ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats.

BACKGROUND: Seizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive drug-resistant and self-sustaining character, and high morbidity and mortality. Current treatment approaches are characterized by considerable variations, but official guidelines are lacking. OBJECTIVES: To establish evidence-based guidelines and an agreement among board-certified specialists for the appropriate management of SE and CS in dogs and cats. ANIMALS: None. MATERIALS AND METHODS: A panel of 5 specialists was formed to assess and summarize evidence in the peer-reviewed literature with the aim to establish consensus clinical recommendations. Evidence from veterinary pharmacokinetic studies, basic research, and human medicine also was used to support the panel's recommendations, especially for the interventions where veterinary clinical evidence was lacking. RESULTS: The majority of the evidence was on the first-line management (ie, benzodiazepines and their various administration routes) in both species. Overall, there was less evidence available on the management of emergency seizure disorders in cats in contrast to dogs. Most recommendations made by the panel were supported by a combination of a moderate level of veterinary clinical evidence and pharmacokinetic data as well as studies in humans and basic research studies. CONCLUSIONS AND CLINICAL RELEVANCE: Successful management of seizure emergencies should include an early, rapid, and stage-based treatment approach consisting of interventions with moderate to preferably high ACVIM recommendations; management of complications and underlying causes related to seizure emergencies should accompany antiseizure medications.

Prevalence of nonconvulsive seizures and nonconvulsive status epilepticus in dogs and cats with a history of cluster seizures: A retrospective study.

BACKGROUND: Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) are frequently observed in human patients. Diagnosis of NCS and NCSE only can be achieved by the use of electroencephalography (EEG). Electroencephalographic monitoring is rare in veterinary medicine and consequently there is limited data on frequency of NCS and NCSE. OBJECTIVES: Determine the prevalence of NCS and NCSE in dogs and cats with a history of cluster seizures. ANIMALS: Twenty-six dogs and 12 cats. METHODS: Retrospective study. Medical records of dogs and cats with cluster seizures were reviewed. Electroencephalography was performed in order to identify electrographic seizure activity after the apparent cessation of convulsive seizure activity. RESULTS: Nonconvulsive seizures were detected in 9 dogs and 2 cats out of the 38 patients (29%). Nonconvulsive status epilepticus was detected in 4 dogs and 2 cats (16%). Five patients had both NCS and NCSE. A decreased level of consciousness was evident in 6/11 patients with NCS, 3/6 also had NCSE. Mortality rate for patients with NCS (73%) and NCSE (67%) was much higher than that for patients with no seizure activity on EEG (27%). CONCLUSION AND CLINICAL IMPORTANCE: Prevalence of NCS and NCSE is high in dogs and cats with a history of cluster seizures. Nonconvulsive seizures and NCSE are difficult to detect clinically and are associated with higher in hospital mortality rates. Results indicate that prompt EEG monitoring should be performed in dogs and cats with cluster seizures.

Propofol versus sodium thiopentone for the treatment of status epilepticus and refractory status epilepticus in dogs.

AIMS: To compare the effect on mortality and length of hospital stay of propofol with that of sodium thiopentone for the management of dogs with status epilepticus (SE) and refractory status epilepticus (RSE). METHODS: In this cohort study, medical records of a veterinary referral clinic in Argentina were retrospectively searched for dogs that were hospitalised and required induction of therapeutic coma (TC) with either propofol or sodium thiopentone for the management of SE or RSE of any cause. A logistic regression model was performed to evaluate the association between the type of anaesthetic used and in-hospital mortality adjusting for the type of epilepsy (idiopathic, structural, or reactive). Kaplan-Meier estimated survival curves for the length of hospital stay by the type of anaesthetic drug were compared using the log-rank test (deaths were considered censored events). Cox proportional hazards regression was used to estimate hazard ratios for time to hospital discharge, unadjusted and adjusted for type of epilepsy. RESULTS: A total of 24 dogs with SE were included in the study: eight treated with propofol and 16 treated with sodium thiopentone. Four dogs treated with propofol (proportion = 0.50; 95% CI = 0.15-0.84), and eight treated with sodium thiopentone (proportion = 0.50; 95% CI = 0.50-0.74) died during hospitalisation. The median hospitalisation time was 43 (IQR 24-56) hours for dogs that were treated with propofol and 72 (IQR 64-96) hours for dogs that were treated with sodium thiopentone. There was no evidence of a difference in the median duration of TC in dogs treated with propofol (12 (IQR 8-24) hours) or with sodium thiopentone (12 (IQR 7.5-20) hours; p = 0.946). In the logistic regression model, no evidence of association between the anaesthetic protocol for the management of RSE and in-hospital mortality, adjusted for the type of epilepsy, was found (OR 1.09 (95% CI = 0.17-6.87); p = 0.925). Cox regression analysis revealed a difference in the time to hospital discharge, adjusted by the type of epilepsy, between treatment groups (HR = 0.05 (95% CI = 0.01-0.54); p = 0.013). CONCLUSIONS AND CLINICAL RELEVANCE: The time spent in hospital before discharge was longer in dogs with RSE treated with sodium thiopentone compared to those treated with propofol. However, as the sample size was very small, the results obtained in the present study should be analysed with caution. Further studies including a greater number of dogs are required.

The use of intralipid emulsion therapy to treat status epilepticus in a guinea pig (Cavia porcellus) secondary to severe ivermectin toxicity.

OBJECTIVE: To describe the successful management of ivermectin-induced status epilepticus in a guinea pig (Cavia porcellus) with intravenous lipid emulsion (ILE) therapy. CASE SUMMARY: A 5-week-old, female intact guinea pig was presented to an emergency hospital for status epilepticus 24 hours after oral administration of ivermectin. Approximately 48 hours after exposure, ILE therapy was administered. Within 12-16 hours after ILE therapy, seizures had stopped and the patient's mentation returned to normal. The definitive diagnosis was based on owner history, clinical presentation, and American Society for the Prevention of Cruelty to Animals poison control guidelines. NEW OR UNIQUE INFORMATION PROVIDED: The use of intralipid therapy has been widely documented as a treatment option for numerous toxicities. Its efficacy in treatment for toxicities in both veterinary and human medicines has been well described in various case reports and studies. However, its use and success in small mammals have yet to be documented. In this case report, intralipid therapy is used to successfully treat a seizuring guinea pig that was administered a severely toxic dose of ivermectin. To the authors' knowledge, this is the first report on the successful use of intralipids in a guinea pig from ivermectin toxicosis.

Defining and overcoming the therapeutic obstacles in canine refractory status epilepticus.

Status epilepticus (SE) can be effectively resolved if diagnosis and treatment are addressed at an early stage, although this is not always possible in clinical practice. If untreated, continuous seizure activity leads to refractory SE which does not respond to antiseizure medication. Although refractory SE is a life-threatening emergency, there is a lack of veterinary consensus on its appropriate management. Classical therapeutic approaches often fail to prevent the progression of SE. One of the main reasons for failure or inadequate response, is a lack of understanding of the fundamental progressive pathophysiology occurring during SE. If the therapeutic approach is focussed on the specific pathophysiologic alterations responsible for initiating and maintaining continuous seizure activity, SE could be successfully resolved during its early stages, preventing progression to a refractory state. The aim of this review is to detail the underlying pathophysiology of SE at its different temporal stages in order to determine a more effective therapeutic approach.

Risk factors associated with short-term mortality and recurrence of status epilepticus in dogs.

BACKGROUND: Status epilepticus (SE) is an emergency associated with serious consequences for both patient and owner. Data regarding risk factors for short-term mortality or recurrence in dogs with SE is limited. OBJECTIVE: Identify risk factors associated with short-term mortality (euthanasia or spontaneous death) and recurrence of SE in dogs. ANIMALS: One hundred twenty-four client-owned dogs that sustained an episode of SE. METHODS: Retrospective multicenter study using data collected from medical records of dogs presented in SE to the contributing institutions. Multivariable logistic regression analysis was performed using a manual backwards stepwise approach to identify risk factors associated with short-term mortality and recurrence of SE after discharge. RESULTS: Short-term mortality for affected dogs was 29.8%. Factors significantly associated with short-term mortality included increased patient age, shorter duration of hospitalization, development of SE before arrival, and SE caused by a potentially fatal etiology. Status epilepticus recurred in 27% of dogs that survived to discharge. Factors significantly associated with recurrence of SE included prior history of pharmacoresistant epilepsy and predominance of a focal seizure phenotype. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results may be used to inform clinicians and dog owners regarding risk factors for both short-term mortality and recurrence in dogs with SE.

Intravenous and Intramuscular Allopregnanolone for Early Treatment of Status Epilepticus: Pharmacokinetics, Pharmacodynamics, and Safety in Dogs.

Allopregnanolone (ALLO) is a neurosteroid that modulates synaptic and extrasynaptic GABAA receptors. We hypothesize that ALLO may be useful as first-line treatment of status epilepticus (SE). Our objectives were to (1) characterize ALLO pharmacokinetics-pharmacodynamics PK-PD after intravenous (IV) and intramuscular (IM) administration and (2) compare IV and IM ALLO safety and tolerability. Three healthy dogs and two with a history of epilepsy were used. Single ALLO IV doses ranging from 1-6 mg/kg were infused over 5 minutes or injected IM. Blood samples, vital signs, and sedation assessment were collected up to 8 hours postdose. Intracranial EEG (iEEG) was continuously recorded in one dog. IV ALLO exhibited dose-proportional increases in exposure, which were associated with an increase in absolute power spectral density in all iEEG frequency bands. This relationship was best described by an indirect link PK-PD model where concentration-response was described by a sigmoidal maximum response (Emax) equation. Adverse events included site injection pain with higher IM volumes and ataxia and sedation associated with higher doses. IM administration exhibited incomplete absorption and volume-dependent bioavailability. Robust iEEG changes after IM administration were not observed. Based on PK-PD simulations, a 2 mg/kg dose infused over 5 minutes is predicted to achieve plasma concentrations above the EC50, but below those associated with heavy sedation. This study demonstrates that ALLO is safe and well tolerated when administered at 1-4 mg/kg IV and up to 2 mg/kg IM. The rapid onset of effect after IV infusion suggests that ALLO may be useful in the early treatment of SE. SIGNIFICANCE STATEMENT: The characterization of the pharmacokinetics and pharmacodynamics of allopregnanolone is essential in order to design clinical studies evaluating its effectiveness as an early treatment for status epilepticus in dogs and people. This study has proposed a target dose/therapeutic range for a clinical trial in canine status epilepticus.

Seizure frequency discrepancy between subjective and objective ictal electroencephalography data in dogs.

BACKGROUND: Many studies of epilepsy in veterinary medicine use subjective data (eg, caregiver-derived histories) to determine seizure frequency. Conversely, in people, objective data from electroencephalography (EEG) are mainly used to diagnose epilepsy, measure seizure frequency and evaluate efficacy of antiseizure drugs. These EEG data minimize the possibility of the underreporting of seizures, a known phenomenon in human epileptology. OBJECTIVE: To evaluate the correlation between reported seizure frequency and EEG frequency of ictal paroxysmal discharges (PDs) and to determine whether seizure underreporting phenomenon exists in veterinary epileptology. ANIMALS: Thirty-three ambulatory video-EEG recordings in dogs showing ≥1 ictal PD, excluding dogs with status epilepticus. METHODS: Retrospective observational study. Ictal PDs were counted manually over the entire recording to obtain the frequency of EEG seizures. Caregiver-reported seizure frequency from the medical record was categorized into weekly, daily, hourly, and per minute seizure groupings. The Spearman rank test was used for correlation analysis. RESULTS: The coefficient value (rs ) comparing reported seizure to EEG-confirmed ictal PD frequencies was 0.39 (95% confidence interval [CI] = 0.048-0.64, P = .03). Other rs values comparing history against various seizure types were: 0.36 for motor seizures and 0.37 for nonmotor (absence) seizures. CONCLUSIONS AND CLINICAL IMPORTANCE: A weak correlation was found between the frequency of reported seizures from caregivers (subjective data) and ictal PDs on EEG (objective data). Subjective data may not be reliable enough to determine true seizure frequency given the discrepancy with EEG-confirmed seizure frequency. Confirmation of the seizure underreporting phenomenon in dogs by prospective study should be carried out.

Cerebrospinal fluid lactate concentrations in dogs with seizure disorders.

BACKGROUND: Cerebrospinal fluid (CSF) lactate concentrations increase after seizure activity in many human patients independent of the underlying disease process. The effect of seizure activity on CSF lactate concentration in dogs is unknown. HYPOTHESIS/OBJECTIVES: Cerebrospinal fluid lactate concentration is unaffected by seizure activity in dogs and is more dependent on the underlying disease process causing the seizures. ANIMALS: One-hundred eighteen client-owned dogs with seizure disorders. METHODS: Case series. Cerebrospinal fluid lactate concentration was determined using a commercially available lactate monitor. Seizure semiology, time from last seizure to CSF collection, number of seizures within the 72 hours preceding CSF collection, and clinical diagnosis were recorded. RESULTS: Dogs with focal seizures had higher CSF lactate concentrations than did those with generalized seizures (P = .03). No differences in lactate concentrations were found among dogs with single seizures, cluster seizures or status epilepticus (P = .12), among dogs with CSF collection at different time points after the last seizure activity (P = .39) or among dogs having different numbers of seizures within the 72 hours preceding CSF collection (P = .42). A significant difference (P = .001) was found in CSF lactate concentrations among diagnostic groups, and dogs with inflammatory and neoplastic disease had higher concentrations than did dogs with idiopathic or unknown epilepsy. CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentration is minimally affected by seizure activity in dogs and increased concentrations are more likely associated with the underlying disease process.

Clinical efficacy of combination therapy of itraconazole and prednisolone for treating effusive feline infectious peritonitis.

A 3-month-old male Scottish Fold kitten with pleural fluid and low ratio of albumin to globulin (A/G ratio) was brought to our small animal hospital. Since RNA from the type I feline coronavirus (FCoV) were detected in drained pleural fluid, the cat was tentatively diagnosed with effusive feline infectious peritonitis (FIP). Following the administration of itraconazole and prednisolone, the A/G ratio increased, and the pleural fluid mostly disappeared. The fecal FCoV levels temporarily decreased. However, the cat showed neurological manifestations and was eventually euthanized due to status epilepticus after 38 days of treatment. In conclusion, itraconazole partly exerted a beneficial effect in a cat with FIP. However, further investigation of a possible role of itraconazole in FIP treatment is warranted.

Ketamine-dexmedetomidine combination and controlled mild hypothermia for the treatment of long-lasting and super-refractory status epilepticus in 3 dogs suffering from idiopathic epilepsy.

OBJECTIVE: To describe the use of a ketamine-dexmedetomidine combination and mild hypothermia for the treatment of status epilepticus in 3 dogs that did not respond to GABAergic medication. CASE SERIES SUMMARY: Three dogs, each with a diagnosis of idiopathic epilepsy, were presented to the emergency department in a state of status epilepticus. The dogs were treated unsuccessfully with benzodiazepine as a first-line therapy that was followed by IV propofol anesthesia maintained for at least 12 hours. When general anesthesia was discontinued, seizures reoccurred. All 3 dogs then received a bolus of ketamine (1 mg/kg, IV) over a period of 5 minutes that was followed by a bolus of dexmedetomidine (3 µg/kg, IV) over the same time period and then followed by a continuous infusion for 12 hours of ketamine at a constant rate of 1 mg/kg/h and dexmedetomidine at a variable rate of 3-7 µg/kg/h. Body temperature was maintained between 36.7 and 37.7°C at a state of mild hypothermia throughout treatment. The dogs recovered uneventfully over 48 hours after treatment was discontinued with no evidence of seizures. No notable alterations in physiological parameters were observed during the drug infusions. All dogs were discharged following examinations that showed normal neurological function. NEW OR UNIQUE INFORMATION PROVIDED: This case series highlights the potential benefits of a ketamine-dexmedetomidine infusion combined with mild hypothermia for the treatment of status epilepticus refractory to GABAergic therapy in dogs suffering from idiopathic epilepsy. After the dogs were weaned from the ketamine-dexmedetomidine infusion, all dogs experienced complete recovery. Thus, this case series introduces a novel approach to treat this intense condition.

Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study.

BACKGROUND: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. OBJECTIVES: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. ANIMALS: Client-owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. METHODS: Randomized parallel group clinical trial. Patients were randomly allocated to the IN-MDZ (n = 21) or IV-MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at α < .05. RESULTS: IN-MDZ and IV-MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN-MDZ and IV-MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN-MDZ (100 seconds) was superior (P = .04) to IV-MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN-MDZ and IV-MDZ, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.

Open-label clinical trial of rectally administered levetiracetam as supplemental treatment in dogs with cluster seizures.

BACKGROUND: Treatment options for at-home management of cluster seizures (CS) and status epilepticus (SE) are limited. The pharmacokinetics of levetiracetam (LEV) after rectal administration in both healthy and epileptic dogs has been investigated recently. HYPOTHESIS/OBJECTIVES: To investigate the clinical efficacy of rectally administered LEV in preventing additional seizures in dogs presented for CS and SE. We hypothesized that rectal administration of LEV in addition to a standard treatment protocol would provide better control of seizure activity as compared with the standard treatment protocol alone. ANIMALS: Fifty-seven client-owned dogs with CS or SE. METHODS: Prospective open-label clinical trial. Patients included in the study were assigned to receive either a standard treatment protocol comprising IV/rectal diazepam and IV phenobarbital q8h (control group) or a standard treatment protocol in association with a single dose of 40 mg/kg LEV rectally (rectal LEV group). Dogs that experienced no additional seizures were defined as responders, whereas those that showed additional seizure activity were classified as nonresponders. RESULTS: Twenty-one dogs were assigned to the rectal LEV group, and 36 to control group. Given the small number of cases of SE, statistical analysis was performed only on patients with CS. The response rate was 94% in the rectal LEV group and 48% in the control group (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Rectally administered LEV combined with a standard treatment protocol provided good control of seizure activity in patients with CS. The validity of these results should be confirmed in a double-blinded, placebo-controlled clinical trial.

Pharmacokinetics of rectal levetiracetam as add-on treatment in dogs affected by cluster seizures or status epilepticus.

BACKGROUND: Levetiracetam can be used for seizure control alone or in combination with other antiepileptic medications. A previous study achieved the minimum targeted serum drug concentration after rectal administration of levetiracetam in healthy dogs. The purpose of the present study was to determine the pharmacokinetics of rectal LEV in dogs presented for cluster seizures or status epilepticus and potentially in treatment with other anti-epileptic drugs. Furthermore, preliminary information on response to this treatment as add-on to the standard treatment protocol is reported. RESULTS: Eight client-owned dogs were enrolled. Plasma levetiracetam concentrations (measured at 0, 30, 60, 90, 120, 180, 240, 360, 720, and 1440 min after drug administration) reached the minimum target concentration (5 µg/ml) at 30 min in all but one patient. At T1 (30 min) the mean concentration was 28.2 ± 15.5 µg/ml. Plasma concentrations remained above the targeted minimum concentration in all patients until 240 min and in 7/8 until 360 min. Six out of eight patients experienced no seizures in the 24-h period after hospitalization and were classified as "responders". CONCLUSIONS: Minimum plasma levetiracetam concentration can be reached after rectal administration of 40 mg/kg in dogs affected by cluster seizures and status epilepticus and concurrently receiving other antiepileptic drugs. These preliminary results may encourage the evaluation of rectal levetiracetam as an additional treatment option for cluster seizures and status epilepticus in a larger number of dogs.

Clinical Risk Factors for Early Seizure Recurrence in Dogs Hospitalized for Seizure Evaluation.

BACKGROUND: Epileptic seizures are a common cause for neurological evaluations in dogs. HYPOTHESIS/OBJECTIVES: To determine the timing, frequency, and risk factors for early seizure recurrence (ESR) among dogs admitted to the hospital for seizure evaluation and to facilitate rapid decision making about whether dogs should be placed in the intensive care unit (ICU) or day ward. ANIMALS: Nine-hundred twenty-two dogs referred for seizure investigation; 214 patients were included. METHODS: Retrospective study. Medical records between 2000 and 2017 were reviewed to determine risk factors for ESR. Findings were compared among dogs diagnosed with idiopathic epilepsy (IE), structural epilepsy (StE) and reactive seizures (RS), as well as in all selected cases together. RESULTS: Fifty percent of dogs had a seizure while hospitalized. In the group 53.1 and 52.2% in the StE group, whereas in the RS 40.44% had ESR. The average time to ESR was 7 hours. In IE group, abnormal postictal neurological examination with prosencephalon signs predicted ESR. In StE group, a single generalized or focal seizure 72 hours before hospital admission and abnormal neurologic examination predicted ESR. In the RS group, ERS was predicted by long-term antiepileptic monotheraphy. When all dogs were analyzed together, abnormal neurological examination, the occurrence of cluster seizures, status epilepticus, or combination of them 72 hours before presentation predicted ESR. CONCLUSIONS AND CLINICAL IMPORTANCE: Epileptic seizures recurred in 50% of patients within a mean time of 7 hours. In general, when cluster seizures, status epilepticus or both occurred 72 hours before presentation and neurological examination was abnormal upon presentation, the dog should be placed in ICU for observation.

Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.

BACKGROUND: Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. OBJECTIVE: To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. ANIMALS: Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). METHODS: Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05. RESULTS: IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. CONCLUSIONS AND CLINICAL IMPORTANCE: IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home.

Status epilepticus in dogs and cats, part 2: treatment, monitoring, and prognosis.

OBJECTIVE: To discuss current anticonvulsant drug options and advances in treatment of status epilepticus (SE) and to review the prognosis associated with SE. TREATMENT: When treating a patient with SE, the main goals are to halt seizure activity, prevent further seizures, identify the cause of the seizures, and manage any complications. The veterinary literature indicates that benzodiazepines are the most common class of drugs used for the initial treatment of SE. Although many anticonvulsant drugs are currently available for treatment of SE, there is a lack of evidence demonstrating clear benefit to the use of specific therapeutics for benzodiazepine-refractory SE. Several multicenter, randomized, and placebo-controlled clinical trials are currently investigating the efficacy of new drugs, such as fosphenytoin, for use in canine SE. Another active area of research is the investigation of nonpharmacologic methods of seizure treatment including percutaneous vagal nerve stimulation and transcranial ultrasonic neuromodulation. MONITORING: Electroencephalography (EEG) is underutilized in the management of veterinary seizure disorders. However, recent advances in EEG technology may allow for earlier and proactive therapeutic interventions in epileptic patients, provide objective data collection regarding treatment efficacy, and yield insight into the neurologic status of patients with SE. Most importantly, use of EEG in patients with SE will lead to increased recognition of nonconvulsive seizures and nonconvulsive SE. PROGNOSIS: Mortality associated with SE is as high as 25% in dogs due to direct and indirect causes of death. Dogs with seizure disorders have a decreased lifespan compared to the general population, and epileptic dogs with SE have a significantly abbreviated lifespan compared to epileptics that do not experience SE. In people, nonconvulsive SE has a higher morbidity and mortality than convulsive SE, regardless of patient age or underlying diagnosis.

Status epilepticus in dogs and cats, part 1: etiopathogenesis, epidemiology, and diagnosis.

OBJECTIVE: To review current knowledge of the etiopathogenesis, diagnosis, and consequences of status epilepticus (SE) in veterinary patients. DATA SOURCES: Human and veterinary literature, including clinical and laboratory research and reviews. ETIOPATHOGENESIS: Status epilepticus is a common emergency in dogs and cats, and may be the first manifestation of a seizure disorder. It results from the failure of termination of an isolated seizure. Multiple factors are involved in SE, including initiation and maintenance of neuronal excitability, neuronal network synchronization, and brain microenvironmental contributions to ictogenesis. Underlying etiologies of epilepsy and SE in dogs and cats are generally classified as genetic (idiopathic), structural-metabolic, or unknown. DIAGNOSIS: Diagnosis of convulsive SE is usually made based on historical information and the nature of the seizures. Patient specific variables, such as the history, age of seizure onset, and physical and interictal neurological examination findings can help hone the rule out list, and are used to guide selection and prioritization of diagnostic tests. Electroencephalographic monitoring is routinely used in people to diagnose SE and guide patient care decisions, but is infrequently performed in veterinary medicine. Nonconvulsive status epilepticus has been recognized in veterinary patients; routine electroencephalography would aid in the diagnosis of this phenomenon in dogs and cats. CLINICAL SEQUELAE: Status epilepticus is a medical emergency that can result in life-threatening complications involving the brain and systemic organs. Status epilepticus often requires comprehensive diagnostic testing, treatment with multiple anticonvulsant agents, and intensive supportive care.

Canine status epilepticus treated with fosphenytoin: A proof of principle study.

OBJECTIVES: There are a limited number of marketed intravenous antiepileptic drugs (AEDs) available to treat status epilepticus (SE). All were first developed for chronic therapy of epilepsy, not specifically for SE. Epilepsy and canine SE (CSE) occur naturally in dogs, with prevalence, presentation, and percentage of refractory cases similar to human epilepsy. The objective of this study was to determine if CSE treated with fosphenytoin (FOS) results in a similar responder rate as for people. METHODS: A randomized clinical trial was performed for dogs with CSE. Dogs who presented during a seizure or who had additional seizures after enrolling received intravenous (i.v.) benzodiazepine (BZD) followed immediately by intravenous infusion of 15 mg/kg phenytoin equivalent (PE) of fosphenytoin (FOS) or saline placebo (PBO). If seizures continued, additional AEDs were administered per the standard of care for veterinary patients. Total and unbound plasma phenytoin (PHT) concentrations were measured. RESULTS: Consent was obtained for 50 dogs with CSE. Thirty-one had additional motor seizures and were randomized to the study intervention (22 FOS and 9 PBO). There was a statistically significant difference in the 12 h responder rate, with 63% in the FOS group versus 22% in the placebo group (p = 0.043) having no further seizures. The unbound PHT concentrations at 30 and 60 min were within the therapeutic concentrations for people (1-2 µg/ml) with the exception of one dog. There was mild vomiting in 36% of the FOS group (7/22) within 20 min of FOS administration and none of the placebo group (0/9) (p = 0.064). SIGNIFICANCE: This proof of concept study provides the first evidence that FOS is tolerated and effective in canine SE at PHT concentrations clinically relevant for human SE. Furthermore, naturally occurring CSE can be utilized as a translational platform for future studies of novel SE compounds.