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Background: Post-ictal (PI) clinical signs are a key defining stage of seizure manifestation in dogs. However, this phase remains poorly understood., Objectives: To further characterize PI signs and their relation to other parts of a seizure, and understand the owner's perception of how PI signs affect the quality of life (QOL) of the dog., Animals: Eight-seven dogs with a diagnosis of idiopathic epilepsy from a single institution., Methods: The prospective questionnaire-based study surveying owners of dogs previously and newly diagnosed with idiopathic epilepsy., Results: Post-ictal signs were identified in 79/87 dogs, 5/5 of dogs with focal seizures and 74/82 of dogs with generalized seizures. Median duration of PI signs was 30 minutes (range, 5-4320 minutes). The most common PI signs reported were disorientation (50/79) and wobbliness or clumsiness (49/79). Within a year, a change in PI signs was seen in 18/79 dogs. The administration of benzodiazepines was significantly associated with an increase in duration of PI signs (P = .04). Post-ictal signs had more impact on dogs' quality of life compared with ictal signs (P < .01). Groupings of co-existing PI signs identified included disorientation, blindness and deafness., Conclusion: Post-ictal signs are a commonly reported aspect of seizures in dogs with idiopathic epilepsy, both in focal as well as generalized seizures. Co-existence of signs could provide some valuable insight into the relevance of this particular phase of a seizure. Owner-reported signs and documentation emphasize the need for a better understanding of PI signs in dogs with idiopathic epilepsy., (© 2025 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of the American College of Veterinary Internal Medicine.)

Background: Surgical excision is the treatment of choice for feline intracranial meningioma., Objectives: To report clinical findings, complications, and outcomes following surgery for feline intracranial meningioma., Methods: Medical records (01/2000-01/2017) of cats that underwent surgical excision of an intracranial meningioma at our institution were reviewed. Patient data included signalment, clinical signs, surgical technique, complications, histopathologic diagnosis, survival time, and owners' answers to a satisfaction questionnaire. Survival was assessed using the Kaplan-Meier method and log-rank test., Results: Twenty-six cats were included in this study. The exact cause of death was known in 17 cases and was not related to meningioma in 9/17 cases. Overall median survival time was 881 days (95% confidence interval 518; 1248). The age of the cat did not influence survival ( p = 0.94) or the occurrence of complications ( p = 0.051). Complications occurred in 13/24 cats, including dramatic complications in 4/24 cats. Most complications appeared in the first 24 hours post-surgery (12/13). Males had more postoperative complications ( p = 0.042), including more seizures ( p = 0.016). Cats with cranioplasty had fewer complications ( p = 0.021). Clinical recurrence was confirmed in 3 out of 17 cats. Recurrence-free survival time was 826 days. Most owners (12/14) were satisfied with the outcome., Conclusions: Surgical treatment of intracranial meningioma in cats was associated with a long median survival time but also with a high rate of minor and major postoperative complications, including early postoperative seizures. Cranioplasty may reduce complications. Age at the time of surgery had no effect on outcomes., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Background: Evidence-based recommendations for antiepileptic drug selection in cats beyond phenobarbital are limited, and additional studies are needed for cats where seizures remain inadequately controlled by administration of phenobarbital alone or for cats that cannot safely receive phenobarbital., Objective: To compare seizure frequency in cats before and after oral administration of zonisamide and describe adverse clinical or clinicopathologic effects in this cohort., Animals: Fifty-seven cats with a history of seizures., Methods: Multicenter, retrospective study. Median number of seizures per month and number of seizure days per month were compared before and after administration of zonisamide in all cats, a subgroup of cats with idiopathic epilepsy (IE), and a subgroup of cats receiving zonisamide as sole therapy. Clinical and clinicopathologic adverse effect data were also reported., Results: A median decrease of 1 (P = .001, 95% confidence interval (CI) [-1.0, -0.5]) seizure per month, and 1 (P = .003, 95% CI [-1.5, -0.2]) seizure days per month was found across all cats after oral administration of zonisamide. The subgroup with IE showed median decreases of 1 (P = .03, 95% CI [-2.0, -0.5]) and 2 (P = .01, 95% CI [-2.5, -1.0]), respectively. The most common clinical adverse effects were sedation (17%), ataxia (11%), hyporexia (17%), and emesis (5%). One cat developed mild nonregenerative anemia, 2 cats developed mild metabolic acidosis, and 6 cats showed mild increases in ALT and ALP., Conclusion: Zonisamide was well tolerated and efficacious in controlling seizure activity in most cats., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: High concentrations of complement factors are presented in serum of animal epilepsy models and human patients with epilepsy., Objectives: To determine whether complement dysregulation occurs in dogs with idiopathic epilepsy (IE)., Animals: The study included 49 dogs with IE subgrouped into treatment (n = 19), and nontreatment (n = 30), and 29 healthy dogs., Methods: In this case-control study, the serum concentrations of the third (C3) and fourth (C4) components of the complement system were measured using a canine-specific ELISA kit., Results: Serum C3 and C4 concentrations were significantly higher in dogs with IE (C3, median; 4.901 [IQR; 3.915-6.673] mg/mL, P < .001; C4, 0.327 [0.134-0.557] mg/mL, P = .03) than in healthy control dogs (C3, 3.550 [3.075-4.191] mg/mL; C4, 0.267 [0.131-0.427] mg/mL). No significant differences were observed in serum C3 and C4 concentrations between dogs in the treatment (C3, median; 4.894 [IQR; 4.192-5.715] mg/mL; C4, 0.427 [0.143-0.586] mg/mL) and nontreatment groups (C3, 5.051 [3.702-7.132] mg/mL; C4, 0.258 [0.130-0.489] mg/mL). Dogs with a seizure frequency >3 times/month had significantly higher serum C3 (6.461 [4.695-8.735] mg/mL; P < .01) and C4 (0.451 [0.163-0.675] mg/mL; P = .01) concentrations than those with a seizure frequency ≤3 times/month (C3, 3.859 [3.464-5.142] mg/mL; C4, 0.161 [0.100-0.325] mg/mL)., Conclusions and Clinical Importance: Dysregulation of classical complement pathway was identified in IE dogs. Serum C3 and C4 concentrations could be diagnostic biomarkers for IE in dogs with higher seizure frequency., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Emergency cases can present at any time of the day or night. All small animal practitioners need to have the skills to triage and stabilize common emergency cases even if they ultimately aim to refer the patient to another facility., Objectives and Procedures: The first part of this 3-part review article series covers respiratory distress and seizures. A stepwise approach to categorize and stabilize these cases is outlined, along with helpful tips to optimize the referral experience, if indicated., Results: Having a strong methodical approach to animals in respiratory distress optimizes treatment. Similarly, achieving cessation of seizures, along with having a good understanding of the causes of seizures, allows for patient stabilization., Conclusion and Clinical Relevance: Do NOT refer emergent cases before completing basic stabilization. Many emergency cases do not require emergent referral and can be worked up by the primary veterinarian or sent to a referral clinic on an appointment basis after appropriate stabilization steps are completed., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Juvenile idiopathic epilepsy (JIE) is categorized as a generalized epilepsy. Epilepsy classification entails electrocortical characterization and localization of epileptic discharges (ED) using electroencephalography (EEG)., Hypothesis/objectives: Characterize epilepsy in Egyptian Arabian foals with JIE using EEG., Animals: Sixty-nine foals (JIE, 48; controls, 21)., Methods: Retrospective study. Inclusion criteria consisted of Egyptian Arabian foals: (1) JIE group diagnosed based on witnessed or recorded seizures, and neurological and EEG findings, and (2) control group of healthy nonepileptic age-matched foals. Clinical data were obtained in 48 foals. Electroencephalography with photic stimulation was performed under standing sedation in 37 JIE foals and 21 controls., Results: Abnormalities on EEG were found in 95% of epileptic foals (35 of 37) and in 3 of 21 control asymptomatic foals with affected siblings. Focal ED were detected predominantly in the central vertex with diffusion into the centroparietal or frontocentral regions (n = 35). Generalization of ED occurred in 14 JIE foals. Epileptic discharges commonly were seen during wakefulness (n = 27/37 JIE foals) and sedated sleep (n = 35/37 JIE foals; 3/21 controls). Photic stimulation triggered focal central ED in 15 of 21 JIE foals., Conclusions and Clinical Importance: Juvenile idiopathic epilepsy has a focal onset of ED at the central vertex with spread resulting in clinical generalized tonic-clonic seizures with facial motor activity and loss of consciousness. Electroencephalography with photic stimulation contributes to accurate phenotyping of epilepsy. Foals with this benign self-limiting disorder might serve as a naturally occurring animal model for self-limited epilepsy in children., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

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., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To assess the clinical efficacy and plasma concentrations of levetiracetam in a goat with seizures., Animal: A 5-month-old doeling., Clinical Presentation, Progression, and Procedures: The goat was referred because of progressive anorexia and lethargy over 3 days. Clinical signs consisted of weakness, obtundation, opisthotonos, anisocoria, and cortical blindness. Initial evaluation was most consistent with polioencephalomalacia., Treatment and Outcome: Neurologic improvement occurred within 4 hours of thiamine administration, with appetite returning over 12 hours. On day 3 of hospitalization, the goat suffered acute onset repetitive seizures that were incompletely responsive to standard interventions over 3 hours. Administration of IV levetiracetam (60 mg/kg) produced resolution of seizure activity within 20 minutes. Levetiracetam was continued twice daily IV, then PO after day 6. Plasma concentrations were above or within therapeutic ranges (5 to 45 μg/mL) as previously established for other species, following both IV and PO levetiracetam. Oral administration (60 mg/kg, PO, q 12 h) resulted in plasma levetiracetam concentrations of 48.1 μg/mL 2 hours after a dose and 23.4 μg/mL 2 hours prior to the next dose., Clinical Relevance: Levetiracetam is a newer anticonvulsant commonly used in humans and small animals due to its efficacy, cost, and wide safety margin. Its use has not previously been reported in domestic small ruminants. In this case, levetiracetam showed excellent clinical efficacy in the face of refractory seizures, with no apparent side effects. Plasma concentrations during oral administration were at the high end of the therapeutic range, indicating absorption in a nonmonogastric species. Further studies are warranted to determine optimal dosing in small ruminants.

Background: The long-term effect of implantable vagus nerve stimulators (VNS) on seizures has not been evaluated in epileptic dogs., Objectives: Report seizure frequency in medication-resistant epileptic dogs before and after VNS implantation., Animals: Twelve client-owned dogs with idiopathic epilepsy and >1 seizure day per 3 weeks despite 3 months of appropriate use of 2 antiseizure medications and seizure diaries maintained 6 months before and >12 months after VNS implantation., Methods: Uncontrolled, open-label, before and after study. Mean monthly seizures and inter-seizure periods obtained from contemporaneous seizure diaries in the 6 months before implantation were compared with 0 to 6 months, 7 to 12 months, and subsequent 12-month periods after implantation. The number of dogs with >50% decrease in seizure frequency, >3 times increase in inter-ictal period interval, and seizure freedom for >3 months at the time of death or last follow-up were recorded., Results: Five of 12 dogs were euthanized <12 months after implantation. All 7 remaining dogs showed >50% decrease in seizure frequency until last follow-up, starting at a median of 37 to 48 months after implantation (range, 0-6 to 61-72 months) and a >3-fold increase in mean inter-seizure interval starting a median of 25 to 36 months after implantation (range, 0-6 months to 49-60 months), 3/7 dogs were seizure-free at death or last follow-up., Conclusions and Clinical Importance: Monthly seizure frequencies decreased and inter-seizure intervals increased in all dogs 2 to 3 years after VNS implantation, but a high proportion were euthanized before this time point. Prospective clinical trials are required to establish causality and the magnitude of this association., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Approximately 30% of dogs with idiopathic epilepsy (IE) are drug-resistant. Recent studies have suggested cannabidiol (CBD) may be an effective anticonvulsant in dogs with IE., Objective: To evaluate the addition of CBD to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in dogs with drug-resistant IE., Animals: Fifty-one dogs. Dogs having at least 2 seizures per month while receiving at least 1 ASD were included in the trial., Methods: Double-blinded placebo-controlled crossover study. The 5 mg/kg/day dosage met futility requirements after 12 dogs, and a dosage of 9 mg/kg/day was used in the next 39 dogs. Dogs were randomly assigned to receive CBD or placebo for 3 months, with a 1-month washout period between oils. Total numbers of seizures and seizure days were recorded. Diagnostic testing was performed periodically throughout the trial., Results: At the 9 mg/kg/day dose, 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). Liver enzyme activities increased at both dosages. Decreased appetite and vomiting were more common in the CBD phase (P ≤ .05)., Conclusions and Clinical Importance: Cannabidiol decreased total seizures and seizure days compared to placebo when administered to dogs PO at 9 mg/kg/day. Liver enzymes should be monitored with administration of CBD in dogs., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: The present study aimed to evaluate the postoperative quality of life (QOL) after surgery for the treatment of intracranial meningioma in cats., Methods: The study included 14 cases that underwent craniotomy from May 2009 to March 2021. Owners were contacted via telephone after a median time of 967 (range 227-4209) days after surgery and surveyed with a specially designed questionnaire that consisted of three domains, subdivided into different items. Physical behaviour, including general condition, food intake, mobility and overall impression, was evaluated from 0, reflecting the worst status, to 10, reflecting the best. The development of preoperative existing clinical signs, seizures and concurrent medication were evaluated individually for each patient. The time span necessary for the improvement of each item was recorded. Finally, satisfaction about the decision for surgery was ranked from 0 to 10., Results: Thirteen questionnaires were completed. Three cats were evaluated twice owing to revision surgery. Owners reported a statistically significant ( P  <0.001) improvement from immediately after the operation to 240 days after surgery. Preoperative clinical signs resolved in 95% of cases. All questioned owners would opt for surgery again., Conclusions and Relevance: QOL after surgery for intracranial meningioma in cats seems encouraging regarding our study. Nevertheless, limitations, such as small sample size, recall bias, lack of a control group and validation of the questionnaire, need to be kept in mind when interpreting the results., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Idiopathic epilepsy (IE) is a common, chronic brain dysfunction in dogs. Recently, the effect of feeding a diet enriched with medium-chain triglycerides (MCTs) on seizure frequency has been evaluated in several studies in dogs with IE. However, most dogs with IE in previous studies were treated with phenobarbital as the main antiseizure medication (ASM). In Japan, zonisamide (ZNS) is the most prescribed ASM for dogs with IE. The interaction between ZNS and various nutrients including MCTs and the potential effects on treatment efficacy resulting from combining these therapies have not been previously studied. A prospective, randomized, double-blinded, placebo-controlled, crossover dietary study was conducted. Dogs (n = 7) treated with ZNS were fed either a placebo diet (PL) or Purina ProPlan Veterinary Diet NeuroCare (NC) for 3 months, after which treatments were crossed over and continued for another 3 months. Seizure frequency (seizures/month; sz/m), blood tests including concentrations of ZNS and β-hydroxybutyric acid, and owner's visual analogue scale score were collected from all dogs for both treatment periods., Results: There was no significant difference in the seizure frequency between PL (2.95 ± 0.80 sz/m) and NC (1.90 ± 0.57 sz/m) during the 6 months of trial. Three of 7 dogs showed ≥ 50% seizure reduction, and 1 of those 3 dogs achieved seizure freedom in NC period. However, 2 of 7 dogs had no changes in epileptic seizure frequency, 2 of 7 dogs had a deterioration in seizure frequency in the NC period. Feeding the MCT diet concurrent with ZNS showed no apparent adverse effects and did not affect ZNS concentration., Conclusions: This study indicated that the commercially available MCT-enriched diet (NC) can be safely used concurrently with ZNS for dogs with IE., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Phenobarbital (PB) q12h is the most common treatment recommendation for cats with recurrent epileptic seizures. Medicating cats may be challenging and result in decreased quality of life for both cat and owner. The aim of this retrospective study was to evaluate treatment with oral PB q24h in cats with presumptive idiopathic epilepsy., Methods: Nine cats with presumptive idiopathic epilepsy, receiving oral PB q24h, were included in a retrospective descriptive study., Results: Seizure remission was achieved in 88% (8/9) of the cats and good seizure control in 12% (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). No cats displayed side effects or issues with compliance at the last recorded follow-up., Conclusions and Relevance: Once-a-day administration of PB for feline epilepsy was safe and resulted in satisfactory seizure control for the nine cats included in this study. The results of this study justify exploring this topic further in larger prospective studies.

Background: The anti-epileptic effects of docosahexaenoic acid (DHA) in dogs and humans remain controversial. The dosage and efficacy of DHA were various in the previous reports., Aim: The effects of high-dose DHA supplementation as add-on therapy for idiopathic epilepsy in dogs were evaluated., Methods: An open-label clinical trial was designed in this pilot study. Six dogs (median age: 6 years) with idiopathic epilepsy were included. All the patients were diagnosed with idiopathic epilepsy using magnetic MRI and cerebrospinal fluid examination (median: 2.0 years before the trial). They had 5-45 seizures and/or auras (median: 9.0) in the month before starting DHA supplementation. DHA was adjunctively administered at doses of 69-166 mg/kg/day without changing other prescriptions., Results: Four of the six patients completed the 6-month observation period. All the patients showed a decrease in seizure frequency of 50% or more within 2-3 months after the start of the administration, and three patients decreased to a frequency of 0-1 per month after 5-6 months. No clear adverse events were observed in the general condition or blood test results in any patients., Conclusion: Although the sample size was small and the study was not a randomized controlled trial, the data suggest that add-on supplementation of DHA could be useful in reducing the frequency of seizures in canine idiopathic epilepsy., Competing Interests: The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Background: Idiopathic epilepsy in cats is a more common disease than previously thought, but little information is available about the medical treatment of feline idiopathic epilepsy., Aim: To assess the therapeutic efficacy and safety of antiseizure medication (ASM) for a minimum of 6 months, including zonisamide (ZNS), in feline idiopathic epilepsy at a referral hospital in Japan., Methods: Twenty cats diagnosed with idiopathic epilepsy treated with ASMs were retrospectively included., Results: Nine cats that were finally treated with phenobarbital (PB) monotherapy reached the primary goal (the seizure frequency after the treatment intervention was less than one seizure every 3 months). Three cats were treated with ZNS monotherapy and two reached the primary goal. Eight cats finally received combination therapy. Two of the three cats receiving PB and ZNS therapy achieved the primary goal, but one was considered no responder. Five cats [PB + diazepam (DZP), ZNS + DZP, and ZNS + levetiracetam + DZP] decreased the seizure frequency and reached the primary goal in all but one cat reached the secondary goal. Adverse events were observed in eight patients, but these were curable. Two patients had vomiting after ZNS monotherapy, one had diarrhea, and another was an increase in sleeping hours., Conclusion: PB was frequently used and seemed effective as both monotherapy and combination therapy. Some cats were treated with ASM protocols containing ZNS. ZNS may be available to treat idiopathic epilepsy in cats. However, ZNS administration may cause adverse events, such as gastrointestinal toxicity, in cats., Competing Interests: The authors declared no potential conflicts of interest for this research, authorship, and/or publication of this article.

Background: Autoimmune mechanisms represent a novel category for causes of seizures and epilepsies in humans, and LGI1-antibody associated limbic encephalitis occurs in cats., Hypothesis/objectives: To investigate the presence of neural antibodies in dogs with epilepsy or dyskinesia of unknown cause using human and murine assays modified for use in dogs., Animals: Fifty-eight dogs with epilepsy of unknown cause or suspected dyskinesia and 57 control dogs., Methods: Serum and CSF samples were collected prospectively as part of the diagnostic work-up. Clinical data including onset and seizure/episode type were retrieved from the medical records. Screening for neural antibodies was done with cell-based assays transfected with human genes for typical autoimmune encephalitis antigens and tissue-based immunofluorescence assays on mouse hippocampus slices in serum and CSF samples from affected dogs and controls. The commercial human und murine assays were modified with canine-specific secondary antibody. Positive controls were from human samples., Results: The commercial assays used in this study did not provide unequivocal evidence for presence of neural antibodies in dogs including one dog with histopathologically proven limbic encephalitis. Low titer IgLON5 antibodies were present in serum from one dog from the epilepsy/dyskinesia group and in one dog from the control group., Conclusion and Clinical Importance: Specific neural antibodies were not detected using mouse and human target antigens in dogs with epilepsy and dyskinesia of unknown origin. These findings emphasize the need for canine-specific assays and the importance of control groups., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

A 6-year-old female spayed Great Dane was evaluated for acute onset cluster seizures. Magnetic resonance imaging (MRI) identified a mass in the olfactory bulbs with a large mucoid component caudal to the primary mass. The mass was removed via transfrontal craniotomy and histopathology revealed a tyrosine crystalline-rich, fibrous meningioma with a high mitotic index. Repeat MRI at 6 months showed no detectable tumor regrowth. The dog is clinically normal with no seizures at the time of publication 10 months after surgery. This meningioma subtype is rare in humans. This unique meningioma occurred in a dog of younger age and uncommon breed for intracranial meningioma. Biological progression of this tumor subtype is unknown; however, growth rate might be slow despite the high mitotic index., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Metaldehyde poisoning in dogs is well known and described issue. Several studies focused on the incidence, epidemiological features, and clinical and pathological findings associated with this intoxication. However, there are no prospective studies of metaldehyde poisoning and late-onset seizures., Aims: To prospectively describe clinical signs, therapeutic management, outcomes, and delayed-onset seizures due to metaldehyde poisoning in dogs., Methods: A 15-month prospective study on dogs with a diagnosis of metaldehyde poisoning, either via phone call to the animal poison control center or analysis at the toxicology laboratory in Lyon, France. Clinical signs, therapeutic management and outcomes, and the late onset of seizures were assessed for at least 3 years., Results: Twenty-six dogs were enrolled in the study. The most prevalent clinical signs were ataxia (18 dogs), convulsions (17), hypersalivation (15), and tremors (15). Treatment was symptomatic (e.g., activated charcoal, emetic therapy, and intravenous fluids) with anticonvulsant therapy (mainly diazepam). The overall survival rate was 81% (21/26 dogs). All dogs that received active charcoal (11/11) or emetic therapy (4/4) survived. Twelve of 17 dogs had convulsions and survived; 9 were followed up for at least 3 years after poisoning, and none had any other seizure episode or neurological sequelae., Conclusion: This prospective study describes clinical signs, therapeutic management and outcome of metaldehyde poisoning in dogs, and late-onset neurologic sequelae. None of the nine cases that were followed for 3 years developed neurological signs after metaldehyde poisoning. Therefore, long-term antiepileptic therapy is not indicated., Competing Interests: The Author declares that there is no conflict of interest.

A 1-year-old, intact female, mixed-breed dog (border collie and springer spaniel) was initially evaluated for lethargy, fever, and ataxia and subsequently evaluated 2.5 y later following the onset of seizures. Over a 3-year interval, the dog underwent 3 computed tomography (CT) and 1 magnetic resonance imaging (MRI) examinations. A voluminous hyperattenuating lesion with a mass effect, exhibiting weak postcontrast enhancement and associated with surrounding diffuse parenchymal hypoattenuation, was observed in the first CT examination (3 d after initial clinical signs). The second CT examination (11 d later) revealed a hypoattenuating lesion with ring postcontrast enhancement. A clear reduction of the size of the mass, which presented as hyperattenuating with a severely postcontrast-enhanced center, was noted in the third CT examination (2.5 y after initial clinical signs and 3 mo after onset of seizures). The MRI examination, performed 3 mo after the third CT examination, showed a small lesion, T2*-gradient echo hypointense, with no peripheral halo noted in T2-weighted fluid-attenuated inversion recovery and with serpentiform enhancement from within the lesion to the meningeal region. These sequential imaging findings were consistent with intracerebral hemorrhage. Key clinical message: To the authors' knowledge, this is the first case of hyperthermia associated with intracerebral hemorrhage in a dog, although this is a common finding in human medicine. An intracerebral hemorrhage should be included in the differential diagnosis of an intracerebral mass, and performing sequential imaging examinations can help clarify the diagnosis., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

The endocannabinoid system (ECS) is an integral neuromodulatory system involved in neuronal development, synaptic plasticity, and homeostasis regarding immunity, as well as brain and other physiological functions such as anxiety, pain, metabolic regulation, and bone growth. Cannabis is a plant that contains exogenous cannabinoids, which have the potential for profound interplay within the ECS as enzymatic inhibitors or receptor-mediated interactions. Activation of cannabinoid receptors leads to various intracellular signaling processes that are involved in cellular functions, but those interactions are diverse due to different affinities of each cannabinoid with relevant receptors. Among the exogenous cannabinoids, cannabidiol (CBD) has drawn attention due to its potential anticancer, antiangiogenic, anti-inflammatory, and antiseizure properties using in vitro and in vivo models. Although scientific evidence is limited in dogs, there appears to be cautious optimism regarding the utilization of CBD in conjunction with other therapeutics for a range of disorders. This review will primarily focus on current scientific research on the efficacy of CBD on seizure, anxiety, osteoarthritis, and atopic dermatitis, following a brief discussion of endo- and exogenous cannabinoids, ECS, their molecular mechanism, and potential side effects in veterinary medicine. Cannabinoid pharmacology and pharmacokinetics will be addressed in the companion Currents in One Health by Schwark and Wakshlag, AJVR, May 2023.

Objective: To investigate caregivers' assessments of outcome in dogs with idiopathic epilepsy (IE) administered levetiracetam (LEV), zonisamide (ZNS), or phenobarbital (PB) monotherapy., Animals: 100 dogs with IE administered LEV (n = 34), ZNS (31), or PB (35) monotherapy between January 1, 2003, and February 6, 2019, and survey responses from their caregivers., Procedures: Information on duration of therapy, adverse effects (AEs), and outcome was obtained from medical record review and caregiver questionnaire., Results: A significant improvement in mean quality of life score was reported during monotherapy (7.7; SD, 2.14) compared to before treatment (6.25; SD, 2.63; P < .0001), with no difference identified between monotherapy groups. Compared to ZNS monotherapy, dogs prescribed PB monotherapy had a significantly younger median age at seizure onset (2.6 vs 4.3 years; P = .024). A significant relationship was identified between the occurrence of reported AEs and monotherapy group, with a higher prevalence in the PB group (77% [27/35]) and a lower prevalence in the ZNS group (39% [12/31]; P = .0066). Treatment failure rates for PB, LEV, and ZNS monotherapy were 51%, 35%, and 45%, respectively, with failure attributed most commonly to inadequate seizure control. No significant difference was identified between groups with respect to rate of or time to failure., Clinical Relevance: Most caregivers reported a favorable outcome with administration of LEV, ZNS, or PB monotherapy to dogs with IE. Phenobarbital is associated with the highest prevalence of AEs but no difference in quality of life score. Prospective controlled studies are needed to further compare the efficacy and safety of these monotherapies in dogs with IE.

Background: Epilepsy is the most common chronic neurological disease in dogs. More than two-thirds of these patients suffer from associated behavioural comorbidities. The latter could have their origin in partially overlapping pathomechanisms, with the intestinal microbiome as a potential key link between them. The current arsenal of drugs for epilepsy management remains limited. Most canine patients continue to have seizures despite treatment and the occurrence of comorbidities is not sufficiently addressed, limiting quality of life of affected dogs and owners. Therefore, novel additional epilepsy management options are urgently needed. The microbiome-gut-brain axis may serve as a new target for the development of innovative multimodal therapeutic approaches to overcome current shortcomings in epilepsy management., Methods: A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial was designed to investigate the potential of the psychobiotic Bifidobacterium longum on behavioural comorbidities in canine epilepsy. Seizure semiology will be evaluated as a secondary outcome measure. Thirty-four privately owned dogs are planned to be included in the ongoing study meeting the following inclusion criteria: Dogs displaying increased anxiety/fear behaviour since the start of the idiopathic epilepsy. Tier II confidence level of the International Veterinary Epilepsy Task Force for the diagnosis of idiopathic epilepsy, with a maximum seizure interval of 3 month and a minimum of three generalised seizures within that period and chronically treated with at least one antiseizure drug without improvement in seizure frequency Each dog will receive the allocated supplement (probiotic vs. placebo) alongside its normal diet for a 3-month period. After a three-week wash out period, the second phase starts by administering the respective other supplement for another 3 months., Discussion: The current study considers modern high-quality standards for epilepsy medication trials. Common biasing effects should be limited to a possible minimum (regression-to-the mean effect, placebo effect, observer effect), ensuring a high validity and accuracy of the acquired results, thus enabling a representative nature of the efficacy of Bifidobacterium longum as add-on supplement for dogs suffering from epilepsy and its comorbidities. This publication should provide a description of the study procedure and data acquisition methods, including prognosed statistical analysis., (© 2023. The Author(s).)

Background: In dogs with a congenital extrahepatic portosystemic shunt (EHPSS), outcome after surgical attenuation is difficult to predict., Objectives: Develop a minimally invasive test to predict outcome after surgical EHPSS attenuation and establish risk factors for postattenuation seizures (PAS)., Animals: Eighty-five client-owned dogs referred for surgical attenuation of a single EHPSS., Methods: mRNA expression of 8 genes was measured in preoperatively collected venous blood samples. Outcome was determined at a median of 92 days (range, 26-208) postoperatively by evaluating clinical performance, blood test results and abdominal ultrasonography. Multivariable logistic regression was used to construct models predicting clinical and complete recovery. The associations between putative predictors and PAS were studied using univariable analyses., Results: Five of 85 dogs developed PAS. Risk factors were age, white blood cell (WBC) count and expression of hepatocyte growth factor activator and LysM and putative peptidoglycan-binding domain-containing protein 2. Clinical recovery was observed in 72 of 85 dogs and complete recovery in 51 of 80 dogs (median follow-up, 92 days). The model predicting clinical recovery included albumin, WBC count, and methionine adenosyltransferase 2 alpha (MAT2α) expression, whereas the model predicting complete recovery included albumin, and connective tissue growth factor precursor and MAT2α expression. The areas under the receiver operating characteristic curves were 0.886 (95% confidence interval [CI]: 0.783, 0.990) and 0.794 (95% CI: 0.686, 0.902), respectively., Conclusions and Clinical Importance: Two models were constructed for predicting outcome after EHPSS attenuation using venous blood samples. The model predicting clinical recovery showed the best diagnostic properties. Clinical application requires further validation., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: Cerebrospinal fluid (CSF) analysis is used in the diagnostic investigation of cats with epileptic seizures. The aim of this retrospective study was to evaluate the diagnostic value of CSF analysis in cats with epileptic seizures that have unremarkable brain MRI or only hippocampal signal changes., Methods: Unremarkable brain MRI or MRI studies with signal alterations in the hippocampus only in cats with suspected epilepsy and CFS analysis performed at the Small Animal Internal Department or Diagnostic Imaging Department at Vetmeduni Vienna, Austria, between 2011 and 2017 were reviewed. Total nucleated cell count, total protein, blood contamination and cytology data from CSF analysis were evaluated., Results: In total, 87 cats were included. Seventy cats (80.5%) had unremarkable MRI, five (5.7%) had hippocampal signal changes with contrast enhancement and 12 (13.8%) had hippocampal signal changes without contrast enhancement. Overall, four cats (4.6%) had abnormalities on CSF analysis; all (100%) had an increased total nucleated cell count (22 cells/μl, 7 cells/μl, 6 cells/μl and 6 cells/μl, respectively), and no cat had increased total protein (100%), although in one cat total protein was not evaluated. Three of these cats had unremarkable MRI and one had hippocampal signal changes without contrast enhancement. The median duration of epileptic signs prior to the MRI study was 2 days., Conclusions and Relevance: Our results show that, in our cohort of epileptic cats with unremarkable brain MRI or with hippocampal signal changes, CSF analysis was usually normal. This should be considered before performing a CSF tap.

Case Description: A 9-month-old intact male domestic shorthair cat was evaluated for increasing frequency of generalized tonic-clonic seizures., Clinical Findings: The cat was reported to have had episodes of circling between the seizures. Upon examination, the cat had bilateral inconsistent menace response but otherwise normal physical and neurological examinations., Diagnostics: Magnetic resonance imaging (MRI) of the brain identified multifocal, small, rounded intra-axial lesions within the subcortical white matter containing fluid with similar characteristics as cerebrospinal fluid. Evaluation of urine organic acids showed increased excretion of 2-hydroxyglutaric acid. An XM&#95;023255678.2:c.397C>T nonsense variant in the L2HGDH gene encoding L-2-hydroxyglutarate dehydrogenase was identified using whole genome sequencing., Treatment and Outcome: Levetiracetam treatment was initiated at 20 mg/kg PO q8h, but the cat died after a seizure 10 days later., Clinical Relevance: We report the second pathogenic gene variant in L-2-hydroxyglutaric aciduria in cats and describe for the first time multicystic cerebral lesions on MRI., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: Hypertensive encephalopathy in cats is an important entity but is underestimated in clinical practice. This could be explained, in part, by non-specific clinical signs. The objective of this study was to characterise the clinical manifestations of hypertensive encephalopathy in cats., Methods: Cats with systemic hypertension (SHT) recognised by routine screening, associated with underlying predisposing disease or a clinical presentation suggestive of SHT (neurological or non-neurological), were prospectively enrolled over a 2-year period. Confirmation of SHT was based on at least two sets of measurements of systolic blood pressure >160 mmHg by Doppler sphygmomanometry., Results: Fifty-six hypertensive cats with a median age of 16.5 years were identified; 31 had neurological signs. In 16/31 cats, neurological abnormalities were the primary complaint. The other 15 cats were first presented to the medicine or ophthalmology service, and neurological disease was recognised based on the cat's history. The most common neurological signs were ataxia, various manifestations of seizures and altered behaviour. Individual cats also showed paresis, pleurothotonus, cervical ventroflexion, stupor and facial nerve paralysis. In 28/30 cats, retinal lesions were detected. Of these 28 cats, six presented with a primary complaint of visual deficits, and neurological signs were not the primary complaint; nine presented with non-specific medical issues, without suspicion of SHT-induced organ damage; in 13 cats, neurological issues were the primary complaint and fundic abnormalities were detected subsequently., Conclusions and Relevance: SHT is common in older cats and the brain is an important target organ; however, neurological deficits are commonly ignored in cats with SHT. Gait abnormalities, (partial) seizures and even mild behavioural changes should prompt clinicians to consider the presence of SHT. A fundic examination in cats with suspected hypertensive encephalopathy is a sensitive test to support the diagnosis.

Background: Focal epileptic motor seizures manifested by limb contraction have been recognized anecdotally in Pomeranians., Objectives: To investigate clinical features of idiopathic epilepsy (IE) and epilepsy of unknown cause (EUC) in Pomeranians as well as the ADAM23 haplotype frequency previously reported as a common risk haplotype for epilepsy in several breeds of dogs., Animals: Twenty-eight Pomeranians, including 15 with IE and 13 with EUC. Nine Pomeranians with epilepsy and 8 control Pomeranians were used for ADAM23 risk haplotype analysis., Methods: Case series study including both retrospectively and prospectively collected cases. The ADAM23 haplotype was determined by direct sequencing of PCR amplicons. Data were analyzed descriptively., Results: Focal epileptic seizures (FS) were the predominant type of seizure in 22 of 28 dogs (78.6%). Among these, 12 of the IE dogs (80.0%) and 10 of the EUC dogs (76.9%) showed FS. Notably, 21 of 22 Pomeranians with FS (95.5%) showed limb contraction during ictal periods. Some dogs with FS also showed immobility, generalized tremors, difficulty walking or moving, autonomic signs, orofacial automatisms or some combination during ictal events. Ten dogs with FS and limb contraction had electroencephalography (EEG) performed, and interictal epileptiform discharges were identified in 9 dogs. The haplotype frequency of ADAM23 in cases was lower (27.8%) than that of the controls (56.3%)., Conclusions and Clinical Importance: In our study, FS was the predominant type of seizure in Pomeranians, and almost all cases with FS showed limb contraction, regardless of whether having IE or EUC., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Meningioangiomatosis (MA) is a rare proliferative meningovascular entity that has been described mainly in humans and dogs. Here we describe MA in a 13-y-old spayed female domestic shorthaired cat that died 5 d after acute change in behavior, open-mouth breathing, seizures, hyperthermia, and inability to walk. On MRI, the lesion appeared predominantly as extraparenchymal hemorrhage. Autopsy changes consisted of a dark-red, hemorrhagic plaque that expanded the leptomeninges and outer neuroparenchyma of the right piriform and temporal telencephalic lobes, chalky white nodules in the peripancreatic fat, and yellow fluid in the abdomen. Histologically, the lesion in the brain consisted of leptomeningeal thickening by spindle cells that effaced the subarachnoid spaces and extended perivascularly into the underlying cerebral cortex. Spindle cells were arranged as streams or whorls around blood vessels, and had slender eosinophilic cytoplasm and elongated nuclei with coarsely stippled chromatin and 1 or 2 distinct nucleoli. There was extensive hemorrhage, clusters of hemosiderin-laden macrophages, and mineralization throughout. Spindle cells had positive immunolabeling for vimentin. A striking MRI and gross feature in our case was the extensive hemorrhage associated with the MA lesion. Additional findings included suppurative pancreatitis with peritonitis and supraspinatus myonecrosis.

The objective of this study was to calculate lateral ventricles dimension in Cavalier King Charles Spaniel dogs with Chiari-like malformation and investigate the association between ventriculomegaly and signalment, clinical signs, ventricular asymmetry, grade of Chiari-like malformation, syringomyelia and index of medullary kinking. Retrospectively, 43 client-owned Cavalier King Charles Spaniels, older than 1 year of age, with magnetic resonance imaging diagnosis of Chiari-like malformation were enrolled. Initial and follow-up (up to 36 months) clinical status was graded. Images were reviewed to quantify the enlargement of lateral ventricles, evaluate ventricular symmetry, grade of Chiari-like malformation, grade of syringomyelia and medullary kinking index. Cases presenting epileptic seizures during the evaluation period were also recorded. The most common initial clinical signs were scratching and neck pain. Ventriculomegaly was identified in 70% of dogs, Chiari-like malformation grade 2 was observed in 77% of cases, ventricular asymmetry and syringomyelia were identified in 54% and 80% of dogs, respectively; the median medullary kinking index was 37.77%. Moreover, 28% of dogs presented epileptic seizures. No significant association was identified between dimension of lateral ventricles and signalment, clinical signs, and imaging findings; no significant association was identified between ventriculomegaly and epilepsy (P≥0.05). In conclusion, the prevalence of ventriculomegaly in Cavalier King Charles Spaniels is high but this finding does not seem related to the severity of clinical signs, presence of Chiari-like malformation, syringomyelia and craniocervical junction abnormalities such as medullary kinking.

Background: Idiopathic or genetic epilepsy commonly affects dogs; affected dogs are often refractory to anti-seizure drug therapy. Felbamate is an anti-seizure drug with established pharmacokinetic and safety data for dogs, but little published evidence of efficacy for managing generalized seizures in this species., Aim: The purpose of this retrospective case series was to evaluate the clinical efficacy and tolerability of oral felbamate in six presumptive epileptic dogs experiencing generalized seizures., Methods: Medical records from six dogs with presumptive idiopathic/genetic epilepsy manifesting as generalized seizure activity, for which oral felbamate was used as an add-on treatment, were reviewed. The number of seizures recorded for the 3-month period immediately before instituting felbamate was recorded for each dog. Short-term (3 months) and long-term (6 months or greater) seizure frequency post-felbamate therapy was recorded for each dog and compared with baseline., Results: Overall, dogs experienced a reduction (82%) in seizures after adding felbamate in the short term, with 5/6 dogs (83%) classified as responders (50% or greater reduction in seizures) and 3/6 dogs (50%) attaining seizure-free status. Mean and median long-term follow-up times were 13 and 11 months, respectively (range: 6 to 23 months). Four of the 6 dogs (67%) remained drug responders at final follow-up, with an average seizure reduction of 98%, 2 of which remained seizure-free at 8 and 21 months. Two dogs (33%) experienced increased seizure activity during long-term follow-up (12 and 23 months) and were considered non-responders. The non-responder dogs had an average long-term seizure reduction of 33%. No dog experienced any obvious adverse effects associated with felbamate administration. However, one dog not included in the analysis because of insufficient (<3 month) post-felbamate follow-up, was weaned off felbamate because of suspected hepatotoxicity., Conclusion: Our small case series suggests that oral felbamate might show promise as an add-on drug for epileptic dogs experiencing generalized seizures resistant to drug therapy. These results warrant a more controlled, prospective investigation into felbamate as a therapeutic agent for canine epilepsy.

Background: Antiparasitic drug toxicosis is commonly described in dogs and cats, but reports on the management of antiparasitic drug toxicities in pet rabbits are scarce. Here, we describe the successful clinical management of two pet rabbits with fipronil toxicosis., Cases Description: The first case was a 5-month-old, intact female, rabbit that presented with the acute onset of seizures, obtunded mentation, and in lateral recumbency, while the second rabbit was a 1-year-old, intact male, rabbit that presented with anorexia and lethargy. In both cases, the owners reported to have administered a 0.5 ml fipronil vial topically on the skin as an antiparasitic drug between 4 and 6 hours prior to presentation. Complete blood count and serum biochemistry were unremarkable and both rabbits tested negative on Encephalitozoon cuniculi serology. Both animals were decontaminated by bathing with tepid water and dishwashing soap. The rabbit with seizures received on admission intravenous midazolam. In both cases, overnight hospitalization, intravenous isotonic crystalloid fluids, and assisted-feeding by oral syringe were provided until voluntary feeding was resumed. Both rabbits rapidly improved approximately 12 hours of initiating supportive care. Complete resolution of clinical signs and return of normal appetite and defecation occurred within 24 hours of hospitalization in both animals. No recurrence of neurological signs was reported in the rabbit presenting with seizures on a follow-up period of 1 month., Conclusion: The outcome of these cases suggests that supportive treatment of fipronil toxicity in pet rabbits can be successful if administered promptly., Competing Interests: The authors declare that there is no conflict of interest.

Objectives: The primary objective of this study was to investigate the prevalence of epileptic seizures and of presumed idiopathic epilepsy (PIE, describing epilepsy of unknown origin) in a cohort of British Shorthair (BSH) cats in Sweden. The secondary objective was to describe epileptic seizure characteristics and outcome for cats with PIE., Methods: Owners of BSH cats born between 2006 and 2016 and registered with SVERAK (the Swedish Cat Clubs' National Association) were invited to reply to a questionnaire about their cat's general health. Owners who indicated that their cat had experienced epileptic seizures were invited to participate in an in-depth telephone interview about the epileptic seizures. The clinical characteristics of epileptic seizures in BSH cats were determined from the results of the interview., Results: In this population comprising 1645 BSH cats (representing 28% of registered BSHs), the prevalence of epileptic seizures was 0.9% and for PIE it was 0.7%. BSH cats with PIE presented with infrequent but consistent epileptic seizures. 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., Conclusions and Relevance: The prevalence of PIE in this population of BSH cats was 0.7%. The prevalence of epileptic seizures was 0.9%. In general, PIE in the BSH cat displayed a relatively benign phenotype where progression of epileptic seizures was uncommon.

Case Series Summary: Seven cases of feline hippocampal and piriform lobe necrosis (FHN) are described, with particular emphasis on clinical, radiographic and histopathological correlations. FHN is an uncommon acute epileptic condition resembling human autoimmune limbic encephalitis and temporal lobe epilepsy. 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., Relevance and Novel Information: Following a review of the literature, including potential complicating factors and comparisons with human medicine, the hippocampus and piriform lobe are proposed as the neuroanatomical localisation for focal seizures with orofacial involvement in cats, regardless of aetiology.

Background: Myoclonus is observed in older Cavalier King Charles Spaniels (CKCS) but a full description is lacking., Objectives: The presence, age of onset, characteristics and treatment of myoclonic episodes were retrospectively evaluated in a cohort of CKCS which presented to 1 board-certified neurologist. Clinical data, imaging studies, presence of seizures and their management, as well as other comorbidities were noted., Animals: Thirty-nine CKCS that were presented to 2 institutions between 2001 and 2018 with signs consistent with myoclonus. Clinical examination, blood sampling, advanced diagnostic imaging, cerebrospinal fluid analysis, and record keeping of other comorbidities was performed., Methods: This is a retrospective case series, describing the presence of myoclonus in CKCS., Results: Clinical signs reported were spontaneous in onset, lasted a few seconds and consisted of rapid blinking with head nodding and variable extension down the thoracic limbs. Myoclonus occasionally led to stumbling of the thoracic limbs or collapse. Mean age of onset was 8.38 years (SD ±1.96). Thirteen of 39 dogs with myoclonus had paroxysmal events, such as generalized seizures (9/13)., Conclusions and Clinical Importance: Myoclonus occurs in middle-aged to older CKCS and seems to be another epiphenomena of this breed. A link to epilepsy might be present., (© 2022 Fitzpatrick Referrals Limited. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To determine the most common indications for cranial surgery and identify risk factors associated with the occurrence of complications and death in the perioperative period following cranial surgery., Animals: 150 dogs and 15 cats., Procedures: For this multi-institutional retrospective case series, medical records of dogs and cats that underwent cranial surgery at any of the 4 participating institutions between 1995 and 2016 were reviewed. Variables were evaluated included species, sex, age, neurolocalization, history of preoperative seizures, surgical approach, histological results, perioperative complications, and outcome. Logistic regression analysis was performed to assess for risk factors for complications., Results: The most common neurolocalization was the forebrain (110/165 [66.7%]), with 94 (57.0%) animals having had seizures preoperatively. The rostrotentorial (116/165 [70.3%]) and caudotentorial (32/165 [19.4%]) surgical approaches were most commonly reported. The most common indication was the treatment of meningioma (75/142 [52.8%]). Complications arose in 58 of the 165 (35.2%) cases within 24 hours and in 86 (52.1%) cases 1 to 10 days postoperatively. Perioperative complications included hypotension (38/165 [23.0%]) and anemia (27/165 [16.4%]). During the postoperative period, the most common complications were neurologic deficits, seizures, postoperative anemia, and aspiration pneumonia. The mortality rate with death or euthanasia perioperatively or ≤ 10 days postoperatively was 14.5% (24/165). Long-term complications occurred in 65 of the 165 (39.4%) animals, with seizures and neurologic deficits being the most common., Clinical Relevance: Cranial surgery was performed most commonly for the removal of neoplastic lesions in dogs and cats, and most complications were not life-threatening.

Background: The blood-brain barrier (BBB), which separates the intravascular and neuropil compartments, characterizes the vascular bed of the brain and is essential for its proper function. Recent advances in imaging techniques have driven the development of methods for quantitative assessment of BBB permeability., Hypothesis/objectives: Permeability of the BBB can be assessed quantitatively in dogs with meningoencephalitis of unknown origin (MUO) and its status is associated with the occurrence of seizures., Animals: Forty dogs with MUO and 12 dogs without MUO., Methods: Retrospective, prospective cohort study. Both dynamic contrast enhancement (DCE) and subtraction enhancement analysis (SEA) methods were used to evaluate of BBB permeability in affected (DCE, n = 8; SEA, n = 32) and control dogs (DCE, n = 6; SEA, n = 6). Association between BBB dysfunction (BBBD) score and clinical characteristics was examined. In brain regions where BBBD was identified by DCE or SEA magnetic resonance imaging (MRI) analysis, immunofluorescent staining for albumin, glial fibrillary acidic protein, ionized calcium binding adaptor molecule, and phosphorylated mothers against decapentaplegic homolog 2 were performed to detect albumin extravasation, reactive astrocytes, activated microglia, and transforming growth factor beta signaling, respectively., Results: Dogs with BBBD had significantly higher seizure prevalence (72% vs 19%; P = .01) when compared to MUO dogs with no BBBD. The addition of SEA to routine MRI evaluation increased the identification rate of brain pathology in dogs with MUO from 50% to 72%., Conclusions and Clinical Importance: Imaging-based assessment of BBB integrity has the potential to predict risk of seizures in dogs with MUO., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Seizures in the early postoperative period after intracranial surgery may affect outcome in dogs., Objectives: To determine the incidence of early postoperative seizures (EPS) in dogs with brain tumors, identify specific risk factors for EPS, and determine if EPS affects outcome., Animals: Eighty-eight dogs that underwent 125 intracranial surgeries for diagnosis and treatment of rostrotentorial brain tumors., Methods: Retrospective cohort study. All patients with a diagnosis of rostrotentorial brain tumor from 2006 to 2020 were included. Early postoperative seizures were diagnosed by observation of seizure activity within 14 days of neurosurgery. Previously diagnosed structural epilepsy, perioperative anticonvulsant drug (ACD) use, magnetic resonance imaging (MRI), and tumor characteristics were evaluated. Outcome measures included neurologic and nonneurologic complications, duration of hospitalization, and survival to discharge., Results: Dogs with rostrotentorial brain tumors had EPS after 16/125 (12.8%) neurosurgical procedures (95% confidence interval [CI], 7%-19%). Presence of previous structural epilepsy was not associated with EPS risk (P = 1). Perioperative ACD use also was not associated with EPS (P = .06). Dogs with EPS had longer hospitalization (P < .001), were more likely to have neurologic complications postsurgery (P = .01), and were less likely to survive to discharge (P = .01)., Conclusions and Clinical Importance: It is difficult to predict which dogs are at risk of EPS because the presence of previous structural epilepsy and the use of perioperative ACDs was not associated with EPS. However, seizures in the early postoperative period are clinically important because affected dogs had prolonged hospitalization, more neurologic complications, and decreased short-term survival., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To evaluate the effect on seizure frequency of add-on telmisartan treatment in dogs with refractory idiopathic epilepsy., Animals: 11 client-owned dogs with idiopathic epilepsy and ≥ 2 generalized seizures/mon that were currently being treated with ≥ 2 antiepileptic drugs., Procedures: Telmisartan was administered at a dosage of 0.25 to 1 mg/kg, PO, every 12 hours for 4 to 16 months. Seizure frequencies before and during telmisartan treatment were recorded., Results: 10 dogs completed the 4-month treatment protocol. One dog was excluded owing to a transient increase in serum creatinine concentration; no adverse effects of telmisartan were observed in the remaining 10 dogs. A reduction in seizure frequency greater than an estimated expected placebo effect of 30% was evident in 7 of the 10 dogs. Long-term (12 to 16 months) follow-up information was available for 6 dogs, of which 4 had a further reduction in seizure frequency. Differences in seizure frequency were not statistically significant. No significant difference was found in serum phenobarbital concentration throughout the treatment period in the 7 dogs that were tested., Clinical Relevance: Telmisartan has the potential to reduce seizure frequency when administered as an add-on antiepileptic drug in dogs with refractory idiopathic epilepsy. A randomized, double-blind, placebo-controlled trial is needed to determine the true efficacy of telmisartan. On the basis of our results, a sample size of 54 dogs with refractory idiopathic epilepsy would be needed.

Objective: To investigate the association between changes in cerebral blood flow and electrographic epileptic seizure in dogs using transcranial Doppler ultrasonography (TCD)., Animals: 6 healthy Beagle dogs., Procedures: Each dog was administered pentetrazol (1.5 mg/kg/min) or saline (0.9% NaCl) solution under general anesthesia with continuous infusion of propofol. Both pentetrazol and saline solution were administered to all 6 dogs, with at least 28 days interval between the experiments. Blood flow waveforms in the middle cerebral artery and the basilar artery were obtained using TCD at baseline, after pentetrazol administration, and after diazepam administration. TCD velocities, including peak systolic velocity, end-diastolic velocity, and mean velocity and resistance variables, were determined from the Doppler waveforms., Results: During ictal-phase of pentetrazol-induced seizures, the TCD velocities significantly increased in the basilar and middle cerebral arteries while TCD vascular resistance variables did not change in either artery. The TCD velocities significantly decreased after diazepam administration. Systemic parameters, such as the heart rate, mean arterial pressure, systemic vascular resistance, cardiac index, end-tidal carbon dioxide, oxygen saturation, and body temperature, did not change significantly during seizures., Clinical Relevance: This study showed that cerebral blood flow, as obtained from TCD velocities, increased by 130% during ictal-phase of pentetrazol-induced seizures in dogs. The elevated velocities returned to baseline after seizure suppression. Thus, TCD may be used to detect electrographic seizures during the treatment of status epilepticus in dogs, and further clinical studies clarifying the association between changes in cerebral blood flow and non-convulsive seizure cases are needed.

Background: Canine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog's quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable., Methods: 57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/μL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response., Results: Ten dogs with IE had strongly elevated stimulated Th17 cells/μL within the blood (>100 Th17 cells/μL). A slight positive correlation between stimulated Th17 cells/μL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/μL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively)., Conclusion: In single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy., Competing Interests: The authors have declared that no competing interests exist.

A 4-year-old neutered male St. Bernard-mastiff crossbred dog showed clinical signs of lethargy and anorexia after being administered phenobarbital for the treatment of idiosyncratic seizures. A complete blood (cell) count revealed pancytopenia. Auto-agglutination and Coombs tests were negative suggesting that an immunemediated cause was unlikely; therefore, an idiosyncratic reaction to phenobarbital was suspected. Supportive care and control of seizures with zonisamide was initiated and clinical signs improved. Blood values were monitored closely and returned to normal after 3 wk., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: The diagnosis of idiopathic epilepsy (IE) in dogs is based on exclusion of other potential causes of seizures. Recently, 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., Hypothesis/objectives: Effects on the magnetic field evoked by intrinsic epileptic activity can be detected by MRI in the canine brain. As proof-of-concept, the novel MRI sequence to detect neuronal currents was applied in dogs., Animals: Twelve dogs with IE and 5 control dogs without a history of epileptic seizures were examined., Methods: Prospective case-control study as proof-of-concept. All dogs underwent a clinical neurological examination, scalp electroencephalography, cerebrospinal fluid analysis, and MRI. The MRI examination included a spin-locking (SL) experiment applying a low-power on-resonance radiofrequency pulse in a predefined frequency domain in the range of oscillations generated by the epileptogenic tissue., Results: In 11 of 12 dogs with IE, rotary saturation effects were detected by the MRI sequence. Four of 5 control dogs did not show rotary saturation effects. One control dog with a diagnosis of neuronal ceroid lipofuscinosis had SL-related effects, but did not have epileptic seizures clinically., Conclusions and Clinical Importance: 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., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Clinical signs and their progression in Beagles with Lafora disease are poorly described., Objectives: To describe clinical signs in Beagles with Lafora disease., Animals: Twenty-eight Beagles with Lafora disease confirmed by genetic testing or histopathology., Methods: Retrospective multicenter case series. Data regarding signalment, clinical signs, diagnostic tests and treatment were retrieved from hospital data files. A questionnaire was sent to owners asking about neurological deficits, changes in cognitive functions, behavioral changes, response to treatment and survival time., Results: Onset of clinical signs was 8.3 years (mean; range, 6.3-13.3). All dogs had myoclonic episodes as an initial clinical sign with tonic-clonic seizures in n = 11/28 (39%) and n = 12/28 (43%) later developing tonic-clonic seizures. Deficits of coordination (n = 21/25; 84%), impaired vision (n = 15/26; 58%), and impaired hearing (n = 13/26; 50%) developed later. Mental decline was observed as loss of house training (urination; n = 8/25; 32%), difficulties performing learned tasks (n = 9/25; 36%), and difficulties learning new tasks (n = 7/23; 30%). Common behavioral changes were: increased photosensitivity (n = 20/26; 77%), staring into space (n = 16/25; 64%), reduced stress resistance (n = 15/26; 58%), increased noise sensitivity (n = 14/26; 54%), and separation anxiety (n = 11/25; 44%). Twenty-one dogs were alive (median age 11.9 years; range, 9.8-18.6), and 7 dogs were dead (mean age 12.1 years; SD: 1.3; range, 10.5-12.6) at time of writing., Conclusions and Clinical Importance: Lafora disease in Beagles causes significant behavioral changes, and mental decline as well as neurological deficits in addition to myoclonic episodes and generalized tonic-clonic seizures. Nevertheless, a relatively normal life span can be expected., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Naso-ethmoidal meningoencephalocele is usually a congenital anomaly consisting of a protrusion of cerebral tissue and meninges into the ethmoidal labyrinth. The condition is a rare cause of structural epilepsy in dogs. We report the clinical presentation, surgical intervention, postoperative complications and outcome in a dog with drug resistant epilepsy secondary to a meningoencephalocele., Case Presentation: A 3.3-year-old male neutered Tamaskan Dog was referred for assessment of epileptic seizures secondary to a previously diagnosed left-sided naso-ethmoidal meningoencephalocele. The dog was drug resistant to medical management with phenobarbital, potassium bromide and levetiracetam. Surgical intervention was performed by a transfrontal craniotomy with resection of the meningoencephalocele and closure of the dural defect. Twenty-four hours after surgery the dog demonstrated progressive cervical hyperaesthesia caused by tension pneumocephalus and pneumorrhachis. Replacement of the fascial graft resulted in immediate resolution of the dog's neurological signs. Within 5 months after surgery the dog progressively developed sneezing and haemorrhagic nasal discharge, caused by sinonasal aspergillosis. Systemic medical management with oral itraconazole (7 mg/kg orally q12h) was well-tolerated and resulted in resolution of the clinical signs. The itraconazole was tapered with no relapsing upper airway signs. The dog's frequency of epileptic seizures was not affected by surgical resection of the meningoencephalocele. No treatment adjustments of the anti-epileptic medication have been necessary during the follow-up period of 15 months., Conclusions: Surgical resection of the meningoencephalocele did not affect the seizure frequency of the dog. Further research on prognostic factors associated with surgical treatment of meningoencephaloceles in dogs is necessary. Careful monitoring for postsurgical complications allows prompt initiation of appropriate treatment.

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 (r s ) comparing reported seizure to EEG-confirmed ictal PD frequencies was 0.39 (95% confidence interval [CI] = 0.048-0.64, P = .03). Other r s 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., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

A 10-y-old intact male Labrador Retriever dog had a history of ataxia, inability to stand, and grand mal seizures. Complete blood count and serum biochemistry profiles revealed profound hypoglycemia, mildly increased alanine aminotransferase (ALT) activity, mild hypernatremia, and lymphopenia. The seizures could not be controlled with intravenous dextrose, diazepam, or propofol. The dog was euthanized given poor quality of life, and an autopsy was performed. Primary autopsy findings included firm hepatic masses that ranged from dark-red to tan, with the largest ~1.5 cm diameter, and pulmonary edema. Histologic examination of the hepatic masses revealed redundant, several-cell-thick cords, and packeted or acinar arrangements of polygonal cells, supported on a fibrovascular stroma. The neoplastic cells were immunopositive for insulin, synaptophysin, and neuron-specific enolase immunohistochemistry; granules in the tumor cells had an affinity for Grimelius silver stain. The histologic features, as well as the immunohistochemical staining profile, identified the neoplasm as a primary multifocal hepatic neuroendocrine carcinoma. Neuroendocrine carcinomas are rare in dogs and usually occur in the gastrointestinal or respiratory tract.

Objectives: The aim of this study was to determine whether transient postictal hyperammonaemia exists in cats., Methods: The medical records of all feline patients that presented at a Swedish veterinary hospital between 2008 and 2018 were retrospectively reviewed to find those that had a recent or ongoing epileptic seizure. To qualify for inclusion, the medical record had to include information on at least one ammonia value taken in close proximity to, or during, an active seizure, the cat must have exceeded the normal upper limit of blood ammonia concentration on initial testing (reference interval 0-95 μmol/l), and there needed to be a follow-up ammonia value available within a maximum of 3 days., Results: Five cats were included in the study, and they had blood ammonia concentrations on initial testing ranging from 146 to 195 µmol/l. They were all retested within a period of 2 h to 3 days of the original reading. All five cats had a spontaneous decrease in ammonia levels without any specific treatment for hyperammonaemia., Conclusions and Relevance: Pursuant to the findings of this retrospective study, transient hyperammonaemia may be noted after epileptic seizure in cats. Consequently, a differential diagnostic list in feline patients with hyperammonaemia could, depending on the context, include non-hepatic-related pathologies, such as epileptic seizures.

Cholinergic modulation of hippocampal network function is implicated in multiple behavioral and cognitive states. Activation of nicotinic and muscarinic acetylcholine receptors affects neuronal excitability, synaptic transmission and rhythmic oscillations in the hippocampus. In this work, we studied the ability of the cholinergic system to sustain hippocampal epileptiform activity independently from glutamate and GABA transmission. Simultaneous CA3 and CA1 field potential recordings were obtained during the perfusion of hippocampal slices with the aCSF containing AMPA, NMDA and GABA receptor antagonists. Under these conditions, spontaneous epileptiform discharges synchronous between CA3 and CA1 were recorded. Epileptiform discharges were blocked by addition of the calcium-channel blocker Cd2+ and disappeared in CA1 after a surgical cut between CA3 and CA1. Cholinergic antagonist mecamylamine abolished CA3-CA1 synchronous epileptiform discharges, while antagonists of α7 and α4β2 nAChRs, MLA and DhβE, had no effect. Our results suggest that activation of nicotinic acetylcholine receptors can sustain CA3-CA1 synchronous epileptiform activity independently from AMPA, NMDA and GABA transmission. In addition, mecamylamine, but not α7 and α4β2 nAChRs antagonists, reduced bicuculline-induced seizure-like activity. The ability of mecamylamine to decrease hippocampal network synchronization might be associated with its therapeutic effects in a wide variety of CNS disorders including addiction, depression and anxiety., Competing Interests: The authors have declared that no competing interests exist.