Daytime and nocturnal activity in treated dogs with idiopathic epilepsy compared to matched unaffected controls.

BACKGROUND: In dogs, antiepileptic drugs (AED) cause lethargy but quantitative data regarding the effects of AED on activity levels are not available, and little is known about how AEDs affect sleep quality. OBJECTIVE: To quantitatively compare activity levels and nocturnal activity in dogs previously diagnosed with idiopathic epilepsy (IE) receiving AEDs compared to age- and breed-matched control dogs. ANIMALS: Sixty-two dogs with IE and 310 control dogs. METHODS: This is a 3-month prospective parallel observational study. An activity monitoring device for dogs was used to measure daily activity levels and sleep scores in all dogs. RESULTS: Dogs with IE treated with AEDs had an 18% average lower baseline activity level compared to control dogs (P = .005; point estimate = 0.82, 95% confidence interval [CI], 0.75-0.90). The combination of phenobarbital and potassium bromide (KBr) was associated with an average 28% decrease in activity in dogs with IE compared to control dogs (P = .03; point estimate = 0.72; CI, 0.62-0.82). Mean sleep scores were not significantly different in dogs with IE receiving AEDs compared to control dogs (P = .43). However, higher dosages of KBr were associated with lower sleep scores (P = .01). CONCLUSIONS: Dogs with IE receiving AEDs have lower activity levels, but no difference in sleep scores, compared to controls. The combination of phenobarbital and KBr had the largest decrease in activity between groups. Higher doses of KBr may affect nocturnal activity in epileptic dogs.

Update on Anticonvulsant Therapy in the Emergent Small Animal Patient.

Seizures are common in veterinary patients and control is critical to the overall patient health. The benzodiazepine class of drugs (diazepam, midazolam, and lorazepam) often are the drug class of choice; however, levetiracetam and propofol also have been gaining favor as anticonvulsant drugs for acute seizure management. After cessation of seizures, practitioners then can discuss long-term seizure control on a case-by-case basis with clients.

Case-control study of risk factors for granulomatous meningoencephalomyelitis in dogs.

OBJECTIVE: To identify environmental and other variables associated with a diagnosis of granulomatous meningoencephalomyelitis (GME) in dogs. DESIGN: Case-control study. ANIMALS: 31 dogs that received a histologic diagnosis of GME (case dogs) from January 2003 to January 2014 and 91 age- and breed-matched dogs. PROCEDURES: Data were obtained from each dog's medical records regarding home address, signalment, body weight, body condition score (BCS), vaccination history, and date of diagnosis (case dogs) or visit (control dogs). Home address data were used to determine the human population density in each dog's geographic region. Seasonal distributions of GME diagnoses in the case group were evaluated for differences. Case and control dogs were compared with respect to the remaining variables. RESULTS: For case dogs, no significant difference was identified among seasons in the distribution of GME diagnoses; however, such diagnoses were more common in the spring than in other seasons. No significant differences were identified between case and control dogs in age, body weight, BCS, human population density, season of diagnosis or visit, or time of last vaccination. Although females appeared more likely than males to have a GME diagnosis, this association was not significant and did not change when BCS, time since last vaccination, or human population density was considered. CONCLUSIONS AND CLINICAL RELEVANCE: None of the evaluated factors, including investigated environmental triggers, were associated with a GME diagnosis in the dogs of this study. Additional research is warranted involving dogs from a broader geographic area.

Prospective crossover clinical trial comparing transdermal with oral phenobarbital administration in epileptic cats.

OBJECTIVES: The aim of this study was to compare serum phenobarbital concentrations, adverse events and client satisfaction during 14 weeks of transdermal vs oral phenobarbital administration to epileptic cats. METHODS: This was a prospective, fixed-order, crossover pilot study. Nine client-owned cats with presumptive or diagnosed idiopathic epilepsy were enrolled. Oral phenobarbital (PO-PB) was administered for weeks 1-14 (median starting dosage of 3.8 mg/kg [2.0-5.4 mg/kg/day] q12h); transdermal phenobarbital (TD-PB) was administered for weeks 14-28 (median starting dosage 18.8 mg/kg/day [17.6-24.0 mg/kg/day] q12h). Serum phenobarbital concentrations (S-PB) were measured at weeks 2, 14, 16 and 28. Client satisfaction questionnaires and biochemistry were evaluated at 14 and 28 weeks. RESULTS: Median S-PB concentrations during oral administration were 21 µg/ml (observed range 11-40 µg/ml) at week 2 and 22 µg/ml (8-35 µg/ml) at week 14, and at the higher TD dosage were 18 µg/ml (0-42 µg/ml) at week 16 and 17 µg/ml (7-50 µg/ml) at week 28. Phenobarbital concentrations were significantly correlated with PO dosage at week 2 (r = 0.75, P = 0.03) but not at weeks 16 and 28. Significantly more dose adjustments were needed during the TD phase (P = 0.03), but 6/9 owners (67%) still preferred TD to PO administration. Adverse effects were mild and comparable in both groups. CONCLUSIONS AND RELEVANCE: Therapeutic S-PB concentrations were achievable in some cats using TD-PB at 18 mg/kg/day q12h. Poor correlation between TD dosage and S-PB concentrations was observed and more dosage adjustments were required during TD administration. These findings necessitate close therapeutic drug monitoring if TD-PB is prescribed.

Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats.

BACKGROUND: Repeated oral administration of antiepileptic drugs can be challenging for cat owners, resulting in reduced compliance, poor seizure control, and reduced quality of life for cats. Levetiracetam (LEV) has several properties that make it an appealing drug for transdermal application. OBJECTIVES: The aims were to (1) determine if transdermal LEV, in a lipophilic, liposomic cream vehicle, resulted in serum concentrations above 5 µg/mL; (2) identify clinical adverse effects; and (3) evaluate the concentration of LEV in a lipophilic liposomic cream at set intervals. ANIMALS: Six healthy, client-owned cats weighing ≤5 kg. METHODS: Prospective clinical trial. Transdermal LEV was applied to the inner pinna at a dosage of 60 mg/kg (400 mg/mL concentration) at home for 6 days. Day 7, cats were hospitalized for blood sample collection for LEV concentration at times 0 (before dose administration), 0.5, 1, 2, 3, and 4 hours after administration. RESULTS: Median (range) timed serum concentrations were 16.6 (8.6-39.6) µg/mL, 16.1 (6.8-34.4) µg/mL, 15.4 (10.1-36.7) µg/mL, 17.4 (9.2-32.7) µg/mL, 15.1 (8.3-25.9) µg/mL, and 14.8 (11.9-28.4) µg/mL, respectively. Adverse events were limited to sedation (1/6 cats) and pinna crusting (1/6 cats). The LEV, in the proposed vehicle, retained concentration above 95% at 400 mg/mL up to 5 weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: Thrice daily transdermal LEV resulted in median serum concentrations ≥5 µg/mL throughout the sampling period and clinical adverse events were minimal. Transdermal LEV can provide an alternative for cats resistant to administration of other forms of anticonvulsant medication.

Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats.

BACKGROUND: Multiple dose administration of antiepileptic drugs to cats presents a challenge for owners. Extended release levetiracetam (XRL) has once daily recommended dosing interval, but multiple dose administration of XRL has not been evaluated in cats. OBJECTIVE: Evaluate serum levetiracetam concentrations and adverse clinical effects after 11 days of once daily XRL administration to healthy cats. ANIMALS: Nine healthy privately owned cats, body weight ≥ 5 kg METHODS: Extended release levetiracetam (500 mg/cat) was administered PO q24h for 10 days. On day 11, blood was collected at trough, 4, 6, and 8 hours after tablet administration. Owners maintained records of adverse effects throughout study. Levetiracetam was quantitated in serum using immunoassay validated in cats. RESULTS: Median dose 94.3 mg/kg q24h. Median (range) trough, 4, 6, and 8 hour serum levetiracetam concentrations were 7.0 (2.3-14.1), 82.6 (7.8-125.3), 92.3 (13.3-97.3), and 72 (22.8-96.4) µg/mL, respectively. Peak was not observed in 4 cats because of missed samples (n = 2) and failure to reach maximal concentration (Cmax ) by 8 hours (n = 2). Median time of maximal concentration (Tmax ) for the remaining 5 cats 5.2 (range 4-6) hours. Adverse effects were minimal and included ataxia (n = 1), sedation (n = 1), and vomiting or regurgitation (n = 1). All signs resolved without dose adjustment or additional treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Mean trough serum levetiracetam concentrations were ≥5 µg/mL and adverse effects were minimal throughout dosing period, indicating that the drug was well tolerated. Once daily XRL (500 mg/cat) administration may provide an easier alternative to 3 times daily dosing of intermediate-release levetiracetam for epileptic cats.

Feline Epilepsy.

Seizures occur commonly in cats and can be classified as idiopathic epilepsy, structural epilepsy, or reactive seizures. Pursuit of a diagnosis may include a complete blood count, serum biochemistry, brain MRI, and cerebrospinal fluid analysis as indicated. Antiepileptic drugs should be considered if a cat is having frequent seizures, or any 1 seizure longer than 5 minutes. Phenobarbital is often the drug of choice; however, levetiracetam may be more useful for certain types of epilepsy in cats. Long-term prognosis depends on the underlying diagnosis and response to therapy.

RETROSPECTIVE STUDY EVALUATING ASSOCIATIONS BETWEEN MIDLINE BRAIN SHIFT ON MAGNETIC RESONANCE IMAGING AND SURVIVAL IN DOGS DIAGNOSED WITH MENINGOENCEPHALITIS OF UNKNOWN ETIOLOGY.

Difficulty has been encountered when trying to identify ante mortem prognostic indicators for dogs with meningoencephalitis of unknown etiology (MUE). Identifying MRI imaging parameters associated with prognosis may impact treatment decision-making for clinician and owner. Our hypotheses for this retrospective cohort study are that dogs diagnosed with MUE that had midline shift on brain MRI would have a poorer survival compared to dogs without midline shift; and that younger age, lower weight, and low cerebrospinal fluid (CSF) cell count would be correlated with improved survival. Medical records were reviewed from two institutions. Inclusion criteria included: clinical signs referable to intracranial disease, brain MRI at presentation, abnormal CSF analysis, and negative infectious disease testing. Magnetic resonance imaging scans were evaluated for midline shift using the T2-weighted transverse image at the interthalamic adhesion and at the site of maximal deviation. Fifty-two dogs met the inclusion criteria. Median midline deviation was 0.12 cm. Median survival for dogs with no shift was 906 days and with shift was 84 days. Survival was not significantly different between groups (P = 0.11). This remained true when correcting for age (P = 0.22) and CSF TNCC (total nucleated cell count) (P = 0.12). Age at the time of diagnosis (P = 0.02) and CSF TNCC (P = 0.03) were significantly associated with survival. Cerebrospinal fluid protein value (P = 0.84) and weight (P = 0.82) were not significantly associated with survival. In this study of 52 dogs with MUE, MRI evidence of midline brain shift between 0.04 and 0.3 cm at the level of the interthalamic adhesion was not associated with shorter survival.

Efficacy of glucocorticoid monotherapy for treatment of canine meningoencephalomyelitis of unknown etiology: a prospective study in 16 dogs.

Canine non-infectious, inflammatory meningoencephalomyelitis is termed meningoencephalomyelitis of unknown etiology (MUE) and may affect dogs of any age, breed or gender. Treatment with immunosuppressive medication has been widely reported, however no prospective clinical trials with a standard glucocorticoid monotherapy are available. The objectives were to compare the cerebrospinal fluid (CSF) analysis at diagnosis and after treatment with a standard glucocorticoid (GC) dose and to determine the survival time in dogs with MUE. We hypothesized that abnormal CSF findings would normalize in dogs with MUE, and survival time would be longer than previously reported for glucocortocoid therapy alone. Inclusion criteria were: (1) normal minimum database, (2) no GC use within 5 days, (3) magnetic resonance imaging performed, (4) negative infectious disease titres, and (5) abnormal CSF analysis. All dogs received GC therapy at 1 mg/kg per os q 12 h. Responders had normal CSF analysis at 1 month. Sixteen dogs met the inclusion criteria. Median total nucleated cell count (TNCC) and protein concentration at time of diagnosis were 39 cells/µL (0-1400 cells/µL), and 49 mg/dL (25-293 mg/dL), respectively. Median TNCC and protein concentration at 1 month were 1 cell/µL (0-120 cells/µL), and 24 mg/dL (13-175 mg/dL), respectively. Seven of 16 dogs (44%) were responders. There was no significant difference in survival between the CSF responders and CSF non-responders (P = 0.85). Overall median survival was 602 days (45-654 days). This study supports using GC therapy in dogs with MUE.

Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 µg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 µg/ml throughout the day (observed range 0-11 µg/ml). Group 2 median concentrations were 26.0 µg/ml (observed range 18.0-37.0 µg/ml). For group 3, median concentrations ranged from 15.0-17.0 µg/ml throughout the day (range 5-29 µg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally.

Evaluation of therapeutic phenobarbital concentrations and application of a classification system for seizures in cats: 30 cases (2004-2013).

OBJECTIVE: To determine the percentage of cats with a phenobarbital (PB) concentration between 15 and 45 µg/mL that had a ≥ 50% reduction in the number of seizures and to investigate applicability of the 2011 International League Against Epilepsy (ILAE) classification system in cats. DESIGN: Retrospective case series. ANIMALS: 30 cats with suspected or confirmed epilepsy. PROCEDURES: Medical records for 2004 to 2013 at 3 veterinary hospitals were searched. Information collected included signalment, duration of observation before treatment, frequency of seizures before PB administration, seizure phenotype, dose of PB, serum PB concentration, number of seizures after PB administration, duration of follow-up monitoring, and survival time. A modified 2011 ILAE classification system was applied to all cats. RESULTS: Seizure control was achieved in 28 of 30 (93%) cats with a serum PB concentration of 15 to 45 µg/mL. This comprised 10 of 11 cats with structural epilepsy, 14 of 15 cats with unknown epilepsy, and 4 of 4 cats with presumptive unknown epilepsy. Thirteen cats had no additional seizures after initiation of PB treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Seizure control was achieved in most cats with a serum PB concentration between 15 and 45 µg/mL, regardless of the cause of the seizures. A modified 2011 ILAE classification was applied to cats with seizures and enabled classification of cats without specific genetic testing and without identified structural or inflammatory disease. This classification system should be incorporated into veterinary neurology nomenclature to standardize communication between veterinarians and improve comparisons among species.