This case report describes an episode of acute ataxia, tremor, vertical nystagmus and progressive weakness in a mixed breed dog treated with high doses of metronidazole. Complete blood cell count, serum biochemistry, coagulation profile, blood pressure measurement, urinalysis, computed tomography of the brain and cerebrospinal fluid examination were unremarkable. Metronidazole had been administered at a dose of 65 mg/ kg/day and neurotoxicity was, therefore, suspected. Drug concentrations in the patient's serum and cerebrospinal fluid were measured using high-performance liquid chromatography and compared to control dogs. Metronidazole administration was immediately discontinued; supportive care consisted of fluid therapy and diazepam treatment. The neurological status of the patient improved rapidly within 72 h. The aim of this case report is to describe the clinical presentation of metronidazole intoxication in a mixed breed dog and to interpret the chromatographic analysis which can be a beneficial diagnostic and screening tool in dogs intoxicated with metronidazole.Keywords: vestibular diseases; cerebellar dysfunction; canine diseases; gamma-aminobutyric acid; chromatography Metronidazole (MTZ) is an injectable and oral synthetic, nitroimidazole antibacterial and antiprotozoal agent. It is commonly used in veterinary practice to treat a wide variety of conditions (Watson 1980;Tams 1984;Happonen et al. 2000;Olson et al. 2005;Cattin et al. 2008;Jergens et al. 2010;Senhorinho et al. 2012). The mode of action requires strict anaerobic conditions; susceptible infectious agents include Bacteroides sp., Clostridium sp., Giardia sp. etc. (Rossignol et al. 1984;Even et al. 1998; Plumb 1999;Marks and Kather 2003;Hausen et al. 2011). MTZ is primarily metabolised in the liver and crosses the blood-brain barrier rapidly; in mice, the unaltered drug accumulates in the cerebellum and hippocampal areas (Plumb 1999;Olson et al. 2005). The recommended dosage for long-term treatment in dogs is 10 mg/kg p.o. twice or three times a day (Plumb 1999). Adverse effects include neurological disorders, lethargy, weakness, neutropenia, hepatotoxicity, haematuria, nausea, vomiting and diarrhoea (Plumb 1999;Weiss 2005). MTZ toxicity can develop suddenly and if unrecognised, can lead to rapid deterioration and death (Wright and Tyler 2003). In cases of acute toxicity from a chronic overdose in dogs, the drug should be discontinued and the patients treated supportively and symptomatically (Wright and Tyler 2003). The aim of this case report is to describe a metronidazole-induced neurotoxicity with subsequent chromatographic analysis in a dog. Case descriptionA six and a half-year-old 7.2-kg uncastrated male mixed breed dog was presented for neurological exSupported by the Ministry of Education, Youth and Sports of the Czech Republic (Institutional research development).

A 5-month-old female Sphynx cat was presented to the Small Animal Clinic of the University of Veterinary and Pharmaceutical Sciences Brno with a 6-week history of intermittent inspiratory dyspnea and bilateral serous nasal discharge. The cat had no other signs of disease. On physical examination, tachycardia and stridor were observed. Blood analysis was unremarkable. Serologic results of feline leukemia virus (FeLV) antigen and feline immunodeficiency virus antibody testing were negative. A full-body computed tomography revealed a mass encompassing the whole nasal cavity, as well as osteolysis of nasal conchae and maxilla and fluid-filled paranasal sinuses (frontal, sphenopalatinal), without regional lymphadenopathy. An endoscopy of nasopharynx and nasal cavity revealed a smooth, pink, multilobate mass in the nasal cavity expanding to the nasopharynx. Biopsy from both the nasopharyngeal and nasal part of the mass was performed using flexible biopsy forceps, and impression smears were prepared ( Figure 1). A B Figure 1. Impression smears (A and B) of a nasal mass in a young cat, aqueous Romanowsky, 9100 objective. Diagnosis: Chondroblastic osteosarcoma (OSA)Cytologic impression smears of the mass were moderately cellular ( Figure 1A). Individual plump and ovoid mesenchymal cells with round to ovoid eccentric nuclei, prominent nucleoli, and abundant basophilic cytoplasm, occasionally with clear vacuoles, were observed. Anisocytosis, anisokaryosis, multiple nucleoli, loose chromatin, and sporadic normal mitoses were also present. These cells were considered osteoblasts. Large multinucleated cells with variable numbers of uniform, round nuclei (4-20 per cell) consistent with osteoclasts were also seen ( Figure 1B). Histopathologic evaluation of H&E-stained sections from the biopsy samples from the nasal cavity and the nasopharynx (Figure 2A) revealed pleomorphic, oval-to spindle-shaped mesenchymal cells involving mucosa and submucosa. Significant cell atypia (anisocytosis, anisokaryosis, prominent nucleoli, and nuclei hyperchromasia) was present. Numerous large multinucleated cells were observed. Within the extracellular matrix, osteoid production and focal chondroid differentiation of neoplastic cells ( Figure 2B) was seen. Tumor invasion into blood vessels was absent. Small foci of coagulation necrosis and hemorrhage and mixed inflammatory infiltrates were found. The final diagnosis was chondroblastic OSA.

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The aim of the study was to assess serum hyaluronic acid (HA) and transforming growth factor beta 1 (TGF-β1) concentrations: 1) to differentiate hepatic fibrosis from other forms of liver disease, and 2) for the non-invasive staging of canine liver fibrosis. We also evaluated the association between serum HA concentration and the size of the shunt vessel as an indirect marker of decreased liver clearance in patients with single congenital vascular anomaly. Forty-one healthy client-owned dogs and forty dogs diagnosed with hepatobiliary disease were enrolled in the prospective study. Patients were divided into 4 subgroups: 1) congenital portosystemic shunts (CPSS); 2) parenchymal diseases (a. mild and moderate fibrosis, b. advanced fibrosis and cirrhosis); 3) hepatic neoplasia; 4) biliary tract disorders based on thorough clinical, ultrasound and histopathological examination. Serum HA and TGF-β1 concentrations were measured using ELISA. The HA concentration was significantly increased in patients with advanced liver fibrosis/cirrhosis (P < 0.001) and CPSS (P < 0.001) compared to healthy dogs. Using a cut-off HA concentration of 135.94 ng/ml, the sensitivity and specificity for diagnosis for advanced liver fibrosis/cirrhosis was 100% (95% CI, 50.6–100) and 90.8% (95% CI, 81.6–95.7), respectively. The TGF-β1 levels did not significantly differ among groups (P = 0.180). Negligible correlation was found between serum HA concentration and the size of portosystemic shunt vessel (rs = 0.07; P = 0.831). These findings suggest that serum HA concentration is a potential non-invasive biomarker for advanced liver fibrosis and/or cirrhosis in dogs. The utility of measuring serum concentration of TGF-β1 for diagnosing canine liver fibrosis was not supported.