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Sample records for idiopathic epilepsy caused

  1. [Genetics of idiopathic epilepsies].

    PubMed

    Weber, Y G; Lerche, H

    2013-02-01

    Idiopathic epilepsies are genetically determined. They are characterized by the observed seizure types, an age-dependent onset, electroencephalographic criteria and concomitant symptoms, such as movement disorders or developmental delay. The main subtypes are the idiopathic (i) generalized, (ii) the focal epilepsies including the benign syndromes of early childhood and (iii) the epileptic encephalopathies as well as the fever-associated syndromes. In recent years, an increasing number of mutations have been identified in genes encoding ion channels, proteins associated to the vesical synaptic cycle or proteins involved in energy metabolism. These mechanisms are pathophysiologically plausible as they influence neuronal excitability. The large number of genetic defects in epilepsy complicates the genetic diagnostic analysis but novel genetic methods are available covering all known genes at a reasonable price. The proof of a genetic defect leads to a definitive diagnosis, is important for the prognostic and genetic counselling and may influence therapeutic decisions in some cases, so that genetic diagnostic testing is becoming increasingly more important and meaningful in many cases in daily clinical practice. PMID:23392265

  2. Seizures of idiopathic generalized epilepsies.

    PubMed

    Durón, Reyna M; Medina, Marco T; Martínez-Juárez, Iris E; Bailey, Julia N; Perez-Gosiengfiao, Katerina Tanya; Ramos-Ramírez, Ricardo; López-Ruiz, Minerva; Alonso, María Elisa; Ortega, Ramón H Castro; Pascual-Castroviejo, Ignacio; Machado-Salas, Jesús; Mija, Lizardo; Delgado-Escueta, Antonio V

    2005-01-01

    Idiopathic generalized epilepsies (IGEs) comprise at least 40% of epilepsies in the United States, 20% in Mexico, and 8% in Central America. Here, we review seizure phenotypes across IGE syndromes, their response to treatment and advances in molecular genetics that influence nosology. Our review included the Medline database from 1945 to 2005 and our prospectively collected Genetic Epilepsy Studies (GENESS) Consortium database. Generalized seizures occur with different and similar semiologies, frequencies, and patterns, ages at onset, and outcomes in different IGEs, suggesting common neuroanatomical pathways for seizure phenotypes. However, the same seizure phenotypes respond differently to the same treatments in different IGEs, suggesting different molecular defects across syndromes. De novo mutations in SCN1A in sporadic Dravet syndrome and germline mutations in SCN1A, SCN1B, and SCN2A in generalized epilepsies with febrile seizures plus have unraveled the heterogenous myoclonic epilepsies of infancy and early childhood. Mutations in GABRA1, GABRG2, and GABRB3 are associated with absence seizures, while mutations in CLCN2 and myoclonin/EFHC1 substantiate juvenile myoclonic epilepsy as a clinical entity. Refined understanding of seizure phenotypes, their semiology, frequencies, and patterns together with the identification of molecular lesions in IGEs continue to accelerate the development of molecular epileptology. PMID:16302874

  3. Genetics of idiopathic generalized epilepsies.

    PubMed

    Gardiner, Mark

    2005-01-01

    The idiopathic generalized epilepsies (IGEs) are considered to be primarily genetic in origin. They encompass a number of rare mendelian or monogenic epilepsies and more common forms which are familial but manifest as complex, non-mendelian traits. Recent advances have demonstrated that many monogenic IGEs are ion channelopathies. These include benign familial neonatal convulsions due to mutations in KCNQ2 or KCNQ3, generalized epilepsy with febrile seizures plus due to mutations in SCN1A, SCN2A, SCN1B, and GABRG2, autosomal-dominant juvenile myoclonic epilepsy (JME) due to a mutation in GABRA1 and mutations in CLCN2 associated with several IGE sub-types. There has also been progress in understanding the non-mendelian IGEs. A haplotype in the Malic Enzyme 2 gene, ME2, increases the risk for IGE in the homozygous state. Five missense mutations have been identified in EFHC1 in 6 of 44 families with JME. Rare sequence variants have been identified in CACNA1H in sporadic patients with childhood absence epilepsy in the Chinese Han population. These advances should lead to new approaches to diagnosis and treatment. PMID:16302872

  4. Idiopathic epilepsy and school achievement.

    PubMed

    Sturniolo, M G; Galletti, F

    1994-05-01

    Forty one children (20 boys, 21 girls) aged 6-10.8 years (mean age 8.6 years) who were affected with idiopathic epilepsy underwent neuropsychological (Wechsler Intelligence Scale for Children, Bender test) and behavioural assessment (Personality Inventory for Children; this was also used in a matched control group). Further information was obtained by teachers' reports. School underachievement occurred in 25 children (61%). Statistical analysis showed no influence of sex, social background, age of onset, seizure type, duration of illness, features seen on electroencephalography, and treatment. School failure was due to poor performance in almost all academic fields, and was associated with higher visuomotor impairment; children showing good school performance had a higher mean IQ and less visuomotor impairment. The behaviour of children with epilepsy who had a good academic performance did not differ from that of their healthy peers. Emotional maladjustment (social skill impairment, depression, poor motivation, and low self esteem) was associated with poor school performance. Such problems, that may complicate the course of idiopathic epilepsy and require an appropriate educational programme, should be carefully considered by the clinician. PMID:8017966

  5. Idiopathic focal epilepsies: the "lost tribe".

    PubMed

    Pal, Deb K; Ferrie, Colin; Addis, Laura; Akiyama, Tomoyuki; Capovilla, Giuseppe; Caraballo, Roberto; de Saint-Martin, Anne; Fejerman, Natalio; Guerrini, Renzo; Hamandi, Khalid; Helbig, Ingo; Ioannides, Andreas A; Kobayashi, Katsuhiro; Lal, Dennis; Lesca, Gaetan; Muhle, Hiltrud; Neubauer, Bernd A; Pisano, Tiziana; Rudolf, Gabrielle; Seegmuller, Caroline; Shibata, Takashi; Smith, Anna; Striano, Pasquale; Strug, Lisa J; Szepetowski, Pierre; Valeta, Thalia; Yoshinaga, Harumi; Koutroumanidis, Michalis

    2016-09-01

    The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The

  6. Channelopathies can cause epilepsy in man.

    PubMed

    Steinlein, Ortrud K

    2002-01-01

    Idiopathic epilepsies, which account for up to 40% of all epilepsies, are mainly caused by genetic factors. Most idiopathic epilepsies are due to oligogenic or multifactorial rather than monogenetic inheritance. Nevertheless, most of what is known today about the molecular genetics of idiopathic epilepsies has been found by analysing large families with rare monogenetic forms of the disease. For the first time, gene defects can be linked to certain epilepsies. Mutations in the CHRNA4 or CHRNB subunits of the neuronal nicotinic acetylcholine receptor lead to familial nocturnal frontal lobe epilepsy, while defects in the voltage-gated potassium channels KCNQ2 and KCNQ3 have recently been found to cause benign familial neonatal convulsions. The voltage-gated sodium channel subunits SCN1B, SCN1A and SCN2A as well as the GABRG2 subunit of the GABA(A) receptor are involved in the pathology of the newly described syndrome generalized epilepsy with febrile seizures plus. These rare monogenetic epilepsies can serve as models for further genetic analysis of the common forms of idiopathic epilepsies. PMID:11888238

  7. Genetic polymorphisms and idiopathic generalized epilepsies.

    PubMed

    Lucarini, Nazzareno; Verrotti, Alberto; Napolioni, Valerio; Bosco, Guido; Curatolo, Paolo

    2007-09-01

    In recent years, progress in understanding the genetic basis of idiopathic generalized epilepsies has proven challenging because of their complex inheritance patterns and genetic heterogeneity. Genetic polymorphisms offer a convenient avenue for a better understanding of the genetic basis of idiopathic generalized epilepsy by providing evidence for the involvement of a given gene in these disorders, and by clarifying its pathogenetic mechanisms. Many of these genes encode for some important central nervous system ion channels (KCNJ10, KCNJ3, KCNQ2/KCNQ3, CLCN2, GABRG2, GABRA1, SCN1B, and SCN1A), while many others encode for ubiquitary enzymes that play crucial roles in various metabolic pathways (HP, ACP1, ME2, LGI4, OPRM1, GRIK1, BRD2, EFHC1, and EFHC2). We review the main genetic polymorphisms reported in idiopathic generalized epilepsy, and discusses their possible functional significance in the pathogenesis of seizures. PMID:17765802

  8. Mutant GABA(A) receptor subunits in genetic (idiopathic) epilepsy.

    PubMed

    Hirose, Shinichi

    2014-01-01

    The γ-aminobutyric acid receptor type A (GABAA receptor) is a ligand-gated chloride channel that mediates major inhibitory functions in the central nervous system. GABAA receptors function mainly as pentamers containing α, β, and either γ or δ subunits. A number of antiepileptic drugs have agonistic effects on GABAA receptors. Hence, dysfunctions of GABAA receptors have been postulated to play important roles in the etiology of epilepsy. In fact, mutations or genetic variations of the genes encoding the α1, α6, β2, β3, γ2, or δ subunits (GABRA1, GABRA6, GABRB2, GABRB3, GABRG2, and GABRD, respectively) have been associated with human epilepsy, both with and without febrile seizures. Epilepsy resulting from mutations is commonly one of following, genetic (idiopathic) generalized epilepsy (e.g., juvenile myoclonic epilepsy), childhood absence epilepsy, genetic epilepsy with febrile seizures, or Dravet syndrome. Recently, mutations of GABRA1, GABRB2, and GABRB3 were associated with infantile spasms and Lennox-Gastaut syndrome. These mutations compromise hyperpolarization through GABAA receptors, which is believed to cause seizures. Interestingly, most of the insufficiencies are not caused by receptor gating abnormalities, but by complex mechanisms, including endoplasmic reticulum (ER)-associated degradation, nonsense-mediated mRNA decay, intracellular trafficking defects, and ER stress. Thus, GABAA receptor subunit mutations are now thought to participate in the pathomechanisms of epilepsy, and an improved understanding of these mutations should facilitate our understanding of epilepsy and the development of new therapies. PMID:25194483

  9. Prevalence of Celiac Disease in Turkish Children with Idiopathic Epilepsy

    PubMed Central

    Işikay, Sedat; Hizli, Şamil; Yilmaz, Kutluhan

    2014-01-01

    Objective: This study has examined the prevalence of celiac disease in Turkish children with idiopathic epilepsy. Methods: Children with idiopathic epilepsy were screened for celiac disease using the IgA anti-tissue transglutaminase antibody and compared with the healthy control group in order to find the association of celiac disease (CD) with idiopathic epilepsy. Upper gastrointestinal endoscopy and small intestinal biopsies were offered to all antibody-positive patients. Findings : A total of 214 children with the diagnosis of idiopathic epilepsy and 166 healthy children as control group were studied. Of the patients recruited, 55.1% had generalized epilepsy, and 44.9% had partial epilepsy. In 33 patients with partial epilepsy, electroclinical features were consistent with a diagnosis of childhood partial epilepsy with occipital paroxysms (CPEO). Two of 33 patients with CPEO had positive IgA anti-tissue transglutaminase antibodies in serology. Pathological examination of small intestinal biopsy specimens showed total villous atrophy in both of them. The prevalence of celiac disease among children with idiopathic epilepsy and CPEO was 0.9% and 6%, respectively. Conclusion: The results of the present study revealed that prevalence of CD is increased in children with epilepsy. On the other hand, as high as 6% prevalence of CD among patients with CPEO found in this study should be kept in mind and the clinicians should be aware of this association. PMID:25562021

  10. Factors associated with behavioral problems in children with idiopathic epilepsy.

    PubMed

    Dafoulis, Vaios; Kalyva, Efrosini

    2012-06-01

    The present study examined whether the perceived behavioral problems of children with idiopathic epilepsy differed from those of healthy controls according to parent proxy-reports and which factors are associated with these problems. The parents of 106 children with idiopathic epilepsy and 305 healthy controls aged 6-9 years old completed the Vanderbilt ADHD Diagnostic Parent Rating Scale and the Strengths and Difficulties Questionnaire. The 106 children with idiopathic epilepsy were also interviewed using the K-SADS-PL. The parents of children with idiopathic epilepsy reported more hyperactivity, emotional and conduct problems than the parents of healthy controls, as well as less prosocial behavior. Parents detected no differences in peer problems, inattention, oppositional/defiant disorder, and anxiety/depression. Age of onset of epilepsy (later), the number of administered antiepileptic drugs (polytherapy), and gender (male) predicted behavioral problems in children with idiopathic epilepsy. The frequency of seizures was associated with behavioral problems, while age was not. Finally, children with benign focal epilepsy were rated by their parents as having less behavioral problems than children with generalized epilepsy. PMID:22348790

  11. Genetic Causes of Generalized Epilepsies.

    PubMed

    Helbig, Ingo

    2015-06-01

    Generalized epilepsies, particularly the idiopathic or genetic generalized epilepsies (GGEs), represent some of the most common epilepsies. Clinical genetic data including family studies and twin studies provide compelling evidence for a prominent genetic impact. The first decade of the 21st century was marked by progress in understanding the basic biology of generalized epilepsies including generalized/genetic epilepsies with febrile seizures plus (GEFS+) and GGE through studies of large families, discovering causative mutations in SCN1A, SCN1B, GABRG2, and GABRA1. Subsequently, recurrent microdeletions at 15q13.3, 16p13.11, and 15q11.2 were found to be relevant risk factors for nonfamilial GGE. Genes for epileptic encephalopathies such as SLC2A1 were rediscovered in GGE, highlighting the biological continuum between different epilepsies. Genome-wide studies examining common genetic risk factors identified common variants in SCN1A, indicating a convergence of shared pathophysiological pathways in various types of epilepsies. In the era of next-generation sequencing, however, the GGEs appear more complex than expected, and small or moderately sized studies give only a limited genetic perspective. Thus, there is a strong impetus for large collaborative investigations on an international level. PMID:26060908

  12. Advances on the genetics of mendelian idiopathic epilepsies.

    PubMed

    Baulac, Stéphanie; Baulac, Michel

    2009-11-01

    Genetic factors play an increasingly recognized role in idiopathic epilepsies. Since 1995, positional cloning strategies in multi-generational families with autosomal dominant transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4, CHRNA2, CHRNB2, SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGI1) and numerous loci for febrile seizures and epilepsies. To date, all genes with the exception of LGI1 (leucine-rich glioma inactivated 1), encode neuronal ion channel or neurotransmitter receptor subunits. Molecular approaches have revealed great genetic heterogeneity, with the vast majority of genes remaining to be identified. One of the major challenges is now to understand phenotype-genotype correlations. This review focuses on the current knowledge on the molecular basis of these rare Mendelian autosomal dominant forms of idiopathic epilepsies. PMID:19853223

  13. Advances on the genetics of Mendelian idiopathic epilepsies.

    PubMed

    Baulac, Stéphanie; Baulac, Michel

    2010-12-01

    Genetic factors play an increasingly recognized role in idiopathic epilepsies. Since 1995, positional cloning strategies in multigenerational families with autosomal dominant transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4, CHRNA2, CHRNB2, SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGI1) and numerous loci for febrile seizures and epilepsies. To date, all genes with the exception of LGI1, encode neuronal ion channel or neurotransmitter receptor subunits. Molecular approaches have revealed great genetic heterogeneity, with most genes remaining to be identified. One of the major challenges is now to understand phenotype-genotype correlations. This review focuses on the current knowledge on the molecular basis of these rare mendelian autosomal dominant forms of idiopathic epilepsies. PMID:20832659

  14. Benign idiopathic partial epilepsy and brain lesion.

    PubMed

    Stephani, U; Doose, H

    1999-03-01

    A 14-year-old girl had severe head trauma from a dog bite at the age of 9 days. This resulted in extensive brain damage, tetraplegia, mental retardation, and epilepsy. The seizures were of rolandic type, and the EEG showed multifocal sharp waves. The course was benign. The initial diagnosis of a pure symptomatic epilepsy was revised after demonstrating typical benign focal sharp waves in the EEG of the healthy sister. Thus a phenocopy of a benign partial epilepsy by the brain lesion could be excluded with sufficient certainty. This observation allows the conclusion that the genetic disposition underlying the sharp-wave trait characteristic of benign partial epilepsies can be involved also in the pathogenesis of seemingly pure symptomatic epilepsies. EEG studies on siblings of such patients are needed to exclude possible phenocopies. PMID:10080522

  15. Correlation between quantitative EEG and MRI in idiopathic generalized epilepsy.

    PubMed

    Betting, Luiz E; Li, Li M; Lopes-Cendes, Iscia; Guerreiro, Marilisa M; Guerreiro, Carlos A M; Cendes, Fernando

    2010-09-01

    The objective of this study was to investigate the relationship between the focal discharges sometimes observed in the electroencephalogram of patients with idiopathic generalized epilepsies and subtle structural magnetic resonance imaging abnormalities. The main hypothesis to be assessed is that focal discharges may arise from areas of structural abnormality which can be detected by quantitative neuroimaging. Focal discharges were used for quantitative electroencephalogram source detection. Neuroimaging investigations consisted of voxel-based morphometry and region of interest volumetry. For voxel-based morphometry, volumetric MRI were acquired and processed. The images of each patient were individually compared with a control group. Statistical analysis was used to detect differences in gray matter volumes. Region of interest-based morphometry was automatically performed and used essentially to confirm voxel-based morphometry findings. The localization of the focal discharges on the electroencephalogram was compared to the neuroimaging results. Twenty-two patients with idiopathic generalized epilepsies were evaluated. Gray matter abnormalities were detected by voxel-based morphometry analysis in 77% of the patients. There was a good concordance between EEG source detection and voxel-based morphometry. On average, the nearest voxels detected by these methods were 19 mm (mm) apart and the most statistically significant voxels were 34 mm apart. This study suggests that in some cases subtle gray matter abnormalities are associated with focal epileptiform discharges observed in the electroencephalograms of patients with idiopathic generalized epilepsies. PMID:20082332

  16. Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases

    PubMed Central

    Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe

    2015-01-01

    Study Objectives: The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Methods and Results: Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Conclusions: Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. Citation: Baiardi S, Vandi S, Pizza F, Alvisi L, Toscani L, Zambrelli E, Tinuper P, Mayer G, Plazzi G. Narcolepsy type 1 and

  17. Voxel-based morphometry in patients with idiopathic generalized epilepsies.

    PubMed

    Betting, Luiz Eduardo; Mory, Susana Barreto; Li, Li Min; Lopes-Cendes, Iscia; Guerreiro, Marilisa M; Guerreiro, Carlos A M; Cendes, Fernando

    2006-08-15

    Idiopathic generalized epilepsies (IGE) are a group of frequent age-related epilepsy syndromes. IGE are clinically characterized by generalized tonic-clonic, myoclonic and absence seizures. According to predominant seizure type and age of onset, IGE are divided in subsyndromes: childhood absence and juvenile absence epilepsy (AE), juvenile myoclonic epilepsy (JME) and generalized tonic-clonic seizures on awakening (GTCS). The limits between these subsyndromes are not well defined, supporting the existence of only one major syndrome. Visual assessment of routine magnetic resonance imaging (MRI) in patients with IGE is normal. MRI voxel-based morphometry (VBM) uses automatically segmented gray and white matter for comparisons, eliminating the investigator bias. We used VBM to study 120 individuals (47 controls, 44 with JME, 24 with AE and 15 with GTCS) to investigate the presence of subtle structural abnormalities in IGE subsyndromes. VBM was performed searching for abnormalities on gray matter concentration (GMC) between patients groups and controls. Compared to controls, JME presented increased GMC in frontobasal region and AE showed increased GMC in the superior mesiofrontal region. The GTCS group did not differ from controls. There were no areas of reduced GMC with the statistical level selected. Region of interest analysis showed increased GMC in the anterior portion of the thalamus in patients with absence seizures. Our results support subtle GMC abnormalities in patients with JME and AE when compared to controls. These findings suggest the existence of different patterns of cortical abnormalities in IGE subsyndromes. PMID:16702001

  18. Focal interictal epileptiform discharges in idiopathic generalized epilepsy.

    PubMed

    Esmail, Eman H; Nawito, Amani M; Labib, Dalia M; Basheer, Mye A

    2016-07-01

    Are idiopathic generalized epilepsies (IGEs) truly generalized? Do IGEs represent a continuum or rather distinct syndromes? Focal changes in the electroencephalography (EEG) have been reported in IGEs. The aim of this work is to investigate focal interictal epileptiform discharges (IEDs) in IGEs, and their relation to clinical variables. Forty-one IGE patients (classified according to ILAE, 2001) were recruited from a tertiary center (age 23 ± 10.938 years). Their files were reviewed and they were subjected to clinical examination and interictal EEG. Patients with focal IEDs were compared to those without focal IEDs. Nine patients had juvenile myoclonic epilepsy (JME) and 32 had idiopathic epilepsy with generalized tonic-clonic seizures only (EGTCSA). Focal IEDs were found in 20 patients, mostly in the frontal (45.5 %) and temporal (31.8 %) distribution. Patients with focal IEDs were treated with a larger number of combined antiepileptic drugs (AEDs) (p value = 0.022). No significant difference was found between the two groups regarding age, sex, age at onset, epilepsy syndrome, seizure frequency, family history, AEDs used (sodium valproate and carbamazepine) and their doses. Seventeen EGTCSA patients had focal IEDs. They were treated with larger number of combined AEDs (p value = 0.0142). No significant difference was found between the EGTCSA patients with and those without focal IEDs regarding age, sex, age at onset, seizure frequency, family history and AEDs doses. Caution must be applied in the interpretation of interictal focal IEDs. These focal changes may be related to prognosis, however this needs further investigation. PMID:26956566

  19. Obesity and its association with generalised epilepsy, idiopathic syndrome, and family history of epilepsy.

    PubMed

    Ladino, Lady D; Hernández-Ronquillo, Lizbeth; Téllez-Zenteno, José F

    2014-09-01

    Aim. Previous studies support the concept that obesity is a common comorbid condition in patients with epilepsy (PWE). In this study, we present the body mass index (BMI) and data from a survey to assess physical activity in a sample of PWE from an epilepsy clinic. Methods. Between June of 2011 and January of 2013, 100 PWE from an adult epilepsy clinic were included. We obtained BMI, waist circumference, and information regarding physical activity using a standardised questionnaire. Clinical, demographic, electrographic, and imaging parameters were collected from charts. Results. Mean age of patients was 40 ± 14 (18-77) years. The BMI distribution was as follows: 2 patients (2%) underweight, 26 (26%) normal weight, 34 (34%) overweight, 25 (25%) obese, and 13 (13%) with morbid obesity. In our study, obesity was defined as having a BMI ≥ 30. We found 38 (38%) patients in this range. There was no difference in the rate of drug-resistant epilepsy between obese and non-obese patients (55 vs. 55%; p=0.05). Leisure time habit was reported in 82% of obese patients and 79% of patients without obesity. Overall, the most frequent activity was walking (70%). Factors associated with obesity were generalised epilepsy (OR: 2.7, 1.1-6.6; p=0.012), idiopathic syndrome (OR: 2.7, 1.04-7; p=0.018), and family history of epilepsy (OR: 6.1, 1.5-24.2; p=0.002). Conclusion. Our study suggests an association between obesity, idiopathic generalised epilepsy, and family history of epilepsy. Our study shows that PWE are physically active and there is no clear relation between exercise and obesity. We could not identify any association between drug-resistant epilepsy and obesity. Absence of direct comparison with a control non-epileptic population; a cross-sectional design not allowing evaluation of a causal association among variables; and reliance on self-reported physical activity are to be considered as limitations of the present study. PMID:25179745

  20. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies

    PubMed Central

    de Kovel, Carolien G. F.; Trucks, Holger; Helbig, Ingo; Mefford, Heather C.; Baker, Carl; Leu, Costin; Kluck, Christian; Muhle, Hiltrud; von Spiczak, Sarah; Ostertag, Philipp; Obermeier, Tanja; Kleefuß-Lie, Ailing A.; Hallmann, Kerstin; Steffens, Michael; Gaus, Verena; Klein, Karl M.; Hamer, Hajo M.; Rosenow, Felix; Brilstra, Eva H.; Kasteleijn-Nolst Trenité, Dorothée; Swinkels, Marielle E. M.; Weber, Yvonne G.; Unterberger, Iris; Zimprich, Fritz; Urak, Lydia; Feucht, Martha; Fuchs, Karoline; Møller, Rikke S.; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Rückert, Ina-Maria; Wichmann, Heinz-Erich; Franke, Andre; Schreiber, Stefan; Nürnberg, Peter; Elger, Christian E.; Lerche, Holger; Stephani, Ulrich; Koeleman, Bobby P. C.; Lindhout, Dick; Eichler, Evan E.

    2010-01-01

    patients with idiopathic generalized epilepsy in this cohort with known 15q13.3 microdeletions (IGE/control: 9/0), parental transmission could be examined in 14 families. While 10 microdeletions were inherited (seven maternal and three paternal transmissions), four microdeletions occurred de novo at 15q13.3 (n = 1), 16p13.11 (n = 2) and 22q11.2 (n = 1). Eight of the transmitting parents were clinically unaffected, suggesting that the microdeletion itself is not sufficient to cause the epilepsy phenotype. Although the microdeletions investigated are individually rare (<1%) in patients with idiopathic generalized epilepsy, they collectively seem to account for a significant fraction of the genetic variance in common idiopathic generalized epilepsy syndromes. The present results indicate an involvement of microdeletions at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic susceptibility effect to a broad range of neuropsychiatric disorders. PMID:19843651

  1. Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies.

    PubMed

    Yalçın, Ozlem

    2012-03-01

    Idiopathic absence epilepsies (IAE), that have high prevalence particularly among children and adolescents, are complex disorders mainly caused by genetic factors. Childhood absence epilepsy and juvenile absence epilepsy are among the most common subtypes of IAEs. While the role of ion channels has been the primary focus of epilepsy research, the analysis of mutation and association in both patients with absence epilepsies and animal models revealed the involvement of GABA receptors and calcium channels, but also of novel non-ion channel proteins in inducing spike wave discharges (SWD). Functional studies on a mutated variant of these proteins also support their role in the epileptogenesis of absence seizures. Studies in animal models point to both the thalamus and cortex as the origin of SWDs: the abnormalities in the components of these circuits leading to seizure activity. This review examines the current research on mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 and CACNG3), and novel non-ion channel proteins, taking into account the results of functional studies on these variants. PMID:22206818

  2. Idiopathic (primary) generalized epilepsy. Traditional versus new antiepileptic drugs.

    PubMed

    Yadegari, Samira; Bahrami, Parviz

    2013-04-01

    Idiopathic generalized epilepsies (IGE) are genetic based seizures with normal neurologic exam, intelligence, and imaging studies. Based on the age of onset and prominent seizure type, different syndromes were identified. The purpose of this study is to summarize the characteristics, prognosis, and choices of antiepileptic drugs (AED) in common syndromes of IGE. In addition, we review the updated role of new AEDs in specific syndromes of IGE. The first choice AED is usually valproate. Most drug trials on the effects of new AEDs compared them with placebo and not valproate. However, some of the broad spectrum new AEDs may be considered as the first choice in specific conditions. In true refractory patients, combination therapy and vagal nerve stimulation could be the next option. In the proper management of IGE, neurologists should consider the predominant seizure type, patient gender, co-morbidities, and antiepileptic drugs that may aggravate a specific seizure type. PMID:23545607

  3. International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs.

    PubMed

    Hülsmeyer, Velia-Isabel; Fischer, Andrea; Mandigers, Paul J J; DeRisio, Luisa; Berendt, Mette; Rusbridge, Clare; Bhatti, Sofie F M; Pakozdy, Akos; Patterson, Edward E; Platt, Simon; Packer, Rowena M A; Volk, Holger A

    2015-01-01

    Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management of the dog with epilepsy in everyday clinical practice and furthermore may promote canine epilepsy research. The following manuscript reviews the evidence available for breeds which have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background, and highlights different breed specific clinical features (e.g. age at onset, sex, seizure type), treatment response, prevalence rates and proposed inheritance reported in the literature. In addition, certain breed-specific diseases that may act as potential differentials for idiopathic epilepsy are highlighted. PMID:26316206

  4. Early prediction of medication refractoriness in children with idiopathic epilepsy based on scalp EEG analysis.

    PubMed

    Lin, Lung-Chang; Ouyang, Chen-Sen; Chiang, Ching-Tai; Yang, Rei-Cheng; Wu, Rong-Ching; Wu, Hui-Chuan

    2014-11-01

    Refractory epilepsy often has deleterious effects on an individual's health and quality of life. Early identification of patients whose seizures are refractory to antiepileptic drugs is important in considering the use of alternative treatments. Although idiopathic epilepsy is regarded as having a significantly lower risk factor of developing refractory epilepsy, still a subset of patients with idiopathic epilepsy might be refractory to medical treatment. In this study, we developed an effective method to predict the refractoriness of idiopathic epilepsy. Sixteen EEG segments from 12 well-controlled patients and 14 EEG segments from 11 refractory patients were analyzed at the time of first EEG recordings before antiepileptic drug treatment. Ten crucial EEG feature descriptors were selected for classification. Three of 10 were related to decorrelation time, and four of 10 were related to relative power of delta/gamma. There were significantly higher values in these seven feature descriptors in the well-controlled group as compared to the refractory group. On the contrary, the remaining three feature descriptors related to spectral edge frequency, kurtosis, and energy of wavelet coefficients demonstrated significantly lower values in the well-controlled group as compared to the refractory group. The analyses yielded a weighted precision rate of 94.2%, and a 93.3% recall rate. Therefore, the developed method is a useful tool in identifying the possibility of developing refractory epilepsy in patients with idiopathic epilepsy. PMID:25164248

  5. Risk factors for cluster seizures in canine idiopathic epilepsy.

    PubMed

    Packer, Rowena M A; Shihab, Nadia K; Torres, Bruno B J; Volk, Holger A

    2016-04-01

    Cluster seizures (CS), two or more seizures within a 24-hour period, are reported in 38-77% of dogs with idiopathic epilepsy (IE). Negative outcomes associated with CS include a reduced likelihood of achieving seizure freedom, decreased survival time and increased likelihood of euthanasia. Previous studies have found factors including breed, sex and neuter status are associated with CS in dogs with IE; however, only one UK study in a multi-breed study of CS in IE patients exists to the author's knowledge, and thus further data is required to confirm these results. Data from 384 dogs treated at a multi-breed canine specific epilepsy clinic were retrospectively collected from electronic patient records. 384 dogs were included in the study, of which nearly half had a history of CS (49.1%). Dogs with a history of CS had a younger age at onset than those without (p=0.033). In a multivariate model, three variables predicted risk of CS: a history of status epilepticus (p=0.047), age at seizure onset (p=0.066) and breed (German Shepherd Dog) (p<0.001). Dogs with a history of status epilepticus and dogs with an older age at seizure onset were less likely to be affected by cluster seizures. German Shepherd Dogs (71% experiencing CS) were significantly more likely to suffer from CS compared to Labrador Retrievers (25%) (p<0.001). There was no association between sex, neuter status, body size and CS. Further studies into the pathophysiology and genetics of CS are required to further understand this phenomenon. PMID:27033922

  6. Association of serum trace elements and minerals with genetic generalized epilepsy and idiopathic intractable epilepsy.

    PubMed

    Prasad, D K V; Shaheen, Uzma; Satyanarayana, U; Surya Prabha, T; Jyothy, A; Munshi, Anjana

    2014-12-01

    Certain minerals and trace elements are essential for the development of healthy nervous system. Altered serum levels of these elements may lead to the development of various diseases including epilepsy. The present study was designed to evaluate the association of serum calcium, magnesium, zinc and copper in the development of genetic generalized epilepsy [GGE; erstwhile known as idiopathic generalized epilepsy (IGE)] as well as idiopathic intractable epilepsy (IIE), in which seizures persist despite treatment with at least two or three antiepileptic drugs tolerated at reasonable dosage. 200 GGE patients and equal number of healthy controls were recruited for study with their written informed consent. The patients were further divided into responders and non-responders based on their response to antiepileptic drugs. Copper and zinc levels were assayed by atomic absorption spectrophotometer whereas calcium and magnesium were analyzed by Human Star 600 fully automated biochemistry analyzer. The patients with GGE had significant low levels of calcium, magnesium and zinc (1.85 ± 0.33, 0.69 ± 0.13 mmol/L and 11.33 ± 3.32 µmol/L respectively) and the corresponding values for controls were 2.27 ± 0.22, 0.89 ± 0.15, 12.71 ± 3.24 (p < 0.05). Significant high levels of copper were found in patients as compared to controls (26.69 ± 8.79 µmol/L; 16.64 ± 3.64) (p < 0.05). Significantly decreased levels of zinc were noted in non-responders (10.38 ± 2.99) compared to responders (12.62 ± 3.30) (p < 0.05). No significant difference was observed in serum calcium, magnesium and copper levels between responders and non-responders. In conclusion, low levels of calcium, magnesium, zinc and high levels of copper were found to be associated with GGE. Further, the patients with IIE were also found to have low levels of zinc. PMID:25255736

  7. Quality-of-life aspects in idiopathic epilepsy in dogs.

    PubMed

    Wessmann, A; Volk, H A; Packer, R M A; Ortega, M; Anderson, T J

    2016-09-01

    Quality of life (QoL) plays a significant role in the treatment of dogs with idiopathic epilepsy (IE), yet is so far understudied. This study describes the outcome evaluation of an online questionnaire based on the carer's perception focusing on 62 QoL questions in 159 dogs with IE. Results showed that seizure frequency, but not seizure severity or presence of cluster seizures, was significantly associated with carer-perceived dog's QoL. Dogs receiving third-line antiepileptic drugs had a significantly lower perceived QoL than those that did not. Generalised linear mixed model analysis demonstrated that severity of the side effects sleeping more and ataxia were significantly associated with carer-perceived dog's QoL, with higher severities predicting lower QoL scores. The degree of carer acceptability of seizure frequency and severity was significantly associated with the dog's reported seizure frequency and severity. Moreover, there was a significant association between IE-related QoL changes of the dog and the carer, with reductions in perceived canine QoL scores associated with reductions in carer QoL, and vice versa. In conclusion, aspects of canine IE can affect both the carer and their dog's QoL. This has implications for the management and requires consideration when treatment options and outcomes are discussed. PMID:27329504

  8. Towards identification of an epilepsy gene in a large family with idiopathic generalized epilepsy

    SciTech Connect

    Roussear, M.; Lopes-Cendes, I.; Berkovic, S.F.

    1994-09-01

    To identify the disease gene in a large, multiplex family segregating an autosomal dominant form of idiopathic generalized epilepsy (IGE). The IGEs have been recognized for several decades as being genetically determined. However, large pedigrees with a clear Mendelian inheritance are not commonly available. This, and the presence of locus heterogeneity have been obstacles to the identification of linkage in several IGE syndromes. We have identified a large IGE kindred with fifty-eight living individuals, including 26 affecteds, showing a clear autosomal dominant inheritance with incomplete penetrance. Forty-fur informative individuals, including 23 affecteds, were selected for the linkage studies. We have chosen 200 polymorphic microsatellite markers, about 20 cM apart, throughout the human autosomes as a genome-search linkage strategy. To date, 47 markers, representing 30% of the human genome, have been excluded for linkage in the Australian kindred. As our study progresses, we will report up-to-date results.

  9. Investigation of the possible association of NEDD4-2 (NEDD4L) gene with idiopathic photosensitive epilepsy.

    PubMed

    Vanli-Yavuz, Ebru Nur; Ozdemir, Ozkan; Demirkan, Ayse; Catal, Suzin; Bebek, Nerses; Ozbek, Ugur; Baykan, Betul

    2015-09-01

    NEDD4-2 alias NEDD4L (neural precursor cell expressed, developmentally downregulated) gene was reported as a candidate gene for epileptic photo-sensitivity. We aimed to investigate this possible association of NEDD4-2 variants with idiopathic photosensitive epilepsy. Consecutive patients who had been followed up at our epilepsy center and diagnosed with idiopathic epilepsy according to ILAE criteria and clear-cut photoparoxysmal responses in their electroencephalograms and 100 ethnically matched healthy subjects were included in the study. The regions around previously reported three variants, namely, S233L, E271A and H515P were tracked with DHPLC and the samples showing variations were sequenced. 81 patients (63 females) aged between 12-63 years (45 had juvenile myoclonic epilepsy, 11 childhood absence epilepsy, 14 juvenile absence epilepsy, 7 late onset idiopathic generalized epilepsy, 1 unclassified idiopathic generalized epilepsy, and 3 patients with idiopathic photosensitive occipital lobe epilepsy) were included in this study. We found only one heterozygous S233L variant in a 23-year-old man who has photosensitive form of juvenile absence epilepsy and pattern sensitivity to striped carpets. Other two variants were not found in any of the other patients and controls. Our results suggest that three screened NEDD4-2 variants do not play a leading role in the pathogenesis of photosensitive epilepsy in the Turkish population. PMID:25542253

  10. Role of KCNQ2 and KCNQ3 genes in juvenile idiopathic epilepsy in Arabian foals.

    PubMed

    Lichter-Peled, Anat; Polani, Sagi; Stanyon, Roscoe; Rocchi, Mariano; Kahila Bar-Gal, Gila

    2013-04-01

    Juvenile idiopathic epilepsy (JIE) in Arabian foals resembles benign-familial neonatal convulsion (BFNC) syndrome, a rare idiopathic epilepsy of new-born humans. BFNC syndrome exhibits genetic heterogeneity, as has been hypothesised to occur in Arabian foals, and is known to be caused by mutations in the voltage-gated potassium channel subunit KCNQ2 and KCNQ3 genes. The close phenotypic characteristics of both Arabian foals and children suggest these epileptic syndromes are caused by the same genetic disorder. In horses, the KCNQ2 and KCNQ3 genes are located on the terminal region of chromosomes 22 and 9, respectively, essentially homologous to their location on chromosomes 20q13.3 and 8q24 in humans. Gene trees for the KCNQ2 and KCNQ3 genes between horses and other mammals, particularly humans and mice, were constructed and compared to widely accepted mammalian phylogenetic trees. The KCNQ2 gene tree exhibited close clustering between horses and humans, relative to horses and mice, in contrast to the evolutionary trees of other mammals. Distance values between the horse and human groups were lower as opposed to those found between the horse and mouse groups. The similarity between the horse and the human, especially for the KCNQ2 gene, where the majority of mutations causing BFNC have been found, supports the hypothesis of similar heritable and genetic patterns of the disease in both species and suggests that contrary to the classic mouse-model concept, humans may be a more suitable model for the study of JIE in Arabian foals. PMID:23182620

  11. Volumetric and shape analysis of thalamus in idiopathic generalized epilepsy.

    PubMed

    Kim, Ji Hyun; Kim, Jung Bin; Seo, Woo-Keun; Suh, Sang-Il; Koh, Seong-Beom

    2013-07-01

    Previous studies using voxel-based morphometry (VBM) provided emerging evidence of structural changes of the thalamus in idiopathic generalized epilepsy (IGE). However, the location of atrophy within the thalamus in IGE has been somewhat inconsistent across the studies. We, therefore, examined the location of thalamic atrophy and its relationship with clinical factors in IGE, using multiple analytic methods. Fifty IGE patients and 50 controls were scanned on a 3T MRI. Structural evaluation consisted of automated thalamic volumetry, VBM, and thalamic shape analysis. Group comparison between patients and controls was made to assess thalamic atrophy. Within-group correlations between thalamic atrophy and clinical variables were further performed in patients. Both thalamic volumes were reduced in IGE patients, and were negatively correlated with disease duration. The VBM showed a significant regional grey matter volume reduction in bilateral anterior-medial thalami in patients compared to controls. Voxel values extracted from the anterior-medial thalamic cluster were negatively correlated with disease duration. Vertex-based shape analysis revealed regional atrophy on the anterior-medial and posterior-dorsal aspects of thalamus bilaterally in patients compared to controls. Correlation analysis showed that anterior-medial and posterior-dorsal aspects of bilateral thalami were negatively correlated with disease duration. Combining multiple analyses, we demonstrated regional atrophy of anterior-medial and posterior-dorsal thalamus in patients with IGE. Given the anatomical connection of these thalamic regions with the frontal lobe, our finding of greater thalamic atrophy in relation to increasing disease duration further supports the pathophysiological concept of thalamo-frontal network abnormality underlying IGE, and may implicate frontal cognitive dysfunctions and disease progression. PMID:23512576

  12. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy

    PubMed Central

    Krauss, Gregory L.; Wechsler, Robert T.; Wang, Xue-Feng; DiVentura, Bree; Brandt, Christian; Trinka, Eugen; O'Brien, Terence J.; Laurenza, Antonio; Patten, Anna; Bibbiani, Francesco

    2015-01-01

    Objective: To assess efficacy and safety of adjunctive perampanel in patients with drug-resistant, primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE). Methods: In this multicenter, double-blind study (ClinicalTrials.gov identifier: NCT01393743; funded by Eisai Inc.), patients 12 years or older with PGTC seizures and IGE were randomized to placebo or perampanel during a 4-week titration period (perampanel uptitrated from 2 to 8 mg/d, or highest tolerated dose) and 13-week maintenance period. The primary endpoint was percent change in PGTC seizure frequency per 28 days (titration plus maintenance vs baseline). The key secondary endpoint (primary endpoint for European Union registration) was 50% PGTC seizure responder rate (patients achieving ≥50% reduction in PGTC seizure frequency; maintenance vs baseline). Treatment-emergent adverse events were monitored. Results: Of 164 randomized patients, 162 comprised the full analysis set (placebo, 81; perampanel, 81). Compared with placebo, perampanel conferred a greater median percent change in PGTC seizure frequency per 28 days (−38.4% vs −76.5%; p < 0.0001) and greater 50% PGTC seizure responder rate (39.5% vs 64.2%; p = 0.0019). During maintenance, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved PGTC seizure freedom. For the safety analysis (placebo, 82; perampanel, 81), the most frequent treatment-emergent adverse events with perampanel were dizziness (32.1%) and fatigue (14.8%). Conclusions: Adjunctive perampanel was well tolerated and improved control of drug-resistant PGTC seizures in patients with IGE. Classification of evidence: This study provides Class I evidence that adjunctive perampanel reduces PGTC seizure frequency, compared with placebo, in patients with drug-resistant PGTC seizures in IGE. PMID:26296511

  13. Epilepsy

    MedlinePlus

    Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters ... may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, ...

  14. Identification of a Novel Idiopathic Epilepsy Locus in Belgian Shepherd Dogs

    PubMed Central

    Seppälä, Eija H.; Koskinen, Lotta L. E.; Gulløv, Christina H.; Jokinen, Päivi; Karlskov-Mortensen, Peter; Bergamasco, Luciana; Baranowska Körberg, Izabella; Cizinauskas, Sigitas; Oberbauer, Anita M.; Berendt, Mette; Fredholm, Merete; Lohi, Hannes

    2012-01-01

    Epilepsy is the most common neurological disorder in dogs, with an incidence ranging from 0.5% to up to 20% in particular breeds. Canine epilepsy can be etiologically defined as idiopathic or symptomatic. Epileptic seizures may be classified as focal with or without secondary generalization, or as primary generalized. Nine genes have been identified for symptomatic (storage diseases) and one for idiopathic epilepsy in different breeds. However, the genetic background of common canine epilepsies remains unknown. We have studied the clinical and genetic background of epilepsy in Belgian Shepherds. We collected 159 cases and 148 controls and confirmed the presence of epilepsy through epilepsy questionnaires and clinical examinations. The MRI was normal while interictal EEG revealed abnormalities and variable foci in the clinically examined affected dogs. A genome-wide association study using Affymetrix 50K SNP arrays in 40 cases and 44 controls mapped the epilepsy locus on CFA37, which was replicated in an independent cohort (81 cases and 88 controls; combined p = 9.70×10−10, OR = 3.3). Fine mapping study defined a ∼1 Mb region including 12 genes of which none are known epilepsy genes or encode ion channels. Exonic sequencing was performed for two candidate genes, KLF7 and ADAM23. No variation was found in KLF7 but a highly-associated non-synonymous variant, G1203A (R387H) was present in the ADAM23 gene (p = 3.7×10−8, OR = 3.9 for homozygosity). Homozygosity for a two-SNP haplotype within the ADAM23 gene conferred the highest risk for epilepsy (p = 6.28×10−11, OR = 7.4). ADAM23 interacts with known epilepsy proteins LGI1 and LGI2. However, our data suggests that the ADAM23 variant is a polymorphism and we have initiated a targeted re-sequencing study across the locus to identify the causative mutation. It would establish the affected breed as a novel therapeutic model, help to develop a DNA test for breeding purposes and introduce a

  15. Behavior and Social Competency in Idiopathic and Cryptogenic Childhood Epilepsy

    ERIC Educational Resources Information Center

    Berg, Anne T.; Vickrey, Barbara G.; Testa, Francine M.; Levy, Susan R.; Shinnar, Shlomo; DiMario, Francis

    2007-01-01

    Behavioral and related disorders are frequently reported in association with childhood epilepsy but the reasons for this are unclear. In a long-term prospective, community-based study of newly-diagnosed childhood epilepsy, behavioral assessments (Child Behavior Checklist) were performed in children 8 to 9 years after the initial diagnosis of…

  16. Inter-rater reliability of the EEG reading in patients with childhood idiopathic epilepsy.

    PubMed

    Piccinelli, Paolo; Viri, Maurizio; Zucca, Claudio; Borgatti, Renato; Romeo, Antonino; Giordano, Laura; Balottin, Umberto; Beghi, Ettore

    2005-01-01

    The level of agreement in the interpretation of EEG records by different experienced readers working in three child neurology tertiary centers has been evaluated. EEG recordings randomly chosen from patients with idiopathic epilepsy were included. Optimal or suboptimal agreement was found for presence of ictal and interictal discharges. Contrary to ictal discharges, the distribution and location of interictal discharges was not unanimously interpreted and agreement was unsatisfactory when assessing the background activity. PMID:16118044

  17. Lymphoedema caused by idiopathic lymphatic thrombus.

    PubMed

    Hara, Hisako; Mihara, Makoto; Seki, Yukio; Koshima, Isao

    2013-12-01

    Primary lymphoedema includes some diseases whose genetic anomaly is detected and others whose pathology is unknown. In this article, we report a lymphatic thrombus found in a limb with lymphoedema during lymphatico-venous anastomosis (LVA). A 32-year-old man was aware of oedema in his left calcar pedis 3 years previously, which appeared without any trigger. Indocyanine green lymphography indicated lymphatic stasis in the left calf and thigh region, and we performed LVA for the patient. During the operation, we found yellow vessels, which were thought to be lymphatic vessels filled with a yellow solid substance, just beneath the superficial fascia at the left ankle. Pathological examination of the thrombi revealed hyaline material mixed with cell components. The cells were categorised as lymphatic endothelial cells, as they were positive for podoplanin. There was no evidence of malignancy. Causes of idiopathic lymphatic thrombus such as this may be one of the causes of so-called primary lymphoedema, and evaluation of such cases may be the first step towards elucidating the mechanisms involved in the development of primary lymphoedema. PMID:23643778

  18. Determination of haptoglobin genotype in an Iranian population with idiopathic generalized epilepsy

    PubMed Central

    Al-balaghee, Sukaina; Al-balaghee, Zeinab; Shabani, Ashraf; Ghadam, Parinaz; Bandehpour, Mojgan; Askari Mehr, Ali; Kazemi, Bahram

    2015-01-01

    Background: Haptoglobin (Hp) is a plasma α2-sialoglycoprotein that contains alpha and beta chains. It displays in three common phenotypes, Hp1-1, Hp2-1, and Hp2-2. Proteins expressed by polymorphic genes have grossly different molecular sizes resulting in different diffusion rates in the brain. Haptoglobin expressed by the Hp2-2 genotype has lower hemoglobin-binding capacity than Hp1-1 or Hp2-1 and is associated with idiopathic generalized epilepsy. Methods: To determine polymorphism in haptoglobin genes in patients with idiopathic generalized tonic-clonic seizures, 42 men, 42 women, and 50 controls were selected for this study. Genomic DNA was extracted from blood and studied by polymerase chain reactions (PCR). Results: The amplified fragments for the Hp1-1 and Hp2-2 genotypes were 1757 and 3481 base pairs (bp) respectively, and the Hp2-1 genotype had both fragments, in addition to a 349-bp fragment. The distribution of the three major Hp phenotypes in epilepsy patients was 28.6 (1-1), 38.1 (2-1), and 33.3% (2-2) in the men, and 31 (1-1), 40.5 (2-1), and 28.6% (2-2) in the women. The distribution of Hp genotypes in controls was 22 (1-1), 40 (2-1), and 38% (2-2). Conclusion: We show that all Hp genotypes participate in idiopathic generalized epilepsy. PMID:26989737

  19. Idiopathic Generalized Epilepsy and Hypokalemic Periodic Paralysis in a Family of South Indian Descent

    PubMed Central

    Subramanian, Muthiah; Senthil, N.; Sujatha, S.

    2015-01-01

    Inherited channelopathies are a heterogeneous group of disorders resulting from dysfunction of ion channels in cellular membranes. They may manifest as diseases affecting skeletal muscle contraction, the conduction system of the heart, nervous system function, and vision syndromes. We describe a family of South Indian descent with hypokalemic periodic paralysis in which four members also have idiopathic generalized epilepsy. Hypokalemic periodic paralysis is a genetically heterogeneous channelopathy that has been linked to mutations in genes encoding three ion channels CACNIAS, SCN4A, and KCNJ2 predominantly. Although data on specific gene in idiopathic generalized epilepsy is relatively scarce, mutations of voltage gated sodium channel subunit genes (CACNB4) and nonsense mutations in voltage gated calcium channels (CACNA1A) have been linked to idiopathic generalized epilepsy in two families. We speculate that gene mutations altering the ability of the beta subunit to interact with the alpha subunit of the CaV1.1 channel and mutations in the pore-forming potassium channel subunit may be possible explanations for the combined manifestation of both diseases. Functional analysis of voltage gated calcium channel and other ion channels mutations may provide additional support and insight for the causal role of these mutations. The understanding of mutations in ion-channel genes will lead to improved diagnosis and treatment of such inherited channelopathies. PMID:25893123

  20. Idiopathic generalized epilepsy and hypokalemic periodic paralysis in a family of South Indian descent.

    PubMed

    Subramanian, Muthiah; Senthil, N; Sujatha, S

    2015-01-01

    Inherited channelopathies are a heterogeneous group of disorders resulting from dysfunction of ion channels in cellular membranes. They may manifest as diseases affecting skeletal muscle contraction, the conduction system of the heart, nervous system function, and vision syndromes. We describe a family of South Indian descent with hypokalemic periodic paralysis in which four members also have idiopathic generalized epilepsy. Hypokalemic periodic paralysis is a genetically heterogeneous channelopathy that has been linked to mutations in genes encoding three ion channels CACNIAS, SCN4A, and KCNJ2 predominantly. Although data on specific gene in idiopathic generalized epilepsy is relatively scarce, mutations of voltage gated sodium channel subunit genes (CACNB4) and nonsense mutations in voltage gated calcium channels (CACNA1A) have been linked to idiopathic generalized epilepsy in two families. We speculate that gene mutations altering the ability of the beta subunit to interact with the alpha subunit of the CaV1.1 channel and mutations in the pore-forming potassium channel subunit may be possible explanations for the combined manifestation of both diseases. Functional analysis of voltage gated calcium channel and other ion channels mutations may provide additional support and insight for the causal role of these mutations. The understanding of mutations in ion-channel genes will lead to improved diagnosis and treatment of such inherited channelopathies. PMID:25893123

  1. Evaluation of quality of life of carers of Italian spinoni with idiopathic epilepsy

    PubMed Central

    De Risio, Luisa; Freeman, Julia; Shea, Anita

    2016-01-01

    The carers of all UK Kennel Club registered Italian spinoni (IS) born between January 1, 2000 and December 31, 2011 were invited to participate in the study. The carers of 47 of 63 IS diagnosed with idiopathic epilepsy (IE) returned the questionnaire, which included numerous questions on various aspects of IE including the effect of IE on the dog's carer's quality of life. Median epileptic seizure number in the three months before study end or death was five epileptic seizures, 72 per cent of dogs had cluster seizures, 94 per cent of dogs were administered one or more antiepileptic medications and 36 per cent of dogs were euthanased due to poorly controlled IE. Seventy-one per cent and 65 per cent of the participants were moderately to extremely worried about the frequency and severity of their dog's epileptic seizures, respectively. Caring for an IS with IE caused conflict with the carer's work, education or daily activity often or very often in 50 per cent of the participants. Overall the limitations on the carer's life due to caring for an IS with IE were considered as very to extremely bothersome in 29 per cent of the participants, a little to moderately bothersome in 40 per cent of the participants and not at all bothersome in 31 per cent of the participants. PMID:27403328

  2. [Progress in molecular genetics of epilepsy].

    PubMed

    Tang, Beisha; Zhang, Yuhu

    2002-12-01

    Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function. PMID:12476426

  3. Developmental dyscalculia in children and adolescents with idiopathic epilepsies in a Brazilian sample.

    PubMed

    Thomé, Ursula; Paixão Alves, Sandra Regina da; Guerreiro, Sabrina Mendonça; Machado da Costa, Célia Regina Carvalho; Souza Moreira, Fernanda de; Bandeira Lima, Andrea; Ferreira Tavares, Maria Rita; Souza Maia Filho, Heber

    2014-04-01

    Epilepsy is one of the most prevalent chronic disorders of childhood which can threaten child development and mental health. Among cognitive disorders, dyscalculia is one of the most important. In this study, 39 children and adolescents with idiopathic epilepsy underwent clinical and neuropsychological assessment to determine the intellectual level, math skills, reading and writing performance and neuropsychological profile. It was observed that the mathematical ability was below schooling expectations in a higher frequency than expected. There were no significant differences in mathematical performance among groups divided by number of antiepileptic drugs used, duration of disease and types and frequency of seizures. There was a positive correlation with intelligence quotient and attentional and reading level. These results suggest the existence not only of dyscalculia, but the concurrence of attentional and reading problems for the poor mathematical performance in this population. PMID:24760092

  4. Transient neuromyopathy after bromide intoxication in a dog with idiopathic epilepsy

    PubMed Central

    2012-01-01

    A seven-year old Australian Shepherd, suffering from idiopathic epilepsy under treatment with phenobarbitone and potassium bromide, was presented with generalised lower motor neuron signs. Electrophysiology and muscle-nerve biopsies revealed a neuromyopathy. The serum bromide concentration was increased more than two-fold above the upper reference value. Clinical signs disappeared after applying diuretics and reducing the potassium bromide dose rate. This is the first case report describing electrophysiological and histopathological findings associated with bromide induced lower motor neuron dysfunction in a dog. PMID:23216950

  5. Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy

    PubMed Central

    Wang, H; Kuo, M; Chou, M; Hung, P; Lin, K; Hsieh, M; Chang, M

    2005-01-01

    Aim: To study the difference between pyridoxine (PN) and its active form, pyridoxal phosphate, (PLP) in control of idiopathic intractable epilepsy in children. Methods: Among 574 children with active epilepsy, 94 (aged 8 months to 15 years) were diagnosed with idiopathic intractable epilepsy for more than six months. All received intravenous PLP 10 mg/kg, then 10 mg/kg/day in four divided doses. If seizures recurred within 24 hours, another dose of 40 mg/kg was given, followed by 50 mg/kg/day in four divided doses. For those patients whose seizures were totally controlled, PLP was replaced by the same dose of oral PN. If the seizure recurred, intravenous PLP was infused followed by oral PLP 50 mg/kg/day. Results: Fifty seven patients had generalised seizures (of whom 13 had infantile spasms) and 37 had focal seizure. Eleven had dramatic and sustained responses to PLP; of these, five also responded to PN. Within six months of treatment with PLP or PN, five of the 11 patients were seizure free and had their previous antiepileptic medicine tapered off gradually. Two were controlled with pyridoxine and the other three needed PLP to maintain seizure freedom. The remaining six responders needed PLP exclusively for seizure control. Six of the 11 responders to PLP had infantile spasms (46%); four of them needed PLP exclusively. The other five responders were in the remaining 81 patients with other seizure type. Conclusions: PLP could replace PN in the treatment of intractable childhood epilepsy, particularly in the treatment of infantile spasms. PMID:15851435

  6. Congenital ocular motor apraxia associated with idiopathic generalized epilepsy in monozygotic twins.

    PubMed

    Gonzalez-Martin, J A; Kaye, L C; Brown, M; Ellis, I; Appelton, R; Kaye, S B

    2004-06-01

    Identical female twins (age 11 years) with congenital ocular motor apraxia and generalized idiopathic epilepsy are reported. Their presenting symptoms were a long history of abnormal head and eye movements. One twin developed partial sensory seizures. The patients underwent 16-channel EEG, electro-oculographic recordings, MRI of the brain, and genetic and metabolic investigations. EEG findings were consistent with idiopathic generalized epilepsy. Electrooculographic recordings of the saccades confirmed an inability to elicit horizontal saccades without preceding head movement; saccades to the left were better than saccades to the right. MR scans for one twin showed normal findings, however, for the twin who had meningitis they revealed asymmetry between the right and left temporal lobes but no specific abnormality. DNA analysis using a series of autosomal polymorphic markers confirmed the monozygocity of the twins. White blood cell enzyme analysis excluded Sandhoff disease, Tay-Sachs disease, GM1 gangliosidosis, metacromatic leucodystrophy, Gaucher disease, Niemann-Pick disease (A and B), and Krabbe leucodystrophy. Albumin and immunoglobulin (IgA, IgG, and IgM) levels were normal. It is concluded that autosomal recessive inheritance seems the most likely explanation here, as recent studies have found insertion and missense mutations of the aprataxin gene which have been related to an early onset form of ataxia with ocular motor apraxia and hypoalbuminaemia. PMID:15174536

  7. Epilepsy

    MedlinePlus

    Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions ...

  8. GABAergic neuron deficit as an idiopathic generalized epilepsy mechanism: the role of BRD2 haploinsufficiency in juvenile myoclonic epilepsy.

    PubMed

    Velíšek, Libor; Shang, Enyuan; Velíšková, Jana; Chachua, Tamar; Macchiarulo, Stephania; Maglakelidze, Giorgi; Wolgemuth, Debra J; Greenberg, David A

    2011-01-01

    Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/- mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/- males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/- female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/- vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/- mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/- mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE. PMID:21887291

  9. Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy

    PubMed Central

    Kahle, Kristopher T; Merner, Nancy D; Friedel, Perrine; Silayeva, Liliya; Liang, Bo; Khanna, Arjun; Shang, Yuze; Lachance-Touchette, Pamela; Bourassa, Cynthia; Levert, Annie; Dion, Patrick A; Walcott, Brian; Spiegelman, Dan; Dionne-Laporte, Alexandre; Hodgkinson, Alan; Awadalla, Philip; Nikbakht, Hamid; Majewski, Jacek; Cossette, Patrick; Deeb, Tarek Z; Moss, Stephen J; Medina, Igor; Rouleau, Guy A

    2014-01-01

    The KCC2 cotransporter establishes the low neuronal Cl− levels required for GABAA and glycine (Gly) receptor-mediated inhibition, and KCC2 deficiency in model organisms results in network hyperexcitability. However, no mutations in KCC2 have been documented in human disease. Here, we report two non-synonymous functional variants in human KCC2, R952H and R1049C, exhibiting clear statistical association with idiopathic generalized epilepsy (IGE). These variants reside in conserved residues in the KCC2 cytoplasmic C-terminus, exhibit significantly impaired Cl−-extrusion capacities resulting in less hyperpolarized Gly equilibrium potentials (EGly), and impair KCC2 stimulatory phosphorylation at serine 940, a key regulatory site. These data describe a novel KCC2 variant significantly associated with a human disease and suggest genetically encoded impairment of KCC2 functional regulation may be a risk factor for the development of human IGE. PMID:24928908

  10. Common pediatric epilepsy syndromes.

    PubMed

    Park, Jun T; Shahid, Asim M; Jammoul, Adham

    2015-02-01

    Benign rolandic epilepsy (BRE), childhood idiopathic occipital epilepsy (CIOE), childhood absence epilepsy (CAE), and juvenile myoclonic epilepsy (JME) are some of the common epilepsy syndromes in the pediatric age group. Among the four, BRE is the most commonly encountered. BRE remits by age 16 years with many children requiring no treatment. Seizures in CAE also remit at the rate of approximately 80%; whereas, JME is considered a lifelong condition even with the use of antiepileptic drugs (AEDs). Neonates and infants may also present with seizures that are self-limited with no associated psychomotor disturbances. Benign familial neonatal convulsions caused by a channelopathy, and inherited in an autosomal dominant manner, have a favorable outcome with spontaneous resolution. Benign idiopathic neonatal seizures, also referred to as "fifth-day fits," are an example of another epilepsy syndrome in infants that carries a good prognosis. BRE, CIOE, benign familial neonatal convulsions, benign idiopathic neonatal seizures, and benign myoclonic epilepsy in infancy are characterized as "benign" idiopathic age-related epilepsies as they have favorable implications, no structural brain abnormality, are sensitive to AEDs, have a high remission rate, and have no associated psychomotor disturbances. However, sometimes selected patients may have associated comorbidities such as cognitive and language delay for which the term "benign" may not be appropriate. PMID:25658216

  11. Lack of an association between candidate gene loci and idiopathic generalized epilepsy in Kuwaiti Arab children.

    PubMed

    Haider, M Z; Habeeb, Y; Al-Nakkas, E; Al-Anzi, H; Zaki, M; Al-Tawari, A; Al-Bloushi, M

    2005-10-01

    Idiopathic generalized epilepsies (IGEs) are the most common types of epilepsy in childhood and adolescence. A variety of data suggest that IGEs have a predominant genetic etiology. Recently, a number of gene mutations have been found to be associated with various types of epilepsy in mainly the Caucasian populations. The objective of this study was to investigate the association of three different candidate genes with IGE in Kuwaiti Arab children. This study includes 123 Kuwaiti patients with a confirmed diagnosis of epilepsy. Most of the patients have had a diagnostic EEG with generalized spike-wave discharges (GSWs). All patients were evaluated by using a validated seizure questionnaire. The clinical type of epilepsy was determined by a trained neurologist/pediatrician. The study also include 100 controls, the control subjects were children which did not have any history of neurological disorders. Blood samples were collected from all patients and control subjects after taking informed consent. DNA was isolated and analyzed by molecular methods. A FokI polymorphism in neuronal nicotinic acetylcholine receptor alpha-4 subunit (CHRNA4) gene was detected by PCR-RFLP method. A missense mutation (Ser248Phe) in CHRNA4 gene was analyzed by PCR-RFLP using HpaII. A C121W mutation in sodium-channel beta-1 subunit (SCN1B) gene was screened by a PCR-RFLP method using HinPI. A 2-bp deletion in Cystatin B gene was detected by PCR-RFLP using XcmI. The incidence of three FokI polymorphism genotypes in Kuwaiti IGE patients was 1,1 (85%), 1,2 (14%) and 2,2 (1%) respectively. The missense mutation Ser248Phe of CHRNA4 gene was not detected at all in Kuwaiti IGE patients. The C387G transversion resulting in C121W change in third exon of the SCN1B gene was detected in 3/123 patients (2%). The patients carrying this mutation also exhibited febrile seizures. The incidence of 2 bp deletion in the cystatin B gene was found to be 4% (5/123 IGE patients). The data obtained from molecular

  12. Long-Term Clinical and Electroencephalography (EEG) Consequences of Idiopathic Partial Epilepsies.

    PubMed

    Dörtcan, Nimet; Tekin Guveli, Betul; Dervent, Aysin

    2016-01-01

    BACKGROUND Idiopathic partial epilepsies of childhood (IPE) affect a considerable proportion of children. Three main electroclinical syndromes of IPE are the Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS), Panayiotopoulos Syndrome (PS), and Childhood Epilepsy with Occipital Paroxysms (CEOP). In this study we investigated the long-term prognosis of patients with IPE and discussed the semiological and electroencephalography (EEG) data in terms of syndromic characteristics. MATERIAL AND METHODS This study included a group of consecutive patients with IPE who had been followed since 1990. Demographic and clinical variables were investigated. Patients were divided into 3 groups - A: Cases suitable for a single IPE (BECTS, PS and CEOP); B: cases with intermediate characteristics within IPEs; and C: cases with both IPE and IGE characteristics. Long-term data regarding the individual seizure types and EEG findings were re-evaluated. RESULTS A total of 61 patients were included in the study. Mean follow-up duration was 7.8±4.50 years. The mean age at onset of seizures was 7.7 years. There were 40 patients in group A 40, 14 in group B, and 7 in group C. Seizure and EEG characteristics were also explored independently from the syndromic approach. Incidence of autonomic seizures is considerably high at 2-5 years and incidence of oromotor seizures is high at age 9-11 years. The EEG is most abnormal at 6-8 years. The vast majority (86%) of epileptic activity (EA) with parietooccipital is present at 2-5 years, whereas EA with fronto-temporal or multiple sites become more abundant between ages 6 and 11. CONCLUSIONS Results of the present study provide support for the age-related characteristics of the seizures and EEGs in IPE syndromes. Acknowledgement of those phenomena may improve the management of IPEs and give a better estimate of the future consequences. PMID:27138132

  13. Epilepsy

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Epilepsy KidsHealth > For Kids > Epilepsy Print A A A ... With Epilepsy Different? en español Epilepsia What Is Epilepsy? Epilepsy comes from a Greek word meaning "to ...

  14. Relationship Between Large-Scale Functional and Structural Covariance Networks in Idiopathic Generalized Epilepsy

    PubMed Central

    Zhang, Zhiqiang; Mantini, Dante; Xu, Qiang; Wang, Zhengge; Chen, Guanghui; Jiao, Qing; Zang, Yu-Feng

    2013-01-01

    Abstract The human brain can be modeled as a network, whose structure can be revealed by either anatomical or functional connectivity analyses. Little is known, so far, about the topological features of the large-scale interregional functional covariance network (FCN) in the brain. Further, the relationship between the FCN and the structural covariance network (SCN) has not been characterized yet, in the intact as well as in the diseased brain. Here, we studied 59 patients with idiopathic generalized epilepsy characterized by tonic–clonic seizures and 59 healthy controls. We estimated the FCN and the SCN by measuring amplitude of low-frequency fluctuations (ALFF) and gray matter volume (GMV), respectively, and then we conducted graph theoretical analyses. Our ALFF-based FCN and GMV-based results revealed that the normal human brain is characterized by specific topological properties such as small worldness and highly-connected hub regions. The patients had an altered overall topology compared to the controls, suggesting that epilepsy is primarily a disorder of the cerebral network organization. Further, the patients had altered nodal characteristics in the subcortical and medial temporal regions and default-mode regions, for both the FCN and SCN. Importantly, the correspondence between the FCN and SCN was significantly larger in patients than in the controls. These results support the hypothesis that the SCN reflects shared long-term trophic mechanisms within functionally synchronous systems. They can also provide crucial information for understanding the interactions between the whole-brain network organization and pathology in generalized tonic–clonic seizures. PMID:23510272

  15. Novel α1 and γ2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy.

    PubMed

    Lachance-Touchette, Pamela; Brown, Patricia; Meloche, Caroline; Kinirons, Peter; Lapointe, Line; Lacasse, Hélène; Lortie, Anne; Carmant, Lionel; Bedford, Fiona; Bowie, Derek; Cossette, Patrick

    2011-07-01

    Epilepsy is a heterogeneous neurological disease affecting approximately 50 million people worldwide. Genetic factors play an important role in both the onset and severity of the condition, with mutations in several ion-channel genes being implicated, including those encoding the GABA(A) receptor. Here, we evaluated the frequency of additional mutations in the GABA(A) receptor by direct sequencing of the complete open reading frame of the GABRA1 and GABRG2 genes from a cohort of French Canadian families with idiopathic generalized epilepsy (IGE). Using this approach, we have identified three novel mutations that were absent in over 400 control chromosomes. In GABRA1, two mutations were found, with the first being a 25-bp insertion that was associated with intron retention (i.e. K353delins18X) and the second corresponding to a single point mutation that replaced the aspartate 219 residue with an asparagine (i.e. D219N). Electrophysiological analysis revealed that K353delins18X and D219N altered GABA(A) receptor function by reducing the total surface expression of mature protein and/or by curtailing neurotransmitter effectiveness. Both defects would be expected to have a detrimental effect on inhibitory control of neuronal circuits. In contrast, the single point mutation identified in the GABRG2 gene, namely P83S, was indistinguishable from the wildtype subunit in terms of surface expression and functionality. This finding was all the more intriguing as the mutation exhibited a high degree of penetrance in three generations of one French Canadian family. Further experimentation will be required to understand how this mutation contributes to the occurrence of IGE in these individuals. PMID:21714819

  16. Epilepsy

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Epilepsy KidsHealth > For Teens > Epilepsy Print A A A ... embarrass himself or scare his friends. What Is Epilepsy? Epilepsy is a condition of the nervous system ...

  17. Epilepsy

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Epilepsy Information Page Clinical Trials Epilepsy Surgery This study ... en Español Additional resources from MedlinePlus What is Epilepsy? The epilepsies are a spectrum of brain disorders ...

  18. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy.

    PubMed

    Elshahabi, Adham; Klamer, Silke; Sahib, Ashish Kaul; Lerche, Holger; Braun, Christoph; Focke, Niels K

    2015-01-01

    Idiopathic/genetic generalized epilepsy (IGE/GGE) is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease. PMID:26368933

  19. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy

    PubMed Central

    Elshahabi, Adham; Klamer, Silke; Sahib, Ashish Kaul; Lerche, Holger; Braun, Christoph; Focke, Niels K.

    2015-01-01

    Idiopathic/genetic generalized epilepsy (IGE/GGE) is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease. PMID:26368933

  20. The genetic absence epilepsy rat from Strasbourg as a model to decipher the neuronal and network mechanisms of generalized idiopathic epilepsies.

    PubMed

    Depaulis, Antoine; David, Olivier; Charpier, Stéphane

    2016-02-15

    First characterized in 1982, the genetic absence epilepsy rat from Strasbourg (GAERS) has emerged as an animal model highly reminiscent of a specific form of idiopathic generalized epilepsy. Both its electrophysiological (spike-and-wave discharges) and behavioral (behavioral arrest) features fit well with those observed in human patients with typical absence epilepsy and required by clinicians for diagnostic purposes. In addition, its sensitivity to antiepileptic drugs closely matches what has been described in the clinic, making this model one of the most predictive. Here, we report how the GAERS, thanks to its spontaneous, highly recurrent and easily recognizable seizures on electroencephalographic recordings, allows to address several key-questions about the pathophysiology and genetics of absence epilepsy. In particular, it offers the unique possibility to explore simultaneously the neural circuits involved in the generation of seizures at different levels of integration, using multiscale methodologies, from intracellular recording to functional magnetic resonance imaging. In addition, it has recently allowed to perform proofs of concept for innovative therapeutic strategies such as responsive deep brain stimulation or synchrotron-generated irradiation based radiosurgery. PMID:26068173

  1. [Orofacial idiopathic pain: clinical signs, causes and mechanisms].

    PubMed

    Woda, A; Pionchon, P

    2001-03-01

    Atypical facial pain, stomatodynia, atypical odontalgia, masticatory muscle and some temporomandibular joint disorders are grouped together under the category of orofacial idiopathic pain as they reveal numerous common clinical features. For each of these entities, problems of definition and terminology are discussed. Epidemiological and demographic data and a semiological description are given. Proposed diagnostic criteria and some of the causes or mechanisms common to these entities are also described in this article. Firstly, the rôle of female hormones in the physiology and treatment of certain patients is suggested with regard to the marked prevalence of changes in oestrogen levels in patients with orofacial idiopathic pain. Postmenopausal osteoporosis and the hypothesis of neuralgia due to the presence of cavities of osteonecrosis are placed within the context of atypical facial pain. A neuropathic component is suggested for these pain entities. These latter may be linked to a phenomenon of central sensitisation that is induced and maintained by activity in the peripheral tissues. Clinical features of both atypical facial pain and atypical odontalgia have led several authors to advocate the existence of a sympathetic mechanism in the physiopathology of these entities. Moreover, some arguments emphasize similarities with Complex Regional Pain Syndromes of limbs. Lastly, psychosocial components are also considered as a common factor, but it is currently impossible to determine if the pain is the cause or the result of psychosocial problems. Currently, none of these mechanisms can be considered as a single established etiological factor. Indeed, each of these mechanisms can be observed in all types of orofacial idiopathic pain. This leads to the hypothesis that these different mechanisms may act on each target tissue but the details of interaction are still unknown. PMID:11319488

  2. Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies.

    PubMed

    Niemeyer, María Isabel; Yusef, Yamil R; Cornejo, Isabel; Flores, Carlos A; Sepúlveda, Francisco V; Cid, L Pablo

    2004-09-16

    The ClC-2 Cl- channel has been postulated to play a role in the inhibitory GABA response in neurons or to participate in astrocyte-dependent extracellular electrolyte homeostasis. Three different mutations in the CLCN2 gene, encoding the voltage-dependent homodimeric ClC-2 channel, have been associated with idiopathic generalized epilepsy (IGE). We study their function in vitro by patch clamp and confocal microscopy in transiently transfected HEK-293 cells. A first mutation predicts a premature stop codon (M200fsX231). An altered splicing, due to an 11-bp deletion in intron 2 (IVS2-14del11), predicts exon 3 skipping (Delta74-117). A third is a missense mutation (G715E). M200fsX231 and Delta74-117 are nonfunctional and do not affect the function of the normal (wild type, WT) channel. Neither M200fsX231 nor Delta74-117 reach the plasma membrane. Concerning the IVS2-14del11 mutation, we find no difference in the proportion of exon-skipped to normally spliced mRNA using a minigene approach and, on this basis, predict no alteration in channel expression in affected individuals. G715E has voltage dependence and intracellular Cl- dependence indistinguishable from WT channels. ClC-2 channels are shown to be sensitive to intracellular replacement of ATP by AMP, which accelerates the opening and closing kinetics. This effect is diminished in the G715E mutant and not significant in WT+G715E coexpression. We do not know whether, in a situation of cellular ATP depletion, this might become pathological in individuals carrying the mutation. We postulate that loss of function mutation M200fsX231 of ClC-2 might contribute to the IGE phenotype through a haploinsufficiency mechanism. PMID:15252188

  3. Frequency-Specific Alterations of Local Synchronization in Idiopathic Generalized Epilepsy

    PubMed Central

    Wang, Jue; Zhang, Zhiqiang; Ji, Gong-Jun; Xu, Qiang; Huang, Yubin; Wang, Zhengge; Jiao, Qing; Yang, Fang; Zang, Yu-Feng; Liao, Wei; Lu, Guangming

    2015-01-01

    Abstract Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a “conscious perception network,” which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands. PMID:26266394

  4. Cognitive impairment in childhood onset epilepsy: up-to-date information about its causes

    PubMed Central

    Kim, Eun-Hee

    2016-01-01

    Cognitive impairment associated with childhood-onset epilepsy is an important consequence in the developing brain owing to its negative effects on neurodevelopmental and social outcomes. While the cause of cognitive impairment in epilepsy appears to be multifactorial, epilepsy-related factors such as type of epilepsy and underlying etiology, age at onset, frequency of seizures, duration of epilepsy, and its treatment are considered important. In recent studies, antecedent cognitive impairment before the first recognized seizure and microstructural and functional alteration of the brain at onset of epilepsy suggest the presence of a common neurobiological mechanism between epilepsy and cognitive comorbidity. However, the overall impact of cognitive comorbidity in children with epilepsy and the independent contribution of each of these factors to cognitive impairment have not been clearly delineated. This review article focuses on the significant contributors to cognitive impairment in children with epilepsy. PMID:27186225

  5. Idiopathic bilateral diaphragmatic dysfunction as a cause of dyspnea

    PubMed Central

    MacBruce, D; Safdar, S; Katpally, K; Shaaban, Hamid; Adelman, M

    2016-01-01

    Diaphragmatic paralysis is an unusual and often underrecognized cause of dyspnea. We present a case of bilateral diaphragmatic paralysis with no identifiable etiology. Our patient is a 73-year-old female with a history of smoking who presented with dyspnea and orthopnea. She was treated for obstructive lung disease with no improvement in dyspnea despite adequate therapy. She had pulmonary function tests (PFTs) that revealed marked decrease in vital capacity and was unable to perform lung volume maneuvers supine due to marked dyspnea. The maximal inspiratory pressure was 37 in the upright position and decreased to 27 in the supine position. She was given a presumptive diagnosis of idiopathic bilateral diaphragmatic dysfunction. Given the history, physical exam, and PFT findings, we felt that the patient did not need further invasive testing. The patient was treated with noninvasive mechanical ventilation due to hypercapnia and her symptoms improved. PMID:27186002

  6. Effectiveness of Rufinamide in the Treatment of Idiopathic Generalized Epilepsy With Atypical Evolution: Case Report and Review of the Literature.

    PubMed

    Albini, Mariarita; Morano, Alessandra; Fanella, Martina; Lapenta, Leonardo; Casciato, Sara; Fattouch, Jinane; Manfredi, Mario; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2016-04-01

    Rufinamide (RFD) is a novel drug that was recently approved as an adjunctive treatment for Lennox-Gastaut syndrome. Despite its reported effectiveness in generalized seizures (tonic, atonic, or tonic-clonic) in this syndrome, few data on its use in idiopathic generalized epilepsy are available. Indeed, the scientific evidence to date is limited to anecdotal cases or isolated clinical experiences. We report an uncommon, though paradigmatic, case of a woman affected by juvenile absence epilepsy (JAE) who, following a prolonged seizure-freedom period and the consequent withdrawal of valproate, presented a seizure relapse accompanied by a worsening in her electroclinical pattern. In view of this atypical evolution of JAE, characterized by drug-resistant seizures (absence and generalized tonic-clonic) and the progressive increase in electroencephalographic (EEG) abnormalities, several antiepileptic drugs were used, though to no benefit. The use of RFD instead led to a gradual control of the seizures and normalization of the EEG findings. In addition to this clinical experience, we briefly review the literature on the use of RFD in refractory generalized epilepsy. PMID:25420625

  7. Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3.

    PubMed

    Korenke, Georg-Christoph; Eggert, Marlene; Thiele, Holger; Nürnberg, Peter; Sander, Thomas; Steinlein, Ortrud K

    2016-03-01

    Mutations in NPRL3, one of three genes that encode proteins of the mTORC1-regulating GATOR1 complex, have recently been reported to cause cortical dysplasia with focal epilepsy. We have now analyzed a multiplex epilepsy family by whole exome sequencing and identified a frameshift mutation (NM_001077350.2; c.1522delG; p.E508Rfs*46) within exon 13 of NPRL3. This truncating mutation causes an epilepsy phenotype characterized by early childhood onset of mainly nocturnal frontal lobe epilepsy. The penetrance in our family was low (three affected out of six mutation carriers), compared to families with either ion channel- or DEPDC5-associated familial nocturnal frontal lobe epilepsy. The absence of apparent structural brain abnormalities suggests that mutations in NPRL3 are not necessarily associated with focal cortical dysplasia but might be able to cause epilepsy by different, yet unknown pathomechanisms. PMID:26786403

  8. High frequency of a single nucleotide substitution (c.-6-180T>G) of the canine MDR1/ABCB1 gene associated with phenobarbital-resistant idiopathic epilepsy in Border Collie dogs.

    PubMed

    Mizukami, Keijiro; Yabuki, Akira; Chang, Hye-Sook; Uddin, Mohammad Mejbah; Rahman, Mohammad Mahbubur; Kushida, Kazuya; Kohyama, Moeko; Yamato, Osamu

    2013-01-01

    A single nucleotide substitution (c.-6-180T>G) associated with resistance to phenobarbital therapy has been found in the canine MDR1/ABCB1 gene in Border Collies with idiopathic epilepsy. In the present study, a PCR-restriction fragment length polymorphism assay was developed for genotyping this mutation, and a genotyping survey was carried out in a population of 472 Border Collies in Japan to determine the current allele frequency. The survey demonstrated the frequencies of the T/T wild type, T/G heterozygote, and G/G mutant homozygote to be 60.0%, 30.3%, and 9.8%, respectively, indicating that the frequency of the mutant G allele is extremely high (24.9%) in Border Collies. The results suggest that this high mutation frequency of the mutation is likely to cause a high prevalence of phenobarbital-resistant epilepsy in Border Collies. PMID:24302812

  9. Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myocloni epilepsy: No evidence for an epilepsy locus in the HLA region

    SciTech Connect

    Whitehouse, W.P.; Rees, M.; Curtis, D.; Sundqvist, A.; Parker, K.; Chung, E.; Baralle, D.; Gardiner, R.M.

    1993-09-01

    Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6889, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype. 39 refs., 4 figs., 2 tabs.

  10. Pseudoangiomatous Stromal Hyperplasia: A Rare Cause of Idiopathic Gigantomastia

    PubMed Central

    Roy, Mélissa; Lee, James; Aldekhayel, Salah

    2015-01-01

    Summary: Gigantomastia remains a rare clinical diagnosis with significant physical and psychological impacts on patients. We present the case of a 40-year-old woman with idiopathic breast enlargement. Further histological analysis of the breast tissue revealed pseudoangiomatous stromal hyperplasia. This is the first reported case of diffuse breast enlargement resulting from pseudoangiomatous stromal hyperplasia. PMID:26495214

  11. Pseudoangiomatous Stromal Hyperplasia: A Rare Cause of Idiopathic Gigantomastia.

    PubMed

    Roy, Mélissa; Lee, James; Aldekhayel, Salah; Dionisopoulos, Tassos

    2015-09-01

    Gigantomastia remains a rare clinical diagnosis with significant physical and psychological impacts on patients. We present the case of a 40-year-old woman with idiopathic breast enlargement. Further histological analysis of the breast tissue revealed pseudoangiomatous stromal hyperplasia. This is the first reported case of diffuse breast enlargement resulting from pseudoangiomatous stromal hyperplasia. PMID:26495214

  12. Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

    PubMed Central

    Dazzo, Emanuela; Fanciulli, Manuela; Serioli, Elena; Minervini, Giovanni; Pulitano, Patrizia; Binelli, Simona; Di Bonaventura, Carlo; Luisi, Concetta; Pasini, Elena; Striano, Salvatore; Striano, Pasquale; Coppola, Giangennaro; Chiavegato, Angela; Radovic, Slobodanka; Spadotto, Alessandro; Uzzau, Sergio; La Neve, Angela; Giallonardo, Anna Teresa; Mecarelli, Oriano; Tosatto, Silvio C.E.; Ottman, Ruth; Michelucci, Roberto; Nobile, Carlo

    2015-01-01

    Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain. PMID:26046367

  13. Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy.

    PubMed

    Dazzo, Emanuela; Fanciulli, Manuela; Serioli, Elena; Minervini, Giovanni; Pulitano, Patrizia; Binelli, Simona; Di Bonaventura, Carlo; Luisi, Concetta; Pasini, Elena; Striano, Salvatore; Striano, Pasquale; Coppola, Giangennaro; Chiavegato, Angela; Radovic, Slobodanka; Spadotto, Alessandro; Uzzau, Sergio; La Neve, Angela; Giallonardo, Anna Teresa; Mecarelli, Oriano; Tosatto, Silvio C E; Ottman, Ruth; Michelucci, Roberto; Nobile, Carlo

    2015-06-01

    Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain. PMID:26046367

  14. A prospective study of the modified Atkins diet for adults with idiopathic generalized epilepsy.

    PubMed

    Kverneland, Magnhild; Selmer, Kaja K; Nakken, Karl O; Iversen, Per O; Taubøll, Erik

    2015-12-01

    For children with pharmacoresistant epilepsy, the ketogenic diet is an established treatment option worldwide. However, for adults, this treatment is less frequently offered, and its efficacy less well-documented. The aim of this study was to examine efficacy and tolerability of such a diet as an adjuvant therapy to antiepileptic drugs for adult patients with pharmacoresistant generalized epilepsy. Thirteen patients (12 women) aged 16-57 years were included prospectively. They were treated with a modified Atkins diet for 12 weeks. Nine of the 13 participants had juvenile myoclonic epilepsy (JME), two had childhood absence epilepsy, one had Jeavons syndrome, and one had generalized epilepsy of unknown type. Six participants, all with JME, completed the 12-week study period. Among these six, four had >50% seizure reduction. Their seizure severity, using the revised Liverpool Seizure Severity Scale, was reduced by 1, 5, 57.5, and 70 points, respectively (scale: 1-100 points). In three of these four responders, quality of life, assessed by QOLIE-89, increased more than 20 points (scale: 0-100 points). Mean reduction of body weight after 12 weeks on diet was 6.5 (range: 4.3-8.1) kg. Lack of motivation, poor compliance, and seizure aggravation were the main reasons for premature termination of the diet. Apart from one patient who developed gallstones when ending the treatment after 10 months, no adverse effects were noted. In conclusion, using a modified Atkins diet for 12 weeks led to a clinically relevant reduction of seizure frequency in four of thirteen adult patients with pharmacoresistant generalized epilepsy. All responders were diagnosed with JME. In three of the four, the benefits of diet were so considerable that they chose to continue the treatment. PMID:26588588

  15. Epilepsy prevalence, potential causes and social beliefs in Ebonyi State and Benue State, Nigeria.

    PubMed

    Osakwe, Chijioke; Otte, Willem M; Alo, Chimhurumnanya

    2014-02-01

    Epilepsy is a common neurological disorder in Nigeria. Many individuals are affected in rural areas, although prevalence data is not available. In this study we aimed to establish the prevalence of epilepsy in a rural community in south-east Nigeria, a community suspected for having a high number of people living with epilepsy. We compared this with the prevalence in a nearby semi-urban community in north-central Nigeria. In both communities we identified potential causes of epilepsy and obtained information on the social beliefs regarding epilepsy. We used door-to-door surveys and focus group discussions. The epilepsy prevalence in the rural community was 20.8/1000 [95% confidence interval (CI): 15.7-27.4]. The prevalence in the semi-rural community was lower, namely 4.7/1000 [CI: 3.2-6.9]. The difference in prevalence was highly significant (χ(2)-test, p<0.0001). In both communities most people with epilepsy were in the age range of 7-24 years. Causes that might be contributory to the prevalence of epilepsy in both communities included poor obstetric practices, frequent febrile convulsions, head trauma, meningitis and neurocysticercosis. In both communities we found stigma of people with epilepsy. In conclusion, the epilepsy prevalence in the semi-urban community is similar to that in industrialized countries. In contrast, the rural community has a much higher prevalence. This may require the establishment of specific community-based epilepsy control programs. Community interventions should focus on treatment of acute epilepsy and on stigma reduction. PMID:24300028

  16. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy.

    PubMed

    Law, Tsz Hong; Davies, Emma S S; Pan, Yuanlong; Zanghi, Brian; Want, Elizabeth; Volk, Holger A

    2015-11-14

    Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68-43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·041 (sd 0·004) v. 0·031 (sd 0·016) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment. PMID:26337751

  17. RFT1-congenital disorder of glycosylation (CDG) syndrome: a cause of early-onset severe epilepsy.

    PubMed

    Aeby, Alec; Prigogine, Cynthia; Vilain, Catheline; Malfilatre, Geneviève; Jaeken, Jaak; Lederer, Damien; Van Bogaert, Patrick

    2016-03-01

    RFT1-congenital disorder of glycosylation (CDG) syndrome, a recessive N-glycosylation disorder caused by mutation in the RFT1 gene, is a very rare subtype of CDG syndrome associated with deafness, developmental delay, and non-specific epilepsy. The aim of this report is to describe the electroclinical presentation of epilepsy associated with this condition. [Published with video sequences online]. PMID:26892341

  18. Baseline Cognition, Behavior, and Motor Skills in Children with New-Onset, Idiopathic Epilepsy

    ERIC Educational Resources Information Center

    Bhise, Vikram V.; Burack, Gail D.; Mandelbaum, David E.

    2010-01-01

    Aim: Epilepsy is associated with difficulties in cognition and behavior in children. These problems have been attributed to genetics, ongoing seizures, psychosocial issues, underlying abnormality of the brain, and/or antiepileptic drugs. In a previous study, we found baseline cognitive differences between children with partial versus generalized…

  19. When the face says it all: dysmorphology in identifying syndromic causes of epilepsy.

    PubMed

    Dixit, Abhijit; Suri, Mohnish

    2016-04-01

    Identifying the underlying cause of epilepsy often helps in choosing the appropriate management, suggests the long-term prognosis and clarifies the risk of the same condition in relatives. Epilepsy has many causes and a small but significant proportion of affected people have an identifiable genetic cause. Here, we discuss the role of genetic testing in adults with epilepsy, focusing on dysmorphic features noticeable on physical examination that might provide a strong clue to a specific genetic syndrome. We give illustrative examples of recognisable facial 'gestalt'. An astute clinician can recognise such clues and significantly shorten the process of making the underlying diagnosis in their patient. PMID:26864574

  20. LGI2 Truncation Causes a Remitting Focal Epilepsy in Dogs

    PubMed Central

    Seppälä, Eija H.; Jokinen, Tarja S.; Fukata, Masaki; Fukata, Yuko; Webster, Matthew T.; Karlsson, Elinor K.; Kilpinen, Sami K.; Steffen, Frank; Dietschi, Elisabeth; Leeb, Tosso; Eklund, Ranja; Zhao, Xiaochu; Rilstone, Jennifer J.; Lindblad-Toh, Kerstin; Minassian, Berge A.; Lohi, Hannes

    2011-01-01

    One quadrillion synapses are laid in the first two years of postnatal construction of the human brain, which are then pruned until age 10 to 500 trillion synapses composing the final network. Genetic epilepsies are the most common neurological diseases with onset during pruning, affecting 0.5% of 2–10-year-old children, and these epilepsies are often characterized by spontaneous remission. We previously described a remitting epilepsy in the Lagotto romagnolo canine breed. Here, we identify the gene defect and affected neurochemical pathway. We reconstructed a large Lagotto pedigree of around 34 affected animals. Using genome-wide association in 11 discordant sib-pairs from this pedigree, we mapped the disease locus to a 1.7 Mb region of homozygosity in chromosome 3 where we identified a protein-truncating mutation in the Lgi2 gene, a homologue of the human epilepsy gene LGI1. We show that LGI2, like LGI1, is neuronally secreted and acts on metalloproteinase-lacking members of the ADAM family of neuronal receptors, which function in synapse remodeling, and that LGI2 truncation, like LGI1 truncations, prevents secretion and ADAM interaction. The resulting epilepsy onsets at around seven weeks (equivalent to human two years), and remits by four months (human eight years), versus onset after age eight in the majority of human patients with LGI1 mutations. Finally, we show that Lgi2 is expressed highly in the immediate post-natal period until halfway through pruning, unlike Lgi1, which is expressed in the latter part of pruning and beyond. LGI2 acts at least in part through the same ADAM receptors as LGI1, but earlier, ensuring electrical stability (absence of epilepsy) during pruning years, preceding this same function performed by LGI1 in later years. LGI2 should be considered a candidate gene for common remitting childhood epilepsies, and LGI2-to-LGI1 transition for mechanisms of childhood epilepsy remission. PMID:21829378

  1. The causes of new-onset epilepsy and seizures in the elderly

    PubMed Central

    Liu, Shasha; Yu, Weihua; Lü, Yang

    2016-01-01

    With increasing age, the prevalence and incidence of epilepsy and seizures increases correspondingly. New-onset epilepsy in elderly people often has underlying etiology, including cerebrovascular diseases, primary neuron degenerative disorders, intracerebral tumors, and traumatic head injury. In addition, an acute symptomatic seizure cannot be called epilepsy, which manifests usually as a common symptom secondary to metabolic or toxicity factors in older people. In this review, we have mainly focused on the causes of new-onset epilepsy and seizures in elderly people. This knowledge will certainly help us to understand the reasons for high incidences of epilepsy and seizures in elderly people. We look forward to controlling epileptic seizures via the treatment of primary diseases in the future. PMID:27382285

  2. Comparing the effects of first-line antiepileptic drugs on the gait of dogs with idiopathic epilepsy.

    PubMed

    Suiter, E J; Packer, R M A; Volk, H A

    2016-06-25

    Idiopathic epilepsy (IE) is a common chronic neurological disease of the dog. Previous studies of anti-epileptic drug (AED) treatment have indicated that acceptable AED adverse effects are as important to owners as reductions in seizure frequency. AEDs in both dogs and human beings are frequently associated with the adverse-effect ataxia. The aim of this study was to compare ataxia levels in dogs with IE treated chronically with phenobarbitone or imepitoin, the two currently available first-line AED treatments. The gait of 6 imepitoin-treated dogs, 8 phenobarbitone-treated dogs and 10 age-matched healthy control dogs were compared. Fifty strides from a walking gait were analysed for each dog, quantifying ataxia via the variability in six established gait parameters. Three variables differed significantly between groups: lateral distance between (i) pelvic paw placements, (ii) thoracic paw placements and (iii) stance time, which were significantly more variable in the phenobarbitone-treated dogs than imepitoin-treated or control dogs. These results indicate that dogs treated with phenobarbitone experience ataxia compared with controls and imepitoin-treated dogs. Conversely, there was no difference between imepitoin-treated dogs and controls. These results along with further research are needed to quantify AEDs adverse effects, to help vets and owners make more informed drug-choices. PMID:27302918

  3. [Epilepsy as a cause of removal from the Armed Forces].

    PubMed

    Cossío Díaz, José Ramón

    2011-01-01

    Recently, the First Chamber of the Supreme Court of Justice decided two important cases where the Ministers were urged to evaluate whether a provision of the Social Security Institute for the Mexican Armed Forces Statute making“epilepsy and other forms of seizures or equivalents” a cause of removal from the Army on the basis of “uselessness in the service” violates the equality and non-discrimination principle laid down in article 1 of the Federal Constitution. Four Supreme Court Ministers declared that the provision was constitutional. Justice Minister Cossío Díaz disagreed and wrote a separate opinion where he holds that the aforementioned provision is unconstitutional, since its excessively wide and undetermined language opens the door to declarations of “uselessness for the service” without ensuring this rests in every case in a genuine incapacity to develop a job in the Army.Before reaching this conclusion Justice Minister Cossío asked for information to the National Institute of Neurology and Neurosurgery. It was on these basis that he sustained that the aforementioned legal provision does not satisfy an adequate means-end correlation, since it allows the Army to withdraw from service –on the basis of “uselessness”–persons whose medical condition is sometimes episodic; others curable; others, if not curable, pharmaceutically controlled; and, in cases where it does limit the kinds of activity, that the person can develop, it does so in a way that can only be determined by an intensely individualized basis. PMID:21894236

  4. First-drug treatment failures in 42 Turkish children with idiopathic childhood occipital epilepsies

    PubMed Central

    Incecik, Faruk; Herguner, Ozlem M.; Altunbasak, Sakir

    2015-01-01

    Background: The early and late benign occipital epilepsies of childhood (BOEC) are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. The purpose of this study was to identify predictors of failure to respond to the initial antiepileptic drug (AED). Materials and Methods: A total of 42 children with BOEC were enrolled. Predictive factors were analyzed by survival methods. Results: Among the 42, 25 patients (59.5%) were boys and 17 (40.5%) were girls and the mean age at the seizure onset was 7.46 ± 2.65 years (4–14 years). Of the 42 patients, 34 (81.0%) were treated relatively successfully with the first AED treatment, and 8 (19.0%) were not responded initial AED treatment. There was no correlation between response to initial AED treatment and sex, consanguinity, epilepsy history of family, age of seizure onset, frequency of seizures, history of status epilepticus, duration of starting first treatment, findings on electroencephalogram. However, history of febrile seizure and type of BOEC were significantly associated with failure risk. Conclusions: Factors predicting failure to respond to the AED were history of febrile seizure and type of BOEC in children with BOEC. PMID:26167008

  5. Brivaracetam in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus.

    PubMed

    Strzelczyk, Adam; Klein, Karl Martin; Willems, Laurent M; Rosenow, Felix; Bauer, Sebastian

    2016-01-01

    Brivaracetam is the latest approved antiepileptic drug in focal epilepsy and exhibits high affinity as SV2A-ligand. More than two thousand patients have received brivaracetam within randomized placebo-controlled trials. Significant median seizure reduction rates of 30.5% to 53.1% for 50 mg/d, 32.5% to 37.2% for 100 mg/d and 35.6% for 200 mg/d were reported. Likewise, 50% responder rates were 32.7% to 55.8% for 50 mg/d, 36% to 38.9% for 100 mg/d and 37.8% for 200 mg/d. Overall, brivaracetam is well tolerated. The main adverse events are fatigue, dizziness, and somnolence. Immediate switch from levetiracetam to brivaracetam at a conversion ratio between 10:1 to 15:1 is feasible, and might alleviate the behavioral side effects associated with levetiracetam. Brivaracetam has the potential to perform as an important, possibly broad-spectrum AED, initially in patients with drug-refractory epilepsies. Its intravenous formulation may be a new and desirable alternative for status epilepticus, but there is so far no experience in these patients. PMID:26891946

  6. Diagnosing and Solving School Learning Disabilities in Epilepsy: Part 2--A List of Causes

    ERIC Educational Resources Information Center

    Mittan, Robert J.

    2010-01-01

    The possible causes of learning difficulties in children with epilepsy are long and complex. In order to see that a child is given an adequate evaluation, an understanding of what these many causes are and how those causes may be interrelated is necessary. This article discusses the first three of the six categories of the causes: (1) Organic; (2)…

  7. DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy.

    PubMed

    Striano, Pasquale; Serioli, Elena; Santulli, Lia; Manna, Ida; Labate, Angelo; Dazzo, Emanuela; Pasini, Elena; Gambardella, Antonio; Michelucci, Roberto; Striano, Salvatore; Nobile, Carlo

    2015-10-01

    Mutations in the DEPDC5 (DEP domain-containing protein 5) gene are a major cause of familial focal epilepsy with variable foci (FFEVF) and are predicted to account for 12-37% of families with inherited focal epilepsies. To assess the clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we screened a collection of Italian families with either autosomal dominant lateral temporal epilepsy (ADLTE) or familial mesial temporal lobe epilepsy (FMTLE). The probands of 28 families classified as ADLTE and 17 families as FMTLE were screened for DEPDC5 mutations by whole exome or targeted massive parallel sequencing. Putative mutations were validated by Sanger sequencing. We identified a DEPDC5 nonsense mutation (c.918C>G; p.Tyr306*) in a family with two affected members, clinically classified as FMTLE. The proband had temporal lobe seizures with prominent psychic symptoms (déjà vu, derealization, and forced thoughts); her mother had temporal lobe seizures, mainly featuring visceral epigastric auras and anxiety. In total, we found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies. PMID:26216793

  8. Common subtypes of idiopathic generalized epilepsies: Lack of linkage to D20S19 close to candidate loci (EBN1, EEGV1) on chromosome 20

    SciTech Connect

    Sander, T.; Schmitz, B.; Janz, D.

    1996-02-16

    Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). A trait locus (EBN1) for a rare subtype of IGEs, the benign neonatal familial convulsions, and a susceptibility gene (EEGV1) for the common human low-voltage electroencephalogram have been mapped close together with D20S19 to the chromosomal region 20q13.2. Both loci are potential candidates for the susceptibility to IGE spectra with age-related onset beyond the neonatal period. The present study tested the hypothesis that a putative susceptibility locus linked to D20S19 predisposes to spectra of IGEs with age-related onset from childhood to adolescence. Linkage analyses were conducted in 60 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy. Our results provide evidence against linkage of a putative susceptibility gene for four hierarchically broadened IGE spectra with D20S19 assuming tentative single-locus genetic models. The extent of an {open_quotes}exclusion region{close_quotes} (lod scores below -2) varied from 0.5 cM up to 22 cM on either side of D2OSl9 depending on the trait assumed. These results are contrary to the expectation that a susceptibility gene in vicinity to D20S19 confers a common major gene effect to the expression of IGE spectra with age-related onset from childhood to adolescence. 50 refs., 1 fig., 1 tab.

  9. Epilepsy

    SciTech Connect

    Fisher, R.S.; Frost, J.J. )

    1991-04-01

    As surgical treatments for adult and pediatric forms of epilepsy have become more refined, methods for noninvasive localization of epileptogenic foci have become increasingly important. Detection of focal brain metabolic or flow abnormalities is now well recognized as an essential step in the presurgical evaluation of many patients with epilepsy. Positron emission tomography (PET) scanning is most beneficial when used in the context of the total clinical evaluation of patients, including scalp EEG, invasive EEG, neuropsychologic testing, etc. Metabolic PET studies also give insight into pathophysiologic mechanisms of epilepsy. The dynamic nature of the interictal hypometabolism observed with 18(F)FDG in some patients suggests that excitatory or inhibitory neurotransmitters and their receptors may be involved. An exciting current application of PET scanning is the use of tracers for neurotransmitter receptors in the study of epilepsy patients. Mu and non-mu opiate receptors have been extensively studied and are beginning to give new insights into this disorder. Increased labeling of mu receptors in temporal neocortex using 11C-carfentanil has been demonstrated and, in some patients, supplements the clinical localization information from 18(F)FDG studies. Increased mu opiate receptor number or affinity is thought to play a role in anticonvulsant mechanisms. Specificity of increased mu receptors is supported by the absence of significant changes in non-mu opiate receptors. Other brain receptors are also of interest for future studies, particularly those for excitatory neurotransmitters. Combined studies of flow, metabolism, and neuroreceptors may elucidate the factors responsible for initiation and termination of seizures, thus improving patient treatment.95 references.

  10. Epilepsy.

    PubMed

    Krishnamurthy, Kaarkuzhali B

    2016-02-01

    This issue provides a clinical overview of epilepsy, focusing on diagnosis, prevention, treatment, and further considerations. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers. PMID:26829918

  11. Seizures and epilepsy in oncological practice: causes, course, mechanisms and treatment

    PubMed Central

    Singh, Gagandeep; Rees, Jeremy H; Sander, Josemir W

    2007-01-01

    There are few data available on the causes and mechanistic basis, outcome and treatment of seizures and epilepsy in people with systemic cancer. Seizures and epilepsy in people with cancers other than primary brain tumours are reviewed here. Articles published in English, which discussed the neurological manifestations and complications of cancer and its treatment, were searched and information on the frequency, aetiology, and course of seizures and epilepsy was extracted. The frequency, aetiology and outcome of seizure disorders in patients with cancer differ from those in the general population. Intracranial metastasis, cancer drugs and metabolic disturbances are the most common causes. Infections, cerebrovascular complications of systemic cancer and paraneoplastic disorders are among the rarer causes of seizures in patients with neoplasms. Several drugs used in the treatment of cancer, or complications arising from their use, can trigger seizures through varied mechanisms. Most drug‐induced seizures are provoked and do not require long‐term treatment with antiepileptic drugs. PMID:17369589

  12. Congenital Muscular Dystrophy and Generalized Epilepsy Caused by GMPPB Mutations

    PubMed Central

    Raphael, Alya R.; Couthouis, Julien; Sakamuri, Sarada; Siskind, Carly; Vogel, Hannes; Day, John W.; Gitler, Aaron D.

    2014-01-01

    The alpha-dystroglycanopathies are genetically heterogeneous muscular dystrophies that result from hypoglycosylation of alpha-dystroglycan (α-DG). Alpha-dystroglycan is an essential link between the extracellular matrix and the muscle fiber sarcolemma, and proper glycosylation is critical for its ability to bind to ligands in the extracellular matrix. We sought to identify the genetic basis of alpha-dystroglycanopathy in a family wherein the affected individuals presented with congenital muscular dystrophy, brain abnormalities and generalized epilepsy. We performed whole exome sequencing and identified compound heterozygous GMPPB mutations in the affected children. GMPPB is an enzyme in the glycosylation pathway, and GMPPB mutation were recently linked to eight cases of alpha-dystroglycanopathy with a range of symptoms. We identified a novel mutation in GMPPB (p.I219T) as well as a previously published mutation (p.R287Q). Thus, our work further confirms a role for GMPPB defects in alpha-dystroglycanopathy, and suggests that glycosylation may play a role in the neuronal membrane channels or networks involved in the physiology of generalized epilepsy syndromes. PMID:24780531

  13. The Human Epilepsy Mutation GABRG2(Q390X) Causes Chronic Subunit Accumulation and Neurodegeneration

    PubMed Central

    Kang, Jing-Qiong; Shen, Wangzhen; Zhou, Chengwen; Xu, Dong; Macdonald, Robert L.

    2015-01-01

    Genetic epilepsy and neurodegenerative diseases are two common neurological disorders conventionally viewed as being unrelated. A subset of patients with severe genetic epilepsies with impaired development and often death respond poorly to anticonvulsant drug therapy, suggesting a need for new therapeutic targets. Previously, we reported that multiple GABAA receptor epilepsy mutations caused protein misfolding and abnormal receptor trafficking. Here we establish in a novel model of a severe human genetic epileptic encephalopathy, the Gabrg2+/Q390X knock-in mouse, that in addition to impairing inhibitory neurotransmission, mutant GABAA receptor γ2(Q390X) subunits accumulated and aggregated intracellularly, activated caspase 3 and caused widespread, age-dependent neurodegeneration. These novel findings suggest that the fundamental protein metabolism and cellular consequences of the epilepsy-associated mutant γ2(Q390X) ion channel subunit are not fundamentally different from those associated with neurodegeneration. The study has far-reaching significance for identification of conserved pathological cascades and mechanism-based therapies that overlap genetic epilepsies and neurodegenerative diseases. PMID:26005849

  14. De Novo Mutations in SIK1 Cause a Spectrum of Developmental Epilepsies

    PubMed Central

    Hansen, Jeanne; Snow, Chelsi; Tuttle, Emily; Ghoneim, Dalia H.; Yang, Chun-Song; Spencer, Adam; Gunter, Sonya A.; Smyser, Christopher D.; Gurnett, Christina A.; Shinawi, Marwan; Dobyns, William B.; Wheless, James; Halterman, Marc W.; Jansen, Laura A.; Paschal, Bryce M.; Paciorkowski, Alex R.

    2015-01-01

    Developmental epilepsies are age-dependent seizure disorders for which genetic causes have been increasingly identified. Here we report six unrelated individuals with mutations in salt-inducible kinase 1 (SIK1) in a series of 101 persons with early myoclonic encephalopathy, Ohtahara syndrome, and infantile spasms. Individuals with SIK1 mutations had short survival in cases with neonatal epilepsy onset, and an autism plus developmental syndrome after infantile spasms in others. All six mutations occurred outside the kinase domain of SIK1 and each of the mutants displayed autophosphorylation and kinase activity toward HDAC5. Three mutations generated truncated forms of SIK1 that were resistant to degradation and also showed changes in sub-cellular localization compared to wild-type SIK1. We also report the human neuropathologic examination of SIK1-related developmental epilepsy, with normal neuronal morphology and lamination but abnormal SIK1 protein cellular localization. Therefore, these results expand the genetic etiologies of developmental epilepsies by demonstrating SIK1 mutations as a cause of severe developmental epilepsy. PMID:25839329

  15. Cerebellar Dysfunction and Ataxia in Patients with Epilepsy: Coincidence, Consequence, or Cause?

    PubMed Central

    Marcián, Václav; Filip, Pavel; Bareš, Martin; Brázdil, Milan

    2016-01-01

    Basic epilepsy teachings assert that seizures arise from the cerebral cortex, glossing over infratentorial structures such as the cerebellum that are believed to modulate rather than generate seizures. Nonetheless, ataxia and other clinical findings in epileptic patients are slowly but inevitably drawing attention to this neural node. Tracing the evolution of this line of inquiry from the observed coincidence of cerebellar atrophy and cerebellar dysfunction (most apparently manifested as ataxia) in epilepsy to their close association, this review considers converging clinical, physiological, histological, and neuroimaging evidence that support incorporating the cerebellum into epilepsy pathology. We examine reports of still controversial cerebellar epilepsy, studies of cerebellar stimulation alleviating paroxysmal epileptic activity, studies and case reports of cerebellar lesions directly associated with seizures, and conditions in which ataxia is accompanied by epileptic seizures. Finally, the review substantiates the role of this complex brain structure in epilepsy whether by coincidence, as a consequence of deleterious cortical epileptic activity or antiepileptic drugs, or the very cause of the disease. PMID:27375960

  16. Assessment of Time and Frequency Domain Parameters of Heart Rate Variability and Interictal Cardiac Rhythm Abnormalities in Drug-naïve Patients with Idiopathic Generalized Epilepsy

    PubMed Central

    Kilinc, Ozden; Cincin, Altug; Pehlivan, Aslihan; Midi, Ipek; Kepez, Alper; Agan, Kadriye

    2016-01-01

    Background and Purpose: Epilepsy is a disease known to occur with autonomous phenomenons. Earlier studies indicate decreased heart rate variability (HRV) during ictal and interictal periods among epilepsy patients. In this study, we aim to investigate cardiac rhythm abnormalities and HRV during interictal period between drug-naïve patients with idiopathic generalized epilepsy (IGE) and healthy control group. Methods: Twenty-six patients with IGE and 26 healthy individuals included in the study. In order to eliminate any structural cardiac pathology, transthoracic echocardiography was performed in all subjects and time and frequency domain parameters of HRV were evaluated after 24-hour rhythm holter monitoring. Results: Between two groups, no significant difference was detected in terms of mean heart rate and maximum duration between the start of the Q waves and the end of the T waves (QT intervals). In the time domain analysis of HRV, no statically significant difference was detected for standard deviation of all R - R intervals and root-mean-square of successive differences between patient and control group (p = 0,070 and p = 0,104 respectively). In the frequency domain analysis of HRV, patients tended to display lower total power and very low frequency power than did healthy subjects, but the differences were not statistically significant. Conclusions: Our results suggest that there is no major effect of the epilepsy on HRV in patients with IGE. It should be emphasized that, in this study, HRV was evaluated only in patients with IGE and that the results are not proper to be generalized for patients with partial seizures. PMID:27390676

  17. Epilepsy - overview

    MedlinePlus

    Epilepsy is a brain disorder in which a person has repeated seizures over time. Seizures are episodes ... Epilepsy occurs when permanent changes in the brain cause it to be too excitable or irritable. As ...

  18. Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability

    PubMed Central

    Lam, Wayne W.K.; Millichap, John J.; Soares, Dinesh C.; Chin, Richard; McLellan, Ailsa; FitzPatrick, David R.; Elmslie, Frances; Lees, Melissa M.; Schaefer, G. Bradley

    2016-01-01

    Background Exome sequencing has led to the discovery of mutations in novel causative genes for epilepsy. One such gene is EEF1A2, encoding a neuromuscular specific translation elongation factor, which has been found to be mutated de novo in five cases of severe epilepsy. We now report on a further seven cases, each with a different mutation, of which five are newly described. Methods New cases were identified and sequenced through the Deciphering Developmental Disabilities project, via direct contact with neurologists or geneticists, or recruited via our website. Results All the mutations cause epilepsy and intellectual disability, but with a much wider range of severity than previously identified. All new cases share specific subtle facial dysmorphic features. Each mutation occurs at an evolutionarily highly conserved amino acid position indicating strong structural or functional selective pressure. Conclusions EEF1A2 should be considered as a causative gene not only in cases of epileptic encephalopathy but also in children with less severe epilepsy and intellectual disability. The emergence of a possible discernible phenotype, a broad nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth may help in identifying patients with mutations in EEF1A2. PMID:27441201

  19. Epilepsy

    MedlinePlus

    ... and it is not a sign of low intelligence. It is also not contagious. Seizures do not ... example, a partial seizure may cause changes in emotions, or to the senses (for example, hallucinations, numbness, ...

  20. Idiopathic hypersomnia

    MedlinePlus

    ... page, please enable JavaScript. Idiopathic hypersomnia is a sleep disorder in which a person is excessively sleepy ( hypersomnia ) ... other potential causes of excessive daytime sleepiness. Other sleep disorders that may cause daytime sleepiness include: Narcolepsy Obstructive ...

  1. Hlf is a genetic modifier of epilepsy caused by voltage-gated sodium channel mutations.

    PubMed

    Hawkins, Nicole A; Kearney, Jennifer A

    2016-01-01

    Mutations in voltage-gated sodium channel genes cause several types of human epilepsies. Often, individuals with the same sodium channel mutation exhibit diverse phenotypes. This suggests that factors beyond the primary mutation influence disease severity, including genetic modifiers. Mouse epilepsy models with voltage-gated sodium channel mutations exhibit strain-dependent phenotype variability, supporting a contribution of genetic modifiers in epilepsy. The Scn2a(Q54) (Q54) mouse model has a strain-dependent epilepsy phenotype. Q54 mice on the C57BL/6J (B6) strain exhibit delayed seizure onset and improved survival compared to [B6xSJL/J]F1.Q54 mice. We previously mapped two dominant modifier loci that influence Q54 seizure susceptibility and identified Hlf (hepatic leukemia factor) as a candidate modifier gene at one locus. Hlf and other PAR bZIP transcription factors had previously been associated with spontaneous seizures in mice thought to be caused by down-regulation of the pyridoxine pathway. An Hlf targeted knockout mouse model was used to evaluate the effect of Hlf deletion on Q54 phenotype severity. Hlf(KO/KO);Q54 double mutant mice exhibited elevated frequency and reduced survival compared to Q54 controls. To determine if direct modulation of the pyridoxine pathway could alter the Q54 phenotype, mice were maintained on a pyridoxine-deficient diet for 6 weeks. Dietary pyridoxine deficiency resulted in elevated seizure frequency and decreased survival in Q54 mice compared to control diet. To determine if Hlf could modify other epilepsies, Hlf(KO/+) mice were crossed with the Scn1a(KO/+) Dravet syndrome mouse model to examine the effect on premature lethality. Hlf(KO/+);Scn1a(KO/+) offspring exhibited decreased survival compared to Scn1a(KO/+) controls. Together these results demonstrate that Hlf is a genetic modifier of epilepsy caused by voltage-gated sodium channel mutations and that modulation of the pyridoxine pathway can also influence phenotype

  2. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

    PubMed

    Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

    2014-12-01

    Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes. PMID:25362483

  3. Altered expression of neuropeptide Y receptors caused by focal cortical dysplasia in human intractable epilepsy

    PubMed Central

    Luo, Hanjiang; Guan, Yuguang; Zhou, Jian; Qi, Xueling; Li, Tianfu; Xu, Zhiqing David; Luan, Guo-Ming

    2016-01-01

    Focal cortical dysplasia (FCD) is a common cause of pharmacologically-intractable epilepsy, however, the precise mechanisms underlying the epileptogenicity of FCD remains to be determined. Neuropeptide Y (NPY), an endogenous anticonvulsant in the central nervous system, plays an important role in the regulation of neuronal excitability. Increased expression of NPY and its receptors has been identified in the hippocampus of patients with mesial temporal lobe epilepsy, presumed to act as an endogenous anticonvulsant mechanism. Therefore, we investigated whether expression changes in NPY receptors occurs in patients with FCD. We specifically investigated the expression of seizure-related NPY receptor subtypes Y1, Y2, and Y5 in patients with FCD versus autopsy controls. We found that Y1R and Y2R were up-regulated at the mRNA and protein levels in the temporal and frontal lobes in FCD lesions. By contrast, there was no significant change in either receptor detected in parietal lesions. Notably, overexpression of Y5R was consistently observed in all FCD lesions. Our results demonstrate the altered expression of Y1R, Y2R and Y5R occurs in FCD lesions within the temporal, frontal and parietal lobe. Abnormal NPY receptor subtype expression may be associated with the onset and progression of epileptic activity and may act as a therapeutic candidate for the treatment of refractory epilepsy caused by FCD. PMID:26943580

  4. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes

    PubMed Central

    May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M. Arfan; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G.; Cilio, Maria Roberta; Kunz, Wolfram S.; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R.; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A.

    2016-01-01

    Objective The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10−4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions. PMID:26990884

  5. Spontaneous idiopathic bilateral adrenal haemorrhage: a rare cause of abdominal pain.

    PubMed

    Nazir, Salik; Sivarajah, Surendra; Fiscus, Valena; York, Eugene

    2016-01-01

    We describe a case of a 62-year-old woman with a history of chronic obstructive pulmonary disease and gastro-oesophageal reflux disease who presented to the emergency department with left lower quadrant abdominal pain, flank pain with nausea and no history of preceding trauma. The patient had finished a course of azithromycin and oral methylprednisolone 1 day prior to presentation. Abdominal and pelvic CT scan identified changes suggestive of bilateral adrenal haemorrhage. The patient did not show signs of acute adrenal insufficiency but was started on steroid replacement therapy because of concerns about possible disease progression. All recognised causes of adrenal haemorrhage were excluded suggesting this was a case of spontaneous idiopathic bilateral adrenal haemorrhage, a rarely reported phenomenon in the literature. The patient was discharged after clinical improvement following 6 days in hospital, taking oral steroid replacement. PMID:27166002

  6. Idiopathic anaphylaxis.

    PubMed

    Greenberger, Paul A

    2007-05-01

    Idiopathic anaphylaxis is a prednisone-responsive condition without external cause, but it can coexist with food-, medication-, or exercise-induced anaphylaxis. Mast cell activation may occur at night or after foods that have been eaten with impunity many times previously. Idiopathic anaphylaxis can be classified into frequent (if there are six or more episodes per year or two episodes in the last 2 months) or infrequent (if episodes occur less often). Idiopathic anaphylaxis-generalized consists of urticaria or angioedema associated with severe respiratory distress, syncope or hypotension, and gastrointestinal symptoms. Idiopathic anaphylaxis-angioedema consists of massive tongue enlargement or severe pharyngeal or laryngeal swelling with urticaria or peripheral angioedema. The differential diagnosis of idiopathic anaphylaxis is reviewed, and treatment approaches are presented. PMID:17493503

  7. Idiopathic hypersomnia

    MedlinePlus

    Hypersomnia - idiopathic; Drowsiness - idiopathic; Somnolence - idiopathic ... extremely sleepy. It is different from narcolepsy because idiopathic hypersomnia does not usually involve suddenly falling asleep (sleep ...

  8. Patterns of postictal cerebral perfusion in idiopathic generalized epilepsy: a multi-delay multi-parametric arterial spin labelling perfusion MRI study

    PubMed Central

    Chen, Guangxiang; Lei, Du; Ren, Jiechuan; Zuo, Panli; Suo, Xueling; Wang, Danny J. J.; Wang, Meiyun; Zhou, Dong; Gong, Qiyong

    2016-01-01

    The cerebral haemodynamic status of idiopathic generalized epilepsy (IGE) is a very complicated process. Little attention has been paid to cerebral blood flow (CBF) alterations in IGE detected by arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI). However, the selection of an optimal delay time is difficult for single-delay ASL. Multi-delay multi-parametric ASL perfusion MRI overcomes the limitations of single-delay ASL. We applied multi-delay multi-parametric ASL perfusion MRI to investigate the patterns of postictal cerebral perfusion in IGE patients with absence seizures. A total of 21 IGE patients with absence seizures and 24 healthy control subjects were enrolled. IGE patients exhibited prolonged arterial transit time (ATT) in the left superior temporal gyrus. The mean CBF of IGE patients was significantly increased in the left middle temporal gyrus, left parahippocampal gyrus and left fusiform gyrus. Prolonged ATT in the left superior temporal gyrus was negatively correlated with the age at onset in IGE patients. This study demonstrated that cortical dysfunction in the temporal lobe and fusiform gyrus may be related to epileptic activity in IGE patients with absence seizures. This information can play an important role in elucidating the pathophysiological mechanism of IGE from a cerebral haemodynamic perspective. PMID:27374369

  9. Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

    SciTech Connect

    Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T. )

    1990-05-01

    A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.

  10. Seizure and Psychosocial Outcomes of Childhood and Juvenile Onset Generalized Epilepsies: Wolf in Sheep's Clothing, or Well-Dressed Wolf?

    PubMed

    Nickels, Katherine

    2015-01-01

    Studies of generalized electroclinical syndromes can provide guidance regarding long-term seizure, cognitive, and psychosocial outcomes. Childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and idiopathic generalized epilepsy with generalized tonic-clonic seizures alone are electroclinical syndromes typically associated with normal intellect and good response to antiseizure medications. However, studies have demonstrated significantly poorer psychosocial outcomes than expected for these syndromes, regardless of seizure control. Potential causes for this include underlying abnormalities in social skills, social stigma, and underlying abnormalities in brain development and maturation. PMID:26316843

  11. International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol.

    PubMed

    Rusbridge, Clare; Long, Sam; Jovanovik, Jelena; Milne, Marjorie; Berendt, Mette; Bhatti, Sofie F M; De Risio, Luisa; Farqhuar, Robyn G; Fischer, Andrea; Matiasek, Kaspar; Muñana, Karen; Patterson, Edward E; Pakozdy, Akos; Penderis, Jacques; Platt, Simon; Podell, Michael; Potschka, Heidrun; Stein, Veronika M; Tipold, Andrea; Volk, Holger A

    2015-01-01

    Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature.There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6-7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed. PMID:26319136

  12. Idiopathic scoliosis.

    PubMed

    Yaman, Onur; Dalbayrak, Sedat

    2014-01-01

    Scoliosis refers to curves exceeding 10 degrees observed through posterioanterior direct radiography. In fact, the diagnosis for idiopathic scoliosis is accepted to exclude already available causes. The aim of this paper was to review the etiopathogenesis, classification systems and the treatment management of idiopathic scoliosis. A search in the National Library of Medicine (Pubmed) database using the key words 'idiopathic' and 'scoliosis' was performed. For the literature review, papers concerning the etiopathogenesis, classification and treatment were selected among these articles. A search in the National Library of Medicine (Pubmed) database using the key words 'idiopathic' and 'scoliosis' yielded 4518 articles published between 1947 and 2013. The main hypothesis put forward included genetic factors, hormonal factors, bone and connective tissue anomalies. King, Lenke, Coonrad and Peking Union Medical College (PUMC) classifications were the main classification systems for idiopathic scoliosis. Exercise, bracing and anterior, posterior or combined surgery when indicated are the choices for the treatment. Every idiopathic scoliosis case has to be managed to its own characteristics. It is the post-operative appearance that the surgeons are perhaps the least interested but the adolescent patients the most interested in. The aim of scoliosis surgery is to restore the spine without neurological deficit. PMID:25269032

  13. Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model.

    PubMed

    Douaud, Marine; Feve, Katia; Pituello, Fabienne; Gourichon, David; Boitard, Simon; Leguern, Eric; Coquerelle, Gérard; Vieaud, Agathe; Batini, Cesira; Naquet, Robert; Vignal, Alain; Tixier-Boichard, Michèle; Pitel, Frédérique

    2011-01-01

    Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans. PMID:22046416

  14. Treatment of resistant epilepsy.

    PubMed

    Pickrell, William Owen; Smith, Phil E M

    2014-12-01

    Treatment resistance affects around 20% of people with epilepsy and carries a significant comorbidity. It is important to ensure that the diagnosis of epilepsy is secure and the underlying cause of the epilepsy is investigated thoroughly. Management involves early referral for epilepsy surgery when suitable, optimisation of pharmacological treatment, and consideration of comorbidities such as depression. PMID:25468911

  15. [Partial infarction of the kidney caused by spontaneous idiopathic dissection of the renal artery].

    PubMed

    Dahmani, Laurent; Murat, François-Joseph; Ouaki, Frédéric; Irani, Jacques; Dore, Bertrand

    2003-09-01

    Idiopathic spontaneous renal artery dissection (SRAD) is a rare disease and must be taken into account in the differential diagnosis of low back pain. It may be due to various aetiologies, secondary to degenerative or traumatic diseases, or it may be idiopathic. Intravenous urography is usually normal. Abdominal CT usually visualizes the renal infarction and selective arteriography confirms the diagnosis of renal artery dissection. Medical treatment and surveillance provide effective management of the disease. However, surgical management may be proposed either immediately or secondarily. SRAD usually has a favourable course, but, in the longer term, may be complicated by organic renal failure and renovascular hypertension. PMID:14650302

  16. Mutations affecting GABAergic signaling in seizures and epilepsy

    PubMed Central

    Galanopoulou, Aristea S.

    2010-01-01

    The causes of epilepsies and epileptic seizures are multifactorial. Genetic predisposition may contribute in certain types of epilepsies and seizures, whether idiopathic or symptomatic of genetic origin. Although these are not very common, they have offered a unique opportunity to investigate the molecular mechanisms underlying epileptogenesis and ictogenesis. Among the implicated gene mutations, a number of GABAA receptor subunit mutations have been recently identified that contribute to several idiopathic epilepsies, febrile seizures, and rarely to certain types of symptomatic epilepsies, like the severe myoclonic epilepsy of infancy. Deletion of GABAA receptor genes has also been linked to Angelman syndrome. Furthermore, mutations of proteins controlling chloride homeostasis, which indirectly defines the functional consequences of GABAA signaling, have been identified. These include the chloride channel 2 (CLCN2) and the potassium chloride cotransporter KCC3. The pathogenic role of CLCN2 mutations has not been clearly demonstrated and may represent either susceptibility genes or, in certain cases, innocuous polymorphisms. KCC3 mutations have been associated with hereditary motor and sensory polyneuropathy with corpus callosum agenesis (Andermann syndrome) that often manifests with epileptic seizures. This review summarizes the recent progress in the genetic linkages of epilepsies and seizures to the above genes and discusses potential pathogenic mechanisms that contribute to the age, sex, and conditional expression of these seizures in carriers of these mutations. PMID:20352446

  17. Diffuse idiopathic skeletal hyperostosis of cervical spine - An unusual cause of difficult flexible fiber optic intubation

    PubMed Central

    Baxi, Vaibhavi; Gaiwal, Sucheta

    2010-01-01

    This is a report of anterior osteophytes on the cervical vertebra resulting in distortion of the airway and leading to difficulty during intubation. The osteophytes associated with the syndrome of diffuse idiopathic skeletal hyperostosis were at the C2-3 and C6-7, T1 level and resulted in anterior displacement of the pharynx and the trachea respectively. PMID:20668561

  18. Pediatric epilepsy syndromes.

    PubMed

    Wirrell, Elaine; Nickels, Katherine C

    2010-06-01

    Epilepsy syndromes denote specific constellations of clinical seizure type(s), EEG findings, and other characteristic clinical features. Most syndromes recognized in epilepsy are genetic and developmental disorders that begin in the pediatric years. Epilepsy syndromes are divided into idiopathic (primary) types, in which the presumed etiology is genetic, versus symptomatic (secondary) types, in which there is either an underlying etiology that is known or presumed based on other evidence of brain dysfunction. Epilepsies are also classified by those with generalized seizures and those with localization-related seizures. Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome for children with epilepsy. In this chapter, clinical and electrographic features as well as inheritance patterns of common pediatric epilepsy syndromes are discussed. PMID:22810315

  19. Genetics Home Reference: Northern epilepsy

    MedlinePlus

    ... Understand Genetics Home Health Conditions Northern epilepsy Northern epilepsy Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Northern epilepsy is a genetic condition that causes recurrent seizures ( ...

  20. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy

    PubMed Central

    Muona, Mikko; Berkovic, Samuel F; Dibbens, Leanne M; Oliver, Karen L; Maljevic, Snezana; Bayly, Marta A; Joensuu, Tarja; Canafoglia, Laura; Franceschetti, Silvana; Michelucci, Roberto; Markkinen, Salla; Heron, Sarah E; Hildebrand, Michael S; Andermann, Eva; Andermann, Frederick; Gambardella, Antonio; Tinuper, Paolo; Licchetta, Laura; Scheffer, Ingrid E; Criscuolo, Chiara; Filla, Alessandro; Ferlazzo, Edoardo; Ahmad, Jamil; Ahmad, Adeel; Baykan, Betul; Said, Edith; Topcu, Meral; Riguzzi, Patrizia; King, Mary D; Ozkara, Cigdem; Andrade, Danielle M; Engelsen, Bernt A; Crespel, Arielle; Lindenau, Matthias; Lohmann, Ebba; Saletti, Veronica; Massano, João; Privitera, Michael; Espay, Alberto J; Kauffmann, Birgit; Duchowny, Michael; Møller, Rikke S; Straussberg, Rachel; Afawi, Zaid; Ben-Zeev, Bruria; Samocha, Kaitlin E; Daly, Mark J; Petrou, Steven; Lerche, Holger; Palotie, Aarno; Lehesjoki, Anna-Elina

    2014-01-01

    Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures, and ataxia. We exome-sequenced 84 unrelated PME patients of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation c.959G>A (p.Arg320His) in KCNC1 was identified as a novel major cause for PME. Eleven unrelated exome-sequenced (13%) and two patients in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated K+ channels, major determinants of high-frequency neuronal firing. Functional analysis of the p.Arg320His mutant channel revealed a dominant-negative loss-of-function effect. Ten patients had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6, SERPINI1). Identification of mutations in PRNP, SACS, and TBC1D24 expand their phenotypic spectrum to PME. These findings provide important insights into the molecular genetic basis of PME and reveal the role of de novo mutations in this disease entity. PMID:25401298

  1. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy.

    PubMed

    Muona, Mikko; Berkovic, Samuel F; Dibbens, Leanne M; Oliver, Karen L; Maljevic, Snezana; Bayly, Marta A; Joensuu, Tarja; Canafoglia, Laura; Franceschetti, Silvana; Michelucci, Roberto; Markkinen, Salla; Heron, Sarah E; Hildebrand, Michael S; Andermann, Eva; Andermann, Frederick; Gambardella, Antonio; Tinuper, Paolo; Licchetta, Laura; Scheffer, Ingrid E; Criscuolo, Chiara; Filla, Alessandro; Ferlazzo, Edoardo; Ahmad, Jamil; Ahmad, Adeel; Baykan, Betul; Said, Edith; Topcu, Meral; Riguzzi, Patrizia; King, Mary D; Ozkara, Cigdem; Andrade, Danielle M; Engelsen, Bernt A; Crespel, Arielle; Lindenau, Matthias; Lohmann, Ebba; Saletti, Veronica; Massano, João; Privitera, Michael; Espay, Alberto J; Kauffmann, Birgit; Duchowny, Michael; Møller, Rikke S; Straussberg, Rachel; Afawi, Zaid; Ben-Zeev, Bruria; Samocha, Kaitlin E; Daly, Mark J; Petrou, Steven; Lerche, Holger; Palotie, Aarno; Lehesjoki, Anna-Elina

    2015-01-01

    Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity. PMID:25401298

  2. Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: a rare case report.

    PubMed

    Singh, Harpal; Kundal, Ramesh

    2015-01-01

    Idiopathic granulomatous myocarditis is extremely rare, particularly since the introduction of drugs effective against tuberculosis (TB), viruses, fungi and the effective treatment of sarcoidosis. Here is a case of a 65-year-old female prisoner having history of sudden collapse and ultimately death. Autopsy findings of various viscera on histopathological examination show granulomatous pathology, that is, in spleen, liver and in the left ventricular wall of heart. Ziehl-Neelsen staining of the sections show the absence of acid fast bacilli, negative for fungal staining as most of the granulomas are noncaseating type with presence of giant cells having no asteroid body and Schuamann body, real-time polymerase chain reaction for TB is negative. Idiopathic giant cell myocarditis is a disease of relatively young adults, that is, between 3 rd and 4 th decade of life. So, this case is strongly considered to be a case of sudden death due to myocarditis as a result of idiopathic systemic granulomatous pathology, a rare case in in literature. PMID:25673606

  3. Challenges in the pharmacological management of epilepsy and its causes in the elderly.

    PubMed

    Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Aguglia, Umberto

    2016-04-01

    Epilepsy represents the third most common neurological disorders in the elderly after cerebrovascular disorders and dementias. The incidence of new-onset epilepsy peaks in this age group. The most peculiar aetiologies of late-onset epilepsy are stroke, dementia, and brain tumours. However, aetiology remains unknown in about half of the patients. Diagnosis of epilepsy may be challenging due to the frequent absence of ocular witnesses and the high prevalence of seizure-mimics (i.e. transient ischemic attacks, syncope, transient global amnesia or vertigo) in the elderly. The diagnostic difficulties are even greater when patients have cognitive impairment or cardiac diseases. The management of late-onset epilepsy deserves special considerations. The elderly can reach seizure control with low antiepileptic drugs (AEDs) doses, and seizure-freedom is possible in the vast majority of patients. Pharmacological management should take into account pharmacokinetics and pharmacodynamics of AEDs and the frequent occurrence of comorbidities and polytherapy in this age group. Evidences from double-blind and open-label studies indicate lamotrigine, levetiracetam and controlled-release carbamazepine as first line treatment in late-onset epilepsy. PMID:26896787

  4. KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function

    PubMed Central

    Reichold, Markus; Zdebik, Anselm A.; Lieberer, Evelyn; Rapedius, Markus; Schmidt, Katharina; Bandulik, Sascha; Sterner, Christina; Tegtmeier, Ines; Penton, David; Baukrowitz, Thomas; Hulton, Sally-Anne; Witzgall, Ralph; Ben-Zeev, Bruria; Howie, Alexander J.; Kleta, Robert; Bockenhauer, Detlef; Warth, Richard

    2010-01-01

    Mutations of the KCNJ10 (Kir4.1) K+ channel underlie autosomal recessive epilepsy, ataxia, sensorineural deafness, and (a salt-wasting) renal tubulopathy (EAST) syndrome. We investigated the localization of KCNJ10 and the homologous KCNJ16 in kidney and the functional consequences of KCNJ10 mutations found in our patients with EAST syndrome. Kcnj10 and Kcnj16 were found in the basolateral membrane of mouse distal convoluted tubules, connecting tubules, and cortical collecting ducts. In the human kidney, KCNJ10 staining was additionally observed in the basolateral membrane of the cortical thick ascending limb of Henle's loop. EM of distal tubular cells of a patient with EAST syndrome showed reduced basal infoldings in this nephron segment, which likely reflects the morphological consequences of the impaired salt reabsorption capacity. When expressed in CHO and HEK293 cells, the KCNJ10 mutations R65P, G77R, and R175Q caused a marked impairment of channel function. R199X showed complete loss of function. Single-channel analysis revealed a strongly reduced mean open time. Qualitatively similar results were obtained with coexpression of KCNJ10/KCNJ16, suggesting a dominance of KCNJ10 function in native renal KCNJ10/KCNJ16 heteromers. The decrease in the current of R65P and R175Q was mainly caused by a remarkable shift of pH sensitivity to the alkaline range. In summary, EAST mutations of KCNJ10 lead to impaired channel function and structural changes in distal convoluted tubules. Intriguingly, the metabolic alkalosis present in patients carrying the R65P mutation possibly improves residual function of KCNJ10, which shows higher activity at alkaline pH. PMID:20651251

  5. Evaluating the Efficacy of Teaching Methods Regarding Prevention of Human Epilepsy Caused by Taenia solium Neurocysticercosis in Western Kenya

    PubMed Central

    Wohlgemut, Jared; Dewey, Cate; Levy, Mike; Mutua, Florence

    2010-01-01

    Taenia solium neurocysticercosis is a major cause of adult-onset epilepsy in developing countries. A questionnaire was administered to 282 Kenyan farmers, followed by a workshop, a second questionnaire, one-on-one training, and a third questionnaire. People who attended workshops were more likely to know how T. solium causes epilepsy in humans in the third visit than the second (P = 0.001). The likelihood that farmers would tether their pigs 100% of the time, limiting exposure to tapeworm eggs, increased after the first (P < 0.001) and second visits (P < 0.001). Farmers were more likely to have heard of Cysticercus cellulosae in the second (P = 0.001) and third visits (P = 0.007), and to know how pigs acquire infection in the second (P = 0.03) and third visits (P = 0.003). Farmers with at least a grade 8 education were more likely to know how T. solium is transmitted to humans in the second (P = 0.001) and third visits (P = 0.009), and were more likely to understand the relationship between epilepsy and T. solium in the second (P = 0.03) and third visits (P = 0.03). Grade 8 education may enhance learning from written material. Workshops followed by individual on-farm training enhanced knowledge acquisition and behavior changes. Training local government extension workers contributed to the sustainability of this project. PMID:20348512

  6. Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?

    PubMed

    Horvath, Gabriella A; Demos, Michelle; Shyr, Casper; Matthews, Allison; Zhang, Linhua; Race, Simone; Stockler-Ipsiroglu, Sylvia; Van Allen, Margot I; Mancarci, Ogan; Toker, Lilah; Pavlidis, Paul; Ross, Colin J; Wasserman, Wyeth W; Trump, Natalie; Heales, Simon; Pope, Simon; Cross, J Helen; van Karnebeek, Clara D M

    2016-01-01

    We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities. PMID:26647175

  7. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

    PubMed

    van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

    2015-12-01

    A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. PMID:26535877

  8. X-Linked adrenoleukodystrophy is a frequent cause of idiopathic Addison`s disease in young adult male patients

    SciTech Connect

    Laureti, S.; Casucci, G.; Santeusanio, F.

    1996-02-01

    X-Linked adrenoleukodystrophy (ALD) is a genetic disease associated with demyelination of the central nervous system, adrenal insufficiency, and accumulation of very long chain fatty acids in tissue and body fluids. ALD is due to mutation of a gene located in Xq28 that encodes a peroxisomal transporter protein of unknown function. The most common phenotype of ALD is the cerebral form (45%) that develops in boys between 5-12 yr. Adrenomyeloneuropathy (AMN) involves the spinal cord and peripheral nerves in young adults (35%). Adrenal insufficiency (Addison`s disease) is frequently associated with AMN or cerebral ALD and may remain the only clinical expression of ALD (8% of cases). The prevalence of ALD among adults with Addison`s disease remains unknown. To evaluate this prevalence, we performed biochemical analysis of very long chain fatty acids in 14 male patients (age ranging from 12-45 yr at diagnosis) previously diagnosed as having primary idiopathic adrenocortical insufficiency. In 5 of 14 patients (35%), elevated plasma concentrations of very long chain fatty acids were detected. None of these patients had adrenocortical antibodies. By electrophysiological tests and magnetic resonance imaging it was determined that two patients had cerebral ALD, one had adrenomyeloneuropathy with cerebral involvement, and two had preclinical AMN. Our data support the hypothesis that ALD is a frequent cause of idiopathic Addison`s disease in children and adults. 30 refs., 5 tabs.

  9. Understanding the burden of idiopathic generalized epilepsy in the United States, Europe, and Brazil: An analysis from the National Health and Wellness Survey.

    PubMed

    Gupta, Shaloo; Kwan, Patrick; Faught, Edward; Tsong, Wan; Forsythe, Anna; Ryvlin, Phillipe

    2016-02-01

    The aim of this study was to understand the current burden of primary generalized tonic-clonic seizures (PGTCS) associated with idiopathic generalized epilepsy (IGE) as a function of seizure frequency. We analyzed data for (IGE) as a proxy measure of PGTCS. Little is known about the quality of life (QoL), health utility, productivity, healthcare resource utilization (HRU), and cost burden of PGTCS or IGE. Patients were identified from the US (2011, 2012, & 2013), 5EU (2011 & 2013), and Brazil (2011 & 2012) National Health and Wellness Survey, a nationally representative, internet-based survey of adults (18+ years). Patients that self-reported a diagnosis of IGE were categorized into seizure frequencies of: ≥1 seizure per week, 1-3 seizures per month, 1-4 seizures per year, or <1 seizure per year. QoL was measured using the SF-36v2 Mental (MCS) and Physical Component Summary (PCS) scores, health utilities with the SF-6D, productivity with the Work Productivity and Activity Impairment (WPAI) questionnaire, and HRU as reported in the past six months. Unit costs were estimated from the literature and multiplied against HRU values to calculate direct costs and WPAI values to calculate indirect costs. Generalized linear regression was utilized to examine the relationship between seizure frequency and each measure of burden with adjustment for covariates. Out of the general population surveyed, IGE was self-reported in 782 of 176,093 (US), 172 of 30,000 (UK), 106 of 30,001 (Germany), 87 of 30,000 (France), 31 of 12,011 (Spain), 22 of 17,500 (Italy), and 34 of 24,000 (Brazil). Persistent seizures (≥1 per year) were reported in over 40% of patients with IGE (10-15% with ≥1 seizure per week, 10-15% with 1-3 seizures per month, 20-25% with 1-4 seizures per year). Over 75% were treated with antiepileptic drugs (AEDs). Compared with those having <1 seizure per year (reference group), patients in the two most frequent seizure categories reported worse MCS and PCS scores

  10. Idiopathic pulmonary hemosiderosis: a rare cause of iron-deficiency anemia in childhood.

    PubMed

    Poggi, Vincenzo; Lo Vecchio, Andrea; Menna, Francesco; Menna, Giuseppe

    2011-05-01

    Idiopathic pulmonary hemosiderosis is a chronic, rare disorder confined to the lung, which is commonly characterized by the triad of recurrent hemoptysis, diffuse parenchyma infiltrates on chest radiography, and iron-deficiency anemia. Diagnosis may be difficult and the clinical course may be widely variable. Here, we describe an 8-year-old boy whose isolated symptom on presentation was iron-deficiency anemia. Presence of hemoptysis and bilateral alveolar infiltrates on chest x-ray led to the diagnosis of pulmonary hemosiderosis, subsequently confirmed by the finding of hemosiderin-laden macrophages by bronchoalveolar lavage. The patient was started on prednisolone 2 mg/kg/d and no further bleeding episodes were noted after the onset of therapy. PMID:21516015

  11. Disruption of Fgf13 Causes Synaptic Excitatory–Inhibitory Imbalance and Genetic Epilepsy and Febrile Seizures Plus

    PubMed Central

    Puranam, Ram S.; He, Xiao Ping; Yao, Lijun; Le, Tri; Jang, Wonjo; Rehder, Catherine W.; Lewis, Darrell V.

    2015-01-01

    We identified a family in which a translocation between chromosomes X and 14 was associated with cognitive impairment and a complex genetic disorder termed “Genetic Epilepsy and Febrile Seizures Plus” (GEFS+). We demonstrate that the breakpoint on the X chromosome disrupted a gene that encodes an auxiliary protein of voltage-gated Na+ channels, fibroblast growth factor 13 (Fgf13). Female mice in which one Fgf13 allele was deleted exhibited hyperthermia-induced seizures and epilepsy. Anatomic studies revealed expression of Fgf13 mRNA in both excitatory and inhibitory neurons of hippocampus. Electrophysiological recordings revealed decreased inhibitory and increased excitatory synaptic inputs in hippocampal neurons of Fgf13 mutants. We speculate that reduced expression of Fgf13 impairs excitability of inhibitory interneurons, resulting in enhanced excitability within local circuits of hippocampus and the clinical phenotype of epilepsy. These findings reveal a novel cause of this syndrome and underscore the powerful role of FGF13 in control of neuronal excitability. PMID:26063919

  12. Idiopathic spinal cord herniation of the cervical cord: unusual cause of proximal muscle weakness in upper limbs.

    PubMed

    Rajapakse, Dilina; Mapara, Leah; Maniharan, Sathiyaseelan

    2016-01-01

    Idiopathic spinal cord herniation (ISCH) is a recognised rare cause of progressive and potentially curable myelopathy. Around 170 cases have been described in the literature, all to be found between the T2 and T8 vertebrae. We report a case of ISCH in the cervical region. A 23-year-old man with no history of trauma presented with a 6-year history of bilateral mild resting hand tremor and left scapular pain radiating to the left arm for a duration of 8 months. Nerve conduction studies showed some denervation changes of the upper limbs and bulbar regions. MRI of the spine showed anterior midline herniation of the spinal cord at the level of C7 vertebra with an associated collection of cerebrospinal fluid in the extradural space in the cervical region. Owing to the non-progressive nature of symptoms, currently the patient is managed conservatively. PMID:27190115

  13. Mutations in TBC1D24, a Gene Associated With Epilepsy, Also Cause Nonsyndromic Deafness DFNB86

    PubMed Central

    Rehman, Atteeq U.; Santos-Cortez, Regie Lyn P.; Morell, Robert J.; Drummond, Meghan C.; Ito, Taku; Lee, Kwanghyuk; Khan, Asma A.; Basra, Muhammad Asim R.; Wasif, Naveed; Ayub, Muhammad; Ali, Rana A.; Raza, Syed I.; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael; Riazuddin, Saima; Billington, Neil; Khan, Shaheen N.; Friedman, Penelope L.; Griffith, Andrew J.; Ahmad, Wasim; Riazuddin, Sheikh; Leal, Suzanne M.; Friedman, Thomas B.

    2014-01-01

    Inherited deafness is clinically and genetically heterogeneous. We recently mapped DFNB86, a locus associated with nonsyndromic deafness, to chromosome 16p. In this study, whole-exome sequencing was performed with genomic DNA from affected individuals from three large consanguineous families in which markers linked to DFNB86 segregate with profound deafness. Analyses of these data revealed homozygous mutation c.208G>T (p.Asp70Tyr) or c.878G>C (p.Arg293Pro) in TBC1D24 as the underlying cause of deafness in the three families. Sanger sequence analysis of TBC1D24 in an additional large family in which deafness segregates with DFNB86 identified the c.208G>T (p.Asp70Tyr) substitution. These mutations affect TBC1D24 amino acid residues that are conserved in orthologs ranging from fruit fly to human. Neither variant was observed in databases of single-nucleotide variants or in 634 chromosomes from ethnically matched control subjects. TBC1D24 in the mouse inner ear was immunolocalized predominantly to spiral ganglion neurons, indicating that DFNB86 deafness might be an auditory neuropathy spectrum disorder. Previously, six recessive mutations in TBC1D24 were reported to cause seizures (hearing loss was not reported) ranging in severity from epilepsy with otherwise normal development to epileptic encephalopathy resulting in childhood death. Two of our four families in which deafness segregates with mutant alleles of TBC1D24 were available for neurological examination. Cosegregation of epilepsy and deafness was not observed in these two families. Although the causal relationship between genotype and phenotype is not presently understood, our findings, combined with published data, indicate that recessive alleles of TBC1D24 can cause either epilepsy or nonsyndromic deafness. PMID:24387994

  14. Clinical case of the month. Idiopathic pulmonary hemosiderosis presenting as a rare cause of iron deficiency anemia in a toddler--a diagnostic challenge.

    PubMed

    Sankararaman, Senthilkumar; Shah, Kinjal; Maddox, Kevin; Velayuthan, Sujithra; Scott, L Keith

    2012-01-01

    Iron deficiency anemia is the most common cause of anemia in all age groups. Idiopathic pulmonary hemosiderosis is an extremely rare etiology of iron deficiency anemia seen predominantly in the pediatric population. Idiopathic pulmonary hemosiderosis is characterized by the triad of symptoms consisting of iron deficiency anemia, diffuse pulmonary infiltrates, and hemoptysis. The clinical presentation is extremely variable, and all three symptoms may not always be seen. Due to the rarity of the disease and the variability in clinical presentation, diagnosis is usually delayed. Early diagnosis and treatment with corticosteroids prevents further episodes of recurrent alveolar hemorrhage and improves the clinical outcome. Hence, a high index of suspicion is required for the diagnosis of this condition in young patients presenting with severe iron deficiency anemia and diffuse pulmonary infiltrates. We report a toddler with idiopathic pulmonary hemosiderosis whose initial clinical presentation was severe iron deficiency anemia. PMID:23362597

  15. Epilepsy in autism: A pathophysiological consideration.

    PubMed

    Nomura, Yoshiko; Nagao, Yuri; Kimura, Kazue; Hachimori, Kei; Segawa, Masaya

    2010-11-01

    Eighty cases of idiopathic autism with epilepsy and 97 cases without epilepsy were studied to evaluate the pathophysiology of epilepsy in autism. The initial visit to this clinic ranged 8months-30years 3months of age, and the current ages are 5years 8months-42years 3months, 60% reaching to over 30years of age. The average follow up duration is 22.2years±9.4years. The ages of onset of epilepsy were from 7months to 30years of age, with the two peaks at 3.2years and 16.7years. EEG central focus appeared earlier than frontal focus. Abnormality of locomotion and atonic NREM were observed more frequently in epileptic group. These suggest the neuronal system related to abnormality of locomotion and atonic NREM, which are the hypofunction of the brainstem monoaminergic system, is the pathomechanism underling the epilepsy in autism. By showing the abnormal sleep-wake rhythm and locomotion being the very initial symptoms in autism, we had shown the hypofunction of the brainstem monoaminergic system is the initial pathomechanism of autism. Thus, epilepsy in autism is not the secondary manifestation, but one of the pathognomonic symptoms of autism. The brainstem monoaminergic system project to the wider cortical area, and the initial monoaminergic hypofunction may lead to the central focus which appears earlier. The failure of the monoaminergic (serotonergic) system causes dysfunction of the pedunculo-pontine nucleus (PPN) and induces dysfunction of the dopamine (DA) system, and with development of the DA receptor supersensitivity consequently disinhibits the thalamo-frontal pathway, which after maturation of this pathway in teens cause the epileptogenesis in the frontal cortex. PMID:20805019

  16. An appraisal of the new operational definition of epilepsy--then and now.

    PubMed

    Malkan, Ashish; Beran, Roy G

    2014-12-01

    The focus to define epilepsy in the newly proposed classification has shifted from the conceptual perspective to practical application thought to better reflect that which is happening to the patient. Within the new definition, a single unprovoked or reflex seizure can be considered as epilepsy if the recurrence risk is similar to that following two unprovoked seizures. Epilepsy is considered to be resolved if the individual had an age-dependent epilepsy syndrome and has passed the applicable age or if the person has remained seizure-free for the last ten years without seizure medications for the last five years. This new operational definition of epilepsy may change the epileptologist's approach regarding when and how long to treat patients with seizures. The new definition also has significant psychosocial and employment-related implications for the patients. With regard to etiology, the terms idiopathic, symptomatic, and cryptogenic have been replaced by genetic, structural/metabolic, and unknown. This reflects a better understanding of the underlying cause of epilepsy based on genetic tests and better neuroimaging. The terms 'simple partial' and 'complex partial' seizures have been replaced by 'focal motor/sensory' and 'focal dyscognitive' seizures, thereby ending the ambiguity associated with the former terms and the difficulty encountered with definitions of altered states of consciousness. These changes, reflective of a better insight into the pathogenesis of seizures and epilepsy, are expected to be more pragmatic and assist when managing patients with epilepsy. PMID:25461219

  17. Causes and Prognosis of Visual Acuity Loss at the Time of Initial Presentation in Idiopathic Intracranial Hypertension

    PubMed Central

    Chen, John J.; Thurtell, Matthew J.; Longmuir, Reid A.; Garvin, Mona K.; Wang, Jui-Kai; Wall, Michael; Kardon, Randy H.

    2015-01-01

    Purpose. To determine the etiology and prognosis of visual acuity loss in idiopathic intracranial hypertension (IIH) at presentation and to provide objective measures to predict visual outcome. Methods. A retrospective review of 660 patients with IIH (2009–2013) identified 31 patients (4.7%) with 48 eyes having best-corrected visual acuity (BCVA) of 20/25 or worse on initial presentation. Fundus photography, optical coherence tomography (OCT) of the optic disc and macula, and perimetry were used to determine the causes and prognosis of vision loss. Segmentation of the macula OCT was performed using the Iowa Reference Algorithm to determine the retinal ganglion cell-inner plexiform layer complex (GCL-IPL) thickness. Results. Outer retinal changes alone caused decreased BCVA at initial presentation in 22 eyes (46%): subretinal fluid in 16, chorioretinal folds in 5, and peripapillary choroidal neovascularization in 1. The vision loss was reversible except for some eyes with chorioretinal folds. Optic neuropathy alone caused decreased BCVA in 10 eyes (21%) and coexisting outer retinal changes and optic neuropathy caused decreased BCVA in 16 eyes (33%). A GCL-IPL thickness less than or equal to 70 μm at initial presentation or progressive thinning of greater than or equal to 10 μm within 2 to 3 weeks compared with baseline correlated with poor visual outcome. Conclusions. Visual acuity loss in IIH can be caused by both outer retinal changes and optic neuropathy. Vision loss from outer retinal changes is mostly reversible. The outcome of patients with coexisting outer retinal changes and optic neuropathy or optic neuropathy alone depends on the degree of optic neuropathy, which can be predicted by the GCL-IPL thickness. PMID:26070058

  18. Autoimmune and inflammatory epilepsies.

    PubMed

    Nabbout, Rima

    2012-09-01

    The role of immunity and inflammation in epilepsy have long been suggested by the anticonvulsant activity of steroids in some infancy and childhood epilepsies. The role of fever and infection in exacerbating seizures due to possible proinflammatory molecules, the increased frequency of seizures in systemic autoimmune diseases like systemic lupus erythematous, and, recently, the detection of autoantibodies in some unexplained epilepsies reinforced the causal place of immunity and inflammation in epilepsies with unknown etiology. In this article, we summarize epilepsies where clinical and biologic data strongly support the pathogenic role of autoantibodies (e.g., limbic encephalitides, N-methyl-d-aspartate [NMDA] encephalitis) and epilepsies where immune-mediated inflammation occurs, but the full pathogenic cascade is either not clear (e.g., Rasmussen's encephalitis) or only strongly hypothesized (idiopathic hemiconvulsion-hemiplegia syndrome [IHHS] and fever-induced refractory epilepsy in school-aged children [FIRES]). We emphasize the electroclinical features that would help to diagnose these conditions, allowing early immunomodulating therapy. Finally, we raise some questions that remain unclear regarding diagnosis, mechanisms, and future therapies. PMID:22946722

  19. Functional Loss of Bmsei Causes Thermosensitive Epilepsy in Contractile Mutant Silkworm, Bombyx mori

    NASA Astrophysics Data System (ADS)

    Nie, Hongyi; Cheng, Tingcai; Huang, Xiaofeng; Zhou, Mengting; Zhang, Yinxia; Dai, Fangyin; Mita, Kazuei; Xia, Qingyou; Liu, Chun

    2015-07-01

    The thermoprotective mechanisms of insects remain largely unknown. We reported the Bombyx mori contractile (cot) behavioral mutant with thermo-sensitive seizures phenotype. At elevated temperatures, the cot mutant exhibit seizures associated with strong contractions, rolling, vomiting, and a temporary lack of movement. We narrowed a region containing cot to ~268 kb by positional cloning and identified the mutant gene as Bmsei which encoded a potassium channel protein. Bmsei was present in both the cell membrane and cytoplasm in wild-type ganglia but faint in cot. Furthermore, Bmsei was markedly decreased upon high temperature treatment in cot mutant. With the RNAi method and injecting potassium channel blockers, the wild type silkworm was induced the cot phenotype. These results demonstrated that Bmsei was responsible for the cot mutant phenotype and played an important role in thermoprotection in silkworm. Meanwhile, comparative proteomic approach was used to investigate the proteomic differences. The results showed that the protein of Hsp-1 and Tn1 were significantly decreased and increased on protein level in cot mutant after thermo-stimulus, respectively. Our data provide insights into the mechanism of thermoprotection in insect. As cot phenotype closely resembles human epilepsy, cot might be a potential model for the mechanism of epilepsy in future.

  20. Functional Loss of Bmsei Causes Thermosensitive Epilepsy in Contractile Mutant Silkworm, Bombyx mori

    PubMed Central

    Nie, Hongyi; Cheng, Tingcai; Huang, Xiaofeng; Zhou, Mengting; Zhang, Yinxia; Dai, Fangyin; Mita, Kazuei; Xia, Qingyou; Liu, Chun

    2015-01-01

    The thermoprotective mechanisms of insects remain largely unknown. We reported the Bombyx mori contractile (cot) behavioral mutant with thermo-sensitive seizures phenotype. At elevated temperatures, the cot mutant exhibit seizures associated with strong contractions, rolling, vomiting, and a temporary lack of movement. We narrowed a region containing cot to ~268 kb by positional cloning and identified the mutant gene as Bmsei which encoded a potassium channel protein. Bmsei was present in both the cell membrane and cytoplasm in wild-type ganglia but faint in cot. Furthermore, Bmsei was markedly decreased upon high temperature treatment in cot mutant. With the RNAi method and injecting potassium channel blockers, the wild type silkworm was induced the cot phenotype. These results demonstrated that Bmsei was responsible for the cot mutant phenotype and played an important role in thermoprotection in silkworm. Meanwhile, comparative proteomic approach was used to investigate the proteomic differences. The results showed that the protein of Hsp-1 and Tn1 were significantly decreased and increased on protein level in cot mutant after thermo-stimulus, respectively. Our data provide insights into the mechanism of thermoprotection in insect. As cot phenotype closely resembles human epilepsy, cot might be a potential model for the mechanism of epilepsy in future. PMID:26198671

  1. Investigation into the cause of mortality in 49 cases of idiopathic inflammatory myopathy: A single center study

    PubMed Central

    XIAO, YIZHI; ZUO, XIAOXIA; YOU, YUNHUI; LUO, HUI; DUAN, LIPING; ZHANG, WEIRU; LI, YISHA; XIE, YANLI; ZHOU, YAOU; NING, WANGBIN; LI, TONG; LIU, SIJIA; ZHU, HONGLIN; JIANG, YING; WU, SIYAO; ZHAO, HONGJUN

    2016-01-01

    Idiopathic inflammatory myopathy (IIM) is an autoimmune disease characterized by chronic muscle weakness and myositis with unknown etiology. IIM may affect the function of multiple organs and has a poor prognosis. In the present study, the causes of mortality in patients with IIM admitted to the Xiangya Hospital during the last 14 years were investigated. The investigation included an analysis of frequent causes of IIM, and of infections and associated complications. A cohort study was conducted on 676 patients with IIM that were admitted to Xiangya Hospital from January, 2001 to January, 2015. There were 49 patient mortalities (7.2% of the total cases), of which 34 mortalities were infection-associated and 15 were not infection-associated. The proportion of infection-associated IIM mortalities had increased since 2001. Of the 34 infection-associated mortalities, 31 cases (63.3%) were of fungal and bacterial infections, most frequently infecting the lungs and the blood. Klebsiella pneumoniae and Acinetobacter baumannii were the most commonly isolated pathogens, and co-infection with the two pathogens was observed in the majority of cases. In the IIM mortalities not associated with infection, there were 2 acute myocardial infarction cases, 2 acute interstitial lung disease cases, 4 malignancies and 1 case of each of the following: Arrhythmia, pneumothorax, ventilator weakness, pulmonary artery hypertension, gastrointestinal bleeding, liver failure and renal failure. Three mortalities were secondary to viral hepatitis in the present study. Pathogenic infection was the most frequent cause of mortality in patients with IIM. The remaining causes of mortality included secondary to heart failure, lung dysfunction and malignancy. Following the ubiquitous application of glucocorticoids and immunosuppressants, the proportion of infection-associated mortalities increased in patients with IIM. Thus, in addition to focusing on the primary disease, infection should receive

  2. Long-term ascorbic acid administration causes anticonvulsant activity during moderate and long-duration swimming exercise in experimental epilepsy.

    PubMed

    Tutkun, Erkut; Arslan, Gokhan; Soslu, Recep; Ayyildiz, Mustafa; Agar, Erdal

    2015-01-01

    The benefits of regular exercise on brain health are undeniable. Long-term exercise increases the production of reactive oxygen species in brain. Therefore, athletes often consume antioxidant supplements to remedy exercise-related damage and fatigue during exercise. The aim of this study is to evaluate the role of ascorbic acid in the effects of different intensities of swimming exercise on the brain susceptibility to experimental epilepsy in rats. Ascorbic acid was administered intraperitoneally (ip) during three different swimming exercise programme for 90 days (15 min, 30 min, 90 min/day). The anticonvulsant activity regarding the frequency of epileptiform activity appeared in the 80 min after 500 units intracortical penicillin injection in 30 min and 90 min/day exercise groups. The administration of ascorbic acid (100 mg/kg, ip) did not alter the anticonvulsant properties seen in the in short-duration (15 min/day) swimming exercise group. The amplitude of epileptiform activity also became significant in the 110 and 120 min after penicillin injection in the moderate (30 min/day) and long duration (60 min/day) groups, respectively. The results of the present study provide electrophysiologic evidence that long-term administration of ascorbic acid causes anticonvulsant activities in the moderate and long-duration swimming exercise. Antioxidant supplementation such as ascorbic acid might be suggested for moderate and long-duration swimming exercise in epilepsy. PMID:26232995

  3. Duplications upstream and downstream of SHOX identified as novel causes of Leri-Weill dyschondrosteosis or idiopathic short stature.

    PubMed

    Bunyan, David J; Baffico, Maria; Capone, Lucia; Vannelli, Silvia; Iughetti, Lorenzo; Schmitt, Sébastien; Taylor, Emma-Jane; Herridge, Adam A; Shears, Deborah; Forabosco, Antonino; Coviello, Domenico A

    2016-04-01

    Leri-Weill dyschondrosteosis is a pseudoautosomal dominantly-inherited skeletal dysplasia ascribed to haploinsufficiency of the SHOX gene caused by deletions, point mutations, or partial duplications of the gene, or to heterozygous deletions upstream or downstream of the intact SHOX gene involving conserved non-coding cis-regulatory DNA elements that show enhancer activity. Recently, two SHOX conserved non-coding element duplications, one upstream and one downstream, were reported in patients referred with idiopathic short stature. To further evaluate the role of these duplications in SHOX-related disorders, we describe seven patients (five with Leri-Weill dyschondrosteosis and two with short stature) all of whom have duplications of part of the upstream or downstream conserved non-coding element regions, identified by multiplex ligation-dependent probe amplification. In addition, we show data from 32 patients with an apparently identical downstream duplication that includes a proposed putative regulatory element (identified by multiplex ligation-dependent probe amplification or array comparative genome hybridization), which results in a variable phenotype from normal to mild Leri-Weill dyschondrosteosis. These additional data provide further evidence that duplications of upstream and downstream long range cis-regulatory DNA elements can result in a SHOX-related phenotype. © 2015 Wiley Periodicals, Inc. PMID:26698168

  4. Juvenile idiopathic arthritis

    MedlinePlus

    Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ... The cause of juvenile idiopathic arthritis (JIA) is not known. It ... illness . This means the body attacks and destroys healthy body ...

  5. Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures

    PubMed Central

    Carvill, Gemma L.; McMahon, Jacinta M.; Schneider, Amy; Zemel, Matthew; Myers, Candace T.; Saykally, Julia; Nguyen, John; Robbiano, Angela; Zara, Federico; Specchio, Nicola; Mecarelli, Oriano; Smith, Robert L.; Leventer, Richard J.; Møller, Rikke S.; Nikanorova, Marina; Dimova, Petia; Jordanova, Albena; Petrou, Steven; Helbig, Ingo; Striano, Pasquale; Weckhuysen, Sarah; Berkovic, Samuel F.; Scheffer, Ingrid E.; Mefford, Heather C.

    2015-01-01

    GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for re-uptake of GABA from the synapse. In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutations in seven individuals, all of whom have epilepsy with myoclonic-atonic seizures (MAE). We describe two truncations and four missense alterations, all of which most likely lead to loss of function of GAT-1 and thus reduced GABA re-uptake from the synapse. These individuals share many of the electrophysiological properties of Gat1-deficient mice, including spontaneous spike-wave discharges. Overall, pathogenic mutations occurred in 6/160 individuals with MAE, accounting for ∼4% of unsolved MAE cases. PMID:25865495

  6. Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.

    PubMed

    Schlingmann, Karl P; Ruminska, Justyna; Kaufmann, Martin; Dursun, Ismail; Patti, Monica; Kranz, Birgitta; Pronicka, Ewa; Ciara, Elzbieta; Akcay, Teoman; Bulus, Derya; Cornelissen, Elisabeth A M; Gawlik, Aneta; Sikora, Przemysław; Patzer, Ludwig; Galiano, Matthias; Boyadzhiev, Veselin; Dumic, Miroslav; Vivante, Asaf; Kleta, Robert; Dekel, Benjamin; Levtchenko, Elena; Bindels, René J; Rust, Stephan; Forster, Ian C; Hernando, Nati; Jones, Glenville; Wagner, Carsten A; Konrad, Martin

    2016-02-01

    Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH. PMID:26047794

  7. [Current management of epilepsy].

    PubMed

    Mizobuchi, Masahiro

    2013-09-01

    Epilepsy is one of the most common neurological disorders. Global neurological knowledge is essential for differential diagnosis of epileptic syndromes due to the diversity of ictal semiology, causes and syndromes. Neurologists play an important role in planning the medical care for patients with epilepsy, as medication is the most fundamental therapeutic strategy. Some patients with early-onset epilepsy require joint care by pediatric neurologists, those with intractable epilepsy by neurosurgeons, and those with psychological comorbidity by psychiatrists, and neurologists should play a coordinating role. While there is a great need for neurologists to participate in epilepsy care, neurologists in Japan currently do not participate substantially in the epilepsy management system. It is necessary to train more neurologists who can provide epilepsy care and conduct basic and clinical research on epilepsy by providing continuous education on epilepsy for general neurologists as well as pre- and post-graduate medical students. Most of the patients who require long-term treatment experience many medical problems and social handicaps, such as adverse effects of medication, social stigma, educational disadvantages and difficulties in obtaining driver's license. To improve the quality of life of patients with epilepsy, it is desirable to build broad medical-social networks participated by patients, doctors, neurological nurses, psychologists, social workers, school teachers, managers of employment support facilities and care givers. PMID:24018740

  8. Epilepsy - resources

    MedlinePlus

    Resources - epilepsy ... The following organizations are good resources for information on epilepsy : Epilepsy Foundation -- www.efa.org National Institute of Neurologic Disorders and Stroke -- www.ninds.nih.gov/disorders/ ...

  9. Understanding relationships between autism, intelligence, and epilepsy: a cross-disorder approach

    PubMed Central

    VAN EEGHEN, AGNIES M; PULSIFER, MARGARET B; MERKER, VANESSA L; NEUMEYER, ANN M; VAN EEGHEN, ELMER E; THIBERT, RONALD L; COLE, ANDREW J; LEIGH, FAWN A; PLOTKIN, SCOTT R; THIELE, ELIZABETH A

    2014-01-01

    Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. Method The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood-onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype. Results A total of 180 SRS questionnaires were filled out in the TSC, NF1, and EUC outpatient clinics at the Massachusetts General Hospital (90 females, 90 males; mean age 21y, range 4–63y), and SRS data from 210 patients with ASD recruited from an autism research collaboration (167 males, 43 females; mean age 9y range 4–22y) and 130 unaffected siblings were available. Regression models showed a significant association between SRS scores and intelligence outcomes (p<0.001) and various seizure variables (p<0.02), but not with a specific underlying disorder or genotype. The level of autistic features was strongly associated with intelligence outcomes in patients with TSC and epilepsy (p<0.01); in patients with NF1 these relationships were weaker (p=0.25). For all study groups, autistic trait subdomains covaried with neurocognitive comorbidity, with endophenotypes similar to that of idiopathic autism. Interpretation Our data show that in TSC and childhood-onset epilepsy, the severity and phenotype of autistic features are inextricably linked with intelligence and epilepsy outcomes. Such relationships were weaker for individuals with NF1. Findings suggest that ASDs are not specific for these conditions. PMID:23205844

  10. Idiopathic headshaking: is it still idiopathic?

    PubMed

    Pickles, Kirstie; Madigan, John; Aleman, Monica

    2014-07-01

    The clinical syndrome of equine idiopathic headshaking (HSK) was first described in the veterinary literature over 100 years ago, and the disorder continues to be a cause of substantial distress for the horse, frustration for the owner and therapeutic challenge for the veterinarian. This review presents a summary of the current knowledge of clinical signs, signalment, aetiopathogenesis, anatomy, diagnosis and treatment of idiopathic HSK. Recent advances in understanding the pathogenesis of the disease will be discussed with reference to human trigeminal neuralgia, along with the implications this may have for potential therapies. PMID:24821361

  11. Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.

    PubMed

    Schwarz, N; Hahn, A; Bast, T; Müller, S; Löffler, H; Maljevic, S; Gaily, E; Prehl, I; Biskup, S; Joensuu, T; Lehesjoki, A-E; Neubauer, B A; Lerche, H; Hedrich, U B S

    2016-02-01

    Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by -4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na(+) current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia. PMID:26645390

  12. Long-term treatment outcome of two patients with pyridoxine-dependent epilepsy caused by ALDH7A1 mutations: normal neurocognitive outcome.

    PubMed

    Nasr, Enas; Mamak, Eva; Feigenbaum, Anette; Donner, Elizabeth J; Mercimek-Mahmutoglu, Saadet

    2015-04-01

    Pyridoxine-dependent epilepsy is an autosomal recessively inherited disorder of lysine catabolism caused by mutations in the ALDH7A1 gene. We report 2 patients with normal neurocognitive outcome (full-scale IQ of 108 and 74) and their more than 10 years' treatment outcome on pyridoxine monotherapy. Both patients had specific borderline impairments in visual processing speed. More long-term treatment outcome reports will increase our knowledge about the natural history of the disease. PMID:24789515

  13. Increased neuronal firing in computer simulations of sodium channel mutations that cause generalized epilepsy with febrile seizures plus.

    PubMed

    Spampanato, Jay; Aradi, Ildiko; Soltesz, Ivan; Goldin, Alan L

    2004-05-01

    Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant familial syndrome with a complex seizure phenotype. It is caused by mutations in one of 3 voltage-gated sodium channel subunit genes (SCN1B, SCN1A, and SCN2A) and the GABA(A) receptor gamma2 subunit gene (GBRG2). The biophysical characterization of 3 mutations (T875M, W1204R, and R1648H) in SCN1A, the gene encoding the CNS voltage-gated sodium channel alpha subunit Na(v)1.1, demonstrated a variety of functional effects. The T875M mutation enhanced slow inactivation, the W1204R mutation shifted the voltage dependency of activation and inactivation in the negative direction, and the R1648H mutation accelerated recovery from inactivation. To determine how these changes affect neuronal firing, we used the NEURON simulation software to design a computational model based on the experimentally determined properties of each GEFS+ mutant sodium channel and a delayed rectifier potassium channel. The model predicted that W1204R decreased the threshold, T875M increased the threshold, and R1648H did not affect the threshold for firing a single action potential. Despite the different effects on the threshold for firing a single action potential, all of the mutations resulted in an increased propensity to fire repetitive action potentials. In addition, each mutation was capable of driving repetitive firing in a mixed population of mutant and wild-type channels, consistent with the dominant nature of these mutations. These results suggest a common physiological mechanism for epileptogenesis resulting from sodium channel mutations that cause GEFS+. PMID:14702334

  14. Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive Seizures in a Rat Model of Post-Traumatic Epilepsy

    PubMed Central

    Campbell, John N.; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B.

    2014-01-01

    Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later. PMID:25580467

  15. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels

    PubMed Central

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-01-01

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1–KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4–S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  16. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels.

    PubMed

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-05-21

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  17. Pulsed radiofrequency treatment for idiopathic trigeminal neuralgia: a retrospective analysis of the causes for ineffective pain relief.

    PubMed

    Luo, F; Meng, L; Wang, T; Yu, X; Shen, Y; Ji, N

    2013-09-01

    We retrospectively analyzed the reasons for ineffective pain relief in patients with idiopathic trigeminal neuralgia (TN) who had undergone pulsed radiofrequency (PRF) treatment guided by computed tomography scan. We found that intraoperative PRF output voltage and electrical field intensity was significantly higher (p < 0.05) in the group who had received effective treatment than in the ineffective group. These findings suggest that optimizing PRF parameters and increasing the intraoperative output voltage (electric field intensity) may therefore, provide better pain relief in patients with TN. PMID:23322665

  18. International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe.

    PubMed

    Bhatti, Sofie F M; De Risio, Luisa; Muñana, Karen; Penderis, Jacques; Stein, Veronika M; Tipold, Andrea; Berendt, Mette; Farquhar, Robyn G; Fischer, Andrea; Long, Sam; Löscher, Wolfgang; Mandigers, Paul J J; Matiasek, Kaspar; Pakozdy, Akos; Patterson, Edward E; Platt, Simon; Podell, Michael; Potschka, Heidrun; Rusbridge, Clare; Volk, Holger A

    2015-01-01

    In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors' experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible. PMID:26316233

  19. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    MedlinePlus

    ... myoclonic epilepsy spinal muscular atrophy with progressive myoclonic epilepsy Enable Javascript to view the expand/collapse boxes. ... All Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

  20. Na channel gene mutations in epilepsy--the functional consequences.

    PubMed

    Yamakawa, Kazuhiro

    2006-08-01

    Mutations of voltage-gated sodium channel genes SCN1A, SCN2A, and SCN1B have been identified in several types of epilepsies including generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI). In both SCN1A and SCN2A, missense mutations tend to result in benign idiopathic epilepsy, whereas truncation mutations lead to severe and intractable epilepsy. However, the results obtained by the biophysical analyses using cultured cell systems still remain elusive. Now studies in animal models harboring sodium channel gene mutations should be eagerly pursued. PMID:16806834

  1. Psychiatric Comorbidity in Children with New Onset Epilepsy

    ERIC Educational Resources Information Center

    Jones, Jana E.; Watson, Ryann; Sheth, Raj; Caplan, Rochelle; Koehn, Monica; Seidenberg, Michael; Hermann, Bruce

    2007-01-01

    The aim of this study was to characterize the distribution, timing, and risk factors for psychiatric comorbidity in children with recent onset epilepsy. Children aged 8 to 18 years with recent onset epilepsy (less than 1 year in duration) of idiopathic etiology (n=53) and a healthy comparison group (n=50) underwent a structured psychiatric…

  2. Infections, inflammation and epilepsy.

    PubMed

    Vezzani, Annamaria; Fujinami, Robert S; White, H Steve; Preux, Pierre-Marie; Blümcke, Ingmar; Sander, Josemir W; Löscher, Wolfgang

    2016-02-01

    Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing structural or functional derangement of brain physiology may lead to seizures, and different conditions may express themselves solely by recurrent seizures and thus be labelled "epilepsy." Worldwide, epilepsy is the most common serious neurological condition. The range of risk factors for the development of epilepsy varies with age and geographic location. Congenital, developmental and genetic conditions are mostly associated with the development of epilepsy in childhood, adolescence and early adulthood. Head trauma, infections of the central nervous system (CNS) and tumours may occur at any age and may lead to the development of epilepsy. Infections of the CNS are a major risk factor for epilepsy. The reported risk of unprovoked seizures in population-based cohorts of survivors of CNS infections from developed countries is between 6.8 and 8.3 %, and is much higher in resource-poor countries. In this review, the various viral, bacterial, fungal and parasitic infectious diseases of the CNS which result in seizures and epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as well as the role of experimental models to study mechanisms of epileptogenesis induced by infectious agents, is reviewed. The sterile (non-infectious) inflammatory response that occurs following brain insults is also discussed, as well as its overlap with inflammation due to infections, and the potential role in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures is reviewed. Potential strategies to prevent epilepsy resulting from brain infections and non-infectious inflammation are also considered. PMID:26423537

  3. Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner.

    PubMed

    Lachance-Touchette, Pamela; Choudhury, Mayukh; Stoica, Ana; Di Cristo, Graziella; Cossette, Patrick

    2014-01-01

    Mutations in genes encoding for GABAA receptor subunits is a well-established cause of genetic generalized epilepsy. GABA neurotransmission is implicated in several developmental processes including neurite outgrowth and synapse formation. Alteration in excitatory/inhibitory synaptic activities plays a critical role in epilepsy, thus here we investigated whether mutations in α1 subunit of GABAA receptor may affect dendritic spine and GABAergic bouton formation. In particular, we examined the effects of three mutations of the GABRA1 gene (D219N, A322D and K353delins18X) that were found in a cohort of French Canadian families with genetic generalized epilepsy. We used a novel single-cell genetic approach, by preparing cortical organotypic cultures from GABRA1 (flox/flox) mice and simultaneously inactivating endogenous GABRA1 and transfecting mutant α1 subunits in single glutamatergic pyramidal cells and basket GABAergic interneurons by biolistic transfection. We found that GABRA1 (-/-) GABAergic cells showed reduced innervation field, which was rescued by co-expressing α1-A322D and α1-WT but not α1-D219N. We further found that the expression of the most severe GABRA1 missense mutation (α1-A322D) induced a striking increase of spine density in pyramidal cells along with an increase in the number of mushroom-like spines. In addition, α1-A322D expression in GABAergic cells slightly increased perisomatic bouton density, whereas other mutations did not alter bouton formation. All together, these results suggest that the effects of different GABAAR mutations on GABAergic bouton and dendritic spine formation are specific to the mutation and cannot be always explained by a simple loss-of-function gene model. The use of single cell genetic manipulation in organotypic cultures may provide a better understanding of the specific and distinct neural circuit alterations caused by different GABAA receptor subunit mutations and will help define the pathophysiology of genetic

  4. Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner

    PubMed Central

    Lachance-Touchette, Pamela; Choudhury, Mayukh; Stoica, Ana; Di Cristo, Graziella; Cossette, Patrick

    2014-01-01

    Mutations in genes encoding for GABAA receptor subunits is a well-established cause of genetic generalized epilepsy. GABA neurotransmission is implicated in several developmental processes including neurite outgrowth and synapse formation. Alteration in excitatory/inhibitory synaptic activities plays a critical role in epilepsy, thus here we investigated whether mutations in α1 subunit of GABAA receptor may affect dendritic spine and GABAergic bouton formation. In particular, we examined the effects of three mutations of the GABRA1 gene (D219N, A322D and K353delins18X) that were found in a cohort of French Canadian families with genetic generalized epilepsy. We used a novel single-cell genetic approach, by preparing cortical organotypic cultures from GABRA1flox/flox mice and simultaneously inactivating endogenous GABRA1 and transfecting mutant α1 subunits in single glutamatergic pyramidal cells and basket GABAergic interneurons by biolistic transfection. We found that GABRA1−/− GABAergic cells showed reduced innervation field, which was rescued by co-expressing α1-A322D and α1-WT but not α1-D219N. We further found that the expression of the most severe GABRA1 missense mutation (α1-A322D) induced a striking increase of spine density in pyramidal cells along with an increase in the number of mushroom-like spines. In addition, α1-A322D expression in GABAergic cells slightly increased perisomatic bouton density, whereas other mutations did not alter bouton formation. All together, these results suggest that the effects of different GABAAR mutations on GABAergic bouton and dendritic spine formation are specific to the mutation and cannot be always explained by a simple loss-of-function gene model. The use of single cell genetic manipulation in organotypic cultures may provide a better understanding of the specific and distinct neural circuit alterations caused by different GABAA receptor subunit mutations and will help define the pathophysiology of genetic

  5. Epilepsy Foundation

    MedlinePlus

    ... Community Conference 2015 Epilepsy Pipeline Community Conference Purple Pumpkin Project Hidden Truths, The Mind Unraveled Downtown Downstairs ... Community Conference 2015 Epilepsy Pipeline Community Conference Purple Pumpkin Project Hidden Truths, The Mind Unraveled Downtown Downstairs ...

  6. Recognizing and preventing epilepsy-related mortality

    PubMed Central

    Spruill, Tanya; Thurman, David; Friedman, Daniel

    2016-01-01

    Epilepsy is associated with a high rate of premature mortality from direct and indirect effects of seizures, epilepsy, and antiseizure therapies. Sudden unexpected death in epilepsy (SUDEP) is the second leading neurologic cause of total lost potential life-years after stroke, yet SUDEP may account for less than half of all epilepsy-related deaths. Some epilepsy groups are especially vulnerable: individuals from low socioeconomic status groups and those with comorbid psychiatric illness die more often than controls. Despite clear evidence of an important public health problem, efforts to assess and prevent epilepsy-related deaths remain inadequate. We discuss factors contributing to the underestimation of SUDEP and other epilepsy-related causes of death. We suggest the need for a systematic classification of deaths directly due to epilepsy (e.g., SUDEP, drowning), due to acute symptomatic seizures, and indirectly due to epilepsy (e.g., suicide, chronic effects of antiseizure medications). Accurately estimating the frequency of epilepsy-related mortality is essential to support the development and assessment of preventive interventions. We propose that educational interventions and public health campaigns targeting medication adherence, psychiatric comorbidity, and other modifiable risk factors may reduce epilepsy-related mortality. Educational campaigns regarding sudden infant death syndrome and fires, which kill far fewer Americans than epilepsy, have been widely implemented. We have done too little to prevent epilepsy-related deaths. Everyone with epilepsy and everyone who treats people with epilepsy need to know that controlling seizures will save lives. PMID:26674330

  7. Ictal analgesia in temporal lobe epilepsy - The mechanism of seizure-related burns.

    PubMed

    Szűcs, Anna; Horváth, András; Rásonyi, György; Fabó, Dániel; Szabó, Géza; Sákovics, Anna; Kamondi, Anita

    2015-08-01

    Seizure-related injuries have major impact in the excess mortality and morbidity of epilepsy patients. Experimental data suggest that analgesia may develop during seizures contributing to the severity of seizure-related accidents, especially burns. We aimed to identify those seizure-types that may lead to burn-injuries by seizure-related analgesia. In our tertiary epilepsy centre, we asked 100 epilepsy patients having a history of seizure-related injury, to complete our burn-and-pain questionnaire. Fifty-one patients completed the survey; their epileptology data were collected and those with a seizure-related burn were interviewed. Forty-two out of the 51 patients (82%) had partial epilepsy and 9 (18%) had idiopathic generalised epilepsy. Twenty-six persons (51%) reported decreased pain perception during or after seizures in general. Twelve patients (23%) had suffered one or more seizure-related burn. Five of them fell onto a hot surface or fire accidentally, during generalized tonic-clonic seizures. Seven out of the 12 burnt patients (58%) grasped a hot object or reached into boiling fluid during complex partial seizures; without experiencing-, or reacting in response to pain. These patients had temporal lobe epilepsy, 5 of them had left temporal seizure onset. Our hypothesis based on the circumstantial analysis of our patients' burn-injuries; is that temporal lobe seizures may cause ictal/postictal analgesia. It may be caused by the seizure-related epileptic facilitation of the periaqueductal gray matter; the central pain-inhibiting structure of the brain. Seizure-related endogenous opioid-release my have a contributory role in inhibiting pain-perception. Ictal analgesia warrants better burn-prevention in temporal lobe epilepsy patients. Understanding the mechanism of ictal analgesia and specifying those seizures-types prone to cause it; may help indentifying human pain-inhibiting pathways. PMID:25953092

  8. Mitochondrial disease and epilepsy.

    PubMed

    Rahman, Shamima

    2012-05-01

    Mitochondrial respiratory chain disorders are relatively common inborn errors of energy metabolism, with a combined prevalence of one in 5000. These disorders typically affect tissues with high energy requirements, and cerebral involvement occurs frequently in childhood, often manifesting in seizures. Mitochondrial diseases are genetically heterogeneous; to date, mutations have been reported in all 37 mitochondrially encoded genes and more than 80 nuclear genes. The major genetic causes of mitochondrial epilepsy are mitochondrial DNA mutations (including those typically associated with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS] and myoclonic epilepsy with ragged red fibres [MERRF] syndromes); mutations in POLG (classically associated with Alpers syndrome but also presenting as the mitochondrial recessive ataxia syndrome [MIRAS], spinocerebellar ataxia with epilepsy [SCAE], and myoclonus, epilepsy, myopathy, sensory ataxia [MEMSA] syndromes in older individuals) and other disorders of mitochondrial DNA maintenance; complex I deficiency; disorders of coenzyme Q(10) biosynthesis; and disorders of mitochondrial translation such as RARS2 mutations. It is not clear why some genetic defects, but not others, are particularly associated with seizures. Epilepsy may be the presenting feature of mitochondrial disease but is often part of a multisystem clinical presentation. Mitochondrial epilepsy may be very difficult to manage, and is often a poor prognostic feature. At present there are no curative treatments for mitochondrial disease. Individuals with mitochondrial epilepsy are frequently prescribed multiple anticonvulsants, and the role of vitamins and other nutritional supplements and the ketogenic diet remain unproven. PMID:22283595

  9. Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy.

    PubMed

    Simons, Cas; Rash, Lachlan D; Crawford, Joanna; Ma, Linlin; Cristofori-Armstrong, Ben; Miller, David; Ru, Kelin; Baillie, Gregory J; Alanay, Yasemin; Jacquinet, Adeline; Debray, François-Guillaume; Verloes, Alain; Shen, Joseph; Yesil, Gözde; Guler, Serhat; Yuksel, Adnan; Cleary, John G; Grimmond, Sean M; McGaughran, Julie; King, Glenn F; Gabbett, Michael T; Taft, Ryan J

    2015-01-01

    Temple-Baraitser syndrome (TBS) is a multisystem developmental disorder characterized by intellectual disability, epilepsy, and hypoplasia or aplasia of the nails of the thumb and great toe. Here we report damaging de novo mutations in KCNH1 (encoding a protein called ether à go-go, EAG1 or KV10.1), a voltage-gated potassium channel that is predominantly expressed in the central nervous system (CNS), in six individuals with TBS. Characterization of the mutant channels in both Xenopus laevis oocytes and human HEK293T cells showed a decreased threshold of activation and delayed deactivation, demonstrating that TBS-associated KCNH1 mutations lead to deleterious gain of function. Consistent with this result, we find that two mothers of children with TBS, who have epilepsy but are otherwise healthy, are low-level (10% and 27%) mosaic carriers of pathogenic KCNH1 mutations. Consistent with recent reports, this finding demonstrates that the etiology of many unresolved CNS disorders, including epilepsies, might be explained by pathogenic mosaic mutations. PMID:25420144

  10. Do ATP-binding cassette transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which antiepileptic drugs are affected.

    PubMed

    Löscher, Wolfgang; Luna-Tortós, Carlos; Römermann, Kerstin; Fedrowitz, Maren

    2011-01-01

    Resistance to multiple antiepileptic drugs (AEDs) is a common problem in epilepsy, affecting at least 30% of patients. One prominent hypothesis to explain this resistance suggests an inadequate penetration or excess efflux of AEDs across the blood - brain barrier (BBB) as a result of overexpressed efflux transporters such as P-glycoprotein (Pgp), the encoded product of the multidrug resistance- 1 (MDR1, ABCB1) gene. Pgp and MDR1 are markedly increased in epileptogenic brain tissue of patients with AED-resistant partial epilepsy and following seizures in rodent models of partial epilepsy. In rodent models, AED-resistant rats exhibit higher Pgp levels than responsive animals; increased Pgp expression is associated with lower brain levels of AEDs; and, most importantly, co-administration of Pgp inhibitors reverses AED resistance. Thus, it is reasonable to conclude that Pgp plays a significant role in mediating resistance to AEDs in rodent models of epilepsy - however, whether this phenomenon extends to at least some human refractory epilepsy remains unclear, particularly because it is still a matter of debate which AEDs, if any, are transported by human Pgp. The difficulty in determining which AEDs are substrates of human Pgp is mainly a consequence of the fact that AEDs are highly permeable compounds, which are not easily identified as Pgp substrates in in vitro models of the BBB, such as monolayer (Transwell(®)) efflux assays. By using a modified assay (concentration equilibrium transport assay; CETA), which minimizes the influence of high transcellular permeability, two groups have recently demonstrated that several major AEDs are transported by human Pgp. Importantly, it was demonstrated in these studies that Pgp-mediated transport highly depends on the AED concentration and may not be identified if concentrations below or above the therapeutic range are used. In addition to the efflux transporters, seizure-induced alterations in BBB integrity and activity of

  11. Talking about epilepsy: Challenges parents face when communicating with their child about epilepsy and epilepsy-related issues.

    PubMed

    O'Toole, Stephanie; Lambert, Veronica; Gallagher, Pamela; Shahwan, Amre; Austin, Joan K

    2016-04-01

    The aim of this qualitative study was to explore the challenges that parents of children with epilepsy experienced when engaging in dialog with their child about epilepsy and epilepsy-related issues. Using a qualitative exploratory approach, interviews were conducted with 34 parents of children with epilepsy (aged 6-16years), consisting of 27 mothers and 7 fathers. Data were transcribed verbatim and thematically analyzed. Findings revealed five main themes: normalizing epilepsy, the invisibility of epilepsy, information concealment, fear of misinforming the child, and difficulty in discussing particular epilepsy-related issues. Many of the communicative challenges experienced by parents impacted on their ability to engage openly in parent-child dialog about epilepsy in the home. Parents face specific challenges when choosing to communicate with their child about epilepsy, relating to creating a sense of normality, reducing fear of causing their child worry, and having a lack of epilepsy-related knowledge. Healthcare professionals who work closely with families living with epilepsy should remain mindful of the importance of discussing family communication surrounding epilepsy and the challenges parents of children with epilepsy face when talking about epilepsy within the home. PMID:26900774

  12. International veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs.

    PubMed

    De Risio, Luisa; Bhatti, Sofie; Muñana, Karen; Penderis, Jacques; Stein, Veronika; Tipold, Andrea; Berendt, Mette; Farqhuar, Robyn; Fischer, Andrea; Long, Sam; Mandigers, Paul J J; Matiasek, Kaspar; Packer, Rowena M A; Pakozdy, Akos; Patterson, Ned; Platt, Simon; Podell, Michael; Potschka, Heidrun; Batlle, Martí Pumarola; Rusbridge, Clare; Volk, Holger A

    2015-01-01

    This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset

  13. Epilepsy associated tumors: Review article

    PubMed Central

    Giulioni, Marco; Marucci, Gianluca; Martinoni, Matteo; Marliani, Anna Federica; Toni, Francesco; Bartiromo, Fiorina; Volpi, Lilia; Riguzzi, Patrizia; Bisulli, Francesca; Naldi, Ilaria; Michelucci, Roberto; Baruzzi, Agostino; Tinuper, Paolo; Rubboli, Guido

    2014-01-01

    Long-term epilepsy associated tumors (LEAT) represent a well known cause of focal epilepsies. Glioneuronal tumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly arising in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic network with complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation. PMID:25405186

  14. Epilepsy in the developing world.

    PubMed

    Carpio, Arturo; Hauser, W Allen

    2009-07-01

    Developing countries (DCs) and developed countries have geographic, economic, and social differences. The prevalence and incidence of epilepsy are higher in DCs than in developed countries. However, within DCs, given the high incidence of epilepsy, the prevalence is relatively low, which may be due to high mortality for people with epilepsy (PWE). Neurocysticercosis is one of the main causes of symptomatic epilepsy in many DCs. Prognosis in DCs seems similar to that in developed countries. Because phenobarbital and phenytoin are available and inexpensive, they are the drugs most often used in DCs. The cost of newer antiepileptic drugs and the limited availability of resources for epilepsy care in DCs mean that care for PWE in DCs is marginalized and that many people receive no pharmacologic treatment. The most cost-effective way to decrease the treatment gap in DCs would be to deliver the epilepsy services through primary health care. PMID:19515285

  15. Epilepsy associated tumors: Review article.

    PubMed

    Giulioni, Marco; Marucci, Gianluca; Martinoni, Matteo; Marliani, Anna Federica; Toni, Francesco; Bartiromo, Fiorina; Volpi, Lilia; Riguzzi, Patrizia; Bisulli, Francesca; Naldi, Ilaria; Michelucci, Roberto; Baruzzi, Agostino; Tinuper, Paolo; Rubboli, Guido

    2014-11-16

    Long-term epilepsy associated tumors (LEAT) represent a well known cause of focal epilepsies. Glioneuronal tumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly arising in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic network with complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation. PMID:25405186

  16. A gene defect causing a novel progressive epilepsy with mental retardation, EPMR, maps to chromosome 8p

    SciTech Connect

    Ranta, S.; Tahvanainen, E.; Karila, E.

    1994-09-01

    EPMR (progressive epilepsy with mental retardation) is a newly discovered autosomal recessively inherited disorder which occurs with high frequency in an isolated rural population in Finland. So far 25 patients have been identified, 21 of whom are alive. Twenty-three patients share a common ancestor from the 18th century. The main features of EPMR are: normal early development, tonic-clonic seizures with onset between ages 5 and 10, and mental retardation which begins approximately 2 years after the onset of epilepsy and soon leads to deepening mental retardation. Adult patients do not manage their daily life without help. The EEG is normal at the onset of epilepsy but later progressive slowing of the background activity occurs. The etiology and pathogenesis of EPMR remain known. As this is a novel disease entity without any definitive diagnostic marker we wished to begin its elucidation by first defining its gene locus. A random search for linkage in four multiplex families (only 20 individuals tested) resulted in the finding of linkage to marker D8S264 with a lod score of 4.45 at zero recombination. The EPMR gene resides in a 7 centimorgan interval between marker loci AFM185xb2 and D8S262 with a maximum multipoint lod score of 7.03 at 1.8 centimorgans proximal to D8S264. Physically this region is very distal on 8p. Of the sixteen EPMR chromosomes haplotyped 15 were identical or almost identical. One chromosome, however, had a distinctly different haplotype raising the possibility of there being two different mutations or one very old mutation. These findings are a starting point toward isolating and characterizing the gene and its protein product. Physical mapping has been initiated by isolating nine YACs from the region.

  17. Epilepsy Workshop for Public School Personnel.

    ERIC Educational Resources Information Center

    Rassel, Gary; And Others

    1981-01-01

    Epilepsy is one of the most misunderstood and stigmatized disorders in society. A four-hour workshop was conducted over two days with the first two hours discussing types of epilepsy, causes, treatment, and medication. The second part of the study focused on social and psychological implications of epilepsy. (JN)

  18. Epilepsy, cognition and behavior.

    PubMed

    Gulati, Sheffali; Yoganathan, Sangeetha; Chakrabarty, Biswaroop

    2014-10-01

    Epilepsy is defined as two or more unprovoked seizures. Epileptic patients have intellectual disability and behavioral co-morbidities to the tune of up to 25 and 75% respectively. Various factors like underlying etiology, socioeconomic environment at home, age at onset, seizure semiology, seizure descriptors like duration, severity and frequency, therapy related adverse effects secondary to antiepileptic drugs and epilepsy surgery have been implicated for the causation of cognitive and behavioral impairment in epilepsy. Cognitive epilepsy has emerged as a specific entity. This may manifest as a transient behavioral or cognitive change, insidous onset subacute to chronic encephalopathy or more catastrophic in the form of nonconvulsive status epilepticus. Cognitive impairment seen in epileptic children include difficulties in learning, memory, problem solving as well as concept formation. Anxiety, depression and attention deficit hyperkinetic disorders are the most common psychiatric co-morbidities seen. Investigating a child with epilepsy for cognitive and behavioral impairment is difficult as these tests would require cooperation from the patient's side to a significant extent. A rational approach towards treatment would be judicious selection of antiepileptic drugs, treatment of underlying cause, appropriate management of behavioral co-morbidities including psychopharmacotherapy and a trial of immunotherapy (particularly in cognitive epilepsies), wherever appropriate. PMID:25073691

  19. Array-Based Gene Discovery with Three Unrelated Subjects Shows SCARB2/LIMP-2 Deficiency Causes Myoclonus Epilepsy and Glomerulosclerosis

    PubMed Central

    Berkovic, Samuel F.; Dibbens, Leanne M.; Oshlack, Alicia; Silver, Jeremy D.; Katerelos, Marina; Vears, Danya F.; Lüllmann-Rauch, Renate; Blanz, Judith; Zhang, Ke Wei; Stankovich, Jim; Kalnins, Renate M.; Dowling, John P.; Andermann, Eva; Andermann, Frederick; Faldini, Enrico; D'Hooge, Rudi; Vadlamudi, Lata; Macdonell, Richard A.; Hodgson, Bree L.; Bayly, Marta A.; Savige, Judy; Mulley, John C.; Smyth, Gordon K.; Power, David A.; Saftig, Paul; Bahlo, Melanie

    2008-01-01

    Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies. PMID:18308289

  20. Brain Slump Caused by Jugular Venous Stenoses Treated by Stenting: A Hypothesis to Link Spontaneous Intracranial Hypotension with Idiopathic Intracranial Hypertension.

    PubMed

    Higgins, Nicholas; Trivedi, Rikin; Greenwood, Richard; Pickard, John

    2015-07-01

    Spontaneous intracranial hypotension, of which brain slump is an extreme expression, is caused by a cerebrospinal fluid leak. The reason the leak develops in the first place, however, is unknown, and some cases can be very difficult to manage. We describe a patient with severe symptoms of spontaneous intracranial hypotension and brain slump documented by magnetic resonance imaging whose clinical syndrome and structural brain anomaly resolved completely after treatment directed exclusively at improving cranial venous outflow. Diagnostics included computed tomography (CT) venography, catheter venography, and jugular venoplasty. CT venography showed narrowing of both internal jugular veins below the skull base. Catheter venography confirmed that these were associated with pressure gradients. Jugular venoplasty performed on two separate occasions as a clinical test gave temporary respite. Lasting remission (2 years of follow-up) was achieved by stenting the dominant internal jugular vein. These findings and this outcome suggest a mechanism for the development of spontaneous intracranial hypotension that would link it to idiopathic intracranial hypertension and have cranial venous outflow obstruction as the underlying cause. PMID:26251803

  1. Brain Slump Caused by Jugular Venous Stenoses Treated by Stenting: A Hypothesis to Link Spontaneous Intracranial Hypotension with Idiopathic Intracranial Hypertension

    PubMed Central

    Higgins, Nicholas; Trivedi, Rikin; Greenwood, Richard; Pickard, John

    2015-01-01

    Spontaneous intracranial hypotension, of which brain slump is an extreme expression, is caused by a cerebrospinal fluid leak. The reason the leak develops in the first place, however, is unknown, and some cases can be very difficult to manage. We describe a patient with severe symptoms of spontaneous intracranial hypotension and brain slump documented by magnetic resonance imaging whose clinical syndrome and structural brain anomaly resolved completely after treatment directed exclusively at improving cranial venous outflow. Diagnostics included computed tomography (CT) venography, catheter venography, and jugular venoplasty. CT venography showed narrowing of both internal jugular veins below the skull base. Catheter venography confirmed that these were associated with pressure gradients. Jugular venoplasty performed on two separate occasions as a clinical test gave temporary respite. Lasting remission (2 years of follow-up) was achieved by stenting the dominant internal jugular vein. These findings and this outcome suggest a mechanism for the development of spontaneous intracranial hypotension that would link it to idiopathic intracranial hypertension and have cranial venous outflow obstruction as the underlying cause. PMID:26251803

  2. Idiopathic hypersomnia.

    PubMed

    Billiard, Michel; Sonka, Karel

    2016-10-01

    Idiopathic hypersomnia continues to evolve from the concept of "sleep drunkenness" introduced by Bedrich Roth in Prague in 1956 and the description of idiopathic hypersomnia with two forms, polysymptomatic and monosymptomatic, by the same Bedrich Roth in 1976. The diagnostic criteria of idiopathic hypersomnia have varied with the successive revisions of the International classifications of sleep disorders, including the recent 3rd edition. No epidemiological studies have been conducted so far. Disease onset occurs most often during adolescence or young adulthood. A familial background is often present but rigorous studies are still lacking. The key manifestation is hypersomnolence. It is often accompanied by sleep of long duration and debilitating sleep inertia. Polysomnography (PSG) followed by a multiple sleep latency test (MSLT) is mandatory, as well as a 24 h PSG or a 2-wk actigraphy in association with a sleep log to ensure a total 24-h sleep time longer than or equal to 66O minutes, when the mean sleep latency on the MSLT is longer than 8 min. Yet, MSLT is neither sensitive nor specific and the polysomnographic diagnostic criteria require continuous readjustment and biologic markers are still lacking. Idiopathic hypersomnia is most often a chronic condition though spontaneous remission may occur. The condition is disabling, sometimes even more so than narcolepsy type 1 or 2. Based on neurochemical, genetic and immunological analyses as well as on exploration of the homeostatic and circadian processes of sleep, various pathophysiological hypotheses have been proposed. Differential diagnosis involves a number of diseases and it is not yet clear whether idiopathic hypersomnia and narcolepsy type 2 are not the same condition. Until now, the treatment of idiopathic hypersomnia has mirrored that of the sleepiness of narcolepsy type 1 or 2. The first randomized, double-blind, placebo-controlled trials of modafinil have just been published, as well as a double

  3. Musicogenic epilepsy.

    PubMed

    Stern, John

    2015-01-01

    Musicogenic epilepsy, which is a form of reflex epilepsy, is characterized by the triggering of epileptic seizures by specific music experiences. Individuals with musicogenic epilepsy differ in the music trigger, but may have similar seizures. Typically, these seizures are focal dyscognitive and have a temporal-lobe origin with a limbic system distribution. As such, the music trigger is likely related to either an emotional or memory aspect of music perception. Investigations into musicogenic epilepsy may lead to a better understanding of seizure propagation within the brain and of neurologic aspects of the music experience. Successful treatment of medication-resistant musicogenic epilepsy has been achieved with anterior temporal-lobe resection. PMID:25726285

  4. A Mutation in the Golgi Qb-SNARE Gene GOSR2 Causes Progressive Myoclonus Epilepsy with Early Ataxia

    PubMed Central

    Corbett, Mark A.; Schwake, Michael; Bahlo, Melanie; Dibbens, Leanne M.; Lin, Meng; Gandolfo, Luke C.; Vears, Danya F.; O'Sullivan, John D.; Robertson, Thomas; Bayly, Marta A.; Gardner, Alison E.; Vlaar, Annemarie M.; Korenke, G. Christoph; Bloem, Bastiaan R.; de Coo, Irenaeus F.; Verhagen, Judith M.A.; Lehesjoki, Anna-Elina; Gecz, Jozef; Berkovic, Samuel F.

    2011-01-01

    The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi. PMID:21549339

  5. The Role of Calcium Channels in Epilepsy.

    PubMed

    Rajakulendran, Sanjeev; Hanna, Michael G

    2016-01-01

    A central theme in the quest to unravel the genetic basis of epilepsy has been the effort to elucidate the roles played by inherited defects in ion channels. The ubiquitous expression of voltage-gated calcium channels (VGCCs) throughout the central nervous system (CNS), along with their involvement in fundamental processes, such as neuronal excitability and synaptic transmission, has made them attractive candidates. Recent insights provided by the identification of mutations in the P/Q-type calcium channel in humans and rodents with epilepsy and the finding of thalamic T-type calcium channel dysfunction in the absence of seizures have raised expectations of a causal role of calcium channels in the polygenic inheritance of idiopathic epilepsy. In this review, we consider how genetic variation in neuronal VGCCs may influence the development of epilepsy. PMID:26729757

  6. Musicogenic epilepsy.

    PubMed Central

    Brien, S E; Murray, T J

    1984-01-01

    A case of musicogenic epilepsy is reported in which the seizures were precipitated by singing voices. It was found that some singers' voices were particularly epileptogenic and that some of their songs, but not others, would precipitate a seizure. A study of the "offending" songs and singers did not reveal a common key, chord, harmonic interval, pitch or rhythm, and the emotional feeling or intensity of the music did not seem to be relevant. However, the voices that caused the seizures had a throaty, "metallic" quality. Such a singing voice results from incorrect positioning of the larynx such that it is not allowed to descend fully during singing; consequently, the vowel sounds produced must be manipulated by the lips or jaw to be distinguished. This trait is most common in singers with a low voice range who sing softly and use a microphone. It is not seen in trained operatic or musical theatre singers. The results of repeated testing showed that the seizures in this patient were caused by listening to singers who positioned the larynx incorrectly. PMID:6498678

  7. Ossified Posterior Longitudinal Ligament With Massive Ossification of the Anterior Longitudinal Ligament Causing Dysphagia in a Diffuse Idiopathic Skeletal Hyperostosis Patient.

    PubMed

    Murayama, Kazuhiro; Inoue, Shinichi; Tachibana, Toshiya; Maruo, Keishi; Arizumi, Fumihiro; Tsuji, Shotaro; Yoshiya, Shinichi

    2015-08-01

    Descriptive case report.To report a case of a diffuse idiopathic skeletal hyperostosis (DISH) patient with both massive ossification of the anterior longitudinal ligament (OALL) leading to severe dysphagia as well as ossification of the posterior longitudinal ligament (OPLL) causing mild cervical myelopathy, warranting not only an anterior approach but also a posterior one.Although DISH can cause massive OALL in the cervical spine, severe dysphagia resulting from DISH is a rare occurrence. OALLs are frequently associated with OPLL. Treatment for a DISH patient with OPLL in setting of OALL-caused dysphagia is largely unknown.A 70-year-old man presented with severe dysphagia with mild cervical myelopathy. Neurological examination showed mild spastic paralysis and hyper reflex in his lower extremities. Plane radiographs and computed tomography of the cervical spine revealed a discontinuous massive OALL at C4-5 and continuous type OPLL at C2-6. Magnetic resonance imaging revealed pronounced spinal cord compression due to OPLL at C4-5. Esophagram demonstrated extrinsic compression secondary to OALL at C4-5.We performed posterior decompressive laminectomy with posterior lateral mass screw fixation, as well as both resection of OALL and interbody fusion at C4-5 by the anterior approach. We performed posterior decompressive laminectomy with posterior lateral mass screw fixation, as well as both resection of OALL and interbody fusion at C4-5 by the anterior approach. Severe dysphagia markedly improved without any complications.We considered that this patient not only required osteophytectomy and fusion by the anterior approach but also required decompression and spinal fusion by the posterior approach to prevent both deterioration of cervical myelopathy and recurrence of OALL after surgery. PMID:26266365

  8. Mechanisms involved in the reduction of GABAA receptor alpha1-subunit expression caused by the epilepsy mutation A322D in the trafficking-competent receptor.

    PubMed

    Bradley, Clarrisa A; Taghibiglou, Changiz; Collingridge, Graham L; Wang, Yu Tian

    2008-08-01

    A mutation in the alpha1-subunit (A322D) of GABA(A)Rs is responsible for juvenile myoclonic epilepsy in a large Canadian family. Previous work has identified that this mutant affects the cell expression and function of recombinant GABA(A)Rs, expressed in HEK293 cells. Here we have extended these observations by showing that the mutation promotes association with the endoplasmic reticulum chaperone calnexin and accelerates the degradation rate of the subunits approximately 2.5-fold. We also find that the mutation causes the subunit to be degraded largely by a lysosomal-dependent process. Furthermore, we find that the mutation results in receptors that are inserted into the plasma membrane but are more rapidly endocytosed by a dynamin and caveolin1-dependent mechanism. These results suggest that the mutant subunit can form functional receptors, but that these have a shorter lifetime on the plasma membrane. PMID:18534981

  9. Odor-associated idiopathic anaphylaxis. A case report.

    PubMed

    Saunders, R L; Halpern, G M; Gershwin, M E

    1995-01-01

    A 44 year old woman is described who appears to have idiopathic anaphylaxis triggered by chemical odors. Her case and a general discussion of anaphylaxis are presented. The known causes of anaphylaxis and a discourse on idiopathic anaphylaxis are given. The treatment of idiopathic anaphylaxis is discussed. PMID:7631593

  10. Idiopathic Focal Eosinophilic Enteritis (IFEE), an Emerging Cause of Abdominal Pain in Horses: The Effect of Age, Time and Geographical Location on Risk

    PubMed Central

    Archer, Debra C.; Costain, Deborah A.; Sherlock, Chris

    2014-01-01

    Background Idiopathic focal eosinophilic enteritis (IFEE) is an emerging cause of abdominal pain (colic) in horses that frequently requires surgical intervention to prevent death. The epidemiology of IFEE is poorly understood and it is difficult to diagnose pre-operatively. The aetiology of this condition and methods of possible prevention are currently unknown. The aims of this study were to investigate temporal and spatial heterogeneity in IFEE risk and to ascertain the effect of horse age on risk. Methodology/Principal Findings A retrospective, nested case-control study was undertaken using data from 85 IFEE cases and 848 randomly selected controls admitted to a UK equine hospital for exploratory laparotomy to investigate the cause of colic over a 10-year period. Generalised additive models (GAMs) were used to quantify temporal and age effects on the odds of IFEE and to provide mapped estimates of ‘residual’ risk over the study region. The relative risk of IFEE increased over the study period (p = 0.001) and a seasonal pattern was evident (p<0.01) with greatest risk of IFEE being identified between the months of July and November. IFEE risk decreased with increasing age (p<0.001) with younger (0–5 years old) horses being at greatest risk. The mapped surface estimate exhibited significantly atypical sub-regions (p<0.001) with increased IFEE risk in horses residing in the North-West of the study region. Conclusions/Significance IFEE was found to exhibit both spatial and temporal variation in risk and is more likely to occur in younger horses. This information may help to identify horses at increased risk of IFEE, provide clues about the aetiology of this condition and to identify areas that require further research. PMID:25463382

  11. Musicogenic epilepsy.

    PubMed

    Berman, I W

    1981-01-10

    Musicogenic epilepsy is a form of temporal lobe epilepsy, and belongs to the group of reflex epilepsies. Convulsions are generally triggered by a specific passage of music. It is not as rare as is generally assumed, and physicians and neurologists were aware of the condition as early as the latter part of the 19th century. Many of its sufferers have above-average musicality. In some patients autonomic manifestations are conspicuous, but their role as preciptation factors is not clear. Electro-encephalographic studies have shown conclusively that musicogenic epilepsy is not hysterical. Most but not all of its victims respond well to anti-ictal medication. Psychotherapy has a place in the treatment of some patients. PMID:7006106

  12. Epilepsy - overview

    MedlinePlus

    ... look at the brain and nervous system. An EEG (electroencephalogram) will be done to check the electrical ... epilepsy surgery, you may need to: Wear an EEG recorder for days or weeks as you go ...

  13. Epilepsy (partial)

    PubMed Central

    2011-01-01

    Introduction About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of starting antiepileptic drug treatment following a single seizure? What are the effects of drug monotherapy in people with partial epilepsy? What are the effects of additional drug treatments in people with drug-resistant partial epilepsy? What is the risk of relapse in people in remission when withdrawing antiepileptic drugs? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or

  14. Four New Families with Autosomal Dominant Partial Epilepsy with Auditory Features: Clinical Description and Linkage to Chromosome 10q24

    PubMed Central

    Winawer, Melodie R.; Boneschi, Filippo Martinelli; Barker-Cummings, Christie; Lee, Joseph H.; Liu, Jianjun; Mekios, Constantine; Gilliam, T. Conrad; Pedley, Timothy A.; Hauser, W. Allen; Ottman, Ruth

    2009-01-01

    Summary Purpose Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization. Methods We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2. Results In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (θ = 0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93. Conclusions These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway. PMID:11879388

  15. GLUT1 deficiency syndrome as a cause of encephalopathy that includes cognitive disability, treatment-resistant infantile epilepsy and a complex movement disorder

    PubMed Central

    Graham, John M.

    2012-01-01

    Glucose transporter-1 (GLUT1) deficiency syndrome is caused by heterozygous mutations in the SLC2A1 gene, resulting in impaired glucose transport into the brain. It is characterized by a low glucose concentration in the cerebrospinal fluid (hypoglycorrhachia) in the absence of hypoglycemia, in combination with low to normal lactate in the cerebrospinal fluid (CSF). It often results in treatment-resistant infantile epilepsy with progressive developmental disabilities and a complex movement disorder. Recognizing GLUT1 deficiency syndrome is important, since initiation of a ketogenic diet can reduce the frequency of seizures and the severity of the movement disorder. There can be a considerable delay in diagnosing GLUT1 deficiency syndrome, and this point is illustrated by the natural history of this disorder in a 21-year-old woman with severe, progressive neurological disabilities. Her encephalopathy consisted of treatment-resistant seizures, a complex movement disorder, progressive intellectual disability, and deceleration of her head growth after late infancy. Focused evaluation at age 21 revealed GLUT1 deficiency caused by a novel heterozygous missence mutation in exon 7 (c.938C > A; p.Ser313Try) in SLC2A1 as the cause for her disabilities. PMID:22212417

  16. A novel HSD17B10 mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression.

    PubMed

    Falk, Marni J; Gai, Xiaowu; Shigematsu, Megumi; Vilardo, Elisa; Takase, Ryuichi; McCormick, Elizabeth; Christian, Thomas; Place, Emily; Pierce, Eric A; Consugar, Mark; Gamper, Howard B; Rossmanith, Walter; Hou, Ya-Ming

    2016-05-01

    We report a Caucasian boy with intractable epilepsy and global developmental delay. Whole-exome sequencing identified the likely genetic etiology as a novel p.K212E mutation in the X-linked gene HSD17B10 for mitochondrial short-chain dehydrogenase/reductase SDR5C1. Mutations in HSD17B10 cause the HSD10 disease, traditionally classified as a metabolic disorder due to the role of SDR5C1 in fatty and amino acid metabolism. However, SDR5C1 is also an essential subunit of human mitochondrial RNase P, the enzyme responsible for 5'-processing and methylation of purine-9 of mitochondrial tRNAs. Here we show that the p.K212E mutation impairs the SDR5C1-dependent mitochondrial RNase P activities, and suggest that the pathogenicity of p.K212E is due to a general mitochondrial dysfunction caused by reduction in SDR5C1-dependent maturation of mitochondrial tRNAs. PMID:26950678

  17. What Causes Idiopathic Pulmonary Fibrosis?

    MedlinePlus

    ... of 10 people who have IPF also have gastroesophageal reflux disease (GERD). GERD is a condition in which acid from your ... up into your throat. Some people who have GERD may regularly breathe in tiny drops of acid ...

  18. Idiopathic gingival fibromatosis

    PubMed Central

    Dani, Nitin Hemchandra; Khanna, Dinkar Parveen; Bhatt, Vaibhavi Hitesh; Joshi, Chaitanya Pradeep

    2015-01-01

    Idiopathic gingival fibromatosis (IGF) is a rare hereditary condition characterized by slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva caused by increase in submucosal connective tissue elements, mostly associated with some syndrome. This case report describes a case of nonsyndromic generalized IGF in an 18-year-old male patient who presented with generalized gingival enlargement. The enlarged tissue was surgically removed by internal bevel gingivectomy and ledge and wedge procedure. The patient was regularly monitored clinically for improvement in his periodontal condition as well as for any recurrence of gingival overgrowth. PMID:26941525

  19. History of epilepsy: nosological concepts and classification.

    PubMed

    Wolf, Peter

    2014-09-01

    The purpose of this review is to provide insight into the development of the nosological views of the epilepsies, from prehistoric times to the present, and highlight how these views are reflected by terminology and classification. Even the earliest written documents reveal awareness that there are multiple forms of epilepsy, and it is surprising that they should be included under the same disease concept, perhaps because the generalised tonic-clonic seizure served as a common denominator. The Hippocratic doctrine that the seat of epilepsy is in the brain may be rooted in earlier knowledge of traumatic seizures. Galenus differentiated cases where the brain was the primary site of origin from others where epilepsy was concomitant with illness in other parts of the body. This laid the fundament for the distinction between idiopathic and symptomatic epilepsies, the definition of which changed considerably over time. The description of the multiple seizure types as they are known at present started in the late 18th century. Attempts to classify seizure types began in the late 19th century, when Jackson formulated a comprehensive pathophysiological definition of epilepsy. Electroencephalography supported a second dichotomy, between seizures with localised onset and others with immediate involvement of both hemispheres which became known as "generalised". In recent years, advanced methods of studying brain function in vivo, including the generation of both spontaneous and reflex epileptic seizures, have revolutionised our understanding of focal and "generalised" human ictogenesis. Both involve complex neuronal networks which are currently being investigated. PMID:25256654

  20. Association of Family History of Epilepsy with Earlier Age Onset of Juvenile Myoclonic Epilepsy

    PubMed Central

    2016-01-01

    Objective Juvenile myoclonic epilepsy (JME) is supposedly the most frequent subtype of idiopathic generalized epilepsies (IGE). The aim of this study was to determine the prevalence of JME and comparison of patients’ demographics as well as timeline of the disease between positive family history epileptic patients (PFHE) and negative family history epileptic patients (NFHE) among sample of Iranian epileptic patients. Materials & Methods From Feb. 2006 to Oct. 2009, 1915 definite epileptic patients (873 females) referred to epilepsy clinics in Isfahan, central Iran, were surveyed and among them, 194 JME patients were diagnosed. JME was diagnosed by its specific clinical and EEG criteria. Patients were divided into two groups as PFHE and NFHE and data were compared between them. Results JME was responsible for 10% (194 patients) of all types of epilepsies. Of JME patients, 53% were female. In terms of family history of epilepsy, 40% were positive. No significant differences was found between PFHE and NFHE groups as for gender (P>0.05). Age of epilepsy onset was significantly earlier in PFHE patients (15 vs. 22 yr, P<0.001). Occurrence of JME before 18 yr old among PFHE patients was significantly higher (OR=2.356, P=0.007). Conclusion A family history of epilepsy might be associated with an earlier age of onset in patients with JME. PMID:27247579

  1. Antiepileptic Drug Withdrawal in Dogs with Epilepsy

    PubMed Central

    Gesell, Felix Kaspar; Hoppe, Sonja; Löscher, Wolfgang; Tipold, Andrea

    2015-01-01

    Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs). In human beings with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free) for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases, the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects, and the idea that the medication could be unnecessary. Following AED withdrawal, four of these dogs remained seizure free, seven dogs suffered from seizure recurrence, of which only three dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication. PMID:26664952

  2. Functional Investigation of a Non-coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation

    PubMed Central

    Guo, Long; Yamashita, Hiroshi; Kou, Ikuyo; Takimoto, Aki; Meguro-Horike, Makiko; Horike, Shin-ichi; Sakuma, Tetsushi; Miura, Shigenori; Adachi, Taiji; Yamamoto, Takashi; Ikegawa, Shiro; Hiraki, Yuji; Shukunami, Chisa

    2016-01-01

    Previously, we identified an adolescent idiopathic scoliosis susceptibility locus near human ladybird homeobox 1 (LBX1) and FLJ41350 by a genome-wide association study. Here, we characterized the associated non-coding variant and investigated the function of these genes. A chromosome conformation capture assay revealed that the genome region with the most significantly associated single nucleotide polymorphism (rs11190870) physically interacted with the promoter region of LBX1-FLJ41350. The promoter in the direction of LBX1, combined with a 590-bp region including rs11190870, had higher transcriptional activity with the risk allele than that with the non-risk allele in HEK 293T cells. The ubiquitous overexpression of human LBX1 or either of the zebrafish lbx genes (lbx1a, lbx1b, and lbx2), but not FLJ41350, in zebrafish embryos caused body curvature followed by death prior to vertebral column formation. Such body axis deformation was not observed in transcription activator-like effector nucleases mediated knockout zebrafish of lbx1b or lbx2. Mosaic expression of lbx1b driven by the GATA2 minimal promoter and the lbx1b enhancer in zebrafish significantly alleviated the embryonic lethal phenotype to allow observation of the later onset of the spinal curvature with or without vertebral malformation. Deformation of the embryonic body axis by lbx1b overexpression was associated with defects in convergent extension, which is a component of the main axis-elongation machinery in gastrulating embryos. In embryos overexpressing lbx1b, wnt5b, a ligand of the non-canonical Wnt/planar cell polarity (PCP) pathway, was significantly downregulated. Injection of mRNA for wnt5b or RhoA, a key downstream effector of Wnt/PCP signaling, rescued the defective convergent extension phenotype and attenuated the lbx1b-induced curvature of the body axis. Thus, our study presents a novel pathological feature of LBX1 and its zebrafish homologs in body axis deformation at various stages of

  3. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

  4. Autism and epilepsy: a retrospective follow-up study.

    PubMed

    Hara, Hitoshi

    2007-09-01

    So-called "idiopathic" autism, which exhibited no major complications before diagnosis is well-known as one of the risk factors for epilepsy. This retrospective follow-up study aimed to clarify the characteristics of epilepsy in the autism; onset of seizure, seizure types, EEG findings and epilepsy outcome and the differences as a group between the autism with epilepsy and those without epilepsy. One hundred thirty individuals with autistic disorder or atypical autism diagnosed in childhood were followed up over 10 years and were evaluated almost every year up to 18-35 years of age. Their medical records related to perinatal conditions, IQ, social maturity scores and several factors of epilepsy were reviewed in October 2005. Thirty-three of the follow-up group (25%) exhibited epileptic seizures. The onset of epilepsy was distributed from 8 to 26 years of age. Two types of seizure were observed; partial seizure with secondarily generalized seizure and generalized seizure. Twenty of the epileptics (61%) showed the partial seizure. Although 18% of the non-epileptic group exhibited epileptic discharges on EEG, 68% of the epileptic group revealed epileptiform EEG findings before the onset of epilepsy. No differences were observed concerning the sex ratio, autistic disorder/atypical autism and past history of febrile seizures between the epileptic and non-epileptic groups. Lower IQ, lower social maturity score and higher frequency of prescribed psychotropics were observed in the epileptic group compared to the non-epileptics. Idiopathic autism was confirmed as the high risk factor for epilepsy. Epileptiform EEG findings predict subsequent onset of epileptic seizures in adolescence. Epilepsy is one of negative factors on cognitive, adaptive and behavioral/emotional outcomes for individuals with autism. PMID:17321709

  5. Behavioral and Movement Disorders due to Long-Lasting Myoclonic Status Epilepticus Misdiagnosed as ADHD in a Patient With Juvenile Myoclonic Epilepsy: Electroclinical Findings and Related Hemodynamic Changes.

    PubMed

    Fanella, Martina; Carnì, Marco; Morano, Alessandra; Albini, Mariarita; Lapenta, Leonardo; Casciato, Sara; Fattouch, Jinane; Di Castro, Elisabetta; Colonnese, Claudio; Vaudano, Anna Elisabetta; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2016-01-01

    Epilepsy and attention-deficit/hyperactivity disorder (ADHD) likely share common underlying neural mechanisms, as often suggested by both the evidence of electroencephalography (EEG) abnormalities in ADHD patients without epilepsy and the coexistence of these 2 conditions. The differential diagnosis between epilepsy and ADHD may consequently be challenging. In this report, we describe a patient presenting with a clinical association of "tics" and behavioral disorders that appeared 6 months before our first observation and had previously been interpreted as ADHD. A video-EEG evaluation documented an electroclinical pattern of myoclonic status epilepticus. On the basis of the revised clinical data, the EEG findings, the good response to valproate, the long-lasting myoclonic status epilepticus, and the enduring epileptic abnormalities likely causing behavioral disturbances, the patient's symptoms were interpreted as being the expression of untreated juvenile myoclonic epilepsy. The EEG-functional magnetic resonance imaging study revealed, during clinical generalized spike-and-wave and polyspike-and-wave discharges, positive blood oxygen level-dependent (BOLD) signal changes bilaterally in the thalamus, the prefrontal cortex (Brodmann area 6, supplementary motor area) and the cerebellum, and negative BOLD signal changes in the regions of the default mode network. Such findings, which are typical of BOLD changes observed in idiopathic generalized epilepsy, may also shed light on the anatomofunctional network underlying ADHD. PMID:25733678

  6. Paraneoplastic epilepsy.

    PubMed

    Serafini, Anna; Lukas, Rimas V; VanHaerents, Stephen; Warnke, Peter; Tao, James X; Rose, Sandra; Wu, Shasha

    2016-08-01

    Epilepsy can be a manifestation of paraneoplastic syndromes which are the consequence of an immune reaction to neuronal elements driven by an underlying malignancy affecting other organs and tissues. The antibodies commonly found in paraneoplastic encephalitis can be divided into two main groups depending on the target antigen: 1) antibodies against neuronal cell surface antigens, such as against neurotransmitter (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid (GABA)) receptors, ion channels (voltage-gated potassium channel (VGKC)), and channel-complex proteins (leucine rich, glioma inactivated-1 glycoprotein (LGI1) and contactin-associated protein-2 (CASPR2)) and 2) antibodies against intracellular neuronal antigens (Hu/antineuronal nuclear antibody-1 (ANNA-1), Ma2/Ta, glutamate decarboxylase 65 (GAD65), less frequently to CV2/collapsin response mediator protein 5 (CRMP5)). In this review, we provide a comprehensive survey of the current literature on paraneoplastic epilepsy indexed by the associated onconeuronal antibodies. While a range of seizure types can be seen with paraneoplastic syndromes, temporal lobe epilepsy is the most common because of the association with limbic encephalitis. Early treatment of the paraneoplastic syndrome with immune modulation/suppression may prevent the more serious potential consequences of paraneoplastic epilepsy. PMID:27304613

  7. Idiopathic cardiomegaly*

    PubMed Central

    1968-01-01

    Cardiomyopathies are certain heart diseases of unknown etiology and pathogenesis, occurring mostly in tropical and subtropical areas, where they constitute a major clinical problem and sometimes a public health problem. The need for international co-operation in the study of such forms of heart disease has long been recognized and WHO convened informal meetings of investigators on various aspects of the subject in 1964, 1965 and 1966. Out of these have arisen co-operative studies co-ordinated by WHO. In November 1967 a fourth informal meeting was held in Kingston, Jamaica, to review the following topics: the progress reports from all co-operating laboratories; the different types of cardiomyopathies; past experience with cardiac registries, and the diagnostic importance of coronary angiography. Steps were taken towards the formulation of a standard terminology, since too many confusing names are currently employed to mean “cardiomegaly of unknown origin”. A common name, “idiopathic cardiomegaly”, was therefore suggested for future use. The account presented here was prepared by Dr Z. Fejfar, Chief Medical Officer, Cardiovascular Diseases, World Health Organization, Geneva, on behalf of the other participants and is a précis of some of the information that was exchanged, some of the views that were expressed and of the suggestions that were made. PMID:4235740

  8. Adolescents' lived experience of epilepsy.

    PubMed

    Eklund, Pernilla Garmy; Sivberg, Bengt

    2003-02-01

    To improve the well-being of adolescents with epilepsy, research is needed on how adolescents cope. In this study, Lazarus' model of stress and coping and Antonovsky's Theory of Sense of Coherence were used as the theoretical framework. The aim was to describe the lived experience of adolescents with epilepsy and their coping skills. The participants were 13-19 years old with an epilepsy diagnosis but without mental retardation or cerebral palsy. The study was performed in southern Sweden at the pediatric department of a university hospital. Semistructured and open-ended interviews were conducted with 13 adolescents. The transcripts were analyzed with manifest and latent content analysis. All the adolescents had developed strategies to cope with the emotional strains caused by epilepsy. They experienced strains from the seizures, limitation of leisure activities, side effects of medication, and feelings of being different. The coping strategies described were finding support, being in control, and experimenting. PMID:12789720

  9. Atypical "benign" partial epilepsy of childhood or pseudo-lennox syndrome. Part II: family study.

    PubMed

    Doose, H; Hahn, A; Neubauer, B A; Pistohl, J; Stephani, U

    2001-02-01

    Atypical benign partial epilepsy of childhood (ABPE = Pseudo-Lennox syndrome) shows semiologic parallels to Lennox-Gastaut syndrome, however--besides the lack of tonic seizures--it has an entirely different etiology and prognosis. Recently Hahn et al [17] investigated the long-term evolution of 43 cases with ABPE. Symptomatology, EEG findings, and course were found to overlap with Rolandic epilepsy, Landau-Kleffner syndrome and ESES. The incidence of seizures in relatives was determined in the whole series investigated by Hahn et al [17]. Five of 56 siblings suffered from seizures (3 Rolandic seizures; one febrile convulsions; one unclassified). Three fathers reported grand mal. In 29 families of the series of Hahn et al EEG recordings were performed: 22 brothers, 19 sisters and 16 pairs of parents. In 29% of the siblings a sharp wave focus was demonstrable. The rate rose to 40% when only siblings investigated at the age of maximum expression (3 to 10 years) were considered. Sharp wave foci were mostly multifocal and indistinguishable from those observed in siblings of children with Rolandic epilepsy. Photoparoxysmal response and generalized spikes and waves during rest and hyperventilation were also found to be significantly elevated (26% and 13% respectively). We conclude that ABPE is a subgroup of idiopathic partial epilepsy of childhood (representing a less benign part of a spectrum) that has to be ranked in a continuum with Rolandic epilepsy. The different clinical phenotype might be caused by a higher expressivity of the identical genetic trait, possibly facilitated by other genetic or acquired factors. Genetic heterogeneity represents another possibility. PMID:11315204

  10. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia.

    PubMed

    Hardies, Katia; de Kovel, Carolien G F; Weckhuysen, Sarah; Asselbergh, Bob; Geuens, Thomas; Deconinck, Tine; Azmi, Abdelkrim; May, Patrick; Brilstra, Eva; Becker, Felicitas; Barisic, Nina; Craiu, Dana; Braun, Kees P J; Lal, Dennis; Thiele, Holger; Schubert, Julian; Weber, Yvonne; van 't Slot, Ruben; Nürnberg, Peter; Balling, Rudi; Timmerman, Vincent; Lerche, Holger; Maudsley, Stuart; Helbig, Ingo; Suls, Arvid; Koeleman, Bobby P C; De Jonghe, Peter

    2015-11-01

    The epileptic encephalopathies are a clinically and aetiologically heterogeneous subgroup of epilepsy syndromes. Most epileptic encephalopathies have a genetic cause and patients are often found to carry a heterozygous de novo mutation in one of the genes associated with the disease entity. Occasionally recessive mutations are identified: a recent publication described a distinct neonatal epileptic encephalopathy (MIM 615905) caused by autosomal recessive mutations in the SLC13A5 gene. Here, we report eight additional patients belonging to four different families with autosomal recessive mutations in SLC13A5. SLC13A5 encodes a high affinity sodium-dependent citrate transporter, which is expressed in the brain. Neurons are considered incapable of de novo synthesis of tricarboxylic acid cycle intermediates; therefore they rely on the uptake of intermediates, such as citrate, to maintain their energy status and neurotransmitter production. The effect of all seven identified mutations (two premature stops and five amino acid substitutions) was studied in vitro, using immunocytochemistry, selective western blot and mass spectrometry. We hereby demonstrate that cells expressing mutant sodium-dependent citrate transporter have a complete loss of citrate uptake due to various cellular loss-of-function mechanisms. In addition, we provide independent proof of the involvement of autosomal recessive SLC13A5 mutations in the development of neonatal epileptic encephalopathies, and highlight teeth hypoplasia as a possible indicator for SLC13A5 screening. All three patients who tried the ketogenic diet responded well to this treatment, and future studies will allow us to ascertain whether this is a recurrent feature in this severe disorder. PMID:26384929

  11. Progressive myoclonic epilepsies

    PubMed Central

    Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico

    2014-01-01

    Objective: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. Methods: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. Results: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Conclusions: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized. PMID:24384641

  12. Genetic etiology of new forms of familial epilepsy.

    PubMed

    Wang, Xuefeng; Lu, Yang

    2008-01-01

    Epilepsy is a common neurological disorder with an incidence of approximately 0.5%. In order to develop better strategies for treatment of epilepsy, more insight on the etiology and pathogenesis of epilepsy is required. In 2001, based on the diagnostic scheme of the International League Against Epilepsy, three new forms of familial epilepsy were identified. These include familial temporal lobe epilepsy, familial focal epilepsy with variable foci, and generalized epilepsy with febrile seizure plus. Mutation of a distinct set of genes has been reported in several forms of epilepsy. Mutation of LGI1 gene has been identified in familial lateral temporal lobe epilepsy while mutations of genes which encode sodium channels and GABAA receptors have been reported in generalized epilepsy with febrile seizure plus. However, no disease-causing gene has yet been found in families with familial mesial temporal lobe epilepsy or those with familial focal epilepsy with variable foci. Here, we review the genetic background of these three familial epilepsy syndromes, and provide a better insight on their genetic etiology. PMID:17981785

  13. Unexplained childhood anaemia: idiopathic pulmonary hemosiderosis.

    PubMed

    Siu, K K; Li, Rever; Lam, S Y

    2015-04-01

    This report demonstrates pulmonary haemorrhage as a differential cause of anaemia. Idiopathic pulmonary hemosiderosis is a rare disease in children; it is classically described as a triad of haemoptysis, pulmonary infiltrates on chest radiograph, and iron-deficiency anaemia. However, anaemia may be the only presenting feature of idiopathic pulmonary hemosiderosis in children due to occult pulmonary haemorrhage. In addition, the serum ferritin is falsely high in idiopathic pulmonary hemosiderosis which increases the diagnostic difficulty. We recommend that pulmonary haemorrhage be suspected in any child presenting with iron-deficiency anaemia and persistent bilateral pulmonary infiltrates. PMID:25904566

  14. Sexual problems in people with refractory epilepsy.

    PubMed

    Henning, Oliver J; Nakken, Karl O; Træen, Bente; Mowinckel, Petter; Lossius, Morten

    2016-08-01

    Sexual dysfunction is an important but often neglected aspect of epilepsy. The objective of this study was to explore the prevalence and types of sexual problems in patients with epilepsy and compare the results with similar data obtained from a representative sample of the general population. At the National Centre for Epilepsy in Norway, 171 of 227 consecutive adult inpatients and outpatients with epilepsy (response rate: 75.3%) and their neurologists participated in a questionnaire study about epilepsy and sexuality. The results were compared with data available from 594 adult Norwegians who had completed the same questionnaire. Patients with epilepsy had a significantly higher prevalence of sexual problems (women: 75.3% vs. 12.0%; men: 63.3% vs. 9.6%). The most commonly reported problems (>30%) were reduced sexual desire, orgasm problems, erection problems, and vaginal dryness. The patients reported considerable dissatisfaction regarding sexual functioning. Significantly more sexual problems were found in patients of both sexes with reduced quality of life and in women with symptoms of depression. We found no significant association between sexual problems and age of epilepsy onset, type of epilepsy, or use of enzyme-inducing antiepileptic drugs. Whereas age at sexual debut did not differ between the patients with epilepsy and the general population, men with epilepsy had a lower number of partners during the last 12months, and the proportion of women with a low frequency of intercourse was higher in the group with epilepsy. In conclusion, sexual problems are significantly greater in Norwegian patients with epilepsy than in the general adult population. As no single epilepsy type or treatment could be identified as a specific predisposing factor, it seems likely that there are multiple causes underlying our results, including both organic and psychosocial factors. PMID:27371882

  15. Symptomatic Epilepsies due to Cerebrovascular Diseases

    PubMed Central

    Dakaj, Nazim; Shatri, Nexhat; Isaku, Enver; Zeqiraj, Kamber

    2014-01-01

    Introduction: Cerebro-vascular diseases (CVD) are the leading cause of symptomatic epilepsies. This study aims to investigate: a) Frequency of epilepsy in patients with CVD; b) Correlation of epilepsy with the type of CVD (ischemic and hemorrhage) and with age. Methodology: It is analyzed medical documentation of 816 hospitalized patients with CVD in the clinic of Neurology in University Clinical Center (UCC) during the period January - December 2010. The study included data on patients presenting with epileptic seizures after CVD, and those with previously diagnosed epilepsy, are not included in the study. The diagnosis of CVD, are established in clinical neurological examination and the brain imaging (computer tomography and magnetic resonance imaging). The diagnosis of epilepsy is established by the criteria of ILAE (International League against Epilepsy) 1983, and epileptic seizures are classified according to the ILAE classification, of 1981. Results: Out of 816 patients with CVD, 692 were with ischemic stroke and 124 with hemorrhage. From 816 patients, epileptic seizures had 81 (10%), of which 9 patients had been diagnosed with epilepsy earlier and they are not included in the study. From 72 (99%) patients with seizures after CVD 25 (33%) have been with ischemia, whereas 47 (67%) with hemorrhage. Conclusion: CVD present fairly frequent cause of symptomatic epilepsies among patients treated in the clinic of Neurology at UCC (about 10%). The biggest number of patients with epilepsy after CVD was with intracerebral hemorrhage. PMID:25685086

  16. Juvenile idiopathic arthritis

    PubMed Central

    Bhatt, Krupa H; Karjodkar, Freny R; Sansare, Kaustubh; Patil, Darshana

    2014-01-01

    Juvenile Idiopathic Arthritis (JIA) is the most chronic musculoskeletal disease of pediatric population. The chronic course of disease has a great impact on oral health. Temporomandibular joint is involved in JIA causing limited mouth opening with progressive open bite, retrognathia, microgenia and bird like appearance. Joints of upper and lower extremities are also involved. Effect on upper limb function leads to difficulty with fine motor movements required for brushing and flossing. This increases incidence of caries and periodontal disease in children. The cause of JIA is still poorly understood and none of the available drugs for JIA can cure the disease. However, prognosis has improved as a result of progress in disease classification and management. The dental practitioner should be familiar with the symptoms and oral manifestations of JIA to help manage as multidisciplinary management is essential. PMID:24808703

  17. Adolescent idiopathic scoliosis.

    PubMed

    Cheng, Jack C; Castelein, René M; Chu, Winnie C; Danielsson, Aina J; Dobbs, Matthew B; Grivas, Theodoros B; Gurnett, Christina A; Luk, Keith D; Moreau, Alain; Newton, Peter O; Stokes, Ian A; Weinstein, Stuart L; Burwell, R Geoffrey

    2015-01-01

    Adolescent idiopathic scoliosis (AIS) is the most common form of structural spinal deformities that have a radiological lateral Cobb angle - a measure of spinal curvature - of ≥10(°). AIS affects between 1% and 4% of adolescents in the early stages of puberty and is more common in young women than in young men. The condition occurs in otherwise healthy individuals and currently has no recognizable cause. In the past few decades, considerable progress has been made towards understanding the clinical patterns and the three-dimensional pathoanatomy of AIS. Advances in biomechanics and technology and their clinical application, supported by limited evidence-based research, have led to improvements in the safety and outcomes of surgical and non-surgical treatments. However, the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear. Thus, at present, both the prevention of AIS and the treatment of its direct underlying cause are not possible. PMID:27188385

  18. Idiopathic Retroperitoneal Fibrosis.

    PubMed

    Vaglio, Augusto; Maritati, Federica

    2016-07-01

    Idiopathic retroperitoneal fibrosis (RPF), reviewed herein, is a rare fibro-inflammatory disease that develops around the abdominal aorta and the iliac arteries, and spreads into the adjacent retroperitoneum, where it frequently causes ureteral obstruction and renal failure. The clinical phenotype of RPF is complex, because it can be associated with fibro-inflammatory disorders involving other organs, is considered part of the spectrum of IgG4-related disease, and often arises in patients with other autoimmune conditions. Obstructive uropathy is the most common complication, although other types of renal involvement may occur, including stenosis of the renal arteries and veins, renal atrophy, and different types of associated GN. Environmental and genetic factors contribute to disease susceptibility, whereas the immunopathogenesis of RPF is mediated by different immune cell types that eventually promote fibroblast activation. The diagnosis is made on the basis of computed tomography or magnetic resonance imaging, and positron emission tomography is a useful tool in disease staging and follow-up. Treatment of idiopathic RPF aims at relieving ureteral obstruction and inducing disease regression, and includes the use of glucocorticoids, combined or not with other traditional immunosuppressants. However, biologic therapies such as the B cell-depleting agent rituximab are emerging as potentially efficacious agents in difficult-to-treat cases. PMID:26860343

  19. Cognitive disorders in pediatric epilepsy.

    PubMed

    Jambaqué, I; Pinabiaux, C; Lassonde, M

    2013-01-01

    Childhood epilepsy may cause cognitive disorders and the intellectual quotient is indeed not normally distributed in epileptic children, a fair proportion of whom show an IQ in the deficient range. Some epileptic syndromes happen during vulnerability periods of brain maturation and interfere with the development of specific cognitive functions. This is the case for the Landau-Kleffner syndrome, which generally appears during speech development and affects language. Similarly, West syndrome - or infantile spasms - is an epileptogenic encephalopathy appearing during the first years of life and induces a major delay in social and oculo-motor development. Specific impairments can also be identified in partial childhood epilepsies in relation with seizure focus localization. For instance, left temporal and frontal epilepsies are frequently associated with verbal impairments. Moreover, episodic memory disorders have been described in children suffering from temporal lobe epilepsy whereas executive deficits (planning, self-control, problem solving) have been reported in frontal lobe epilepsy. In most cases, including its mildest forms, childhood epilepsy induces attention deficits, which may affect academic achievement. These observations militate in favor of individual neuropsychological assessments as well as early interventions in order to provide the child with an optimal individualized treatment program. PMID:23622216

  20. Delirium and epilepsy

    PubMed Central

    Kaplan, Peter W.

    2003-01-01

    Delirium (a state of usually reversible global brain disfunction due to toxic, metabolic, or infectious causes) and epilepsy (a condition of spontaneous, recurrent paroxysmal electrical excitation or dysfunction) are becoming increasingly better understood, and hence easier to diagnose and treat. The clinical features of delirium predominantly involve subacute changes in cognition, awareness, and activity levels, behavioral disturbance, clouding consciousness, and sleep-wake cycle changes. In contrast, epilepsy involves the acute interruption of brain function, often with convulsive activity, falls, and injury. States that may share the clinical features of both, such as nonconvulsive epileptic states, are also important: the cause of brain derangement is one of excessive and abnormal electrical brain activity. In such conditions, the clinical manifestations may resemble states of delirium and confusion, and the absence of convulsive clinical activity is significant. Electroencephalography remains the diagnostic test of choice: it is essential for differentiating these two conditions, enabling the distinctly different treatments and epilepsy. Ongoing research and investigation are essential to better understand the abnormal brat mechanisms underlying delirium, and to develop better tools for objective diagnosis. PMID:22034394

  1. Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy.

    PubMed

    Lal, Dennis; Pernhorst, Katharina; Klein, Karl Martin; Reif, Philipp; Tozzi, Rossana; Toliat, Mohammad R; Winterer, Georg; Neubauer, Bernd; Nürnberg, Peter; Rosenow, Felix; Becker, Felicitas; Lerche, Holger; Kunz, Wolfram S; Kurki, Mitja I; Hoffmann, Per; Becker, Albert J; Perucca, Emilio; Zara, Federico; Sander, Thomas; Weber, Yvonne G

    2015-09-01

    Partial deletions of the RBFOX1 gene encoding the neuronal splicing regulator have been reported in a range of neurodevelopmental diseases including idiopathic/genetic generalized epilepsy (IGE/GGE), childhood focal epilepsy, and self-limited childhood benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy), and autism. The protein regulates alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. Herein, we examined whether structural deletions affecting RBFOX1 exons confer susceptibility to common forms of juvenile and adult focal epilepsy syndromes. We screened 807 unrelated patients with sporadic focal epilepsy, and we identified seven hemizygous exonic RBFOX1 deletions in patients with sporadic focal epilepsy (0.9%) in comparison to one deletion found in 1,502 controls. The phenotypes of the patients carrying RBFOX1 deletions comprise magnetic resonance imaging (MRI)-negative epilepsy of unknown etiology with frontal and temporal origin (n = 5) and two patients with temporal lobe epilepsy with hippocampal sclerosis. The epilepsies were largely pharmacoresistant but not associated with intellectual disability. Our study extends the phenotypic spectrum of RBFOX1 deletions as a risk factor for focal epilepsy and suggests that exonic RBFOX1 deletions are involved in the broad spectrum of focal and generalized epilepsies. PMID:26174448

  2. Chronic Idiopathic Thrombocytogenic Purpura

    PubMed Central

    Pineo, G. F.

    1984-01-01

    Chronic idiopathic thrombocytopenic purpura (ITP) is a relatively common cause of an acquired hemostatic defect. It is important for family physicians to recognize this disorder, because of its insidious onset and the fact that it most commonly affects women of childbearing age. Chronic ITP is due to an antibody in the plasma which attaches to platelets and leads to their destruction in the reticuloendothelial system. The antibody can cross the placenta and affect the fetus. Although the condition may not disappear, in the vast majority of patients it can be controlled with current therapy, including prednisone, splenectomy and immunosuppressive agents. Although the mortality rate is low, patients with severe thrombocytopenia may have significant bleeding problems requiring special measures such as platelet transfusions, intravenous gammaglobulin, plasmapheresis and emergency splenectomy. Upon diagnosis, these patients should be referred to a large, specialized centre. PMID:21279099

  3. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

    MedlinePlus

    ... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

  4. Non-progressive familial idiopathic intracranial calcification: a family report.

    PubMed Central

    Callender, J S

    1995-01-01

    The clinical features and long term outcome of familial idiopathic intracranial calcification in three members of one family are described. The illness presented as psychiatric disorder in all patients, and in one patient, epilepsy and intellectual deterioration were later manifestations. Skull radiographs and CT were performed sequentially, in one patient, over a 22 year period and, in another, CT was carried out eight years apart. In neither patient was there any evidence of progression of calcification. Images PMID:7561925

  5. Non-invasive EEG evaluation in epilepsy diagnosis.

    PubMed

    Rosenow, Felix; Klein, Karl Martin; Hamer, Hajo M

    2015-04-01

    The EEG is an invaluable tool in the diagnosis of epilepsy which guides clinical management. It helps to determine if attacks are of epileptic origin, allows the estimation of the recurrence risk after a first seizure, aids in the diagnosis of the epilepsy syndrome and represents the gold standard in the presurgical evaluation of epilepsy. The EEG can also detect subclinical seizures as a cause of coma. In this review we discuss the sensitivity and specificity of the EEG, present the EEG findings and their significance in different epilepsy syndromes including focal and generalized epilepsies and describe the application of activation procedures. PMID:25779862

  6. Environmental risk factors for temporal lobe epilepsy--is prenatal exposure to the marine algal neurotoxin domoic acid a potentially preventable cause?

    PubMed

    Stewart, Ian

    2010-03-01

    Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is one of the more common forms of chronic epilepsy. Its aetiology is unknown, though an early developmental insult is thought by some to be an important trigger. There is not a strong genetic predisposition; gene-environment interactions are more significant considerations. Environmental risk factors for TLE-HS are under-researched. Domoic acid (DA) is an environmental neurotoxin of algal origin that can contaminate marine food webs. DA can cross the placenta, is significantly more toxic to the developing brain compared to the adult brain, and has affected humans and marine wildlife through mass poisonings. DA coincidentally has a decades-long history of use as a chemical model of temporal lobe epilepsy, along with its close structural analogue kainic acid (also of algal origin). The principal hypothesis presented here is that dietary exposure to doses of DA that are sub-clinical in pregnant women may be sufficient to damage the foetal hippocampus and initiate epileptogenesis. The hypothesis could be tested both experimentally by in vivo proof-of-concept animal studies that expand on current knowledge of prenatal susceptibility to DA neurotoxicity, and by epidemiological investigations directed towards dietary exposure to marine food products. If only a small proportion of the attributable risk for TLE-HS is found to be due to gestational exposure to DA, the public health implications would still be of great significance, as this would represent a potentially preventable exposure. Other potent neurotoxins are produced by marine microalgae and freshwater cyanobacteria. These structurally and mechanistically diverse toxins can also contaminate water supplies, seafood and shellfish. Several operate by modulating ion channels, so may also be of interest to epilepsy researchers. DA is also the subject of preliminary scrutiny in strandings involving odontocete cetaceans. The implications of such work are

  7. What I learnt from studying epilepsy: epileptology and myself.

    PubMed

    Akimoto, Haruo

    2004-04-01

    My life work with epilepsy has allowed me to learn a great deal. As an old soldier, I would like to give an account of some important milestones in my lifetime learning. The first factor that linked me to epilepsy was listening to a lecture delivered by Dr Yushi Uchimura on 'The pathogenesis of Ammon's horn sclerosis' at a conference of the Japanese Society of Neurology (now Japanese Society of Psychiatry and Neurology) in 1928 when I was a 4th year medical student at Tokyo University. The following year, I started to study under Dr Uchimura at the Department of Psychiatry, Hokkaido University School of Medicine. Another factor that linked me to clinical care and research of epilepsy as a psychiatrist was my encounter with the two volumes of 'Selected Writing of John Hughlings Jackson' edited by J. Taylor. Jackson's greatest asset and contribution to modern epileptology include (i) the discovery of 'Jacksonian epilepsy', (ii) 'conceptual revolution of epilepsy' by recognizing transient mental disorders as seizures, (iii) modern definition of epilepsy by defining epileptic seizures as discharges in the gray matter, and (iv) discovery of 'new epilepsy' (now temporal lobe epilepsy). In 1940, I reported clinical courses indistinguishable from schizophrenia in epilepsy cases. Through my studies, I disputed the then prevailing interpretation of this condition as epilepsy complicating schizophrenia, and proved that these cases were in fact epileptic mental disorders caused by epilepsy. Many patients with epilepsy require medical care as well as rehabilitation and welfare support. We need to further promote the facilities for rehabilitation and employment in the community for persons with epilepsy, such as co-operatives and welfare worksites. The issues that epileptology and epilepsy face in the 21st century is to realize the goals of liberating epilepsy from social stigma and protecting all the citizen's rights for persons with epilepsy. PMID:15009812

  8. Genetics and Idiopathic Interstitial Pneumonias.

    PubMed

    Chu, Sarah G; El-Chemaly, Souheil; Rosas, Ivan O

    2016-06-01

    Significant progress has been made in elucidating the genetics of parenchymal lung diseases, particularly idiopathic interstitial pneumonias (IIPs). IIPs are a heterogeneous group of diffuse interstitial lung diseases of uncertain etiology, diagnosed only after known causes of interstitial lung disease have been excluded. Idiopathic pulmonary fibrosis is the most common IIP. Through candidate gene approaches and genome wide association studies, much light has been shed on the genetic origins of IIPs, enhancing our understanding of risk factors and pathogenesis. However, significant work remains to be accomplished in identifying novel genetic variants and characterizing the function of validated candidate genes in lung pathobiology, their interplay with environmental factors, and ultimately translating these discoveries to patient care. PMID:27231858

  9. Obtaining genetic testing in pediatric epilepsy.

    PubMed

    Ream, Margie A; Patel, Anup D

    2015-10-01

    The steps from patient evaluation to genetic diagnosis remain complicated. We discuss some of the genetic testing methods available along with their general advantages and disadvantages. We briefly review common pediatric epilepsy syndromes with strong genetic association and provide a potentially useful algorithm for genetic testing in drug-resistant epilepsy. We performed an extensive literature review of available information as it pertains to genetic testing and genetics in pediatric epilepsy. If a genetic disorder is suspected as the cause of epilepsy, based on drug resistance, family history, or clinical phenotype, timely diagnosis may reduce overall cost, limit the diagnostic odyssey that can bring much anxiety to families, improve prognostic accuracy, and lead to targeted therapy. Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors, unless the ordering neurologist has a strong background in and understanding of genetics. Genetic testing can play an important role in the care provided to patients with epilepsy. PMID:26345167

  10. Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice.

    PubMed

    Matsushita, Yuki; Sakai, Yasunari; Shimmura, Mitsunori; Shigeto, Hiroshi; Nishio, Miki; Akamine, Satoshi; Sanefuji, Masafumi; Ishizaki, Yoshito; Torisu, Hiroyuki; Nakabeppu, Yusaku; Suzuki, Akira; Takada, Hidetoshi; Hara, Toshiro

    2016-01-01

    Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8-10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6-8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain. PMID:26961412

  11. Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice

    PubMed Central

    Matsushita, Yuki; Sakai, Yasunari; Shimmura, Mitsunori; Shigeto, Hiroshi; Nishio, Miki; Akamine, Satoshi; Sanefuji, Masafumi; Ishizaki, Yoshito; Torisu, Hiroyuki; Nakabeppu, Yusaku; Suzuki, Akira; Takada, Hidetoshi; Hara, Toshiro

    2016-01-01

    Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8–10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6–8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain. PMID:26961412

  12. Uniparental disomy as a cause of spinal muscular atrophy and progressive myoclonic epilepsy: phenotypic homogeneity due to the homozygous c.125C>T mutation in ASAH1.

    PubMed

    Giráldez, Beatriz G; Guerrero-López, Rosa; Ortega-Moreno, Laura; Verdú, Alfonso; Carrascosa-Romero, M Carmen; García-Campos, Óscar; García-Muñozguren, Susana; Pardal-Fernández, José Manuel; Serratosa, José M

    2015-03-01

    Spinal muscular atrophy and progressive myoclonic epilepsy (SMAPME, OMIM#159950) is a rare autosomal recessive disorder characterized by the combination of progressive myoclonic epilepsy and muscular weakness due to lower motor neuron disease. Mutations in ASAH1, previously associated only to Farber disease, have been recently described in seven patients with SMAPME. A homozygous c.125C>T mutation was initially found in six patients with a clinical homogeneous phenotype. A heterozygous compound mutation found in an additional patient has broadened the clinical and genetic spectrum of clinical SMAPME. We report a new case of a 13-year-old girl with SMAPME with the homozygous ASAH1 c.125C>T mutation, unique in that it is due to paternal uniparental disomy. She experienced muscle weakness from the age of three due to lower motor neuron involvement that lead to severe handicap and onset in late childhood of a progressive myoclonic epilepsy. This clinical picture fully overlaps with that of previously reported patients with this mutation and supports our view that the clinical phenotype associated with the homozygous c.125C>T mutation constitutes a clinically homogenous and recognizable disease. PMID:25578555

  13. Lennox-Gastaut syndrome and epilepsy with myoclonic-astatic seizures.

    PubMed

    Kaminska, Anna; Oguni, Hirokazu

    2013-01-01

    Among nonsymptomatic epilepsies exhibiting several types of generalized seizures in children two syndromes were progressively identified: epilepsy with myoclonic-astatic seizures (MAE) and nonsymptomatic Lennox-Gastaut syndrome (LGS). Various approaches based on etiology, electroclinical semiology, and mathematical analysis have progressively helped to distinguish these two conditions. Both conditions preferentially affect boys. The course is stereotyped in MAE, characterized by progressive worsening of epilepsy, usual pharmacoresistance at onset and tonic-clonic seizures, myoclonus and frequent episodes of myoclonic status epilepticus. EEG shows 3Hz spike wave bursts characteristic of idiopathic generalized epilepsy together with slowing of the tracing. In LGS, major seizures are mainly atypical absences and tonic seizures with 0.5-2Hz slow spike-waves and eventually focal anomalies. Prognosis in both syndromes ranges from recovery without sequelae to pharmacoresistant epilepsy that has improved over the past 2 decades with the new generation antiepileptic compounds. Iatrogenic factors may contribute to the poor prognosis, mainly in MAE. Pathophysiology remains speculative for both syndromes: although both share factors of brain maturation, MAE is probably mainly related to genetic predisposition whereas LGS results from some unidentified cortical brain malformation. In unfavorable cases, there may therefore be a continuum between both syndromes. They need to be distinguished from other epilepsy syndromes and inborn errors of metabolism that begin in the same age range: atypical idiopathic benign epilepsy, frontal lobe epilepsy with secondary bisynchrony, ring chromosome 20, ceroid lipofuscinosis, and nonsymptomatic late-onset spasms. PMID:23622212

  14. [Epilepsy with higher brain dysfunction].

    PubMed

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Kuroda, Takeshi; Fujita, Kazuhisa; Itaya, Kazuhiro; Ishigaki, Seiichiro; Kawamura, Mitsuru

    2013-02-01

    Acquired higher brain dysfunction is for the most part due to cerebral vascular disease, but epilepsy may also be a cause. In this study with five patients, we discuss the advantages of anti-epileptic drugs (AEDs) for persistent higher brain dysfunction. The patients showed chronic amnesia or acute aphasia, with associated symptoms like personality change. All five cases affected automatism or convulsive attack, though only after the emergence of higher brain dysfunction and administration of AEDs. There were underlying diseases like cerebral arteriovenous malformation in four cases, but the other patient had none. Electroencephalogram and single photon emission computed tomography revealed one case of aphasia epilepsy with higher brain dysfunction. These results suggest the potential therapeutic efficacy of AEDs for persistent higher brain dysfunction, and we must differentiate epilepsy with higher brain dysfunction from dementia or cerebral vascular disease. PMID:23399676

  15. Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.

    PubMed

    Klassen, Tara; Davis, Caleb; Goldman, Alica; Burgess, Dan; Chen, Tim; Wheeler, David; McPherson, John; Bourquin, Traci; Lewis, Lora; Villasana, Donna; Morgan, Margaret; Muzny, Donna; Gibbs, Richard; Noebels, Jeffrey

    2011-06-24

    Ion channel mutations are an important cause of rare Mendelian disorders affecting brain, heart, and other tissues. We performed parallel exome sequencing of 237 channel genes in a well-characterized human sample, comparing variant profiles of unaffected individuals to those with the most common neuronal excitability disorder, sporadic idiopathic epilepsy. Rare missense variation in known Mendelian disease genes is prevalent in both groups at similar complexity, revealing that even deleterious ion channel mutations confer uncertain risk to an individual depending on the other variants with which they are combined. Our findings indicate that variant discovery via large scale sequencing efforts is only a first step in illuminating the complex allelic architecture underlying personal disease risk. We propose that in silico modeling of channel variation in realistic cell and network models will be crucial to future strategies assessing mutation profile pathogenicity and drug response in individuals with a broad spectrum of excitability disorders. PMID:21703448

  16. Childhood epilepsy and sleep

    PubMed Central

    Al-Biltagi, Mohammed A

    2014-01-01

    Sleep and epilepsy are two well recognized conditions that interact with each other in a complex bi-directional way. Some types of epilepsies have increased activity during sleep disturbing it; while sleep deprivation aggravates epilepsy due to decreased seizure threshold. Epilepsy can deteriorate the sleep-related disorders and at the same time; the parasomnias can worsen the epilepsy. The secretion of sleep-related hormones can also be affected by the occurrence of seizures and supplementation of epileptic patients with some of these sleep-related hormones may have a beneficial role in controlling epilepsy. PMID:25254184

  17. [Eponyms and epilepsy (history of Eastern civilizations)].

    PubMed

    Janković, S M; Sokić, D V; Lević, Z M; Susić, V; Drulović, J; Stojsavljević, N; Veskov, R; Ivanus, J

    1996-01-01

    considered as life threatening events. Persian history of epilepsy, except from the 6th century Zoroastrian "Avesta" document, lacks the written or spoken medical heritage untill the 7th century A.D. and the Arabic conquest of the entire Moslem world. On the other hand, Islamic medicine should be freed from the simple prejudice that the Moslem authors were only the translators of Greek medicine; contrary to such a view, their work contains a high degree of individuality. Although Mohammed introduced a lot of novelty into medicine, Khoran and the Sayings do not explicitly refer to epilepsy. Of importance is to notice that Moslem medicine did not have demons in the "repertoire" of direct causes of epilepsy. The causes and the cures of epilepsy were more magic-mystical and occult in nature, which is reminiscent of the European, as well as Serbian Middle age attitudes. Avicenna recognized difference between children and adult epilepsy. He considered insomnia and afternoon siesta as well as intensive sounds and light to be a provocative factors, whereby we see that at least empirically he knew of sleep (deprivation), startle and reflex epilepsy. The XIII century invasion of Mongols brought about the recession in Moslem Medicine; it recovered only in the XVIII century under the strong influence of European medicine handed over to us through Jewish doctors of various nationalities. The story of the China history of epilepsy has its debut approximately in the 8th century B. C. Medical texts from this period name epilepsy "Dian" and "Xian" which meant "the falling sickness" and "convulsions", respectively. Chinese medical terminology often interchangeably used the words "mania", "madness" and "psychosis" for "epilepsy" which, aside from a prominent language barrier, brings additional confusion. Although Chinese documents gave the first description of the grand mal epileptic attack already in the 8th century B. C. (ABSTRACT TRUNCATED) PMID:9102852

  18. American Epilepsy Society

    MedlinePlus

    ... and pricing here . View the preliminary program here . Epilepsy Currents Generic Substitution of AEDs: Is it Time ... in a multicenter prospective infantile spasms cohort More Epilepsy Professional News AES Releases New Guildeline for Treatment ...

  19. Listening to Epilepsy.

    ERIC Educational Resources Information Center

    Brunquell, Phillip J.

    1994-01-01

    This paper discusses what epilepsy is and what it is not, defines types of epileptic seizures, identifies epilepsy syndromes, discusses antiepileptic drugs, describes seizure surgery, and examines issues of quality of life. (JDD)

  20. Epilepsy and Mood

    MedlinePlus

    ... Editors David C. Spencer, MD Steven Karceski, MD Epilepsy and mood Update Steven Karceski, MD In their ... important and worrisome topic for peo- ple with epilepsy. In short, a patient may wonder, “ Will the ...

  1. Recognizing and preventing epilepsy-related mortality: A call for action.

    PubMed

    Devinsky, Orrin; Spruill, Tanya; Thurman, David; Friedman, Daniel

    2016-02-23

    Epilepsy is associated with a high rate of premature mortality from direct and indirect effects of seizures, epilepsy, and antiseizure therapies. Sudden unexpected death in epilepsy (SUDEP) is the second leading neurologic cause of total lost potential life-years after stroke, yet SUDEP may account for less than half of all epilepsy-related deaths. Some epilepsy groups are especially vulnerable: individuals from low socioeconomic status groups and those with comorbid psychiatric illness die more often than controls. Despite clear evidence of an important public health problem, efforts to assess and prevent epilepsy-related deaths remain inadequate. We discuss factors contributing to the underestimation of SUDEP and other epilepsy-related causes of death. We suggest the need for a systematic classification of deaths directly due to epilepsy (e.g., SUDEP, drowning), due to acute symptomatic seizures, and indirectly due to epilepsy (e.g., suicide, chronic effects of antiseizure medications). Accurately estimating the frequency of epilepsy-related mortality is essential to support the development and assessment of preventive interventions. We propose that educational interventions and public health campaigns targeting medication adherence, psychiatric comorbidity, and other modifiable risk factors may reduce epilepsy-related mortality. Educational campaigns regarding sudden infant death syndrome and fires, which kill far fewer Americans than epilepsy, have been widely implemented. We have done too little to prevent epilepsy-related deaths. Everyone with epilepsy and everyone who treats people with epilepsy need to know that controlling seizures will save lives. PMID:26674330

  2. Animal models to study aetiopathology of epilepsy: what are the features to model?

    PubMed

    Guillemain, Isabelle; Kahane, Philippe; Depaulis, Antoine

    2012-09-01

    In order to understand the physiopathology of epilepsies and develop antiepileptic drugs, animal models have been developed. These models appear to be valuable predictors of treatment efficacy; however, several of the currently used models remain questionable and probably inappropriate for the search for new treatments, in particular for epilepsies that cannot be treated by current antiepileptic drugs. In the present review, we report the results of a recent survey conducted by neurologists in charge of an epilepsy programme based at different hospitals in France. The 36 experts were questioned, via the internet, on the most critical features of four prototypic forms of epilepsy (idiopathic generalised epilepsies with convulsive seizures, absence epilepsy, focal epilepsy associated with dysplasia, and focal epilepsy associated with hippocampal sclerosis) that should be taken into account with regards to the relevance of animal models of epilepsy. Their answers suggest that most current models for focal epilepsies associated with either dysplasia or hippocampal sclerosis do not address the most relevant features. The models currently used in mice and rats are discussed in light of the data obtained in our survey. PMID:22947423

  3. Intellectual Disability and Epilepsy in Down Syndrome

    PubMed Central

    BARCA, Diana; TARTA-ARSENE, Oana; DICA, Alice; ILIESCU, Catrinel; BUDISTEANU, Magdalena; MOTOESCU, Cristina; BUTOIANU, Niculina; CRAIU, Dana

    2014-01-01

    Down Syndrome (DS) is the most common genetic cause of mental retardation, with a reported frequency of epilepsy between 1.4-17% (1). There is a paucity of data in the literature regarding epilepsy in Down syndrome and its relation to intellectual disability. Objectives: The purpose of this article is to analyze the association of epilepsy in children with DS - frequency and type of seizures, treatment, outcome and to compare cognitive impairment of children with DS and epilepsy and DS without epilepsy from our cohort. Methods: A four years systematic retrospective analysis of the database of the Pediatric Neurology Clinic (January 2010 - December 2013) identified a cohort of 39 pediatric cases with DS and neurological symptoms, 9 of them (23%) associating epileptic seizures. Following data were analysed: clinical and neurological examination, type/s of seizures, electroencephalography (EEG), cerebral magnetic resonance imaging (MRI), psychological examination, psychiatric evaluation in selected cases, electrocardiography (ECG), cardiac ultrasonography, ophthalmologic examination. Results: 23% (9 patients) of the children with DS of our cohort presented epilepsy. Five patients had epileptic spasms (56%), one of these further developed astatic seizures. Focal seizures were observed in three patients (33%) and absence with eyelid myoclonias in one patient (11%). Two of the nine patients with DS and epilepsy had generalized seizures, both with very good response to levetiracetam (LEV). EEG was abnormal at seizure onset, and was improved after treatment. Of the nine children with DS and epilepsy, two (22%) presented mild mental retardation and seven (78%) had moderate to severe cognitive delay. Of the 30 children with DS and without epilepsy, 21 (70%) had mild mental retardation and 9 (30%) had moderate to severe cognitive impairment. Conclusions: The most frequent epileptic syndrome associated with DS is West syndrome, with good response to specific antiepileptics

  4. Neurological morbidity of severe epilepsy.

    PubMed

    Janz, D

    1988-01-01

    The "severity" of a disease is a relative expression and its definition will vary depending on the perspective of the observer. The patient's subjective perception of the disease, the way it is regarded socially by the community, and the doctor's objective assessment rarely coincide. In fact, they are frequently diametrically opposed. As far as the patient's personal perception of epilepsy is concerned, there has apparently been no satisfactory attempt thus far at a systematic grading of the subjective handicap, despite the growth of interest in psychological matters and the self-help movement. Similarly, social ability or disability cannot be adequately assessed on the basis of medical criteria such as frequency and type of seizures. We present a grading system which will serve as an example of an appropriate method of assessing social abilities, and which will permit the patient's occupational potential to be estimated in relation to the risk of accidents resulting from seizures. From the medical point of view, the impairment of a patient's abilities due to epilepsy is a function of the patient's responsiveness to treatment. We present a critical review of the factors which have an effect on the therapeutic prognosis: the causes of epilepsy, underlying structural lesions, the incidence of convulsive status epilepticus, various types of attacks, and the different epileptic syndromes. Taking two examples--epilepsy presenting in the form of absence and epilepsy with complex focal seizures--we show that ultimately the "severity of epilepsy" can only be defined from the medical standpoint on the basis of several factors whose value is of a predictive nature. PMID:3292232

  5. [Idiopathic Pulmonary Fibrosis].

    PubMed

    Prasse, A

    2015-10-01

    Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and a disease of the elderly. Cigarette smoking and longterm exposure to substances harming alveolar epithelial cells are risk factors for the development of IPF. There is also evidence for a genetic susceptibility. IPF is defined as the idiopathic variant of Usual Interstitial Pneumonitis (UIP). Diagnosis of IPF is complex and based on the exclusion of other diseases associated with an UIP pattern. The only cure is lung transplantation. In the last years there was a breakthrough in the treatment of IPF. With pirfenidone and nintedanib there are now two compounds approved for the treatment of IPF. PMID:26444136

  6. [Idiopathic pulmonary trunk aneurysm].

    PubMed

    Uehara, Mayuko; Kuroda, Yosuke; Ohori, Syunsuke; Mawatari, Toru; Morishita, Kiyofumi

    2010-07-01

    Pulmonary trunk aneurysm is generally associated with congenital cardiac defects, pulmonary hypertension, or infection. Idiopathic pulmonary trunk aneurysm without any associated diseases is a rare lesion and has seldom been reported. Here, we report a case of a 68-year-old woman with idiopathic pulmonary trunk aneurysm. The maximum diameter of the aneurysm was 53 mm while she was 142 cm in height. We successfully performed aneurysmorrhaphy and her postoperative course was uneventful. Aneurysmorrhaphy was an effective technique for idiopathic pulmonary trunk aneurysm without pulmonary hypertention. PMID:20662238

  7. Surgery for childhood epilepsy

    PubMed Central

    Jayalakshmi, Sita; Panigrahi, Manas; Nanda, Subrat Kumar; Vadapalli, Rammohan

    2014-01-01

    Approximately 60% of all patients with epilepsy suffer from focal epilepsy syndromes. In about 15% of these patients, the seizures are not adequately controlled with antiepileptic drugs; such patients are potential candidates for surgical treatment and the major proportion is in the pediatric group (18 years old or less). Epilepsy surgery in children who have been carefully chosen can result in either seizure freedom or a marked (>90%) reduction in seizures in approximately two-thirds of children with intractable seizures. Advances in structural and functional neuroimaging, neurosurgery, and neuroanaesthesia have improved the outcomes of surgery for children with intractable epilepsy. Early surgery improves the quality of life and cognitive and developmental outcome and allows the child to lead a normal life. Surgically remediable epilepsies should be identified early and include temporal lobe epilepsy with hippocampal sclerosis, lesional temporal and extratemporal epilepsy, hemispherical epilepsy, and gelastic epilepsy with hypothalamic hamartoma. These syndromes have both acquired and congenital etiologies and can be treated by resective or disconnective surgery. Palliative procedures are performed in children with diffuse and multifocal epilepsies who are not candidates for resective surgery. The palliative procedures include corpus callosotomy and vagal nerve stimulation while deep brain stimulation in epilepsy is still under evaluation. For children with “surgically remediable epilepsy,” surgery should be offered as a procedure of choice rather than as a treatment of last resort. PMID:24791093

  8. Homozygous TBC1D24 mutation in two siblings with familial infantile myoclonic epilepsy (FIME) and moderate intellectual disability.

    PubMed

    Poulat, Anne-Lise; Ville, Dorothée; de Bellescize, Julitta; André-Obadia, Nathalie; Cacciagli, Pierre; Milh, Mathieu; Villard, Laurent; Lesca, Gaetan

    2015-03-01

    Mutations in the TBC1D24 gene were first reported in an Italian family with a unique epileptic phenotype consisting of drug-responsive, early-onset idiopathic myoclonic seizures. Patients presented with isolated bilateral or focal myoclonia, which could evolve to long-lasting attacks without loss of consciousness, with a peculiar reflex component, and were associated with generalized tonic-clonic seizures. This entity was named "familial infantile myoclonic epilepsy" (FIME). More recently, TBC1D24 mutations have been shown to cause a variable range of disorders, including epilepsy of various seizure types and severity, non-syndromic deafness, and DOORS syndrome. We report on the electro-clinical features of two brothers, born to first-cousin parents, affected with infantile-onset myoclonic epilepsy. The peculiar epileptic presentation prompted us to perform direct sequencing of the TBC1D24 gene. The patients had very early onset of focal myoclonic fits with variable topography, lasting a few minutes to several hours, without loss of consciousness, which frequently evolved to generalized myoclonus or myoclonic status. Reflex myoclonia were noticed in one patient. Neurological outcome was marked by moderate intellectual disability. Despite the high frequency of seizures, repeated EEG recordings showed normal background rhythm and rare interictal spikes and waves. We found a homozygous missense mutation, c.457G>A/p.Glu153Lys, in the two affected brothers. This observation combined with recent data from the literature, suggest that mutations in TBCD24 cause a pathological continuum, with FIME at the "benign" end and severe drug-refractory epileptic encephalopathy on the severe end. Early-onset myoclonic epilepsy with focal and generalized myoclonic seizures is a common characteristic of this continuum. PMID:25769375

  9. Idiopathic Pulmonary Fibrosis

    MedlinePlus

    ... the NHLBI on Twitter. What Is Idiopathic Pulmonary Fibrosis? Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a ... time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, your lungs can' ...

  10. Idiopathic cardiomegaly in Africa.

    PubMed

    Ikeme, A C

    1976-01-01

    Idiopathic cardiomegaly is probably the commonest single diagnosis other than hypertension made in tropical and subtropical African cardiovascular practice. Understanding of the nature of this disease has been hampered by failure to recognize the possibility that the term "idiopathic cardiomegaly" may embrace several disease entities. Evidence suggests that many factors, sometimes acting singly, but often acting in combination, may be responsible for the genesis of so-called idiopathic myocardial failure. The future attitude to research should not be one of excluding well-defined forms from the concept of idiopathic cardiomegaly, but one of clinicopathological classification, which should be a prelude to the search, within each moiety of this group of disorders, for a specific or dominant etiological factor. PMID:829042