Web-Vet Neurology Specialists
Epilepsy
Epilepsy represents a heterogeneous disease consisting of diverse aetiologies, electrophysiological and behavioural seizure patterns, and responses to pharmacological intervention. As such, the pathogenesis of epilepsy is multifactorial.
The approach to and treatment of seizure disorders in small animals is similar in many respects to the treatment of various other ailments in veterinary medicine: an antecedent historical problem arises, a proper diagnosis is made to confirm the condition, and therapy is initiated to treat the underlying disease or signs of the disease. Seizures are the manifestation of a change in forebrain activity. Thus, by default, all animals with epileptic seizures are classified as having a forebrain neurolocalization.
This section of the website is supported by PRN Pharmacal, and their potassium bromide product KBroVet-CA1.
Consensus Statements
ACVIM Consensus Statement on the management of status epilepticus (SE) and cluster seizures (CS) in dogs and cats
The objective of this consensus statement was to establish evidence-based guidelines for the appropriate management of SE and CS in dogs and cats.
Successful management of seizure emergencies should include an early, rapid, and stage-based treatment approach consisting of interventions with a high level of evidence-based recommendation; management of complications and underlying causes related to seizure emergencies should accompany antiseizure medications. Read this article for a thorough description of what drugs to use and how to use them.
International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals
In this document the International Veterinary Epilepsy Task Force (IVETF) discusses the current understanding of canine epilepsy and presents a proposal for terminology and classification of epilepsy and epileptic seizures, in addition to a classification system that reflects new thoughts from the human field.
International veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs
The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in clinical and research settings.
Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid (CSF) analysis. Tier III is based on the factors listed in tier I and II and identification of EEG abnormalities characteristic for seizure disorders.
International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe
In this consensus proposal, an overview is given on the aim for the use of anticonvulsant treatment, when to start long-term treatment in canine epilepsy and which veterinary drugs are currently in use for dogs. The consensus proposal for drug treatment protocols is based on current published evidence-based literature as well as the cascade regulation for the prescription or veterinary drugs in Europe. Importantly, the recommendation for when to initiate anticonvulsant medications includes the following criteria:
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Interictal period of ≤ 6 months (i.e. 2 or more epileptic seizures within a 6 month period)
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Status epilepticus or cluster seizures
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The postictal signs are considered especially severe (e.g. aggression, blindness) or last longer than 24 hours
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The epileptic seizure frequency and/or duration is increasing and/or seizure severity is deteriorating over 3 interictal periods
International veterinary epilepsy task force consensus proposal: outcome of therapeutic interventions in canine and feline epilepsy
This paper represents a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures.
It also provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered.
2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs
The goal of this consensus statement was to establish guidelines for treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life.
Canine Epilepsy
This article reviews manifestations of comorbidities in canine epilepsy with an emphasis on patterns of clinical signs and their effects on quality of life. Cognitive and behavioral alterations in epileptic dogs are mainly represented by fear-/anxiety-related behavior and cognitive impairment. Reduced trainability and altered reactions to daily situations are common results of comorbid changes posing obstacles in the everyday life of owners and their dogs. In addition, clinical signs similar to attention deficit hyperactivity disorder in humans have been reported
This review compares the pathogenesis of canine epilepsy and its most commonly recognized comorbidities: cognitive impairment, attention deficit hyperactivity disorder (ADHD)-like behavior, fear, and anxiety.
The anatomical and functional origins of epilepsy and the behavioral co-morbidities along with the roles of inflammation and neurotransmitters are discussed in this study.
The Postictal Phase in Canine Idiopathic Epilepsy: Semiology, Management, and Impact on the Quality of Life from the Owners’ Perspective
The postictal phase has been minimally studied in both human and veterinary medicine. This study aimed to understand the clinical signs of the post-ictal period, assess its impact on the quality of life, highlight its importance in managing seizure disorders, and explore potential therapeutic approaches for post-ictal symptom management.
This survey based study of 292 epileptic dog owners revealed signs which included disorientation, compulsive walking, ataxia, and blindness. Nearly 61% of the owners felt that the severity of postictal signs was moderate or severe. Rescue antiseizure medications did not have an effect on controlling the postictal signs based on 71% of the responders. In contrast, 77% of the respondents reported that other measures such as rest, physical closeness, and a quiet and dark environment had a positive impact on the postictal phase.
Idiopathic epilepsy & epilepsy of unknown cause in Irish setters
This study focuses on phenotypic characteristics of idiopathic epilepsy and epilepsy of unknown cause in Irish Setters and looks at its mode of inheritance.
The mean age of seizure onset was 41 months. Five of the dogs included in the study had an onset of seizures >6 years of age. These dogs were classified with epilepsy of unknown cause. Primary generalized tonic-clonic seizures were the most common type of seizure and were seen in almost all dogs. Cluster seizures were reported in 54% of the studied population.
Prevalence of idiopathic epilepsy and structural epilepsy in 74 Boxer dogs in a referral hospital
The aim of this retrospective study was to evaluate the prevalence of structural and idiopathic epilepsy in the Boxer population.
Five dogs (6.8%) were diagnosed with idiopathic epilepsy, of which one was <6 months old. Sixty-nine dogs (93.2%) were diagnosed with structural epilepsy - 81.8% of the patients had a suspected intra-axial tumor and 22.7% of dogs with an intracranial pathology had a normal neurological examination. In conclusion, the most common cause of epilepsy in boxer dogs is a suspected intracranial neoplasia regardless of the age at presentation
Phenotypic Characterization of Idiopathic Epilepsy (IE) in Border Collies (BCs)
The aim of this retrospective study was to describe the phenotype of BCs with IE and assess associations between phenotypic variables and owner-provided quality-of-life (QoL) scores.
The median age at onset of the first epileptic seizure in 116 BCs was 33.5 months (6–188). Age at onset was significantly lower for dogs having experienced cluster seizures (CSs), status epilepticus (SE), or both (median 27 months) vs. dogs that had not experienced CS or SE (median 43 months) - 30% had SE and 60% had CS with 22% having both.
Owners scored their dog's QoL to have declined by a median of 30% during the course of life with IE with 39% of owners scoring their dog's QoL to have declined by ≥50%
Pathophysiology of drug-resistant canine epilepsy
Drug resistance continues to be a major clinical problem in the therapeutic management of canine epilepsies with substantial implications for quality of life and survival times.
Seizure frequency and the occurrence of cluster seizures have been linked with a poor response to anti-seizure medications. Moreover, evidence exists that the genetic background and alterations in epigenetic mechanisms might influence the efficacy of anti-seizure medications in dogs with epilepsy.
This paper reviews the pathophysiology of anti-convulsant drug resistance in dogs.
Approach to canine epileptic seizures in primary care practices
This study looked at epileptic dogs in first opinion practice in the UK to see what our colleagues do for management. 517 dogs were included in this study:
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Sixty-seven dogs (13.0%) received anti-seizure drugs at first presentation; this was significantly more likely in dogs presented with cluster seizures
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321 dogs presented for 1 seizure; 7 were started on anticonvulsants
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86 presented for clusters; 50% were started on anticonvulsants.
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Imepitoin was most frequently used for clusters despite there being no license for this
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165 dogs presented for 1 seizure and had >6 month follow-up - 20% of these had no more seizures.
CANNABIDIOL IN CANINE EPILEPSY - WHERE ARE WE AT?
The anticonvulsant effect of cannabidiol (CBD) is a hot topic of conversation at the moment on social media with high interest from dog owners sometimes faced with a pet poorly responding to anticonvulsants. This review published in The Veterinary Journal provides an overview about the current state of knowledge regarding anti-seizure effects of CBD and the application of CBD in dogs with epilepsy.
Neurosurgery in canine epilepsy
This review summarizes current standards of intracranial epilepsy surgery in human medicine and describes its current status and expectation in veterinary medicine. Intracranial epilepsy surgery is classified generally into resection surgery, represented by cortical resection, lobectomy, and lesionectomy, and disconnection surgery, such as corpus callosotomy and multiple subpial transection. In dogs with drug-resistant epilepsy, corpus callosotomy is available as a disconnection surgery for generalized epilepsy
This systematic review including a meta-analytic approach was designed to evaluate existing evidence for the safety profile of anti-epileptic drugs (AEDs) in canine patients.
Ninety studies, including six conference proceedings, reporting clinical outcomes of AEDs' adverse effects were identified. Few studies were designed as blinded randomised controlled clinical trials. Many studies included low canine populations with unclear criteria of subject enrolment and short treatment periods. Direct comparisons suggested that imepitoin and levetiracetam might have a better safety profile than phenobarbital, whilst the latter might have a better safety profile than potassium bromide. However, none of these comparisons showed a statistically significant difference. Comparisons between other AEDs were not possible as a considerable amount of studies lacked power calculations or adequate data to allow further statistical analysis. Individual AED assessments indicated that levetiracetam might be one of the safest AEDs, followed by imepitoin and then phenobarbital and potassium bromide; these findings were all supported by a strong level of evidence. The safety profile in other AEDs was variable, but weak evidence was found to permit firm conclusions or to compare their safety to other AEDs.
Evaluation of Quality of Life (QoL) in Dogs with Idiopathic Epilepsy
The objective of this study was to develop a list of key questions evaluating QoL in dogs with idiopathic epilepsy (IE) and their carers. The study aimed to refine 90 QoL online questions down to the least number of questions representing useful themes without loss of descriptive value.
36 questions were left with seven themes:“Seizure severity and frequency”, “Adverse effects of antiepileptic drug (AED)”, “Restrictions on the carer's life”, “Frustrations over caring for a dog with IE”, “Carer distaste of AED adverse effects”, “Carer anxiety around the seizure event”, “Perceptions on rectal diazepam use”.
Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED)
Sudden Unexpected death in epilepsy (SUDEP) in people refers to deaths with epilepsy that are not caused by injury, drowning, or other known causes, and in post mortem examination no obvious reason for death can be found. Studies suggest that each year, there are about 1.16 cases of SUDEP for every 1,000 people with epilepsy, although estimates vary. A probable SUDEP (pSUDEP) is defined as SUDEP not confirmed by post-mortem examination.
In this retrospective study, the authors evaluate (via on online questionnaire) the occurrence of pSUDED in dogs with epilepsy. The results of this study suggest that dogs with idiopathic epilepsy (IE), especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. The percentage of pSUDED in this cohort of 264 dogs with IE was 4.5% (or 10% evaluating only 120 dead dogs with IE). Life expectance in dogs with pSUDED was found to be on average 1.5 yrs shorter than in dogs with IE.
As increased activity has been shown to reduce seizure frequency in people with epilepsy, the goal of this study was to evaluate the relationship between deviation from baseline activity and seizure incidence in dogs with epilepsy.
Activity and seizure data were obtained using a canine activity monitoring device and owner observed seizure logs in 53 dogs with idiopathic epilepsy receiving anti-epileptic drugs.
Seizure incidence was significantly more likely when activity was 10%, 20%, or 30% above baseline activity in the 24 hours before the day of a documented seizure. However, when activity levels were 40% and 50% above baseline, the effect diminished
Premature Death, Risk Factors, and Life Patterns in Dogs with Epilepsy
This study evaluated 63 dogs diagnosed with epilepsy for premature death.
The median age at death of dogs was 7.0 years. The life span of dogs in which euthanasia or death was directly caused by their epileptic condition was significantly shorter as compared with epileptic dogs that were euthanized because of other causes. The median number of years that a dog lived with epilepsy was 2.3 years. Females lived longer with epilepsy than males. Seizure type (primary generalized versus focal seizures) was not significantly associated with survival time. The remission rate of epilepsy (spontaneous remission and remission with treatment) was 15%.
Fly-catching syndrome (FCS) is a rare canine condition of sudden, occasional, or constant episodes of biting the air. It may be accompanied by jumping, licking, and swallowing. The etiology of FCS is unknown and controversial. Various explanations for its occurrence have included epileptoid disorders such as visual cortex epileptiform disturbances and simple and complex focal seizures as well as compulsive disorders, hallucinatory behavior, and stereotypy. A retrospective multicenter analysis of 24 dogs with clinical symptoms of FCS is reported in this paper.
EEG revealed spike activity in 8 (38%) of the 21 cases, 7 of which had activity in the occipital lobes. Thirty-six percent of dogs responded to phenobarbitone, while 100% of the dogs responded to fluoxetine.
Epileptic seizures triggered by eating in dogs
This study aimed to document the occurrence of seizures triggered by eating (STE) in 10 dogs and describe their clinical features. Cases were included if >50% of the seizures that occurred were related to eating.
Four cases only had STE and 6 cases had both STE and spontaneous seizures.Four of the dogs were retrievers. The most common seizure type was focal evolving to become generalized. Nine dogs were diagnosed with idiopathic epilepsy. One dog had a presumptive diagnosis of glioma. Anti-seizure treatment and food management strategies were successfully used in many of the dogs.
This study looks at risks factors of developing post-encephalitic epilepsy (PEE) in dogs with MUO. Half of the dogs with MUO experienced acute symptomatic seizures (ASS) and almost a quarter developed PEE. The presence of ASS and hippocampal lesions on MRI was the strongest predictor of PEE. Dogs with PEE were younger and had a significantly shorter survival time when compared to dogs without PEE. 20% of dogs with PEE developed drug‐resistant epilepsy.
Clinical features and outcome of 10 dogs with suspected idiopathic vestibular epilepsy
In human medicine, vestibular epilepsy is described as focal seizures with signs of vestibular disease as the only or main symptoms and these signs can range from mild disequilibrium to dizziness and vertigo. Vestibular seizures have been described to be short duration, of a few seconds, with an abrupt ending - see video below. The events are electrophysiologically detectable at the level of the temporal and parietal lobes of the cerebral cortex but MRI of affected people has not revealed a structural cause. Importantly though these events need to be differentiated from the so-called vestibular paroxysmia which are "episodes of spinning or non‐spinning vertigo, lasting from seconds to minutes, which occur spontaneously or after changes in body position in the absence of other potential underlying differential diagnoses".
This paper describes 10 dogs with recurrent vestibular episodes, in terms of their clinical features, phenotypical manifestations, and outcome. Advanced imaging was normal in all cases and the CSF evaluated from 4 of the dogs was also considered normal. 5/10 dogs were Pugs!
Frequency of non-generalized tonic clonic seizures in a referral population of dogs
Non-generalized tonic-clonic seizures (non-GTCS) include both focal and absence seizures. Absence seizures are a type of generalized onset seizure, with periods of unresponsiveness or staring and may include facial/head twitches, similar clinical signs to focal seizures distinguishable as characteristic brain activity seen on an EEG.
The objective of this retrospective study was to investigate the frequency of non-GTCS in dogs and evaluating the distribution of seizure types using EEG. 53–63 % of 528 seizure cases were described as generalized tonic clonic seizures (GTCS), 9–15 % GTCS with additional events (focal onsets or unconnected absence seizures), and 29–35 % with suspected non-GTCS. EEG confirmed absence seizures in 12 of 44 cases, with 5 cases having a history of GTCS and seven without prior GTCS.
Feline Epilepsy
Clinical comparison of primary versus secondary epilepsy in 125 cats
This study investigated the aetiology and compared primary epilepsy (PE) with secondary epilepsy (SE) in terms of signalment, history, ictal pattern, clinical and neurological findings. Seizure aetiology was classified as PE in 47 (38%) and SE in 78 (62%) cats. SE was caused mainly by intracranial neoplasia (16), hippocampal necrosis (14), toxicosis (eight), and encephalitis (seven). A significant difference between PE and SE was found in: age, body weight, duration of seizure, occurrence of status epilepticus and neurological deficits. Status epilepticus, altered interictal neurological status and seizure onset over the age of 7 years indicated SE more frequently than PE.
Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy
A systematic review was constructed to assess current evidence for the efficacy and tolerability of available anti-convulsant drugs in cats.
Individual assessments of drug efficacy and safety profile showed that phenobarbital might currently be considered as the first choice anti-seizure drug in cats, followed by levetiracetam and imepitoin. Only imepitoin’s safety profile was supported by a strong level of evidence.
Even though this review is based upon the evidence of 40 studies, it is obvious that more work is needed in this area for us to know how to best treat epilepsy in cats.
Treatment and long-term follow-up of cats with suspected primary epilepsy
This study evaluates the treatment and outcome of cats with suspected primary epilepsy. Phenobarbital therapy was used alone or in combination with other anti-epileptic drugs.
About 40–50% of cases became seizure-free, 20–30% were considered good-to-moderately controlled (1-10 seizures per year) and about 30% were poorly controlled > 10 seizures per year). The duration of seizure events after treatment decreased in 26/36 cats and was unchanged in eight cats. The subjective severity of seizure also decreased in 25 cats and was unchanged in nine cats. Twenty-six cats had a good quality of life, nine cats an impaired quality of life and one cat a bad quality of life.
Despite being free of seizures for years, cessation of treatment may lead to recurrence of seizures in most cats.
Feline Temporal Lobe Epilepsy - a review
Feline temporal lobe epilepsy (TLE) is a syndrome with characteristic ictal signs including orofacial automatisms with lip-smacking, facial twitching, and chewing together with mydriasis and/or hypersalivation. It is important to recognize that feline TLE is not itself an aetiological category but can be caused by many different aetiologies ranging from vascular, neoplastic, inflammatory or unknown etiologies. MRI in these affected cats often shows changes in signal intensity of the hippocampal region especially on T2 and FLAIR as well as volume changes in the hippocampus, in addition to changes related to the underlying aetiology if a structural one is present. Prognosis in these cases depends on the underlying aetiology, how promptly antiseizure treatment (phenobarbital and/or levetiracetam) can be initiated, how severe the epileptic seizures are, and how severe the hippocampal pathology is. This paper provides up-to-date information in current knowledge on feline TLE including emerging surgical options.
Seven cases of feline hippocampal and piriform lobe necrosis (FHN) are described, with particular emphasis on clinical, radiographic and histopathological correlations.
Seizures are typically focal and feature uni- or bilateral orofacial or head twitching, hypersalivation, lip smacking, mydriasis, vocalisation and motionless staring, with inter-ictal behavioural changes such as unprovoked aggression and rapid running. Emerging evidence supports an autoimmune aetiology, although disruption of hippocampal architecture secondary to brain neoplasia has also been recognised. Most commonly, however, the underlying cause remains unknown. Diagnosis is achieved clinically and with brain MRI; electroencephalography and voltage-gated potassium channel-complex autoantibodies are currently the subject of research. Affected cats are frequently refractory to conventional antiepileptic treatment.
A feline model of spontaneously occurring autoimmune limbic encephalitis
Antibodies against leucine-rich glioma-inactivated 1 (LGI1) is one of the most prevalent forms of autoimmune encephalitis (AE) in humans, and this was recently described in cats with limbic encephalitis (LE). In this study, a large cohort (n = 32) of cats with AE, tested positive for voltage gated potassium channel (VGKC)-antibodies, of which 26 (81%) harboured LGI1-antibodies. Their clinical features as well as long-term outcomes up to 5 years are described.
Epilepsy in British Shorthair cats in Sweden
This study investigated the prevalence of epileptic seizures and of presumed idiopathic epilepsy (PIE) in 1645 British Shorthair (BSH) cats in Sweden as well as described the epileptic seizure characteristics and outcome for cats with PIE.
The prevalence of epileptic seizures was 0.9% and for PIE it was 0.7%. Twenty-seven percent of BSH cats with epileptic seizures had cluster seizures but none presented with status epilepticus. None of the BSH cats was treated with antiepileptic drugs, and none of the owners reported epileptic seizure remission in their cat.
Diagnosis
Differentiation between epileptic seizures and mimics such as syncope, paroxysmal dyskinesia, narcolepsy/cataplexy, myokymia, vestibular 'attacks' or metabolic causes of collapse can be very challenging. The differentiation between epileptic seizures and these mimics is important, as their diagnostic and therapeutic measures may differ significantly. In this recent study published in the Veterinary Journal, the authors explore the use of serum phosphorus concentration (sPi) as a marker to differentiate generalized tonic-clonic seizures (GTCS) from syncope on the basis that transient hypophosphatemia is often detected in humans following GTCS. They concluded that given its high specificity, hypophosphatemia, especially when combined with increased CK and with sPi concentration < 0.97 mmol/L, in samples collected ≤ 3 h post-TLOC may be highly useful in clinical practice for ruling in a GTCS episode.
Above is a video of a previous patient of ours presented with episodes of collapse caused by cardiac arrhythmia.
A novel magnetic resonance imaging (MRI) sequence that utilizes a variant of the rotary saturation approach has been suggested to detect weak transient magnetic field oscillations generated by neuronal currents in humans with epilepsy.
This study evaluated the sequence in dogs with idiopathic epilepsy.
The proposed MRI method detected neuronal currents in dogs with epileptic seizures and represents a potential new line of research to investigate neuronal currents possibly related to IE in dogs.
The image above is taken from this paper.
Peri-ictal magnetic resonance imaging characteristics in dogs with suspected idiopathic epilepsy
The aim of this study is to characterize and describe seizure-induced changes detected by MRI. Eighty-one client-owned dogs diagnosed with idiopathic epilepsy were evaluated with standard MRI sequences in addition to diffusion and perfusion weighted imaging where available.
Seizure-induced changes were T2-hyperintense with no suppression of signal on FLAIR. Lesions were T1-isointense or hypointense, local mass effect and contrast enhancement. The majority of changes were bilateral and symmetrical. The most common areas affected were the hippocampus, cingulate gyrus, hippocampus and piriform lobes. Diffusion (DWI) characteristics were a mixed-pattern of restricted, facilitated, and normal diffusion. Perfusion (PWI) showed either hypoperfusion or hyperperfusion.
Emergency Seizures
Risk factors associated with short-term mortality and recurrence of status epilepticus in dogs
This study of dogs with status epilepticus (SE) found that short-term mortality was almost 30% and factors associated with this included increased patient age, shorter duration of hospitalization, development of SE before arrival, and SE caused by a potentially fatal aetiologies.
In addition SE was found to recur in 27% of dogs that survived to discharge which was associated with prior history of pharmacoresistant epilepsy and predominance of a focal seizure phenotype.
A retrospective study on the use of CRI of diazepam (DZP) or propofol (PPF) for canine CS or SE. The 37 dogs included in this case series included dogs with idiopathic epilepsy, structural epilepsy as well as metabolic or toxic causes of seizure activity. The authors carefully noted some limitations of this study which included the absence of randomization in the choice of CRI between DZP and PPF as well as clinical efficacy being defined as cessation of physical manifestation of seizure activity rather than EEG burst suppression.
This study however documents the use of CRI of DZP or PPF in a large sample of dogs with various causes of seizures.The medications appeared to be tolerated without major side effects and helped control seizure activity in most patients regardless of seizure etiology
Continuous rate infusion of midazolam as emergent treatment for seizures in dogs
This retrospective study looks at the use of midazolam CRI in dogs with cluster seizures (CS) or status epilepticus (SE). The authors suggest a starting dose of 0.1 to 0.25 mg/kg/hr with subsequent dose escalation as required to control seizure activity, to a maximum of 2 mg/kg/h. In this study, seizures were controlled in 85% of dogs with idiopathic epilepsy, 74% with structural epilepsy, 75% with unknown epilepsy and 57% with reactive seizures. Adverse effects were reported in 22.6% and were mild in all cases. Median duration of CRI was 25 hrs.
This review provides an outline of the management of SE at home and in a hospital setting, discussing considerations and challenges of the various routes of BZD administration, and evaluating the impact of intranasal drug administration (nose-brain pathway) for controlling canine SE at home and within hospital settings.
NMDA receptor antagonists, like ketamine, are able to end the maintenance phase of chronic status epileptics (SE), sometimes called self-sustaining SE. NMDA receptor activation only occurs in the later phases of SE, perpetuating the seizure activity, so NMDA antagonists are suspected to be beneficial during prolonged or refractory SE. Ketamine may also have neuroprotective effects by inhibiting NMDA receptor-mediated excitotoxicity associated with prolonged seizure activity (despite some evidence that excessive antagonism of the NMDA receptors can be detrimental).
In this retrospective study of 15 dogs, the authors use a bolus of 5 mg/kg IV solely or in combination with other anticonvulsants to treat prolonged and/or repeated seizure activity in cases of cluster seizures (CS), SE and refractory SE. While the effect on achieving termination of CS episodes was limited, a good response was observed in cases of SE/RSE that exhibit prolonged, uninterrupted seizure activity and resistance to benzodiazepines. The effectiveness of ketamine CRI in these patients still remains to be evaluated.
A serious adverse event secondary to rapid intravenous levetiracetam injection in a dog
An 8-year-old female spayed Chihuahua was evaluated for cluster seizures and tachypnea. The patient was administered an intravenous dose of undiluted levetiracetam (60 mg/kg) and immediately developed tachycardia, hyperglycemia, hypotension, and a dull mentation. The patient’s blood pressure and mentation did not respond to intravenous fluid boluses but improved immediately after administration of epinephrine intravenously. The patient subsequently developed respiratory failure necessitating mechanical ventilation, prior to cardiac arrest. Necropsy examination noted a pulmonary inflammatory cell infiltrate, pulmonary edema, and interstitial pneumonia
Circadian and multiday seizure periodicities, and seizure clusters in canine epilepsy
This study characterizes circadian and multiday seizure periodicities, and seizure clusters in dogs with naturally occurring focal epilepsy. In this retrospective cohort study, 16 dogs were continuously monitored with ambulatory intracranial EEG devices.
The study findings show that seizure timing in dogs with naturally occurring epilepsy is not random, and that circadian and multiday seizure periodicities, and seizure clusters are common.
Non-convulsive seizures (NCS) and non-convulsive status epilepticus (NCSE) are infrequently observed in veterinary medicine because their diagnosis can only can be achieved by the use of electroencephalography (EEG). They can be present in dogs and cats without any physical manifestations or with minimal muscular movements such as ear twitching.
This study aimed to determine the prevalence of NCS and NCSE in 26 dogs and 12 cats with a history of cluster seizures. 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%). Based on this study, prompt EEG monitoring should be performed in dogs and cats with cluster seizures.
The objective of this study was to compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in 44 dogs with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus.
IN-MDZ and IV-MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively. The median seizure cessation time was 33 and 64 seconds for IN-MDZ and IV-MDZ, respectively. 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).
The objective of this study was 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).
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.
Isoflurane treatment for refractory and super-refractory status epilepticus in dogs
This retrospective study evaluated 20 dogs with refractory status epilepticus (RSE) and super-refractory SE (SRSE; status lasting more than 24 hours) treated with isoflurane (ISO). Inspiratory ISO ranged between 0.5 and 4.0%. The median time of the anesthetic cycles with ISO was 12.67 h (4.00–62.00).
The clinical termination of seizure activity was achieved 100% of all episodes. In 73.1% of the episodes, ISO administration resulted in successful RSE/SRSE treatment. Poor outcome was recorded in 27% of the episodes because RSE/SRSE reoccurred after ISO discontinuation, and the dogs were euthanatized or died due to cardiac arrest.
Therapeutic Studies
Anti-convulsant Medications
The objective of this study was to evaluate the antiseizure efficacy and tolerability of ZNS monotherapy in 56 dogs with newly diagnosed idiopathic epilepsy (IE).
76% had a ≥ 50% reduction in seizure frequency, and 55% achieved seizure freedom.
For 90% of the dogs with ≥50% reduction in seizure frequency, the mean ZNS dose was 4.8 (range, 2.7-8.6) mg/kg q12h.
In 7 of the 56 dogs (13%), reduced activity, decreased appetite, vomiting, hindlimb weakness, soft stools, or constipation was observed, albeit mild and temporary.
The aim of the study was to compare antiseizure efficacy and tolerability of two add-on treatment strategies in dogs with drug-resistant idiopathic epilepsy. The study design was a prospective, open-label, non-blinded, comparative treatment trial.
Twenty-six dogs with drug-resistant idiopathic epilepsy and a history of cluster seizures were included. Dogs received either add-on treatment with pregabalin (PGB) 4 mg/kg twice daily or a dose increase in levetiracetam (LEV). 14% and 8% respectively achieved treatment success which was a 3-fold extension of the longest baseline inter-seizure interval and to a minimum of 3 months.
Myoclonic seizures are considered a type of generalised seizure characterised by brief, jerking movements of the body. This study aims to describe cases of suspected canine myoclonic seizure of idiopathic aetiology and to discuss the successful use of the anticonvulsant levetiracetam as treatment in each of these cases.
Five dogs were included, all of which had suspected myoclonic seizures. All dogs were treated with levetiracetam. Two dogs experienced long-term myoclonic seizure freedom (duration seizure-free of at least 1 year), and two dogs experienced marked decreased myoclonic seizure frequency.
Once-a-day oral treatment with phenobarbital in cats with presumptive idiopathic epilepsy
The aim of this retrospective study was to evaluate once daily treatment with oral phenobarbital (PB) in cats with presumptive idiopathic epilepsy.
Nine cats with presumptive idiopathic epilepsy, receiving once daily oral PB were included in a retrospective descriptive study.
Seizure remission was achieved in 8/9 of the cats and good seizure control in 1/9 of the cats, treated with a mean dose of oral PB of 2.6 mg/kg q24h (range 1.4–3.8 mg/kg). No cats required an increase of their PB frequency at any time during a mean follow-up period of 3.5 years (range 1.1–8.0 years).
Treatment in canine epilepsy – a systematic review
In 2014 these authors conducted a systematic review designed to evaluate existing evidence for the effectiveness of AEDs for presumptive canine idiopathic epilepsy. Individual studies were evaluated based on the quality of evidence, and the outcome measures reported. The authors evaluated 26 studies. A good level of evidence supported the efficacy of oral phenobarbital and imepitoin and fair level of evidence supported the efficacy of oral potassium bromide and levetiracetam.
A systematic review of the safety of potassium bromide in dogs
The aim of this study was to critically evaluate and summarize available information within 111 publications on the safety of potassium bromide in dogs.
Reversible neurologic signs were the most consistently reported toxicoses and were generally associated with adjunctive potassium bromide treatment or high serum bromide concentrations. Dermatologic and respiratory abnormalities were rare in dogs. Insufficient information was available to assess the effects of potassium bromide on behavior or to determine the incidence of vomiting, weight gain, polyphagia, pancreatitis, polyuria, polydipsia, or reproductive abnormalities associated with potassium bromide administration. Evidence suggested that administration of potassium bromide with food may alleviate gastrointestinal irritation and that monitoring for polyphagia, thyroid hormone abnormalities, and high serum bromide concentrations may be beneficial.
Behavioral Changes Under Levetiracetam Treatment in Dogs
This study evaluated the incidence of behavioral changes in 84 epileptic dogs treated with levetiracetam (LEV) based on information obtained in a questionnaire completed by dog owners. Dogs with recurrent seizures receiving LEV as monotherapy, add on treatment or pulse therapy met inclusion criteria. Approximately half of the dogs in the study population were reported to have preexisting behavioral changes before treatment with LEV, and some of these dogs were reported to experience a worsening of behavioral changes (14/44) (anxiety (n = 11), attention seeking behavior (n = 8), depression (n = 6), aimless behavior (n = 6), aggression (n = 6), hyperactivity (n = 3), and decreased learning ability (n = 1)). One quarter of the dogs without pre-existing behavioral abnormalities developed positive behavioral changes such as increased activity (n = 4), more energy (n = 4), calmer mood (n = 3), higher tolerance to environmental stress (n = 3), increased obedience (n = 1), and a joyful mood (n = 1).
Adverse outcomes associated with switching between bioequivalent brand name and generic antiepileptic drug products is a subject of concern.
This study compared bioavailability of phenobarbital after single dose administration of Luminal® vet vs. Phenoleptil® with a crossover design in 8 healthy Beagle dogs.. Both drugs were administered at a dose of 100 mg/dog, resulting in 8 mg/kg phenobarbital on average. The study found no significant difference. However, the study concludes that individual dogs may exhibit lower plasma levels after administration of a generic formulation that could be clinically meaningful.
Factors influencing serum concentrations of levetiracetam in dogs with epilepsy
The aim of this study was to determine factors that could influence serum levetiracetam concentrations and justify dose adjustment in 69 epileptic dogs.
As expected, phenobarbital co-administration significantly decreased serum levetiracetam concentration in a dose dependent manner.
Based on this study, a levetiracetam dosage of 99–216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 μg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified.
Therapeutic Studies
Diet
This study examined the effect of a ketogenic medium chain triglycerides (MCT)-enriched diet administered for one month on the fecal microbiota of epileptic (n = 11) (six with drug-sensitive epilepsy, DSE; five with drug-refractory epilepsy, DRE) and non-epileptic beagle dogs (n=12).
Baseline microbiota patterns were similar in non-epileptic beagles and dogs with DSE but significantly different from dogs with DRE. In non-epileptic and DSE groups, the MCT diet decreased the relative abundance of Firmicutes and increased that of Bacteroidetes and Fusobacteria, but the opposite effect was observed in dogs with DRE.
These results suggest that the MCT diet effect would depend on individual baseline microbiota patterns and that ketogenic diets could help reduce gut microbiota differences between dogs with DRE and DSE.
A diet enriched with medium-chain triglycerides (MCTs) on seizure frequency has been evaluated in several studies in dogs with idiopathic epilepsy (IE). This prospective, randomized, double-blinded, placebo-controlled, crossover dietary study evaluated dogs treated with zonisamide and a palcebo diet or an MCT enriched diet. The study found that the commercially available MCT-enriched diet (NeuroCare) can be safely used concurrently with ZNS for dogs with IE
The authors aimed to identify changes in the metabolome and neurotransmitters levels relevant to epilepsy and behavioural comorbidities associated with the consuming of an MCT supplement (MCT-DS) in dogs with idiopathic epilepsy (IE).
Five dogs (30%) had an overall reduction in seizure frequency of ≥50%, and were classified as MCT-responders, while 23 dogs showed a ≤50% reduction, and were defined as MCT non-responders. Amino-acid metabolism was significantly influenced by MCT consumption compared to the control oil.
A significantly increased γ-aminobutyric acid (GABA) concentration was detected during the MCT-phase accompanied by a significant shift of the GABA-glutamate balance. MCT-Responders had significantly lowered urinary concentrations of histamine, glutamate, and serotonin under MCT consumption.
The aim of this study was to evaluate the short-term efficacy of MCTs administered as an add-on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles.
Twenty-eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used.
A 6-month multicenter, prospective, randomized, double-blinded, placebo-controlled crossover trial was completed, comparing an MCT-DS with a control-DS. A 9% metabolic energy-based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months.
Seizure frequency and seizure-day frequency were significantly lower when dogs were fed MCT-DS in comparison with the control-DS. Two dogs were free of seizures, 3 had ≥50% reduction in seizure frequency,
This study aimed to evaluate the efficacy and tolerability of a commercially available diet enriched with 6.5% medium chain triglyceride (MCT) oil in dogs (n=21) with at least a tier 1 idiopathic epilepsy diagnosis, without cluster seizure.
The mean seizure frequency per month significantly decreased 32% compared with the baseline monthly seizure frequency recorded during the month immediately before feeding the diet. Similarly, the seizure days rate (days/month) also declined by 42% cent.
Gut-microbiota-directed strategies to treat epilepsy: clinical and experimental evidence
A growing appreciation that the intestinal microbiota might exert changes on the central nervous system via the gut-brain has emerged as a new research frontier in neurological disorders.
This paper reviews the scientific evidence on the gut microbiota's role in epilepsy, both in clinical and experimental studies, to better understand how targeting the gut microbiota could serve as a diagnostic or prognostic research tool. Translating microbial molecular mechanisms to medical settings could fill the gaps related to alternative therapies for patients with epilepsy, mainly in cases with refractory phenotypes and this is discussed in this paper.
Gut Microbiota in Canine Idiopathic Epilepsy: Effects of Disease and Treatment
The aim of this study was to investigate the changes in gut microbiota from dogs with idiopathic epilepsy and the possible effect of antiepileptic drugs on the modulation of the composition of this microbiota.
In comparison with control dogs, drug-naive epileptic individuals showed a significantly reduced abundance of GABA and SCFAs-producing bacteria, as well as bacteria associated with reduced risk for brain disease. The use of phenobarbital or imepitoin monotherapy during one month in epileptic dogs did not modify the gut microbiota composition. These results open up the possibility of studying probiotic interventions in epilepsy.
A new multicenter study investigated the effect of fecal microbiota transplantation on behavioral comorbidities in 9 dogs with drug-resistant epilepsy.
The therapy was performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. A comprehensive behavioral analysis was conducted which showed that the dogs exhibited improvement in attention deficit hyperactivity (ADHD)-like behavior, fear- and anxiety-like behavior and quality of life. Furthermore, there was a reduction in measured excitatory neurotransmitters (glutamate and aspartate) with increases in inhibitory neurotransmitter GABA.
Therapeutic Studies
Cannabinoids
Interesting study looking at the use of cannabidiol (CBD) and cannabidiolic acid (CBDA)-rich hemp products for the management of refractory epilepsy in dogs. All dogs included in this study had been treated for over a year and remained only partially responsive to common highest tolerable doses of antiseizure medication yet still had at least one epileptic event per month. Of the 14 dogs included in this cohort, 6 dogs had 50% or greater reduction in epileptic activity while on treatment, whereas none had reductions of 50% or greater while on placebo. Adverse events were minimal, but included somnolence (3/14) and transient increases of ataxia (4/14) during CBD/CBDA-rich hemp extract treatment. The authors conclude that a use 2 mg/kg every 12 hrs of a CBD/CBDA-rich hemp extract can have a potential benefit for some dogs in reducing the incidence of epileptic seizures, when used concurrently with other antiseizure medications.
The objective of this study was to evaluate the addition of cannabidiol (CBD) to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in 51 dogs with drug-resistant idiopathic epilepsy.
At 9 mg/kg/day, the decrease in total seizure frequency was significant compared with placebo. A 24.1% decrease in seizure days occurred in dogs receiving CBD and a 5.8% increase occurred in dogs receiving placebo (P ≤ .05). No significant difference was found in the number of responders (≥50% decrease in total seizures or seizure days). Decreased appetite and vomiting were more common in the CBD phase.
Therapeutic Studies
Surgical and Neurostimulation Therapies
In this study, the authors look at the feasibility of non-invasive vagus nerve stimulation as an adjunctive treatment in a small number of dogs with refractory seizures. Although the efficacy warrants to be assessed on a larger scale of dogs, this treatment was found to be safe, easy to administer with mild adverse events.
Case Report: 1-Year Follow-Up of Vagus Nerve Stimulation in a Dog With Drug-Resistant Epilepsy
This case report suggests the potential benefit of VNS as adjunctive non-pharmacological therapy and the benefit of gradual adjustments of stimulation parameters while avoiding adverse effects in a dog with drug-resistant epilepsy (DRE).
The frequency of generalised tonic-clonic seizures was reduced by 87% after implantation of the VNS with improvement in this dog personality and quality of life of both the dog and the owner.
This case report provides some solid basis for future research in the use of VNS in dogs with DRE.
This image below is from the article and shows the pulse generator placed subcutaneously and electrode at the level of the left vagosympathetic trunk.
Transcranial magnetic stimulation is a neuromodulatory technique that applies magnetic pulses to the brain via a ‘coil.’ An electric current is delivered to the coil, which acts as the magnetic field generator in the procedure. The generated magnetic field induces an electrical current in the brain. Different coil types are used to elicit different magnetic field patterns, and using more focal points can elicit a deeper magnetic field to stimulate deeper cortical layers. Used in humans most commonly for refractory depression, this paper describes its use in drug-resistant epileptic dogs showing some positive impact for several months.