Neurology and Neurosurgery Resident University of Illinois Champaign, Illinois
Meningoencephalomyelitis of unknown etiology (MUE) is a common cause of non-infectious inflammatory disease of the central nervous system in dogs. It is an important disease in the field of veterinary medicine given the severity of neurological signs that can be seen at the time of diagnosis, its guarded prognosis, and the large financial investment required by owners for diagnostic testing and treatment. Cytosine arabinoside (CA) has become an attractive treatment to be given with corticosteroids as CA is associated with favorable survival times and low incidence of systemic side effects in dogs. Various dosing recommendations exist, most of which indicating inpatient treatment, with no consensus of a standard of care. The purpose of this study was to evaluate the pharmacokinetics of a novel one-day SC CA protocol in dogs with (MUE). Eight client-owned dogs that had MRI and CSF findings compatible with antemortem diagnosis of MUE, along with pertinent negative infectious disease testing, were prospectively enrolled in the study. All eight dogs received a standard CA constant rate infusion (CRI) protocol (200 mg/m2 IV over 24 h) as treatment for MUE. Four weeks later, the SC protocol (50mg/m2 every 2 h for 4 treatments) was administered. Prior to initiating each protocol, a CBC and chemistry were performed to assess for adverse effects. Blood samples were collected 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, and 24 h after initiating each protocol. Plasma CA concentrations were measured using a validated high-pressure liquid chromatography assay. Steady state was defined as plasma CA concentrations exceeding 1µg/mL at 1 and 8 h following initiation of treatment, consistent with previous studies. The Wilcoxon signed rank test was used to compare pharmacokinetic parameters of interest between protocols. No adverse effects were observed in CBC and chemistry panels performed prior to administering each CA protocol. Peak CA concentration (Cmax) for the SC protocol was significantly higher than for the CRI protocol, measuring 3.4µg/mL (1.6-9.7µg/mL) and 1.09µg/mL (0.77-1.67µg/mL), respectively (p=0.0156). CA concentration at 1 and 8h following initiation of treatment was significantly higher for the SC protocol compared to the CRI protocol (p=0.0078). CA concentrations were above 1µg/mL for a significantly longer period of time for the SC protocol versus the CRI protocol, measuring 9.25 h (4.5-10.5 h) and 3.125 h (0-9.75 h), respectively (p=0.039). The investigated SC protocol administered over 8 h provided superior CA plasma levels for a longer duration of time than a standard CRI protocol administered over 24 h. Furthermore, the proposed SC protocol is amenable to outpatient treatment, reducing stress associated with hospitalization and limiting repeated IV catheterization.