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Pathogenic heterozygous variants in CACNA1A are associated with familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6, and more recently, neurodevelopmental disorders. We describe a severe, early-onset phenotype including severe muscular hypotonia, early-onset epileptic seizures, apnoea, optic atrophy and dysphagia in three siblings carrying compound heterozygous frameshift variants in CACNA1A. Two male patients died at the age of 5 or 14 months of suspected SIDS or severe developmental epileptic encephalopathy (DEE) with refractory seizures and apnoea. A male child (index patient) developed severe early-onset DEE including seizures and ictal apnoea at the age of 4 weeks. Another male child developed generalized epilepsy and mild intellectual impairment in late infancy, and his mother and his maternal uncle were identified as carriers of a known CACNA1A pathogenic variant [c.2602delG heterozygous, p. (Ala868Profs*24)] with a diagnosis of episodic ataxia type 2. This maternal pathogenic variant c.2602delG was detected in the index patient and child 2. Trio-Exome sequencing identified an additional heterozygous pathogenic variant in the CACNA1A gene, c.5476delC, p.(His1826Thrfs*30) in the index patient and child 2, which was inherited from the asymptomatic father. In conclusion, the novel compound heterozygosity for two frameshift pathogenic variants, maternally [c.2602delG, p.(Ala868Profs*24)] and paternally [c.5476delC, p.(His1826Thrfs*3)] is associated with a severe phenotype of early-onset DEE. This observation highlights the necessity of additional analyses to clarify unusual phenotypes even if a pathogenic variant has already been identified, and expands the clinical spectrum of CACNA1A -related disorders. [ABSTRACT FROM AUTHOR]

Objective: Although >30% of epilepsy patients have drug‐resistant epilepsy (DRE), typically those with generalized or multifocal disease have not traditionally been considered surgical candidates. Responsive neurostimulation (RNS) of the centromedian (CM) region of the thalamus now appears to be a promising therapeutic option for this patient population. We present outcomes following CM RNS for 13 patients with idiopathic generalized epilepsy (IGE) and eight with multifocal onsets that rapidly generalize to bilateral tonic–clonic (focal to bilateral tonic–clonic [FBTC]) seizures. Methods: A retrospective review of all patients undergoing bilateral CM RNS by the senior author through July 2022 were reviewed. Electrodes were localized and volumes of tissue activation were modeled in Lead‐DBS. Changes in patient seizure frequency were extracted from electronic medical records. Results: Twenty‐one patients with DRE underwent bilateral CM RNS implantation. For 17 patients with at least 1 year of postimplantation follow‐up, average seizure reduction from preoperative baseline was 82.6% (SD = 19.0%, median = 91.7%), with 18% of patients Engel class 1, 29% Engel class 2, 53% Engel class 3, and 0% Engel class 4. There was a trend for average seizure reduction to be greater for patients with nonlesional FBTC seizures than for other patients. For patients achieving at least Engel class 3 outcome, median time to worthwhile seizure reduction was 203.5 days (interquartile range = 110.5–343.75 days). Patients with IGE with myoclonic seizures had a significantly shorter time to worthwhile seizure reduction than other patients. The surgical targeting strategy evolved after the first four subjects to achieve greater anatomic accuracy. Significance: Patients with both primary and rapidly generalized epilepsy who underwent CM RNS experienced substantial seizure relief. Subsets of these patient populations may particularly benefit from CM RNS. The refinement of lead targeting, tuning of RNS system parameters, and patient selection are ongoing areas of investigation. [ABSTRACT FROM AUTHOR]

Pathogenic heterozygous variants in CACNA1A are associated with familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6, and more recently, neurodevelopmental disorders. We describe a severe, early-onset phenotype including severe muscular hypotonia, early-onset epileptic seizures, apnoea, optic atrophy and dysphagia in three siblings carrying compound heterozygous frameshift variants in CACNA1A. Two male patients died at the age of 5 or 14 months of suspected SIDS or severe developmental epileptic encephalopathy (DEE) with refractory seizures and apnoea. A male child (index patient) developed severe early-onset DEE including seizures and ictal apnoea at the age of 4 weeks. Another male child developed generalized epilepsy and mild intellectual impairment in late infancy, and his mother and his maternal uncle were identified as carriers of a known CACNA1A pathogenic variant [c.2602delG heterozygous, p. (Ala868Profs*24)] with a diagnosis of episodic ataxia type 2. This maternal pathogenic variant c.2602delG was detected in the index patient and child 2. Trio-Exome sequencing identified an additional heterozygous pathogenic variant in the CACNA1A gene, c.5476delC, p.(His1826Thrfs*30) in the index patient and child 2, which was inherited from the asymptomatic father. In conclusion, the novel compound heterozygosity for two frameshift pathogenic variants, maternally [c.2602delG, p.(Ala868Profs*24)] and paternally [c.5476delC, p.(His1826Thrfs*3)] is associated with a severe phenotype of early-onset DEE. This observation highlights the necessity of additional analyses to clarify unusual phenotypes even if a pathogenic variant has already been identified, and expands the clinical spectrum of CACNA1A-related disorders.

• Déjà Vu is classically associated with focal seizures originating from the medial temporal lobe. • 3 % of Idiopathic Generalized Epilepsy patients reported Déjà Vu (ranging from 0 to 11 % in the studies). Any type of aura was reported by 40 %. • Clinicians should recognize that Déjà Vu and other auras may experienced in Idiopathic generalized Epilepsy. • Recognizing this pitfall is crucial to avoiding diagnostic and treatment errors. Déjà vu (DV), a French term meaning "already seen," refers to inappropriate sensation of familiarity in the present moment, as if it had been experienced before without a specific recollection of when or where. Traditionally, DV has been closely associated with focal seizures originating from the medial temporal lobe. However, there are occasional reports of DV occurring in idiopathic generalized epilepsies (IGEs). The objective of our study was to assess the presence and frequency of DV in individuals with IGE. We used the Preferred Reporting Items for Systematic Review and Meta-Analysis for protocols (PRISMA-P) and searched PubMed and Embase from January 2000 to July 2022. 5 studies were included with a total of 1177 IGE and 1026 with temporal lobe epilepsy (TLE) patients. The frequency of DV in IGE ranged from 0 to 11 %, and the average was 3 %, compared to 19.6 % in TLE. Broadly, 40 % of patients with IGE reported some type of aura. EEG correlation of DV in IGE was not appropriately evaluated in the studies. Clinicians should be aware that individuals with IGE may experience DV and other types of auras. Recognizing these auras is crucial in order to avoid misdiagnosing IGE as focal epilepsy. This is important to prevent unnecessary investigations and incorrect treatment decisions. [ABSTRACT FROM AUTHOR]

Epilepsies are a group of heterogeneous brain disorder, and antiseizure medications (ASMs) are the mainstay of treatment. Despite the availability of more than 30 drugs, at least one third of individuals with epilepsy are drug-resistant. This emphasizes the need for novel compounds that combine efficacy with improved tolerability. A literature review on the pharmacology, efficacy, tolerability, and safety of azetukalner (XEN1101), a second-generation opener of neuronal potassium channels currently in Phase 3 development as ASM. Results from the phase 2b clinical trial strongly support the ongoing clinical development of azetukalner as a new ASM. Its pharmacokinetic properties support convenient once-daily dosing, eliminating the need for titration at initiation or tapering at the conclusion of treatment. CYP3A4 is the main enzyme involved in its metabolism and drug-drug interactions can affect the drug exposure. Preliminary analysis of an ongoing open-label study reveals no reported pigmentary abnormalities. The upcoming Phase 3 clinical trials are expected to provide further insight into the efficacy, tolerability, and safety of azetukalner in treating focal-onset and primary generalized tonic-clonic seizures. Structurally distinct from currently marketed ASMs, azetukalner has the potential to be the only-in-class Kv7.2/7.3 opener on the market upon regulatory approval. [ABSTRACT FROM AUTHOR]

The involvement of the prefrontal cortical dopaminergic system in the psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or non-convulsive epilepsy. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive form, and KM strain was a model for convulsive epilepsy comorbid with an ASD-like behavioral phenotype. The prefrontal cortex of rats with any epileptic pathology studied demonstrated profound decreases in binding densities to both D1DR and D2DR; the effects were localized in the primary and secondary anterior cingulate cortices, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent of (not correlated with) each other. The particular group of epileptic rats with an ASD-like phenotype (KM strain) displayed changes in the lateral prefrontal cortex: D1DR were lowered, whereas D2DR were elevated, in the dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of the rat archeocortex were localized in the medial prefrontal regions, whereas ASD-related changes were seen in the lateral prefrontal aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD. [ABSTRACT FROM AUTHOR]

Objective: Bilateral tonic–clonic seizures with focal semiology or focal interictal electroencephalography (EEG) can occur in both focal and generalized epilepsy types, leading to diagnostic errors and inappropriate therapy. We investigated the prevalence and prognostic values of focal features in patients with idiopathic generalized epilepsy (IGE), and we propose a decision flowchart to distinguish between focal and generalized epilepsy in patients with bilateral tonic–clonic seizures and focal EEG or semiology. Methods: We retrospectively analyzed video‐EEG recordings of 101 bilateral tonic–clonic seizures from 60 patients (18 with IGE, 42 with focal epilepsy). Diagnosis and therapeutic response were extracted after ≥1‐year follow‐up. The decision flowchart was based on previous observations and assessed concordance between interictal and ictal EEG. Results: Focal semiology in IGE was observed in 75% of seizures and 77.8% of patients, most often corresponding to forced head version (66.7%). In patients with multiple seizures, direction of head version was consistent across seizures. Focal interictal epileptiform discharges (IEDs) were observed in 61.1% of patients with IGE, whereas focal ictal EEG onset only occurred in 13% of seizures and 16.7% of patients. However, later during the seizures, a reproducible pattern of 7‐Hz lateralized ictal rhythm was observed in 56% of seizures, associated with contralateral head version. We did not find correlation between presence of focal features and therapeutic response in IGE patients. Our decision flowchart distinguished between focal and generalized epilepsy in patients with bilateral tonic–clonic seizures and focal features with an accuracy of 96.6%. Significance: Focal semiology associated with bilateral tonic–clonic seizures and focal IEDs are common features in patients with IGE, but focal ictal EEG onset is rare. None of these focal findings appears to influence therapeutic response. By assessing the concordance between interictal and ictal EEG findings, one can accurately distinguish between focal and generalized epilepsies. [ABSTRACT FROM AUTHOR]

Objective: Copy number variants (CNVs) contribute to genetic risk and genetic etiology of both rare and common epilepsies. Whereas many studies have explored the role of CNVs in sporadic or severe cases, fewer have been done in familial generalized and focal epilepsies. Methods: We analyzed exome sequence data from 267 multiplex families and 859 first‐degree relative pairs with a diagnosis of genetic generalized epilepsies or nonacquired focal epilepsies to predict CNVs. Validation and segregation studies were performed using an orthogonal method when possible. Results: We identified CNVs likely to contribute to epilepsy risk or etiology in the probands of 43 of 1116 (3.9%) families, including known recurrent CNVs (16p13.11 deletion, 15q13.3 deletion, 15q11.2 deletion, 16p11.2 duplication, 1q21.1 duplication, and 5‐Mb duplication of 15q11q13). We also identified CNVs affecting monogenic epilepsy genes, including four families with CNVs disrupting the DEPDC5 gene, and a de novo deletion of HNRNPU in one affected individual from a multiplex family. Several large CNVs (>500 kb) of uncertain clinical significance were identified, including a deletion in 18q, a large duplication encompassing the SCN1A gene, and a 15q13.3 duplication (BP4‐BP5). Significance: The overall CNV landscape in common familial epilepsies is similar to that of sporadic epilepsies, with large recurrent deletions at 15q11, 15q13, and 16p13 contributing in 2.5%–3% of families. CNVs that interrupt known epilepsy genes and rare, large CNVs were also identified. Multiple etiologies were found in a subset of families, emphasizing the importance of genetic testing for multiple affected family members. Rare CNVs found in a single proband remain difficult to interpret and require larger cohorts to confirm their potential role in disease. Overall, our work indicates that CNVs contribute to the complex genetic architecture of familial generalized and focal epilepsies, supporting the role for clinical testing in affected individuals. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure‐induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. Methods: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM− (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). Results: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM− subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM− an established association. Burden analysis did not identify any single burdened gene or gene set. Significance: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene–disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM− and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM− remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Although previous studies have reported a bidirectional relationship between ischemic stroke (IS) and epilepsy, the existence of a causal nexus and its directionality remains a topic of controversy. Methods: The single nucleotide polymorphisms (SNPs) associated with IS were extracted from the Genome-Wide Association Study (GWAS) database. Pooled genetic data encompassing all epilepsy cases, as well as generalized and focal epilepsy subtypes, were acquired from the International League Against Epilepsy's GWAS study. In this study, the primary analysis approach utilized the inverse variance weighting (IVW) method as the main analytical technique. To enhance the robustness of the findings against potential pleiotropy, additional sensitivity analyses were conducted. Results: In the forward analysis, the IVW method demonstrated that IS was associated with an increased risk of all epilepsy (odds ratio (OR) = 1.127, 95 % confidence interval (CI) = 1.038–1.224, P = 0.004) and generalized epilepsy (IVW: OR = 1.340, 95 % CI = 1.162–1.546, P = 5.70 × 10–5). There was no substantial causal relationship observed between IS and focal epilepsy (P > 0.05). Furthermore, generalized epilepsy, focal epilepsy, and all epilepsy did not show a causal relationship with IS. Conclusion: This Mendelian randomization (MR) analysis demonstrates that IS increases the risk of developing epilepsy, especially generalized epilepsy. Conversely, no clear causal association was found between epilepsy and the onset of stroke. Therefore, the possible mechanisms of the effect of epilepsy on the pathogenesis of IS still need to be further investigated.

The main goal of epilepsy therapy is to improve the patient’s quality of life (QoL), which is a holistic indicator that reflects satisfaction with life in various areas. Currently existing questionnaires: QOLIE-89, QOLIE-31 and QOLIE-10 are adapted for use in Russia, but require a certain, sometimes considerable amount of time to complete them and then process. The five-point scale for assessing the QoL of epilepsy patients (SCALE 5) requires answering only one question: “Grade your general well-being on a five-point school scale at this moment?” and allows to get the necessary information in seconds, without using special forms and calculation formulas. The QoL is assessed by analogy with a Russian five-point school grading system, where 5 is an excellent grade, 4 is good etc. The resulting score serves as an immediate guideline for the doctor for further treatment of the patient: with a score of 3 (satisfactory), the cause of the reduced QoL should be identified and corrected (whether it is related to the illness, adverse events, anxiety/depression, etc.), and with scores of 2 and 1, immediate intervention is required: correction of therapy, consultation with a psychiatrist, possibly hospitalization. Here we present the results of more than 25 years of using SCALE 5. SCALE 5 is easy for patients to understand and for clinicians to use in the limited time of an outpatient appointment. The typical clinical scenarios and practical recommendations for determining the SCALE 5 score presented in the article are intended to facilitate the work of specialists in the fields of neurology, epileptology and psychiatry.

This survey analyzed data obtained through a questionnaire on the clinical approaches used by veterinarians to treat dogs with epileptic seizures. We found that neurological examinations were performed by 12% of the respondents, blood tests by 85%, and computed tomography by 72%. In addition, serology for infectious disease detection was mentioned by 30% of the respondents, and 72% did not classify epileptic seizures. According to the answers, the treatment of choice was phenobarbital in 100% of cases which was combined with potassium bromide in 19%. Moreover, 51% of the respondents mentioned that they monitored the serum phenobarbital levels. The study results showed disagreements on the conduct and care recommended by the International Veterinary Epilepsy Task Force consensus. [ABSTRACT FROM AUTHOR]

Objectives: The objective were to evaluate structural alterations in the retina and choroid tissue of epilepsy patients and subtypes using enhanced depth imaging optic coherence tomography (EDI-OCT). Methods: 46 epilepsy patients and 50 sex- and age-matched control patients were analyzed in the study. Patients' epilepsy types were recorded. The central macular thickness (CMT), retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and choroidal thickness (CT) were investigated through the Spectralis-OCT device (SD-OCT). Image-J program was used to calculate the total choroidal area (TCA), the luminal area (LA), stromal area (SA), and the choroidal vascularity index (CVI). Results: CMT, TCA, LA, and SA outcomes were substantially reduced in epilepsy patients than in healthy controls. There was no significant difference between CT, RNFL, GCL, CVI results. There were no statistically significant differences between patients with partial and generalized epilepsy (p>0.05 for each). Conclusion: According to the results of our study, epilepsy disease has effects on the posterior segment of the eye. To the best of our knowledge, our study is the first to evaluate CVI in patients with epilepsy and the epilepsy subgroups. [ABSTRACT FROM AUTHOR]

Background: Reflex epilepsy is an epileptic event precipitated by external stimuli such as flashes of light or internal mental process like thinking or calculation and/or associated with photo-paroxysmal response on electroencephalogram [EEG].The Aim of the work: To identify clinical, neuroradiological and EEG findings of children with reflex epilepsy. Patients and Methods: The study included children with reflex epilepsy who attended the outpatient Pediatric Clinics of Neurology Department at Al-Azhar University hospitals in the period between the starting of June 2022 and the end of march 2023, We conducted a hospital-based study [case series]. Reflex epilepsy in children younger than 18 years old is necessary of inclusion. These cases underwent complete neurological history, examination, electro-encephalo-gram and brain magnetic resonance imaging.Results: Twenty of 400 patients had reflex epilepsy and 16 of these patients the most frequent stimuli of seizures were photosensitivity while, one patient had seizures precipitated by hot water, one patient had seizures precipitated by visual stimuli and startle response, one patient had startle epilepsy and one patient had musicogenic epilepsy. Clinical neurological examination was normal in 85% while magnetic resonance imaging of the brain was normal in 80% of patients. 12 out of 20 patients had abnormal EEGs discharges. The most Frequent prescribed drug was sodium valproate followed by levetiracetam.Conclusion: The frequency of reflex epilepsy was 5%, the family history of epilepsy was quite common, head trauma and history of febrile convulsion was significant predisposing factors, most of patients had normal neurological examination, MRI findings and EEG abnormality were detected in 60% of patients.

The review considers pharmacological characteristics of new antiepileptic drugs (AEDs) of the third generation such as eslicarbazepine, lacosamide, retigabine, perampanel, everolimus, brivaracetam, zonisamide. The data on the mechanisms of action, pharmacokinetics, drug interactions, indications for use and side effects are presented. The drugs are recognized as superior in safety and efficacy to previously known AEDs of the first and second generations. The majority of new AEDs is used to control focal seizures, as well as in specific epileptic syndromes (Lennox–Gastaut syndrome, Dravet syndrome), and tuberous sclerosis. The drugs differ in the mechanism of action, pharmacokinetic properties, effectiveness and profile of side effects, which account for an opportunity to apply a personalized approach to patient treatment. Properly selected therapy allows to achieve good control over epileptic seizures as well as lower a risk of disease-related complications. While prescribing AEDs, it is necessary to take into account their pharmacokinetic and pharmacodynamic features.

Objective: Psychoses of epilepsy usually have an acute onset, accompanied by brief symptom duration and a risk of recurrence. Managing these conditions can be challenging due to the potential for seizures associated with certain antipsychotic medications, as well as exacerbating psychosis resulting from some antiepileptic medications. Our objective in this study was to assess the occurrence of psychosis among patients with epilepsy, as well as identify the factors linked to the presence and severity of psychosis in this population. Method: In this study, we included a total of 514 subjects diagnosed with epilepsy referring to our neuropsychiatry clinic affiliated with Tehran University of Medical Sciences from April 2011 to December 2021, among whom 57 patients showed psychotic presentations. We compared baseline and clinical characteristics between patients with psychosis of epilepsy and non-psychosis patients who also had epilepsy. Results: Marital status was the sole demographic factor that displayed a statistically significant difference between the psychosis and non-psychosis groups (P = 0.019). There was no significant difference observed between the two groups regarding family history of epilepsy and age at the onset of the epilepsy. Patients with psychosis experienced significantly more frequent seizures and generalized type (P < 0.001). Participants were matched for demographics and other clinical factors between the refractory and controlled psychosis groups, except for the psychosis frequency (P = 0.007). The type of epilepsy was significantly associated with psychosis when adjusted for the covariates (P < 0.001). Conclusion: Patients with psychosis of epilepsy experienced more episodes of epilepsy than non-psychotics. We identified generalized epilepsy as an independent risk factor for the development of psychosis. Additional cohorts are warranted to explore the factors associated with epilepsy-related psychosis across diverse populations. [ABSTRACT FROM AUTHOR]

ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

Objective: Psychoses of epilepsy usually have an acute onset, accompanied by brief symptom duration and a risk of recurrence. Managing these conditions can be challenging due to the potential for seizures associated with certain antipsychotic medications, as well as exacerbating psychosis resulting from some antiepileptic medications. Our objective in this study was to assess the occurrence of psychosis among patients with epilepsy, as well as identify the factors linked to the presence and severity of psychosis in this population. Method: In this study, we included a total of 514 subjects diagnosed with epilepsy referring to our neuropsychiatry clinic affiliated with Tehran University of Medical Sciences from April 2011 to December 2021, among whom 57 patients showed psychotic presentations. We compared baseline and clinical characteristics between patients with psychosis of epilepsy and non-psychosis patients who also had epilepsy. Results: Marital status was the sole demographic factor that displayed a statistically significant difference between the psychosis and non-psychosis groups (P = 0.019). There was no significant difference observed between the two groups regarding family history of epilepsy and age at the onset of the epilepsy. Patients with psychosis experienced significantly more frequent seizures and generalized type (P < 0.001). Participants were matched for demographics and other clinical factors between the refractory and controlled psychosis groups, except for the psychosis frequency (P = 0.007). The type of epilepsy was significantly associated with psychosis when adjusted for the covariates (P < 0.001). Conclusion: Patients with psychosis of epilepsy experienced more episodes of epilepsy than non-psychotics. We identified generalized epilepsy as an independent risk factor for the development of psychosis. Additional cohorts are warranted to explore the factors associated with epilepsy-related psychosis across diverse populations.

• Prevalence of psychiatric comorbidity in epilepsy was 35%. • The prevalence was equal in focal and generalized epilepsy. • Unknown cause of focal epilepsy was significantly related to psychiatric disorders. • Comorbidity prevalence was independent of seizure control at last follow-up. • The rate of psychiatric disorders was high even in epilepsy resolved. Prevalence of psychiatric disorders in people with epilepsy is high. However, diagnostic validity and information about the nature of the seizure disorders are often poor in population-based studies. In a well validated and classified patient sample, we investigated psychiatric comorbidity according to clinical characteristics. Participants in The Trøndelag Health Study (HUNT) with ≥ 2 diagnostic epilepsy codes during 1987–2019 were identified. Medical records were reviewed, and epilepsy was validated and classified according to ILAE. Psychiatric comorbidity was defined by ICD-codes. In 448 individuals with epilepsy, 35% had at least one psychiatric disorder (anxiety and related disorders 23%, mood disorders 15%, substance abuse and personality disorders 7%, and psychosis 3%). Comorbidity was significantly higher in women than in men (p = 0.007). The prevalence of psychiatric disorders was 37% in both focal and generalized epilepsy. In focal epilepsy, it was significantly lower when etiology was structural (p = 0.011), whereas it was higher when the cause was unknown (p = 0.024). Comorbidity prevalence was 35% both in patients achieving seizure freedom and in those with active epilepsy but 38% among 73 patients with epilepsy resolved. Just over one third of people with epilepsy had psychiatric comorbidities. The prevalence was equal in focal and generalized epilepsy but was significantly higher in focal epilepsy of unknown cause compared to lesional epilepsy. Comorbidity was independent of seizure control at last follow-up but was slightly more common in those with resolved epilepsy, often having non-acquired genetic etiologies possibly linked to neuropsychiatric susceptibility. [Display omitted] [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) was the first device-based therapy for epilepsy, having launched in 1994 in Europe and 1997 in the United States. Since then, significant advances in the understanding of the mechanism of action of VNS and the central neurocircuitry that VNS modulates have impacted how the therapy is practically implemented. However, there has been little change to VNS stimulation parameters since the late 1990s. Short bursts of high frequency stimulation have been of increasing interest to other neuromodulation targets e.g., the spine, and these high frequency bursts elicit unique effects in the central nervous system, especially when applied to the vagus nerve. In the current study, we describe a protocol design that is aimed to assess the impact of high frequency bursts of stimulation, called "Microburst VNS", in subjects with refractory focal and generalized epilepsies treated with this novel stimulation pattern in addition to standard anti-seizuremedications. This protocol also employed an investigational, fMRI-guided titration protocol that permits personalized dosing of Microburst VNS among the treated population depending on the thalamic blood-oxygen-level-dependent signal. The study was registered on clinicaltrials.gov (NCT03446664). The first subject was enrolled in 2018 and the final results are expected in 2023. [ABSTRACT FROM AUTHOR]

The increasing incidence of epilepsy has led to the need for automatic systems that can provide accurate diagnoses in order to improve the life quality of people suffering from this neurological disorder. This paper proposes a method to automatically classify epilepsy types using EEG recordings from two databases. This approach uses the spectral power density of intrinsic mode functions (IMFs) that are obtained through the empirical mode decomposition (EMD) of EEG signals. The spectral power density of IMFs has been applied as features for the classification of focal and non-focal, as well as of focal and generalized EEG signals. The data are then classified using K-nearest Neighbor (KNN) and Naïve Bayes (NB) classifiers. The focal and non-focal data were classified with high accuracy, with KNN and NB classifiers achieving a maximum classification rate of 99.90% and 99.80%, respectively. Focal and generalized epilepsy data were classified with high rates of accuracy during wakefulness and sleep stages, with KNN achieving a maximum rate of 99.49% and NB achieving 99.20%. This method shows significant improvements in the classification of EEG signals in epilepsy compared to previous studies. It could potentially aid clinical decisions for epilepsy patients. [ABSTRACT FROM AUTHOR]

Objective: There are three neurostimulation devices available to treat generalized epilepsy: vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). However, the choice between them is unclear due to lack of head‐to‐head comparisons. A systematic comparison of neurostimulation outcomes in generalized epilepsy has not been performed previously. The goal of this meta‐analysis was to determine whether one of these devices is better than the others to treat generalized epilepsy. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines, a systematic review of PubMed, Embase, and Web of Science was performed for studies reporting seizure outcomes following VNS, RNS, and DBS implantation in generalized drug‐resistant epilepsy between the first pivotal trial study for each modality through August 2022. Specific search criteria were used for VNS ("vagus", "vagal", or "VNS" in the title and "epilepsy" or "seizure"), DBS ("deep brain stimulation", "DBS", "anterior thalamic nucleus", "centromedian nucleus", or "thalamic stimulation" in the title and "epilepsy" or "seizure"), and RNS ("responsive neurostimulation" or "RNS" in the title and "epilepsy" or "seizure"). From 4409 articles identified, 319 underwent full‐text reviews, and 20 studies were included. Data were pooled using a random‐effects model using the meta package in R. Results: Sufficient data for meta‐analysis were available from seven studies for VNS (n = 510) and nine studies for DBS (n = 87). Data from RNS (five studies, n = 18) were insufficient for meta‐analysis. The mean (SD) follow‐up durations were as follows: VNS, 39.1 (23.4) months; DBS, 23.1 (19.6) months; and RNS, 22.3 (10.6) months. Meta‐analysis showed seizure reductions of 48.3% (95% confidence interval [CI] = 38.7%–57.9%) for VNS and 64.8% (95% CI = 54.4%–75.2%) for DBS (p =.02). Significance: Our meta‐analysis indicates that the use of DBS may lead to greater seizure reduction than VNS in generalized epilepsy. Results from RNS use are promising, but further research is required. [ABSTRACT FROM AUTHOR]

Introduction: The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. Methods: This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three ormore previous antiseizuremedications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results: The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p=0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). Discussion: This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures. [ABSTRACT FROM AUTHOR]

ABSTRACT: This survey analyzed data obtained through a questionnaire on the clinical approaches used by veterinarians to treat dogs with epileptic seizures. We found that neurological examinations were performed by 12% of the respondents, blood tests by 85%, and computed tomography by 72%. In addition, serology for infectious disease detection was mentioned by 30% of the respondents, and 72% did not classify epileptic seizures. According to the answers, the treatment of choice was phenobarbital in 100% of cases which was combined with potassium bromide in 19%. Moreover, 51% of the respondents mentioned that they monitored the serum phenobarbital levels. The study results showed disagreements on the conduct and care recommended by the International Veterinary Epilepsy Task Force consensus.

Vagus nerve stimulation (VNS) was the first device-based therapy for epilepsy, having launched in 1994 in Europe and 1997 in the United States. Since then, significant advances in the understanding of the mechanism of action of VNS and the central neurocircuitry that VNS modulates have impacted how the therapy is practically implemented. However, there has been little change to VNS stimulation parameters since the late 1990s. Short bursts of high frequency stimulation have been of increasing interest to other neuromodulation targets e.g., the spine, and these high frequency bursts elicit unique effects in the central nervous system, especially when applied to the vagus nerve. In the current study, we describe a protocol design that is aimed to assess the impact of high frequency bursts of stimulation, called “Microburst VNS”, in subjects with refractory focal and generalized epilepsies treated with this novel stimulation pattern in addition to standard anti-seizure medications. This protocol also employed an investigational, fMRI-guided titration protocol that permits personalized dosing of Microburst VNS among the treated population depending on the thalamic blood-oxygen-level-dependent signal. The study was registered on clinicaltrials.gov (NCT03446664). The first subject was enrolled in 2018 and the final results are expected in 2023.

IntroductionThe PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.MethodsThis post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.ResultsThe Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031).DiscussionThis study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

Background: Effective treatment of epilepsy is a major challenge in the field of neurology. Studies have suggested that melatonin can work in epilepsy with a good safety profile. Objectives: This study was performed to determine the effectiveness of melatonin in seizure outcomes, as well as the quality of sleep in patients with generalized epilepsy. Methods: In this cross‐over clinical trial study, 60 patients with epilepsy with idiopathic generalized tonic‐clonic seizures alone (EGTCS) and under valproic acid treatment received either melatonin or placebo with a washout period of 2 weeks intermittently. Outcome variables included a reduction in the severity and frequency of epilepsy besides improvement in electroencephalogram (EEG) abnormalities and sleep quality. Results: By adding melatonin, a decrease in the mean severity score of epilepsy (according to the Chalfont questionnaire) was 32.33 ± 9.24, while it was 5.58 ± 14.28 in treatment with placebo (p =.002). Evaluation of the number of attacks and EEG results did not disclose any therapeutic efficacy in treatment with melatonin versus placebo. The quality of sleep improved in 40% (first round) and 53.4% (second round) of subjects who received melatonin (p <.001). Conclusions: Considering that the addition of melatonin to routine anti‐seizure treatment was effective in reducing the severity of epilepsy and improving sleep quality, it seems that melatonin can be useful as an adjunct therapy for EGTCS in well‐defined circumstances. [ABSTRACT FROM AUTHOR]

Because epilepsy pathogenesis is affected by serum minerals and antioxidant enzymes, this study was designed to evaluate whether there was a relationship among electrolytes (Na, Ca, K, Cl, P, Mg), trace elements (Fe, Zn, Cu) and oxidative stress in patients with generalized or focal epilepsy. Twenty healthy individuals (control group), and 20 focal and 20 generalized epilepsy patients (patient groups) were included in the study. Control and patient groups were matched with age (30-40 years old), body mass index (25-28) and sex (10 males and 10 females). Serum Na, Ca, K, Cl, P, Mg and Fe levels were analyzed in an autoanalyzer, serum Zn and Cu were analyzed in a mass spectrophotometer, total antioxidant status, total oxidant status and myeloperoxidase levels were measured spectrophotometrically. The oxidative stress index increased (p<0.001) and the serum Na levels decreased (p<0.001) in focal epilepsy patients compared to the controls. It has been concluded these changes may make focal epilepsy pati ents more susceptible to seizures than generalized epilepsy patients. [ABSTRACT FROM AUTHOR]

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• We reviewed 579 consecutive patients who visited for seizure evaluation. • We examined the head-turning sign during the initial medical interview. • Matched data confirmed a significant association between IGE and head-turning sign. • The sign was also associated with myoclonic seizures and comorbid headaches. • The sign may suggest dependence on others or mild cognitive impairment in IGE. Utilizing interictal manifestations for the diagnosis of epilepsy is challenging. We investigated whether an interictal "head-turning sign," typically indicative of dependence on others observed in Alzheimer's disease, can act as a behavioral marker of idiopathic generalized epilepsy. This multicenter study examined 579 consecutive patients, with a mean age of 36.8 ± 20.4 years, who did not have an intellectual disability and had their first outpatient visit for epilepsy evaluation between 2019 and 2023. Patients were categorized into IGE, non-IGE epilepsy, non-epileptic, and psychiatric conditions based on their ultimate diagnostic outcomes to identify difference of the occurrence of the head-turning sign among them. Additionally, we extracted data from patients under the age of 40, specifically adolescents and young adults (AYA). Then we used propensity score matching to confirm the reproducibility of observed differences and to identify associated factors within the AYA age group. The occurrence of the head-turning sign was significantly more prevalent in the IGE group compared to the non-IGE group (20.4 % vs. 2.2 %; P<0.0001) and non-epileptic group (20.4 % vs. 8.3 %; P=0.033). Following the matching, the head-turning sign was still evident in IGE relative to non-IGE patients (14.6 % vs. 4.5; P=0.004), yielding a 94 % specificity for IGE. IGE diagnosis (P<0.0001), myoclonic seizure (P<0.0001), being visited by a parent (P=0.017), and comorbidity with headache (P=0.021) were significantly associated with the head-turning sign. Multivariate analysis revealed that IGE (odds ratio: OR=2.80, P=0.028), attending with a parent (OR=2.92, P=0.029), and comorbidity with headache (OR=4.06, P=0.016) were independently associated with the head-turning sign. We confirmed a substantial association between the interictal "head-turning sign" and IGE. This unique sign may reflect a tendency towards dependence on others in IGE, and may serve as a promising diagnostic auxiliary marker for identifying IGE in the AYA age group. [ABSTRACT FROM AUTHOR]

Epilepsy is characterized by recurrent, chronic, and unprovoked seizures. Epilepsy has a significant negative impact on a patient's quality of life even if seizures are well controlled. In addition to the distress caused by seizures, patients with epilepsy (PwE) may suffer from cognitive impairment with serious social consequences such as poor interpersonal relationships, loss of employment, and reduced social networks. Pathological changes and functional connectivity abnormalities observed in PwE can disrupt the neural network responsible for the theory of mind. Theory of mind is the ability to attribute mental states to other people (intentions, beliefs, and emotions). It is a complex aspect of social cognition and includes cognitive and affective constructs. In recent years, numerous studies have assessed the relationship between social cognition, including the theory of mind, in PwE, and suggested impairment in this domain. Interventions targeting the theory of mind can be potentially helpful in improving the quality of life of PwE. [ABSTRACT FROM AUTHOR]

Abstract Epilepsy has been extensively studied as a common neurological disease. Efforts have been made on rodent and other animal models to reveal the pathogenic mechanisms of epilepsy and develop new drugs for treatment. However, the features of current epilepsy models cannot fully mimic different types of epilepsy in humans, hence non-human primate models of epilepsy are required. The common marmoset (Callithrix jacchus) is a New World monkey that is widely used to study brain function. Here, we present a natural marmoset model of generalized epilepsy. In this unique marmoset family, generalized epilepsy was successfully induced by handling operations in some individuals. We mapped the marmoset family with handling-sensitive epilepsy and found that the epileptic phenotype can be inherited. These marmosets were more sensitive to the epilepsy inducers pentylenetetrazol. Using electrocorticogram (ECoG) recordings, we detected epileptiform discharge in marmosets with a history of seizures. In summary, we report a family of marmosets with generalized seizures induced by handling operations. This epileptic marmoset family provides insights to better understand the mechanism of generalized epilepsy and helps to develop new therapeutic methods.

Background: Progressive myoclonus epilepsy (PME) is a group of heterogeneous genetic disorders characterized by action myoclonus, epileptic seizures, and progressive neurologic deterioration with onset of symptoms in adolescence and adulthood. Unverricht–Lundborg disease (ULD) is the most common type of PME in high-income countries; however, it is under-reported from India due to challenges in clinical recognition and establishment of diagnosis due to lack of availability of genetic studies. Clinical Description: We herewith report three siblings (two girls and a boy) born out of a third-degree consanguineous marriage, with onset of “difficult-to-treat” seizures since early adolescence, with concurrent action myoclonus and ataxia. All three had a waxing and waning course. Electroencephalography exhibited generalized spike-wave and polyspike-wave discharges with photosensitivity while neuroimaging was normal. Management and Outcome: The possibility of PME was considered in view of the clinical phenotype and strong family history. Following detailed elicitation of history, focused physical examination, and rational investigative work-up specific molecular genetic testing were planned for ULD. This showed homozygous expansion of dodecamer (set of 12 nucleotides) repeat in the cystatin B gene in all the three affected siblings. The parents were heterozygous carriers. Genetic counseling was undertaken and anticonvulsant drugs (ACDs) modified accordingly. The definitive diagnosis helped in accurate prognostication and management to improve the quality of life of all three siblings. Conclusion: Clinicians should consider a specific epilepsy syndrome in patients with onset of symptoms in adolescence. ULD is a type of PME with a relatively better course of illness. Establishing the diagnosis has implications on the extent of investigative workup, choice of ACD, and prognosis.

Abstract Background Effective treatment of epilepsy is a major challenge in the field of neurology. Studies have suggested that melatonin can work in epilepsy with a good safety profile. Objectives This study was performed to determine the effectiveness of melatonin in seizure outcomes, as well as the quality of sleep in patients with generalized epilepsy. Methods In this cross‐over clinical trial study, 60 patients with epilepsy with idiopathic generalized tonic‐clonic seizures alone (EGTCS) and under valproic acid treatment received either melatonin or placebo with a washout period of 2 weeks intermittently. Outcome variables included a reduction in the severity and frequency of epilepsy besides improvement in electroencephalogram (EEG) abnormalities and sleep quality. Results By adding melatonin, a decrease in the mean severity score of epilepsy (according to the Chalfont questionnaire) was 32.33 ± 9.24, while it was 5.58 ± 14.28 in treatment with placebo (p = .002). Evaluation of the number of attacks and EEG results did not disclose any therapeutic efficacy in treatment with melatonin versus placebo. The quality of sleep improved in 40% (first round) and 53.4% (second round) of subjects who received melatonin (p < .001). Conclusions Considering that the addition of melatonin to routine anti‐seizure treatment was effective in reducing the severity of epilepsy and improving sleep quality, it seems that melatonin can be useful as an adjunct therapy for EGTCS in well‐defined circumstances.

Objectives: To study the effect of epilepsy on the risk of injury in children. Methods: All first-born singleton children (n = 133055) born in 2001 – 2006 in Finland were included. Data was collected from national registers up to the first hospital-treated injury during the five years following the onset of epilepsy. Four matched controls were chosen for every subject. Results: Epilepsy had been diagnosed in 0.66 % of children. During follow-up, 12 % of 884 children with epilepsy and 9 % of 3536 controls were hospitalized for injuries (HR 1.387 [95 % CI 1.115 – 1.725]; p = 0.0033). Risk for injuries was higher in boys than girls (p = 0.0057). Mean age at the first injury was 6.8 years (SD 3.3, median 7, range 0–13) in subjects and 7.2 years (SD 3.2, median 8, range 1–13) in controls (p = 0.272). The rate of hospitalization did not differ according to the type of epilepsy. The risks of subjects compared to controls were not significantly different concerning the nature of injury or survival. Conclusions: Children with epilepsy are at increased risk for hospital-treated injuries. The spectrum of injuries and the risk for death due to injuries are not different in children with and without epilepsy.

Background: Epilepsy is one of the common neurological disorders affecting approximately 50 million people worldwide. Despite the recent introduction of new antiepileptic drugs, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early recognition of patients with drug-resistant epilepsy may help direct these patients to appropriate nonpharmacological treatment. Purpose: The possible use of serum microRNAs (miRNAs) as noninvasive biomarkers has been explored in various brain diseases, including epilepsy. In this study, we are aiming at analyzing the expression levels of circulating miRNA-153 and miRNA-199a in patients with generalized epilepsy and their correlation with drug resistance. Methods: Our study comprised 40 patients with generalized epilepsy and 20 healthy controls. 22 patients were drug-resistant and 18 patients were drug-responsive. The expression levels of miRNA-153 and -199a in serum were analyzed using quantitative real-time polymerase chain reaction. Data analysis was done by IBM SPSS Statistics 20.0. Results: The expression of miRNA-153 and -199a in serum was significantly downregulated in patients with generalized epilepsy compared with that of the healthy control (P <.001). Combined expression level of serum miRNA-153 and -199a had a sensitivity of 85% and a specificity of 90% in the diagnosis of generalized epilepsy. Furthermore, the expression levels of miRNA-153 and -199a were significantly decreased in drug-resistant patients compared to the drug-responsive group, and the combination of both markers gave the best results in differentiating between the two groups. Conclusion: We suggest that serum miRNAs-153 and -199a expression levels could be potential noninvasive biomarkers supporting the diagnosis of generalized epilepsy. Moreover, they could be used for the early detection of refractory generalized epilepsy. [ABSTRACT FROM AUTHOR]

• PWE had increased values of QTc and QTcd when compared to patients with PNESs. • QTc - QTcd values do not demonstrate any difference between patients with FE and GE. • PR interval is prolonged in PWE with left sided and extratemporal foci. Cardiac disturbances and rhythm abnormalities which potentially lead sudden unexpected death in epilepsy, have been extensively studied in focal epilepsies. However, studies including generalized epilepsies are scarce and it is not clear whether electrocardiogram parameters reflecting vulnerability to ventricular arrhythmias differ between these groups. Medical records of patients who were followed in epilepsy department of a tertiary center between October 2015 and September 2016 were retrospectively reviewed. 66 generalized and 64 focal epilepsy patients with eligible electrophysiological data were analyzed. QTc interval, QTcd and other electrocardiographic indices were compared between patients with focal vs generalized epilepsy. Another analysis was performed in order to disclose any difference between patients with epilepsy (n:130) and psychogenic non-epileptic seizures. A two-tailed p value < 0.05 was considered significant. There was no difference in terms of QTc and QTcd between patients with focal and generalized epilepsy [median: 406 ms vs 404 ms, p = 0.119; and median: 46 ms vs 44 ms, p = 0.497, respectively]. However patients with epilepsy were found to have longer QTc and QTcd when compared to ones with psychogenic non-epileptic seizures (p = 0.035 and p < 0.001, respectively). Current findings demonstrate that patients with epilepsy have longer QTc and QTcd than patients with pure psychogenic non-epileptic seizures. Since there was no difference between patients with focal and generalized epilepsy; QTc interval, QTcd and potential susceptibility to cardiac arrhythmias as a result, could be a consequence of epilepsy itself regardless of origin. [ABSTRACT FROM AUTHOR]

Objectives: Respiratory problems increase the number of epileptic seizures in individuals with epileptic seizures. This study aimed to determine the relationship between the number of seizures, sleep quality, and respiratory problems by evaluating the changes in respiratory parameters of epileptic patients.Methods:Thirty individuals aged 18–40 years with generalized epilepsy were included in the study. Demographic data, number of seizures per week, pulse and blood pressure measurements, age of seizures, and body mass index were recorded. Dyspnea with mMRC; pulmonary function test; level of physical activity (PA) with International physical activity assessment survey (IPAQ); mouth pressure measuring device with respiratory muscle strength; and sleep quality with Pittsburgh Sleep Quality Index (PSQI) were evaluated.Results:Thirty patients with epileptic seizures (mean age: 26.56±6.64 years) were included in the study. The mean; % maximal inspiratory pressure (MIP) 67.44, %Maximal expiratory pressure (MEP) 35.14, MIP 70.47, and MEP 62.24 cmH2 O were found. The forced expiratory volumes/ forced vital capacity (FEV1 /FVC) (41.01%) and FEV1 (62.50%; 2.56 L) was found lower than the standards. The positive correlation between the MEP, MIP, FEV1 (L), and severe PA was found. FVC with sitting, FEV1 (L) with moderate PA, and FEV1 /FVC (%) with PSQI, sitting with educational status were positively correlated (p

Purpose of Review: To summarize current evidence and recent developments in the surgical treatment of drug-resistant generalized epilepsy. Recent Findings: Current surgical treatments of drug-resistant generalized epilepsy include vagus nerve stimulation (VNS), deep brain stimulation (DBS) and corpus callosotomy (CC). Neurostimulation with VNS and/or DBS has been shown to be effective in reducing seizure frequency in patients with generalized epilepsy. DBS for generalized epilepsy is primarily consisted of open-loop stimulation directed at the centromedian (CM) nucleus in the thalamus, though closed-loop stimulation and additional targets are being explored. CC can be effective in treating some seizure types and can be performed using traditional surgical techniques or with the less invasive methods of laser ablation and radiosurgery. Summary: This current literature supports the use of VNS, DBS and CC, alone or in combination, as palliative treatments of drug-resistant generalized epilepsy. [ABSTRACT FROM AUTHOR]

Epilepsy is a group of painful conditions caused by brain disorders, which are characterized by a persistent predisposition to epileptic seizures, as well as neurobiological, cognitive, psychological and social consequences. Currently, the overall prevalence of epilepsy in the world's population is 0.88% and ranges from 0.64% in developed countries to 1.00% in other countries. The prevalence of epilepsy in men is slightly higher than in women, and heredity varies between 25%-70%. According to the current classification, epilepsy includes four main forms: focal epilepsy, generalized epilepsy, combined focal and generalized epilepsy, and indeterminate epilepsy. The most common form of epilepsy is focal epilepsy, which accounts for 60% of all epilepsies. Currently, 14 genes associated with the development of epilepsy have been described, the functions of which are impaired by the presence of single nucleotide polymorphisms (SNPs). These SNPs can be located not only in the coding regions of genes (exons) or regulatory regions (eg., promoters), but also in their non-coding regions (introns), as well as in intergenic regions of DNA near a particular gene. Further research into the genetics of epilepsy should focus on developing new analytical approaches that will help uncover the unknown molecular genetic mechanisms of this group of disorders. Advances in the genetics of epilepsy will have a positive impact on clinical practice. [ABSTRACT FROM AUTHOR]