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.

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.