Peri-ictal headache: An underestimated prognostic finding associated with idiopathic epilepsies.

OBJECTIVE: There are a handful of studies investigating peri-ictal headache (PIH) and its clinical associations in patients with idiopathic/genetic epilepsies (I/GE). This multi-center study aimed to investigate PIH, which is an ignored comorbid condition in patients with I/GE, by headache experts and epileptologists working together. METHODS: The data were collected from a cross-sectional large study, using two structured questionnaires for headache and epilepsy features, fulfilled by neurologists. Headaches were classified according to the International Classification of Headache Disorders, third edition, whereas seizure and syndrome types were diagnosed according to International League Against Epilepsy criteria. The patients with a headache starting 24 hours before the onset of the seizure (preictal) or within 3 hours after the seizure (postictal) were defined as patients with PIH. We compared demographic and clinical differences between two groups of patients with and without PIH statistically and used ROC curves to determine a threshold of the total number of seizure triggers associated with the occurrence of PIH. RESULTS: Among 809 (531 females, 65.6%) consecutive patients with I/GE, 105 (13%) patients reported PIH (22 preictal, 82 postictal headaches, and one with both types). Peri-ictal headache was more frequently reported by females and those having a family history of migraine or epilepsy, and it was significantly associated with lower rates of seizure freedom for more than five years, drug resistance, and use of polytherapy, remarkably. Moreover, ROC curves showed that having more than 3 seizure triggers was associated with the presence of PIH. CONCLUSION: Our findings revealed that PIH may be linked to poor outcomes in I/GEs and seems to be related to a lower ictal threshold precipitated by multiple triggers. Future prospective studies will illuminate the unknown underlying mechanisms and appropriate management strategies for PIH to improve the prognosis.

Prevalence, nature, and severity of the psychiatric comorbidities and their impact on quality of life in adolescents with Juvenile myoclonic epilepsy.

INTRODUCTION: Adults with Juvenile myoclonic epilepsy (JME) are at increased risk for psychiatric comorbidities, personality traits, and abnormality in executive function. But studies on adolescents and their impact on quality of life are scarce in the literature. MATERIALS AND METHODS: This cross-sectional study was performed between August 2019 and October 2022 to compare the prevalence of psychiatric comorbidities in adolescents with JME and age and gender-matched healthy controls. After completing DSM-5 Structured Clinical Interview (SCID-5) initially in all patients, we measured the severity of individual psychiatric problems like anxiety, depression, and somatic symptoms by using an appropriate psychometric scale. We also measured both groups' intelligence quotient (IQ), executive function, and quality of life. RESULTS: One hundred patients with JME (14.3 ± 2.5 years, 48 boys) and 100 controls were enrolled. Psychiatric disorders were observed in 46% of JME and 6% of controls (p < 0.01). Psychiatric comorbidities noted in the patients with JME were: somatic symptom and related disorders(n = 14), anxiety (n = 13), adjustment disorders (n = 12), depression (n = 11), oppositional defiant disorder (n = 6), conduct disorder (n = 5), anorexia nervosa (n = 3), narcissistic (n = 3), histrionic (n = 1), substance-related disorder (n = 1), borderline (n = 2) and antisocial personality disorder (n = 2). The prevalence of depressive disorders, anxiety disorders, adjustment disorders, somatic symptoms, related disorders, and any personality disorder was significantly more in the JME group (p < 0.01 for all). Female gender, higher Epilepsy Stigma Scale score, and lower Epilepsy Outcome Expectancy Scale were significantly associated with depressive disorders (p = 0.04, 0.03, 0.03 respectively). Similarly, for anxiety, only female gender and lower Epilepsy Outcome Expectancy Scale were significant associated factors (p = 0.03, 0.02 respectively). CONCLUSIONS: Psychiatric disorders like anxiety, depression, and personality disorders are more frequent in adolescents with JME than in controls.

DYRK1B haploinsufficiency in a Holstein cattle with epilepsy.

In this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6-month-old Holstein heifer. The seizures were characterized by a brief pre-ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic-clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter-seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice-site variant in DYRK1B (NM_001081515.1: c.-101-1G>A), most likely resulting in haploinsufficiency owing to loss-of-function. This represents a report of a DYRK1B-associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy.

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Whole Exome Sequencing Identifies a Heterozygous Variant in the Cav1.3 Gene CACNA1D Associated with Familial Sinus Node Dysfunction and Focal Idiopathic Epilepsy.

Cav1.3 voltage-gated L-type calcium channels (LTCCs) are involved in cardiac pacemaking, hearing and hormone secretion, but are also expressed postsynaptically in neurons. So far, homozygous loss of function mutations in CACNA1D encoding the Cav1.3 α1-subunit are described in congenital sinus node dysfunction and deafness. In addition, germline mutations in CACNA1D have been linked to neurodevelopmental syndromes including epileptic seizures, autism, intellectual disability and primary hyperaldosteronism. Here, a three-generation family with a syndromal phenotype of sinus node dysfunction, idiopathic epilepsy and attention deficit hyperactivity disorder (ADHD) is investigated. Whole genome sequencing and functional heterologous expression studies were used to identify the disease-causing mechanisms in this novel syndromal disorder. We identified a heterozygous non-synonymous variant (p.Arg930His) in the CACNA1D gene that cosegregated with the combined clinical phenotype in an autosomal dominant manner. Functional heterologous expression studies showed that the CACNA1D variant induces isoform-specific alterations of Cav1.3 channel gating: a gain of ion channel function was observed in the brain-specific short CACNA1D isoform (Cav1.3S), whereas a loss of ion channel function was seen in the long (Cav1.3L) isoform. The combined gain-of-function (GOF) and loss-of-function (LOF) induced by the R930H variant are likely to be associated with the rare combined clinical and syndromal phenotypes in the family. The GOF in the Cav1.3S variant with high neuronal expression is likely to result in epilepsy, whereas the LOF in the long Cav1.3L variant results in sinus node dysfunction.

Benign juvenile idiopathic epilepsy in captive Iberian lynx (Lynx pardinus) in the ex situ conservation program (2005-2019).

BACKGROUND: Benign juvenile idiopathic epilepsy has been described in humans but rarely in animals. The objectives of the study were to describe the clinical signs, clinical data, imaging findings, genetic examinations, treatment, long-term outcome and prognosis in Iberian lynx with juvenile epilepsy. Medical records, video recordings and diagnostic data from 2005 to 2019 were reviewed. RESULTS: Twenty lynx cubs with early onset of epileptic seizures (ES) from the conservation program were included. The average age at seizure onset was 75 days. Isolated and cluster ES were recorded. Focal ES, focal ES evolving into generalized ES with a stereotypical pattern and generalized ES were observed. All the cubs were normal between episodes, had a normal neurological examination and unremarkable investigations. Phenobarbital was used as a first line antiepileptic drug (AED). ES halted 10 days (0-34) after starting treatment in eight out of twenty cubs (40%). Treatment was discontinued in this group after a mean of 578 days and no further ES were reported (mean follow-up longer than 5 years). Eleven animals (55%) continued on AED treatment for a mean of 1306 days (70-3466). An adult-onset was observed for one lynx (5%). Polytherapy was necessary in seven lynxes (35%). The inheritance pattern observed was compatible with an autosomal recessive condition. Based on this assumption, mating between two identified carriers has been avoided since 2012, which may have contributed to the subsequent decrease in prevalence, with no further cases detected in 2018 and 2019. CONCLUSIONS: Lynx pardinus may have an early onset self-limiting ES syndrome characteristic of benign juvenile idiopathic epilepsy. Information obtained from this study strongly suggests a genetic basis for the here presented epilepsy.

The effect of interictal epileptiform discharges on cognitive and academic performance in children with idiopathic epilepsy.

BACKGROUND: Interictal epileptiform discharges (IEDs) have been proven to impair cognitive function. However, it is not clear whether IEDs disrupt academic performance in children with idiopathic epilepsy, and the contribution of cognitive function deficits to impaired academic performance has not been clarified. This study aimed to examine the cognitive deficits and academic impairment in childhood idiopathic epilepsy with IEDs. METHODS: Ninety-seven childhood idiopathic epilepsy with IEDs, 77 childhood idiopathic epilepsy without IEDs, and 71 healthy controls completed a series of cognitive tests. We analyzed the cognitive performance in several domains including language, mathematics, psychomotor speed, spatial ability, memory, general intelligence, attention and executive functioning. Analysis of variance was conducted to compare the performance on all tests between the three groups. RESULTS: Childhood idiopathic epilepsy with IEDs exhibited not only general cognitive deficits in processing speed, spatial ability, and attention, but also arithmetic impairment. Furthermore, general cognitive deficits could account for the impaired arithmetic performance in childhood idiopathic epilepsy with IEDs. CONCLUSIONS: Our study suggested that IEDs in children with idiopathic epilepsy affected both cognitive function and academic performance, and that the cognitive deficits may be responsible for arithmetic performance impairment.

Molecular alterations of the TLR4-signaling cascade in canine epilepsy.

BACKGROUND: Cumulating evidence from rodent models points to a pathophysiological role of inflammatory signaling in the epileptic brain with Toll-like receptor-4 signaling acting as one key factor. However, there is an apparent lack of information about expression alterations affecting this pathway in canine patients with epilepsy. Therefore, we have analyzed the expression pattern of Toll-like receptor 4 and its ligands in brain tissue of canine patients with structural or idiopathic epilepsy in comparison with tissue from laboratory dogs or from owner-kept dogs without neurological diseases. RESULTS: The analysis revealed an overexpression of Toll-like receptor-4 in the CA3 region of dogs with structural epilepsy. Further analysis provided evidence for an upregulation of Toll-like receptor-4 ligands with high mobility group box-1 exhibiting increased expression levels in the CA1 region of dogs with idiopathic and structural epilepsy, and heat shock protein 70 exhibiting increased expression levels in the piriform lobe of dogs with idiopathic epilepsy. In further brain regions, receptor and ligand expression rates proved to be either in the control range or reduced below control levels. CONCLUSIONS: Our study reveals complex molecular alterations affecting the Toll-like receptor signaling cascade, which differ between epilepsy types and between brain regions. Taken together, the data indicate that multi-targeting approaches modulating Toll-like receptor-4 signaling might be of interest for management of canine epilepsy. Further studies are recommended to explore respective molecular alterations in more detail in dogs with different etiologies and to confirm the role of the pro-inflammatory signaling cascade as a putative target.

Benign epilepsy with centrotemporal spikes: Correlating spike frequency and neuropsychology.

OBJECTIVES: Neuropsychological sequelae are a feature of benign epilepsy with centrotemporal spikes (BECTS) in children. A correlation between the frequency of interictal EEG discharges and the cognitive as well as behavioral profile of the patients has been suspected but not proven. MATERIALS AND METHODS: Children with BECTS that had not yet been treated were included into a randomized controlled trial. In the initial visit, EEGs were recorded. The frequency of interictal discharges was quantified. Correlations between the discharge frequency and the performance in a neuropsychological test battery were examined. RESULTS: The cognitive test results were within or slightly above normal range (Culture-free intelligence test: 99.4%-confidence interval [CI]: [50.3, 59.9], test standardized to a population mean of 50). Parent-reported behavioral abnormalities were statistically significantly increased (CBCL total score CI: [51.9, 61.9], population mean as above). Correlations between the frequency of interictal epileptic discharges and the test results could not be identified (lowest encountered P-value: 0.034, not significant after correction for multiple testing). CONCLUSION: The data do not support the hypothesis that the frequency of the interictal EEG discharges influences the neurocognitive performance or behavioral parameters of children with BECTS.

Cognitive functions, electroencephalographic and diffusion tensor imaging changes in children with active idiopathic epilepsy.

INTRODUCTION: Neurocognitive impairment represents one of the most common comorbidities occurring in children with idiopathic epilepsy. Diagnosis of the idiopathic form of epilepsy requires the absence of any macrostructural abnormality in the conventional MRI. Though changes can be seen at the microstructural level imaged using advanced techniques such as the Diffusion Tensor Imaging (DTI). AIM OF THE WORK: The aim of this work is to study the correlation between the microstructural white matter DTI findings, the electroencephalographic changes and the cognitive dysfunction in children with active idiopathic epilepsy. METHODS: A comparative cross-sectional study, included 60 children with epilepsy based on the Stanford-Binet 5th Edition Scores was conducted. Patients were equally assigned to normal cognitive function or cognitive dysfunction groups. The history of the epileptic condition was gathered via personal interviews. All patients underwent brain Electroencephalography (EEG) and DTI, which was analyzed using FSL. RESULTS: The Fractional Anisotropy (FA) was significantly higher whereas the Mean Diffusivity (MD) was significantly lower in the normal cognitive function group than in the cognitive dysfunction group. This altered microstructure was related to the degree of the cognitive performance of the studied children with epilepsy. The microstructural alterations of the neural fibers in children with epilepsy and cognitive dysfunction were significantly related to the younger age of onset of epilepsy, the poor control of the clinical seizures, and the use of multiple antiepileptic medications. CONCLUSION: Children with epilepsy and normal cognitive functions differ in white matter integrity, measured using DTI, compared with children with cognitive dysfunction. These changes have important cognitive consequences.

ADAM23 is a common risk gene for canine idiopathic epilepsy.

BACKGROUND: Idiopathic or genetic adult-onset epilepsy is a common neurological disorder in domestic dogs. Genetic association has been reported only with ADAM23 on CFA 37 in few breeds. To identify novel epilepsy genes, we performed genome-wide association (GWA) analyses in four new breeds, and investigated the association of the previously reported ADAM23 haplotype with the epilepsy phenotype in eight breeds. RESULTS: GWA analysis did not reveal new epilepsy loci. ADAM23 association (p < 0.05) was identified in five breeds. Combined analysis of all eight breeds showed significant association (p = 4.6e-6, OR 1.9). CONCLUSIONS: Our results further support the role of ADAM23 in multiple breeds as a common risk gene for epilepsy with low penetrance. The lack of findings in the GWA analyses points towards inefficient capture of genetic variation by the current SNP arrays, causal variant(s) with low penetrance and possible phenocopies. Future work will include studies on ADAM23 function and expression in canine neurons, as well as whole-genome sequencing in order to identify additional IE genes.

Clinical evaluation of a combination therapy of imepitoin with phenobarbital in dogs with refractory idiopathic epilepsy.

BACKGROUND: Imepitoin was tested as a combination treatment with phenobarbital in an open-label mono-centre cohort study in dogs with drug-resistant epilepsy. Diagnosis of idiopathic epilepsy was based on clinical findings, magnetic resonance imaging and cerebrospinal fluid analysis. Three cohorts were treated. In cohort A, dogs not responding to phenobarbital with or without established add-on treatment of potassium bromide or levetiracetam were treated add-on with imepitoin, starting at 10 mg/kg BID, with titration allowed to 30 mg/kg BID. In cohort B, the only difference to cohort A was that the starting dose of imepitoin was reduced to 5 mg/kg BID. In cohort C, animals not responding to imepitoin at >20 mg/kg BID were treated with phenobarbital add-on starting at 0.5 mg/kg BID. RESULTS: The add-on treatment resulted in a reduction in monthly seizure frequency (MSF) in all three cohorts. A reduction of ≥50% was obtained in 36-42% of all animals, without significant difference between cohorts. The lower starting dose of 5 mg/kg BID imepitoin was better tolerated, and an up-titration to on average of 15 mg/kg BID was sufficient in cohort A and B. In cohort C, a mean add-on dose of 1.5 mg/kg BID phenobarbital was sufficient to achieve a clinically meaningful effect. Six dogs developed a clinically meaningful increase in MSF of ≥ 50%, mostly in cohort A. Neither imepitoin nor phenobarbital add-on treatment was capable of suppressing cluster seizure activity, making cluster seizure activity an important predictor for drug-resistance. CONCLUSION: A combination treatment of imepitoin and phenobarbital is a useful treatment option for a subpopulation of dogs with drug-resistant epilepsy, a low starting dose with 5 mg/kg BID is recommended.

A prospective observational longitudinal study of new-onset seizures and newly diagnosed epilepsy in dogs.

BACKGROUND: Seizures are common in dogs and can be caused by non-epileptic conditions or epilepsy. The clinical course of newly diagnosed epilepsy is sparsely documented. The objective of this study was to prospectively investigate causes for seizures (epileptic and non-epileptic) in a cohort of dogs with new-onset untreated seizures, and for those dogs with newly diagnosed epilepsy to investigate epilepsy type, seizure type and the course of disease over time, including the risk of seizure recurrence. Untreated client-owned dogs experiencing new-onset seizures were prospectively enrolled in a longitudinal observational study including clinical investigations and long-term monitoring at the Copenhagen University Hospital for Companion Animals. A baseline clinical assessment was followed by investigator/owner contact every eight weeks from inclusion to death or end of study. Inclusion of dogs was conducted from November 2010 to September 2012, and the study terminated in June 2014. RESULTS: One hundred and six dogs were included in the study. Seventy-nine dogs (74.5%) were diagnosed with epilepsy: 61 dogs (77.2%) with idiopathic epilepsy, 13 dogs (16.5%) with structural epilepsy and five dogs (6.3%) with suspected structural epilepsy. A non-epileptic cause for seizures was identified in 13 dogs and suspected in 10 dogs. Four dogs in which no cause for seizures was identified experienced only one seizure during the study. In dogs with idiopathic epilepsy 60% had their second epileptic seizure within three months of seizure onset. Twenty-six dogs with idiopathic epilepsy (43%) completed the study without receiving antiepileptic treatment. The natural course of idiopathic epilepsy (uninfluenced by drugs) was illustrated by highly individual and fluctuating seizure patterns, including long periods of remission. Cluster seizures motivated early treatment. In a few dogs with a high seizure frequency owners declined treatment against the investigators advice. CONCLUSIONS: Epilepsy is the most likely diagnosis in dogs presenting with new-onset seizures. The course of idiopathic epilepsy is highly individual and might not necessarily require long-term treatment. This must be considered when advising owners about what to expect with regard to treatment and prognosis.

Retrospective epidemiological study of canine epilepsy in Japan using the International Veterinary Epilepsy Task Force classification 2015 (2003-2013): etiological distribution, risk factors, survival time, and lifespan.

BACKGROUND: Epilepsy is the most common neurological disease in veterinary practice. However, contrary to human medicine, epilepsy classification in veterinary medicine had not been clearly defined until recently. A number of reports on canine epilepsy have been published, reflecting in part updated proposals from the human epilepsy organization, the International League Against Epilepsy. In 2015, the International Veterinary Epilepsy Task Force (IVETF) published a consensus report on the classification and definition of canine epilepsy. The purpose of this retrospective study was to investigate the etiological distribution, survival time of dogs with idiopathic epilepsy (IdE) and structural epilepsy (StE), and risk factors for survival time, according to the recently published IVETF classification. We investigated canine cases with epilepsy that were referred to our teaching hospital in Japan during the past 10 years, and which encompassed a different breed population from Western countries. RESULTS: A total of 358 dogs with epilepsy satisfied our etiological study criteria. Of these, 172 dogs (48 %) were classified as IdE and 76 dogs (21 %) as StE. Of these dogs, 100 dogs (consisting of 65 with IdE and 35 with StE) were included in our survival study. Median survival time from the initial epileptic seizure in dogs with IdE and StE was 10.4 and 4.5 years, respectively. Median lifespan of dogs with IdE and StE was 13.5 and 10.9 years, respectively. Multivariable analysis demonstrated that risk factors for survival time in IdE were high seizure frequency (≥0.3 seizures/month) and focal epileptic seizures. CONCLUSIONS: Focal epileptic seizures were identified as a risk factor for survival time in IdE. Clinicians should carefully differentiate seizure type as it is difficult to identify focal epileptic seizures. With good seizure control, dogs with IdE can survive for nearly the same lifespan as the general dog population. Our results using the IVETF classification are similar to previous studies, although some features were noted in our Japanese canine population (which was composed of mainly small-breed dogs), including a longer lifespan in dogs with epilepsy and a larger percentage of meningoencephalomyelitis of unknown origin in dogs with StE.

Pathogenic EFHC1 mutations are tolerated in healthy individuals dependent on reported ancestry.

OBJECTIVE: Screening for specific coding mutations in the EFHC1 gene has been proposed as a means of assessing susceptibility to juvenile myoclonic epilepsy (JME). To clarify the role of these mutations, especially those reported to be highly penetrant, we sought to measure the frequency of exonic EFHC1 mutations across multiple population samples. METHODS: To find and test variants of large effect, we sequenced all EFHC1 exons in 23 JME and 23 non-JME idiopathic generalized epilepsy (IGE) Hispanic patients, and 60 matched controls. We also genotyped specific EFHC1 variants in IGE cases and controls from multiple ethnic backgrounds, including 17 African American IGE patients, with 24 matched controls, and 92 Caucasian JME patients with 103 matched controls. These variants are reported to be pathogenic, but are also found among unphenotyped individuals in public databases. All subjects were from the New York City metro area and all controls were required to have no family history of seizures. RESULTS: We found the reportedly pathogenic EFHC1 P77T-R221H (rs149055334-rs79761183) JME haplotype in one Hispanic control and in two African American controls. Public databases also show that the EFHC1 P77T-R221H JME haplotype is present in unphenotyped West African ancestry populations, and we show that it can be found at appreciable frequency in healthy individuals with no family history of epilepsy. We also found a novel splice-site mutation in a single Hispanic JME patient, the effect of which is unknown. SIGNIFICANCE: Our findings raise questions about the effect of reportedly pathogenic EFHC1 mutations on JME. One intriguing possibility is that some EFHC1 mutations may be pathogenic only when introduced into specific genetic backgrounds. By focusing on data from multiple populations, including the understudied Hispanic and Black/African American populations, our study highlights that for complex traits like JME, the body of evidence necessary to infer causality is high.

Auditory verbal memory and psychosocial symptoms are related in children with idiopathic epilepsy.

OBJECTIVE: Idiopathic epilepsies are considered to have relatively good prognoses and normal or near normal developmental outcomes. Nevertheless, accumulating studies demonstrate memory and psychosocial deficits in this population, and the prevalence, severity and relationships between these domains are still not well defined. We aimed to assess memory, psychosocial function, and the relationships between these two domains among children with idiopathic epilepsy syndromes using an extended neuropsychological battery and psychosocial questionnaires. METHODS: Cognitive abilities, neuropsychological performance, and socioemotional behavior of 33 early adolescent children, diagnosed with idiopathic epilepsy, ages 9-14years, were assessed and compared with 27 age- and education-matched healthy controls. RESULTS: Compared to controls, patients with stabilized idiopathic epilepsy exhibited higher risks for short-term memory deficits (auditory verbal and visual) (p<0.0001), working memory deficits (p<0.003), auditory verbal long-term memory deficits (p<0.0021), and more frequent psychosocial symptoms (p<0.0001). The severity of auditory verbal memory deficits was related to severity of psychosocial symptoms among the children with epilepsy but not in the healthy controls. SIGNIFICANCE: Results suggest that deficient auditory verbal memory may be compromising psychosocial functioning in children with idiopathic epilepsy, possibly underscoring that cognitive variables, such as auditory verbal memory, should be assessed and treated in this population to prevent secondary symptoms.

[Psychiatric disorders and associated factors in patients with epilepsy in Fez, Morocco]. / Troubles psychiatriques et facteurs associés chez une population de patients épileptiques à Fès, Maroc.

BACKGROUND: The prevalence of psychiatric disorders in epileptic patients remains unclear. OBJECTIVE: This study was conducted in order to determine the prevalence and nature of the psychiatric disorders and the associated factors in patients with idiopathic epilepsy. METHODS: A cross-sectional study was conducted over a period of eighteen months in the psychiatric unit of the University Hospital Hassan II of Fez (Morocco). A questionnaire was completed by the included patients, which specified: the socio-demographic data, personal and family history, and the clinical features of epilepsy and its management. Psychiatric disorders were identified by the Mini International Neuropsychiatric Interview test (MINI). The severity of the depression and anxiety symptoms was investigated using the Beck Depression Inventory (BDI) and the Hamilton Rating Scale. RESULTS: Eighty-nine patients met the inclusion criteria. The average age of patients was 29.7±10.8years. Mood disorders were the leading psychiatric comorbidity: 32.6% among which 25.8% of major depressive episodes, 15.7% of dysthymia and 2.2% of hypomanic episodes. Anxiety disorders came second: 28.1% (among which 19.1% panic disorder, 13.5% agoraphobia, 12.4% generalized anxiety disorder, 10.1% social phobia and 4.5% post-traumatic stress disorder). Female gender, unemployment and poor compliance to antiepileptic drugs are all risk factors for the occurrence of psychiatric disorders in this population.

The concept of symptomatic epilepsy and the complexities of assigning cause in epilepsy.

The concept of symptomatic epilepsy and the difficulties in assigning cause in epilepsy are described. A historical review is given, emphasizing aspects of the history which are relevant today. The historical review is divided into three approximately semicentenial periods (1860-1910, 1910-1960, 1960-present). A definition of symptomatic epilepsy and this is followed by listing of causes of symptomatic epilepsy. The fact that not all the causes of idiopathic epilepsy are genetic is discussed. A category of provoked epilepsy is proposed. The complexities in assigning cause include the following: the multifactorial nature of epilepsy, the distinction between remote and proximate causes, the role of nongenetic factors in idiopathic epilepsy, the role of investigation in determining the range of causes, the fact that not all symptomatic epilepsy is acquired, the nosological position of provoked epilepsy and the view of epilepsy as a process, and the differentiation of new-onset and established epilepsy. The newly proposed ILAE classification of epilepsy and its changes in terminologies and the difficulties in the concept of acute symptomatic epilepsy are discussed, including the inconsistencies and gray areas and the distinction between idiopathic, symptomatic, and provoked epilepsies. Points to be considered in future work are listed.

PER2 rs2304672, CLOCK rs1801260, and PER3 rs57875989 polymorphisms are not associated with juvenile myoclonic epilepsy.

Sleep disturbance is common in several epilepsy types, such as juvenile myoclonic epilepsy (JME). Genetic background could increase susceptibility to seizure and sleep abnormalities. From this perspective, a susceptibility gene for sleep disturbance or chronotype could contribute to the genetic susceptibility threshold for epilepsy and vice versa. Accordingly, we investigated whether functional clock gene polymorphisms (PER2 111C>G, CLOCK 3111T>C, and PER3 VNTR) might influence the risk for JME. All these polymorphisms have recently been reported to be associated with sleep disturbance, diurnal variation, and neurological diseases. The polymorphisms were genotyped in 97 patients and 212 controls using polymerase chain reaction or restriction fragment length polymorphism methods. No significant differences were observed in the genotypic and allelic frequencies of these polymorphisms between cases and controls even when analyses were restricted to patients that presented a diurnal preferential seizure occurrence. We also tested for interactions between polymorphisms by multifactor dimensionality reduction analysis. None of the combined genotypes differed significantly between the groups. These results present no evidence for an association of these polymorphisms with JME. Further studies including other types of epilepsy and/or other functional polymorphisms are required to investigate the possible relationship between clock genes and the genetic susceptibility to chronic seizure.

Analysis of Plasma-Derived Exosomal MicroRNAs as Potential Biomarkers for Canine Idiopathic Epilepsy.

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.