Search Results (59)

Background/Objectives: Idiopathic epilepsy is a lifelong neurologic disorder in dogs, but its genetic basis remains incompletely understood in many breeds. This study aimed to identify risk-associated markers in Siberian Huskies, quantify their effects, assess potential risk modifiers, and characterize the shared haplotype background of the associated signal. Methods: A genome-wide association study was conducted in 113 Siberian Huskies genotyped on the Illumina CanineHD array, integrating association, regression, and haplotype/IBD analyses. An independent follow-up cohort of 57 additional dogs was genotyped at the lead marker by Sanger sequencing. Sex and gonadectomy status/timing were also evaluated as potential modifiers of risk, using multivariable regression and time-to-event analyses. Results: A strong, localized association was identified on canine chromosome 3 (CFA3) within KCNIP4. The lead intronic marker was significantly enriched in cases, with all risk-allele homozygotes affected, most heterozygotes affected, and no control homozygotes observed. Risk-associated chromosomes shared extended haplotypes across the region, consistent with carriers inheriting a common risk haplotype from a relatively recent shared ancestor. Among carriers, male sex was associated with higher odds of epilepsy and earlier seizure onset, with more tentative evidence for a similar association with gonadectomy before 5 years of age. Conclusions: These findings prioritize a CFA3 region encompassing KCNIP4 as a major risk locus for idiopathic epilepsy in Siberian Huskies. Fine-mapping with high-coverage sequencing and functional follow-up will be required to pinpoint the causal variant(s) and support development of risk assessment tools. Until those studies are completed, this marker should be regarded as a research finding rather than a predictive test. Full article

Background: Oxidative stress contributes to the development and progression of epilepsy and is connected with neuroinflammation during epileptic seizures. Cholinesterase has a modulatory role, and oxytocin has antiepileptic properties. The purpose of this study was to assess selective inflammatory (C-Reactive Protein, CRP) and oxidative stress markers [Paraoxonase-1 (PON1), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), cholinesterase, and oxytocin in serum and cerebrospinal fluid (CSF) samples of dogs with different types of epilepsy. Methods: There were four groups of dogs; A: healthy controls; B: idiopathic epilepsy receiving antiepileptic medication; C: idiopathic epilepsy without antiepileptic medication; and D: structural epilepsy. CRP, PON1, CUPRAC, and cholinesterase were evaluated in serum and PON1, CUPRAC, FRAP, cholinesterase and oxytocin were evaluated in CSF samples. Group differences were evaluated using the ANOVA test, followed by post hoc analyses or Kruskal–Wallis/Dunn’s test. Results: Fifty-one serum and 26 CSF samples were analyzed. CSF PON1 was significantly different in group D compared with groups A and C (p = 0.044 and p = 0.008, respectively). CSF cholinesterase was significantly different in group D compared with groups A, B and C (p = 0.003, p = 0.025, and p = 0.033, respectively). Conclusions: Structural epilepsy may influence PON1 and cholinesterase levels in CSF samples. Compared with CSF, serum was not the most suitable biological material to investigate oxidative stress and inflammatory markers. Full article

Epilepsy is a common neurological disorder in cats, but its seizure types, etiologies, and clinical associations remain incompletely characterized compared to dogs. This retrospective study analyzed 118 feline epilepsy cases from two veterinary hospitals in Finland and Lithuania, aiming to evaluate the distribution of seizure types and their associations with demographic, clinical, neurological, diagnostic, and diagnostic test results. Seizures were classified as single generalized (SG), cluster seizures (CS), or status epilepticus (SE). SG and CS occurred with nearly equal frequency (44.9% and 45.8%, respectively), while SE was less common (9.3%). Median age at presentation was 72 months, and no significant differences were found in age, sex, reproductive status, or body weight between seizure types. Abnormal clinical findings (p = 0.009) and neurological abnormalities (p < 0.001) were significantly more frequent in cats with SE, indicating greater neurological compromise in severe seizure forms. MRI was performed in 74.6% of cases and revealed a significant difference in utilization among seizure types (p = 0.004), with lower imaging rates in SE, likely reflecting clinical instability at presentation. Etiology of seizure development was established in 89 cats: idiopathic epilepsy (IE) predominated (80.9%), followed by structural (15.7%) and metabolic/toxic (3.4%) causes. Seizure type and etiology were significantly associated (p = 0.006), with structural epilepsy most common in SE and idiopathic epilepsy prevailing in SG and CS. Among cats with known outcomes (n = 35), seizure control was achieved in 68.6%, while mortality and euthanasia were higher in SE. These findings provide new insight into feline epilepsy by linking seizure type to clinical and etiological profiles, emphasizing that severe presentations are more often associated with neurological abnormalities and structural causes, whereas demographic factors alone do not predict seizure severity. Full article

Background: Inflammation is a common reason for dogs to present to veterinary clinics. Early diagnosis of systemic inflammation is important. Acute phase proteins, like C-reactive protein, are useful but not specific to infection. In human medicine, the intensive care infection score (ICIS) offers a faster, cost-effective alternative using advanced hematological parameters. While ICIS is not available for veterinary use, some components (e.g., neutrophil side fluorescent light) can be measured using analyzers like the Sysmex XN-1000V. Objectives: This study aimed to establish a control group of healthy dogs for the novel parameters neutrophil side fluorescent light (NE-SFL), neutrophil side scattered light (NE-SSC), and neutrophil forward scattered light (NE-FSC) and assess their utility in detecting inflammation in diseases such as sepsis, pyometra, steroid-responsive meningitis-arteritis (SRMA), and idiopathic epilepsy. Methods & Results: Value ranges were calculated based on 21 healthy dogs. Compared to controls, NE-SFL levels were significantly elevated in sepsis, pyometra, and SRMA, while NE-SSC was only elevated in sepsis and pyometra and NE-FSC only in sepsis. No increases were observed in idiopathic epilepsy. Manual gating of the white blood cell differential scattergram was necessary in samples showing high neutrophil toxicity and the presence of bands. Conclusion: NE-SFL and NE-SSC, obtainable from routine complete blood count, may serve as novel, accessible markers for inflammation in dogs. Further research is needed to validate their broader diagnostic use. Full article

Idiopathic epilepsy (IE) is a common chronic neurological disorder in dogs, and both its comorbidities and adverse effects of anti-seizure medication (ASM) can markedly reduce quality of life (QoL) for affected dogs and their caregivers. Concurrent conditions such as lower urinary tract infections (UTIs) may mimic ASM side effects or signs of disease progression, potentially leading to inappropriate dose adjustment or treatment discontinuation. This retrospective case series describes eight dogs with IE and Escherichia coli (E. coli) UTI, presenting with suspected worsening of ASM side effects. Reported deterioration lasted 1–55 days (mean 31), with behavioral changes (n = 5), lethargy (n = 5), new or worsened ataxia (n = 5), urinary incontinence (n = 3), polyuria (n = 3), polydipsia (n = 2), and additional signs such as weakness, exercise intolerance, panting, and cluster seizures. All dogs showed bacteriuria; urinary specific gravity was 1.020 ± 0.013 (mean ± standard deviation) [range; 1.002–1.042]. E. coli (>10⁶ CFU/mL) was isolated in all cases. Treatment with amoxicillin–clavulanic acid resulted in clinical improvement within 24–72 h; five dogs experienced UTI relapse, again with clinical deterioration. Findings emphasize the importance of recognizing and treating UTIs in epileptic dogs to avoid misinterpretation as ASM toxicity and possible worsening of seizure control. Prospective studies are needed to clarify potential links between ASM, urinary dilution, immune modulation, and infection risk. Full article

Neurobehavioral comorbidities in dogs with idiopathic epilepsy (IE) are increasingly recognized, yet their phenotypic variability and clinical implications remain poorly understood. This study aimed to identify behavioral changes following seizure onset and to explore the feasibility of stratifying patients based on neurobehavioral profiles. Seventy client-owned dogs with IE were enrolled and grouped according to treatment: 29 had drug-resistant epilepsy (DRE), 29 were drug-sensitive (DSE), and 12 remained untreated. Owners completed a modified version of the C-BARQ questionnaire, assessing behaviors before and after seizure onset. Nearly one-third of behavioral items showed significant changes, particularly in attachment and attention-seeking behaviors, separation-related behaviors, eating behavior, and signs of cognitive decline such as reduced trainability and dementia-like signs. Principal component analysis followed by cluster analysis revealed two distinct neurobehavioral profiles: Cognitive and Emotional. The Cognitive cluster was associated with a higher total questionnaire score, poorer seizure control (predominantly DRE), and lower owner-perceived quality of life. In contrast, the Emotional cluster was more frequently observed in dogs with DSE or no treatment and was associated with higher quality of life scores. These findings support the clinical relevance of behavioral stratification in canine epilepsy and underscore the need for individualized, multimodal approaches to improve patient care. Full article

Epilepsy is widely known as a network disease. Ictal and interictal activities are generated and spread within the existing networks involving different regions of the brain. Network alterations affect both grey and white matter, deep brain nuclei, including those of the ascending reticular formation. These structures may be involved in a disorganized connectome associated with epilepsy. A growing body of neuroimaging and neuropsychological findings suggests that global and focal network aberrations are closely linked to cognitive deficits in epilepsy patients. This evidence relates equally to focal epilepsies, such as temporal lobe epilepsy or extra-temporal lobe epilepsy, as well as generalized epilepsies, such as juvenile myoclonic epilepsy. Network abnormalities have been associated with a broad range of cognitive impairments, including language, memory, and executive functions, as well as sensory and motor functions. Whole-brain structural connectome models help in the understanding of seizure generation and spread. Identifying key nodes of seizure propagation may help in planning surgical procedures in individual patients by simulating epilepsy surgery on virtual models. Functional connectomic profiles may predict seizure outcomes in patients who undergo deep brain stimulation due to intractable seizures. Therefore, individualized interventional strategies could be developed based on connectome characteristics. Full article

The use of animal models of idiopathic generalized epilepsy (IGE) is of great importance in the field of epilepsy research, with IGE affecting more than 20 million people worldwide. IGEs are characterized by a high degree of genetic heterogeneity, which makes it difficult to understand the underlying mechanisms leading to seizures. The development of animal models, whether spontaneous or resulting from genetic manipulation, has significantly contributed to our understanding of the pathological processes underlying certain IGEs, notably absence epilepsy. Research suggests that the concept of generalized epilepsy covering the whole brain should be replaced by a model in which the thalamus and its various nuclei are integrated into thalamo-cortical loops. These then assume distinct roles in the generation and generalization of seizures, which may differ across the spectrum of IGE disorders. The study of epileptogenesis is also essential: this area of research, grounded in systematic developmental neuroscience, examines the intermediate stages of neuronal activity to determine when, and how, functional development diverges between healthy and pathological states. Understanding nervous system development requires a comprehensive view of how anatomic, molecular, and genetics factors relate to neuronal activity. The emerging use of optogenetic methods and human assembloids will greatly aid our understanding of the mechanisms underlying these processes. Full article

The co-occurrence of autism spectrum disorder (ASD) and epilepsy is a complex neurological condition that presents significant challenges for both patients and clinicians. ASD is a group of complex developmental disorders characterized by the following: (1) Social communication difficulties: challenges in understanding and responding to social cues, initiating and maintaining conversations, and developing and maintaining relationships. (2) Repetitive behaviors: engaging in repetitive actions, such as hand-flapping, rocking, or lining up objects. (3) Restricted interests: focusing intensely on specific topics or activities, often to the exclusion of other interests. (4) Sensory sensitivities: over- or under-sensitivity to sensory input, such as sounds, touch, tastes, smells, or sights. These challenges can significantly impact individuals’ daily lives and require specialized support and interventions. Early diagnosis and intervention can significantly improve the quality of life for individuals with ASD and their families. Epilepsy is a chronic brain disorder characterized by recurrent unprovoked (≥2) seizures that occur >24 h apart. Single seizures are not considered epileptic seizures. Epilepsy is often idiopathic, but various brain disorders, such as malformations, strokes, and tumors, can cause symptomatic epilepsy. While these two conditions were once considered distinct, growing evidence suggests a substantial overlap in their underlying neurobiology. The prevalence of epilepsy in individuals with ASD is significantly higher than in the general population. This review will explore the epidemiology of this comorbidity, delve into the potential mechanisms linking ASD and epilepsy, and discuss the implications for diagnosis, treatment, and management. Full article

Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut bacteria and the brain, which involve metabolic, neural, immunological, and endocrine mechanisms. In fact, a balanced and stable gut microbiota is essential to maintaining normal gut physiology and ensuring appropriate signaling along the gut–brain axis. Conversely, dysbiosis can have detrimental effects on gut physiology and may contribute to the development or exacerbation of neurological conditions, including epilepsy. Considering these findings, this review article aims to deepen the understanding of the mechanisms underlying the microbiota–gut–brain connection in the context of canine idiopathic epilepsy. Moreover, this review presents recent data on innovative gut-related therapeutic strategies for canine idiopathic epilepsy treatment. Full article

Background: Recent studies have described unique aspects of default mode network connectivity in patients with idiopathic generalized epilepsy (IGE). A complete background in this field could be gained by combining this research with spectral analysis. Objectives: An important objective of this study was to compare linear connectivity and power spectral densities across different activity bands of patients with juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic–clonic seizures alone (EGTCSA), and drug-resistant IGE (DR-IGE) with healthy, age-matched controls. Methods: This was an observational case–control study. We performed EEG spectral analysis in MATLAB and connectivity analysis with LORETA for 39 patients with IGE and 12 drug-resistant IGE (DR-IGE) and healthy, age-matched subjects. We defined regions of interest (ROIs) from the default mode network (DMN) and performed connectivity statistics using time-varying spectra for paired samples. Using the same EEG data, we compared mean power spectral density (PSD) with epilepsy subgroups and controls across different activity bands. Results: We obtained a modified value for the mean power spectral density in the beta band for the JME group as follows. The connectivity analysis showed that, in general, there was increased linear connectivity in the DMN for the JAE, JME, and EGCTSA groups compared to the healthy controls. Reduced linear connectivity between regions of the DMN was found for DR-IGE. Conclusions: Spectral analysis of electroencephalography (EEG) for generalized epilepsy syndromes seems to be less informative than connectivity analysis for DMN. DMN connectivity analysis, especially for DR-IGE, opens up the possibility of finding biomarkers related to drug response in IGE. Full article

Background: Idiopathic epilepsy (IE) disproportionately affects Belgian shepherd dogs and although genomic risk markers have been identified previously in the breed, causative variants have not been described. Methods: The current study analyzed differences in whole blood RNA expression associated with IE and with a previously identified IE risk haplotype on canine chromosome (CFA) 14 using a transcriptomics RNA-seq approach. Results: MFSD2A and a likely pseudogene of RPL19, both of which are genes implicated in seizure activity, were upregulated in dogs with IE. Genes in the interferon signaling pathway were downregulated in Belgian shepherds with IE. The CFA14 risk haplotype was associated with upregulation of CLIC1, ACE2, and PIGN and downregulation of EPDR1, all known to be involved with epilepsy or the Wnt/β-catenin signaling pathway. Conclusions: These results highlight the value of assessing gene expression in canine IE research to uncover genomic contributory factors. Full article

Background/Objectives: The purpose of this study was to determine the influence of H. pylori eradication on the serum level of the orally administered valproic acid (VPA) in children with idiopathic generalized epilepsy; Methods: This prospective cohort observational study included 100 children with idiopathic generalized epilepsy, recruited from a neurology clinic from May 2021 to December 2021. The patients were divided into two groups, each containing 50 children. The first group had a positive H. pylori stool antigen and H. pylori-related symptoms, while the second group had a negative antigen. H. pylori Eradication therapy was given to the positive H. pylori group. The serum level of VPA was obtained at baseline and 4 weeks after eradication therapy. Results: Despite there being no significant difference between the H. pylori-positive and H. pylori-negative groups regarding the baseline VPA serum level (79.9 ± 13.9 and 77.9 ± 13.1 mcg/mL), respectively, the serum VPA level had significantly increased after H. pylori eradication therapy (99.4 ± 11 mcg/mL) (p value = 0.000), as opposed to the H. pylori-negative group (85.3 ± 10.9 mcg/mL) (p value = 0.142). Furthermore, there was a statistically significant association with a negative correlation between the VPA serum level after eradication and the number of epileptic attacks per month (p value = 0.033, R value = −0.301) and the dose of VPA (p value = 0.046, R value = −0.284). Conclusions: The eradication of H. pylori resulted in a highly significant improvement in the serum level of the orally given VPA in children with idiopathic generalized epilepsy, as well as an indirect decrease in the frequency of epileptic events per month, allowing for dose reduction. Eradication therapy may have anticonvulsant properties and might indirectly aid in the management of epileptic activity. H. pylori screening for children with idiopathic generalized epilepsy can optimize serum VPA levels, potentially leading to better seizure control. To our knowledge, this is the first study in the literature to describe the effect of H. pylori eradication on the serum level of the orally administered VPA in children with idiopathic generalized epilepsy. Full article

Background: The role of neuroinflammation in epileptogenesis has been previously explored, and several biomarkers have been identified as being relevant in assessing the intensity of the inflammatory process. In human medicine, an increased C reactive protein (CRP) blood concentration and/or neutrophil-to-lymphocyte ratio (NLR) is considered a constant finding of epileptic activity. In veterinary medicine, only a few studies have been published regarding both of these topics. Hypothesis/objectives: Our aim was to assess the C reactive protein blood concentration and the neutrophil-to-lymphocyte ratio in epileptic dogs, regardless of etiology. Method: This retrospective study was based on changes in routine blood parameters in 59 dogs with epileptic activity. Results: An increased C reactive protein concentration was observed mostly in the dogs affected by structural epilepsy, and all epileptic dogs displayed abnormal neutrophil-to-lymphocyte values. Conclusions: Based on the authors’ knowledge, this is the first report regarding the NLR in epileptic dogs. Both the CRP concentration and the NLR might be considered feasible non-specific markers of the neuroinflamation involved in epileptogenesis and might be used in the diagnosis of and therapeutic approach to cluster seizures in dogs with idiopathic epilepsy and in patients with structural epilepsy. Dogs diagnosed with IEis and high CRP concentrations and NLRs may be subject to non-documented cluster seizures. Both CRP and the NLR have limited diagnostic value in dogs with reactive seizures. Full article

While significant strides have been made in comprehending the pathophysiology and treatment of epilepsy, further investigation is warranted to elucidate the factors impacting its development and transmission, particularly within familial contexts. This study sought to explore the prevalence and risk factors associated with epilepsy in the offspring of patients with epilepsy who were treated at a tertiary epilepsy center. Adult patients with confirmed epilepsy (PWE) receiving outpatient care were consecutively enrolled, starting from January 2021 to January 2023. Data were recorded for various variables, including age, gender, epilepsy pathophysiology, cognitive impairment, and family history of epilepsy. Descriptive statistics, various statistical tests, and multivariate logistic regression analyses were employed to analyze the data. A total of 1456 PWE were included. Among them, 463 patients (31.8%) had children. Twenty-five patients had offspring diagnosed with epilepsy, representing a prevalence of 5.4%. Analysis of the offspring with epilepsy revealed older ages, a higher proportion of parents with idiopathic epilepsy, and a greater prevalence of a positive family history of epilepsy. Multivariate logistic regression analysis demonstrated a significant association between a family history of epilepsy and increased epilepsy risk in offspring. Genetic syndrome-immanent predisposition, advanced age, and a family history of epilepsy were identified as significant risk factors for epilepsy in offspring by means of this mono-center study. Full article