Pharmacokinetics of a cytosine arabinoside subcutaneous protocol in dogs with meningoencephalomyelitis of unknown aetiology.

Cytosine arabinoside (CA) is a commonly used treatment for dogs with meningoencephalomyelitis of unknown aetiology (MUE) with various proposed protocols, many requiring 24 hours (h) of hospitalization or two visits within 24 h. This is a unidirectional study evaluating the pharmacokinetics of a CA subcutaneous (SC) protocol and a standard constant rate infusion (CRI) protocol in 8 dogs with MUE. Dogs received the CRI (200 mg/m2 IV over 24 h), followed by a SC protocol (50 mg/m2 every 2 h for 4 treatments) four weeks later. Plasma CA concentrations were measured by high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS). Median peak CA concentration for the SC protocol (3.40 µg/ml, range 1.60-9.70 µg/ml) was significantly higher than the CRI (1.09 µg/ml, range 0.77-1.67 µg/ml; p = .02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA1 2.28 µg/ml, range 0.97-2.67; CA8 1.83 µg/ml, range 0.77-2.84) compared to the CRI (CA1 0.01 µg/ml, range 0-0.45; CA8 0.74 µg/ml, range 0.67-1.11; p = .01). While the PK properties of CA when administered as a CRI has been previously investigated, this study demonstrated that CA when administered via repeated 50 mg/m2 injections every 2 h over an 8-h period, provided sustained plasma levels above its therapeutic target and for a significantly longer duration of time than did a standard CRI protocol.

Case Report: Meningoencephalomyelitis of Unknown Etiology Manifesting as a Bilateral Cranial Polyneuropathy in 3 Dogs.

A bilateral cranial polyneuropathy was the primary magnetic resonance imaging (MRI) finding in three medium to large breed dogs diagnosed with meningoencephalomyelitis of unknown etiology. All three dogs presented with a progressive history of vestibular ataxia with either central vestibular or multifocal central nervous system (CNS) neuroanatomical localization. Brain MRI revealed variable degree of bilateral enlargement and/or increased contrast enhancement of the optic, oculomotor, trigeminal, facial, and vestibulocochlear nerves, as well as enhancement of the orbital fissure (oculomotor, trochlear, ophthalmic branch of trigeminal, and abducens nerves). There was evidence of intracranial and cranial cervical meningeal contrast enhancement in all three dogs and of cervical spinal cord lesions in 2. In all cases, more cranial nerves were affected than indicated by neurological examination. Cerebrospinal fluid (CSF) analysis was consistent with a mononuclear pleocytosis in 2 cases and a mixed cell (predominantly lymphocytic) pleocytosis in 1 case. All dogs were treated with immune suppressing medications and showed clinical improvement, although some cranial nerve deficits were persistent at follow up 2 months later. These are the first known cases of MUE diagnosed ante-mortem in a canine population documenting bilaterally symmetrical lesions affecting multiple cranial nerves. While MUE is a common cause of non-infectious inflammatory disease in dogs, it likely encompasses more classifications than have previously been reported, and should remain a differential for dogs of all ages and sizes presenting with cranial nerve deficits.

Behavioral Changes in Dogs With Idiopathic Epilepsy Compared to Other Medical Populations.

Anxiety related behaviors have been reported in humans diagnosed with idiopathic epilepsy (IE) and such traits may be altered depending on seizure phase. The purpose of this study was to determine the presence and severity of anxiety related behaviors in dogs with IE compared to other medical populations, and to determine if behavioral changes were associated with seizure control. In this retrospective cross-sectional study, the owners of 102 dogs presenting for wellness examination (37), epilepsy (38), and intervertebral disc disease (27) were surveyed utilizing a questionnaire developed based on the shortened Canine Behavioral Assessment and Research Questionnaire (mini-CBARQ), previously validated for its ability to analyze canine behavior. Veterinarians of participating dogs completed a questionnaire to verify diagnoses. Dogs with IE and IVDD had a higher likelihood of being fearful/anxious when approached by an unfamiliar dog compared to the wellness group. Dogs with IE receiving polytherapy had decreased excitement before a walk (P = 0.0007) or car trip (P = 0.027), increased fear/anxiety when groomed (P = 0.0197), and increased shaking, shivering, or trembling when left alone (P = 0.0004) compared to dogs receiving monotherapy. Polytherapy dogs had increased agitation when their owner/others showed affection toward other people/dogs during preictal (Pperson = 0.005, Panimal = 0.0083), postictal (Pperson = 0.001, Panimal = 0.0068), and interictal (Pperson = 0.0083, Panimal = 0.02) period compared to monotherapy dogs. Seizure frequency and severity was not correlated with anxiety related behavior in dogs with IE. While seizure phase was associated with behavior changes in 38% (14/37) of our epileptic population, one specific seizure phase was not more likely to produce behavior changes than another. Behavioral changes noted in dogs with IE raises further questions about how this disease affects QoL. Research was presented in abstract form at the ACVIM Forum, Denver, CO, USA, June 2016.

The utility of intraoperative impression smear cytology of intracranial granular cell tumors: Three cases.

Two adult male dogs (a 7-year-old shorthaired Chihuahua and 14-year-old Shih Tzu) and one adult female dog (a 9-year-old Maltese) presented for evaluation of new-onset seizure activity. Magnetic resonance imaging of the brain demonstrated a large, poorly marginated T2-weighted hyperintense, and strong contrast enhancing extra-axial mass in each case. A surgical biopsy for histopathologic evaluation was elected in all cases, and intraoperative impression smears were successfully obtained. Intraoperative cytology identified a homogenous population of round to polygonal cells with central to eccentric nuclei, coarse chromatin, and variably amphophilic to eosinophilic granular cytoplasm. Cytologic findings led to a suspected diagnosis of granular cell tumor (GCT) in all cases. Histopathologic review identified a densely cellular, unencapsulated neoplastic mass comprised of sheets of large round to polygonal cells with abundant eosinophilic cytoplasm containing numerous eosinophilic intracytoplasmic granules, confirming the diagnosis of GCT in all cases. The cases reported here are unique in that they reveal an accurate intraoperative cytologic diagnosis of a rare canine central nervous system neoplasm. Intraoperative cytology of the intracranial masses could provide clinicians with important and quick diagnostic and prognostic information; therefore, expediting decisions made intraoperatively. Further research is warranted to determine the diagnostic accuracy of intraoperative cytology for neoplasia in veterinary patients.