Search Results (51)

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

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. Treatment with steroids is usually successful; however, in a small percentage of patients, steroid resistance is observed. The most frequent histologic kidney feature of steroid-resistant nephrotic syndrome (SRNS) is focal segmental glomerulosclerosis (FSGS). Genetic testing has become a valuable diagnostic tool in defining the etiology of SRNS, leading to the identification of a genetic cause. The TRIM8 gene is expressed in various tissues, including kidney cells and the central nervous system (CNS). An association between a mutation in the TRIM8 gene and an early onset of FSGS has been proposed but is not well described. We present a 17-year-old boy with epilepsy, early mild developmental delay, a low IgG serum level, and proteinuria, secondary to FSGS. A Next-Generation Sequencing (NGS)-based analysis revealed a heterozygous de novo pathogenic variant in the TRIM8 gene (c.1200C>G, p.Tyr400Ter). TRIM8 gene sequencing should be considered in individuals with early onset of FSGS, particularly accompanied by symptoms of cortical dysfunction, such as epilepsy and intellectual disability. Full article

We report the case of a four-year-old male patient with a complex medical history born prematurely as the result of intrauterine growth restriction due to placental insufficiency. His clinical manifestations included severe neurodevelopmental deficits, global developmental delay, Pierre-Robin sequence, and intractable epilepsy with both generalized and focal features. The proband’s low levels of citrulline and lactic acidosis provoked by administration of Depakoke were evocative of a mitochondrial etiology. The proband’s genotype–phenotype correlation remained undefined in the absence of nuclear and mitochondrial pathogenic variants detected by deep sequencing of both genomes. However, live-cell mitochondrial metabolic investigations provided evidence of a deficient oxidative-phosphorylation pathway responsible for adenosine triphosphate (ATP) synthesis, leading to chronic energy crisis in the proband. In addition, our metabolic analysis revealed metabolic plasticity in favor of glycolysis for ATP synthesis. Our mitochondrial morphometric analysis by transmission electron microscopy confirmed the suspected mitochondrial etiology, as the proband’s mitochondria exhibited an immature morphology with poorly developed and rare cristae. Thus, our results support the concept that suboptimal levels of intrauterine oxygen and nutrients alter fetal mitochondrial metabolic reprogramming toward oxidative phosphorylation (OXPHOS) leading to a deficient postnatal mitochondrial energy metabolism. In conclusion, our collective studies shed light on the long-term postnatal mitochondrial pathophysiology caused by intrauterine growth restriction due to idiopathic placental insufficiency and its negative impact on the energy-demanding development of the fetal and postnatal brain. Full article

Idiopathic epilepsy (IE) has been known to be inherited in the Belgian Tervuren for many decades. Risk genotypes for IE in this breed have recently been identified on Canis familiaris chromosomes (CFA) 14 and 37. In the current study, the allele frequencies of these loci were analyzed to determine whether dog breeders had employed a purposeful selection against IE, leading to a reduction in risk-associated allele frequency within the breed over time. The allele frequencies of two generational groupings of Belgian Tervuren with and without IE were compared. Allele frequencies for risk-associated alleles on CFA14 were unchanged between 1985 and 2015, whereas those on CFA37 increased during that time in the control population (p < 0.05). In contrast, dogs with IE showed a decrease (p < 0.05) in the IE risk-associated allele frequency at the CFA37 locus. Seizure prevalence in the Belgian Tervuren appears to be increasing. These results suggest that, despite awareness that IE is inherited, selection against IE has not been successful. Full article

Epilepsy is one of the most prevalent complex neurological diseases in both the canine and human species, with the idiopathic form as its most common diagnosis. MicroRNAs (miRNAs) are small, noncoding RNA molecules that play a role in gene regulation processes and appear to be a promising biological target for convulsion control. These molecules have been reported as constituents of the internal content of exosomes, which are small extracellular vesicles released by cells. In this study, exosome samples were isolated from the plasma of 23 dogs, including 9 dogs with epilepsy responsive to treatment, 6 dogs with drug-resistant epilepsy, and 8 control dogs. Plasma exosomes were then characterized by electron transmission microscopy, nanoparticle tracking analysis, and dot blotting. Afterwards, the microRNA-enriched RNA content of exosomes was isolated, and miRNA quantification was performed by quantitative real-time PCR. Seven circulating miRNAs that have been previously described in the literature as potential diagnostic or prognostic biomarkers for epilepsy were evaluated. We observed significant differences in miR-16 (p < 0.001), miR-93-5p (p < 0.001), miR-142 (p < 0.001), miR-574 (p < 0.01), and miR-27 (p < 0.05) levels in dogs with refractory epilepsy compared to the control group. In drug-sensitive epileptic dogs, miR-142 (p < 0.01) showed significant differences compared to healthy dogs. Moreover, distinct levels of miR-16 (p < 0.05), miR-93-5p (p < 0.01), miR-132 (p < 0.05), and miR-574 (p < 0.05) were also found between drug-sensitive and drug-resistant epileptic dogs. Our results present plasma-circulating exosomes as an advantageous source of epileptic biomarkers, highlighting the potential of miRNAs as prognostic and diagnostic biomarkers of canine idiopathic epilepsy. Full article

Over the last decade, the comorbidity between Autism Spectrum Disorder (ASD) and epilepsy has been widely demonstrated, and many hypotheses regarding the common neurobiological bases of these disorders have been put forward. A variable, but significant, prevalence of abnormalities on electroencephalogram (EEG) has been documented in non-epileptic children with ASD; therefore, several scientific studies have recently tried to demonstrate the role of these abnormalities as a possible biomarker of altered neural connectivity in ASD individuals. This narrative review intends to summarize the main findings of the recent scientific literature regarding abnormalities detected with standard EEG in children/adolescents with idiopathic ASD. Research using three different databases (PubMed, Scopus and Google Scholar) was conducted, resulting in the selection of 10 original articles. Despite an important lack of studies on preschoolers and a deep heterogeneity in results, some authors speculated on a possible association between EEG abnormalities and ASD characteristics, in particular, the severity of symptoms. Although this correlation needs to be more strongly elucidated, these findings may encourage future studies aimed at demonstrating the role of electrical brain abnormalities as an early biomarker of neural circuit alterations in ASD, highlighting the potential diagnostic, prognostic and therapeutic value of EEG in this field. Full article