Background: In dogs with congenital portosystemic shunts (CPS), postligation seizures can be challenging to treat and often result in mortality. Levetiracetam (LEV) is a novel anticonvulsive drug that is commonly used in humans with seizure disorders who have hepatic comorbidity.Objectives: To compare the incidence of postoperative seizures in dogs that underwent surgical attenuation of an extrahepatic CPS and preoperatively received either LEV or no anticonvulsant medication.Animals: A total of 126 dogs undergoing attenuation of an extrahepatic CPS that preoperatively received either LEV or no anticonvulsant medication.Methods: Retrospective case review. Information obtained included signalment, duration of clinical signs, presence of neurologic abnormalities before surgery, preoperative bile acid and ammonia concentrations, diagnostic imaging modality, duration of hospitalization, postoperative complications including seizures, and discharge status. Bayesian Poisson regression was used to estimate the risk of seizures in LEV-treated dogs when compared with untreated dogs.Results: Levetiracetam was administered to 33% (42/126) of dogs. No dog treated with LEV experienced postoperative seizures, whereas 5% (4/84) of dogs not treated with LEV experienced postoperative seizures. The relative risk of seizures was significantly (P < .0002) < 1 for the LEV-treated dogs, indicating LEV protection against development of postoperative seizures. No dog that experienced postoperative seizures survived to discharge from the hospital.Conclusions and Clinical Importance: Levetiracetam administered at 20 mg/kg PO q8h for a minimum of 24 hours before surgery significantly decreased the risk of postoperative seizures and death in dogs undergoing surgical attenuation of extrahepatic CPS with ameroid ring constrictors.

Aims: To retrospectively assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients. Background: Natalizumab is highly effective for the treatment of relapsing–remitting multiple sclerosis (RRMS), but its use is complicated by opportunistic JCV infection. This virus can result in progressive multifocal leukoencephalopathy (PML). Serial assessment of JCV serostatus is mandated during natalizumab treatment. Methods: Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia ( n = 865) and 11 MS treatment centres in Brazil ( n = 136) were assessed for change in JCV serostatus, duration of exposure to natalizumab and prior immunosuppression. Sensitivity analyses examined whether sex, age, tertiary centre, prior immunosuppression or number of JCV tests affected time to seroconversion. Results: From a cohort of 1001 natalizumab-treated patients, durable positive seroconversion was observed in 83 of 345 initially JCV negative patients (24.1%; 7.3% per year). Conversely, 16 of 165 initially JCV positive patients experienced durable negative seroconversion (9.7%; 3.8% per year). Forty patients (3.9%) had fluctuating serostatus. Time-to-event analysis did not identify a relationship between JCV seroconversion and duration of natalizumab exposure. Prior exposure to immunosuppression was not associated with an increased hazard of positive JCV seroconversion. Male sex was associated with increased JCV seroconversion risk [adjusted hazard ratio 2.09 (95% confidence interval 1.17–3.71) p = 0.012]. Conclusion: In this large international cohort of natalizumab-treated patients we observed an annual durable positive seroconversion rate of 7.3%. This rate exceeds that noted in registration and post-marketing studies for natalizumab. This rate also greatly exceeds that predicted by epidemiological studies of JCV seroconversion in healthy populations. Taken together, our findings support emerging evidence that natalizumab causes off-target immune changes that may be trophic for JCV seroconversion. In addition, male sex may be associated with increased positive JCV seroconversion.

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ObjectivesTo analyse John Cunningham virus (JCV) serology in natalizumab treated patients over time and assess whether seroconversion was influenced by natalizumab treatment and prior immunosuppressive therapy.MethodsPatients treated with natalizumab for relapsing-remitting multiple sclerosis at six tertiary hospitals in Melbourne, Australia (n=960) were longitudinally assessed for change in JCV serostatus. Duration of exposure to natalizumab and exposure to prior immunosuppressive therapy was documented.ResultsTwo hundred and ninety-four patients (30.6%) had positive JCV serostatus when commencing natalizumab while 666 patients (69.4%) were JCV negative. JCV serostatus changed in 148 of 960 longitudinally followed patients (15.4%) over a mean observation period of 2.7 years. Durable positive seroconversion was seen in 81 of 666 initially JCV negative patients (12.2% over 2.7 years, 4.4% per year). Conversely, durable negative seroconversion was seen in 17 of 294 initially JCV positive patients (5.8% in 2.7 years, 2.1% per year). Fluctuating JCV serostatus was seen in 50 of 960 patients (5.2%). Durable positive seroconversion was more common early in therapy with natalizumab, with 31.9% occurring in the first year of exposure. Positive seroconversion rates were not increased in patients who had received prior treatment with methylprednisolone. No positive seroconversion events were documented in patients exposed to mitoxantrone.ConclusionsIn contrast to recently published data from colleagues in France and Germany, in our longitudinal cohort study rates of durable positive JCV seroconversion correlate closely with expected background rates of JCV seroconversion in the general population. In addition, JCV seroconversion and positive serostatus is not increased in patients with prior exposure to immunosuppressive agents. The low seroconversion rates seen after the first year of exposure suggests that less frequent JCV testing of natalizumab treated patients may be safe.