Cerebrospinal fluid metabolomics is a promising research technology in the elucidation of nervous system disorders. Therefore, in this work, a cerebrospinal fluid (CSF) metabolomics method using liquid chromatography coupled to mass spectrometry was optimized and validated to cover a wide range of metabolites. An acceptable coefficient of variance regarding instrumental, within-lab and intra-assay precision was found for 95, 70 and 96 of 102 targeted metabolites, together with 1256, 676 and 976 untargeted compounds, respectively. Moreover, approximately 75% of targeted metabolites and 50% of untargeted compounds displayed good linearity across different dilution ranges. Consequently, metabolic alterations in CSF of dogs with idiopathic epilepsy (IE) were studied by comparing CSF of dogs diagnosed with IE (Tier II) to dogs with non-brain related disease. Targeted metabolome analysis revealed higher levels of cortisol, creatinine, glucose, hippuric acid, mannose, pantothenol, and 2-phenylethylamine (P values < 0.05) in CSF of dogs with IE, whereas CSF of dogs with IE showed lower levels of spermidine (P value = 0.02). Untargeted CSF metabolic fingerprints discriminated dogs with IE from dogs with non-brain related disease using Orthogonal Partial Least Squares Discriminant Analysis (R2(Y) = 0.997, Q2(Y) = 0.828), from which norepinephrine was putatively identified as an important discriminative metabolite.

In feline idiopathic epilepsy (IE), the options for antiseizure medications (ASMs) remain limited with no licensed drugs available in cats in Europe. This study aimed to evaluate and compare efficacy and safety of imepitoin and phenobarbital through a multicenter, single-blinded, randomized, placebo-controlled trial. A total of 37 cats were included in this study. The study treatment evaluation period lasted for 15 weeks. In the imepitoin group (n = 16), monthly seizure frequency was significantly reduced (p = 0.028; mean pre-treatment, 6.1; mean post-treatment, 3.0), though monthly seizure days (p = 0.055; mean pre-treatment, 4.4; mean post-treatment, 2.6) and number of cluster seizures (p = 1.00; mean pre-treatment, 0.9; mean post-treatment, 0.3) did not show significant changes. The responder rate (i.e., > 50% reduction in seizure frequency post treatment) was 62%. In the phenobarbital group (n = 10), treatment led to a significant reduction in monthly seizure frequency (p = 0.0026; mean pre-treatment, 8.1; mean post-treatment, 1.3) and seizure days (p = 0.0011; mean pre-treatment, 5.7; mean post-treatment, 0.5), but not in the number of cluster seizures (p = 0.82; mean pre-treatment, 1.3; mean post-treatment, 0.4). The responder rate was 90%. When compared, the reduction in seizure days was significantly higher for phenobarbital compared to imepitoin (p = 0.036), while no significant difference was found for seizure frequency (p = 0.13) and responder rate (p = 0.1). The time to first seizure event after starting treatment was significantly longer in the phenobarbital group compared to imepitoin (p = 0.047) and placebo (p = 0.0017), but not between imepitoin and placebo (p = 0.078). Adverse effects of mild to moderate severity were observed in 90% of the phenobarbital group (primarily sedation and ataxia) and 88% of the imepitoin group (primarily ataxia and increased ALT activity). Both phenobarbital and imepitoin demonstrated efficacy and safety in feline IE. While seizure frequency reduction did not differ significantly between treatments, phenobarbital was associated with a prolonged time to first seizure event after treatment initiation. Adverse effects were common but the majority of these effects were mild to moderate and transient.

Background: Emerging evidence indicates that epilepsy extends beyond the brain, involving systemic metabolic, immune, and microbiome perturbations that shape neuronal excitability and treatment response. Canine idiopathic epilepsy (CE) offers a naturally occurring model with strong electrophysiological, pharmacological, and clinical homology to human epilepsies. Methods: This scoping review was conducted according to the PRISMA-ScR guidelines. A systematic literature search was performed in Web of Science and MEDLINE (PubMed) to identify original studies reporting metabolic, immunometabolic, or neurochemical alterations in CE compared with healthy controls. Eligible studies included peer-reviewed original research involving client-owned dogs diagnosed with CE according to international consensus criteria (IVETF guidelines). Studies focusing exclusively on genetics or neuroimaging without metabolic outcomes were excluded. Titles, abstracts, and full texts were screened for eligibility, and data were extracted from included studies using a standardized approach. Identified metabolic domains were synthesized narratively and grouped into functional systems, including amino acid and lipid metabolism, micronutrients, neurotransmission, oxidative stress, inflammation and immunology, endocannabinoid signalling, microRNAs, and gut-brain axis-related pathways. In a second step, the identified metabolic domains were evaluated for translational relevance through a targeted, non-systematic narrative synthesis of the human epilepsy literature. This approach aimed to assess cross-species parallels and to provide a conceptual framework to guide future research, rather than to perform a comprehensive systematic review of metabolic alterations in human epilepsy. Results: Across CE studies, consistent alterations were observed in multiple interconnected functional systems, including metabolic, immune, and gut-brain axis pathways, in agreement with findings reported for human epilepsy. These data support a model of epileptogenesis involving systemic dysfunction beyond the central nervous system. Translationally, these findings suggest opportunities for biomarker development, patient stratification, and mechanism-based interventions, including dietary and metabolic approaches (e.g., medium-chain triglyceride supplementation), microbiome modulation, and immunometabolic targeting. The current evidence is limited by small and heterogeneous cohorts, potential confounding effects of antiseizure medications, variability in dietary and fasting conditions, breed-related effects, and a predominance of associative over causal relationships. Conclusions: This review positions CE as a reference framework for future research into epilepsy metabolism, integrating current evidence and its translational relevance to human disease. The findings support a shift toward a systems-level view of epileptogenesis, involving interconnected metabolic, immune, and gut-brain axis pathways beyond the brain. CE represents a valuable translational model to identify shared mechanisms, inform biomarker discovery, and guide the development of mechanism-based therapeutic strategies across veterinary and human epilepsy.

Caring for dogs with chronic behavioral problems often leads to emotional exhaustion, guilt, and reduced treatment adherence among caregivers, particularly when behavioral interventions fail without a clear medical explanation. This case series describes two dogs, initially treated for aggression, compulsivity, and hyperreactivity, who were subsequently diagnosed through advanced imaging with porencephaly and Chiari-like malformation with syringomyelia. Identification of these structural abnormalities enabled caregivers to understand the neurological basis of their dogs’ behaviors, reducing uncertainty and strengthening engagement with ongoing management.By providing diagnostic clarification, advanced imaging supported more structured clinical decision-making and helped caregivers adjust expectations from cure to long-term management. In both cases, this shift reduced frustration and improved adherence to treatment strategies.These cases underscore the importance of considering neurological differentials in complex behavioral presentations and highlight the value of a multidisciplinary approach. Optimizing welfare in such cases requires not only appropriate medical intervention but also clear communication and sustained caregiver support throughout the diagnostic and treatment process.

Here we describe an 8-year-old intact male Jack Russell Terrier with a 9-month history of slowly progressive gait disturbances that advanced over 2 years to generalized stiffness without ataxia and severe bilateral hyperflexion of all limbs. Gait evaluation showed high lifting of both pelvic limbs resulting in a hopping movement in the rear end; the right pelvic limb was kept lifted, making the dog trot on the 3 other limbs. Both thoracic limbs were lifted higher than normal. Complete blood count and serum biochemistry analysis including creatine kinase activity were normal. Electrophysiological examination showed no abnormalities. Muscle biopsy samples collected at a later stage of the disease showed no abnormalities. A homozygous frameshift variant in SETX (senataxin) was identified and is predicted to truncate about 85% of the protein. The SETX variant adds a new gene variant to the list affecting Jack Russell Terriers with gait abnormalities.

Different conditions affecting the spinal meningeal layers have been reported in human and veterinary medicine. In veterinary medicine, two separate conditions have been reported. Spinal arachnoid diverticula (SAD) have been well documented for decades, while constrictive myelopathy (CM) in pugs was identified more recently. However, the distinction between SAD and CM in dogs can be challenging. There is a lack of understanding about the pathophysiology of these puzzling conditions, which impacts the ability to select the most appropriate treatment. In humans, four different spinal meningeal diseases are described, including intradural or extradural spinal arachnoid cysts, spinal arachnoid webs, spinal adhesive arachnoiditis, and idiopathic spinal cord herniation. Similar challenges to veterinary medicine are also encountered in human medicine. This brief comparative review aims to emphasize the parallels and obstacles found in both veterinary and human medicine and to explore potential future developments. The term ‘spinal meningeal adhesive disease’ is proposed as a unified term in veterinary medicine for pathologies affecting the meninges of the spinal cord (SAD and CM), potentially causing progressive clinical signs of myelopathy.

Repetitive transcranial magnetic stimulation (rTMS) is an effective, non-invasive management option for canine drug-resistant idiopathic epilepsy, but optimal stimulation protocols have not yet been established. The hypothesis is that treatment duration influences the therapeutic outcome of rTMS in dogs with drug-resistant idiopathic epilepsy. The objective is to compare and critically review the effect of different rTMS treatment durations on clinical outcomes in these patients. Two previously published rTMS protocols (5-day vs. 3-day), using the same total number of pulses and a coil output of ≥ 70

BACKGROUND:Paroxysmal dyskinesia (PxD) has not been characterized in Dachshunds. HYPOTHESIS/OBJECTIVES:Describe the phenotype, treatment, and outcome of PxD in Dachshunds. ANIMALS:Sixty-two Dachshunds with presumptive PxD. METHODS:Observational, retrospective, multicenter study of dogs diagnosed with PxD between 2017 and 2025, with prospective information using an owner questionnaire. RESULTS:Median age at presentation was 3.2 years (range, 1-11 years). Episodes were characterized by shifting (55/62; 88.7%), single (4/62; 6.5%) limb or cervical dystonia (28/62; 45.2%), tremors (25/62; 40.3%), dystonic head tremors (15/62; 35.5%), truncal sway (20/62, 32.3%), kyphosis (17/62; 27.4%), and ataxia (15/62, 24.2%) or head sway (12/62, 19.4%). Shifting limb dystonia was exhibited in all (19/55; 34.5%), pelvic (7/55; 12.7%), or thoracic (1/55; 1.8 %) limbs. Ptyalism (25/62; 40.3%), vomiting (23/62; 37.1%), or lip smacking (25/62; 40.3%) were common. All dogs were diagnosed with presumptive idiopathic paroxysmal non-kinesigenic dyskinesia. Most common treatments were gluten-free diet (42/62; 67.7%), levetiracetam (9/62; 14.5%), phenobarbital (5/62; 8.1%), or no treatment (18/62; 29%). Follow-up was available for 49 of 62 (79%) dogs with a median follow-up of 543 days (range, 5-2903 days). Twenty-six of 49 (53%) dogs had a decrease, 19 of 49 (38.8%) had no change and 4 of 49 (8.2%) had an increase in the frequency or intensity of episodes. CONCLUSIONS AND CLINICAL IMPORTANCE:Paroxysmal dyskinesia occurs in young Dachshunds. Shifting limb dystonia is a common feature, and it can affect the pelvic limbs exclusively, mimicking spinal cord disease. Most dogs experienced a decrease in numbers of events regardless of treatment.

IntroductionCanine epilepsy is a common and complex neurological disease that occurs in almost all dogs. In the Netherlands, there are nine pedigree dog breeds, and all of them have numerous small populations, with moderate to high inbreeding coefficients. The goal of this study is to characterise epilepsy within these breeds and to estimate the prevalence for each of these nine breeds: Dutch Partridge dog, three variants of the Dutch Shepherd, Dutch Smoushound, Kooiker dog, Markiesje dog, Saarloos Wolfdog, Schapendoes dog, Stabyhoun, and Wetterhoun.MethodAn online questionnaire was distributed to establish the phenotypic characterisation of idiopathic epilepsy (IE) and epilepsy of unknown cause (EUC). The prevalence was estimated using data from breeders’ associations, as well as cases seen by the investigators but unknown to the breed clubs.ResultsThe estimated prevalence of IE and EUC was for the Dutch Partridge dog 2.63%, short haired Dutch Shepherd 0.72%, rough haired Dutch Shepherd 1.21%, long haired Dutch Shepherd 0.42%, the Dutch Smoushound 2.22%, Kooiker dog 0.4%, Markiesje dog 0.84%, Saarloos Wolfdog 1.9%, Schapendoes dog 0.23%, Stabyhoun 1.5%, and Wetterhoun 2.8%. All breed clubs use breeding advice to reduce the frequency of IE/EUC, and within the Dutch Shepherd shorthaired, Kooiker dog, Smoushound, and Saarloos Wolfdog, the frequency has dropped over the years. Within all breeds, generalised tonic–clonic seizures (GTCS) were the most frequently observed type of seizures next to cluster seizures (CS) and status epilepticus (SE). Roughly, pre-ictal and post-ictal signs could be observed in half of all epileptic dogs. Anti-seizure medication (ASM) was administered to 78% of the dogs, and 70% of those experienced side effects. Only in the Wetterhoun was the need for an anti-seizure medication (ASM) less. Less than 50% of the Wetterhouns needed an ASM. The most common ASM across all breeds was phenobarbital (PB).ConclusionPrevalence varied across the nine breeds, regardless of their population size. The phenotypic characteristics of IE/EUC are comparable with those of other dog breeds. Breeding strategy appeared to be the most effective in the Dutch Smoushound and Kooiker dog.

Emerging evidence indicates that epilepsy extends beyond the brain, involving systemic metabolic, immune, and microbiome perturbations that shape neuronal excitability and treatment response. Canine idiopathic epilepsy (CE) offers a naturally occurring, genetically diverse model with strong electrophysiological, pharmacological, and clinical homology to human epilepsies. In this review, we synthesise canine and human data on metabolic pathways (amino acids, lipids, vitamins, minerals, trace elements), the gut–brain axis and neurotransmitter signalling, inflammation and immunity, oxidative stress, the endocannabinoid system, and microRNAs. Across these systems, consistent alterations are reported in CE, paralleling human findings and supporting a view of epileptogenesis that expands beyond the brain. We highlight opportunities for translation, like biomarkers and stratifiers, dietary/metabolic interventions (e.g., MCT‑based nutrition), microbiome modulation, and immunometabolic targets, alongside critical pitfalls: small, heterogeneous cohorts, antiseizure medication confounding, variable fasting or diet status, breed effects and correlation without causal testing. Taken together, CE can bridge experimental models and clinical practice, advancing epilepsy research beyond the brain toward mechanism‑guided, multisystem therapeutics, offering a win-win for both species alike.

A 7-month-old Belgian Malinois puppy was presented for progressively worsening ataxia and episodes of aggression. General physical examination was unremarkable, and neurological examination revealed ambulatory tetraparesis, spinocerebellar ataxia, thoracic limb pseudo-hypermetria, exaggerated head movements, bilateral vestibular signs and a bilateral divergent strabismus. A magnetic resonance imaging (MRI) of the brain and cervical spinal cord revealed a generalized cerebral atrophy. The dog woke up from anesthesia in a severe episode of disorientation and aggression, wherefore he was euthanized. Histopathology of the brain revealed diffuse and widespread oligodendroglial dysplasia with myelinated fibers disorganization. A disease-associated nonsense variant in NECAP1 (NC_049248.1:g.8636271G>A on chromosome 27), introducing a stop codon at codon 48 (XM_038576681.1:c.142C>T (p.Arg48*)) and truncating the only isoform by 83%, was identified by whole genome sequencing (WGS). The variant segregated in the affected family with a recessive mode of inheritance, but was not present in 158 undiagnosed Belgian Malinois from the Belgian population. The exact same variant, as well as another NECAP1 variant (c.301 + 1G>A), have been associated with early onset epileptic encephalopathy (EOEE) in humans, a disease that is characterized by intractable epileptic seizures and profound global developmental delay in young children. In conclusion, a previously unreported leukoencephalomyelopathy with oligodendroglial dysplasia causes spinocerebellar ataxia and abnormal behavior in Belgian Malinois.

ABSTRACT Background Myasthenia gravis (MG) is categorized into several subgroups, including seronegative MG. Seronegative human patients are well documented, but seronegative dogs remain clinically uncharacterized and their prevalence unknown. Objectives This study aims to evaluate the clinical presentation, diagnosis, treatment, and outcome of canine MG subgroups. Animals One hundred sixty‐seven owner‐owned dogs diagnosed with MG from three referral centers. Methods Retrospective case series. We classified myasthenic dogs into subgroups, adhering to human guidelines. Results We classified 167 dogs into four subgroups: acetylcholine receptor (AChR) antibody‐positive generalized (49.7%, n = 83/167), focal (19.2%, n = 32/167) and thymoma‐associated MG (9%, n = 15/167) and seronegative MG (22.2%, n = 37/167). Dogs with thymoma‐associated MG were older (median 102 months; Interquartile Range (IQR) 96–120; p < 0.001) and seronegative dogs were younger (median 30 months; IQR 11.5–66; p = 0.017), compared to the generalized subgroup (median 67 months; IQR 36–96). Seronegative dogs presented less frequently with megaesophagus, compared to the generalized subgroup (63.8% vs. 85.7%; Odds Ratio 3.4; 95% confidence intervals (C.I.) 1.4–8.9; p = 0.025). Myasthenic dogs' survival time was significantly reduced when thymoma (Hazard Ratio (H.R.) 3.7; 95% C.I. 1.4–9.9; p = 0.028) or esophageal weakness (H.R. 3.8; 95% C.I. 2.0–7.0; p < 0.001) was present. Conversely, a higher likelihood of remission was achieved when esophageal weakness was absent (H.R. 3.8; 95% C.I. 1.4–10.0; p = 0.007). Conclusion and Clinical Importance Dogs with seronegative MG are more common than previously reported. Myasthenic subgroups differ in presentation and outcome, with esophageal weakness key to survival and remission. Diagnostic tests for seronegative dogs and effective treatments for esophageal weakness in myasthenic dogs are urgently needed.

Idiopathic epilepsy (IE) is the most common chronic neurological disease in dogs, and a natural animal model for human epilepsy types with genetic and unknown etiology. The microbiota-gut-brain axis (MGBA) is a promising target for improving brain health in individuals where brain function is hampered. It’s role in the pathophysiology of epilepsy remains however unclear. We aimed to identify differences in fecal metabolome and microbiome between healthy and dogs with IE. To this purpose, fecal samples of healthy (n = 39) and dogs with IE (n = 49) were metabolically profiled (n = 148 metabolites) and fingerprinted (n = 3690 features) using liquid chromatography coupled to mass spectrometry, and the bacterial phylogeny examined using 16 S rRNA sequencing. Dogs with IE were categorized as drug-resistant (DR) (n = 27) or mild phenotype (MP) (n = 22). In dogs with DR IE compared to healthy, fecal metabolites such as histamine (P = 0.022) and microbiome genera such as Escherichia-Shigella (P = 0.021) increased, associated with a proinflammatory environment. In dogs with MP IE compared to healthy, alterations associated with anti-inflammatory properties, such as increased fecal serotonin (P = 0.034) and Blautia hominis (P = 0.012) were revealed. Overall, a role for the MGBA communication in canine IE was established.

ABSTRACT Background Diseases associated with generalized tremors in dogs have not been extensively investigated in a large population of dogs. Hypothesis/Objectives Describe semiology, tremor phenotype, and diseases associated with generalized tremors in dogs, and identify clinical features that could be associated with the underlying disease. Animals A total of 198 dogs. Methods Retrospective, single‐center study of dogs with generalized tremors and a final or presumptive diagnosis between January 2003 and December 2023. Results The most common diseases associated with generalized tremors in dogs were intoxication (91/198; 46%), idiopathic generalized tremor syndrome (IGTS; 49/198; 24.7%), hypocalcemia (13/198; 6.6%), meningoencephalitis of unknown origin (MUO; 9/198; 4.5%), hypoglycemia (6/198; 3%), hypercalcemia (5/198; 2.5%) and degenerative encephalopathies (5/198; 2.5%). Dogs with IGTS were females (p = 0.002), younger (p = 0.002) with an acute progressive lateralizing presentation (p < 0.001 for all three), compared to dogs with intoxication that were males (p = 0.002), young and middle‐aged (p = 0.002) with a hyperacute nonprogressive symmetric presentation (p < 0.001 for all three). Behavioral changes (p = 0.01), hypersalivation (p = 0.04), abnormal mentation (p = 0.01), bilateral mydriasis (p = 0.02) or generalized hyperesthesia (p = 0.002) were common in intoxication, whereas hyporexia and vestibulocerebellar signs (p < 0.001 both) were common in IGTS. Dogs manifested only tremors in intoxication (45%) compared with IGTS (22%; p = 0.01). Improvement within 48 h from the onset of signs without corticosteroid treatment occurred exclusively in dogs with intoxication (p < 0.001). Conclusions and Clinical Importance Intoxication and IGTS were the most common diseases associated with generalized tremors in dogs. Historical and clinical features may aid the clinician in adjusting their differential diagnoses and formulating a diagnostic and treatment plan.

In human medicine, questions regarding heritable disorders are dealt with by clinical geneticists and genetic counselors and both the field, their roles and the tools they use are well-defined. Even though the prevalence of diseases is far higher and scientific literature agrees on expectations towards an increased importance, this does not seem to be the case in veterinary medicine. While we hypothesize that there will be an overlap, some characteristics uniquely linked to veterinary medicine might not be covered. To investigate this in-depth and in an attempt to define the field, we compared the internationally accepted definitions and its subparts on genetic counseling in human medicine with what is found in veterinary literature and what was seen in cats and dogs presented at our dedicated small animals clinical genetics/genetic counseling clinic. The results were used in a stepwise analysis that lead to a set of three potential definitions (i.e. on what genetic counseling is, who provides it and which tools are used) that fullfill four criteria (i.e. definitions have to be clear/self-explanatory, minimally sufficient, complete and valid). The short version of the definition of genetic counseling in veterinary medicine is: "Genetic counseling is the process of helping animal owners and breeders understand – and adapt to – the medical, psychological, familial implications of genetic contributions to disease.” Genetic counseling in small animal practice is currently provided by veterinarians and the tools that are used, can be divided in five categories. The signalment of the patients revealed that both cats (30

Abstract Background Spinal arachnoid diverticulum (SAD) is considered a rare disease in cats. Previous reports mainly classified SAD in cats as acquired. Hypothesis/Objectives The aim of this study was to describe the signalment, clinical presentation, diagnostic imaging findings, and outcome in a group of cats with SAD. Animals Twenty‐one client‐owned cats. Methods Multicenter observational retrospective review of the medical records of cats diagnosed with SAD by magnetic resonance imaging. Results Most cats were Domestic Short Hair (67%), male (63%), and had a wide range of ages (18 weeks to 13 years old). Neuroanatomical localization was consistent with a T3‐L3 myelopathy in 18 cats (86%) and C1‐C5 myelopathy in 3 cats (14%). One cat with a C1‐C5 myelopathy demonstrated bilateral vestibular clinical signs. One cat (5%) had fecal incontinence. Most cats demonstrated a chronic, progressive, nonlateralized, nonpainful myelopathy. No underlying previous or concurrent spinal condition was found in 48% of the cats. No difference in age, body weight, breed, sex, treatment, or outcome was found between cats with or without a concurrent spinal disorder. One cat was euthanized after diagnosis. Six cats improved, 1 deteriorated and 1 remained static after surgery, whereas 3 cats improved, 5 deteriorated and 4 remained static after medical management on the short‐term outcome. Overall, 73% (8/11) of the cats deteriorated on available long‐term follow‐up information. Conclusions and Clinical Importance Spinal arachnoid diverticulum should be considered for cats with chronic, progressive, symmetrical, nonpainful myelopathy, particularly if male and with a history of spinal disease or surgery.

OBJECTIVE:Idiopathic epilepsy (IE) is the most common chronic neurological disease in dogs and an established natural animal model for human epilepsy types with genetic and unknown etiology. However, the metabolic pathways underlying IE remain largely unknown. METHODS:Plasma samples of healthy dogs (n = 39) and dogs with IE (n = 49) were metabolically profiled (n = 121 known target metabolites) and fingerprinted (n = 1825 untargeted features) using liquid chromatography coupled to mass spectrometry. Dogs with IE were classified as mild phenotype (MP; n = 22) or drug-resistant (DR; n = 27). All dogs received the same standard adult maintenance diet for a minimum of 20 days (35 ± 11 days) before sampling. Data were analyzed using a combination of univariate (one-way analysis of variance or Kruskal-Wallis rank sum test), multivariate (limma, orthogonal partial least squares-discriminant analysis), and pathway enrichment statistical analysis. RESULTS:In dogs with both DR and MP IE, a distinct plasma metabolic profile and fingerprint compared to healthy dogs was observed. Metabolic pathways involved in these alterations included oxidative stress, inflammation, and amino acid metabolism. Moreover, significantly lower plasma concentrations of vitamin B6 were found in MP (p = .001) and DR (p = .005) compared to healthy dogs. SIGNIFICANCE:Our data provide new insights into the metabolic pathways underlying IE in dogs, further substantiating its potential as a natural animal model for humans with epilepsy, reflected by related metabolic changes in oxidative stress metabolites and vitamin B6. Even more, several metabolites within the uncovered pathways offer promising therapeutic targets for the management of IE, primarily for dogs, and ultimately for humans.

Although tremors are common neurological presentations, there is little known about their clinical features and underlying etiologies in cats. The aim of this study was to evaluate the clinical features, and underlying diagnoses in cats with tremors. We hypothesized that the results of this study would provide clinically useful information for clinicians when evaluating cats with tremors. This is a retrospective, single-center, study of cats with tremors between 2004 and 2023. Inclusion criteria included complete medical records, presence or report of tremor or twitch, and a final or presumptive diagnosis. One hundred five cats met the inclusion criteria. The most common diagnoses associated with tremors were degenerative encephalopathy (19/105; 18.1 %), feline infectious peritonitis (FIP) (17/105; 16.2 %), congenital portosystemic shunt (17/105; 16.2 %), intoxication (16/105 15.2 %) and polyneuropathy (8/105; 7.6 %). Most common degenerative encephalopathies were suspected cerebellar cortical degeneration (7/19; 50 %) and lysosomal storage diseases (7/19; 50 %) and manifested intention head tremors. Intention head tremors were also seen in cats with FIP and thiamine deficiency encephalopathy. Portosystemic shunt tremors were of variable features, focal or generalised, intentional, nonintentional or both. The most common intoxication was permethrin ingestion and was most commonly associated with generalized tremors as the main presenting complaint. The most common type of tremor in cats with a polyneuropathy was a generalised tremor or limb tremor. Different tremor phenotypes occur and are associated with specific underlying diagnoses in cats. This information can aid clinicians on the best way to approach cats with a variety of tremor phenotypes.

REM sleep behavior disorder (RBD) is a disease characterized by the loss of lower motor neuron inhibition responsible for skeletal muscle atonia during REM sleep. It has been reported in humans, dogs and cats, and can be idiopathic or secondary to a neurodegenerative disease. Five young adult Russian Blue cats from two related families were presented for progressively worsening RBD episodes frequently associated with urinary loss. Three of these cats also suffered urinary retention with overflow incontinence between RBD episodes. Neurological examination revealed a large bladder in three cats and a bilateral mydriasis with absent pupillary light reflexes in two cats; further examinations were unremarkable. Treatment attempts were unsatisfactory, with four cats being euthanized. Histopathology of the brain did not reveal any abnormalities. A disease-associated 23-bp deletion in exon 1 of FAM8A1 (NC_058372.1:g.11622168_11622190del), introducing a frameshift at codon 162 and a premature stop codon at codon 276 (XM_019831563.3:c.485_507del p.(Gln162Profs*115)), was identified by whole genome sequencing. The variant segregated in the affected families with a recessive mode of inheritance, showed an allele frequency of 1.5% in West-European Russian Blue cats (N = 68) and was not present in 276 cats belonging to 32 other breeds (including the closely related Nebelung breed). The variant FAM8A1 isoform is predicted to affect the assembly and activity of the endoplasmic reticulum-associated protein degradation pathway, which plays an important role in cell homeostasis. RBD and urinary retention syndrome is a hereditary encephalopathy affecting Russian Blue cats. A genetic test now allows diagnosis and prevention of this debilitating disease.

BACKGROUND:Meningoencephalitis of unknown origin (MUO) is an idiopathic immune-mediated central nervous system disease. Glucocorticosteroids are the main treatment, often combined with cytosine arabinoside (CA). METHODS:This retrospective, descriptive study evaluated the outcome of a 69-week protocol using glucocorticosteroids and CA (two initial constant rate infusions followed by recurrent subcutaneous injections) in dogs diagnosed with MUO. Outcomes (e.g., treatment success, relapse or death) at 25, 69 and 93 weeks were descriptively analysed and compared to similar protocols reported in the literature. Relapse timing was documented at different treatment stages and glucocorticosteroid dosages. RESULTS:Thirty-five dogs met the inclusion criteria, of which six (17.1%) died within the first 7 days after diagnosis. Overall, 62.9% completed the 93-week follow-up, with 42.9% showing no relapse. Relapse occurred in 40% of dogs, with 20% of these relapsed dogs dying. The majority of dogs relapsed during the treatment protocol. LIMITATIONS:Limitations include the study's retrospective and descriptive nature, small sample size and lack of histopathological confirmation. CONCLUSION:The treatment protocol used in this study does not demonstrate superiority over protocols used in earlier studies. This study emphasises the need for long-term follow-up to detect relapses after treatment discontinuation.