Epilepsy In Males Research Articles

Social cognition in an adult epilepsy patient with developmental amnesia

ABSTRACT Reports on social cognition in patients with developmental amnesia resulting from bilateral hippocampal lesions are rare, although the link between social cognition and temporal lobe structures is well established. We present the case of a 23-year-old male epilepsy patient, BM, with developmental amnesia due to perinatal cerebral hypoxia. The patient was examined with neuroimaging and neuropsychological methods and compared to IQ-matched patients with epilepsy to control for effects of epilepsy. In addition, we used a test battery that evaluates emotion recognition and theory of mind to study his social cognition abilities. Structural high-resolution magnetic resonance imaging showed bilateral hippocampal atrophy. The comparison to controls showed that, in addition to the well-documented memory disorders in developmental amnesia, BM showed remarkable deficits in 9 out of 17 social cognitive tasks assessing emotion recognition and theory of mind. In contrast, BM’s performance on tasks of executive functions was largely preserved. The relevance of deficits in social cognition for patients with developmental amnesia is discussed.

Prevalence and treatment of neurological and psychiatric disorders among tertiary hospitals in Pakistan; findings and implications

ABSTRACT Introduction Mental health and neurological disorders are prevalent in Pakistan. However, there are considerable concerns with their management due to issues of access, availability of trained personnel and stigma alongside paucity of such data. Consequently, there is a need to document current treatment approaches starting with tertiary hospitals in Pakistan where patients with more severe mental and neurological disorders are typically treated. Subsequently, use the findings to help direct future policies and initiatives. Methods Multi-centered, cross-sectional, prospective study principally evaluating current medicine usage among patients attending tertiary hospitals in Pakistan with psychiatric and neurological disorders. In addition, possible factors contributing to the prevalence of these disorders in this population to help with future care. All 23 tertiary care hospitals in the ten major Districts in Pakistan were included, which cover 75% of the population. Results 57,664 patients were evaluated of which 35.3% were females. Both females and males had multiple brain disorders and multiple co-morbidities. Schizophrenia was the most prevalent disorder overall among both females (25.2%) and males (30.4%). A median of six medicines were prescribed per patient, with antipsychotics and antidepressants the most prescribed medicines. Clozapine was the most prescribed medicine in males (12.25%) and females (11.83%) including for psychiatric disorders, with sodium valproate the most prescribed medicine in epilepsy in males (42.44% of all anti-epileptic medicines) as well as females (46.38%). There was a greater prevalence of both disorders among the lower classes. A greater prevalence of schizophrenia was seen in patients abusing alcohol and smokers. The divorce rate was higher among the studied patients and the prevalence of depression was higher among the widowed population. Conclusions There were concerns with the quality of prescribing including the extent of polypharmacy as well as possible overuse of clozapine especially in patients with epilepsy, both of which need addressing.

The GRIA3 c.2477G > A Variant Causes an Exaggerated Startle Reflex, Chorea, and Multifocal Myoclonus.

Hemizygous mutations in GRIA3 encoding the GluA3 subunit of the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are known to be associated with neurodevelopmental disorders, including intellectual disability, hypotonia, an autism spectrum disorder, sleep disturbances, and epilepsy in males. To describe a new and consistent phenotype in 4 affected male patients associated with an undescribed deleterious variant in GRIA3. We evaluated a large French family in which segregate a singular phenotype according to an apparent X-linked mode of inheritance. Molecular analyses using next generation sequencing and in vitro functional studies using 2-electrode voltage clamp recordings on Xenopus laevis oocytes and a β-lactamase reporter assay in transfected human embryonic kidney (HEK293) cells were performed. In addition to mild intellectual disability and dysarthria, affected patients presented a tightly consistent early-onset movement disorder combining an exaggerated startle reflex with generalized chorea and multifocal myoclonus. The unreported GRIA3 missense variant c.2477G > A; p.(Gly826Asp) affecting the fourth transmembrane domain of the protein was identified in index patients and their unaffected mothers. Functional studies revealed that variant receptors show decreased current response evoked by agonist (ie, kainic acid and glutamate) and reduced expression on the cell surface in favor of pathogenicity by a loss-of-function mechanism. Taken together, our results suggest that apart from known GRIA3-related disorders, an undescribed mutation-specific singular movement disorder does exist. We thus advocate considering GRIA3 mutations in the differential diagnosis of hyperekplexia and generalized chorea with myoclonus. © 2020 International Parkinson and Movement Disorder Society.

IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients

PurposeVariants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences.MethodsWe collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms.ResultsIQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments.ConclusionThis study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.

The genetic variants in 3' untranslated region of voltage-gated sodium channel alpha 1 subunit gene affect the mRNA-microRNA interactions and associate with epilepsy.

BackgroundmRNA expression in a cell or subcellular organelle is precisely regulated for the purpose of gene function regulation. The 3’ untranslated region (3’UTR) of mRNA is the binding target of microRNA and RNA binding proteins. Their interactions regulate mRNA level in specific subcellular regions and determine the intensity of gene repression. The mutations in the coding region of voltage-gated sodium channel alpha 1 subunit gene, SCN1A, were identified in epileptic patients and confirmed as causative factors of epilepsy. We investigated if there were genetic variants in 3’UTR of SCN1A, affecting the microRNA-mRNA 3’UTR interaction and SCN1A gene repression, potentially associated with epilepsy.ResultsIn this case–control study, we identified twelve variants, NM_001202435.1:n.6277A > G, n.6568_6571del, n.6761C > T, n.6874A > T, n.6907 T > C, n.6978A > G, n.7065_7066insG, n.7282 T > C, n.7338_7344del, n.7385 T > A, n.7996C > T, and n.8212C > T in 3’UTR of SCN1A gene. We found that the variant of n.6978A > G in all our samples was completely mutated (G/G). In male group, T allele in n.7282 T > C was associated with epilepsy, while C allele was significantly less frequent in epileptic patients than in normal males (OR 0.424). Consequently, the haplotype “CTTACATGACGA” / “CTCTA” was significantly less frequent in male epileptic patients (0.173) than in normal males (0.305). The frequency of haplotype block found in females, "TTTAACA", "TTCAACA", and "CTTAACA" was 0.499, 0.254 and 0.234 respectively. Within STarMir model analysis, the “CTCTA” haplotype showed significantly higher site accessibility to microRNA targeting and higher downstream sequence accessibility for nonconserved binding than that of other haplotypes. Overall, the male genotypes have the higher accessibility of the downstream 30nt block of nonconserved site than the female genotypes.ConclusionsNM_001202435.1:n.7282 T > C is the genetic variant associated with epilepsy in males, and the related haplotype “CTTACATGACGA” / “CTCTA” in the region of chr2: 165991297–165989081, which has high site accessibility for microRNA binding, is the genetic protective factor against epilepsy in males. In female subset, the frequencies of haplotype block "TTTAACA", "TTCAACA", and "CTTAACA" were 0.499,0.254 and 0.234 respectively. Alleles and haplotypes distribution did not differ in female cases in comparison to female controls.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0417-y) contains supplementary material, which is available to authorized users.

Association of Tag SNPs and Rare CNVs of the MIR155HG/miR-155 Gene with Epilepsy in the Chinese Han Population.

Background. miR-155 likely acts as an important modulator in the inflammatory mechanism of epilepsy, and this study investigated its association with epilepsy from the perspective of molecular genetics. Methods. This study enrolled 249 epileptic patients and 289 healthy individuals of the Chinese Han population; 4 tag single-nucleotide polymorphisms (SNPs: rs969885, rs12483428, rs987195, and rs4817027) of the MIR155HG/miR-155 gene were selected, and their association with epilepsy was investigated. Additionally, this study determined the copy numbers of the MIR155HG/miR-155 gene. Results. The TCA haplotype (rs12483428-rs987195-rs4817027) and the AA genotype at rs4817027 conferred higher vulnerability to epilepsy in males. Stratification by age of onset revealed that the CC haplotype (rs969885-rs987195) was a genetic susceptibility factor for early-onset epilepsy. Further stratification by drug-resistant status indicated the CC haplotype (rs969885-rs987195) and the AA genotype at rs4817027 were genetic susceptibility factors for drug-resistant epilepsy (DRE) but the CG haplotype (rs987195-rs969885) was a genetically protective factor against DRE. Besides, 3 epileptic patients with copy number variants of the MIR155HG/miR-155 gene were observed. Conclusions. This study first demonstrates the association of MIR155HG/miR-155 tag SNPs with epilepsy and shows that rare CNVs were found exclusively in epileptic patients, clarifying the genetic role of miR-155 in epilepsy.

Soy Infant Formula and Seizures in Children with Autism: A Retrospective Study

Seizures are a common phenotype in many neurodevelopmental disorders including fragile X syndrome, Down syndrome and autism. We hypothesized that phytoestrogens in soy-based infant formula were contributing to lower seizure threshold in these disorders. Herein, we evaluated the dependence of seizure incidence on infant formula in a population of autistic children. Medical record data were obtained on 1,949 autistic children from the SFARI Simplex Collection. An autism diagnosis was determined by scores on the ADI-R and ADOS exams. The database included data on infant formula use, seizure incidence, the specific type of seizure exhibited and IQ. Soy-based formula was utilized in 17.5% of the study population. Females comprised 13.4% of the subjects. There was a 2.6-fold higher rate of febrile seizures [4.2% versus 1.6%, OR = 2.6, 95% CI = 1.3–5.3], a 2.1-fold higher rate of epilepsy comorbidity [3.6% versus 1.7%, OR = 2.2, 95% CI = 1.1–4.7] and a 4-fold higher rate of simple partial seizures [1.2% versus 0.3%, OR = 4.8, 95% CI = 1.0–23] in the autistic children fed soy-based formula. No statistically significant associations were found with other outcomes including: IQ, age of seizure onset, infantile spasms and atonic, generalized tonic clonic, absence and complex partial seizures. Limitations of the study included: infant formula and seizure data were based on parental recall, there were significantly less female subjects, and there was lack of data regarding critical confounders such as the reasons the subjects used soy formula, age at which soy formula was initiated and the length of time on soy formula. Despite these limitations, our results suggest that the use of soy-based infant formula may be associated with febrile seizures in both genders and with a diagnosis of epilepsy in males in autistic children. Given the lack of data on critical confounders and the retrospective nature of the study, a prospective study is required to confirm the association.

Prevalence and Risk Factors of Epilepsy Among School Children in Eastern Turkey

Epilepsy is a serious chronic brain disorder of childhood. We performed a cross-sectional prevalence study, determined the prevalence of childhood epilepsy, and identified the significance of certain risk factors for epilepsy among 1625 primary-school students aged 6-14 years, living in the center of Kars province. A questionnaire was prepared according to the definitions and principles of the Commission on Epidemiology and Prognosis, International League Against Epilepsy. Twenty-two children were diagnosed as epileptic. The point prevalence of active epilepsy in males was 4.9/1000, and in females 12.4/1000, representing a total of 8.6/1000. The cumulative prevalence in males was 11.0/1000, and 16.1/1000 in females, representing a total of 13.5/1000. Febrile convulsions, family history of epilepsy, serious maternal illness during pregnancy, a history of head trauma, antenatal/postnatal problems, and a history of neonatal jaundice were statistically significantly related to the development of epilepsy.

Does normal variation in birthweight confer susceptibility to health problems? A co-twin control study

ABSTRACTPopulation-based twin data were used to study whether normal variation in birthweight confersdisadvantage for a variety of health outcomes from birth through young adulthood. The sample consists of5,864 identical and fraternal twins and includes 2,570 intact pairs. Variation in birthweight may beassociated with an increased risk for epilepsy in males and with refractive disorders, chronic ear infectionsand intestinal problems in women. Two variants of the co-twin control design, based on identical twinsonly, were used to control for genetic and shared environmental effects that influence both birthweight andthe health outcome. Results indicated that the prevalence of health outcomes was not greater among thelighter twin from birthweight discordant pairs. Furthermore, intra-pair differences in birthweight betweenmembers of pairs who were health-discordant were significant only for nearsightedness among the MZmales. Due to lack of statistical power these results should be interpreted with caution.

Association of epilepsy with different groups of microcephaly

Sixty-six participants (33 males, 33 females) with microcephaly (MC), age range from 2 to 19 years old, were evaluated. MC was classified pathogenetically into isolated MC (IMC) and multiple MC (MMC) and classified etiologically into primary MC (PMC) and secondary MC (SMC). Both IMC and MMC were further classified. Overall prevalence of epilepsy was 40.9%. Furthermore, there was a significantly higher prevalence of epilepsy in males. Main seizure type was generalized tonic-clonic seizures. Generally, learning disability (LD) was diagnosed in 93.9% and profound LD was evident in 43.9% of participants. There was an inverse correlation between severity of epilepsy and IQ but a positive correlation between severity of epilepsy and degree of LD. Differences in the success rate between monotherapy and polytherapy or response to antiepileptic drugs were not observed. Results suggest that epilepsy may be associated with the lower cognitive ability of the participants with microcephaly. The pathogenetic classification proposed is of value in delineating the prevalence of epilepsy and LD in the different varieties of MC as compared with the etiological classification.

The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes

Infantile spasms, mental retardation, autism, and dystonia represent disabling diseases for which little etiologic information is available. Mutations in the Aristaless related homeobox gene (ARX) have been found in patients with these conditions. This discovery provides important genetic information and may ultimately offer treatment options for these patients. Recent work has demonstrated that mutations in ARX cause X-linked West syndrome, X-linked myoclonic epilepsy with spasticity and intellectual disability, Partington syndrome (mental retardation, ataxia, and dystonia), as well as nonsyndromic forms of mental retardation. Patients with these aforementioned diseases and ARX mutations were not reported to have brain imaging abnormalities. In contrast, mutations in ARX mutations have also been found in X-linked lissencephaly with abnormal genitalia, which typically includes severe brain malformations (lissencephaly, agenesis of the corpus callosum, and midbrain malformations), intractable seizures, and a severely shortened lifespan. ARX knockout mice manifest defects in overall neuroblast proliferation as well as selective abnormalities in gamma-aminobutyric acid-ergic interneuron migration. Consistent with these findings in mice, phenotype/genotype studies in humans suggest that truncating mutations cause X-linked lissencephaly with abnormal genitalia, and insertion/missense mutations result in epilepsy and mental retardation without cortical dysplasia. Mutations in the homeobox gene, ARX, cause a diverse spectrum of disease that includes cognitive impairment, epilepsy, and in another group of patients severe cortical malformations. Although the precise prevalence of ARX mutations is unclear, ARX may rival Fragile X as a cause of mental retardation and epilepsy in males.

Association of morphological characteristics with precocious puberty and/or gelastic seizures in hypothalamic hamartoma.

The pathogenesis of central precocious puberty (PP) and/or gelastic seizures due to a hypothalamic hamartoma (HH) is still under debate. We evaluated the association of clinical symptoms with morphology and localization of the HH in 34 patients. The majority (86.4%) of HHs in patients with isolated PP (n = 22; 68.2% females) revealed a parahypothalamic position without affecting the third ventricle (91%). Half of them were pedunculated, and 40.9% showed a diameter less than 10 mm. In contrast, 11 of 12 patients with seizures, eight of whom were male, presented with a sessile intrahypothalamic hamartoma, 10 of which distorted the third ventricle. Logistic regression analysis revealed an increased relative risk (RR) for epilepsy in males (RR, 4.3; 95% confidence interval, 0.96-19). However, combination of the risk factor gender with intrahypothalamic position (RR, 19; 1.3-285) and distortion of the third ventricle (RR, 10; 0.6-164) reduced the risk associated with male gender to 1.1. The position of a HH and involvement of the third ventricle are likely to be more predictive for clinical characteristics than size and shape. Male gender was associated with an intrahypothalamic HH and epilepsy, suggesting a sexually dimorphic developmental pattern of this heterotopic mass.

Association of epilepsy with different groups of microcephaly.

Sixty-six participants (33 males, 33 females) with microcephaly (MC), age range from 2 to 19 years old, were evaluated. MC was classified pathogenetically into isolated MC (IMC) and multiple MC (MMC) and classified etiologically into primary MC (PMC) and secondary MC (SMC). Both IMC and MMC were further classified. Overall prevalence of epilepsy was 40.9%. Furthermore, there was a significantly higher prevalence of epilepsy in males. Main seizure type was generalized tonic-clonic seizures. Generally, learning disability (LD) was diagnosed in 93.9% and profound LD was evident in 43.9% of participants. There was an inverse correlation between severity of epilepsy and IQ but a positive correlation between severity of epilepsy and degree of LD. Differences in the success rate between monotherapy and polytherapy or response to antiepileptic drugs were not observed. Results suggest that epilepsy may be associated with the lower cognitive ability of the participants with microcephaly. The pathogenetic classification proposed is of value in delineating the prevalence of epilepsy and LD in the different varieties of MC as compared with the etiological classification.

Depression and partial epilepsy: relevance of laterality of the epileptic focus.

In a prospective study of 50 epileptic patients (20 with a left hemisphere epileptic focus, 20 with a right one and 10 with a cryptogenic generalized epilepsy), the authors show that depression as appreciated by the H.A.R.D. score, is more frequent and severe in partial epilepsy in males, and when the epileptic focus is localized on left hemisphere. This association is related to the duration of epilepsy, the number of seizures, but not to age or medication status. Vulnerability of left hemisphere to depression is analysed, and neuro-chemical mechanisms are discussed.