern, Veterinary Specialist Services
Dr Farrah Harris is a 2020 University of Queensland graduate who is currently completing a small animal rotating internship at Veterinary Specialist Services (VSS) located in Jindalee in Brisbane.
She has a special interest in surgery and plans to complete a surgical internship in 2021.