Sleep-disordered breathing in epilepsy: epidemiology, mechanisms, and treatment.

PubMed

Sivathamboo, Shobi; Perucca, Piero; Velakoulis, Dennis; Jones, Nigel C; Goldin, Jeremy; Kwan, Patrick; O'Brien, Terence J

2018-04-01

Epilepsy is a group of neurological conditions in which there is a pathological and enduring predisposition to generate recurrent seizures. Evidence over the last few decades suggests that epilepsy may be associated with increased sleep-disordered breathing, which may contribute towards sleep fragmentation, daytime somnolence, reduced seizure control, and cardiovascular-related morbidity and mortality. Chronic sleep-disordered breathing can result in loss of gray matter and cause deficits to memory and global cognitive function. Sleep-disordered breathing is a novel and independent predictor of sudden cardiac death and, as such, may be involved in the mechanisms leading to sudden unexpected death in epilepsy. Despite this, the long-term consequences of sleep-disordered breathing in epilepsy remain unknown, and there are no guidelines for screening or treating this population. There is currently insufficient evidence to indicate continuous positive airway pressure (CPAP) for the primary or secondary prevention of cardiovascular disease, and recent evidence has failed to show any reduction of fatal or nonfatal cardiovascular endpoints. Treatment of sleep-disordered breathing may potentially improve seizure control, daytime somnolence, and neurocognitive outcomes, but few studies have examined this relationship. In this review, we examine sleep-disordered breathing in epilepsy, and discuss the potential effect of epilepsy treatments. We consider the role of CPAP and other interventions for sleep-disordered breathing and discuss their implications for epilepsy management.

Attention Deficit Hyperactivity Disorder (ADHD) in Childhood Epilepsy

ERIC Educational Resources Information Center

Reilly, Colin J.

2011-01-01

ADHD and epilepsy common are both common childhood disorders and both can have significant negative consequences on a child's behavioural, learning, and social development. Both conditions can co-occur and population studies suggest that the prevalence of ADHD in childhood epilepsy is between 12 and 17%. The prevalence of epilepsy in ADHD is lower…

Consciousness as a useful concept in epilepsy classification.

PubMed

Blumenfeld, Hal; Meador, Kimford J

2014-08-01

Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms "dyscognitive" or "dialeptic" should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic-clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Treatment of epilepsy in patients with myasthenia gravis: Is really harder than it looks?

PubMed

Lorenzoni, Paulo José; Ducci, Renata Dal-Prá; Tensini, Tallulah Spina; Dalledone, Giuliano; Kay, Claudia Suemi Kamoi; de Paola, Luciano; Werneck, Lineu Cesar; Scola, Rosana Herminia; Silvado, Carlos

2017-10-01

The relationship between myasthenia gravis (MG) and epilepsy has been rarely reported. As consequence, there are no specific guidelines for the management of these conditions when they mutually occur. We reported on three patients in whom epilepsy and MG are coexisting, but in different clinical settings. Two patients were treated with antiepileptic drugs which improved their symptoms. One patient has controlled the seizures after a successful anterior temporal lobectomy with no appreciable consequences to her MG. We discuss the difficulties in the management of epilepsy in patients with MG. In addition, we report on the first epileptic surgery in a MG patient, indicating that this surgical procedure as a safe option for the treatment of intractable epilepsy in patients with MG. Copyright © 2017. Published by Elsevier Ltd.

Working Together to Improve the Lives of People Affected by Epilepsy in Zambia

ERIC Educational Resources Information Center

Birbeck, Gretchen L.

2012-01-01

Epilepsy is a neurologic disorder that results in recurrent, unprovoked seizures. The biomedical burden of epilepsy can be substantial, but for many the social consequences may be just as extreme, with epilepsy victims suffering from social abandonment as well as economic and physical vulnerabilities. Since its founding in 2000, the Chikankata…

Behavioral alterations in the pilocarpine model of temporal lobe epilepsy in mice.

PubMed

Gröticke, Ina; Hoffmann, Katrin; Löscher, Wolfgang

2007-10-01

Psychiatric disorders frequently occur in patients with epilepsy, but the relationship between epilepsy and psychopathology is poorly understood. Frequent comorbidities in epilepsy patients comprise major depression, anxiety disorders, psychosis and cognitive dysfunction. Animal models of epilepsy, such as the pilocarpine model of acquired epilepsy, are useful to study the relationship between epilepsy and behavioral dysfunctions. However, despite the advantages of mice in studying the genetic underpinning of behavioral alterations in epilepsy, mice have only rarely been used to characterize behavioral correlates of epilepsy. This prompted us to study the behavioral and cognitive alterations developing in NMRI mice in the pilocarpine model of epilepsy, using an anxiety test battery as well as tests for depression, drug-induced psychosis, spatial memory, and motor functions. In order to ensure the occurrence of status epilepticus (SE) and decrease mortality, individual dosing of pilocarpine was performed by ramping up the dose until onset of SE. This protocol was used for studying the consequences of SE, i.e. hippocampal damage, incidence of epilepsy with spontaneous recurrent seizures, and behavioral alterations. SE was terminated by diazepam after either 60, 90 or 120 min. All mice that survived SE developed epilepsy, but the severity of hippocampal damage varied depending on SE length. In all anxiety tests, except the elevated plus maze test, epileptic mice exhibited significant increases of anxiety-related behavior. Surprisingly, a decrease in depression-like behavior was observed in the forced swimming and tail suspension tests. Furthermore, epileptic mice were less sensitive than controls to most of the behavioral effects induced by MK-801 (dizocilpine). Learning and memory were impaired in epileptic mice irrespective of SE duration. Thus, the pilocarpine-treated mice seem to reflect several of the behavioral and cognitive disturbances that are associated with epilepsy in humans. This makes these animals an ideal model to study the neurobiological mechanisms underlying the association between epilepsy and psychopathology.

Learning disorders in children with epilepsy.

PubMed

Pavlou, Evangelos; Gkampeta, Anastasia

2011-03-01

Learning Disorders (LD) are defined as disorders that interfere with academic performance or with daily activities that require reading, writing or mathematical skills in subjects with a normal intelligence quotient (IQ). The prevalence of LD in the general population has been found to be 2-10%, and reading disorders are the most frequent subtype. Epilepsy is one of the most common serious neurological disorders in childhood. LD are more common in children with epilepsy than in the general population. As a consequence, the risk of cognitive impairment in children with epilepsy is high, and a review of the literature needs to be fully presented. Narrative review including articles regarding LD in children with various epileptic syndromes published in the international medical literature. LD are more frequent among children with epilepsy. The etiology is multifactorial, being affected by the type of epileptic syndrome, the age of onset and the antiepileptic treatment being selected. LD can be either permanent or state-dependent. Each category has different treatment protocols and prognosis. Despite the fact that the findings of the studies discussed in our article support the evidence that epilepsy in childhood impairs the cognitive function, we should not underestimate the role of demographic and psychosocial factors on academic performance of children with epilepsy. Despite the high prevalence of LD, a healthy family and school environment can help reduce its impact on the patient's quality of life. © Springer-Verlag 2010

[Epilepsy-new diagnostic tools, old drugs? : Therapeutic consequences of epilepsy genetics].

PubMed

Tacke, M; Neubauer, B A; Gerstl, L; Roser, T; Rémi, J; Borggraefe, I

2017-12-01

Recent advances in the field of epilepsy genetics have led to an increased fraction of patients with epilepsies where the etiology of the disease could be identified. Nevertheless, there is some criticism regarding the use of epilepsy genetics because in many cases the identification of a pathogenetic mutation does not lead to an adaptation of therapy or to an improved prognosis. In addition, the interpretation of genetic results might be complicated due to the considerable numbers of variants of unclear significance. This publication presents the arguments in favour of a broad use of genetic investigations for children with epilepsies. Several diseases where a genetic diagnosis does in fact have direct therapeutic consequences are mentioned. In addition, the indirect impact of an established etiology, encompassing the avoidance of unnecessary diagnostic measures, possibility of genetic counselling, and the easing of the psychologic burden for the caregivers, should not be underestimated. The arguments in favour of broad genetic diagnostics prevail notwithstanding the lack of relevant new developments regarding the therapy.

DNM1 encephalopathy

PubMed Central

von Spiczak, Sarah; Helbig, Katherine L.; Shinde, Deepali N.; Huether, Robert; Pendziwiat, Manuela; Lourenço, Charles; Nunes, Mark E.; Sarco, Dean P.; Kaplan, Richard A.; Dlugos, Dennis J.; Kirsch, Heidi; Slavotinek, Anne; Cilio, Maria R.; Cervenka, Mackenzie C.; Cohen, Julie S.; McClellan, Rebecca; Fatemi, Ali; Yuen, Amy; Sagawa, Yoshimi; Littlejohn, Rebecca; McLean, Scott D.; Hernandez-Hernandez, Laura; Maher, Bridget; Møller, Rikke S.; Palmer, Elizabeth; Lawson, John A.; Campbell, Colleen A.; Joshi, Charuta N.; Kolbe, Diana L.; Hollingsworth, Georgie; Neubauer, Bernd A.; Muhle, Hiltrud; Stephani, Ulrich; Scheffer, Ingrid E.; Pena, Sérgio D.J.; Sisodiya, Sanjay M.

2017-01-01

Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. Methods: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. Results: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. Conclusions: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention. PMID:28667181

Epilepsy and violence: case series concerning physical trauma in children of persons with epilepsy

PubMed Central

Gauffin, Helena; Landtblom, Anne-Marie

2014-01-01

Historically, epilepsy has been associated with violence, but more recent studies have emphasized genetic and psychosocial factors as more important. The case series presented here aim to highlight the difficult situation the affected children are in. We report on three cases when children have been traumatized and, in one case, even been killed by their parent who was diagnosed with epilepsy. In the first case, we describe a woman with juvenile myoclonic epilepsy who was sentenced to forensic psychiatry care for killing her child. She lived under difficult psychosocial circumstances and a suicide attempt contributed to what happened. The second case describes a man with post-traumatic seizures who was sentenced for child abuse. Ictal or postictal violence was considered in these two cases but a causal link between the violence and epilepsy has not been established. In the third case, we describe a woman with focal epilepsy and psychogenic non-epileptic seizures (PNESs). Her child was hurt and frightened in relation to violent seizures, which were regarded as PNESs. This case series demonstrates that children of parents with epilepsy can be in a vulnerable situation. No causality has been established between the seizures and these events, so consequently other factors such as psychosocial stress, low cognitive function, and a suicide attempt must also be considered as important. When a child is hurt by a parent with epilepsy the patient must be closely examined to determine the role of the seizures. Children can also be affected by PNESs. It is essential to notice especially those children of parents with epilepsy who live under difficult psychosocial circumstances and offer extra support when necessary. PMID:25484586

Simulating memory outcome before right selective amygdalohippocampectomy.

PubMed

Patrikelis, Panayiotis; Lucci, Giuliana; Siatouni, Anna; Zalonis, Ioannis; Sakas, Damianos E; Gatzonis, Stylianos

2013-01-01

In this paper we present the case of a left-sided speech dominant patient with right medial temporal sclerosis (RMTS) and pharmacoresistant epilepsy who showed improved verbal memory during intracarotid amobarbital test (IAT) at his right hemisphere as compared with his own performance before the drug injection (baseline), as well as after right selective amygdalohippocampectomy. We suggest that the defective verbal memory shown by this patient is due to abnormal activity of his right hippocampus that interfered with the function of his left hippocampus. This hypothesis was demonstrated by the fact that disconnection of the two hippocampi, either by anesthetisation or by resection of the right hippocampus, disengaged the left hippocampus and, consequently improved its function. This paper main objective is twofold: first to contribute to the field of neuropsychology of epilepsy surgery by emphasising on postoperative memory outcomes in right medial temporal lobe epilepsy (RMTLE) patients, particularly those undergoing amygdalohippocampectomy, as the pattern of memory changes after resection of the right temporal lobe is less clear; second, by focusing on memory performance asymmetries during IAT, and comparatively considering them with neuropsychological memory performance, because of their possible prognostic-simulating value.

The Structural Plasticity of White Matter Networks Following Anterior Temporal Lobe Resection

ERIC Educational Resources Information Center

Yogarajah, Mahinda; Focke, Niels K.; Bonelli, Silvia B.; Thompson, Pamela; Vollmar, Christian; McEvoy, Andrew W.; Alexander, Daniel C.; Symms, Mark R.; Koepp, Matthias J.; Duncan, John S.

2010-01-01

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy…

Consciousness as a useful concept in epilepsy classification

PubMed Central

Blumenfeld, Hal; Meador, Kimford J.

2014-01-01

Summary Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms “dyscognitive” or “dialeptic” should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic–clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions. PMID:24981294

The Metabotropic Purinergic P2Y Receptor Family as Novel Drug Target in Epilepsy.

PubMed

Alves, Mariana; Beamer, Edward; Engel, Tobias

2018-01-01

Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype. Consequently, targeting signaling molecules involved in inflammatory processes may represent new avenues to improve treatment in epilepsy. Nucleotides such as adenosine-5'-triphosphate (ATP) and uridine-5'-triphosphate (UTP) are released in the brain into the extracellular space during pathological conditions such as increased neuronal firing or cell death. Once released, these nucleotides bind to and activate specific purinergic receptors termed P2 receptors where they mediate the release of gliotransmitters and drive neuronal hyperexcitation and neuroinflammatory processes. This includes the fast acting ionotropic P2X channels and slower-acting G-protein-coupled P2Y receptors. While the expression and function of P2X receptors has been well-established in experimental models of epilepsy, emerging evidence is now also suggesting a prominent role for the P2Y receptor subfamily in seizure generation and the maintenance of epilepsy. In this review we discuss data supporting a role for the P2Y receptor family in epilepsy and the most recent finding demonstrating their involvement during seizure-induced pathology and in epilepsy.

[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

The history of eponyms for epilepsy in the lands of the Eastern globe present the portrait of the attitudes of both the laymen and skilled people towards the disease and patient, as well as to the Nature itself. As opposed to the West which during the Middle ages changed its concepts of epilepsy as the organic brain disease for the sublime 'alchemic' position, the people of the East were more prone to consider from the beginning of their civilization till the XIX century that epilepsy is the consequence of the evanescent spiritual and extracorporal forces which by themselves were out of their reach. As compared to the western civilization, the historical resources are, often as a consequence of a linguistic barriers, more scarce-as consequently is the number of eponyms, but are nevertheless picturesque. The medical science from Babylonian period presumed that epileptic manifestations are the consequence of the demonic or ill spiritual actions. There existed an attitude that at the beginning of an epileptic attack the patient was possessed by a demon (the Akkadic, i.e., Babylonian verb "sibtu" denoting epilepsy, had the meaning "to seize" or "to be obsessed"); at the end of the clonic phase the demon departed from the body. Different demons were responsible for different forms of epilepsy such as nocturnal and children epilepsy, absence epilepsy and pure convulsions, simple and complex automatisms, and gelastic epilepsy. Thus, the doctors from the period of Babylon aside from making primordial classification of epilepsies, knew about their clinical picture (prodromal symptoms and aura, Jackson's epilepsy. Todd's paralysis), postictal phenomena and intericatl emotional instability; provocative factors were also known (sleep deprivation, emotions, as well as alcohol, albeit in a negative sense-as a cure for epilepsy). There is no doubt than in the period of Babylon the clinical picture of serial fits and its progress to status epilepticus were clearly recognized and 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)

The Need for Antiepileptic Drug Chronotherapy to Treat Selected Childhood Epilepsy Syndromes and Avert the Harmful Consequences of Drug Resistance

PubMed Central

Manganaro, Sheryl; Loddenkemper, Tobias; Rotenberg, Alexander

2017-01-01

Antiepileptic drug (AED) chronotherapy involves the delivery of a greater AED dose at the time of greatest seizure susceptibility usually associated with predictable seizure peaks. Although research has proven AED chronotherapy, commonly known as differential dosing, to be safe, well tolerated, and highly effective in managing cyclic seizure patterns in selected childhood epilepsies, conventional, equally divided AED dosing remains the standard of care. Differential dosing is more often applied in the emergency management of acute seizure clustering resulting from drug resistance—a harmful epilepsy-related consequence that affects 30% of children. Moreover, drug resistance is a major risk factor in status epilepticus and sudden, unexpected death in epilepsy. Although these facts should promote the wider use of differential dosing in selected cases, a credible hypothesis is needed that defines the differential dosing strategy and application in cyclic epilepsy and for the greater purpose of preventing harmful outcomes. PMID:29308021

Attention and executive functions in the early course of pediatric epilepsy.

PubMed

Reuner, Gitta; Kadish, Navah Esther; Doering, Jan Henje; Balke, Doreen; Schubert-Bast, Susanne

2016-07-01

Our prospective study aimed at exploring attention and executive functions in children with new-onset epilepsy prior to and during the early course of antiepileptic treatment. Sociodemographic and epilepsy-related factors were analyzed as potential predictors both of impaired cognitive functions as well as for changes in cognitive functioning in the early course of illness. From a total group of 115 children aged six to 17years without major disabilities, 76 children were assessed longitudinally with a screening tool for attention and executive functions (EpiTrack Junior®). Sociodemographic variables (gender, age at epilepsy onset, need of special education) and epilepsy-related variables (etiology of epilepsy, semiology of seizures, number of seizures) were considered as potential predictors for impaired functions prior to treatment and for deterioration/amelioration in cognitive functions in the early course. Attention and executive functions of children with new-onset epilepsy were significantly more often impaired when compared with a healthy population, but less often when compared with children with chronic epilepsy. The majority of children showed stable cognitive functioning in the early course of treatment. The risk of impaired cognitive functions was significantly heightened when etiology of epilepsy was unknown or not classifiable. The chance for improvement of functioning was lowered by having a genetic epilepsy, or an unknown semiology of seizures. Children with new-onset epilepsy are at high risk for impaired attention and executive functions even prior to antiepileptic treatment, especially when etiology of their epilepsy remains unclear. The high stability of cognitive functioning in the early course can be used in counseling of families who worry about negative side effects of drug treatment. Finally, a systematic assessment of cognitive functions in children with new-onset epilepsy is necessary to detect subtle deficits in the early course and adjust treatment accordingly. Copyright © 2016 Elsevier Inc. All rights reserved.

Thalamocortical Connections and Executive Function in Pediatric Temporal and Frontal Lobe Epilepsy.

PubMed

Law, N; Smith, M L; Widjaja, E

2018-06-07

Largely accepted in the literature is the role the interconnections between the thalamus and cortex play in generalized epilepsy. However, thalamocortical involvement is less understood in focal epilepsy in terms of the effect of seizures on thalamocortical circuitry in the developing brain and subsequent cognitive outcome. We investigated thalamocortical pathway microstructure in pediatric frontal lobe epilepsy and temporal lobe epilepsy and examined the associations between pathway microstructure and measures of executive function. We examined thalamocortical connections in 24 children with frontal lobe epilepsy, 17 patients with temporal lobe epilepsy, and 25 healthy children using DTI. We investigated several executive function measures in patients and controls, which were distilled into latent executive function components to compare among groups, and the associations between measures of thalamocortical microstructure and executive function. We found no differences in thalamocortical pathway microstructure between the groups, but aspects of executive function (mental flexibility/inhibition/shifting) were impaired in the frontal lobe epilepsy group compared with controls. In patients with frontal lobe epilepsy, younger age at seizure onset and a greater number of antiepileptic drugs were associated with DTI indices indicative of damaged/less developed thalamocortical pathways. In patients with temporal lobe epilepsy, poorer performance on all measures of executive function was associated with DTI indices reflective of damaged/less developed pathways. Our results give insight into vulnerable neural networks in pediatric focal epilepsy and suggest thalamocortical pathway damage as a potential mechanism of executive function impairment in temporal lobe epilepsy but not frontal lobe epilepsy. Identifying structure-function relations can help inform how we measure functional and cognitive/behavioral outcomes in these populations. © 2018 by American Journal of Neuroradiology.

[The mind and epilepsy: opinions and viewpoints over the course of time].

PubMed

Vaney, C

1989-07-18

Among the very few diseases that can be traced back to ancient times none has stimulated human phantasy as much as epilepsy, and the many names given to epilepsy reflects the different trends of thinking on the topic over the past two and a half thousand years. The ancient Greek believed epilepsy to be a sacred disease with the body being invaded by a God. The view that demons and evil spirits rather than Gods were responsible for the disease prevailed throughout the middle ages, influenced by Christian thinking. This led people with epilepsy to be treated, as the mentally ill, with contempt and pity. Up to the latter half of the 19th century epilepsy remained an integral part of psychiatry. The concept of the epileptic personality, stating that the behaviour and consequently the seizures themselves came from a constitutional hereditary psychopathic make-up, was deeply entrenched. The process of distinguishing epilepsy from insanity began with the development of neurology as a new and independent discipline, helped by the discovery of electroencephalography EEG and potent antiepileptic drugs. It became more widely accepted that most epileptic patients have normal mental states. It was argued that the psychiatric consequences of having epilepsy depended on the existence of pathological brain lesions, side-effects of inadequate drugs and the psychological stress of living with a chronic and debilitating disease.

Functional difficulties and school limitations of children with epilepsy: findings from the 2009-2010 National Survey of Children with Special Health Care Needs.

PubMed

Pastor, Patricia N; Reuben, Cynthia A; Kobau, Rosemarie; Helmers, Sandra L; Lukacs, Susan

2015-04-01

Epilepsy is a common serious neurologic disorder in children. However, most studies of children's functional difficulties and school limitations have used samples from tertiary care or other clinical settings. To compare functional difficulties and school limitations of a national sample of US children with special health care needs (CSHCN) with and without epilepsy. Data from the 2009-2010 National Survey of CSHCN for 31,897 children aged 6-17 years with and without epilepsy were analyzed for CSHCN in two groups: 1) CSHCN with selected comorbid conditions (intellectual disability, cerebral palsy, autism, or traumatic brain injury) and 2) CSHCN without these conditions. Functional difficulties and school limitations, adjusted for the effect of sociodemographic characteristics, were examined by epilepsy and comorbid conditions. Three percent of CSHCN had epilepsy. Among CSHCN with epilepsy 53% had comorbid conditions. Overall CSHCN with epilepsy, both with and without comorbid conditions, had more functional difficulties than CSHCN without epilepsy. For example, after adjustment for sociodemographic characteristics a higher percentage of children with epilepsy, compared to children without epilepsy, had difficulty with communication (with conditions: 53% vs. 37%, without conditions: 13% vs. 5%). Results for school limitations were similar. After adjustment, a higher percentage of children with epilepsy, compared to children without epilepsy, missed 11 + school days in the past year (with conditions: 36% vs. 18%, without conditions: 21% vs. 15%). CSHCN with epilepsy, compared to CSHCN without epilepsy, were more likely to have functional difficulties and limitations in school attendance regardless of comorbid conditions. Published by Elsevier Inc.

Psychotic illness in patients with epilepsy

PubMed Central

Tadokoro, Yukari; Oshima, Tomohiro

2012-01-01

Apart from the rather rare ictal psychotic events, such as non-convulsive status epilepticus, modern epileptic psychoses have been categorized into three main types; chronic and acute interictal psychoses (IIPs) and postictal psychosis (PIP). Together, they comprise 95% of psychoses in patients with epilepsy (PWE). Four major questions, that is, “Is psychosis in PWE a direct consequence of epilepsy or schizophrenia induced by epilepsy?”, “Is psychosis in PWE homogeneous or heterogeneous?”, “Does psychosis in PWE have symptomatological differences from schizophrenia and related disorders?”, “Is psychosis in PWE uniquely associated with temporal lobe epilepsy (TLE)?” are tried to be answered in this review with relevant case presentations. In the final section, we propose a tentative classification of psychotic illness in PWE, with special attention to those who have undergone epilepsy surgery. Psychotic disorders in PWE are often overlooked, mistreated, and consequently lingering on needlessly. While early diagnosis is unanimously supported as a first step to avoid this delay, necessity of switching from antiepileptic drugs with supposedly adverse psychotopic effects. to others is more controversial. To elucidate the riddle of alternative psychosis, we need badly further reliable data. PMID:23139703

An estimate of the prevalence of epilepsy in Sub-Saharan Africa: A systematic analysis.

PubMed

Paul, Abigail; Adeloye, Davies; George-Carey, Rhiannon; Kolčić, Ivana; Grant, Liz; Chan, Kit Yee

2012-12-01

Epilepsy is a leading serious neurological condition worldwide and has particularly significant physical, economic and social consequences in Sub-Saharan Africa. This paper aims to contribute to the understanding of epilepsy prevalence in this region and how this varies by age and sex so as to inform understanding of the disease characteristics as well as the development of infrastructure, services and policies. A parallel systematic analysis of Medline, Embase and Global Health returned 32 studies that satisfied pre-defined quality criteria. Relevant data was extracted, tabulated and analyzed. We modelled the available information and used the UN population figures for Africa to determine the age-specific and overall burden of epilepsy. Active epilepsy was estimated to affect 4.4 million people in Sub-Saharan Africa, whilst lifetime epilepsy was estimated to affect 5.4 million. The prevalence of active epilepsy peaks in the 20-29 age group at 11.5/1000 and again in the 40-49 age group at 8.2/1000. The lowest prevalence value of 3.1/1000 is seen in the 60+ age group. This binomial pattern is also seen in both men and women, with the second peak more pronounced in women at 14.6/1000. The high prevalence of epilepsy, especially in young adults, has important consequences for both the workforce and community structures. An estimation of disease burden would be a beneficial outcome of further research, as would research into appropriate methods of improving health care for and tackling discrimination against people with epilepsy.

Melatonin and childhood refractory epilepsy--a pilot study.

PubMed

Paprocka, Justyna; Dec, Renata; Jamroz, Ewa; Marszał, Elzbieta

2010-09-01

The aim of the study was to assess diurnal melatonin secretion in children with refractory epilepsy (N=74) as compared to children without epileptic seizures (N=37) and to compare melatonin secretion in children with focal and generalized refractory epilepsy. In the study group 4 subgroups were defined: children with focal symptomatic epilepsy, focal cryptogenic epilepsy, generalized symptomatic epilepsy, and generalized cryptogenic epilepsy. Melatonin level was measured every 3 hours using the RIA method. Analysis of diurnal melatonin secretion indicated a lower level of the hormone in patients with refractory epilepsy. The daily rhythm of melatonin secretion in the study group was maintained, with a peak shift of melatonin secretion especially visible in the subgroup with generalized symptomatic refractory epilepsy in the age group between 6 months and 3 years of age. The hypothesis may be formed that a lowered level of melatonin in the study group in relation to the comparison group is the consequence of the natural course of epilepsy or is influenced by antiepileptic drugs.

Long-term socioeconomic consequences and health care costs of childhood and adolescent-onset epilepsy.

PubMed

Jennum, Poul; Christensen, Jakob; Ibsen, Rikke; Kjellberg, Jakob

2016-07-01

To estimate long-term socioeconomic consequences and health care costs of epilepsy with onset in childhood and adolescence. A historical prospective cohort study of Danish individuals with epilepsy, age up to 20 years at time of diagnosis between January 1981 and December 2012. Information about marital status, parenthood, educational level, employment status, income, use of the health care system, and cost of medicine was obtained from nationwide administrative and health registers. We identified 12,756 and 28,319 people with diagnosed with epilepsy, ages 0-5 and 6-20 years at onset, respectively. Using follow-up data for a maximum of 30 years, 1,394 of those ages 0-5 years at onset were compared with 2,897 controls persons without epilepsy, and 10,195 of those ages 6-20 years at onset were compared with 20,678 controls without epilepsy. Compared with people without the epilepsy, those with epilepsy tended to have a lower level of education, to be less likely to be married, to be more likely to live alone, and to have higher divorce and unemployment rates, lower employment rates, and people with epilepsy were more likely to receive disability pension and social security. Income was lower from employment, which in part was compensated by social security, sick pay, disability pension and unemployment benefit, sick pay (public-funded), disability pension, and other public transfers. Predicted health care costs 30 years after epilepsy onset were significantly higher among persons with epilepsy onset at 0-5 and 6-20 years, including costs for outpatient and inpatient services (hospital services), emergency room use, primary health care sector (general practice), and use of medication. The long-term negative effects on all aspects of health care and social domains, including marital status, parental socioeconomic status, educational level, employment status, and use of welfare benefits compared with controls without epilepsy calls for increased awareness on childhood- and adolescent-onset epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

famoses: a modular educational program for children with epilepsy and their parents.

PubMed

Wohlrab, Gabriele Christine; Rinnert, Susanne; Bettendorf, Ulrich; Fischbach, Heilwig; Heinen, Gerd; Klein, Petra; Kluger, Gerhard; Jacob, Karin; Rahn, Dagmar; Winter, Rita; Pfäfflin, Margarete

2007-02-01

It is known that most adult patients with epilepsy often have poor knowledge of their disorder, treatment options, and social and vocational consequences, despite the huge amount of information available. Being pressed for time, health care professionals often are not able to provide the repetitive counseling and instruction necessary to address epilepsy care adequately. Therefore educational programs are considered extremely important in filling the gap. For German-speaking countries, two educational programs called famoses, modulares Schulungsprogramm Epilepsie fur Familien [modular service package epilepsy for families], were developed by a multidisciplinary group of neuropediatricians, psychologists, social workers, and educators. The aims of the famoses programs are to improve children's and parents' knowledge about epilepsy and to help patients of childhood age and their parents achieve a better understanding of their disease, gain more self-confidence, and reduce specific fears regarding epilepsy. famoses comprises two different educational programs: famoses for kids with epilepsy within the developmental period of ages 7 to 13, and famoses for parents or caretakers. The programs are designed for interactive small-group education. The child-centered educational program is based on a fictional story: The children are sailors on a virtual cruise, sailing from island to island, accompanied by educated trainers. On each island there is something new to discover about epilepsy. The parent (and caretaker)-centered educational program covers different topics-overview and content of the program, basic knowledge, diagnostics, therapy, prognosis and development, and living with epilepsy-within six modules. The program was implemented in Germany and Switzerland in the spring of 2005 and is now operating in different epilepsy centers. Within comprehensive therapeutic management of epilepsy, educational programs for patients, and for parents (caretakers) of children with epilepsy, are considered to be extremely important. Such educational programs have two main goals: to increase knowledge about the disorder, and to strengthen the patients' responsibility for themselves, with the consequence of living with as few limitations as possible. famoses is an effective component of this comprehensive care. The program has been operating successfully in different epilepsy centers in Germany and Switzerland since the spring of 2005.

Common and Distinctive Patterns of Cognitive Dysfunction in Children With Benign Epilepsy Syndromes.

PubMed

Cheng, Dazhi; Yan, Xiuxian; Gao, Zhijie; Xu, Keming; Zhou, Xinlin; Chen, Qian

2017-07-01

Childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes are the most common forms of benign epilepsy syndromes. Although cognitive dysfunctions occur in children with both childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes, the similarity between their patterns of underlying cognitive impairments is not well understood. To describe these patterns, we examined multiple cognitive functions in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. In this study, 43 children with childhood absence epilepsy, 47 children with benign childhood epilepsy with centrotemporal spikes, and 64 control subjects were recruited; all received a standardized assessment (i.e., computerized test battery) assessing processing speed, spatial skills, calculation, language ability, intelligence, visual attention, and executive function. Groups were compared in these cognitive domains. Simple regression analysis was used to analyze the effects of epilepsy-related clinical variables on cognitive test scores. Compared with control subjects, children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes showed cognitive deficits in intelligence and executive function, but performed normally in language processing. Impairment in visual attention was specific to patients with childhood absence epilepsy, whereas impaired spatial ability was specific to the children with benign childhood epilepsy with centrotemporal spikes. Simple regression analysis showed syndrome-related clinical variables did not affect cognitive functions. This study provides evidence of both common and distinctive cognitive features underlying the relative cognitive difficulties in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. Our data suggest that clinicians should pay particular attention to the specific cognitive deficits in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes, to allow for more discriminative and potentially more effective interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Epilepsy-related clinical factors and psychosocial functions in pediatric epilepsy.

PubMed

Eom, Soyong; Eun, So-Hee; Kang, Hoon-Chul; Eun, Baik-Lin; Nam, Sang Ook; Kim, Sun Jun; Chung, Hee Jung; Kwon, Soon Hak; Lee, Young-Mock; Lee, Joon Soo; Kim, Dong Wook; Oh, Kyung Ja; Kim, Heung Dong

2014-08-01

The aim of this study was to identify the different influencing patterns of demographic and epilepsy-related variables on various aspects of psychosocial function in pediatric epilepsy. Five hundred ninety-eight patients with pediatric epilepsy between the ages of 4 and 18 years (boys=360, 60% and girls=238, 40%) and their parents participated in the study. Parents completed the Social Maturity Scale (SMS), the Korean version of the Child Behavior Checklist (K-CBCL), and the Korean version of the Quality of Life in Childhood Epilepsy Questionnaire (K-QOLCE) to assess daily living function, behavior, and quality of life. The Children's Global Assessment Scale (CGAS) was completed by clinicians to assess general adaptive function. Demographic variables, such as age and sex of child, and epilepsy-related clinical variables, including seizure type, seizure frequency, duration of epilepsy, and number of medications, were obtained from medical records. Demographic and epilepsy-related clinical variables had a strong influence (22-32%) on the cognition-related domain such as general adaptive function, school/total competence, and quality of life for cognitive function while a comparatively smaller effect (2-16%) on the more psychological domain including behavioral, emotional, and social variables. Younger age, shorter duration of illness, and smaller number of medications showed a strong positive impact on psychosocial function in pediatric epilepsy, particularly for adaptive function, competence, and quality-of-life aspects. Given the wide range of impact of demographic and clinical variables on various facets of psychosocial functions, more specific understanding of the various aspects of factors and their particular pattern of influence may enable more effective therapeutic approaches that address both the medical and psychological needs in pediatric epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Thalamic stimulation to improve level of consciousness after seizures: evaluation of electrophysiology and behavior.

PubMed

Gummadavelli, Abhijeet; Motelow, Joshua E; Smith, Nicholas; Zhan, Qiong; Schiff, Nicholas D; Blumenfeld, Hal

2015-01-01

Understanding the neural mechanisms that support human consciousness is an important frontier in neuroscience and medicine. We previously developed a rodent model of temporal lobe seizures that recapitulates the human electroencephalography (EEG) signature of ictal and postictal neocortical slow waves associated with behavioral impairments in level of consciousness. The mechanism of slow-wave production in epilepsy may involve suppression of the subcortical arousal systems including the brainstem and intralaminar thalamic nuclei. We hypothesized that intralaminar thalamic stimulation may lead to electrophysiologic and functional rescue from postictal slow waves and behavioral arrest. We electrically stimulated the central lateral thalamic nucleus (a member of the intralaminar nuclei) under anesthesia and after electrically induced hippocampal seizures in anesthetized and in awake-behaving animal model preparations. We demonstrated a proof-of-principle restoration of electrophysiologic and behavioral measures of consciousness by stimulating the intralaminar thalamic nuclei after seizures. We measured decreased cortical slow waves and increased desynchronization and multiunit activity in the cortex with thalamic stimulation following seizures. Functionally, thalamic stimulation produced resumption of exploratory behaviors in the postictal state. Targeting of nodes in the neural circuitry of consciousness has important medical implications. Impaired consciousness with epilepsy has dangerous consequences including decreased school/work performance, social stigmatization, and impaired airway protection. These data suggest a novel therapeutic approach for restoring consciousness after seizures. If paired with responsive neurostimulation, this may allow rapid implementation to improve level of consciousness in patients with epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

[The psychosocial challenges of epilepsy and the role of the clinical nurse specialist].

PubMed

Chartrand, Dominic

2015-01-01

Epilepsy in children is a complex disease with significant psychosocial consequences for the child and their family. The intervention of a multidisciplinary team enables the care to be adapted and provides support for the families. At Sainte-Justine Hospital in Montreal, Canada, the nurse clinician specialised in epilepsy plays a key role in this team. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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.

Increased Functional MEG Connectivity as a Hallmark of MRI-Negative Focal and Generalized Epilepsy.

PubMed

Li Hegner, Yiwen; Marquetand, Justus; Elshahabi, Adham; Klamer, Silke; Lerche, Holger; Braun, Christoph; Focke, Niels K

2018-05-15

Epilepsy is one of the most prevalent neurological diseases with a high morbidity. Accumulating evidence has shown that epilepsy is an archetypical neural network disorder. Here we developed a non-invasive cortical functional connectivity analysis based on magnetoencephalography (MEG) to assess commonalities and differences in the network phenotype in different epilepsy syndromes (non-lesional/cryptogenic focal and idiopathic/genetic generalized epilepsy). Thirty-seven epilepsy patients with normal structural brain anatomy underwent a 30-min resting state MEG measurement with eyes closed. We only analyzed interictal epochs without epileptiform discharges. The imaginary part of coherency was calculated as an indicator of cortical functional connectivity in five classical frequency bands. This connectivity measure was computed between all sources on individually reconstructed cortical surfaces that were surface-aligned to a common template. In comparison to healthy controls, both focal and generalized epilepsy patients showed widespread increased functional connectivity in several frequency bands, demonstrating the potential of elevated functional connectivity as a common pathophysiological hallmark in different epilepsy types. Furthermore, the comparison between focal and generalized epilepsies revealed increased network connectivity in bilateral mesio-frontal and motor regions specifically for the generalized epilepsy patients. Our study indicated that the surface-based normalization of MEG sources of individual brains enables the comparison of imaging findings across subjects and groups on a united platform, which leads to a straightforward and effective disclosure of pathological network characteristics in epilepsy. This approach may allow for the definition of more specific markers of different epilepsy syndromes, and increased MEG-based resting-state functional connectivity seems to be a common feature in MRI-negative epilepsy syndromes.

Epilepsy treatment and creativity.

PubMed

Zubkov, Sarah; Friedman, Daniel

2016-04-01

Creativity can be defined as the ability to understand, develop, and express, in a systematic fashion, novel orderly relationships. It is sometimes difficult to separate cognitive skills requisite for the creative process from the drive that generates unique new ideas and associations. Epilepsy itself may affect the creative process. The treatment of epilepsy and its comorbidities, by altering or disrupting the same neural networks through antiseizure drugs (ASDs), treatment of epilepsy comorbidities, ablative surgery, or neurostimulation may also affect creativity. In this review, we discuss the potential mechanisms by which treatment can influence the creative process and review the literature on the consequences of therapy on different aspects of creativity in people with epilepsy. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". Copyright © 2016 Elsevier Inc. All rights reserved.

Postoperative seizure freedom does not normalize altered connectivity in temporal lobe epilepsy.

PubMed

Maccotta, Luigi; Lopez, Mayra A; Adeyemo, Babatunde; Ances, Beau M; Day, Brian K; Eisenman, Lawrence N; Dowling, Joshua L; Leuthardt, Eric C; Schlaggar, Bradley L; Hogan, Robert Edward

2017-11-01

Specific changes in the functional connectivity of brain networks occur in patients with epilepsy. Yet whether such changes reflect a stable disease effect or one that is a function of active seizure burden remains unclear. Here, we longitudinally assessed the connectivity of canonical cognitive functional networks in patients with intractable temporal lobe epilepsy (TLE), both before and after patients underwent epilepsy surgery and achieved seizure freedom. Seventeen patients with intractable TLE who underwent epilepsy surgery with Engel class I outcome and 17 matched healthy controls took part in the study. The functional connectivity of a set of cognitive functional networks derived from typical cognitive tasks was assessed in patients, preoperatively and postoperatively, as well as in controls, using stringent methods of artifact reduction. Preoperatively, functional networks in TLE patients differed significantly from healthy controls, with differences that largely, but not exclusively, involved the default mode and temporal/auditory subnetworks. However, undergoing epilepsy surgery and achieving seizure freedom did not lead to significant changes in network connectivity, with postoperative functional network abnormalities closely mirroring the preoperative state. This result argues for a stable chronic effect of the disease on brain connectivity, with changes that are largely "burned in" by the time a patient with intractable TLE undergoes epilepsy surgery, which typically occurs years after the initial diagnosis. The result has potential implications for the treatment of intractable epilepsy, suggesting that delaying surgical intervention that may achieve seizure freedom may lead to functional network changes that are no longer reversible by the time of epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The impact of bilingualism on working memory in pediatric epilepsy

PubMed Central

Veenstra, Amy L.; Riley, Jeffrey D.; Barrett, Lauren E.; Muhonen, Michael G.; Zupanc, Mary; Romain, Jonathan E.; Lin, Jack J.; Mucci, Grace

2016-01-01

Impairments in executive skills broadly span across multiple childhood epilepsy syndromes and can adversely affect quality of life. Bilingualism has been previously shown to correlate with enhanced executive functioning in healthy individuals. This study seeks to determine whether the bilingual advantage in executive functioning exists in the context of pediatric epilepsy. We retrospectively analyzed neuropsychological data in 52 children with epilepsy and compared executive function scores in monolingual versus bilingual children with epilepsy, while controlling for socioeconomic status and ethnicity. Bilingual children performed significantly better on the Working Memory scale than did monolingual children. There were no significant differences on the remaining executive function variables. The bilingual advantage appears to persist for working memory in children with epilepsy. These findings suggest that bilingualism is potentially a protective variable in the face of epilepsy-related working memory dysfunction. PMID:26720703

Global and regional functional connectivity maps of neural oscillations in focal epilepsy

PubMed Central

Englot, Dario J.; Hinkley, Leighton B.; Kort, Naomi S.; Imber, Brandon S.; Mizuiri, Danielle; Honma, Susanne M.; Findlay, Anne M.; Garrett, Coleman; Cheung, Paige L.; Mantle, Mary; Tarapore, Phiroz E.; Knowlton, Robert C.; Chang, Edward F.; Nagarajan, Srikantan S.

2015-01-01

Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning. PMID:25981965

Christianity and epilepsy.

PubMed

Owczarek, K; Jędrzejczak, J

2013-01-01

Epileptic seizures have been known from time immemorial. Throughout the ages, however, ideas concerning the aetiology and treatment of epilepsy have changed considerably. Epilepsy is mentioned many times in the Pentateuch, where it is portrayed as a mysterious condition, whose symptoms, course and contingencies evade rational laws and explanations. In the Middle Ages, the accepted view which prevailed in social consciousness was that patients with epilepsy were possessed by Satan and other impure spirits. One common method of treatment of epileptic seizures was to submit the patient to cruel exorcisms. Patients were frequently injured in the process and some of them even died. Our understanding of epilepsy and its social consequences has improved considerably within the last century. The most significant progress as far as diagnosis and treatment of epilepsy is concerned took place in the last four decades of the twentieth century. Although we now know much more about epilepsy than we used to, this knowledge is still insufficiently popularized.

The interictal language profile in adult epilepsy.

PubMed

Bartha-Doering, Lisa; Trinka, Eugen

2014-10-01

The purpose of this study was to systematically review the literature on the interictal language profile in adult patients with epilepsy. An extensive literature search was performed using MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, PASCAL, and PSYNDEXplus databases. Key aspects of inclusion criteria were adult patients with epilepsy, patient number >10, and in-depth qualitative investigations of a specific language modality or administration of tests of at least two different language modalities, including comprehension, naming, repetition, reading, writing, and spontaneous speech. Our search strategy yielded 933 articles on epilepsy and language. Of these, 31 met final eligibility criteria. Most included articles focused on temporal lobe epilepsy; only three studies were interested in the language profile of patients with idiopathic generalized epilepsies, and one study on frontal lobe epilepsy met inclusion criteria. Study results showed a pronounced heterogeneity of language abilities in patients with epilepsy, varying from intact language profiles to impairment in several language functions. However, at least 17% of patients displayed deficits in more than one language function, with naming, reading comprehension, spontaneous speech, and discourse production being most often affected. This review underscores the need to evaluate different language functions-including spontaneous speech, discourse abilities, naming, auditory and reading comprehension, reading, writing, and repetition-individually in order to obtain a reliable profile of language functioning in patients with epilepsy. Moreover, our findings show that in contrast to the huge scientific interest of memory functions in epilepsy, the examination of language functions so far played a minor role in epilepsy research, emphasizing the need for future research activities in this field. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Being parents with epilepsy: thoughts on its consequences and difficulties affecting their children.

PubMed

Gauffin, Helena; Flensner, Gullvi; Landtblom, Anne-Marie

2015-01-01

Parents with epilepsy can be concerned about the consequences of epilepsy affecting their children. The aim of this paper is to describe aspects of what it means being a parent having epilepsy, focusing the parents' perspectives and their thoughts on having children. Fourteen adults aged 18-35 years with epilepsy and subjective memory decline took part in focus-group interviews. The interviews were conducted according to a semi-structured guideline. Material containing aspects of parenthood was extracted from the original interviews and a secondary analysis was done according to a content-analysis guideline. Interviews with two parents for the Swedish book Leva med epilepsi [To live with epilepsy] by AM Landtblom (Stockholm: Bilda ide; 2009) were analyzed according to the same method. Four themes emerged: (1) a persistent feeling of insecurity, since a seizure can occur at any time and the child could be hurt; (2) a feeling of inadequacy - of not being able to take full responsibility for one's child; (3) acknowledgment that one's children are forced to take more responsibility than other children do; and (4) a feeling of guilt - of not being able to fulfill one's expectations of being the parent one would like to be. The parents with epilepsy are deeply concerned about how epilepsy affects the lives of their children. These parents are always aware that a seizure may occur and reflect on how this can affect their child. They try to foresee possible dangerous situations and prevent them. These parents were sad that they could not always take full responsibility for their child and could not live up to their own expectations of parenthood. Supportive programs may be of importance since fear for the safety of the child increases the psychosocial burden of epilepsy. There were also a few parents who did not acknowledge the safety issue of their child - the authors believe that it is important to identify these parents and provide extra information and support to them.

Childhood epilepsy: a critical review of cost-of-illness studies.

PubMed

Argumosa, Ana; Herranz, Josè Luis

2004-03-01

Epilepsy is an illness with multiple consequences and costs for children, families and society. There are only a few studies published on the cost of childhood epilepsy. The different methodologies used in these studies make it difficult to compare them or even to compare the cost of childhood epilepsy treatment with that of adult epilepsy. Nevertheless, studies highlight important differences in the distribution of costs associated with childhood epilepsy and epilepsy in adults. It is understandable that direct costs represent the higher percentage of the total cost associated with childhood epilepsy treatment, given the higher number of hospital admissions and investigations, as well as the complexity of therapeutic trials, while indirect costs represent the greater proportion in adult epilepsy treatment. In addition to age, the total cost associated with epilepsy also depends on other factors such as seizure frequency, the moment at which the illness cost is estimated and the local health care system. In summary, chronic illnesses not only have an influence on the physical and psychological development of children, they also impose costs on the family and society. Childhood epilepsy has greater economic costs than those generated by more prevalent, chronic illnesses.

Social functioning in pediatric epilepsy reported by parents and teachers: Contributions of medically related variables, verbal skills, and parental anxiety.

PubMed

Carson, Audrey M; Chapieski, Lynn

2016-09-01

Children with epilepsy are at increased risk for deficits in social functioning, though the underlying causes are not well-understood. We examined multiple seizure-related, demographic, and cognitive variables in a group of 93 pediatric patients with intractable seizures who were at risk for social skills deficits and social problems at home and in the classroom. Verbal intelligence and parental anxiety about epilepsy were found to be the two primary predictors of social functioning in children with epilepsy as reported by parents and teachers. Though other social variables and secondarily generalized seizures were significantly correlated with certain aspects of parent-reported social functioning, the impact of these variables appeared to be mediated through verbal intelligence and/or parental anxiety about epilepsy. These findings emphasize the importance of family characteristics on social functioning in children with epilepsy and also suggest that parental anxiety about their child's epilepsy may be a specific risk factor for this population. The findings from this study suggest that the factors associated with social functioning in children with epilepsy are similar regardless of whether social functioning is assessed by the parent or the classroom teacher. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effects of temporal lobe epilepsy and idiopathic epilepsy on cognitive function and emotion in children].

PubMed

Yang, Xiao-Yan; Long, Li-Li; Xiao, Bo

2016-07-01

To investigate the effects of temporal lobe epilepsy and idiopathic epilepsy on cognitive function and emotion in children and the risk factors for cognitive impairment. A retrospective analysis was performed for the clinical data of 38 children with temporal lobe epilepsy and 40 children with idiopathic epilepsy. The controls were 42 healthy children. All subjects received the following neuropsychological tests: Montreal Cognitive Assessment (MoCA) scale, verbal fluency test, digit span test, block design test, Social Anxiety Scale for Children (SASC), and Depression Self-rating Scale for Children (DSRSC). Compared with the control group, the temporal lobe epilepsy and idiopathic epilepsy groups showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). Compared with the idiopathic epilepsy group, the temporal lobe epilepsy group showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). In the temporal lobe epilepsy group, MoCA score was negatively correlated with SASC score, DSRSC score, and seizure frequency (r=-0.571, -0.529, and -0.545 respectively; P<0.01). In the idiopathic epilepsy group, MoCA score was also negatively correlated with SASC score, DSRSC score, and seizure frequency (r=-0.542, -0.487, and -0.555 respectively; P<0.01). Children with temporal lobe epilepsy and idiopathic epilepsy show impaired whole cognition, verbal fluency, memory, and executive function and have anxiety and depression, which are more significant in children with temporal lobe epilepsy. High levels of anxiety, depression, and seizure frequency are risk factors for impaired cognitive function.

Semantic Processing Impairment in Patients with Temporal Lobe Epilepsy

PubMed Central

Jaimes-Bautista, Amanda G.; Rodríguez-Camacho, Mario; Martínez-Juárez, Iris E.; Rodríguez-Agudelo, Yaneth

2015-01-01

The impairment in episodic memory system is the best-known cognitive deficit in patients with temporal lobe epilepsy (TLE). Recent studies have shown evidence of semantic disorders, but they have been less studied than episodic memory. The semantic dysfunction in TLE has various cognitive manifestations, such as the presence of language disorders characterized by defects in naming, verbal fluency, or remote semantic information retrieval, which affects the ability of patients to interact with their surroundings. This paper is a review of recent research about the consequences of TLE on semantic processing, considering neuropsychological, electrophysiological, and neuroimaging findings, as well as the functional role of the hippocampus in semantic processing. The evidence from these studies shows disturbance of semantic memory in patients with TLE and supports the theory of declarative memory of the hippocampus. Functional neuroimaging studies show an inefficient compensatory functional reorganization of semantic networks and electrophysiological studies show a lack of N400 effect that could indicate that the deficit in semantic processing in patients with TLE could be due to a failure in the mechanisms of automatic access to lexicon. PMID:26257956

"I don't like talking about it because that's not who I am": Challenges children face during epilepsy-related family communication.

PubMed

O'Toole, S; Lambert, V; Gallagher, P; Shahwan, A; Austin, J K

2016-09-01

Childhood epilepsy not only significantly impacts a child's social relationships and psychosocial wellbeing, but it can also cause disruptions in family relations. Children living with epilepsy often rely on parental figures for guidance in relation to their condition. A paucity of research has examined the challenges for children when communicating about epilepsy with parental figures. This qualitative study explored the challenges faced by children when talking about epilepsy with their parent(s). Semi-structured interviews were conducted with 29 children (aged 6-16 years) living with epilepsy. Participants were recruited from a neurology department of a major pediatric hospital and from a national epilepsy association. Interviews were transcribed verbatim and thematically analyzed. Findings revealed four themes: communication impeding normalcy, parental overprotection, parental reactions to epilepsy-related communication, and restriction of activities as a consequence of epilepsy-related communication. The study highlights the need for a greater understanding of parent-child dialogue surrounding epilepsy and where challenges lie for children in conversing about their condition. Parents and health care professionals play a pivotal role in facilitating an environment where children feel comfortable talking about epilepsy. This information will be instrumental in the development of a communication-based intervention for families living with epilepsy. © The Author(s) 2016.

Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study.

PubMed

Luo, Cheng; Qiu, Chuan; Guo, Zhiwei; Fang, Jiajia; Li, Qifu; Lei, Xu; Xia, Yang; Lai, Yongxiu; Gong, Qiyong; Zhou, Dong; Yao, Dezhong

2011-01-01

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.

Aberrant functional connectivity between motor and language networks in rolandic epilepsy.

PubMed

Besseling, René M H; Overvliet, Geke M; Jansen, Jacobus F A; van der Kruijs, Sylvie J M; Vles, Johannes S H; Ebus, Saskia C M; Hofman, Paul A M; de Louw, Anton J A; Aldenkamp, Albert P; Backes, Walter H

2013-12-01

Rolandic epilepsy (RE) is an idiopathic focal childhood epilepsy with a well-established neuropsychological profile of language impairment. The aim of this study is to provide a functional correlate that links rolandic (sensorimotor) pathology to language problems using functional MRI. Twenty-three children with RE (8-14 years old) and 21 matched controls underwent extensive language assessment (Clinical Evaluation of Language Fundamentals). fMRI was performed at rest and using word generation, reading, and finger tapping paradigms. Since no activation group differences were found, regions of interest (ROIs) were defined at pooled (patients and controls combined) activation maxima and in contralateral homotopic cortex, and used to assess language lateralization as well as for a resting-state connectivity analysis. Furthermore, the association between connection strength and language performance was investigated. Reduced language performance was found in the children with RE. Bilateral activation was found for both language tasks with some predominance of the left hemisphere in both groups. Compared to controls, patient connectivity was decreased between the left sensorimotor area and right inferior frontal gyrus (p<0.01). For this connection, lower connectivity was associated with lower language scores in the patient group (r=0.49, p=0.02), but not in the controls. Language laterality analysis revealed bilateral language representation in the age range under study (8-14 years). As a consequence, the connection of reduced functional connectivity we found represents an impaired interplay between motor and language networks, and aberrant functional connectivity associated with poorer language performance. These findings provide a first neuronal correlate in terms of aberrant resting-state functional connectivity for language impairment in RE. Copyright © 2013 Elsevier B.V. All rights reserved.

Pattern of executive functioning in adolescents with epilepsy: A multimethod measurement approach.

PubMed

Modi, Avani C; Vannest, Jennifer; Combs, Angela; Turnier, Luke; Wade, Shari L

2018-03-01

Youth with epilepsy demonstrate deficits in executive functioning (EF), the skills necessary for goal-directed behavior (e.g., problem-solving, initiating, monitoring, organization, planning, and working memory). Despite 30-50% of youth with epilepsy demonstrating EF deficits, no extant studies have utilized both performance and questionnaire-based measures to examine the pattern of EF deficits in adolescents with epilepsy. Study aims were to 1) identify the pattern of EF deficits in adolescents with epilepsy and 2) identify which assessment tools are most sensitive to EF deficits in this population (adolescents, ages 13-17, with epilepsy). An exploratory aim was to examine group differences on measures of EF by epilepsy type. Standard performance-based neuropsychological measures (Wechsler Intelligence Scale for Children - Version V or Wechsler Adult Intelligence Scale Working Memory Index-Version IV, Delis Kaplan Executive Functioning System, NIH Toolbox, Test of Everyday Attention for Children) and the Behavior Rating Inventory of Executive Functioning (BRIEF) comprised the multimethod assessment battery. Depending on the measure, 30% of adolescents with epilepsy had deficits in working memory, 17% in cognitive flexibility/problem solving, 6% in inhibition, and 18% in planning/organization. Attention was a significant problem for 15% of adolescents with epilepsy. Correlations among the various EF measures were quite poor. Across various EF domains, results indicated that adolescents with localization-related epilepsy demonstrated better EF skills compared to adolescents with unclassified epilepsy. Overall, our findings suggest that executive functioning deficits are selective and different from those observed in other neurological populations (e.g., attention deficit hyperactivity disorder (ADHD), traumatic brain injury) where problems with self-regulation (i.e., inhibition, planning/organization) are more pronounced. These findings support utilizing multiple measures, including both performance-based neuropsychological tests and parent- and self-reports, to assess executive functioning difficulties in adolescents with epilepsy as they are uniquely sensitive to executive functioning domains. Adolescents with unclassified epilepsy also appear to be at higher risk for EF deficits and thus represent an important group to target for intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Validation of the Neuro-QoL measurement system in children with epilepsy.

PubMed

Lai, Jin-Shei; Nowinski, Cindy J; Zelko, Frank; Wortman, Katy; Burns, James; Nordli, Douglas R; Cella, David

2015-05-01

Children with epilepsy often face complex psychosocial consequences that are not fully captured by existing patient-reported outcome (PRO) measures. The Neurology Quality of Life Measurement System "Neuro-QoL" was developed to provide a set of common PRO measures that address issues important to people with neurologic disorders. This paper reports Neuro-QoL (anxiety, depression, interaction with peers, fatigue, pain, cognitive function, stigma, and upper and lower extremity functions) validation in children with epilepsy. Patients (aged 10-18years) diagnosed with epilepsy completed Neuro-QoL and legacy measures at time 1 (initial study visit) and 6-month follow-up. Internal consistency reliability was also evaluated. Concurrent validity was assessed by comparing Neuro-QoL measures with more established "legacy" measures of the same concepts. Clinical validity was evaluated by comparing mean Neuro-QoL scores of patients grouped by clinical anchors such as disease severity. Responsiveness of the Neuro-QoL from time 1 (initial study visit) to 6months was evaluated using self-reported change as the primary anchor. Sixty-one patients (mean age=13.4years; 62.3% male, 75.9% white) participated. Most patients (64.2%) had been seizure-free in the 3months prior to participation, and seizure frequency was otherwise described as follows: 17.8% daily, 13.3% weekly, 35.6% monthly, and 33.3% yearly. All patients were taking antiepileptic drugs. Patients reported better function/less symptoms compared to the reference groups. Internal consistency (alpha) coefficients ranged from 0.76 to 0.87. Patients with different seizure frequencies differed on anxiety (p<.01) and cognitive function (p<.05). Compared to patients on polytherapy, those on monotherapy had better upper extremity scores (p<.05). Compared to those with localized seizures, those experiencing generalized seizures reported worse stigma (p<.05). Depression, anxiety, lower extremity, fatigue, pain, interaction with peers, and stigma also significantly discriminated patients with different levels of quality of life (p≤.05). All Neuro-QoL measures were significantly correlated with other measures assessing similar domains. Stigma was related to self-reported change in several areas of functioning but in sometimes unexpected directions. The Neurology Quality of Life Measurement System is a valid and reliable assessment tool for children with epilepsy and can be used in research and clinical settings. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of epilepsy on the adolescent adolescent.

PubMed

Marin, Susana

2005-01-01

Epilepsy is the most common serious neurologic condition affecting adolescents, coinciding with a time of dramatic change in growth, hormones, psychology, and social situations. Adolescents with epilepsy are sensitive to peer norms and beliefs and may limit disclosure of their chronic illness to feel less different or stigmatized. They may also explore the world of alcohol and recreational drugs, like others in their peer group, as well as experiment with their own medications. The goal of treatment should be maintenance of a normal lifestyle with complete seizure control, minimal adverse effects, and achievement of normal adolescent milestones. Adolescents with epilepsy have an increased incidence of depression because of the combination of the unpredictable nature of epilepsy, a perceived lack of control, uncontrollable adverse events, and negative perceptions of themselves. The purpose of this article is to summarize the physical, developmental, emotional, and cognitive effects of epilepsy on adolescents. By increasing the awareness of healthcare providers, interventions designed to prevent further negative consequences can be considered for adolescents with epilepsy.

The Relationship between Sleep and Epilepsy: The Effect on Cognitive Functioning in Children

ERIC Educational Resources Information Center

Parisi, Pasquale; Bruni, Oliviero; Pia Villa, Maria; Verrotti, Alberto; Miano, Silvia; Luchetti, Anna; Curatolo, Paolo

2010-01-01

Aim: The purpose of this review was to examine the possible pathophysiological links between epilepsy, cognition, sleep macro- and microstructure, and sleep disorders to highlight the contributions and interactions of sleep and epilepsy on cognitive functioning in children with epilepsy. Method: PubMed was used as the medical database source. No…

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

PubMed

Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

2015-06-01

The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

Risky Decision Making in Juvenile Myoclonic Epilepsy.

PubMed

Unterberger, Iris; Zamarian, Laura; Prieschl, Manuela; Bergmann, Melanie; Walser, Gerald; Luef, Gerhard; Javor, Andrija; Ransmayr, Gerhard; Delazer, Margarete

2018-01-01

It is not known whether patients with juvenile myoclonic epilepsy (JME) differ from healthy people in decision making under risk, i.e., when the decision-making context offers explicit information about options, probabilities, and consequences already from the beginning. In this study, we adopted the Game of Dice Task-Double to investigate decision making under risk in a group of 36 patients with JME (mean age 25.25/SD 5.29 years) and a group of 38 healthy controls (mean age 26.03/SD 4.84 years). Participants also underwent a comprehensive neuropsychological assessment focused on frontal executive functions. Significant group differences were found in tests of psychomotor speed and divided attention, with the patients scoring lower than the controls. Importantly, patients made risky decisions more frequently than controls. In the patient group, poor decision making was associated with poor executive control, poor response inhibition, and a short interval since the last seizure episode. Executive control and response inhibition could predict 42% of variance in the frequency of risky decisions. This study indicates that patients with JME with poorer executive functions are more likely to make risky decisions than healthy controls. Decision making under risk is of major importance in every-day life, especially with regard to treatment decisions and adherence to long-term medical therapy. Since even a single disadvantageous decision may have long-lasting consequences, this finding is of high relevance.

Rethinking cognition and behavior in the new classification for childhood epilepsy: Examples from frontal lobe and temporal lobe epilepsies.

PubMed

Smith, Mary Lou

2016-11-01

The new approach to classification of the epilepsies emphasizes the role of dysfunction in networks in defining types of epilepsies. This paper reviews the structural and neuropsychological deficits in two types of childhood epilepsy: frontal lobe and temporal lobe epilepsy. The evidence for and against a pattern of specificity of deficits in executive function and memory associated with these two types of epilepsies is presented. The evidence varies with the methodologies used in the studies, but direct comparison of the two types of epilepsies does not suggest a clear-cut mapping of function onto structure. These findings are discussed in light of the concept of network dysfunction. The evidence supports the conceptualization of epilepsy as a network disease. Implications for future work in the neuropsychology of pediatric epilepsy are suggested. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Adults with an epilepsy history, notably those 45-64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history.

PubMed

Zack, Matthew; Luncheon, Cecily

2018-06-13

From 95,196 sample adults in the combined 2010, 2013, and 2015 U.S. National Health Interview Survey, we estimated the association between histories of epilepsy and heart disease after accounting for sociodemographic characteristics and behavioral risk factors. Adults 18 years old or older with an epilepsy history reported heart disease (21%) about nine percentage points more often than those without such a history (12%), overall and within levels of characteristics and risk factors. These increases in heart disease history for adults with an epilepsy history compared with adults without such a history were greater in those 45-64 years old or at the lowest family income levels. These increases of heart disease in adults with an epilepsy history highlight two needs-to prevent the occurrence of heart disease and to reduce its consequences. Because comorbidity from heart disease can complicate epilepsy management, physicians caring for those with epilepsy should be aware of these increased risks, identify risk factors for heart disease, and recommend to their patients with epilepsy ways to diminish these risks. Copyright © 2018 Elsevier Inc. All rights reserved.

Adaptive functioning in children with epilepsy and learning problems.

PubMed

Buelow, Janice M; Perkins, Susan M; Johnson, Cynthia S; Byars, Anna W; Fastenau, Philip S; Dunn, David W; Austin, Joan K

2012-10-01

In the study we describe adaptive functioning in children with epilepsy whose primary caregivers identified them as having learning problems. This was a cross-sectional study of 50 children with epilepsy and learning problems. Caregivers supplied information regarding the child's adaptive functioning and behavior problems. Children rated their self-concept and completed a battery of neuropsychological tests. Mean estimated IQ (PPVT-III) in the participant children was 72.8 (SD = 18.3). On average, children scored 2 standard deviations below the norm on the Vineland Adaptive Behavior Scale-II and this was true even for children with epilepsy who had estimated IQ in the normal range. In conclusion, children with epilepsy and learning problems had relatively low adaptive functioning scores and substantial neuropsychological and mental health problems. In epilepsy, adaptive behavior screening can be very informative and guide further evaluation and intervention, even in those children whose IQ is in the normal range.

Epilepsy, behavior, and art (Epilepsy, Brain, and Mind, part 1).

PubMed

Rektor, Ivan; Schachter, Steven C; Arzy, Shahar; Baloyannis, Stavros J; Bazil, Carl; Brázdil, Milan; Engel, Jerome; Helmstaedter, Gerhard; Hesdorffer, Dale C; Jones-Gotman, Marilyn; Kesner, Ladislav; Komárek, Vladimír; Krämer, Günter; Leppik, Ilo E; Mann, Michael W; Mula, Marco; Risse, Gail L; Stoker, Guy W; Kasteleijn-Nolst Trenité, Dorothée G A; Trimble, Michael; Tyrliková, Ivana; Korczyn, Amos D

2013-08-01

Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art. Copyright © 2013. Published by Elsevier Inc.

Overview and perspectives of employment in people with epilepsy.

PubMed

de Boer, Hanneke M

2005-01-01

Even though it is now the viewpoint of the majority of professionals working in epilepsy care that most people with epilepsy should and can perform on the labor market as does anybody else, research tells a different story. Most figures concerning employment rates of people with epilepsy indicate that they do not perform as well on the labor market as others do. Although both research figures and research groups vary, generally unemployment rates are higher for people with epilepsy than for the general population. Early studies showed that the situation for people with epilepsy was rather grim. Later studies showed similar outcomes. Unemployment rates vary between groups and countries. Research shows that being employed is an important ingredient of the quality of life of people with epilepsy. The World Health Organization also recognizes the importance of employment as a part of social health, and therefore, improving the quality of life. It is important to know the perspectives on the labor market for people with epilepsy and what the possible problems are. I describe a Dutch research project and give an overview of the findings concerning the employment and consequent employability of people with epilepsy and questions pertaining to employment and epilepsy. Possible interventions [i.e., public education and employment programs for people with epilepsy with the aim to improve the (re)integration of people with epilepsy into the labor market, thus improving the quality of life of (potential) employees with epilepsy], are described extensively.

Laser-Bioplasma Interaction: The Epilepsy-Topion-Bioplasma, (the Seizure Onset Area) Upon the Action of the Optical-Fiber-Guided Multi-Ultraviolet-Photon Beams

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

2016-10-01

The ultraviolet photons may control the imbalance of sodium and potassium ions in the brain bioplasma and, consequently, may prove to be efficient in the prevention of epileptic seizures. A novel method is based on the multi-ultraviolet-photon beam interaction with the epilepsy-topion-bioplasma, (nonlinear coupling of an ultra high frequency mode to the brain beta phonons). It is hypothesized that epilepsy is a chaotic-dynamics phenomenon: small electrical changes in the epilepsy-topion-bioplasma lead, (within the 10s of milliseconds), to the onset of chaos, (seizure-excessive electrical discharge), and subsequent cascading into adjacent areas.

Epilepsy: A Spectrum Disorder

PubMed Central

Sirven, Joseph I.

2015-01-01

Epilepsy, a disorder of unprovoked seizures is a multifaceted disease affecting individuals of all ages with a particular predilection for the very young and old. In addition to seizures, many patients often report cognitive and psychiatric problems associated with both the seizures themselves and its therapy. Epilepsy has numerous etiologies both idiopathic and acquired with a wide range of therapeutic responses. Despite numerous treatments available to control repetitive seizures including medications, diets, immunotherapy, surgery, and neuromodulatory devices, a large percentage of patients continue to suffer the consequences of uncontrolled seizures, which include psychosocial stigma and death. PMID:26328931

Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study.

PubMed

Vollmar, Christian; O'Muircheartaigh, Jonathan; Barker, Gareth J; Symms, Mark R; Thompson, Pamela; Kumari, Veena; Duncan, John S; Janz, Dieter; Richardson, Mark P; Koepp, Matthias J

2011-06-01

Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.

SCN3A deficiency associated with increased seizure susceptibility

PubMed Central

Lamar, Tyra; Vanoye, Carlos G.; Calhoun, Jeffrey; Wong, Jennifer C.; Dutton, Stacey B.B.; Jorge, Benjamin S.; Velinov, Milen; Escayg, Andrew; Kearney, Jennifer A.

2017-01-01

Mutations in voltage-gated sodium channels expressed highly in the brain (SCN1A, SCN2A, SCN3A, and SCN8A) are responsible for an increasing number of epilepsy syndromes. In particular, mutations in the SCN3A gene, encoding the pore-forming Nav1.3 α subunit, have been identified in patients with focal epilepsy. Biophysical characterization of epilepsy-associated SCN3A variants suggests that both gain- and loss-of-function SCN3A mutations may lead to increased seizure susceptibility. In this report, we identified a novel SCN3A variant (L247P) by whole exome sequencing of a child with focal epilepsy, developmental delay, and autonomic nervous system dysfunction. Voltage clamp analysis showed no detectable sodium current in a heterologous expression system expressing the SCN3A-L247P variant. Furthermore, cell surface biotinylation demonstrated a reduction in the amount of SCN3A-L247P at the cell surface, suggesting the SCN3A-L247P variant is a trafficking-deficient mutant. To further explore the possible clinical consequences of reduced SCN3A activity, we investigated the effect of a hypomorphic Scn3a allele (Scn3aHyp) on seizure susceptibility and behavior using a gene trap mouse line. Heterozygous Scn3a mutant mice (Scn3a+/Hyp) did not exhibit spontaneous seizures nor were they susceptible to hyperthermia-induced seizures. However, they displayed increased susceptibility to electroconvulsive (6 Hz) and chemiconvulsive (flurothyl and kainic acid) induced seizures. Scn3a+/Hyp mice also exhibited deficits in locomotor activity and motor learning. Taken together, these results provide evidence that loss-of-function of SCN3A caused by reduced protein expression or deficient trafficking to the plasma membrane may contribute to increased seizure susceptibility. PMID:28235671

Low Rate of Intraoperative Seizures During Awake Craniotomy in a Prospective Cohort with 374 Supratentorial Brain Lesions: Electrocorticography Is Not Mandatory.

PubMed

Boetto, Julien; Bertram, Luc; Moulinié, Gérard; Herbet, Guillaume; Moritz-Gasser, Sylvie; Duffau, Hugues

2015-12-01

Awake craniotomy (AC) in brain lesions has allowed an improvement of both oncologic and functional results. However, intraoperative seizures (IOSs) were reported as a cause of failure of AC. Here, we analyze the incidence, risk factors, and consequences of IOSs in a prospective cohort of 374 ACs without electrocorticography (ECoG). We performed a prospective study including all patients who underwent AC for an intra-axial supratentorial cerebral lesion from 2009-2014 in our department. Occurrence of IOS was analyzed with respect to medical and epilepsy history, tumor characteristics, operative technique, and postoperative outcomes. The study comprised 374 patients with a major incidence of low-grade glioma (86%). Most of the patients (83%) had epilepsy history before surgery (20% had intractable seizures). Preoperative mean Karnofsky performance scale (KPS) score was 91. IOSs occurred in 13 patients (3.4%). All IOSs were partial seizures, which quickly resolved by irrigation with cold Ringer lactate. No procedure failed because of IOS, and the rate of aborted AC whatever the cause was nil. Mean stimulation current intensity for cortical and subcortical mapping was 2.25 ± 0.6 mA. Presurgical refractory epilepsy was not associated with a higher incidence of IOS. Three months after surgery, no patients had severe or disabling permanent worsening, even within the IOS group (mean KPS score of 93.7). AC for intra-axial brain lesion can be safely and reproducibly achieved without ECoG, with a low rate of IOS and excellent functional results, even in patients with preoperative intractable epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural and functional changes during epileptogenesis in the mouse model of medial temporal lobe epilepsy.

PubMed

Dietrich, Yvan; Eliat, Pierre-Antoine; Dieuset, Gabriel; Saint-Jalmes, Herve; Pineau, Charles; Wendling, Fabrice; Martin, Benoit

2016-08-01

An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the `latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury.

Ivermectin Treatment in Patients With Onchocerciasis-Associated Epilepsy: Protocol of a Randomized Clinical Trial

PubMed Central

Mandro, Michel; Mukendi, Deby; Dolo, Housseini; Suykerbuyk, Patrick; Van Oijen, Marieke

2017-01-01

Background Many studies have reported an association between epilepsy, nodding syndrome (NS), and onchocerciasis (river blindness). A high prevalence of epilepsy has been noted particularly in onchocerciasis hyperendemic areas where onchocerciasis is not or insufficiently controlled with mass ivermectin distribution. There is evidence that increasing the coverage of ivermectin reduces the incidence of epilepsy, and anecdotal evidence suggests a reduction in seizure frequency in onchocerciasis-associated epilepsy (OAE) patients who receive ivermectin. Finding an alternative treatment for epilepsy in these patients will have major consequences. Objective The goal of the study is to assess whether ivermectin treatment decreases the frequency of seizures and leads to seizure freedom in OAE patients, including patients with NS. If we are able to demonstrate such an effect, this would strengthen the argument that onchocerciasis is causing epilepsy and therefore we should increase our efforts to eliminate onchocerciasis. Methods We will conduct a randomized clinical trial in the Democratic Republic of Congo to compare seizure freedom in onchocerciasis-infested epilepsy patients who receive immediate ivermectin treatment with delayed (after 4 months) ivermectin treatment. All participants will simultaneously receive antiepilepsy drugs (AEDs) according to local guidelines for epilepsy treatment. The primary endpoint is seizure freedom defined as no seizures during the 4 month of follow-up. Secondary endpoint is significant (>50%) seizure reduction compared to baseline seizure frequency. Reduction of seizures will be compared between ivermectin and nonivermectin arms. Results Start of enrollment is planned for August 2017, and we expect to have enrolled all 110 participants by December 2017. Results are expected in June 2018. Conclusions If ivermectin treatment in addition to AEDs is able to lead to seizure freedom or significantly reduces seizure frequency in OAE patients, this will have major consequences for epilepsy treatment in onchocerciasis-endemic regions. Ivermectin is donated for free and in non Loa-Loa–endemic regions has negligible side effects. Reducing the burden of epilepsy will have a major impact on quality of life and socioeconomic status of families with affected members in Africa. Trial Registration ClinicalTrials.gov NCT03052998; https://clinicaltrials.gov/ct2/show/NCT03052998 (Archived by WebCite at http://www.webcitation.org/6roFVQSG0) PMID:28855148

Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures.

PubMed

Jilek-Aall, L

1999-03-01

Epilepsy when manifested as grand mal seizure provokes strong and ambivalent feelings in those witnessing it. Terms such as morbus sacer, denoting both a sacred and demoniac condition, or folk names indicating divine punishment, have expressed these feelings in European societies from antiquity to the Middle Ages and beyond. An atmosphere of fear, shame and mysticism surrounds epilepsy even in our days in many non-Western and also in Western cultures. In the course of work and studies in Tanzania, where I organized the Mahenge Clinic for Epilepsy in 1960, and in other parts of Africa, I found that epilepsy is conceived of as an "African'' affliction, a manifestation of supernatural forces that makes it difficult to reach epilepsy sufferers with modern medical treatment. Epilepsy is traditionally looked on as caused by ancestral spirits or attributed to possession by evil spirits. It is also thought to be due to witchcraft, and "poisoning," and often taken to be contagious. Epilepsy may, under Christian missionary teaching, have come to be considered as due to demoniac possession or divine punishment for sins, in accordance with biblical examples. In many parts of Africa, syncretic amalgamation of indigenous traditions with Judeo-Christian doctrines influenced popular attitudes toward epilepsy. We demonstrated that persistent efforts at health education in the context of organized treatment of epilepsy can result in a change of popular notions about epilepsy and consequently lead to significant improvement in the quality of life of epilepsy sufferers.

Multisensory temporal function and EEG complexity in patients with epilepsy and psychogenic nonepileptic events.

PubMed

Noel, Jean-Paul; Kurela, LeAnne; Baum, Sarah H; Yu, Hong; Neimat, Joseph S; Gallagher, Martin J; Wallace, Mark

2017-05-01

Cognitive and perceptual comorbidities frequently accompany epilepsy and psychogenic nonepileptic events (PNEE). However, and despite the fact that perceptual function is built upon a multisensory foundation, little knowledge exists concerning multisensory function in these populations. Here, we characterized facets of multisensory processing abilities in patients with epilepsy and PNEE, and probed the relationship between individual resting-state EEG complexity and these psychophysical measures in each patient. We prospectively studied a cohort of patients with epilepsy (N=18) and PNEE (N=20) patients who were admitted to Vanderbilt's Epilepsy Monitoring Unit (EMU) and weaned off of anticonvulsant drugs. Unaffected age-matched persons staying with the patients in the EMU (N=15) were also recruited as controls. All participants performed two tests of multisensory function: an audio-visual simultaneity judgment and an audio-visual redundant target task. Further, in the cohort of patients with epilepsy and PNEE we quantified resting state EEG gamma power and complexity. Compared with both patients with epilepsy and control subjects, patients with PNEE exhibited significantly poorer acuity in audiovisual temporal function as evidenced in significantly larger temporal binding windows (i.e., they perceived larger stimulus asynchronies as being presented simultaneously). These differences appeared to be specific for temporal function, as there was no difference among the three groups in a non-temporally based measure of multisensory function - the redundant target task. Further, patients with PNEE exhibited more complex resting state EEG patterns as compared to their patients with epilepsy, and EEG complexity correlated with multisensory temporal performance on a subject-by-subject manner. Taken together, findings seem to indicate that patients with PNEE bind information from audition and vision over larger temporal intervals when compared with control subjects as well as patients with epilepsy. This difference in multisensory function appears to be specific to the temporal domain, and may be a contributing factor to the behavioral and perceptual alterations seen in this population. Published by Elsevier Inc.

Why epilepsy challenges social life.

PubMed

Steiger, Bettina K; Jokeit, Hennric

2017-01-01

Social bonds are at the center of our daily living and are an essential determinant of our quality of life. In people with epilepsy, numerous factors can impede cognitive and affective functions necessary for smooth social interactions. Psychological and psychiatric complications are common in epilepsy and may hinder the processing of social information. In addition, neuropsychological deficits such as slowed processing speed, memory loss or attentional difficulties may interfere with enjoyable reciprocity of social interactions. We consider societal, psychological, and neuropsychological aspects of social life with particular emphasis on socio-cognitive functions in temporal lobe epilepsy. Deficits in emotion recognition and theory of mind, two main aspects of social cognition, are frequently observed in individuals with mesial temporal lobe epilepsy. Results from behavioural studies targeting these functions will be presented with a focus on their relevance for patients' daily life. Furthermore, we will broach the issue of pitfalls in current diagnostic tools and potential directions for future research. By giving a broad overview of individual and interpersonal determinants of social functioning in epilepsy, we hope to provide a basis for future research to establish social cognition as a key component in the comprehensive assessment and care of those with epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Improving understanding, promoting social inclusion, and fostering empowerment related to epilepsy: Epilepsy Foundation public awareness campaigns — 2001 through 2013☆

PubMed Central

Price, P.; Kobau, R.; Buelow, J.; Austin, J.; Lowenberg, K.

2015-01-01

It is a significant public health concern that epilepsy, the fourth most common neurological disorder in the United States, is generally poorly understood by both the public and those living with the condition. Lack of understanding may magnify the challenges faced by those with epilepsy, including limiting treatment opportunities, effective management of symptoms, and full participation in daily life activities. Insufficient awareness of epilepsy and appropriate seizure first aid among the public and professionals can result in insufficient treatment, inappropriate seizure response, physical restraint, social exclusion, or other negative consequences. To address the need for increased public education and awareness about epilepsy, the national Epilepsy Foundation, supported by the Centers for Disease Control and Prevention, has conducted yearly multifaceted public education and awareness campaigns designed to reach the broad population and targeted segments of the population including youth, young adults, racial/ethnic groups (i.e., African-, Hispanic-, and Asian-Americans), and people with epilepsy and their caregivers. Campaign channels have included traditional media, social media, and community opinion leaders and celebrity spokespersons. The key activities of these campaigns, conducted from 2001 to 2013, are summarized in this report. PMID:25726152

Epilepsy in India II: Impact, burden, and need for a multisectoral public health response.

PubMed

Amudhan, Senthil; Gururaj, Gopalkrishna; Satishchandra, Parthasarathy

2015-01-01

Epilepsy is a common neurological disorder whose consequences are influenced socially and culturally, especially in India. This review (second of the two part series) was carried out to understand the social impact and economic burden to develop comprehensive program for control and prevention of epilepsy. Epilepsy is known to have adverse effect on education, employment, marriage, and other essential social opportunities. Economic burden associated with epilepsy is very high with treatment and travel costs emerging as an important contributing factor. A vicious cycle between economic burden and poor disease outcome is clear. There is no significant change in the perception, stigma, and discrimination of epilepsy across the country despite improvement in educational and social parameters over the time. The huge treatment gap and poor quality of life is further worsened by the associated comorbidities and conditions. Thus, a multidisciplinary response is needed to address the burden and impact of epilepsy which calls for an integrated and multipronged approach for epilepsy care, prevention, and rehabilitation. Service delivery, capacity building, integration into the existing program, mobilizing public support, and increasing public awareness will be the hallmarks of such an integrated approach in a public health model.

Improving understanding, promoting social inclusion, and fostering empowerment related to epilepsy: Epilepsy Foundation public awareness campaigns--2001 through 2013.

PubMed

Price, P; Kobau, R; Buelow, J; Austin, J; Lowenberg, K

2015-03-01

It is a significant public health concern that epilepsy, the fourth most common neurological disorder in the United States, is generally poorly understood by both the public and those living with the condition. Lack of understanding may magnify the challenges faced by those with epilepsy, including limiting treatment opportunities, effective management of symptoms, and full participation in daily life activities. Insufficient awareness of epilepsy and appropriate seizure first aid among the public and professionals can result in insufficient treatment, inappropriate seizure response, physical restraint, social exclusion, or other negative consequences. To address the need for increased public education and awareness about epilepsy, the national Epilepsy Foundation, supported by the Centers for Disease Control and Prevention, has conducted yearly multifaceted public education and awareness campaigns designed to reach the broad population and targeted segments of the population including youth, young adults, racial/ethnic groups (i.e., African-, Hispanic-, and Asian-Americans), and people with epilepsy and their caregivers. Campaign channels have included traditional media, social media, and community opinion leaders and celebrity spokespersons. The key activities of these campaigns, conducted from 2001 to 2013, are summarized in this report. Published by Elsevier Inc.

Epilepsy in India II: Impact, burden, and need for a multisectoral public health response

PubMed Central

Amudhan, Senthil; Gururaj, Gopalkrishna; Satishchandra, Parthasarathy

2015-01-01

Epilepsy is a common neurological disorder whose consequences are influenced socially and culturally, especially in India. This review (second of the two part series) was carried out to understand the social impact and economic burden to develop comprehensive program for control and prevention of epilepsy. Epilepsy is known to have adverse effect on education, employment, marriage, and other essential social opportunities. Economic burden associated with epilepsy is very high with treatment and travel costs emerging as an important contributing factor. A vicious cycle between economic burden and poor disease outcome is clear. There is no significant change in the perception, stigma, and discrimination of epilepsy across the country despite improvement in educational and social parameters over the time. The huge treatment gap and poor quality of life is further worsened by the associated comorbidities and conditions. Thus, a multidisciplinary response is needed to address the burden and impact of epilepsy which calls for an integrated and multipronged approach for epilepsy care, prevention, and rehabilitation. Service delivery, capacity building, integration into the existing program, mobilizing public support, and increasing public awareness will be the hallmarks of such an integrated approach in a public health model. PMID:26713005

From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer’s Disease

PubMed Central

Dulla, Chris G.; Coulter, Douglas A.; Ziburkus, Jokubas

2015-01-01

Complex circuitry with feed-forward and feed-back systems regulate neuronal activity throughout the brain. Cell biological, electrical, and neurotransmitter systems enable neural networks to process and drive the entire spectrum of cognitive, behavioral, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits relies on hundreds, if not thousands, of unique molecular interactions. Even single molecule dysfunctions can be disrupting to neural circuit activity, leading to neurological pathology. Here, we sample our current understanding of how molecular aberrations lead to disruptions in networks using three neurological pathologies as exemplars: epilepsy, traumatic brain injury (TBI), and Alzheimer’s disease (AD). Epilepsy provides a window into how total destabilization of network balance can occur. TBI is an abrupt physical disruption that manifests in both acute and chronic neurological deficits. Last, in AD progressive cell loss leads to devastating cognitive consequences. Interestingly, all three of these neurological diseases are interrelated. The goal of this review, therefore, is to identify molecular changes that may lead to network dysfunction, elaborate on how altered network activity and circuit structure can contribute to neurological disease, and suggest common threads that may lie at the heart of molecular circuit dysfunction. PMID:25948650

From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer's Disease.

PubMed

Dulla, Chris G; Coulter, Douglas A; Ziburkus, Jokubas

2016-06-01

Complex circuitry with feed-forward and feed-back systems regulate neuronal activity throughout the brain. Cell biological, electrical, and neurotransmitter systems enable neural networks to process and drive the entire spectrum of cognitive, behavioral, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits relies on hundreds, if not thousands, of unique molecular interactions. Even single molecule dysfunctions can be disrupting to neural circuit activity, leading to neurological pathology. Here, we sample our current understanding of how molecular aberrations lead to disruptions in networks using three neurological pathologies as exemplars: epilepsy, traumatic brain injury (TBI), and Alzheimer's disease (AD). Epilepsy provides a window into how total destabilization of network balance can occur. TBI is an abrupt physical disruption that manifests in both acute and chronic neurological deficits. Last, in AD progressive cell loss leads to devastating cognitive consequences. Interestingly, all three of these neurological diseases are interrelated. The goal of this review, therefore, is to identify molecular changes that may lead to network dysfunction, elaborate on how altered network activity and circuit structure can contribute to neurological disease, and suggest common threads that may lie at the heart of molecular circuit dysfunction. © The Author(s) 2015.

Eye movement desensitization and reprocessing in an adolescent with epilepsy and mild intellectual disability.

PubMed

Rodenburg, Roos; Benjamin, Anja; Meijer, Anne Marie; Jongeneel, Ruud

2009-09-01

Intellectual disability is a comorbid condition in epilepsy. People with epilepsy and intellectual disability are at high risk of developing behavioral problems. Among the many contributors to behavioral problems in people with epilepsy and intellectual disability are those of traumatic experiences. As such, behavioral problems can be seen as a reflection of these traumatic experiences. Among established trauma therapies, eye movement desensitization and reprocessing (EMDR) is an emerging treatment that is effective in adults and also seems to be effective in children. This article is a case report of EMDR in an adolescent with epilepsy and mild intellectual disability, in whom the EMDR children's protocol was used. The aim was to assess whether clinical trauma status significantly diminished to nonclinical status posttreatment. Change in trauma symptoms was evaluated with the Reliable Change Index (RCI). Results showed a significant decrease in trauma symptoms toward nonclinical status from pretreatment to posttreatment. EMDR consequences for epilepsy and intellectual disability are discussed.

[Depression and epilepsy : Two clinical pictures with common causes?].

PubMed

Borgmann, M; Holtkamp, M; Adli, M; Behr, J

2016-07-01

Epilepsy and depressive disorders show a high rate of comorbidity. Thus, neurobiological similarities and a bidirectional relationship in terms of pathogenesis have been suggested. The aim of this article is to present the common neurobiological features of both disorders, to characterize the bidirectional relationship and to provide an overview of therapeutic consequences. A review of the current literature and evaluation of studies on the topics of depression and epilepsy are presented. Epilepsy and depression share common neurobiological features. In epileptic patients depression should be diagnosed early and reliably as the successful treatment has a great influence on the prognosis, quality of life and suicide risk in these individuals. In therapeutic doses, antidepressive medication with noradrenergic and specific serotonergic antidepressants (NaSSA) or selective serotonin reuptake inhibitors (SSRI) imparts no clinically relevant epileptogenic potential; however, it increases the quality of life and could have anticonvulsant effects in patients with epilepsy. Clomipramine, bupropion and maprotiline, however, should not be administered to patients with epilepsy as they are known to lower the seizure threshold.

Third International Congress on Epilepsy, Brain, and Mind: Part 2.

PubMed

Rektor, Ivan; Schachter, Steven C; Arya, Ravindra; Arzy, Shahar; Braakman, Hilde; Brodie, Martin J; Brugger, Peter; Chang, Bernard S; Guekht, Alla; Hermann, Bruce; Hesdorffer, Dale C; Jones-Gotman, Marilyn; Kanner, Andres M; Garcia-Larrea, Luis; Mareš, Pavel; Mula, Marco; Neufeld, Miri; Risse, Gail L; Ryvlin, Philippe; Seeck, Margitta; Tomson, Torbjörn; Korczyn, Amos D

2015-09-01

Epilepsy is both a disease of the brain and the mind. Here, we present the second of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Humanistic, biologic, and therapeutic aspects of epilepsy, particularly those related to the mind, were discussed. The extended summaries provide current overviews of epilepsy, cognitive impairment, and treatment, including brain functional connectivity and functional organization; juvenile myoclonic epilepsy; cognitive problems in newly diagnosed epilepsy; SUDEP including studies on prevention and involvement of the serotoninergic system; aggression and antiepileptic drugs; body, mind, and brain, including pain, orientation, the "self-location", Gourmand syndrome, and obesity; euphoria, obsessions, and compulsions; and circumstantiality and psychiatric comorbidities. Copyright © 2015 Elsevier Inc. All rights reserved.

Physics of the Brain: Interaction of the Optical-Fiber-Guided Multi-Ultraviolet-Photon Beams with the Epilepsy Topion, (the Seizure Onset Area)

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

A novel method for the possible prevention of epileptic seizures is proposed, based on the multi-ultraviolet-photon beam interaction with the epilepsy topion, (nonlinear coupling of an ultra high frequency mode to the brain beta phonons). It is hypothesized that epilepsy is a chaotic-dynamics phenomenon: small electrical changes in the epilepsy-topion lead, (within the 10s of milliseconds), to the onset of chaos, (seizure--excessive electrical discharge), and subsequent cascading into adjacent areas. The ultraviolet photons may control the imbalance of sodium and potassium ions and, consequently, may prove to be efficient in the prevention of epileptic seizures. Supported by Nikola Tesla Labs, Stefan University.

The treatment of epilepsy in developing countries: where do we go from here?

PubMed Central

Scott, R. A.; Lhatoo, S. D.; Sander, J. W.

2001-01-01

Epilepsy is the most common serious neurological disorder and is one of the world's most prevalent noncommunicable diseases. As the understanding of its physical and social burden has increased it has moved higher up the world health agenda. Over four-fifths of the 50 million people with epilepsy are thought to be in developing countries; much of this condition results from preventable causes. Around 90% of people with epilepsy in developing countries are not receiving appropriate treatment. Consequently, people with epilepsy continue to be stigmatized and have a lower quality of life than people with other chronic illnesses. However, bridging the treatment gap and reducing the burden of epilepsy is not straightforward and faces many constraints. Cultural attitudes, a lack of prioritization, poor health system infrastructure, and inadequate supplies of antiepileptic drugs all conspire to hinder appropriate treatment. Nevertheless, there have been successful attempts to provide treatment, which have shown the importance of community-based approaches and also indicate that provision for sustained intervention over the long term is necessary in any treatment programme. Approaches being adopted in the demonstration projects of the Global Campaign Against Epilepsy--implemented by the International League Against Epilepsy, the International Bureau for Epilepsy, and the World Health Organization--may provide further advances. Much remains to be done but it is hoped that current efforts will lead to better treatment of people with epilepsy in developing countries. PMID:11357214

Patients' perception of epilepsy and threat to self-identity: a qualitative approach.

PubMed

Hosseini, Nazafarin; Sharif, Farkhondeh; Ahmadi, Fazlollah; Zare, Mohammad

2013-10-01

A clinical diagnosis of epilepsy often carries a silent social stigma and is associated with metaphysical forces. This qualitative study aimed to explore the Iranian patients' perception of epilepsy where clinical aspects are more benign than the social implications with long-term psychological consequences. Historically, epilepsy has been known as a form of insanity, madness, sorcery, and possession by evil spirits. Thirty participants consisting of 21 patients with epilepsy, 5 family members, and 4 medical staff were selected from urban and rural medical and health care centers, hospitals, physician offices, outpatient clinics, and the Iranian Epilepsy Association. Unstructured and semistructured interviews were applied to obtain data. Transcribed interviews and field notes were analyzed using qualitative content analysis method. Categories and subcategories emerged from the participants' perceptions of epilepsy and its disruptive effects on their self-identity. The main categories derived from data were 1) a different perspective about epilepsy, 2) self-debasement, and 3) being a burden. The major theme found in this study was "identity loss". Our study results highlight the importance of public awareness among community members and healthcare professionals on how patients with epilepsy experience their disease with psychosocial implications. Understanding patients' perspectives can be essential to developing a comprehensive and holistic care plan for patients with epilepsy and addressing their multidimensional needs. Copyright © 2013 Elsevier Inc. All rights reserved.

Executive function and health-related quality of life in pediatric epilepsy.

PubMed

Schraegle, William A; Titus, Jeffrey B

2016-09-01

Children and adolescents with epilepsy often show higher rates of executive functioning deficits and are at an increased risk of diminished health-related quality of life (HRQOL). The purpose of the current study was to determine the extent to which executive dysfunction predicts HRQOL in youth with epilepsy. Data included parental ratings on the Behavior Rating Inventory of Executive Function (BRIEF) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 130 children and adolescents with epilepsy (mean age=11years, 6months; SD=3years, 6months). Our results identified executive dysfunction in nearly half of the sample (49%). Moderate-to-large correlations were identified between the BRIEF and the QOLCE subscales of well-being, cognition, and behavior. The working memory subscale on the BRIEF emerged as the sole significant predictor of HRQOL. These results underscore the significant role of executive function in pediatric epilepsy. Proactive screening for executive dysfunction to identify those at risk of poor HRQOL is merited, and these results bring to question the potential role of behavioral interventions to improve HRQOL in pediatric epilepsy by specifically treating and/or accommodating for executive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Affective disorders and functional (non-epileptic) seizures in persons with epilepsy.

PubMed

Johnson, Keith A; Macfarlane, Matthew D; Looi, Jeffrey Cl

2016-12-01

This paper aims to describe the prevalence, assessment and management of affective disorders as well as functional (non-epileptic) seizures in people with epilepsy. This paper comprises a selective review of the literature of the common affective manifestations of epilepsy. Affective disorders are the most common psychiatric comorbidity seen in people with epilepsy and assessment and management parallels that of the general population. Additionally, people with epilepsy may experience higher rates of mood instability, irritability and euphoria, classified together as a group, interictal dysphoric disorder and resembling an unstable bipolar Type II disorder. Functional seizures present unique challenges in terms of identification of the disorder and a lack of specific management. Given their high prevalence, it is important to be able to recognise affective disorders in people with epilepsy. Management principles parallel those in the general population with specific caution exercised regarding the potential interactions between antidepressant medications and antiepileptic drugs. Functional seizures are more complex and require a coordinated approach involving neurologists, psychiatrists, general practitioners, nursing and allied health. There is very limited evidence to guide psychological and behavioural interventions for neurotic disorders in epilepsy and much more research is needed. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Epilepsy and the law--a view from Thailand.

PubMed

Locharernkul, Chaichon

2007-03-01

Patients with epilepsy often suffer social injustice in many societies. This is a review of current laws dealing with epilepsy and the consequences of this complex disease. The author looked at reported unjust legal and social acts resulting from epileptic seizures and their results. The author found that accusation of criminal acts, accidents while driving, and job loss are relatively common experiences for epileptics. Such events reflect lack of public understanding. There is inadequate legislation to protect epileptics. Most disturbing areas are ictal behavior misinterpreted as crime, driving while experiencing a seizure, and social discrimination. There is no law dealing with epilepsy in Thailand while considerable progress in this field has been made in Western countries. Epilepsy patients are inadequately protected by Thai law. There is an urgent need for education and campaigns for their rights focused on the public, the legal profession, and the health care professionals.

Metabolic and Homeostatic Changes in Seizures and Acquired Epilepsy—Mitochondria, Calcium Dynamics and Reactive Oxygen Species

PubMed Central

Kovac, Stjepana; Dinkova Kostova, Albena T.; Melzer, Nico; Meuth, Sven G.; Gorji, Ali

2017-01-01

Acquired epilepsies can arise as a consequence of brain injury and result in unprovoked seizures that emerge after a latent period of epileptogenesis. These epilepsies pose a major challenge to clinicians as they are present in the majority of patients seen in a common outpatient epilepsy clinic and are prone to pharmacoresistance, highlighting an unmet need for new treatment strategies. Metabolic and homeostatic changes are closely linked to seizures and epilepsy, although, surprisingly, no potential treatment targets to date have been translated into clinical practice. We summarize here the current knowledge about metabolic and homeostatic changes in seizures and acquired epilepsy, maintaining a particular focus on mitochondria, calcium dynamics, reactive oxygen species and key regulators of cellular metabolism such as the Nrf2 pathway. Finally, we highlight research gaps that will need to be addressed in the future which may help to translate these findings into clinical practice. PMID:28885567

Language and social functioning in children and adolescents with epilepsy.

PubMed

Byars, Anna W; deGrauw, Ton J; Johnson, Cynthia S; Perkins, Susan M; Fastenau, Philip S; Dunn, David W; Austin, Joan K

2014-02-01

Individuals with epilepsy have difficulties with social function that are not adequately accounted for by seizure severity or frequency. This study examined the relationship between language ability and social functioning in 193 children with epilepsy over a period of 36months following their first recognized seizure. The findings show that children with persistent seizures have poorer language function, even at the onset of their seizures, than do their healthy siblings, children with no recurrent seizures, and children with recurrent but not persistent seizures. They continue to demonstrate poorer language function 36months later. This poor language function is associated with declining social competence. Intervention aimed at improving social competence should include consideration of potential language deficits that accompany epilepsy and social difficulty. Copyright © 2013 Elsevier Inc. All rights reserved.

Knowledge, attitude and practice towards epilepsy among secondary school students in Enugu, southeast Nigeria.

PubMed

Ezeala-Adikaibe, B A; Achor, J U; Onwukwe, Jojo; Ekenze, O S; Onwuekwe, I O; Chukwu, O; Onyia, H; Ihekwaba, M; Obu, C

2013-05-01

The purpose of this study was to determine the knowledge and attitude of secondary school students to epilepsy and its treatment that could pose as barriers in the treatment and care of epilepsy patients within the community. This study was cross-sectional and descriptive in design using a self administered custom designed multiple choice questionnaire with sections on general information on epilepsy, awareness and perception of epilepsy, treatment of epilepsy/seizures and attitude towards people living with epilepsy. Out of 969 questionnaires analyzed, the majority of the students (87.6%) had heard of epilepsy as a disease. The commonest sources of information were the electronic media (36.4%) and family members (25.6%). More than half (59.4%) had witnessed a convulsion in the past and 8.9% had a family member with epilepsy. Jerking (50.6%) and loss of consciousness (47.4%) were identified as the commonest manifestations of epilepsy. Epilepsy was considered a psychiatric disorder by 51.9% and as an infectious disease by 40.6%. About 39.3% considered epilepsy to be due to spiritual causes, old age or poisoning/bad blood. A total of 63.1% regarded orthodox medicine and prayers as the best means to treat epilepsy, while 6.8% chose herbal remedies. Concerning first aid treatment, 50.6% agreed that an object should be inserted into the mouth, while 49.5% would call for medical help and 28.8% would remove the person from harm. On attitude, 64.9% would not keep a friend with epilepsy, 69.1% would not play with someone with epilepsy, 84.2% would not marry someone with epilepsy. 41.1% of the students said that people with epilepsy should neither marry while 42.2% say they should not have children. Only 39.1.5% had an overall positive attitude towards people living with epilepsy. There is a persisting poor knowledge, attitude and practice of epilepsy among secondary school students in SE Nigeria. Efforts should be made to include basic facts about disorders with social consequences such as epilepsy in school health education curriculum. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Pediatric Epilepsy: Neurology, Functional Imaging, and Neurosurgery.

PubMed

Mountz, James M; Patterson, Christina M; Tamber, Mandeep S

2017-03-01

In this chapter we provide a comprehensive review of the current role that functional imaging can have in the care of the pediatric epilepsy patient from the perspective of the epilepsy neurologist and the epilepsy neurosurgeon. In the neurology section, the diagnosis and classification of epilepsy adapted by the International League Against Epilepsy as well as the etiology and incidence of the disease is presented. The neuroimaging section describes how advanced nuclear medicine imaging methods can be synergized to provide a maximum opportunity to localize an epileptogenic focus. This section described the value of FDG-PET and regional cerebral blood flow SPECT in the identification of an epileptogenic focus. The imaging section also emphasizes the importance on developing a dedicated epilepsy management team, comprised of an epilepsy imaging specialist, epilepsy neurologist and epilepsy neurosurgeon, to provide the maximum benefit to each child with epilepsy. An emphasis is placed on preparation for ictal SPECT injection procedures, including the critical role of an automated injector well as the use of state-of-the-art dedicated nuclear medicine imaging and analysis protocols to correctly localize the epileptogenic focus location. In the final section, surgical options, approaches and expected outcomes for the different classes of epilepsy is presented. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive Function and Heat Shock Protein 70 in Children With Temporal Lobe Epilepsy.

PubMed

Oraby, Azza M; Raouf, Ehab R Abdol; El-Saied, Mostafa M; Abou-Khadra, Maha K; Helal, Suzette I; Hashish, Adel F

2017-01-01

We conducted the present study to examine cognitive function and serum heat shock protein 70 levels among children with temporal lobe epilepsy. The Stanford-Binet Intelligence Test was carried out to examine cognitive function in 30 children with temporal lobe epilepsy and 30 controls. Serum heat shock protein 70 levels were determined with an enzyme-linked immunosorbent assay. The epilepsy group had significantly lower cognitive function testing scores and significantly higher serum heat shock protein 70 levels than the control group; there were significant negative correlations between serum heat shock protein 70 levels and short-term memory and composite scores. Children with uncontrolled seizures had significantly lower verbal reasoning scores and significantly higher serum heat shock protein 70 levels than children with controlled seizures. Children with temporal lobe epilepsy have cognitive dysfunction and elevated levels of serum heat shock protein 70, which may be considered a stress biomarker.

Frequency and predictors of psychological distress after a diagnosis of epilepsy: A community-based study.

PubMed

Xu, Ying; Hackett, Maree L; Glozier, Nick; Nikpour, Armin; Bleasel, Andrew; Somerville, Ernest; Lawson, John; Jan, Stephen; Hyde, Lorne; Todd, Lisa; Martiniuk, Alexandra; Ireland, Carol; Anderson, Craig S

2017-10-01

The objective of the study was to determine the frequency and predictors of psychological distress after a diagnosis of epilepsy. The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) was a prospective, multicenter, community-based study of people of all ages with newly diagnosed epilepsy in Sydney, Australia. Analyses involved multivariate logistic regression and multinomial logit regression to identify predictors of psychological distress, assessed using the Hospital Anxiety and Depression Scale (HADS) and the Strengths and Difficulties Questionnaire (SDQ), as part of structured interviews. Psychological distress occurred in 33% (95% confidence interval [CI] 26 to 40%) and 24% (95% CI 18 to 31%) of 180 adults at baseline and 12months, respectively, and 23% (95% CI 14 to 33%) of 77 children at both time points. Thirty adults and 7 children had distress at baseline who recovered at 12months, while 15 adults and 7 children had new onset of distress during this period. History of psychiatric or behavioral disorder (for adults, odds ratio [OR] 6.82, 95% CI 3.08 to 15.10; for children, OR 28.85, 95% CI 2.88 to 288.60) and higher psychosocial disability (adults, OR 1.17, 95% CI 1.07 to 1.27) or lower family functioning (children, OR 1.80, 95% CI 1.08 to 3.02) were associated with psychological distress (C statistics 0.80 and 0.78). Psychological distress is common and fluctuates in frequency after a diagnosis of epilepsy. Those with premorbid psychological, psychosocial, and family problems are at high risk of this adverse outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

An explanation for sudden death in epilepsy (SUDEP).

PubMed

Stewart, Mark

2018-03-14

This review traces the examination of autonomic, cardiovascular, and respiratory derangements associated with seizure activity in the clinical and preclinical literature generally, and in the author's animal model specifically, and concludes with the author's views on the potential mechanisms for sudden death in epilepsy (SUDEP). An animal model that employs kainic acid-induced seizures on a background of urethane anesthesia has permitted unprecedented access to the behavior of autonomic, cardiovascular, and respiratory systems during seizure activity. The result is a detailed description of the major causes of death and how this animal model can be used to develop and test preventative and interventional strategies. A critical translational step was taken when the rat data were shown to directly parallel data from definite SUDEP cases in the clinical literature. The reasons why ventricular fibrillation as a cause of death is so rarely reported and tools for verifying that seizure-associated laryngospasm can induce obstructive apnea as a cause of death are discussed in detail. Many details of the specific kinetics of activation of brainstem neurons serving autonomic and respiratory function remain to be elucidated, but the boundary conditions described in this review provide an excellent framework for more focused studies. A number of studies conducted in animal models of seizure activity and in epilepsy patients have contributed information on the autonomic, cardiovascular, and respiratory consequences of seizure activity spreading through hypothalamus and brainstem to the periphery. The result is detailed information on the systemic impact of seizure spread and the development of an understanding of the essential mechanistic features of sudden unexpected death in epilepsy (SUDEP). This review summarizes translation of data obtained from animal models to biomarkers that are useful in evaluating data from epilepsy patients.

ILAE Classification of the Epilepsies Position Paper of the ILAE Commission for Classification and Terminology

PubMed Central

Scheffer, Ingrid E; Berkovic, Samuel; Capovilla, Giuseppe; Connolly, Mary B; French, Jacqueline; Guilhoto, Laura; Hirsch, Edouard; Jain, Satish; Mathern, Gary W.; Moshé, Solomon L; Nordli, Douglas R; Perucca, Emilio; Tomson, Torbjörn; Wiebe, Samuel; Zhang, Yue-Hua; Zuberi, Sameer M

2017-01-01

Summary The ILAE Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances which have taken place since the last ratified classification in 1989. As a critical tool for the practising clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies and communication around the world. The new classification originates from a draft document submitted for public comments in 2013 which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century. PMID:28276062

A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder.

PubMed

Fernández-Marmiesse, Ana; Kusumoto, Hirofumi; Rekarte, Saray; Roca, Iria; Zhang, Jin; Myers, Scott J; Traynelis, Stephen F; Couce, Mª Luz; Gutierrez-Solana, Luis; Yuan, Hongjie

2018-04-11

Mutations in the GRIN2A gene, which encodes the GluN2A (glutamate [NMDA] receptor subunit epsilon-1) subunit of the N-methyl-d-aspartate receptor, have been identified in patients with epilepsy-aphasia spectrum disorders, idiopathic focal epilepsies with centrotemporal spikes, and epileptic encephalopathies with severe developmental delay. However, thus far, mutations in this gene have not been associated with a nonepileptic neurodevelopmental disorder with dystonia. The objective of this study was to identify the disease-causing gene in 2 siblings with neurodevelopmental and movement disorders with no epileptiform abnormalities. The study method was targeted next-generation sequencing panel for neuropediatric disorders and subsequent electrophysiological studies. The 2 siblings carry a novel missense mutation in the GRIN2A gene (p.Ala643Asp) that was not detected in genomic DNA isolated from blood cells of their parents, suggesting that the mutation is the consequence of germinal mosaicism in 1 progenitor. In functional studies, the GluN2A-A643D mutation increased the potency of the agonists L-glutamate and glycine and decreased the potency of endogenous negative modulators, including protons, magnesium and zinc but reduced agonist-evoked peak current response in mammalian cells, suggesting that this mutation has a mixed effect on N-methyl-d-aspartate receptor function. De novo GRIN2A mutations can give rise to a neurodevelopmental and movement disorder without epilepsy. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

The role of executive functioning in memory performance in pediatric focal epilepsy.

PubMed

Sepeta, Leigh N; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D; Berl, Madison M

2017-02-01

Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η 2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η 2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η 2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Levetiracetam efficacy on frontal lobe dysfunctions and anger rumination in patients with epilepsy.

PubMed

Gul, Amara; Mehreen, Saima

2018-06-12

This study compared the frontal lobe functioning and anger rumination between patients with epilepsy and healthy individuals. The second objective was to examine the efficacy of levetiracetam therapy on frontal lobe dysfunctions and anger rumination in patients with epilepsy. Participants (50 patients with epilepsy and 50 healthy individuals) completed the Frontal Assessment Battery (FAB) and Anger Rumination Scale (ARS). The patients had two testing sessions: pre- and post-levetiracetam therapies. The results showed that patients with epilepsy had frontal lobe dysfunctions in contrast with healthy individuals. Patients with epilepsy had higher anger rumination than healthy individuals. Compared with baseline performance, frontal lobe dysfunctions and anger rumination were significantly reduced after three months of levetiracetam therapy in patients with epilepsy. It is concluded that levetiracetam therapy may be beneficial in improving frontal lobe functioning and anger rumination thought pattern in patients with epilepsy. However, further studies are required to confirm this evidence. Copyright © 2018 Elsevier Inc. All rights reserved.

Cognitive-behavioral screening in elderly patients with new-onset epilepsy before treatment.

PubMed

Witt, J-A; Werhahn, K J; Krämer, G; Ruckes, C; Trinka, E; Helmstaedter, C

2014-09-01

Cognitive comorbidity at epilepsy onset reflects disease severity and provides a baseline estimate of reserve capacities with regard to the effects of epilepsy and its treatment. Given the high incidence of epilepsy at an older age, this study analyzed objective and subjective cognition as well as quality of life in elderly patients with new-onset focal epilepsy before initiation of anti-epileptic treatment. A total of 257 untreated patients (60-95 years of age) with new-onset epilepsy underwent objective assessment of executive function (EpiTrack) and performed subjective ratings of cognition (Portland Neurotoxicity Scale) and quality of life (QoL; QOLIE-31). According to age-corrected norms, 58% of patients (N=257) demonstrated deficits in executive function; major determinants were cerebrovascular etiology, neurological comorbidity, and higher body mass index. Subjective ratings indicated deficits in up to 27% of patients. Self-perceived deficits were associated with neurological, cardiovascular, and/or psychiatric comorbidity, whereas poorer QoL was related to neurological comorbidity and female gender. Objectively assessed executive functions correlated with subjective social functioning, energy, motor function, and vigilance. We found a relatively high QoL, a low rate of subjective impairment, but a high incidence of objective executive deficits in untreated elderly patients with new-onset epilepsy. Neurological status and body mass index, rather than seizure frequency or severity, were risk factors for cognitive impairment. Given the relevance of cognition in the course of epilepsy and its treatment, routine screening before treatment initiation is highly recommended. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of executive functioning in memory performance in pediatric focal epilepsy

PubMed Central

Sepeta, Leigh N.; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D.; Berl, Madison M.

2016-01-01

Objective Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Methods Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (WASI/DAS), as well as visual (CMS Dot Locations) and verbal episodic memory (WRAML Story Memory and CVLT-C). Executive functioning was measured directly (WISC-IV Digit Span Backward; CELF-IV Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function (BRIEF)). Results Children with focal epilepsy had lower delayed free recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = .12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = .03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = .08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9–19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9–10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extra-temporal, frontal vs. extra-frontal). Significance Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. PMID:28111742

Management of refractory epilepsy.

PubMed

Muñana, Karen R

2013-05-01

The term refractory epilepsy is utilized in veterinary medicine to describe a condition in which an animal with epilepsy fails to attain satisfactory seizure control or suffers intolerable side effects despite appropriate therapy with conventional antiepileptic drugs. Refractory epilepsy is an important problem in small animal practice as it occurs in approximately one-third of dogs with epilepsy. Consequently, there is much interest in identifying ways to more effectively treat this population of animals. More than a dozen new antiepileptic drugs have been approved for humans over the last 2 decades, and several of these drugs, including gabapentin, zonisamide, levetiracetam, and pregabalin, have been evaluated for the treatment of refractory seizures in veterinary patients. Nonmedical methods to treat poorly controlled epilepsy are also being explored. The 2 alternative forms of therapy that have shown the most promise in humans with epilepsy are electrical stimulation of the brain and dietary modification, both of which have also been evaluated in dogs. This overview summarizes the available data on pharmacologic as well as nonmedical treatment options for dogs and cats with refractory epilepsy. Although many forms of therapy are currently being utilized in clinical practice, our knowledge of the safety and efficacy of these treatments is limited. Additional randomized controlled trials are needed to better evaluate these novel therapies for refractory epilepsy in dogs and cats. © 2013 Elsevier Inc. All rights reserved.

A novel mouse model for sudden unexpected death in epilepsy (SUDEP): role of impaired adenosine clearance.

PubMed

Shen, Hai-Ying; Li, Tianfu; Boison, Detlev

2010-03-01

Sudden unexpected death in epilepsy (SUDEP) is a significant cause of mortality in people with epilepsy. Two postulated causes for SUDEP, cardiac and respiratory depression, can both be explained by overstimulation of adenosine receptors. We hypothesized that SUDEP is a consequence of a surge in adenosine as a result of prolonged seizures combined with deficient adenosine clearance; consequently, blockade of adenosine receptors should prevent SUDEP. Here we induced impaired adenosine clearance in adult mice by pharmacologic inhibition of the adenosine-removing enzymes, adenosine kinase and deaminase. Combination of impaired adenosine clearance with kainic acid-induced seizures triggered sudden death in all animals. Most importantly, the adenosine receptor antagonist caffeine, when given after seizure onset, increased survival from 23.75 +/- 1.35 min to 54.86 +/- 6.59 min (p < 0.01). Our data indicate that SUDEP is due to overactivation of adenosine receptors and that caffeine treatment after seizure onset might be beneficial.

Partial monosomy Xq(Xq23 --> qter) and trisomy 4p(4p15.33 --> pter) in a woman with intractable focal epilepsy, borderline intellectual functioning, and dysmorphic features.

PubMed

Bartocci, Arnaldo; Striano, Pasquale; Mancardi, Maria Margherita; Fichera, Marco; Castiglia, Lucia; Galesi, Ornella; Michelucci, Roberto; Elia, Maurizio

2008-06-01

Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.

Effects of Epilepsy on Language Functions: Scoping Review and Data Mining Findings.

PubMed

Dutta, Manaswita; Murray, Laura; Miller, Wendy; Groves, Doyle

2018-03-01

This study involved a scoping review to identify possible gaps in the empirical description of language functioning in epilepsy in adults. With access to social network data, data mining was used to determine if individuals with epilepsy are expressing language-related concerns. For the scoping review, scientific databases were explored to identify pertinent articles. Findings regarding the nature of epilepsy etiologies, patient characteristics, tested language modalities, and language measures were compiled. Data mining focused on social network databases to obtain a set of relevant language-related posts. The search yielded 66 articles. Epilepsy etiologies except temporal lobe epilepsy and older adults were underrepresented. Most studies utilized aphasia tests and primarily assessed single-word productions; few studies included healthy control groups. Data mining revealed several posts regarding epilepsy-related language problems, including word retrieval, reading, writing, verbal memory difficulties, and negative effects of epilepsy treatment on language. Our findings underscore the need for future specification of the integrity of language in epilepsy, particularly with respect to discourse and high-level language abilities. Increased awareness of epilepsy-related language issues and understanding the patients' perspectives about their language concerns will allow researchers and speech-language pathologists to utilize appropriate assessments and improve quality of care.

[Ecological executive function characteristics and effects of executive function on social adaptive function in school-aged children with epilepsy].

PubMed

Xu, X J; Wang, L L; Zhou, N

2016-02-23

To explore the characteristics of ecological executive function in school-aged children with idiopathic or probably symptomatic epilepsy and examine the effects of executive function on social adaptive function. A total of 51 school-aged children with idiopathic or probably symptomatic epilepsy aged 5-12 years at our hospital and 37 normal ones of the same gender, age and educational level were included. The differences in ecological executive function and social adaptive function were compared between the two groups with the Behavior Rating Inventory of Executive Function (BRIEF) and Child Adaptive Behavior Scale, the Pearson's correlation test and multiple stepwise linear regression were used to explore the impact of executive function on social adaptive function. The scores of school-aged children with idiopathic or probably symptomatic epilepsy in global executive composite (GEC), behavioral regulation index (BRI) and metacognition index (MI) of BRIEF ((62±12), (58±13) and (63±12), respectively) were significantly higher than those of the control group ((47±7), (44±6) and (48±8), respectively))(P<0.01). The scores of school-aged children with idiopathic or probably symptomatic epilepsy in adaptive behavior quotient (ADQ), independence, cognition, self-control ((86±22), (32±17), (49±14), (41±16), respectively) were significantly lower than those of the control group ((120±12), (59±14), (59±7) and (68±10), respectively))(P<0.01). Pearson's correlation test showed that the scores of BRIEF, such as GEC, BRI, MI, inhibition, emotional control, monitoring, initiation and working memory had significantly negative correlations with the score of ADQ, independence, self-control ((r=-0.313--0.741, P<0.05)). Also, GEC, inhibition, MI, initiation, working memory, plan, organization and monitoring had significantly negative correlations with the score of cognition ((r=-0.335--0.437, P<0.05)); Multiple stepwise linear regression analysis showed that BRI, inhibition and working memory were closely related with the social adaptive function of school-aged children with idiopathic or probably symptomatic epilepsy. School-aged children with idiopathic or probably symptomatic epilepsy may have significantly ecological executive function impairment and social adaptive function reduction. The aspects of BRI, inhibition and working memory in ecological executive function are significantly related with social adaptive function in school-aged children with epilepsy.

Validation of the Neuro-QoL Measurement System in Children with Epilepsy

PubMed Central

Lai, Jin-Shei; Nowinski, Cindy J.; Zelko, Frank; Wortman, Katy; Burns, James; Nordli, Douglas R.; Cella, David

2015-01-01

OBJECTIVE Children with epilepsy often face complex psychosocial consequences that are not fully captured by existing patient-reported outcome (PRO) measures. The Neurology Quality of Life Measurement System “Neuro-QoL” was developed to provide a set of common PRO measures that address issues important to people with neurologic disorders. This paper reports Neuro-QoL (Anxiety, Depression, Interaction with peers, Fatigue, Pain, Cognition, Stigma, and Upper and Lower Extremity Function) validation in children with epilepsy. METHOD Patients (aged 10–18 years) diagnosed with epilepsy completed Neuro-QoL and legacy measures at time-1 and 6-month follow-up. Internal consistency reliability was also evaluated. Concurrent validity was assessed by comparing Neuro-QoL measures with more established “legacy” measures of the same concepts. Clinical validity was evaluated by comparing mean Neuro-QoL scores of patients grouped by clinical anchors such as disease severity. Responsiveness of the Neuro-QoL from time-1 to 6-month was evaluated using self-reported change as the primary anchor. RESULTS 61 patients (mean age=13.4 years; 62.3% male, 75.9% white) participated. Most patients (64.2%) had been seizure free in the 3 months prior to participation, and seizure frequency was otherwise described as follows: 17.8% daily, 13.3% weekly, 35.6% monthly and 33.3% yearly. All patients were taking anti-epileptic drugs. Patients reported better function/less symptoms compared to the reference groups. Internal consistency (alpha) coefficients ranged from 0.76 – 0.87. Patients with different seizure frequency differed on Anxiety (p<.01) and Cognition (p<.05). Compared to patients on polytherapy, those on monotherapy had better Upper Extremity scores (p<.05). Compared to those with localized seizures, those experiencing generalized seizures reported worse stigma (p<.05). Depression, Anxiety, Lower Extremity, Fatigue, Pain, Interaction with peers, and Stigma also significantly discriminated patients with different levels of quality of life, p<=.05. All Neuro-QoL measures were significantly correlated with other measures assessing similar domains. Stigma was related to self-reported change in several areas of functioning, but in sometimes unexpected directions. SIGNIFICANCE Neuro-QoL is a valid and reliable assessment tool for children with epilepsy and can be used in research and clinical settings. PMID:25862469

Depression in patients with epilepsy in Northwestern Nigeria: Prevalence and clinical correlates

PubMed Central

Owolabi, Shakirah Desola; Owolabi, Lukman Femi; Udofia, Owoidoho; Sale, Shehu

2016-01-01

Background: The impact of seizure disorder on people living with epilepsy (PWE) is worsened by the occurrence of comorbid psychiatric disorders, such as depression, which have been found commonly in PWE. Despite the dire consequences comorbid depression has on PWE, it still remains underdiagnosed and undertreated. Objective: To determine the prevalence of depression and associated clinical factors in PWE in Northwestern Nigeria. Materials and Methods: A total of 255 consecutive patients with epilepsy aged 18 years and above, from two health facilities, were recruited in this cross-sectional study. Following completion of a structured proforma detailing sociodemographic and seizure characteristics, Mini International Neuropsychiatric Interview was administered to diagnose depression in the patients. Results: A total of 255 patients, with a mean age of 32 years (standard deviation = 1.31), comprising 147 (57.6%) males and 108 (42.4%) females were studied. Majority (79.2%) of the patients had primarily generalized seizure type. Overall, depressive disorder was present in 52 (20.4%) patients. A significant association was found between previous hospitalization for epilepsy (P = 0.009), increased frequency of seizures, (P = 0.004), and prolonged duration of epilepsy, (P = 0.006). The independent predictors of depression included duration of epilepsy (P = 0.0001), previous hospitalization for epilepsy (P = 0.011), and frequency of seizures (P = 0.028). Conclusion: Depression was common in PWE. Female gender, previous hospitalization for epilepsy, increased frequency of seizures and prolonged duration of epilepsy were associated with depression in PWE. Previous hospitalization for epilepsy, increased frequency of seizures, and prolonged duration of epilepsy were independent predictors of depression. PMID:27853032

Depression in patients with epilepsy in Northwestern Nigeria: Prevalence and clinical correlates.

PubMed

Owolabi, Shakirah Desola; Owolabi, Lukman Femi; Udofia, Owoidoho; Sale, Shehu

2016-01-01

The impact of seizure disorder on people living with epilepsy (PWE) is worsened by the occurrence of comorbid psychiatric disorders, such as depression, which have been found commonly in PWE. Despite the dire consequences comorbid depression has on PWE, it still remains underdiagnosed and undertreated. To determine the prevalence of depression and associated clinical factors in PWE in Northwestern Nigeria. A total of 255 consecutive patients with epilepsy aged 18 years and above, from two health facilities, were recruited in this cross-sectional study. Following completion of a structured proforma detailing sociodemographic and seizure characteristics, Mini International Neuropsychiatric Interview was administered to diagnose depression in the patients. A total of 255 patients, with a mean age of 32 years (standard deviation = 1.31), comprising 147 (57.6%) males and 108 (42.4%) females were studied. Majority (79.2%) of the patients had primarily generalized seizure type. Overall, depressive disorder was present in 52 (20.4%) patients. A significant association was found between previous hospitalization for epilepsy (P = 0.009), increased frequency of seizures, (P = 0.004), and prolonged duration of epilepsy, (P = 0.006). The independent predictors of depression included duration of epilepsy (P = 0.0001), previous hospitalization for epilepsy (P = 0.011), and frequency of seizures (P = 0.028). Depression was common in PWE. Female gender, previous hospitalization for epilepsy, increased frequency of seizures and prolonged duration of epilepsy were associated with depression in PWE. Previous hospitalization for epilepsy, increased frequency of seizures, and prolonged duration of epilepsy were independent predictors of depression.

Epilepsy, language, and social skills.

PubMed

Caplan, Rochelle

2017-10-04

Language and social skills are essential for intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of individuals' functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important theoretical and clinical implications. This review first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It reviews the findings of studies of social skills and the few studies conducted on the inter-relationship of language and social skills in pediatric and adult epilepsy. The paper concludes with suggested future research and clinical directions that will enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills. Copyright © 2017 Elsevier Inc. All rights reserved.

The human epilepsy mutation GABRG2(Q390X) causes chronic subunit accumulation and neurodegeneration.

PubMed

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

2015-07-01

Genetic epilepsy and neurodegenerative diseases are two common neurological disorders that are conventionally viewed as being unrelated. A subset of patients with severe genetic epilepsies who have impaired development and often go on to die of their disease respond poorly to anticonvulsant drug therapy, suggesting a need for new therapeutic targets. Previously, we reported that multiple GABAA receptor epilepsy mutations result in protein misfolding and abnormal receptor trafficking. We have now developed a model of a severe human genetic epileptic encephalopathy, the Gabrg2(+/Q390X) knock-in mouse. We found 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 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. Our results have far-reaching relevance for the identification of conserved pathological cascades and mechanism-based therapies that are shared between genetic epilepsies and neurodegenerative diseases.

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

Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy.

PubMed

Wei, Feng; Yan, Li-Min; Su, Tao; He, Na; Lin, Zhi-Jian; Wang, Jie; Shi, Yi-Wu; Yi, Yong-Hong; Liao, Wei-Ping

2017-08-01

Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

Clinical and Surgical Factors Associated With Increased Epilepsy Risk in Children With Hydrocephalus.

PubMed

Tully, Hannah M; Kukull, Walter A; Mueller, Beth A

2016-06-01

Children with hydrocephalus are at risk for epilepsy both due to their underlying condition and as a consequence of surgical treatment; however, the relative contributions of these factors remain unknown. The authors sought to characterize epilepsy among children with infancy-onset hydrocephalus and to examine the risks of epilepsy associated with hydrocephalus subtype and with factors related to surgical treatment. We conducted a longitudinal cohort study of all children with infancy-onset hydrocephalus treated at a major regional children's hospital during 2002 to 2012, with follow-up to ascertain risk factors and epilepsy outcome through April 2015. Poisson regression was used to calculate adjusted risk ratios and 95% confidence intervals for associations. Among 379 children with hydrocephalus, 86 (23%) developed epilepsy (mean onset age = 2.7 years), almost one fifth of whom had a history of infantile spasms. Relative to spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes had fourfold higher risks of developing epilepsy. Among children who underwent surgery, surgical infection doubled the risk of epilepsy (risk ratio = 2.0, 95% confidence interval = 1.4 to 3.0). Epilepsy was associated with surgical failure for intracranial reasons but not extracranial reasons (risk ratio = 1.7, 95% confidence interval = 1.1 to 2.7; risk ratio = 1.1, 95% confidence interval = 0.7 to 1.9, respectively). Epilepsy is common among children with hydrocephalus. Compared with children with spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes have a markedly increased risk of epilepsy. Surgical infection doubles the risk of epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of fMRI in the decision-making process: epilepsy surgery for children.

PubMed

Liégeois, Frédérique; Cross, J Helen; Gadian, David G; Connelly, Alan

2006-06-01

Functional MRI (fMRI) is increasingly being used to evaluate children and adolescents who are candidates for surgical treatment of intractable epilepsy. It has the advantage of being noninvasive and well tolerated by young people. By identifying important functional regions within the brain, including unpredictable patterns of functional reorganization, it can aid in surgical decision-making. Here we illustrate this using a number of case studies from the pediatric epilepsy surgery program at our institution. We describe how fMRI, used in conjunction with conventional investigative methods such as neuropsychological assessment, MRI, and electrophysiology, can 1) help to improve functional outcome by enabling resective surgery that spares functional cortex, 2) guide surgical intervention by revealing when reorganization of function has occurred, and 3) show when abnormal cortex is also functionally active, and hence that surgery may not be the best option. Altogether, these roles have reduced the need for invasive procedures that can be both risky and distressing for young people with epilepsy. In our experience, fMRI has significantly contributed to the decision-making process, and improved the counseling and management of young people with intractable epilepsy. Copyright 2006 Wiley-Liss, Inc.

Disrupted intrinsic and remote functional connectivity in heterotopia-related epilepsy.

PubMed

Liu, W; Hu, X; An, D; Gong, Q; Zhou, D

2018-01-01

Several neuroimaging studies have examined neural interactions in patients with periventricular nodular heterotopia (PNH). However, features of the underlying functional network remain poorly understood. In this study, we examined alterations in the local (regional) and remote (interregional) cerebral networks in this disorder. Twenty-eight subjects all having suffered from PNH with epilepsy, as well as 28 age- and sex- matched healthy controls, were enrolled in this study. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were calculated to detect regional neural function and functional network integration, respectively. Compared with healthy controls, patients with PNH-related epilepsy showed decreased ALFF in the ventromedial prefrontal cortex (vmPFC) and precuneus areas. ALFF values in both areas were negative correlated with epilepsy duration (P < .05, Bonferroni-corrected). Furthermore, patients with PNH-related epilepsy had increased remote interregional FC mainly in bilateral prefrontal and parietal cortices, supramarginal gyrus, dorsal cingulate gyrus, and right insula; lower FC was found in posterior brain regions including bilateral parahippocampal gyrus and inferior temporal gyrus. Focal spontaneous hypofunction, as assessed by ALFF, correlates with epilepsy duration in patients with PNH-related epilepsy. Abnormalities existed both within the default-mode network and then across the whole brain, demonstrating that intrinsic brain dysfunction may be related to specific network interactions. Our findings provide novel understanding of the connectivity-based pathophysiological mechanisms of PNH. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cognitive consequences of early versus late antiepileptic drug withdrawal after pediatric epilepsy surgery, the TimeToStop (TTS) trial: study protocol for a randomized controlled trial.

PubMed

Boshuisen, Kim; Lamberink, Herm J; van Schooneveld, Monique Mj; Cross, J Helen; Arzimanoglou, Alexis; van der Tweel, Ingeborg; Geleijns, Karin; Uiterwaal, Cuno Spm; Braun, Kees Pj

2015-10-26

The goals of intentional curative pediatric epilepsy surgery are to achieve seizure-freedom and antiepileptic drug (AED) freedom. Retrospective cohort studies have indicated that early postoperative AED withdrawal unmasks incomplete surgical success and AED dependency sooner, but not at the cost of long-term seizure outcome. Moreover, AED withdrawal seemed to improve cognitive outcome. A randomized trial is needed to confirm these findings. We hypothesized that early AED withdrawal in children is not only safe, but also beneficial with respect to cognitive functioning. This is a multi-center pragmatic randomized clinical trial to investigate whether early AED withdrawal improves cognitive function, in terms of attention, executive function and intelligence, quality of life and behavior, and to confirm safety in terms of eventual seizure freedom, seizure recurrences and "seizure and AED freedom." Patients will be randomly allocated in parallel groups (1:1) to either early or late AED withdrawal. Randomization will be concealed and stratified for preoperative IQ and medical center. In the early withdrawal arm reduction of AEDs will start 4 months after surgery, while in the late withdrawal arm reduction starts 12 months after surgery, with intended complete cessation of drugs after 12 and 20 months respectively. Cognitive outcome measurements will be performed preoperatively, and at 1 and 2 years following surgery, and consist of assessment of attention and executive functioning using the EpiTrack Junior test and intelligence expressed as IQ (Wechsler Intelligence Scales). Seizure outcomes will be assessed at 24 months after surgery, and at 20 months following start of AED reduction. We aim to randomize 180 patients who underwent anticipated curative epilepsy surgery below 16 years of age, were able to perform the EpiTrack Junior test preoperatively, and have no predictors of poor postoperative seizure prognosis (multifocal magnetic resonance imaging (MRI) abnormalities, incomplete resection of the lesion, epileptic postoperative electroencephalogram (EEG) abnormalities, or more than three AEDs at the time of surgery). Growing experience with epilepsy surgery has changed the view towards postoperative medication policy. In a European collaboration, we designed a multi-center pragmatic randomized clinical trial comparing early with late AED withdrawal to investigate benefits and safety of early AED withdrawal. The TTS trial is supported by the Dutch Epilepsy Fund (NL 08-10) ISRCTN88423240/ 08/05/2013.

Self-concept in children and adolescents with epilepsy: The role of family functioning, mothers' emotional symptoms and ADHD.

PubMed

Ekinci, Ozalp; Isik, Uğur; Gunes, Serkan; Yildirim, Canan; Killi, Yunus; Guler, Gülen

2016-09-01

This study aimed to identify the associated factors of poor self-concept in children and adolescents with epilepsy. Fifty-three patients with uncomplicated epilepsy (aged 7-18years) and 28 healthy controls were included. Study measures included the Piers-Harris 2 Self-Concept Scale, Family Assessment Device (FAD), Turgay DSM-IV based ADHD rating Scale (T-DSM-IV-S), Conners' Teacher Rating Scale (CTRS-R), Beck Depression Inventory and State-Trait Anxiety Inventory (STAI). Neurology clinic charts were reviewed for the epilepsy-related variables. While the Piers-Harris 2 total score was not significantly different between the groups, patients with epilepsy had lower (poorer) scores on freedom from anxiety and popularity subscales. Linear regression analysis revealed that the problem solving, affective responsiveness, general functioning and communication scores of FAD; total and inattentiveness scores of T-DSM-IV-S and mothers' Beck scores were associated with the total score of Piers-Harris 2. Epilepsy-related factors were not found to be associated with self-concept scores. Poor self-concept in children with epilepsy is associated with negative family functioning, mothers' emotional symptoms and ADHD, especially the symptoms of inattentiveness. Copyright © 2016. Published by Elsevier B.V.

Functional network changes in the hippocampus contribute to depressive symptoms in epilepsy.

PubMed

Peng, Weifeng; Mao, Lingyan; Yin, Dazhi; Sun, Wei; Wang, He; Zhang, Qianqian; Wang, Jing; Chen, Caizhong; Zeng, Mengsu; Ding, Jing; Wang, Xin

2018-06-01

Our study aimed to investigate the functional connectivity (FC) between the hippocampus and other brain regions in epilepsy patients with depressive symptoms. Epilepsy patients with and without depressive symptoms, assessed using the 17-item Hamilton Depression Rating Scale scores, were enrolled. Healthy volunteers were recruited as the control group. Resting state functional magnetic resonance imaging was performed, and the data were processed using Resting-State fMRI (DPARSFA2.0) software. The regional homogeneity (ReHo) values and the FC between the right hippocampus and other brain regions were analysed. The ReHo value of the cerebellum (particularly the left cerebellar hemisphere) was significantly lower in epilepsy patients than in healthy controls, and was lower in epilepsy patients with depressive symptoms (EP + DS group) than in those without depressive symptoms (EP-DS group, p < 0.05). Additionally, the FC between the right hippocampus and the bilateral cerebellum was significantly greater in the EP + DS group than in the EP-DS group (p < 0.05). Moreover, abnormal ReHo values in the bilateral frontal lobes, including the right anterior cingulate cortex, and changes in the FC between the right hippocampus and the bilateral frontal lobes were found in the EP + DS group. Minor changes in the FC between the temporal and parietal lobes were also found in the epilepsy patients. The functional right hippocampus-cerebellum circuit might contribute to the pathogenesis of depressive symptoms in epilepsy, with the exception of brain areas associated with emotion such as the frontal and temporal lobes. Modulating the hippocampus-cerebellum circuit is a potential therapeutic strategy for epilepsy patients with depressive symptoms. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Neuroimaging in epilepsy.

PubMed

Sidhu, Meneka Kaur; Duncan, John S; Sander, Josemir W

2018-05-17

Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques. Statistical analysis of PET and single photon emission computer tomography (STATISCOM) are superior to qualitative analysis alone in identifying focal abnormalities in MRI-negative patients. These methods have also been used to study mechanisms of epileptogenesis and pharmacoresistance.Recent language fMRI studies aim to localize, and also lateralize language functions. Memory fMRI has been recommended to lateralize mnemonic function and predict outcome after surgery in temporal lobe epilepsy. Combinations of structural, functional and post-processing methods have been used in multimodal and machine learning models to improve the identification of the seizure onset zone and increase understanding of mechanisms underlying structural and functional aberrations in epilepsy.

The neurobiology of cognitive disorders in temporal lobe epilepsy

PubMed Central

Bell, Brian; Lin, Jack J.; Seidenberg, Michael; Hermann, Bruce

2013-01-01

Cognitive impairment and especially memory disruption is a major complicating feature of the epilepsies. In this review we begin with a focus on the problem of memory impairment in temporal lobe epilepsy. We start with a brief overview of the early development of knowledge regarding the anatomic substrates of memory disorder in temporal lobe epilepsy, followed by discussion of the refinement of that knowledge over time as informed by the outcomes of epilepsy surgery (anterior temporal lobectomy) and the clinical efforts to predict those patients at greatest risk of adverse cognitive outcomes following epilepsy surgery. These efforts also yielded new theoretical insights regarding the function of the human hippocampus and a few examples of these insights are touched on briefly. Finally, the vastly changing view of temporal lobe epilepsy is examined including findings demonstrating that anatomic abnormalities extend far outside the temporal lobe, cognitive impairments extend beyond memory function, with linkage of these distributed cognitive and anatomic abnormalities pointing to a new understanding of the anatomic architecture of cognitive impairment in epilepsy. Challenges remain in understanding the origin of these cognitive and anatomic abnormalities, their progression over time, and most importantly, how to intervene to protect cognitive and brain health in epilepsy. PMID:21304484

Family and sexual life in people with epilepsy.

PubMed

Mameniškienė, Rūta; Guk, Jevgenija; Jatužis, Dalius

2017-01-01

Having epilepsy is much more than having seizures. Epilepsy can have a severe negative effect on quality of life, affecting social relationships, academic achievement, housing, employment, and the ability to live and function independently. We undertook a cross-sectional study in a tertiary epilepsy center in Lithuania, aiming to assess the influence of epilepsy and aspects relating to epilepsy (employment, stigma, anxiety) on patients and their families, and to estimate their quality of family life and sexual functioning. We asked patients to complete a questionnaire about their socio-demographic situation, their seizure types and antiepileptic medications, and their quality of family and sexual life. Our results confirmed that epilepsy seriously influences family life. One third of our patients are lonely and half are childless. Epilepsy leads to difficulty in finding a job, especially for men, and unemployment affects their status in the family. People with epilepsy are uncomfortable interacting with those of the opposite sex and tend to conceal their medical condition from their partner. One third have sexual dysfunction, yet only a quarter of them seek professional help. There is a clear need to improve self-confidence and to reduce social stigma in people with epilepsy, and to encourage them to discuss their problems with specialists. Copyright © 2016 Elsevier Inc. All rights reserved.

Accommodating Students with Epilepsy or Seizure Disorders: Effective Strategies for Teachers

ERIC Educational Resources Information Center

Hart Barnett, Juliet E.; Gay, Catherine

2015-01-01

The most common chronic neurological condition in children is epilepsy. Because it often occurs in childhood, epilepsy is likely the most common neurological condition encountered by school professionals including teachers. Given the impact that epilepsy can have on academic functioning and specifically on the day-to-day performance of a student…

[Epilepsy, cognition and ketogenic diet].

PubMed

Garcia-Penas, J J

2018-03-01

Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

PubMed Central

Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

2014-01-01

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy. PMID:25001494

Validation of the PedsQL Epilepsy Module: A pediatric epilepsy-specific health-related quality of life measure.

PubMed

Modi, Avani C; Junger, Katherine F; Mara, Constance A; Kellermann, Tanja; Barrett, Lauren; Wagner, Janelle; Mucci, Grace A; Bailey, Laurie; Almane, Dace; Guilfoyle, Shanna M; Urso, Lauryn; Hater, Brooke; Hustzi, Heather; Smith, Gigi; Herrmann, Bruce; Perry, M Scott; Zupanc, Mary; Varni, James W

2017-11-01

To validate a brief and reliable epilepsy-specific, health-related quality of life (HRQOL) measure in children with various seizure types, treatments, and demographic characteristics. This national validation study was conducted across five epilepsy centers in the United States. Youth 5-18 years and caregivers of youth 2-18 years diagnosed with epilepsy completed the PedsQL Epilepsy Module and additional questionnaires to establish reliability and validity of the epilepsy-specific HRQOL instrument. Demographic and medical data were collected through chart reviews. Factor analysis was conducted, and internal consistency (Cronbach's alphas), test-retest reliability, and construct validity were assessed. Questionnaires were analyzed from 430 children with epilepsy (M age = 9.9 years; range 2-18 years; 46% female; 62% white: non-Hispanic; 76% monotherapy, 54% active seizures) and their caregivers. The final PedsQL Epilepsy Module is a 29-item measure with five subscales (i.e., Impact, Cognitive, Sleep, Executive Functioning, and Mood/Behavior) with parallel child and caregiver reports. Internal consistency coefficients ranged from 0.70-0.94. Construct validity and convergence was demonstrated in several ways, including strong relationships with seizure outcomes, antiepileptic drug (AED) side effects, and well-established measures of executive, cognitive, and emotional/behavioral functioning. The PedsQL Epilepsy Module is a reliable measure of HRQOL with strong evidence of its validity across the epilepsy spectrum in both clinical and research settings. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Hyperventilation revisited: physiological effects and efficacy on focal seizure activation in the era of video-EEG monitoring.

PubMed

Guaranha, Mirian S B; Garzon, Eliana; Buchpiguel, Carlos A; Tazima, Sérgio; Yacubian, Elza M T; Sakamoto, Américo C

2005-01-01

Hyperventilation is an activation method that provokes physiological slowing of brain rhythms, interictal discharges, and seizures, especially in generalized idiopathic epilepsies. In this study we assessed its effectiveness in inducing focal seizures during video-EEG monitoring. We analyzed the effects of hyperventilation (HV) during video-EEG monitoring (video-EEG) of patients with medically intractable focal epilepsies. We excluded children younger than 10 years, mentally retarded patients, and individuals with frequent seizures. We analyzed 97 patients; 24 had positive seizure activation (PSA), and 73 had negative seizure activation (NSA). No differences were found between groups regarding sex, age, age at epilepsy onset, duration of epilepsy, frequency of seizures, and etiology. Temporal lobe epilepsies were significantly more activated than frontal lobe epilepsies. Spontaneous and activated seizures did not differ in terms of their clinical characteristics, and the activation did not affect the performance of ictal single-photon emission computed tomography (SPECT). HV is a safe and effective method of seizure activation during monitoring. It does not modify any of the characteristics of the seizures and allows the obtaining of valuable ictal SPECTs. This observation is clinically relevant and suggests the effectiveness and the potential of HV in shortening the presurgical evaluation, especially of temporal lobe epilepsy patients, consequently reducing its costs and increasing the number of candidates for epilepsy surgery.

Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy.

PubMed

Reddy, Doodipala Samba

2016-01-01

Catamenial epilepsy is a type of refractory epilepsy characterized by seizure clusters around perimenstrual or periovulatory period. The pathophysiology of catamenial epilepsy still remains unclear, yet there are few animal models to study this gender-specific disorder. The pathophysiology of perimenstrual catamenial epilepsy involves the withdrawal of the progesterone-derived GABAergic neurosteroids due to the decline in progesterone level at the time of menstruation. These manifestations can be faithfully reproduced in rodents by specific neuroendocrine manipulations. Since mice and rats, like humans, have ovarian cycles with circulating hormones, they appear to be suitable animal models for studies of perimenstrual seizures. Recently, we created specific experimental models to mimic perimenstrual seizures. Studies in rat and mouse models of catamenial epilepsy show enhanced susceptibility to seizures or increased seizure exacerbations following neurosteroid withdrawal. During such a seizure exacerbation period, there is a striking decrease in the anticonvulsant effect of commonly prescribed antiepileptics, such as benzodiazepines, but an increase in the anticonvulsant potency of exogenous neurosteroids. We discovered an extrasynaptic molecular mechanism of catamenial epilepsy. In essence, extrasynaptic δGABA-A receptors are upregulated during perimenstrual-like neuroendocrine milieu. Consequently, there is enhanced antiseizure efficacy of neurosteroids in catamenial models because δGABA-A receptors confer neurosteroid sensitivity and greater seizure protection. Molecular mechanisms such as these offer a strong rationale for the clinical development of a neurosteroid replacement therapy for catamenial epilepsy.

Cognitive consequences of coexisting temporal lobe developmental malformations and hippocampal sclerosis.

PubMed

Martin, R; Dowler, R; Gilliam, F; Faught, E; Morawetz, R; Kuzniecky, R

1999-09-11

To characterize patterns of cognitive functioning in a well-defined group of patients with MRI-identified coexisting left temporal lobe developmental malformations (TLDM) and mesial temporal sclerosis (MTS), and to examine neuropsychological outcome in this dual-pathology group following epilepsy surgery. Cognitive functioning in patients with left TLDM and MTS (n = 15) was compared with patients with isolated left MTS (n = 40). TLDM and MTS were identified by high-quality MRI protocol. Patients were administered a battery of neuropsychology tests as part of their presurgical workup for possible epilepsy surgery. Unilateral temporal lobe resection was performed on 10 of the dual-pathology patients and 34 of the isolated MTS patients. Postoperative cognitive performance was also assessed. Both groups displayed impairments in verbal and visual memory, language, and academic achievement. Performance on measures of psychometric intelligence, executive function, and attention were not impaired and were similar between groups. Presence of dual pathology was associated with a significantly less efficient verbal encoding strategy on the word list learning task. Postoperatively, declines were noted for both groups across tasks of verbal memory and language. Groups were not different significantly in terms of neuropsychological outcome after surgery. Patients with coexisting TLDM and MTS have impaired cognitive functioning similar to MTS patients-in particular, with regard to episodic memory and language deficits. Temporal lobe resection produces similar cognitive changes in both groups.

Neuropsychology Within a Tertiary Care Epilepsy Center.

PubMed

Morrison, Chris E; MacAllister, William S; Barr, William B

2018-05-01

Epilepsy is a prevalent condition characterized by variations in its clinical presentation, etiology, and amenability to treatment. Through history, neuropsychologists have played a significant role in performing research studies on changes in language, memory, and executive functioning in patients with epilepsy, including those undergoing surgical treatment for medically refractory seizures. These studies provided a foundation for establishing neuropsychologists as critical members of interdisciplinary clinical teams specializing in evaluation and treatment of epilepsy. This article describes a number of elements of specialized neuropsychological practice that have evolved over the years within a tertiary care epilepsy center. Through diagnostic interview and objective testing, the neuropsychologist is able to provide a more complete and objective understanding of a patient's cognitive and behavioral functioning than what is obtained by other clinicians through brief office visits. While assessment of cognition, mood, and behavior is the most commonly provided service to patients with epilepsy from all age groups, there are many instances when neuropsychologists in surgical settings are called to perform more specialized procedures, including the intracarotid amytal (Wada) procedure, electrocortical stimulation mapping of language eloquent brain regions, and functional brain imaging procedures. While working as a neuropsychologist on an interdisciplinary epilepsy care team requires specialized knowledge and clinical training, it is extremely satisfying due to the diversity of the patient population and the particular challenges resulting from the often unique manner that cognition and behavior can be affected in patients with epilepsy across the lifespan.

"I don't want them to look at me and think of my illness, I just want them to look at me and see me": Child perspectives on the challenges associated with disclosing an epilepsy diagnosis to others.

PubMed

Benson, Ailbhe; Lambert, Veronica; Gallagher, Pamela; Shahwan, Amre; Austin, Joan K

2015-12-01

Disclosure of a concealable stigmatized identity, such as epilepsy, to those external to the nuclear family can be complex. Among children living with epilepsy (CWE), diagnosis disclosure has been identified as a quality-of-life issue and a source of psychosocial distress. Despite this, limited empirical evidence exists regarding the disclosure experiences of CWE. This study aimed to identify the contextual factors that act as challenges for CWE when disclosing their epilepsy diagnosis to others external to the nuclear family. This qualitative exploratory study consisted of individual interviews with 29 CWE (aged 6-16 years; mean age=11.17 years; S.D.=2.85). Participants were recruited from a tertiary referral unit in the neurology department of a pediatric hospital and through a national epilepsy association. Interviews were audiotaped and transcribed verbatim. Data were thematically analyzed. The five main challenges to epilepsy diagnosis disclosure for children were: 1) CWE's desire for normalcy, 2) out of sight but in the mind, 3) contending with negative responses to disclosure, 4) the complexity of epilepsy, and 5) self and others' perceptions of epilepsy. These findings provide valuable insight into the factors that present difficulties and impede epilepsy diagnosis disclosure among CWE. Such knowledge is important in informing engagements between health-care professionals (HCPs) and CWE. In particular, HCPs should remain cognisant of the challenges CWE face as they: (i) strive for normalcy and (ii) grapple with comprehending their complex neurological condition. Tackling such disclosure challenges could serve to enhance life quality, improve CWE's openness with others about epilepsy, and consequently work toward reducing epilepsy-related misconceptions and stigma. Copyright © 2015 Elsevier Inc. All rights reserved.

Phenotypic consequences of gene disruption by a balanced de novo translocation involving SLC6A1 and NAA15.

PubMed

Pesz, Karolina; Pienkowski, Victor Murcia; Pollak, Agnieszka; Gasperowicz, Piotr; Sykulski, Maciej; Kosińska, Joanna; Kiszko, Magdalena; Krzykwa, Bogusława; Bartnik-Głaska, Magdalena; Nowakowska, Beata; Rydzanicz, Małgorzata; Sasiadek, Maria Małgorzata; Płoski, Rafał

2018-04-03

Mapping of de novo balanced chromosomal translocations (BCTs) in patients with sporadic poorly characterized disease(s) is an unbiased method of finding candidate gene(s) responsible for the observed symptoms. We present a paediatric patient suffering from epilepsy, developmental delay (DD) and atrial septal defect IIº (ASD) requiring surgery. Karyotyping indicated an apparently balanced de novo reciprocal translocation 46,XX,t(3;4)(p25.3;q31.1), whereas aCGH did not reveal any copy number changes. Using shallow mate-pair whole genome sequencing and direct Sanger sequencing of breakpoint regions we found that translocation disrupted SLC6A1 and NAA15 genes. Our results confirm two previous reports indicating that loss of function of a single allele of SLC6A1 causes epilepsy. In addition, we extend existing evidence that disruption of NAA15 is associated with DD and with congenital heart defects. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.

PubMed

Bourdillon, Pierre; Apra, Caroline; Guénot, Marc; Duffau, Hugues

2017-12-01

To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Examining health-related quality of life, adaptive skills, and psychological functioning in children and adolescents with epilepsy presenting for a neuropsychological evaluation.

PubMed

Clary, Lauren E; Vander Wal, Jillon S; Titus, Jeffrey B

2010-11-01

The purpose of this study was to characterize 132 children and adolescents (mean age = 10 years, 11 months) with epilepsy in terms of psychosocial functioning and to determine the extent to which adaptive skills and psychological functioning predict health-related quality of life (HRQOL), above and beyond demographic and epilepsy-specific characteristics. A chart review was conducted to obtain demographic and epilepsy-specific information as well as caregiver responses on the Behavior Assessment System for Children, Second Edition (BASC-2) Parent Report and the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). In addition to Full Scale IQ and age at seizure onset, the BASC-2 Clinical and Adaptive Skills subscales also predicted HRQOL, indicating that this measure may be particularly helpful in predicting HRQOL above and beyond information routinely collected in a medical setting. It is imperative to evaluate children with epilepsy for psychosocial difficulties and diminished HRQOL to ensure the provision of comprehensive quality care and intervention services. Copyright © 2010 Elsevier Inc. All rights reserved.

The impact of family factors on IQ in pediatric medically refractory epilepsy.

PubMed

Puka, Klajdi; Smith, Mary Lou; Widjaja, Elysa

2017-02-01

To evaluate whether family factors were associated with intellectual functioning among children with medically refractory epilepsy, and whether family factors moderate the relationship between patient/epilepsy-related variables and intellectual functioning. Children aged 4 to 18 years with medically refractory epilepsy who were evaluated for surgical candidacy were recruited. The authors assessed the association of intellectual quotient (IQ) with patient, epilepsy, and family factors. Family factors included parental education, household income, and validated parent-report measures of family functioning, family mastery and social support, and family demands. Univariable analyses showed that higher IQ scores were associated with an older age of epilepsy onset (β = .260, p = .009), fewer antiepileptic drugs (β = .248, p = .013), a shorter duration (β = .384, p < .001) and percentage of life with epilepsy (β = .419, p < .001), unilobar epileptogenic foci relative to multilobar foci (β = .274, p = .006), and lower family demands (β = .211, p = .035). In multivariable analysis, unilobar epileptogenic foci (p = .010) and a shorter percentage of life with epilepsy (p = .001) remained significant predictors of IQ. Exploratory moderation analyses found the relationship between the extent of epileptogenic foci and IQ to be moderated by family demands (p = .004); specifically, patients with unilobar epileptogenic onset had similar IQ scores irrespective of family demands, whereas patients with multilobar foci had lower IQ scores with increasing family demands. Family factors did not have a large impact on IQ among children with medically refractory epilepsy, although the moderating effect of family demands deserves further study. Epilepsy-related factors in this patient group may weaken the link between child IQ and family factors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Self-Management in Epilepsy Care: Putting Teen and Families in the Center--Part One

ERIC Educational Resources Information Center

Shafer, Patricia Osborne; Dilorio, Colleen

2006-01-01

Epilepsy is one of the most common chronic neurological problems in childhood and adolescence. Unfortunately, it is also one of the most misunderstood conditions. Epilepsy can interfere with the physical, emotional and social functioning of youth of all ages, particularly if seizures are uncontrolled. Teenagers living with epilepsy face unique…

A Common Susceptibility Factor of Both Autism and Epilepsy: Functional Deficiency of GABA[subscript A] Receptors

ERIC Educational Resources Information Center

Kang, Jing-Qiong; Barnes, Gregory

2013-01-01

Autism and epilepsy are common childhood neurological disorders with a great heterogeneity of clinical phenotypes as well as risk factors. There is a high co-morbidity of autism and epilepsy. The neuropathology of autism and epilepsy has similar histology implicating the processes of neurogenesis, neural migration, programmed cell death, and…

Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy.

PubMed

Iannetti, Paola; Parisi, Pasquale; Spalice, Alberto; Ruggieri, Martino; Zara, Federico

2009-07-01

We report on the use of the voltage-gated calcium channel blocker (Vg-CCB), verapamil, as an add-on anticonvulsant medication in two girls, 4 and 14 years of age, who were affected by severe myoclonic epilepsy in infancy (SMEI) or Dravet syndrome, a channelopathy caused by abnormalities in the voltage-gated sodium channel neuronal type alpha1 subunit (SCN1A) gene at 2q24. Both girls had pharmacoresistant epilepsy and developmental delay. Mutation analysis for the SCN1A gene revealed a missense mutation in exon 2 in the 4-year-old girl. Verapamil was co-administered in both children with a prompt response in controlling status epilepticus, myoclonic jerks, and partial and generalized seizures. The therapeutic effect lasted 13 months in the 14-year-old girl, while it is still present after a 20-month follow-up period in the 4-year-old girl who, in addition, has experienced improvement in motor and language development. The verapamil vVg-CCB, which crosses the blood-brain barrier (BBB): (a) inhibits the P-glycoprotein, an active efflux transporter protein expressed in normal tissue, including the brain, which is believed to contribute to the in situ phenomenon of multidrug resistance; and (b) may regulate membrane depolarization induced by abnormal sodium channels functions by modulating the abnormal Ca++ influxes into neurons with subsequent cell resting. This is the first report on long-lasting verapamil therapy in SMEI. The functional consequences of such in vivo modulating effects on Ca++ channels could contribute to rational targeting for future molecular therapeutic approaches in pharmacoresistant epileptic channelopathies.

Region-specific connectivity in patients with periventricular nodular heterotopia and epilepsy: A study combining diffusion tensor imaging and functional MRI.

PubMed

Liu, Wenyu; An, Dongmei; Tong, Xin; Niu, Running; Gong, Qiyong; Zhou, Dong

2017-10-01

Periventricular nodular heterotopia (PNH) is an important cause of chronic epilepsy. The purpose of this study was to evaluate region-specific connectivity in PNH patients with epilepsy and assess correlation between connectivity strength and clinical factors including duration and prognosis. Diffusion tensor imaging (DTI) and resting state functional MRI (fMRI) were performed in 28 subjects (mean age 27.4years; range 9-56years). The structural connectivity of fiber bundles passing through the manually-selected segmented nodules and other brain regions were analyzed by tractography. Cortical lobes showing functional correlations to nodules were also determined. For all heterotopic gray matter nodules, including at least one in each subject, the most frequent segments to which nodular heterotopia showed structural (132/151) and functional (146/151) connectivity were discrete regions of the ipsilateral overlying cortex. Agreement between diffusion tensor tractography and functional connectivity analyses was conserved in 81% of all nodules (122/151). In patients with longer duration or refractory epilepsy, the connectivity was significantly stronger, particularly to the frontal and temporal lobes (P<0.05). Nodules in PNH were structurally and functionally connected to the cortex. The extent is stronger in patients with longstanding or intractable epilepsy. These findings suggest the region-specific interactions may help better evaluate prognosis and seek medical or surgical interventions of PNH-related epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of executive functioning in quality of life in pediatric intractable epilepsy.

PubMed

Love, Christina Eguizabal; Webbe, Frank; Kim, Gunha; Lee, Ki Hyeong; Westerveld, Michael; Salinas, Christine M

2016-11-01

Children with epilepsy are vulnerable to executive dysfunction, but the relationship between executive functioning (EF) and quality of life (QOL) in children with epilepsy is not fully delineated. This exploratory study elucidated the relationship between ecological EF and QOL in pediatric intractable epilepsy. Fifty-four consecutively referred pediatric epilepsy surgery candidates and their parents were administered IQ measures, the Behavior Rating Inventory of Executive Function (BRIEF), and the Quality of Life in Childhood Epilepsy (QOLCE) as part of a comprehensive neuropsychological evaluation. A significant difference was found in QOL between those with and without clinical impairments on the BRIEF [t(52)=3.93; p<.001]. That is, children with executive dysfunction had lower overall QOL. All seizure variables and BRIEF scales were associated with overall QOL [F(12, 40)=6.508; p=.001; R 2 =.661]. Working memory from the BRIEF was the most frequently elevated scale in our sample (57%). Those with executive dysfunction had 9.7 times the risk of having poor QOL. Poor EF control according to behavior ratings is significantly related to QOL in intractable pediatric epilepsy. Identification of executive dysfunction in home environments is an essential component of presurgical evaluations and target for intervention, which may improve QOL. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional network alterations and their structural substrate in drug-resistant epilepsy

PubMed Central

Caciagli, Lorenzo; Bernhardt, Boris C.; Hong, Seok-Jun; Bernasconi, Andrea; Bernasconi, Neda

2014-01-01

The advent of MRI has revolutionized the evaluation and management of drug-resistant epilepsy by allowing the detection of the lesion associated with the region that gives rise to seizures. Recent evidence indicates marked chronic alterations in the functional organization of lesional tissue and large-scale cortico-subcortical networks. In this review, we focus on recent methodological developments in functional MRI (fMRI) analysis techniques and their application to the two most common drug-resistant focal epilepsies, i.e., temporal lobe epilepsy related to mesial temporal sclerosis and extra-temporal lobe epilepsy related to focal cortical dysplasia. We put particular emphasis on methodological developments in the analysis of task-free or “resting-state” fMRI to probe the integrity of intrinsic networks on a regional, inter-regional, and connectome-wide level. In temporal lobe epilepsy, these techniques have revealed disrupted connectivity of the ipsilateral mesiotemporal lobe, together with contralateral compensatory reorganization and striking reconfigurations of large-scale networks. In cortical dysplasia, initial observations indicate functional alterations in lesional, peri-lesional, and remote neocortical regions. While future research is needed to critically evaluate the reliability, sensitivity, and specificity, fMRI mapping promises to lend distinct biomarkers for diagnosis, presurgical planning, and outcome prediction. PMID:25565942

Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.

PubMed

Pedersen, Mangor; Omidvarnia, Amir H; Walz, Jennifer M; Jackson, Graeme D

2015-01-01

Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.

Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding

PubMed Central

Pedersen, Mangor; Omidvarnia, Amir H.; Walz, Jennifer M.; Jackson, Graeme D.

2015-01-01

Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications. PMID:26110111

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.

PubMed

Wolf, Peter

2017-06-01

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

Transcranial direct-current stimulation as treatment in epilepsy.

PubMed

Gschwind, Markus; Seeck, Margitta

2016-12-01

Neuromodulation (NM) is a complementary therapy for patients with drug-resistant epilepsy. Vagal nerve stimulation and deep brain stimulation of the anterior thalamus are established techniques and have shown their efficacy in lowering seizure frequency, but they are invasive and rarely render patients seizure-free. Non-invasive NM techniques are therefore increasingly investigated in a clinical context. Areas covered: Current knowledge about transcranial direct-current stimulation (tDCS) and other non-invasive NM in patients with epilepsy, based on the available animal and clinical studies from PubMed search. Expert commentary: tDCS modulates neuronal membrane potentials, and consequently alters cortical excitability. Cathodal stimulation leads to cortical inhibition, which is of particular importance in epilepsy treatment. The antiepileptic efficacy is promising but still lacks systematic studies. The beneficial effect, seen in ~20%, outlasts the duration of stimulation, indicating neuronal plasticity and is therefore of great interest to obtain long-term effects.

A Road Map for Precision Medicine in the Epilepsies

PubMed Central

2015-01-01

Summary Technological advances have paved the way for accelerated genomic discovery and are bringing precision medicine clearly into view. Epilepsy research in particular is well-suited to serve as a model for the development and deployment of targeted therapeutics in precision medicine because of the rapidly expanding genetic knowledge base in epilepsy, the availability of good in vitro and in vivo model systems to efficiently study the biological consequences of genetic mutations, the ability to turn these models into effective drug screening platforms, and the establishment of collaborative research groups. Moving forward, it is critical that we strengthen these collaborations, particularly through integrated research platforms to provide robust analyses both for accurate personal genome analysis and gene and drug discovery. Similarly, the implementation of clinical trial networks will allow the expansion of patient sample populations with genetically defined epilepsy so that drug discovery can be translated into clinical practice. PMID:26416172

Health-related quality of life before and after pediatric epilepsy surgery: the influence of seizure outcome on changes in physical functioning and social functioning.

PubMed

Titus, Jeffrey B; Lee, Amy; Kasasbeh, Aimen; Thio, Liu Lin; Stephenson, Jennifer; Steger-May, Karen; Limbrick, David D; Smyth, Matthew D

2013-06-01

Health-related quality of life (HRQOL) is an important outcome in pediatric epilepsy surgery, but there are few studies that utilize presurgical ratings to assess the effect of surgery on HRQOL. We collected parental ratings on the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 28 children who participated in neuropsychological assessment before and after epilepsy surgery. Our results revealed significant improvements in overall HRQOL after surgery, especially in physical and social activities. These changes were apparent despite generally unchanged intellectual and psychological functioning. Children with better seizure outcome had more improvement in HRQOL; however, improvements were not statistically different among children with Engel class I, II, and III outcomes. Our results suggest that children can experience significant improvements in HRQOL following epilepsy surgery even when neuropsychological functioning remains unchanged. Moreover, improvements in HRQOL appear evident in children who experience any worthwhile improvement in seizure control (Engel class III or better). Copyright © 2013 Elsevier Inc. All rights reserved.

A Functional-Genetic Scheme for Seizure Forecasting in Canine Epilepsy.

PubMed

Bou Assi, Elie; Nguyen, Dang K; Rihana, Sandy; Sawan, Mohamad

2018-06-01

The objective of this work is the development of an accurate seizure forecasting algorithm that considers brain's functional connectivity for electrode selection. We start by proposing Kmeans-directed transfer function, an adaptive functional connectivity method intended for seizure onset zone localization in bilateral intracranial EEG recordings. Electrodes identified as seizure activity sources and sinks are then used to implement a seizure-forecasting algorithm on long-term continuous recordings in dogs with naturally-occurring epilepsy. A precision-recall genetic algorithm is proposed for feature selection in line with a probabilistic support vector machine classifier. Epileptic activity generators were focal in all dogs confirming the diagnosis of focal epilepsy in these animals while sinks spanned both hemispheres in 2 of 3 dogs. Seizure forecasting results show performance improvement compared to previous studies, achieving average sensitivity of 84.82% and time in warning of 0.1. Achieved performances highlight the feasibility of seizure forecasting in canine epilepsy. The ability to improve seizure forecasting provides promise for the development of EEG-triggered closed-loop seizure intervention systems for ambulatory implantation in patients with refractory epilepsy.

Epilepsy surgery in patients with malformations of cortical development.

PubMed

Lüders, Hans; Schuele, Stephan U

2006-04-01

Patients with malformations of cortical development often suffer from intractable focal epilepsy. This review considers recent progress in the selection and seizure outcome of patients undergoing resective epilepsy surgery for this condition. Patients with malformations of cortical development restricted to part or even a whole hemisphere may be candidates for epilepsy surgery even when, due to microscopic malformations, magnetic resonance imaging shows no detectable lesion. Despite recent advances in structural and functional imaging, the majority of patients with this condition undergo invasive evaluation. Patients with focal cortical dysplasia, with and without a detectable lesion on magnetic resonance imaging, often have a favorable outcome with epilepsy surgery. The underlying pathological substrate seems to be a better predictor for surgical outcome in patients with focal cortical dysplasia than the presence of a lesion on magnetic resonance imaging. Epilepsy surgery can be offered in a highly selected subgroup of patients with unilateral nodular heterotopia. Seizures in hemimegalencephaly may respond favorably to hemispherectomy, although most children will continue to have seizures and significant functional impairments. Patients with focal epilepsy due to malformations of cortical development are often intractable to medical management. Resective epilepsy surgery can be beneficial, particularly for patients with focal cortical dysplasia and unilateral hemispheric malformations.

Epilepsy surgery in children: outcomes and complications.

PubMed

Kim, Seung-Ki; Wang, Kyu-Chang; Hwang, Yong-Seung; Kim, Ki Joong; Chae, Jong Hee; Kim, In-One; Cho, Byung-Kyu

2008-04-01

Ideal epilepsy surgery would eliminate seizures without causing any functional deficits. The aim of the present study was to assess seizure outcomes and complications after epilepsy surgery in children with intractable epilepsy. Data obtained in 134 children (75 boys and 59 girls) age 17 years or younger who underwent epilepsy surgery at Seoul National University Children's Hospital between 1993 and 2005 were retrospectively reviewed. Epilepsy surgery included temporal resection (59 cases), extratemporal resection (56 cases), functional hemispherectomy (7 cases), callosotomy (9 cases), multiple subpial transection (1 case), and disconnection of a hamartoma (2 cases). The mean follow-up duration was 62.3 months (range 12-168 months). The overall seizure-free rate was 69% (93 of 134 cases). The seizure-free rate was significantly higher in children who underwent temporal resection than in those in whom extratemporal resection was performed (88 vs 55%, p < 0.05). The most frequent causes of treatment failure were related to the absence of structural abnormality demonstrated on magnetic resonance imaging, development-associated disease, widespread disease documented by postoperative electroencephalography, and limited resection due to the presence of functional cortex. There were no postoperative deaths. Visual field defects were the most common complication after temporal resection (22% [13 of 59 cases]), whereas hemiparesis (mostly transient) was the most common morbidity after extratemporal resection (18% [10 of 56 cases]). Epilepsy surgery is an effective and safe therapeutic modality in childhood. In children with extratemporal epilepsy, more careful interpretation of clinical and investigative data is needed to achieve favorable seizure outcome.

A Model of Post-Traumatic Epilepsy After Penetrating Brain Injuries: Effect of Lesion Size and Metal Fragments

PubMed Central

Kendirli, M. Tansel; Rose, Dominique T.; Bertram, Edward H.

2014-01-01

Objective Penetrating brain injury (PBI) has the highest risk for inducing post-traumatic epilepsy and retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Methods Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-EEG. A separate set of animals was examined for possible acute seizures in the week following the injury. Results 22 of the 23 animals with copper wire developed chronic epilepsy compared to 3 of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Conclusions Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute post-injury seizures. Lesion size may contribute to epilepsy development in lesion only animals. Copper maybe an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. PMID:25470332

Validation of reference genes for quantitative gene expression analysis in experimental epilepsy.

PubMed

Sadangi, Chinmaya; Rosenow, Felix; Norwood, Braxton A

2017-12-01

To grasp the molecular mechanisms and pathophysiology underlying epilepsy development (epileptogenesis) and epilepsy itself, it is important to understand the gene expression changes that occur during these phases. Quantitative real-time polymerase chain reaction (qPCR) is a technique that rapidly and accurately determines gene expression changes. It is crucial, however, that stable reference genes are selected for each experimental condition to ensure that accurate values are obtained for genes of interest. If reference genes are unstably expressed, this can lead to inaccurate data and erroneous conclusions. To date, epilepsy studies have used mostly single, nonvalidated reference genes. This is the first study to systematically evaluate reference genes in male Sprague-Dawley rat models of epilepsy. We assessed 15 potential reference genes in hippocampal tissue obtained from 2 different models during epileptogenesis, 1 model during chronic epilepsy, and a model of noninjurious seizures. Reference gene ranking varied between models and also differed between epileptogenesis and chronic epilepsy time points. There was also some variance between the four mathematical models used to rank reference genes. Notably, we found novel reference genes to be more stably expressed than those most often used in experimental epilepsy studies. The consequence of these findings is that reference genes suitable for one epilepsy model may not be appropriate for others and that reference genes can change over time. It is, therefore, critically important to validate potential reference genes before using them as normalizing factors in expression analysis in order to ensure accurate, valid results. © 2017 Wiley Periodicals, Inc.

Working memory network plasticity after anterior temporal lobe resection: a longitudinal functional magnetic resonance imaging study

PubMed Central

Stretton, Jason; Sidhu, Meneka K.; Winston, Gavin P.; Bartlett, Philippa; McEvoy, Andrew W.; Symms, Mark R.; Koepp, Matthias J.; Thompson, Pamela J.

2014-01-01

Working memory is a crucial cognitive function that is disrupted in temporal lobe epilepsy. It is unclear whether this impairment is a consequence of temporal lobe involvement in working memory processes or due to seizure spread to extratemporal eloquent cortex. Anterior temporal lobe resection controls seizures in 50–80% of patients with drug-resistant temporal lobe epilepsy and the effect of surgery on working memory are poorly understood both at a behavioural and neural level. We investigated the impact of temporal lobe resection on the efficiency and functional anatomy of working memory networks. We studied 33 patients with unilateral medial temporal lobe epilepsy (16 left) before, 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were also assessed in parallel. All subjects had neuropsychological testing and performed a visuospatial working memory functional magnetic resonance imaging paradigm on these three separate occasions. Changes in activation and deactivation patterns were modelled individually and compared between groups. Changes in task performance were included as regressors of interest to assess the efficiency of changes in the networks. Left and right temporal lobe epilepsy patients were impaired on preoperative measures of working memory compared to controls. Working memory performance did not decline following left or right temporal lobe resection, but improved at 3 and 12 months following left and, to a lesser extent, following right anterior temporal lobe resection. After left anterior temporal lobe resection, improved performance correlated with greater deactivation of the left hippocampal remnant and the contralateral right hippocampus. There was a failure of increased deactivation of the left hippocampal remnant at 3 months after left temporal lobe resection compared to control subjects, which had normalized 12 months after surgery. Following right anterior temporal lobe resection there was a progressive increase of activation in the right superior parietal lobe at 3 and 12 months after surgery. There was greater deactivation of the right hippocampal remnant compared to controls between 3 and 12 months after right anterior temporal lobe resection that was associated with lesser improvement in task performance. Working memory improved after anterior temporal lobe resection, particularly following left-sided resections. Postoperative working memory was reliant on the functional capacity of the hippocampal remnant and, following left resections, the functional reserve of the right hippocampus. These data suggest that working memory following temporal lobe resection is dependent on the engagement of the posterior medial temporal lobes and eloquent cortex. PMID:24691395

A systematic review of the risks factors associated with the onset and natural progression of epilepsy.

PubMed

Walsh, Stephanie; Donnan, Jennifer; Fortin, Yannick; Sikora, Lindsey; Morrissey, Andrea; Collins, Kayla; MacDonald, Don

2017-07-01

Epilepsy is a neurological condition that affects more than 50 million individuals worldwide. It presents as unpredictable, temporary and recurrent seizures often having negative physical, psychological and social consequences. To inform disease prevention and management strategies, a comprehensive systematic review of the literature on risk factors for the onset and natural progression of epilepsy was conducted. Computerized bibliographic databases for systematic reviews, meta-analyses, observational studies and genetic association studies published between 1990 and 2013 describing etiological risk factors for epilepsy was searched. The quality of systematic reviews was validated using the AMSTAR tool and articles were reviewed by two referees. A total of 16,958 articles went through stage one review of abstracts and titles. A total of 76 articles on genetic and non-genetic risk factors for the onset and progression of epilepsy met the eligibility criteria for data extraction. Dozens of risk factors were significantly associated with onset of epilepsy. Inconsistent levels of evidence for risk of onset included family history of epilepsy, history of febrile seizures, alcohol consumption, CNS and other infections, brain trauma, head injury, perinatal stroke, preterm birth and three genetic markers. Limited evidence showed that symptomatic epilepsy, focal seizures/syndromes, slow waves on EEG, higher seizure frequency, high stress or anxiety, and lack of sleep decreased the odds of seizure remission. High quality studies were rare and while a large body of work exists, relatively few systematic reviews were found. Copyright © 2016. Published by Elsevier B.V.

Familiarity, knowledge, and attitudes towards epilepsy among attendees of a family clinic in Amman, Jordan.

PubMed

Masri, Amira T; Shakhatreh, Farouq M; Yasein, Nada A; Barghouti, Farihan F; Al-Qudah, Abdelkarim A

2008-01-01

To investigate the present familiarity, knowledge, and attitudes of Jordanians towards epilepsy. This is a cross-sectional study that was conducted over a 6-month period, from April 2006 to October 2006 at the family clinic of Jordan University Hospital, Amman, Jordan. A face-to-face questionnaire interview was conducted with 600 non-epileptic adults who visited the clinic during the study period. The sample matched the overall Jordanian population for literacy rate, however, included a higher proportion of females, and consequently findings may be taken as being only moderately representative of the Jordanian population. Ninety-eight percent of the respondents had heard about epilepsy, 47.3% knew someone with epilepsy, and 39.7% had witnessed a seizure. The major source of knowledge was word of mouth; knowledge about causes and treatment were far below the results reported in western countries. In addition, negative attitudes were present with regard to marriage and employment of epileptic patients (86.8% objected to marriage and 50.8% objected to employment). Eighty-three percent of respondents admitted that their knowledge of epilepsy was not satisfactory and were willing to learn more about epilepsy. The television was believed to be the most efficient and preferred way to disseminate knowledge about epilepsy. Although this study does not represent the whole Jordanian population, however, it demonstrated lack of knowledge and emphasized the extent of negative as well as positive attitudes towards epilepsy in Jordan.

The psychological costs of comparisons: Parents' social comparison moderates the links between family management of epilepsy and children's outcomes.

PubMed

Mendes, Teresa P; Crespo, Carla A; Austin, Joan K

2017-10-01

Parents play a key role in how children deal with epilepsy. When diagnosed with health conditions, people seek comparison information from fellow patients and families, and this information has consequences for how they evaluate their situation. This study examined the moderating role of parents' social comparison orientation in the associations between family management (parental perceptions of family life difficulties and child's daily life) and adaptation outcomes of children with epilepsy (HRQoL and perceived stigma). Participants included 201 dyads of children with epilepsy and either their mother or father. The results showed that when parents perceived higher difficulties managing their child's epilepsy and/or reported that their child was more affected by this condition, children reported higher perceived stigma and worse HRQoL only when parents had a higher social comparison orientation. Our results are innovative in showing that when parents have a higher social comparison orientation, their children may be at increased risk of poorer outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy.

PubMed

van Eijsden, Pieter; Otte, Wim M; van der Hel, W Saskia; van Nieuwenhuizen, Onno; Dijkhuizen, Rick M; de Graaf, Robin A; Braun, Kees P J

2011-04-01

Although epilepsy is historically considered a disease of gray matter, recent diffusion tensor imaging (DTI) studies have shown white matter abnormalities in patients with epilepsy. The histopathologic correlate of these findings, and whether they are a cause or consequence of epilepsy, remains unclear. To characterize these changes and their underlying histopathology, DTI was performed in juvenile rats, 4 and 8 weeks after pilocarpine-induced status epilepticus (SE). In the medial corpus callosum (CC), mean diffusivity and axial diffusivity (MD and λ₁) as well as a myelin staining were significantly reduced at 4 weeks. Only the λ₁ decrease persisted at 8 weeks. In the fornix fimbriae (FF), λ₁ and myelin staining were decreased at both time points, whereas fractional anisotropy (FA) and MD were significantly reduced at 8 weeks only. We conclude that SE induces both transient and chronic white matter changes in the medial CC and FF that are to some degree related to myelin pathology. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2014-09-01

NOTES 14. ABSTRACT Traumatic Brain Injury (TBI) is a well-established inducer of temporal lobe epilepsy (TLE), a frequently medically intractable... epilepsy syndrome. The controlled cortical impact (CCI) model of posttraumatic epilepsy in mice is a well established animal model of TBI that results...reduce development of post-traumatic epilepsy , and did not significantly improve memory function, but did enhance the motor recovery. These findings

Development of a web-based executive functioning intervention for adolescents with epilepsy: The Epilepsy Journey.

PubMed

Modi, Avani C; Schmidt, Matthew; Smith, Aimee W; Turnier, Luke; Glaser, Noah; Wade, Shari L

2017-07-01

Youth with epilepsy exhibit significant deficits in executive functioning (EF), yet there are few interventions to improve EF for adolescents. The aims of the current study were to develop an individually-tailored intervention, called Epilepsy Journey, to improve aspects of EF through an iterative, patient-centered process including focus groups and usability testing. Five adolescents and caregivers participated in focus groups. This input was used to develop ten learning modules based on subscales of the Behavioral Rating Inventory of Executive Functions and key issues that may impact EF in adolescents. Six adolescents participated in usability testing and a usability expert conducted a heuristic evaluation. Demographic information, chart reviews and measures of EF were also completed. Focus group participants and their parents reported difficulties with memory, attention, organization, monitoring, initiation, impulsivity, emotional control, sleep, awareness in schools and managing stress. They also identified successful strategies to address memory and organizational difficulties. Usability testing of the resultant Epilepsy Journey modules revealed problems with navigation and identified features that promoted usability, including progress bars and interactive modules. Program modifications were made after each usability trial resulting in a relatively brief, interactive and readily navigable program. Perceived utility was high with all but one participant. Participants rated the content as helpful and indicated they would recommend Epilepsy Journey to others. Feedback from the focus group and usability testing yielded a feasible, acceptable, relevant and user-friendly web-based intervention for adolescents with epilepsy. The Epilepsy Journey program will be further tested in an open pilot with adolescents with epilepsy and associated EF deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors affecting reorganisation of memory encoding networks in temporal lobe epilepsy

PubMed Central

Sidhu, M.K.; Stretton, J.; Winston, G.P.; Symms, M.; Thompson, P.J.; Koepp, M.J.; Duncan, J.S.

2015-01-01

Summary Aims In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. Methods We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. Results Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. Conclusion Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst longer duration and higher seizure frequency were associated with greater, inefficient, extra-temporal reorganisation. PMID:25616449

Stopping epilepsy treatment in seizure remission: Good or bad or both?

PubMed

Schmidt, Dieter; Sillanpää, Matti

2017-01-01

To review the outcome of epilepsy after stopping antiepileptic drugs in remission. Stopping antiepileptic drugs (AEDs) in remission is routinely done in many patients. Although the consequences of an unexpected relapse seizure in the 2 years after stopping AEDs may cause anguish and social issues, the impact on the long term seizure outlook of the epilepsy is minimal, if any. Discontinuation of drug treatment does not seem to affect the long-term prognosis but exposes patients who were seizure-free for years to a transient two-fold risk of seizures for the first 2 years after stopping AEDs. In addition, 20% of patients who were seizure-free for years, do not become seizure-free immediately after restarting AED treatment after relapse. The list of potential pitfalls is long. Patients with juvenile myoclonic epilepsy, those with prior withdrawal attempts and late remission have a higher risk of relapse. Stopping AEDs in remission does not affect the long-term patterns of epilepsy and some patients report a better general health in a life without AEDs. High-risk patients should not be generally encouraged to stop their AEDs in remission. We need new drugs that combine anti-seizure and antiepileptogenic effects to prevent seizure relapse and flare up of epilepsy after stopping AEDs in remission. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Investigating Inhibitory Control in Children with Epilepsy: An fMRI Study

PubMed Central

Triplett, Regina L.; Velanova, Katerina; Luna, Beatriz; Padmanabhan, Aarthi; Gaillard, William D.; Asato, Miya R.

2014-01-01

SUMMARY Objective Deficits in executive function are increasingly noted in children with epilepsy and have been associated with poor academic and psychosocial outcomes. Impaired inhibitory control contributes to executive dysfunction in children with epilepsy; however, its neuroanatomic basis has not yet been investigated. We used functional Magnetic Resonance Imaging (fMRI) to probe the integrity of activation in brain regions underlying inhibitory control in children with epilepsy. Methods This cross-sectional study consisted of 34 children aged 8 to 17 years: 17 with well-controlled epilepsy and 17 age-and sex-matched controls. Participants performed the antisaccade (AS) task, representative of inhibitory control, during fMRI scanning. We compared AS performance during neutral and reward task conditions and evaluated task-related blood-oxygen level dependent (BOLD) activation. Results Children with epilepsy demonstrated impaired AS performance compared to controls during both neutral (non-reward) and reward trials, but exhibited significant task improvement during reward trials. Post-hoc analysis revealed that younger patients made more errors than older patients and all controls. fMRI results showed preserved activation in task-relevant regions in patients and controls, with the exception of increased activation in the left posterior cingulate gyrus in patients specifically with generalized epilepsy across neutral and reward trials. Significance Despite impaired inhibitory control, children with epilepsy accessed typical neural pathways as did their peers without epilepsy. Children with epilepsy showed improved behavioral performance in response to the reward condition, suggesting potential benefits of the use of incentives in cognitive remediation. PMID:25223606

Pragmatic Communication Deficits in Children with Epilepsy

ERIC Educational Resources Information Center

Broeders, Mark; Geurts, Hilde; Jennekens-Schinkel, Aag

2010-01-01

Background: Various psychiatric and neurological disorders including epilepsy have been associated with language deficits. Pragmatic language deficits, however, have seldom been the focus of earlier studies in children with epilepsy. Moreover, it is unknown whether these pragmatic deficits are related to general intellectual functioning. Both…

Microglia-Neuron Communication in Epilepsy.

PubMed

Eyo, Ukpong B; Murugan, Madhuvika; Wu, Long-Jun

2017-01-01

Epilepsy has remained a significant social concern and financial burden globally. Current therapeutic strategies are based primarily on neurocentric mechanisms that have not proven successful in at least a third of patients, raising the need for novel alternative and complementary approaches. Recent evidence implicates glial cells and neuroinflammation in the pathogenesis of epilepsy with the promise of targeting these cells to complement existing strategies. Specifically, microglial involvement, as a major inflammatory cell in the epileptic brain, has been poorly studied. In this review, we highlight microglial reaction to experimental seizures, discuss microglial control of neuronal activities, and propose the functions of microglia during acute epileptic phenotypes, delayed neurodegeneration, and aberrant neurogenesis. Future research that would help fill in the current gaps in our knowledge includes epilepsy-induced alterations in basic microglial functions, neuro-microglial interactions during chronic epilepsy, and microglial contribution to developmental seizures. Studying the role of microglia in epilepsy could inform therapies to better alleviate the disease. GLIA 2016;65:5-18. © 2016 Wiley Periodicals, Inc.

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

PubMed

Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S; Masnada, Silvia; Rubboli, Guido; Gardella, Elena; Lesca, Gaetan; Ville, Dorothée; Milh, Mathieu; Villard, Laurent; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Mignot, Cyril; Lardennois, Caroline; Nava, Caroline; Schwarz, Niklas; Gérard, Marion; Perrin, Laurence; Doummar, Diane; Auvin, Stéphane; Miranda, Maria J; Hempel, Maja; Brilstra, Eva; Knoers, Nine; Verbeek, Nienke; van Kempen, Marjan; Braun, Kees P; Mancini, Grazia; Biskup, Saskia; Hörtnagel, Konstanze; Döcker, Miriam; Bast, Thomas; Loddenkemper, Tobias; Wong-Kisiel, Lily; Baumeister, Friedrich M; Fazeli, Walid; Striano, Pasquale; Dilena, Robertino; Fontana, Elena; Zara, Federico; Kurlemann, Gerhard; Klepper, Joerg; Thoene, Jess G; Arndt, Daniel H; Deconinck, Nicolas; Schmitt-Mechelke, Thomas; Maier, Oliver; Muhle, Hiltrud; Wical, Beverly; Finetti, Claudio; Brückner, Reinhard; Pietz, Joachim; Golla, Günther; Jillella, Dinesh; Linnet, Karen M; Charles, Perrine; Moog, Ute; Õiglane-Shlik, Eve; Mantovani, John F; Park, Kristen; Deprez, Marie; Lederer, Damien; Mary, Sandrine; Scalais, Emmanuel; Selim, Laila; Van Coster, Rudy; Lagae, Lieven; Nikanorova, Marina; Hjalgrim, Helle; Korenke, G Christoph; Trivisano, Marina; Specchio, Nicola; Ceulemans, Berten; Dorn, Thomas; Helbig, Katherine L; Hardies, Katia; Stamberger, Hannah; de Jonghe, Peter; Weckhuysen, Sarah; Lemke, Johannes R; Krägeloh-Mann, Ingeborg; Helbig, Ingo; Kluger, Gerhard; Lerche, Holger; Møller, Rikke S

2017-05-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells-together with data from the literature-suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function, characterized by slowing of fast inactivation, acceleration of its recovery or increased persistent sodium current. Further, a good response to sodium channel blockers clinically was found to be associated with a relatively small gain-of-function. In contrast, mutations in patients with late-onset forms and an insufficient response to sodium channel blockers were associated with loss-of-function effects, including a depolarizing shift of voltage-dependent activation or a hyperpolarizing shift of channel availability (steady-state inactivation). Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Electrocorticographic Mapping of Expressive Language Function without Requiring the Patient to Speak: A Report of Three Cases

DTIC Science & Technology

2016-09-07

Epilepsy & Behavior Case Reports 6 (2016) 13–18 Contents lists available at ScienceDirect Epilepsy & Behavior Case Reports j ourna l homepage: www.e...Pesters et al. / Epilepsy & Behavior Case Reports 6 (2016) 13–18have noteworthy limitations. First, a thorough ECS interrogation is very time-consuming...prompted recent and increasingly encouraging investigations suggesting that “passive” methodologies , such as electrocorticography (ECoG) or functional

Cognitive impairment in Epilepsy: The Role of Network Abnormalities

PubMed Central

Holmes, Gregory L.

2015-01-01

The challenges to individuals with epilepsy extend far beyond the seizures. Co-morbidities in epilepsy are very common and are often more problematic to individuals than the seizures themselves. In this review, the pathophysiological mechanisms of cognitive impairment are discussed. While etiology of the epilepsy has a significant influence on cognition there is increasing evidence that prolonged or recurrent seizures can cause or exacerbate cognitive impairment. Alterations in signaling pathways and neuronal network function play a major role in both the pathophysiology of epilepsy and the epilepsy comorbidities. However, the biological underpinnings of cognitive impairment can be distinct from the pathophysiological processes that cause seizures. PMID:25905906

Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy.

PubMed

Gleichgerrcht, Ezequiel; Kocher, Madison; Bonilha, Leonardo

2015-11-01

The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the systematic and rigorous evaluation of this form of "big data" are paramount to leverage the full potential of this new approach. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy.

PubMed

Guilfoyle, Shanna M; Follansbee-Junger, Katherine; Smith, Aimee W; Combs, Angela; Ollier, Shannon; Hater, Brooke; Modi, Avani C

2018-01-01

To examine baseline psychological functioning and antiepileptic drug (AED) behavioral side effects in new onset epilepsy and determine, by age, whether baseline psychological functioning predicts AED behavioral side effects 1 month following AED initiation. A retrospective chart review was conducted between July 2011 and December 2014 that included youths with new onset epilepsy. As part of routine interdisciplinary care, caregivers completed the Behavior Assessment System for Children, 2nd Edition: Parent Rating Scale to report on baseline psychological functioning at the diagnostic visit and the Pediatric Epilepsy Side Effects Questionnaire to identify AED behavioral side effects at the 1-month follow-up clinic visit following AED initiation. Children (age = 2-11 years) and adolescents (age = 12-18 years) were examined separately. A total of 380 youths with new onset epilepsy (M age  = 8.9 ± 4.3 years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1% generalized epilepsy, 23.7% unclassified epilepsy) were included. Seventy percent of youths had at-risk or clinically elevated baseline psychological symptoms. Children had significantly greater AED behavioral side effects (M = 25.08 ± 26.36) compared to adolescents (M = 12.36 ± 17.73), regardless of AED. Valproic acid demonstrated significantly greater behavioral side effects compared to all other AEDs, with the exception of levetiracetam. Higher hyperactivity/impulsivity at baseline significantly predicted higher AED behavioral side effects 1 month after AED initiation in both age groups. Younger children seem to be more prone to experience behavioral side effects, and these are likely to be higher if youths with epilepsy have baseline hyperactivity/impulsivity. Baseline psychological screening, specifically hyperactivity, can be used as a precision medicine tool for AED selection. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The chronic and evolving neurological consequences of traumatic brain injury.

PubMed

Wilson, Lindsay; Stewart, William; Dams-O'Connor, Kristen; Diaz-Arrastia, Ramon; Horton, Lindsay; Menon, David K; Polinder, Suzanne

2017-10-01

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Emotional Prosody Processing in Epilepsy: Some Insights on Brain Reorganization.

PubMed

Alba-Ferrara, Lucy; Kochen, Silvia; Hausmann, Markus

2018-01-01

Drug resistant epilepsy is one of the most complex, multifactorial and polygenic neurological syndrome. Besides its dynamicity and variability, it still provides us with a model to study brain-behavior relationship, giving cues on the anatomy and functional representation of brain function. Given that onset zone of focal epileptic seizures often affects different anatomical areas, cortical but limited to one hemisphere, this condition also let us study the functional differences of the left and right cerebral hemispheres. One lateralized function in the human brain is emotional prosody, and it can be a useful ictal sign offering hints on the location of the epileptogenic zone. Besides its importance for effective communication, prosody is not considered an eloquent domain, making resective surgery on its neural correlates feasible. We performed an Electronic databases search (Medline and PsychINFO) from inception to July 2017 for studies about prosody in epilepsy. The search terms included "epilepsy," "seizure," "emotional prosody," and "vocal affect." This review focus on emotional prosody processing in epilepsy as it can give hints regarding plastic functional changes following seizures (preoperatively), resection (post operatively), and also as an ictal sign enabling the assessment of dynamic brain networks. Moreover, it is argued that such reorganization can help to preserve the expression and reception of emotional prosody as a central skill to develop appropriate social interactions.

A model of posttraumatic epilepsy after penetrating brain injuries: effect of lesion size and metal fragments.

PubMed

Kendirli, M Tansel; Rose, Dominique T; Bertram, Edward H

2014-12-01

Penetrating brain injury (PBI) has the highest risk for inducing posttraumatic epilepsy, and those PBIs with retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-electroencephalography (EEG). A separate set of animals was examined for possible acute seizures in the week following the injury. Twenty-two of the 23 animals with copper wire developed chronic epilepsy, compared to three of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute postinjury seizures. Lesion size may contribute to epilepsy development in lesion-only animals. Copper may be an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

The experience of epilepsy in later life: A qualitative exploration of illness representations.

PubMed

Yennadiou, Haris; Wolverson, Emma

2017-05-01

The objective of this study was to explore how older people living with epilepsy appraise their condition through their lived-experience. The common-sense model of illness representations (CSMIR) provides a framework to explain how individuals make sense of and manage health threats. Semi-structured in-depth interviews based on the CSMIR were conducted with ten people with epilepsy who were above the age of 65. The results were analyzed using Interpretative Phenomenological Analysis. Three overarching themes emerged from the analysis: 'the power of epilepsy', 'they say you can live a normal life but you can't' and 'attempts to adjust and cope'. Epilepsy was described as a threatening, persistent, and unpredictable condition associated with distressing experiences. Participants described a process of balancing negative psychosocial consequences including stigma, loss of control, and reliance on other people and medication with parallel co-existing coping strategies. These attempts to manage the condition were characterized by a desire for acceptance and increased awareness of epilepsy, strategies to restore loss of control, and strength derived from supportive relationships. We conclude that there is large scope for psychosocial interventions in healthcare provision for this patient group. The roles of specialist nursing, relationship-centered models, psychotherapy, educational, and self-management programs are highlighted. Copyright © 2017 Elsevier Inc. All rights reserved.

The association between periodontal disease and seizure severity in refractory epilepsy patients.

PubMed

Costa, Andre L F; Yasuda, Clarissa Lin; Shibasaki, Wendel; Nahás-Scocate, Ana Carla Raphaelli; de Freitas, Claudio Fróes; Carvalho, Paulo Eduardo Guedes; Cendes, Fernando

2014-03-01

Periodontal diseases are common in most populations and affect people at all socioeconomic levels. Evidence suggests that patients with epilepsy actually have higher risks of dental disease and increased oral health needs, but the frequency and consequences of poor controlled seizures on dental and periodontal health have not been reported before. We aimed to assess the impact of seizure frequency on periodontal status and oral hygiene in a sample of epilepsy patients. One hundred and nine consecutive patients treated for epilepsy at the outpatient clinic of our University Hospital were invited to take part in an oral examination to determine their periodontal disease status, together with a control group. In addition, seizure frequency and use of medication were documented. In logistic regression model, patients were significantly more susceptible to bad oral hygiene, gingivitis and periodontitis that controls (p<0.001); seizure frequency was significantly related to bad oral hygiene (p=0.010), gingivitis (p<0.001) and periodontitis (p<0.001). Tooth brushing habits and presence of caries were associated with oral health in patients group. Our study found a significant positive correlation between periodontal disease and seizure severity. Epilepsy patients need to focus more on their oral health and quality of oral hygiene. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A Three-Lesson Teaching Unit Significantly Increases High School Students’ Knowledge about Epilepsy and Positively Influences Their Attitude towards This Disease

PubMed Central

Simon, Uwe K.; Gesslbauer, Lisa; Fink, Andreas

2016-01-01

Epilepsy is not a regular topic in many countries’ schools. Thus many people harbor misconceptions about people suffering from this disease. It was our aim to a) examine what grade ten students know and believe about epilepsy, and b) to develop and test a teaching unit to improve their knowledge and attitude. The test group comprised eight grade ten classes from six different Austrian high schools (54 girls and 51 boys aged 14–17), the control group (no intervention) five grade ten classes from the same schools (26 girls and 37 boys aged 14–17). The teaching unit consisted of three 45-min lessons using different methods and material. Changes in knowledge about and attitude towards epilepsy as a result of the intervention were psychometrically assessed in a pre-test intervention post-test design (along with a follow-up assessment two months after the intervention) by means of a questionnaire capturing different facets of epilepsy-related knowledge and attitude. Across all knowledge/attitude domains, students of the test group had a significantly improved knowledge about and a more positive attitude towards epilepsy and people suffering from it after the teaching unit. However, starting levels were different between the five knowledge/attitude domains tested. Medical background knowledge was lowest and consequently associated with the highest increase after the intervention. This study shows that epilepsy-related knowledge of many grade ten high school students is fragmentary and that some harbor beliefs and attitudes which require improvement. Our comprehensive but concise teaching unit significantly increased knowledge about epilepsy and positively influenced attitude towards individuals with epilepsy. Thus we recommend implementing this unit into regular school curricula. PMID:26919557

Genetic association analysis of ATP binding cassette protein family reveals a novel association of ABCB1 genetic variants with epilepsy risk, but not with drug-resistance.

PubMed

Balan, Shabeesh; Bharathan, Sumitha Prameela; Vellichiramal, Neetha Nanoth; Sathyan, Sanish; Joseph, Vijai; Radhakrishnan, Kurupath; Banerjee, Moinak

2014-01-01

Epilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED)-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype for AED-resistant epilepsy); juvenile myoclonic epilepsy (JME) (prototype for AED-responsive epilepsy); and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T) rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004). This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004) and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05) cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency for MTLE-HS in south Indian ancestry from Kerala.

Cognitive functioning in dyskinetic cerebral palsy: Its relation to motor function, communication and epilepsy.

PubMed

Ballester-Plané, Júlia; Laporta-Hoyos, Olga; Macaya, Alfons; Póo, Pilar; Meléndez-Plumed, Mar; Toro-Tamargo, Esther; Gimeno, Francisca; Narberhaus, Ana; Segarra, Dolors; Pueyo, Roser

2018-01-01

Cerebral palsy (CP) is a disorder of motor function often accompanied by cognitive impairment. There is a paucity of research focused on cognition in dyskinetic CP and on the potential effect of related factors. To describe the cognitive profile in dyskinetic CP and to assess its relationship with motor function and associated impairments. Fifty-two subjects with dyskinetic CP (28 males, mean age 24 y 10 mo, SD 13 y) and 52 typically-developing controls (age- and gender-matched) completed a comprehensive neuropsychological assessment. Gross Motor Function Classification System (GMFCS), Communication Function Classification System (CFCS) and epilepsy were recorded. Cognitive performance was compared between control and CP groups, also according different levels of GMFCS. The relationship between cognition, CFCS and epilepsy was examined through partial correlation coefficients, controlling for GMFCS. Dyskinetic CP participants performed worse than controls on all cognitive functions except for verbal memory. Milder cases (GMFCS I) only showed impairment in attention, visuoperception and visual memory. Participants with GMFCS II-III also showed impairment in language-related functions. Severe cases (GMFCS IV-V) showed impairment in intelligence and all specific cognitive functions but verbal memory. CFCS was associated with performance in receptive language functions. Epilepsy was related to performance in intelligence, visuospatial abilities, visual memory, grammar comprehension and learning. Cognitive performance in dyskinetic CP varies with the different levels of motor impairment, with more cognitive functions impaired as motor severity increases. This study also demonstrates the relationship between communication and epilepsy and cognitive functioning, even controlling for the effect of motor severity. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Getting serious about the early-life epilepsies: Lessons from the world of pediatric oncology.

PubMed

Berg, Anne T; Goldman, Stewart

2018-05-01

Early-life epilepsies represent a group of many individually rare and often complex developmental brain disorders associated with lifelong devastating consequences and high risk for early mortality. The quantity and quality of evidence needed to guide the evaluation and treatment to optimize outcomes of affected children is minimal; most children are treated within an evidence-free practice zone based solely on anecdote and lore. The remarkable advances in diagnostics and therapeutics are implemented haphazardly with no systematic effort to understand their effects and value. This stands in stark contrast to the evidence-rich practice of the Children's Oncology Group, where standard of care treatments are identified through rigorous, multicenter research studies, and the vast majority of patients are treated on protocols developed from that research. As a consequence, overall mortality for childhood cancers has declined from ∼90% in the 1950s to ∼20% today. The situations of these 2 rare disease specialties are contrasted, and some suggestions for moving early-life epilepsy onto a fast track for success are offered. Chief amongst these is that early-life epilepsy should be treated with the same urgency as pediatric cancer. The best diagnostics and evidence-based treatments should be used in a systematic fashion right from the start, not after the child and family have been subjected to the ravages of the disorder for months or years. This will require unity and cooperation among physicians, researchers, and institutions across state and national borders. © 2018 American Academy of Neurology.

Reprint of: The new approach to epilepsy classification: Cognition and behavior in adult epilepsy syndromes.

PubMed

Baxendale, Sallie; Thompson, Pamela

2016-11-01

The revised terminology and concepts for the organization of seizures and epilepsy proposed by the ILAE Commission on Classification and Terminology in 2010 allows for a number of new opportunities in the study of cognition and behavior in adults. This review examines the literature that has looked for behavioral and cognitive correlates of the newly recognized genetic epilepsies in adults. While some studies report clear cognitive phenotypes associated with specific genetic mutations in adults with epilepsy, others report remarkable clinical heterogeneity. In the second part of this review, we discuss some of the factors that may influence the findings in this literature. Cognitive function is the product of both genetic and environmental influences. Neuropsychological phenotypes under direct genetic influence may be wider and more subtle than specific deficits within discreet cognitive domains and may be reflected in broader, multidimensional measures of cognitive function than those tapped by scores on standardized tests of function. Future studies must be carefully designed to reflect these factors. It is also imperative that studies with negative findings are assigned as much value as those with positive results and published accordingly. This article is part of a Special Issue titled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Neuroimaging studies towards understanding the central effects of pharmacological cannabis products on patients with epilepsy.

PubMed

Allendorfer, Jane B; Szaflarski, Jerzy P

2017-05-01

Recent interest for the use of cannabis-derived products as therapeutic agents in the treatment of epilepsies has necessitated a reevaluation of their effects on brain and behavior. Overall, prolonged cannabis use is thought to result in functional and structural brain alterations. These effects may be dependent on a number of factors: e.g., which phytocannabinoid is used (e.g., cannabidiol (CBD) vs. tetrahyrocannabinol (THC)), the frequency of use (occasional vs. heavy), and at what age (prenatal, childhood, adulthood) the use began. However, due to the fact that there are over seven hundred constituents that make up the Cannabis sativa plant, it is difficult to determine which compound or combination of compounds is responsible for specific effects when studying recreational users. Therefore, this review focuses only on the functional MRI studies investigating the effects of specific pharmacological preparations of cannabis compounds, specifically THC, tetrahydrocannabivarin (THCV), and CBD, on brain function in healthy individuals and persons with epilepsy with references to non-epilepsy studies only to underline the gaps in research that need to be filled before cannabis-derived products are considered for a wide use in the treatment of epilepsy. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy.

PubMed

Erramuzpe, A; Encinas, J M; Sierra, A; Maletic-Savatic, M; Brewster, A L; Anderson, Anne E; Stramaglia, S; Cortes, Jesus M

2015-01-01

Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry. Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC changes from the initial insult (status epilepticus) and over the latent period, when epileptogenic networks emerge, and at chronic epilepsy, when unprovoked seizures occur as spontaneous events. We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.

Influence of Occupational Status on the Quality of Life of Chinese Adult Patients with Epilepsy

PubMed Central

Gu, Xiang-Min; Ding, Cheng-Yun; Wang, Ning; Xu, Cheng-Feng; Chen, Ze-Jie; Wang, Qin; Yao, Qin; Wang, Fu-Li

2016-01-01

Background: Epilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epilepsy. Methods: This study surveyed 819 subjects clinically diagnosed with epilepsy for more than 1 year in 11 hospitals in Beijing; 586 were employed (71.55%). All subjects completed the case report form with inquiries on demographic data, social factors, and illness. The patients’ quality of life was assessed using the quality of life in patients with epilepsy-31 items (QOLIE-31) questionnaire. Results: The QOLIE-31 score in the employed group was significantly higher than that in the unemployed group. Furthermore, the scores in all the sections (overall quality of life, energy/fatigue, emotional well-being, seizure worry, cognition, social function, and medication effects) of the employed group were higher than those of the unemployed group. Both the employed and unemployed groups achieved the highest difference in social function. The QOLIE-31 score of students was higher than those of farmers and workers. Both the students and workers scored higher in the quality of life compared with the adult peasants living with epilepsy. The students and farmers showed significant differences in QOLIE-31 score, cognition, emotional well-being, overall quality of life, energy/fatigue, and social function. In contrast, no significant difference was noted in seizure worry and medication effects across the three different kinds of occupation. Conclusion: Occupational status might affect the quality of life of Chinese adult patients with epilepsy, and social function is the most important contributing factor. PMID:27231164

Clinic-friendly screening for cognitive and mental health problems in school-aged youth with epilepsy.

PubMed

Asato, Miya R; Doss, Julia L; Plioplys, Sigita

2015-07-01

Cognitive, psychiatric, psychosocial, and behavioral difficulties are common in youth with epilepsy. Collectively, these comorbidities can be referred to as mental health problems as they reflect brain and behavioral function. Detection and treatment of mental health problems remain an unmet need in epilepsy care that can impact epilepsy, psychosocial, scholastic, and quality-of-life outcomes. Given limited resources in everyday pediatric epilepsy practice, this targeted review provides a stratified plan and suggested tools for screening school-aged youth with epilepsy for the presence of mental health problems. Comanagement of epilepsy and associated comorbidities is a newer concept that may help address the complex, long-term needs of patients by using a multidisciplinary team approach and by engaging primary care providers. Copyright © 2015 Elsevier Inc. All rights reserved.

Epilepsy in Onchocerciasis Endemic Areas: Systematic Review and Meta-analysis of Population-Based Surveys

PubMed Central

Pion, Sébastien D. S.; Kaiser, Christoph; Boutros-Toni, Fernand; Cournil, Amandine; Taylor, Melanie M.; Meredith, Stefanie E. O.; Stufe, Ansgar; Bertocchi, Ione; Kipp, Walter; Preux, Pierre-Marie; Boussinesq, Michel

2009-01-01

Objective We sought to evaluate the relationship between onchocerciasis prevalence and that of epilepsy using available data collected at community level. Design We conducted a systematic review and meta-regression of available data. Data Sources Electronic and paper records on subject area ever produced up to February 2008. Review Methods We searched for population-based studies reporting on the prevalence of epilepsy in communities for which onchocerciasis prevalence was available or could be estimated. Two authors independently assessed eligibility and study quality and extracted data. The estimation of point prevalence of onchocerciasis was standardized across studies using appropriate correction factors. Variation in epilepsy prevalence was then analyzed as a function of onchocerciasis endemicity using random-effect logistic models. Results Eight studies from west (Benin and Nigeria), central (Cameroon and Central African Republic) and east Africa (Uganda, Tanzania and Burundi) met the criteria for inclusion and analysis. Ninety-one communities with a total population of 79,270 individuals screened for epilepsy were included in the analysis. The prevalence of epilepsy ranged from 0 to 8.7% whereas that of onchocerciasis ranged from 5.2 to 100%. Variation in epilepsy prevalence was consistent with a logistic function of onchocerciasis prevalence, with epilepsy prevalence being increased, on average, by 0.4% for each 10% increase in onchocerciasis prevalence. Conclusion These results give further evidence that onchocerciasis is associated with epilepsy and that the disease burden of onchocerciasis might have to be re-estimated by taking into account this relationship. PMID:19529767

Memory and phonological awareness in children with Benign Rolandic Epilepsy compared to a matched control group.

PubMed

Northcott, Ellen; Connolly, Anne M; Berroya, Anna; McIntyre, Jenny; Christie, Jane; Taylor, Alan; Bleasel, Andrew F; Lawson, John A; Bye, Ann M E

2007-06-01

In a previous study we demonstrated children with Benign Rolandic Epilepsy have normal intelligence and language ability. However, difficulties in verbal and visual memory and aspects of phonological awareness were found compared to normative data. To address the methodological limitations related to the use of normative data, we compared the same cohort of children with Benign Rolandic Epilepsy to a matched control group. Controls (n=40) matched on age and gender to the Benign Rolandic Epilepsy cohort underwent neuropsychological assessment. The life functioning of the control group was assessed using a modified version of the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). The study confirmed the previous findings of memory and phonological awareness difficulties. In addition, the children with Benign Rolandic Epilepsy had significantly lower IQ scores than the matched control group. Paired sample t-tests showed that on 8 of 11 QOLCE scales, children with Benign Rolandic Epilepsy were rated by parents as having poorer life functioning compared to matched controls, including lower parental ratings on the subscales of memory and language. Benign Rolandic Epilepsy has an excellent seizure prognosis, but this study further emphasizes potential cognitive difficulties. Using an age and gender matched control group, the previous findings of memory and phonological awareness difficulties were validated. These problems in cognition were also identified by parents of children with Benign Rolandic Epilepsy as problematic and impacting upon the child's quality of life.

Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function?

PubMed

Avanzini, Giuliano; Depaulis, Antoine; Tassinari, Alberto; de Curtis, Marco

2013-11-01

Relevant to the definition of epileptic encephalopathy (EE) is the concept that the epileptic activity itself may contribute to bad outcomes, both in terms of epilepsy and cognition, above and beyond what might be expected from the underlying pathology alone, and that these can worsen over time. The review of the clinical and experimental evidence that seizures or interictal electroencephalography (EEG) discharges themselves can induce a progression toward more severe epilepsy and a regression of brain function leads to the following conclusions: The possibility of seizure-dependent worsening is by no means a general one but is limited to some types of epilepsy, namely mesial temporal lobe epilepsy (MTLE) and EEs. Clinical and experimental data concur in indicating that prolonged seizures/status epilepticus (SE) are a risky initial event that can set in motion an epileptogenic process leading to persistent, possibly drug-refractory epilepsies. The mechanisms for SE-related epileptogenic process are incompletely known; they seem to involve inflammation and/or glutamatergic transmission. The evidence of the role of recurrent individual seizures in sustaining epilepsy progression is ambiguous. The correlation between high seizure frequency and bad outcome does not necessarily demonstrate a cause-effect relationship, rather high seizure frequency and bad outcome can both depend on a particularly aggressive epileptogenic process. The results of EE studies challenge the idea of a common seizure-dependent mechanism for epilepsy progression/intellectual deterioration. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

History and Technical Approaches and Considerations for Ablative Surgery for Epilepsy.

PubMed

Sinha, Saurabh; Danish, Shabbar F

2016-01-01

The history of epilepsy surgery is generally noted to have begun in 1886 with Victor Horsley's first report of craniotomies for posttraumatic epilepsy. With increased understanding of brain function and development of electroencephalographic methods, nonlesional epilepsy began to be treated with resection in the 1950s. Methodological improvements and increased understanding of pathophysiology followed, and the advent of stereotaxy and ablative technology in the 1960s and 1970s heralded a new era of minimally invasive, targeted procedures for lesional and nonlesional epilepsy. Current techniques combine stereotactic methods, improved ablative technologies, and electroencephalographic methods for a multidisciplinary approach to the neurosurgical treatment of epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Adaptive functioning in pediatric epilepsy: contributions of seizure-related variables and parental anxiety.

PubMed

Kerne, Valerie; Chapieski, Lynn

2015-02-01

Young people with epilepsy are less likely to achieve the level of independence attained by their peers. We examined the seizure-related variables that placed a group of 97 pediatric patients with intractable seizures at risk for poor adaptive functioning. Analyses evaluated both the direct effects of the medical variables and indirect effects that were mediated through increased parental anxiety about their child's epilepsy. Higher numbers of anticonvulsants, presence of seizures that secondarily generalize, longer duration of seizure disorder, and younger age at onset were all identified as risk factors for poor adaptive functioning. Depending on the specific behavioral domain of adaptive functioning, the effects were sometimes direct and sometimes indirect. Lower levels of parental education and positive family history of seizures were associated with higher levels of parental anxiety. Interventions that target parental anxiety about seizures may mitigate the deleterious effects of epilepsy on social development. Copyright © 2014 Elsevier Inc. All rights reserved.

Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks

PubMed Central

Vaudano, Anna Elisabetta; Ruggieri, Andrea; Avanzini, Pietro; Gessaroli, Giuliana; Cantalupo, Gaetano; Coppola, Antonietta; Sisodiya, Sanjay M.

2017-01-01

Abstract See Hamandi (doi:10.1093/awx049) for a scientific commentary on this article. Photosensitivity is a condition in which lights induce epileptiform activities. This abnormal electroencephalographic response has been associated with hyperexcitability of the visuo-motor system. Here, we evaluate if intrinsic dysfunction of this network is present in brain activity at rest, independently of any stimulus and of any paroxysmal electroencephalographic activity. To address this issue, we investigated the haemodynamic correlates of the spontaneous alpha rhythm, which is considered the hallmark of the brain resting state, in photosensitive patients and in people without photosensitivity. Second, we evaluated the whole-brain functional connectivity of the visual thalamic nuclei in the various populations of subjects under investigation. Forty-four patients with epilepsy and 16 healthy control subjects underwent an electroencephalography-correlated functional magnetic resonance imaging study, during an eyes-closed condition. The following patient groups were included: (i) genetic generalized epilepsy with photosensitivity, 16 subjects (mean age 25 ± 10 years); (ii) genetic generalized epilepsy without photosensitivity, 13 patients (mean age 25 ± 11 years); (iii) focal epilepsy, 15 patients (mean age 25 ± 9 years). For each subject, the posterior alpha power variations were convolved with the standard haemodynamic response function and used as a regressor. Within- and between-groups second level analyses were performed. Whole brain functional connectivity was evaluated for two thalamic regions of interest, based on the haemodynamic findings, which included the posterior thalamus (pulvinar) and the medio-dorsal thalamic nuclei. Genetic generalized epilepsy with photosensitivity demonstrated significantly greater mean alpha-power with respect to controls and other epilepsy groups. In photosensitive epilepsy, alpha-related blood oxygen level-dependent signal changes demonstrated lower decreases relative to all other groups in the occipital, sensory-motor, anterior cingulate and supplementary motor cortices. Coherently, the same brain regions demonstrated abnormal connectivity with the visual thalamus only in epilepsy patients with photosensitivity. As predicted, our findings indicate that the cortical-subcortical network generating the alpha oscillation at rest is different in people with epilepsy and visual sensitivity. This difference consists of a decreased alpha-related inhibition of the visual cortex and sensory-motor networks at rest. These findings represent the substrate of the clinical manifestations (i.e. myoclonus) of the photoparoxysmal response. Moreover, our results provide the first evidence of the existence of a functional link between the circuits that trigger the visual sensitivity phenomenon and those that generate the posterior alpha rhythm. PMID:28334965

A hopelessness model of depressive symptoms in youth with epilepsy.

PubMed

Wagner, Janelle L; Smith, Gigi; Ferguson, Pamela L; Horton, Stephanie; Wilson, Erin

2009-01-01

To test the cognitive diathesis-stress and mediational components of the theory of learned hopelessness in youth with epilepsy. Seventy-seven participants ages 9-17 (35 girls, 42 boys) completed measures of depressive symptoms, hopelessness, self-efficacy for seizure management, and attitude toward epilepsy. Caregivers provided information on seizure activity. Diagnostic and treatment information was obtained via medical record review. Regression analyses revealed that hopelessness mediated the attitude towards epilepsy-depressive symptom relationship. While attitude toward epilepsy and self-efficacy were independent predictors of depressive symptoms, the relationship of attitudes toward epilepsy and depressive symptoms was not enhanced with low self-efficacy for seizure management. Findings support the mediation component of the learned hopelessness theory in youth with epilepsy, suggesting the importance of interventions that assist youth in identifying epilepsy-related aspects of functioning over which they can realistically exercise control and challenging negative thoughts about situations they cannot control.

Knowledge and attitudes toward epilepsy amongst students in the health area: intervention aimed at enlightenment.

PubMed

Tedrus, Glória Maria A S; Fonseca, Lineu Corrêa; Vieira, Ana Lídia da Câmara

2007-12-01

It is known that there is a lack of knowledge about epilepsy amongst the population in general, with consequent prejudice and discrimination towards epileptic patients. Considering the importance of health professionals in the diffusion of knowledge about this neurological condition, the objective of the present study was to evaluate modifications in the knowledge and attitudes of students in the health area with respect to epilepsy, after an intervention including the presentation of specific audio-visual material and a discussion on the basic aspects of epilepsy. Simple self-administered questionnaires were applied to one hundred and sixteen health area students before and after the session of enlightenment. After the session there was significant (p<0.05) improvement in answers to different questions about etiology, epidemiology, education, work, and attitude during the seizure. The results suggest the need to include a routine low complexity educational activity in the curriculum of various courses in the health area.

Neuropsychological profiles and outcomes in children with new onset frontal lobe epilepsy.

PubMed

Matricardi, Sara; Deleo, Francesco; Ragona, Francesca; Rinaldi, Victoria Elisa; Pelliccia, Sarah; Coppola, Giangennaro; Verrotti, Alberto

2016-02-01

Frontal lobe epilepsy (FLE) is the second most frequent type of localization-related epilepsy, and it may impact neurocognitive functioning with high variability. The prevalence of neurocognitive impairment in affected children remains poorly defined. This report outlines the neuropsychological profiles and outcomes in children with new onset FLE, and the impact of epilepsy-related factors, such as seizure frequency and antiepileptic drug (AED) load, on the neurocognitive development. Twenty-three consecutive children (15 males and 8 females) with newly diagnosed cryptogenic FLE were enrolled; median age at epilepsy onset was 7 years (6-9.6 years). They underwent clinical and laboratory evaluation and neuropsychological assessment before starting AED treatment (time 0) and after one year of treatment (time 1). Twenty age-matched patients affected by idiopathic generalized epilepsy (10 male and 10 females) and eighteen age-matched healthy subjects (9 males and 9 females) were enrolled as controls and underwent the same assessment. All patients with FLE showed a significant difference in almost all assessed cognitive domains compared with controls, mainly in frontal functions and memory. At time 1, patients were divided into two groups according to epilepsy-related factors: group 1 (9 patients) with persisting seizures despite AED polytherapy, and group 2 (14 patients) with good seizure control in monotherapy. A significant difference was highlighted in almost all subtests in group 1 compared with group 2, both at time 0 and at time 1. In children with FLE showing a broad range of neurocognitive impairments, the epilepsy-related factors mostly related to a worse neurocognitive outcome are poor seizure control and the use of AED polytherapy, suggesting that epileptic discharges may have a negative impact on the functioning of the involved cerebral regions. Copyright © 2015 Elsevier Inc. All rights reserved.

Stem cell therapy for treatment of epilepsy.

PubMed

Goodarzi, Parisa; Aghayan, Hamid Reza; Soleimani, Masoud; Norouzi-Javidan, Abbas; Mohamadi-Jahani, Fereshteh; Jahangiri, Sharareh; Emami-Razavi, Seyed Hasan; Larijani, Bagher; Arjmand, Babak

2014-01-01

Epilepsy as one of the most common neurological disorders affects more than 50 million people worldwide with a higher prevalence rate in low-income countries. Excessive electrical discharges in neurons following neural cell damage or loss cause recurrent seizures. One of the most common and difficult to treat types of epilepsy is temporal lobe epilepsy (TLE) which results from hippocampal sclerosis. Nowadays, similar to other diseases, epilepsy also is a candidate for treatment with different types of stem cells. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. Two major roles of stem cell therapy in epilepsy are prophylaxis against chronic epilepsy and amelioration cognitive function after the occurrence of TLE. Several animal studies have supported the use of these cells for treating drug-resistant TLE. Although stem cell therapy seems like a promising approach for treatment of epilepsy in the future however, there are some serious safety and ethical concerns that are needed to be eliminated before clinical application.

Quality of life in epilepsy (QOLIE): insights about epilepsy and support groups from people with epilepsy (San Francisco Bay Area, USA).

PubMed

Chung, Kenny; Liu, Yuan; Ivey, Susan L; Huang, Debbie; Chung, Corina; Guo, Wenting; Tseng, Winston; Ma, Daveena

2012-06-01

This study evaluated quality of life (QOL) in people with epilepsy (PWE) in the San Francisco Bay Area. This was a qualitative study examining QOL through the use of focus groups and of the QOLIE-31-P survey instrument. Six focus groups were conducted to examine self-reported challenges due to epilepsy. Focus groups were conducted for individuals who did and did not attend support groups. Individuals with epilepsy reported substantial difficulties with finances, physical and psychosocial functioning. Also, limited knowledge about services and relatively negative feelings toward self were common among newly diagnosed participants. Many of the issues surrounding QOL and challenges were shared across groups. Epilepsy-related social services appeared to be useful in helping PWE cope and in increasing PWE's awareness of key enabling services. Although many individuals with epilepsy reported poor QOL and other challenges, epilepsy-related services may be under-utilized due to a lack of awareness. Copyright © 2012 Elsevier Inc. All rights reserved.

Neuropsychologist's (re-)view: Resective versus ablative amygdalohippocampectomies.

PubMed

Witt, Juri-Alexander; Hoppe, Christian; Helmstaedter, Christoph

2018-05-01

Pharmacoresistant mesial temporal lobe epilepsy (mTLE) represents the major indication for epilepsy surgery. Since epilepsy surgery is an elective treatment option, preserving cognition is a high priority. Given the essential role of temporomesial structures in declarative long-term memory formation, surgical treatment for mTLE is primarily associated with a risk of material-specific memory decline, but other cognitive domains may be affected as well. The major determinants for the neuropsychological outcome are the functional integrity of surgically affected tissues, the functional reserve capacities of the remnant brain, the postoperative seizure outcome, as well as the quantitative and qualitative changes of antiepileptic drugs. Anterior temporal lobectomy has long been the standard procedure for treating mTLE. However, if an exclusive mesial pathology is present, then functional non-pathological tissues of the temporal pole and neocortex are sacrificed. As a result, more selective or tailored surgical approaches have been developed which strive towards minimizing iatrogenic effects. However, whether or not these approaches are equipotential with regard to seizure control is still a matter of debate. The quality of the presurgical diagnostics could also be decisive. Selective surgery should indeed be selective in terms of preventing evitable collateral cortical damage along the approach. Invasivity and risks of collateral damage associated with "open" selective resective surgery are further minimized by stereotactic ablative surgery via thermocoagulation, or eventually even eliminated by gamma knife surgery. From a neuropsychological point of view, this development is consequent and desirable, but no clear scientific evidence of a superior cognitive outcome after radiosurgery or thermocoagulation currently exists. The studies that are available contain significant methodological limitations. Thus, randomized head-to-head cognitive outcome studies of competing selective procedures are needed, which should meet the minimum requirements for study design and neuropsychological evaluations. Finally, none of the surgical treatment variants can systematically prevent memory decline when the hippocampus is targeted. Copyright © 2017 Elsevier B.V. All rights reserved.

Parent-rated emotional-behavioral and executive functioning in childhood epilepsy.

PubMed

Kavanaugh, Brian C; Scarborough, Vanessa Ramos; Salorio, Cynthia F

2015-01-01

The present study examined clinical and demographic risk factors associated with parent-rated emotional-behavioral and executive functioning in children and adolescents with epilepsy. The medical records of 152 children and adolescents with epilepsy referred for neuropsychological evaluation were reviewed. Results indicated that the sample displayed significantly elevated symptoms across the emotional-behavioral and executive domains assessed. Executive functioning and behavioral symptoms had the highest rates of clinically elevated scores, with lowest rates of elevated scores in internalizing and externalizing emotional problems. Only 34% of those participants with clinically significant emotional-behavioral or executive functioning difficulties had a history of psychological or counseling services, highlighting the underserved mental health needs of this population. In regard to clinical factors, the majority of seizure-related variables were not associated with emotional-behavioral or executive functioning. However, the frequency of seizures (i.e., seizure status) was associated with behavioral regulation aspects of executive functioning, and the age at evaluation was associated with externalizing problems and behavioral symptoms. Family psychiatric history (with the exception of ADHD) was associated with all domains of executive and emotional-behavioral functioning. In summary, emotional-behavioral and executive functioning difficulties frequently co-occur with seizures in childhood epilepsy, with both seizure-related and demographic factors contributing to the presentation of such neurobehavioral comorbidities. The present findings provide treatment providers of childhood epilepsy with important information to assist in better identifying children and adolescents who may be at risk for neurobehavioral comorbidities and may benefit from intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

[New developments in epileptogenesis and therapeutic perspectives].

PubMed

Lerche, H; Vezzani, A; Beck, H; Blümcke, I; Weber, Y; Elger, C

2011-08-01

Epileptogenesis describes the mechanisms of how epilepsies are generated. We have chosen four areas in which significant progress has been achieved in understanding epileptogenesis. Those are (1) inflammatory processes which play an increasingly important role for the generation of temporal lobe epilepsy with hippocampal sclerosis (TLE with HS), (2) disturbances of intrinsic properties of neuronal compartments, in particular acquired defects of ion channels of which those in dendrites are described here for TLE with HS, (3) epigenetic effects, which affect for example the methylation of promoters and secondarily can change the expression of specific genes in TLE with HS, and finally (4) the epileptogenesis of idiopathic epilepsies which are caused by inborn genetic alterations affecting mainly ion channels. Apart from aspects of basic research, we will describe clinical consequences and therapeutic perspectives.

Response to Placebo in Clinical Epilepsy Trials - Old Ideas and New Insights

PubMed Central

Goldenholz, Daniel M.; Goldenholz, Shira R

2016-01-01

Randomized placebo controlled trials are a mainstay of modern clinical epilepsy research; the success or failure of innovative therapies depends on proving superiority to a placebo. Consequently, understanding what drives response to placebo (including the “placebo effect”) may facilitate evaluation of new therapies. In this review, part one will explore observations about placebos specific to epilepsy, including the relatively higher placebo response in children, apparent increase in placebo response over the past several decades, geographic variation in placebo effect, relationship to baseline epilepsy characteristics, influence of nocebo on clinical trials, the possible increase in (SUDEP) in placebo arms of trials, and patterns that placebo responses appear to follow in individual patients. Part two will discuss the principal causes of placebo responses, including regression to the mean, anticipation, classical conditioning, the Hawthorne effect, expectations from symbols, and the natural history of disease. Included in part two will be a brief overview of recent advances using simulations from large datasets that have afforded new insights into causes of epilepsy related placebo responses. In part three, new developments in study design will be explored, including sequential parallel comparison, two-way enriched design, time to pre-randomization, delayed start, and cohort reduction techniques. PMID:26921852

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

PubMed

Vogt, Viola Lara; Äikiä, Marja; Del Barrio, Antonio; Boon, Paul; Borbély, Csaba; Bran, Ema; Braun, Kees; Carette, Evelien; Clark, Maria; Cross, Judith Helen; Dimova, Petia; Fabo, Daniel; Foroglou, Nikolaos; Francione, Stefano; Gersamia, Anna; Gil-Nagel, Antonio; Guekht, Alla; Harrison, Sue; Hecimovic, Hrvoje; Heminghyt, Einar; Hirsch, Edouard; Javurkova, Alena; Kälviäinen, Reetta; Kavan, Nicole; Kelemen, Anna; Kimiskidis, Vasilios K; Kirschner, Margarita; Kleitz, Catherine; Kobulashvili, Teia; Kosmidis, Mary H; Kurtish, Selin Yagci; Lesourd, Mathieu; Ljunggren, Sofia; Lossius, Morten Ingvar; Malmgren, Kristina; Mameniskiené, Ruta; Martin-Sanfilippo, Patricia; Marusic, Petr; Miatton, Marijke; Özkara, Çiğdem; Pelle, Federica; Rubboli, Guido; Rudebeck, Sarah; Ryvlin, Philippe; van Schooneveld, Monique; Schmid, Elisabeth; Schmidt, Pia-Magdalena; Seeck, Margitta; Steinhoff, Bernhard J; Shavel-Jessop, Sara; Tarta-Arsene, Oana; Trinka, Eugen; Viggedal, Gerd; Wendling, Anne-Sophie; Witt, Juri-Alexander; Helmstaedter, Christoph

2017-03-01

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Memory Functions following Surgery for Temporal Lobe Epilepsy in Children

ERIC Educational Resources Information Center

Jambaque, Isabelle; Dellatolas, Georges; Fohlen, Martine; Bulteau, Christine; Watier, Laurence; Dorfmuller, Georg; Chiron, Catherine; Delalande, Olivier

2007-01-01

Surgical treatment appears to improve the cognitive prognosis in children undergoing surgery for temporal lobe epilepsy (TLE). The beneficial effects of surgery on memory functions, particularly on material-specific memory, are more difficult to assess because of potentially interacting factors such as age range, intellectual level,…

Improved Cerebral Function in Mesial Temporal Lobe Epilepsy after Subtemporal Amygdalohippocampectomy

ERIC Educational Resources Information Center

Takaya, Shigetoshi; Mikuni, Nobuhiro; Mitsueda, Takahiro; Satow, Takeshi; Taki, Junya; Kinoshita, Masako; Miyamoto, Susumu; Hashimoto, Nobuo; Ikeda, Akio; Fukuyama, Hidenao

2009-01-01

The functional changes that occur throughout the human brain after the selective removal of an epileptogenic lesion remain unclear. Subtemporal selective amygdalohippocampectomy (SAH) has been advocated as a minimally invasive surgical procedure for patients with medically intractable mesial temporal lobe epilepsy (MTLE). We evaluated the effects…

A model-free characterization of recurrences in stationary time series

NASA Astrophysics Data System (ADS)

Chicheportiche, Rémy; Chakraborti, Anirban

2017-05-01

Study of recurrences in earthquakes, climate, financial time-series, etc. is crucial to better forecast disasters and limit their consequences. Most of the previous phenomenological studies of recurrences have involved only a long-ranged autocorrelation function, and ignored the multi-scaling properties induced by potential higher order dependencies. We argue that copulas is a natural model-free framework to study non-linear dependencies in time series and related concepts like recurrences. Consequently, we arrive at the facts that (i) non-linear dependences do impact both the statistics and dynamics of recurrence times, and (ii) the scaling arguments for the unconditional distribution may not be applicable. Hence, fitting and/or simulating the intertemporal distribution of recurrence intervals is very much system specific, and cannot actually benefit from universal features, in contrast to the previous claims. This has important implications in epilepsy prognosis and financial risk management applications.

Female sexual function mediates the effects of medication adherence on quality of life in people with epilepsy.

PubMed

Lin, Chung-Ying; Burri, Andrea; Fridlund, Bengt; Pakpour, Amir H

2017-02-01

The purpose of this study was to understand the mediating effects of female sexual functioning in the association between medication adherence and quality of life (QoL) in Iranian women with epilepsy (WWE). Women's sexual functioning was measured using Female Sexual Function Index; QoL using Quality of Life in Epilepsy; epilepsy severity using Liverpool Seizure Severity Scale; subjective medication adherence using Medication Adherence Report Scale; and objective medication adherence using serum level for antiepileptic drugs in 567 WWE. Medication adherence was measured at baseline, while women's sexual functioning, QoL, and epilepsy severity were measured at the 6-month follow-up. Structural equation modeling and regression models were conducted to examine the mediating role of women's sexual functioning. The mediating effects of sexual functioning in the relationship between medication adherence (including subjective and objective measures) and QoL were supported in the total score of Female Sexual Function Index (coefficient=0.415, SE=0.117, p<0.001 for subjective medication adherence; coefficient=1.980, SE=0.446, p<0.001 for objective medication adherence). Seizure severity was significantly associated with QoL but only when objective medication adherence was measured (coefficient=-0.094, SE=0.036, p=0.009). Our results extended the importance of medication adherence from symptom reduction to the beneficial effects of women's sexual functioning and QoL. Health care providers should be aware of these additional benefits of medication adherence and use these arguments to encourage female patients to take their medication, which can eventually increase their sexual satisfaction and overall QoL. Copyright © 2016 Elsevier Inc. All rights reserved.

Thyroid hormones: Possible roles in epilepsy pathology.

PubMed

Tamijani, Seyedeh Masoumeh Seyedhoseini; Karimi, Benyamin; Amini, Elham; Golpich, Mojtaba; Dargahi, Leila; Ali, Raymond Azman; Ibrahim, Norlinah Mohamed; Mohamed, Zahurin; Ghasemi, Rasoul; Ahmadiani, Abolhassan

2015-09-01

Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Tetanus toxin as a tool for studying epilepsy.

PubMed

Mellanby, J; Hawkins, C; Mellanby, H; Rawlins, J N; Impey, M E

1984-01-01

The use of tetanus toxin, injected into the hippocampus of the rat, to produce an "animal model" of chronic limbic epilepsy is described. This model has yielded information complementary to that derived from other animal models and has several important advantages: while it involves spontaneous seizures, it occurs without gross damage to the brain ; it is eventually reversible in terms of fits and the overall reappearance of the EEG. It can therefore be used to look both at the effects of ongoing epilepsy and also at the long-term changes in brain function induced by previous epilepsy. Evidence is presented that the toxin probably remains localised at the site of injection. The information which has so far been obtained with this model on the relation between epilepsy and abnormal behaviour is summarised. In particular, it appears that the epilepsy produces long-term deficits in the animals' ability to learn and remember of a sort which suggest that an enduring malfunction has been induced in the hippocampus. The significance of the findings for clinical research and for future investigation of the nature of epilepsy are described. It is emphasised that the neurotoxins may be usefully exploited not only for investigating the molecular basis of neuronal mechanisms but also for inducing long-lasting plastic changes in integrated brain function.

[Polish adaptation and validation of Health-Related Quality of Life in Childhood Epilepsy Questionnaire].

PubMed

Mathiak, Krystyna A; Karzel, Katarzyna; Mathiak, Klaus; Ostaszewski, Paweł; Luba, Małgorzata; Wolańczyk, Tomasz

2007-01-01

Epilepsy is a frequent chronic disease in children, having a strong impact on a child's psychosocial functioning. Effective therapy must take into account the wide range of physical, psychological and social needs of patients. The importance of assessing patients' quality of life is becoming increasingly acknowledged. In addition to providing better health care, it may reveal how the disease and its psychosocial outcome interact. Quality of life in epilepsy can be assessed most reliably by disease-specific measures. Health-Related Quality of Life in Childhood Epilepsy (QOLCE) is an English parental questionnaire for children aged between 4 and 18 years. It contains 87 questions that fall into five domains: physical function, emotional well-being, cognitive function, social function and behavioural function. The original scale has a well-grounded theoretical background and good psychometric properties. The aim of the study was to create a Polish version of QOLCE and evaluate its psychometric properties. Parents of 87 patients suffering from epilepsy were recruited in neurological clinics in the Warsaw area. Reliability was very high (Cronbach's alpha = 0.97). The construct validity was confirmed by the correlation between subscales of QOLCE and the Child Behaviour Checklist, as well as selected clinical measures of child's health (duration of disease: r=-0.22, p=0.02; duration of treatment: r=-0.20, p=0.04; number of hospitalizations: r=-0.24, p=0.02). All the psychometric properties were similar to those of the original scale. A Polish scale examining the quality of life was created that takes into account a wide range of psychosocial problems. We confirmed very high reliability and good validity, and thus we recommend the inventory for both research on and clinical diagnostics of Polish children with epilepsy.

Memory reorganization following anterior temporal lobe resection: a longitudinal functional MRI study

PubMed Central

Bonelli, Silvia B.; Thompson, Pamela J.; Yogarajah, Mahinda; Powell, Robert H. W.; Samson, Rebecca S.; McEvoy, Andrew W.; Symms, Mark R.; Koepp, Matthias J.

2013-01-01

Anterior temporal lobe resection controls seizures in 50–60% of patients with intractable temporal lobe epilepsy but may impair memory function, typically verbal memory following left, and visual memory following right anterior temporal lobe resection. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated the reorganization of memory function in patients with temporal lobe epilepsy before and after left or right anterior temporal lobe resection and the efficiency of postoperative memory networks. We studied 46 patients with unilateral medial temporal lobe epilepsy (25/26 left hippocampal sclerosis, 16/20 right hippocampal sclerosis) before and after anterior temporal lobe resection on a 3 T General Electric magnetic resonance imaging scanner. All subjects had neuropsychological testing and performed a functional magnetic resonance imaging memory encoding paradigm for words, pictures and faces, testing verbal and visual memory in a single scanning session, preoperatively and again 4 months after surgery. Event-related analysis revealed that patients with left temporal lobe epilepsy had greater activation in the left posterior medial temporal lobe when successfully encoding words postoperatively than preoperatively. Greater pre- than postoperative activation in the ipsilateral posterior medial temporal lobe for encoding words correlated with better verbal memory outcome after left anterior temporal lobe resection. In contrast, greater postoperative than preoperative activation in the ipsilateral posterior medial temporal lobe correlated with worse postoperative verbal memory performance. These postoperative effects were not observed for visual memory function after right anterior temporal lobe resection. Our findings provide evidence for effective preoperative reorganization of verbal memory function to the ipsilateral posterior medial temporal lobe due to the underlying disease, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after anterior temporal lobe resection. Early postoperative reorganization to ipsilateral posterior or contralateral medial temporal lobe structures does not underpin better performance. Additionally our results suggest that visual memory function in right temporal lobe epilepsy is affected differently by right anterior temporal lobe resection than verbal memory in left temporal lobe epilepsy. PMID:23715092

Course Work and Career Planning for Students with Epilepsy: A Guide for School Counselors.

ERIC Educational Resources Information Center

Epilepsy Foundation of America, Landover, MD.

Intended for secondary school counselors, the pamphlet examines effects of epilepsy on course work and career planning. Briefly covered are the nature of epilepsy, treatment, social impact, and public misunderstanding. Effects on academic achievement are discussed in terms of functional problems related to where the seizure activity is located in…

Epilepsy genetics: clinical beginnings and social consequences.

PubMed

Johnston, J A; Rees, M I; Smith, P E M

2009-07-01

The approach to epilepsy care has transformed in the last 30 years, with more and better anti-epileptic medications, improved cerebral imaging and increased surgical options. Alongside this, developments in neuroscience and molecular genetics have furthered the understanding of epileptogenesis. Future developments in pharmacogenomics hold the promise of antiepileptic drugs matched to specific genotypes. Despite this rapid progress, one-third of epilepsy patients remain refractory to medication, with their seizures impacting upon day-to-day activity, social well-being, independence, economic output and quality of life. International genome collaborations, such as HapMap and the Welcome Trust Case-Control Consortium single nucleotide polymorphism (SNP) mapping project have identified common genetic variations in diseases of major public health importance. Such genetic signposts should help to identify at-risk populations with a view to producing more effective pharmaceutical treatments. Neurological disorders, despite comprising one-fifth of UK acute medical hospital admissions, are surprisingly under-represented in these projects. Epilepsy is the commonest serious neurological disorder worldwide. Although physically, psychologically, socially and financially disabling, it rarely receives deserved attention from physicians, scientists and governmental bodies. As outlined in this article, research into epilepsy genetics presents unique challenges. These help to explain why the identification of its complex genetic traits has lagged well behind other disciplines, particularly the efforts made in neuropsychiatric disorders. Clinical beginnings must underpin any genetic understanding in epilepsy. Success in identifying genetic traits in other disorders does not make the automatic case for genome-wide screening in epilepsy, but such is a desired goal. The essential clinical approach of accurately phenotyping, diagnosing and interpreting the dynamic nature of epilepsy remains fundamental to harvesting its potential translational outcomes.

Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy.

PubMed

Blackmon, Karen

2015-06-01

Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment. This article is part of a Special Issue entitled "Autism and Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

Low-frequency electroacupuncture suppresses focal epilepsy and improves epilepsy-induced sleep disruptions.

PubMed

Yi, Pei-Lu; Lu, Chin-Yu; Jou, Shuo-Bin; Chang, Fang-Chia

2015-07-07

The positive effects of acupuncture at Feng-Chi acupoints on treating epilepsy and insomnia have been well-documented in ancient Chinese literature. However, there is a lack of scientific evidence to elucidate the underlying mechanisms behind these effects. Our previous study demonstrated that high-frequency (100 Hz) electroacupuncture (EA) at Feng-Chi acupoints deteriorates both pilocarpine-induced focal epilepsy and sleep disruptions. This study investigated the effects of low-frequency (10 Hz) EA on epileptic activities and epilepsy-induced sleep disruptions. In rats, the Feng-Chi acupoint is located 3 mm away from the center of a line between the two ears. Rats received 30 min of 10 Hz EA stimuli per day before each day's dark period for three consecutive days. Our results indicated that administration of pilocarpine into the left CeA at the beginning of the dark period induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep during the consequent light period. Low-frequency (10 Hz) EA at Feng-Chi acupoints suppressed pilocarpine-induced epileptiform EEGs, and this effect was in turn blocked by naloxone (a broad-spectrum opioid receptor antagonist), but not by naloxonazine (a μ-receptor antagonist), naltrindole (a δ-receptor antagonist) and nor-binaltorphimine (a κ-receptor antagonist). Ten Hz EA enhanced NREM sleep during the dark period, and this enhancement was blocked by all of the opioid receptor antagonists. On the other hand, 10 Hz EA reversed pilocarpine-induced NREM suppression during the light period, and the EA's effect on the sleep disruption was only blocked by naloxonazine. These results indicate that low-frequency EA stimulation of Feng-Chi acupoints is beneficial in improving epilepsy and epilepsy-induced sleep disruptions, and that opioid receptors in the CeA mediate EA's therapeutic effects.

The relevance of attention deficit hyperactivity disorder in self-limited childhood epilepsy with centrotemporal spikes.

PubMed

Lima, Ellen Marise; Rzezak, Patricia; Dos Santos, Bernardo; Gentil, Letícia; Montenegro, Maria A; Guerreiro, Marilisa M; Valente, Kette D

2018-05-01

In this study, we aimed to evaluate the attentional and executive functions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS) with and without attention-deficit hyperactivity disorder (ADHD) compared with controls and compared with patients with ADHD without epilepsy. We evaluated 12 patients with BCECTS and ADHD (66.7% boys; mean age of 9.67years); 11 children with non-ADHD BCECTS (63.6% boys; mean age of 11.91years); 20 healthy children (75% boys; mean age of 10.15years); and 20 subjects with ADHD without epilepsy (60% boys; mean age of 10.9years). We used a comprehensive battery of neuropsychological tests to evaluate attentional and executive functions in their broad domains. Patients with BCECTS and ADHD had worse performance in Conners' Continuous Performance Test II (reaction time standard error [p=0.008], variability [p=0.033], perseverations [p=0.044] and in reaction time interstimuli interval [p=0.016]). Patients with ADHD showed worse performance in Trail Making Test B errors [p=0.012]. In conclusion, patients with BCECTS and ADHD had worse executive and attentional performance compared with controls than non-ADHD patients with BCECTS. Regardless of the presence of epilepsy, ADHD also negatively impacted executive and attentional functions but in different executive subdomains compared with patients with epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of creative thinking in children with idiopathic epilepsy (absence epilepsy).

PubMed

Di Filippo, T; Parisi, L; Roccella, M

2012-02-01

Creativity represents the silent character of human behaviour. In children with epilepsy, cognitive performance of has mainly been investigated under the assumption that the disorder represents a risk factor for the development of intellectual function. In subjects with different forms of epilepsy, neuropsychologic disorders have been detected even when cognitive-global functioning is unimpaired. The cognitive functions of subjects with epilepsy have been widely studied, but their creativity has been never evaluated to date. The aim of this study was to describe the development of creative thinking in a group of children with absence epilepsy. The test battery included: the Torrance Test of Creative Thinking (TTCT), the Wechsler Intelligence Scale for Children-revised (WISC-R) and the Goodenough Human Figure Drawing Test. Statistical analysis (Mann-Whitney test) showed a statistically significant difference (P <0.05) in test scores between two groups of subjects (children with epilesy vs control group), with higher scores for figure originality, figure fluidity and figure elaboration in the control group. There was a significant correlation (Spearman's rho) between verbal IQ and verbal fluidity and verbal flexibility subscale scores and between performance IQ and figure elaboration, between total IQ and verbal fluidity and verbal flexibility subscales (P <0.05; r >0.30). Low scores on the figure originality subscales seem to confirm the hypothesis that adverse psychodynamic and relational factors impoverish autonomy, flexibility and manipulator interests. The communication channels between subjects with epilepsy and their family members were affected by the disorder, as were the type of emotional dynamics and affective flux.

Genetic Association Analysis of ATP Binding Cassette Protein Family Reveals a Novel Association of ABCB1 Genetic Variants with Epilepsy Risk, but Not with Drug-Resistance

PubMed Central

Balan, Shabeesh; Bharathan, Sumitha Prameela; Vellichiramal, Neetha Nanoth; Sathyan, Sanish; Joseph, Vijai; Radhakrishnan, Kurupath; Banerjee, Moinak

2014-01-01

Epilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED)-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype for AED-resistant epilepsy); juvenile myoclonic epilepsy (JME) (prototype for AED-responsive epilepsy); and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T) rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004). This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004) and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05) cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency for MTLE-HS in south Indian ancestry from Kerala. PMID:24586633

How Sleep Activates Epileptic Networks?

PubMed Central

Halász, Peter

2013-01-01

Background. The relationship between sleep and epilepsy has been long ago studied, and several excellent reviews are available. However, recent development in sleep research, the network concept in epilepsy, and the recognition of high frequency oscillations in epilepsy and more new results may put this matter in a new light. Aim. The review address the multifold interrelationships between sleep and epilepsy networks and with networks of cognitive functions. Material and Methods. The work is a conceptual update of the available clinical data and relevant studies. Results and Conclusions. Studies exploring dynamic microstructure of sleep have found important gating mechanisms for epileptic activation. As a general rule interictal epileptic manifestations seem to be linked to the slow oscillations of sleep and especially to the reactive delta bouts characterized by A1 subtype in the CAP system. Important link between epilepsy and sleep is the interference of epileptiform discharges with the plastic functions in NREM sleep. This is the main reason of cognitive impairment in different forms of early epileptic encephalopathies affecting the brain in a special developmental window. The impairment of cognitive functions via sleep is present especially in epileptic networks involving the thalamocortical system and the hippocampocortical memory encoding system. PMID:24159386

Cognitive changes in people with temporal lobe epilepsy over a 13-year period.

PubMed

Mameniškienė, Rūta; Rimšienė, Justė; Puronaitė, Roma

2016-10-01

The aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13years and to determine what clinical and treatment characteristics may have been associated with these. Thirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13years earlier. There was no significant change in verbal and verbal-logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal-logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal-logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal-logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression. Over a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Functionality of Triggers for Epilepsy Patients Assessed by Text and Data Mining of Medical and Nursing Records.

PubMed

Kivekäs, Eija; Kinnunen, Ulla-Mari; Paananen, Pekka; Kälviäinen, Reetta; Haatainen, Kaisa; Saranto, Kaija

2016-01-01

A trigger is a powerful tool for identifying adverse events to measure the level of any kind of harm caused in patient care. Studies with epilepsy patients have illustrated that using triggers as a methodology with data mining may increase patient well-being. The purpose of this study is to test the functionality and validity of the previously defined triggers to describe the status of epilepsy patient's well-being. In both medical and nursing data, the triggers described patients' well-being comprehensively. The narratives showed that there was overlapping in triggers. The preliminary results of triggers encourage us to develop some reminders to the documentation of epilepsy patient well-being. These provide healthcare professionals with further and more detailed information when necessary.

Abnormal functional network connectivity among resting-state networks in children with frontal lobe epilepsy.

PubMed

Widjaja, E; Zamyadi, M; Raybaud, C; Snead, O C; Smith, M L

2013-12-01

Epilepsy is considered a disorder of neural networks. The aims of this study were to assess functional connectivity within resting-state networks and functional network connectivity across resting-state networks by use of resting-state fMRI in children with frontal lobe epilepsy and to relate changes in resting-state networks with neuropsychological function. Fifteen patients with frontal lobe epilepsy and normal MR imaging and 14 healthy control subjects were recruited. Spatial independent component analysis was used to identify the resting-state networks, including frontal, attention, default mode network, sensorimotor, visual, and auditory networks. The Z-maps of resting-state networks were compared between patients and control subjects. The relation between abnormal connectivity and neuropsychological function was assessed. Correlations from all pair-wise combinations of independent components were performed for each group and compared between groups. The frontal network was the only network that showed reduced connectivity in patients relative to control subjects. The remaining 5 networks demonstrated both reduced and increased functional connectivity within resting-state networks in patients. There was a weak association between connectivity in frontal network and executive function (P = .029) and a significant association between sensorimotor network and fine motor function (P = .004). Control subjects had 79 pair-wise independent components that showed significant temporal coherence across all resting-state networks except for default mode network-auditory network. Patients had 66 pairs of independent components that showed significant temporal coherence across all resting-state networks. Group comparison showed reduced functional network connectivity between default mode network-attention, frontal-sensorimotor, and frontal-visual networks and increased functional network connectivity between frontal-attention, default mode network-sensorimotor, and frontal-visual networks in patients relative to control subjects. We found abnormal functional connectivity within and across resting-state networks in children with frontal lobe epilepsy. Impairment in functional connectivity was associated with impaired neuropsychological function.

Clinical utility of BOLD fMRI in preoperative work-up of epilepsy

PubMed Central

Ganesan, Karthik; Ursekar, Meher

2014-01-01

Surgical techniques have emerged as a viable therapeutic option in patients with drug refractory epilepsy. Pre-surgical evaluation of epilepsy requires a comprehensive, multiparametric, and multimodal approach for precise localization of the epileptogenic focus. Various non-invasive techniques are available at the disposal of the treating physician to detect the epileptogenic focus, which include electroencephalography (EEG), video-EEG, magnetic resonance imaging (MRI), functional MRI including blood oxygen level dependent (BOLD) techniques, single photon emission tomography (SPECT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Currently, non-invasive high-resolution MR imaging techniques play pivotal roles in the preoperative detection of the seizure focus, and represent the foundation for successful epilepsy surgery. BOLD functional magnetic resonance imaging (fMRI) maps allow for precise localization of the eloquent cortex in relation to the seizure focus. This review article focuses on the clinical utility of BOLD (fMRI) in the pre-surgical work-up of epilepsy patients. PMID:24851002

Lipid Binding Defects and Perturbed Synaptogenic Activity of a Collybistin R290H Mutant That Causes Epilepsy and Intellectual Disability*

PubMed Central

Papadopoulos, Theofilos; Schemm, Rudolf; Grubmüller, Helmut; Brose, Nils

2015-01-01

Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects—or synaptopathies—are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the CbR290H mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans. PMID:25678704

Lipid binding defects and perturbed synaptogenic activity of a Collybistin R290H mutant that causes epilepsy and intellectual disability.

PubMed

Papadopoulos, Theofilos; Schemm, Rudolf; Grubmüller, Helmut; Brose, Nils

2015-03-27

Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects--or synaptopathies--are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the Cb(R290H) mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Mesial temporal lobe epilepsy diminishes functional connectivity during emotion perception.

PubMed

Steiger, Bettina K; Muller, Angela M; Spirig, Esther; Toller, Gianina; Jokeit, Hennric

2017-08-01

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with impaired recognition of emotional facial expressions. Correspondingly, imaging studies showed decreased activity of the amygdala and cortical face processing regions in response to emotional faces. However, functional connectivity among regions involved in emotion perception has not been studied so far. To address this, we examined intrinsic functional connectivity (FC) modulated by the perception of dynamic fearful faces among the amygdala and limbic, frontal, temporal and brainstem regions. Regions of interest were identified in an activation analysis by presenting a block-design with dynamic fearful faces and dynamic landscapes to 15 healthy individuals. This led to 10 predominately right-hemispheric regions. Functional connectivity between these regions during the perception of fearful faces was examined in drug-refractory patients with left- (n=16) or right-sided (n=17) MTLE, epilepsy patients with extratemporal seizure onset (n=15) and a second group of 15 healthy controls. Healthy controls showed a widespread functional network modulated by the perception of fearful faces that encompassed bilateral amygdalae, limbic, cortical, subcortical and brainstem regions. In patients with left MTLE, a downsized network of frontal and temporal regions centered on the right amygdala was present. Patients with right MTLE showed almost no significant functional connectivity. A maintained network in the epilepsy control group indicates that findings in mesial temporal lobe epilepsy could not be explained by clinical factors such as seizures and antiepileptic medication. Functional networks underlying facial emotion perception are considerably changed in left and right MTLE. Alterations are present for both hemispheres in either MTLE group, but are more pronounced in right MTLE. Disruption of the functional network architecture possibly contributes to deficits in facial emotion recognition frequently reported in MTLE. Copyright © 2017 Elsevier B.V. All rights reserved.

Indications and expectations for neuropsychological assessment in routine epilepsy care: Report of the ILAE Neuropsychology Task Force, Diagnostic Methods Commission, 2013-2017.

PubMed

Wilson, Sarah J; Baxendale, Sallie; Barr, William; Hamed, Sherifa; Langfitt, John; Samson, Séverine; Watanabe, Masako; Baker, Gus A; Helmstaedter, Christoph; Hermann, Bruce P; Smith, Mary-Lou

2015-05-01

The International League Against Epilepsy (ILAE) Diagnostic Methods Commission charged the Neuropsychology Task Force with the job of developing a set of recommendations to address the following questions: (1) What is the role of a neuropsychological assessment? (2) Who should do a neuropsychological assessment? (3) When should people with epilepsy be referred for a neuropsychological assessment? and (4) What should be expected from a neuropsychological assessment? The recommendations have been broadly written for health care clinicians in established epilepsy settings as well as those setting up new services. They are based on a detailed survey of neuropsychological assessment practices across international epilepsy centers, and formal ranking of specific recommendations for advancing clinical epilepsy care generated by specialist epilepsy neuropsychologists from around the world. They also incorporate the latest research findings to establish minimum standards for training and practice, reflecting the many roles of neuropsychological assessment in the routine care of children and adults with epilepsy. The recommendations endorse routine screening of cognition, mood, and behavior in new-onset epilepsy, and describe the range of situations when more detailed, formal neuropsychological assessment is indicated. They identify a core set of cognitive and psychological domains that should be assessed to provide an objective account of an individual's cognitive, emotional, and psychosocial functioning, including factors likely contributing to deficits identified on qualitative and quantitative examination. The recommendations also endorse routine provision of feedback to patients, families, and clinicians about the implications of the assessment results, including specific clinical recommendations of what can be done to improve a patient's cognitive or psychosocial functioning and alleviate the distress of any difficulties identified. By canvassing the breadth and depth of scope of neuropsychological assessment, this report demonstrates the pivotal role played by this noninvasive and minimally resource intensive investigation in the care of people with epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Determining Changes in Neural Circuits in Tuberous Sclerosis

DTIC Science & Technology

2013-05-01

features of human Tuberous Sclerosis including mosaicism, autism and epilepsy. This research progress deepened our understanding of Tuberous Sclerosis by... autism and epilepsy. This research progress deepened our understanding of Tuberous Sclerosis by linking temporal gene function, mTOR function, physiology...of function of Tsc1 in the brain causes intellectual disability, seizures, sleep disorders, and autism . We took advantage of our CreER/loxP based

KCNT1 gain-of-function in two epilepsy phenotypes is reversed by quinidine

PubMed Central

Milligan, Carol J.; Li, Melody; Gazina, Elena V.; Heron, Sarah E.; Nair, Umesh; Trager, Chantel; Reid, Christopher A.; Venkat, Anu; Younkin, Donald P.; Dlugos, Dennis J.; Petrovski, Slavé; Goldstein, David B.; Dibbens, Leanne M.; Scheffer, Ingrid E.; Berkovic, Samuel F; Petrou, Steven

2014-01-01

Objective Mutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of infancy with migrating focal seizures (EIMFS). More recently, a whole exome sequencing study of epileptic encephalopathies identified an additional de novo mutation in one proband with EIMFS. We aim to investigate the electrophysiological and pharmacological characteristics of hKCNT1 mutations and examine developmental expression levels. Methods Here we use a Xenopus laevis oocyte based automated two-electrode voltage-clamp assay. The effects of quinidine (100 and 300 µM) are also tested. Using quantitative RT-PCR, the relative levels of mouse brain mKcnt1 mRNA expression are determined. Results We demonstrate that KCNT1 mutations implicated in epilepsy cause a marked increase in function. Importantly, there was a significant group difference in gain-of-function between mutations associated with ADNFLE and EIMFS. Finally, exposure to quinidine significantly reduces this gain-of-function for all mutations studied. Interpretation These results establish direction for a targeted therapy and potentially exemplify a translational paradigm for in vitro studies informing novel therapies in a neuropsychiatric disease. PMID:24591078

Developing from child to adult: Risk factors for poor psychosocial outcome in adolescents and young adults with epilepsy.

PubMed

Geerlings, R P J; Aldenkamp, A P; Gottmer-Welschen, L M C; de With, P H N; Zinger, S; van Staa, A L; de Louw, A J A

2015-10-01

Childhood-onset epilepsy during the years of transition to adulthood may affect normal social, physical, and mental development, frequently leading to psychosocial and health-related problems in the long term. This study aimed to describe the main characteristics of patients in transition and to identify risk factors for poor psychosocial outcome in adolescents and young adults with epilepsy. Patients with epilepsy, 15-25years of age, who visited the Kempenhaeghe Epilepsy Transition Clinic from March 2012 to December 2014 were included (n=138). Predefined risk scores for medical, educational/occupational status, and independence/separation/identity were obtained, along with individual risk profile scores for poor psychosocial outcome. Multivariate linear regression analysis and discriminant analysis were used to identify variables associated with an increased risk of poor long-term psychosocial outcome. Demographic, epilepsy-related, and psychosocial variables associated with a high risk of poor long-term outcome were lower intelligence, higher seizure frequency, ongoing seizures, and an unsupportive and unstable family environment. Using the aforementioned factors in combination, we were able to correctly classify the majority (55.1%) of the patients regarding their risk of poor psychosocial outcome. Our analysis may allow early identification of patients at high risk of prevention, preferably at pretransition age. The combination of a chronic refractory epilepsy and an unstable family environment constitutes a higher risk of transition problems and poor outcome in adulthood. As a consequence, early interventions should be put into place to protect youth at risk of poor transition outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Impaired Consciousness in Epilepsy

PubMed Central

Blumenfeld, Hal

2013-01-01

Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost making it impossible for the individual to experience or respond. This has huge consequences for safety, productivity, emotional health and quality of life. To prevent impaired consciousness in epilepsy it is necessary to understand the mechanisms leading to brain dysfunction during seizures. Normally the “consciousness system”—a specialized set of cortical-subcortical structures—maintains alertness, attention and awareness. Recent advances in neuroimaging, electrophysiology and prospective behavioral testing have shed new light on how epileptic seizures disrupt the consciousness system. Diverse seizure types including absence, generalized tonic-clonic and complex partial seizures converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding these mechanisms may lead to improved treatment strategies to prevent impaired consciousness and improve quality of life in people with epilepsy. PMID:22898735

Diagnosing and Solving School Learning Disabilities in Epilepsy: Part 4, Forgotten Problems--The Student

ERIC Educational Resources Information Center

Mittan, Robert J.

2010-01-01

In the last article the author discussed the powerful effect epilepsy has on the social functioning of the classroom and how this impact can affect learning difficulties in the student. Epilepsy also exerts a powerful influence upon the teacher, depending how educated that teacher is and any fears about seizures the teacher may harbor. Fortunately…

Sleep Onset Problems in Two Children with Mild Intellectual Disability and Epilepsy: Assessment and Treatment in the Home Setting

ERIC Educational Resources Information Center

Maas, A. P. H. M.; Didden, R.; de Moor, J. M. H.; Renier, W. O.; Curfs, L. M. G.

2005-01-01

Sleep problems such as bedtime difficulties, frequent night waking and excessive daytime sleepiness are prevalent in children with epilepsy. In the present study, functional assessment of sleep onset problems in two young children with epilepsy was performed. Effects of bedtime fading and antipsychotic medication (pipamperon) in a 6-year-old boy,…

Cognitive outcome of surgery.

PubMed

Gallagher, Anne; Jambaqué, Isabelle; Lassonde, Maryse

2013-01-01

Epilepsy surgery is now widely accepted as an effective therapeutic option for carefully selected children with medically refractory epilepsy. The surgical procedure may cause cognitive deficits or exacerbate existing impairments, but it may also improve cognitive abilities by the restoration of functions located in adjacent or contralateral areas that had been secondarily affected by the epilepsy or the underlying pathology. Compared to adults, better cognitive outcome has been reported in children, a finding probably due to the developing state of the brain, which possesses considerable structural and functional plasticity. More extensive and effective surgery such as hemispherectomy is more commonly used in the pediatric population, and this must also influence surgical outcome. However, studies related to cognitive outcome of epilepsy surgery in children are limited, and controversial results are often reported. In this chapter, we provide a current overview of the literature on cognitive outcomes in children who undergo different types of epilepsy surgery, including focal resections as well as corpus callosotomy and hemispherectomy. Early surgical intervention appears to be a rational option for the treatment of childhood epilepsy since many cognitive deficits are linked to the epileptic process and may disappear when seizures are controlled. Copyright © 2013 Elsevier B.V. All rights reserved.

Deficits in oculomotor performance in pediatric epilepsy

PubMed Central

Asato, Miya R.; Nawarawong, Natalie; Hermann, Bruce; Crumrine, Patricia; Luna, Beatriz

2010-01-01

Summary Purpose Given evidence of limitations in neuropsychological performance in epilepsy, we probed the integrity of components of cognition, including speed of processing, response inhibition, and spatial working memory supporting executive function in pediatric epilepsy patients and matched controls. Methods A total of 44 pairs of controls and medically treated pediatric epilepsy patients with no known brain pathology completed cognitive oculomotor tasks, computerized neuropsychological testing, and psychiatric assessment. Results Patients showed slower reaction time to initiate a saccadic response compared to controls but had intact saccade accuracy. Cognitively driven responses including response inhibition were impaired in the patient group. Patients had increased incidence of comorbid psychopathology but comorbidity did not predict worse functioning compared to patients with no ADHD. Epilepsy type and medication status were not predictive of outcome. More complex neuropsychological performance was impaired in tasks requiring visual memory and sequential processing which was correlated with inhibitory control and antisaccade accuracy. Discussion Pediatric epilepsy may be associated with vulnerabilities that specifically undermine speed of processing and response inhibition but not working memory and may underlie known neuropsychological performance limitations. This particular profile of abnormalities may be associated with seizure-mediated compromises in brain maturation early in development. PMID:21087246

Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.

PubMed

Kellermann, Tanja S; Wagner, Janelle L; Smith, Gigi; Karia, Samir; Eskandari, Ramin

2016-11-01

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians. Surgical treatment of epilepsy can be critical to avoid negative outcomes in functional, cognitive, and behavioral health status. Furthermore, it is often the only method to achieve seizure freedom in refractory epilepsy. Although a large literature base can be found for adults with refractory epilepsy undergoing surgical treatment, less is known about how surgical management affects outcomes in children with epilepsy. The purpose of the review was fourfold: (1) to evaluate the available literature regarding presurgical assessment and postsurgical outcomes in children with medically refractory epilepsy, (2) to identify gaps in our knowledge of surgical treatment and its outcomes in children with epilepsy, (3) to pose questions for further research, and (4) to advocate for a more unified presurgical evaluation protocol including earlier referral for surgical candidacy of pediatric patients with refractory epilepsy. Despite its effectiveness, epilepsy surgery remains an underutilized but evidence-based approach that could lead to positive short- and long-term outcomes for children with refractory epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of lesions and epilepsy on personality and mood in patients with symptomatic epilepsy: a pre- to postoperative follow-up study.

PubMed

Witt, Juri-Alexander; Hollmann, Karsten; Helmstaedter, Christoph

2008-12-01

To discern more static and lesion based from more dynamic epilepsy-driven features of depression and personality in focal symptomatic epilepsy, change in personality and mood was examined as a function of focus lateralization and seizure outcome after epilepsy surgery. Self-reported personality and depression were assessed before and 1 year after epilepsy surgery in 151 consecutive patients with temporal (N=125) or extratemporal lobe epilepsy (N=26). At baseline only depressed mood (31%) and introversion (38%) appeared elevated, the first being more frequent in right lateralized epilepsies, the latter being pronounced in temporal lobe epilepsy. After surgery, seizure freedom was associated with a significant change in neuroticism as well as with improvements in mood and symptoms of an organic psycho-syndrome. Differential changes were observed for seizure-free left (enhanced emotional stabilization) versus right temporal resected patients (decreased anxiety and impulsivity, less vegetative symptoms). Apart from elevated depression and introversion scores which showed some relation to pathology, no major deviant personality features could be discerned. While seizure freedom related improvements may indicate both epilepsy and reactively driven behavioral changes, the differential recovery observed in seizure-free left versus right temporal resected patients indicate epilepsy-specific behavioral dysfunction.

Patterns of language and auditory dysfunction in 6-year-old children with epilepsy.

PubMed

Selassie, Gunilla Rejnö-Habte; Olsson, Ingrid; Jennische, Margareta

2009-01-01

In a previous study we reported difficulty with expressive language and visuoperceptual ability in preschool children with epilepsy and otherwise normal development. The present study analysed speech and language dysfunction for each individual in relation to epilepsy variables, ear preference, and intelligence in these children and described their auditory function. Twenty 6-year-old children with epilepsy (14 females, 6 males; mean age 6:5 y, range 6 y-6 y 11 mo) and 30 reference children without epilepsy (18 females, 12 males; mean age 6:5 y, range 6 y-6 y 11 mo) were assessed for language and auditory ability. Low scores for the children with epilepsy were analysed with respect to speech-language domains, type of epilepsy, site of epileptiform activity, intelligence, and language laterality. Auditory attention, perception, discrimination, and ear preference were measured with a dichotic listening test, and group comparisons were performed. Children with left-sided partial epilepsy had extensive language dysfunction. Most children with partial epilepsy had phonological dysfunction. Language dysfunction was also found in children with generalized and unclassified epilepsies. The children with epilepsy performed significantly worse than the reference children in auditory attention, perception of vowels and discrimination of consonants for the right ear and had more left ear advantage for vowels, indicating undeveloped language laterality.

Graph theoretical analysis reveals disrupted topological properties of whole brain functional networks in temporal lobe epilepsy.

PubMed

Wang, Junjing; Qiu, Shijun; Xu, Yong; Liu, Zhenyin; Wen, Xue; Hu, Xiangshu; Zhang, Ruibin; Li, Meng; Wang, Wensheng; Huang, Ruiwang

2014-09-01

Temporal lobe epilepsy (TLE) is one of the most common forms of drug-resistant epilepsy. Previous studies have indicated that the TLE-related impairments existed in extensive local functional networks. However, little is known about the alterations in the topological properties of whole brain functional networks. In this study, we acquired resting-state BOLD-fMRI (rsfMRI) data from 26 TLE patients and 25 healthy controls, constructed their whole brain functional networks, compared the differences in topological parameters between the TLE patients and the controls, and analyzed the correlation between the altered topological properties and the epilepsy duration. The TLE patients showed significant increases in clustering coefficient and characteristic path length, but significant decrease in global efficiency compared to the controls. We also found altered nodal parameters in several regions in the TLE patients, such as the bilateral angular gyri, left middle temporal gyrus, right hippocampus, triangular part of left inferior frontal gyrus, left inferior parietal but supramarginal and angular gyri, and left parahippocampus gyrus. Further correlation analysis showed that the local efficiency of the TLE patients correlated positively with the epilepsy duration. Our results indicated the disrupted topological properties of whole brain functional networks in TLE patients. Our findings indicated the TLE-related impairments in the whole brain functional networks, which may help us to understand the clinical symptoms of TLE patients and offer a clue for the diagnosis and treatment of the TLE patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

[Early functional hemispherectomy in hemimegalencephaly associated to refractory epilepsy].

PubMed

Fonseca, Luiz Fernando; Melo, Renato Pacheco de; Cukiert, Arthur; Burattini, Jose Augusto; Mariani, Pedro Paulo; Brandão, Ródio; Ceda, Lauro; Baldauf, Cristine Mella; Argentoni, Meire; Forster, Cássio; Baise, Carla

2004-12-01

Hemimegalencephaly (HME) is a rare congenital brain malformation of unknown etiology. Patients with HME can present with an early onset epileptic syndrome which is often refractory to medical treatment and associated to impaired neurological development. Functional hemispherectomy (FH) has proven to be a valuable treatment alternative in patients with refractory epilepsy in this setting. Very few children operated under the age of 6 months and bearing HME and catastrophic epilepsy (CE) have been described in the literature. This study reports on 2 kids younger than 6 months with HME and CE submitted to FH with good clinical outcome.

Health-related quality of life in epilepsy: findings obtained with a new Italian instrument.

PubMed

Piazzini, Ada; Beghi, Ettore; Turner, Katherine; Ferraroni, Monica

2008-07-01

The aim of the present study was to evaluate the Epi-QoL, a new Italian-specific measure of health-related quality of life (HRQOL) for adults with epilepsy; the clinical variables that affected the HRQOL score were also assessed. The Epi-QoL is a 46-item self-administered questionnaire focusing on six domains: Physical Functioning, Cognitive Functioning, Emotional Well-Being, Social Functioning, Seizure Worry, and Medication Effects. Eight hundred fifteen patients recruited from 24 secondary and tertiary Italian centers for the care of epilepsy were assessed. The results supported the reliability and validity of the Epi-QoL as a measure of HRQOL. The variables that significantly affected HRQOL scores were: geographic area, gender, seizure frequency, prognostic categories, number of medications, comorbidity, presence of cognitive impairment, psychiatric disturbances, and disability. We believe that a new specific questionnaire for the evaluation of HRQOL in Italy can contribute much to the understanding of the influence of epilepsy on patients' lives.

How can we explain the frontal presentation of insular lobe epilepsy? The impact of non-linear analysis of insular seizures.

PubMed

Hagiwara, Koichi; Jung, Julien; Bouet, Romain; Abdallah, Chifaou; Guénot, Marc; Garcia-Larrea, Luis; Mauguière, François; Rheims, Sylvain; Isnard, Jean

2017-05-01

For a decade it has been known that the insular lobe epilepsy can mimic frontal lobe epilepsy. We aimed to clarify the pattern of functional coupling occurring during the frontal presentation. We analyzed five insular lobe epilepsy patients. Frontal semiology was predominant for three of them, whereas insular semiology was predominant for the two others. We applied the non-linear regression analysis to stereoelectroencephalography-recorded seizures. A directed functional coupling index was calculated during clonic discharge periods that were accompanied either with frontal or insular semiology. We found significant functional coupling between the insula and mesial frontal/cingulate regions, with the former being a leader region for seizures propagation. Extra-insular regions showed significantly less or even no coupling with the mesial hemispheric regions. The three patients with frontal semiology showed strong couplings with the mesial frontal as well as cingulate regions, including the medial orbitofrontal cortex, pre-SMA/SMA, and the anterior to posterior cingulate. The two patients with the insular semiology only showed couplings between the insula and cingulate regions. The frontal semiology was expressed by strong functional couplings between the insula and mesial frontal regions. The insular origin of seizure should be considered in cryptogenic mesial frontal epilepsies. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

The Role of Neurosteroids in the Pathophysiology and Treatment of Catamenial Epilepsy

PubMed Central

Reddy, Doodipala Samba

2009-01-01

SUMMARY Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period. Generally, a two-fold or greater increase in seizure frequency during a particular phase of the menstrual cycle could be considered as catamenial epilepsy. Based on this criteria, recent clinical studies indicate that catamenial epilepsy affects 31 – 60% of the women with epilepsy. Three types of catamenial seizures (perimenstrual, periovulatory and inadequate luteal) have been identified. However, there is no specific drug available today for catamenial epilepsy, which has not been successfully treated with conventional antiepileptic drugs. Elucidation of the pathophysiology of catamenial epilepsy is a prerequisite to develop specific targeted approaches for treatment or prevention of the disorder. Cyclical changes in the circulating levels of estrogens and progesterone play a central role in the development of catamenial epilepsy. There is emerging evidence that endogenous neurosteroids with anticonvulsant or proconvulsant effects could play a critical role in catamenial epilepsy. It is thought that perimenstrual catamenial epilepsy is associated with the withdrawal of anticonvulsant neurosteroids. Progesterone and other hormonal agents have been shown in limited trials to be moderately effective in catamenial epilepsy, but may cause endocrine side effects. Synthetic neurosteroids, which enhance the tonic GABA-A receptor function, might provide an effective approach for the catamenial epilepsy therapy without producing hormonal side effects. PMID:19406620

Is there a creative functional paradoxical facilitation in juvenile myoclonic epilepsy?

PubMed

Senf, Philine; Scheuren, Lena; Holtkamp, Martin

2016-09-01

In patients with juvenile myoclonic epilepsy (JME), a specific personality profile suggestive of frontal lobe dysfunctions has been described. From a neurobiological point of view, the frontal lobe seems to be crucial for creative processes, although the exact role remains unclear. The theory of creative paradoxical functional facilitation (PFF) assumes that disinhibited frontal lobe function can enhance creative abilities. The aim of the current study was to explore our hypothesis that JME is associated with higher artistic creativity based on the theory of PFF. We assessed 25 patients with JME aged 18 to 40years in regard to neuropsychological creativity testing. Results were compared with those of 25 age-, sex-, and level of education-matched healthy control subjects (HC) and patients with temporal lobe epilepsy (TLE). Creative abilities were assessed using two validated and standardized tests: 1) nonverbal: the incomplete figure task of Torrance Test of Creative Thinking and 2) verbal: verbal creativity test. Additionally, a basic assessment of fluid intelligence (test for problem solving) and frontal lobe function (trail-making test) was administered to all participants. Verbal creativity was impaired in both groups with epilepsy compared with that in HC (specific score: JME vs. HC, p=0.008; TLE vs. HC, p=0.003). In regard to nonverbal creative abilities, both groups with epilepsy exhibited fair performance. Level of fluid intelligence was even in all groups (p=0.433). Only patients with JME showed deficits in the frontal lobe test of psychomotor speed (time in seconds: 67.7 JME vs. 54.6 TLE vs. 52.8 HC; p=0.045). Overall, our study did not reveal increased creativity in JME. The current findings provide insights into creative abilities in two different epilepsy syndromes. Knowledge on specific neuropsychological strengths or deficits in patients with epilepsy may be useful for treatment or counseling. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of epilepsy on autistic symptom severity assessed by the social responsiveness scale in children with autism spectrum disorder.

PubMed

Ko, Chanyoung; Kim, Namwook; Kim, Eunjoo; Song, Dong Ho; Cheon, Keun-Ah

2016-06-27

As the prevalence of autism spectrum disorders in people with epilepsy ranges from 15 to 47 % (Clarke et al. in Epilepsia 46:1970-1977, 2005), it is speculated that there is a special relationship between the two disorders, yet there has been a lack of systematic studies comparing the behavioral phenotype between autistic individuals and autistic individuals with epilepsy. This study aims to investigate how the co-occurrence of epilepsy and Autism Spectrum Disorder (ASD) affects autistic characteristics assessed by the Social Responsiveness Scale (SRS), which has been used as a measure of autism symptoms in previous studies. In this research we referred to all individuals with Autism or Autistic Disorder as individuals with ASD. We reviewed the complete medical records of 182 participants who presented to a single tertiary care referral center from January 1, 2013 to July 28, 2015, and subsequently received complete child and adolescent psychiatric assessments. Of the 182 participants, 22 were diagnosed with Autism Spectrum Disorder and epilepsy. Types of epilepsy observed in these individuals included complex partial seizure, generalized tonic-clonic seizure, or infantile spasm. Using 'Propensity Score Matching' we selected 44 children, diagnosed with only Autism Spectrum Disorder, whose age, gender, and intelligence quotient (IQ) were closely matched with the 22 children diagnosed with Autism Spectrum Disorder and epilepsy. Social functioning of participants was assessed by the social responsiveness scale, which consists of five categories: social awareness, social cognition, social communication, social motivation, and autistic mannerisms. Bivariate analyses were conducted to compare the ASD participants with epilepsy group with the ASD-only group on demographic and clinical characteristics. Chi square and t test p values were calculated when appropriate. There was no significant difference in age (p = 0.172), gender (p > 0.999), IQ (FSIQ, p = 0.139; VIQ, p = 0.114; PIQ, p = 0.295) between the two groups. ASD participants with epilepsy were significantly more impaired than ASD participants on some measures of social functioning such as social awareness (p = 0.03) and social communication (p = 0.027). ASD participants with epilepsy also scored significantly higher on total SRS t-score than ASD participants (p = 0.023). Understanding the relationship between ASD and epilepsy is critical for appropriate management (e.g. social skills training, seizure control) of ASD participants with co-occurring epilepsy. Results of this study suggest that mechanisms involved in producing epilepsy may play a role in producing or augmenting autistic features such as poor social functioning. Prospective study with larger sample sizes is warranted to further explore this association.

Effects of levetiracetam monotherapy on sperm parameters and sex hormones: Data from newly diagnosed patients with epilepsy.

PubMed

Ceylan, Mustafa; Yalcin, Ahmet; Bayraktutan, Omer Faruk; Karabulut, Ibrahim; Sonkaya, Ali Rıza

2016-10-01

Epilepsy has an impact on the reproductive system. Males with epilepsy have lower fertility rates, hypo-sexuality and reduced potency compared with the general population. Anti-epileptic drugs and epilepsy itself are thought to be responsible for this reduced fertility. LEV is a second-generation anti-epileptic agent with low incidences of both adverse effects and drug-drug interactions. In this study, we have investigated the effects of LEV treatment on sex hormones and sperm parameters in newly diagnosed epilepsy patients. We recruited 26 males with newly diagnosed epilepsy and introduced LEV monotherapy. Patients were divided into two groups depending on whether they had partial or generalized seizures. We acquired the results of pre- and post-treatment sperm analyses and serum sex hormone levels. We also recorded the maximum dose, daily dose and treatment duration for each individual. Pre- and post-treatment comparisons and correlations between both sperm and sex hormone parameters and both treatment duration and dose were determined. Pre- and post-treatment sex hormone levels were not significantly different. The total sperm count, percentage of normal morphology and functional sperm count tested after treatment were significantly lower in both groups compared with pre-treatment values (p<0.05). There was a moderate correlation between daily dose and reduction in functional sperm count (r: 0.41, p: 0.034). Our findings confirm that LEV treatment of newly diagnosed epilepsy patients decreases sperm parameters without altering sex hormone levels. Our results may guide the choice of anti-epileptic drug treatment among men with epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Temporal lobe epilepsy: when are invasive recordings needed?

PubMed

Diehl, B; Lüders, H O

2000-01-01

Temporal lobe epilepsy (TLE) is the most common type of medically intractable partial epilepsy amenable to surgery. In the majority of cases, the underlying pathology in temporal lobe epilepsy is mesial temporal sclerosis (MTS). Whereas historically invasive recordings were required for most epilepsy surgeries, indications have dramatically changed since the introduction of high-resolution MRI, which uncovers structural lesions in a high percentage of cases. No invasive recordings are required to perform a temporal lobectomy in patients with intractable epilepsy who have structural imaging suggesting unilateral MTS and concordant interictal and ictal surface EEG recordings, functional imaging, and clinical findings. Invasive testing is needed if there is evidence of bitemporal MTS on structural imaging and/or electrophysiologically, and additional information from functional imaging, neuropsychology, and the intracarotid amobarbital (Wada) test also does not help to lateralize the epileptogenic zone. Depth electrodes can be particularly helpful in this setting. However, no surgery is indicated, even without invasive recordings, if bitemporal-independent seizures are recorded by surface EEG and all additional testing is inconclusive. Other etiologies of TLE such as a tumor, vascular malformation, encephalomalacia, or congenital developmental abnormality account for about 30% of all patients who undergo epilepsy surgery. Epilepsy surgery is indicated after limited electrophysiologic investigations if neuroimaging and electrophysiology converge. However, approaches for resection in lesional temporal lobe epilepsy vary among centers. Completeness of resection is crucial and invasive recordings may be needed to guide the resection by mapping eloquent cortex and/or to determine the extent of the non-MRI-visible epileptogenic area. Specific approaches for the different pathologies are discussed because there is evidence that the relationship between the lesions visible on MRI and the epileptogenic zone varies among lesions of different pathologies, and therefore variable surgical strategies must be applied.

Astrocyte uncoupling as a cause of human temporal lobe epilepsy

PubMed Central

Bedner, Peter; Dupper, Alexander; Hüttmann, Kerstin; Müller, Julia; Herde, Michel K.; Dublin, Pavel; Deshpande, Tushar; Schramm, Johannes; Häussler, Ute; Haas, Carola A.; Henneberger, Christian; Theis, Martin

2015-01-01

Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K+ concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K+ buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention. PMID:25765328

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

PubMed

Schaffer, Yael; Ben Zeev, Bruria; Cohen, Roni; Shuper, Avinoam; Geva, Ronny

2015-07-01

Idiopathic epilepsies are considered to have relatively good prognoses and normal or near normal developmental outcomes. Nevertheless, accumulating studies demonstrate memory and psychosocial deficits in this population, and the prevalence, severity and relationships between these domains are still not well defined. We aimed to assess memory, psychosocial function, and the relationships between these two domains among children with idiopathic epilepsy syndromes using an extended neuropsychological battery and psychosocial questionnaires. Cognitive abilities, neuropsychological performance, and socioemotional behavior of 33 early adolescent children, diagnosed with idiopathic epilepsy, ages 9-14years, were assessed and compared with 27 age- and education-matched healthy controls. Compared to controls, patients with stabilized idiopathic epilepsy exhibited higher risks for short-term memory deficits (auditory verbal and visual) (p<0.0001), working memory deficits (p<0.003), auditory verbal long-term memory deficits (p<0.0021), and more frequent psychosocial symptoms (p<0.0001). The severity of auditory verbal memory deficits was related to severity of psychosocial symptoms among the children with epilepsy but not in the healthy controls. Results suggest that deficient auditory verbal memory may be compromising psychosocial functioning in children with idiopathic epilepsy, possibly underscoring that cognitive variables, such as auditory verbal memory, should be assessed and treated in this population to prevent secondary symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Augmented Currents of an HCN2 Variant in Patients with Febrile Seizure Syndromes

PubMed Central

Dibbens, Leanne M.; Reid, Christopher A.; Hodgson, Bree; Thomas, Evan A.; Phillips, Alison M.; Gazina, Elena; Cromer, Brett A.; Clarke, Alison L.; Baram, Tallie Z.; Scheffer, Ingrid E.; Berkovic, Samuel F.; Petrou, Steven

2012-01-01

The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were ~35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy. PMID:20437590

An Intracranial Electroencephalography (iEEG) Brain Function Mapping Tool with an Application to Epilepsy Surgery Evaluation.

PubMed

Wang, Yinghua; Yan, Jiaqing; Wen, Jianbin; Yu, Tao; Li, Xiaoli

2016-01-01

Before epilepsy surgeries, intracranial electroencephalography (iEEG) is often employed in function mapping and epileptogenic foci localization. Although the implanted electrodes provide crucial information for epileptogenic zone resection, a convenient clinical tool for electrode position registration and Brain Function Mapping (BFM) visualization is still lacking. In this study, we developed a BFM Tool, which facilitates electrode position registration and BFM visualization, with an application to epilepsy surgeries. The BFM Tool mainly utilizes electrode location registration and function mapping based on pre-defined brain models from other software. In addition, the electrode node and mapping properties, such as the node size/color, edge color/thickness, mapping method, can be adjusted easily using the setting panel. Moreover, users may manually import/export location and connectivity data to generate figures for further application. The role of this software is demonstrated by a clinical study of language area localization. The BFM Tool helps clinical doctors and researchers visualize implanted electrodes and brain functions in an easy, quick and flexible manner. Our tool provides convenient electrode registration, easy brain function visualization, and has good performance. It is clinical-oriented and is easy to deploy and use. The BFM tool is suitable for epilepsy and other clinical iEEG applications.

An Intracranial Electroencephalography (iEEG) Brain Function Mapping Tool with an Application to Epilepsy Surgery Evaluation

PubMed Central

Wang, Yinghua; Yan, Jiaqing; Wen, Jianbin; Yu, Tao; Li, Xiaoli

2016-01-01

Objects: Before epilepsy surgeries, intracranial electroencephalography (iEEG) is often employed in function mapping and epileptogenic foci localization. Although the implanted electrodes provide crucial information for epileptogenic zone resection, a convenient clinical tool for electrode position registration and Brain Function Mapping (BFM) visualization is still lacking. In this study, we developed a BFM Tool, which facilitates electrode position registration and BFM visualization, with an application to epilepsy surgeries. Methods: The BFM Tool mainly utilizes electrode location registration and function mapping based on pre-defined brain models from other software. In addition, the electrode node and mapping properties, such as the node size/color, edge color/thickness, mapping method, can be adjusted easily using the setting panel. Moreover, users may manually import/export location and connectivity data to generate figures for further application. The role of this software is demonstrated by a clinical study of language area localization. Results: The BFM Tool helps clinical doctors and researchers visualize implanted electrodes and brain functions in an easy, quick and flexible manner. Conclusions: Our tool provides convenient electrode registration, easy brain function visualization, and has good performance. It is clinical-oriented and is easy to deploy and use. The BFM tool is suitable for epilepsy and other clinical iEEG applications. PMID:27199729

The impact of epilepsy on preschool children and their families.

PubMed

Tanriverdi, Müberra; Mutluay, Fatma Karantay; Tarakçi, Devrim; Güler, Serhat; Iscan, Akin

2016-09-01

This study investigated the possible presence of sensory-motor developmental impairments in preschool children with epilepsy and explored epilepsy impact on their activities and quality of life and on the stress load of their family. Study participants were children aged 2-6years diagnosed with epilepsy without any other comorbidities (epi-only children). The instruments used for assessment included the Neurological, Sensory, Motor, Developmental Assessment (NSMDA) scale for sensory-motor development, the Impact of Childhood Neurologic Disability Scale (ICNDS), and the Impact of Pediatric Epilepsy Scale (IPES) for disease impact on disability and Quality of Life (QoL), as well as the Pediatric Outcomes Data Collection Instrument (PODCI) for functional health status, and the Parental Stress Scale (PSS) for the family stress load. Required data were obtained from direct testing or observation of children's activities and mother-supplied answers to questions. Eighty-two children were investigated. The NSMDA scores were in the normal development range 6-8. Significant moderate impact of the disease on disability and QoL was estimated with the ICNDS and IPES instruments. The PODCI scores were similar to healthy population levels except for the happiness dimension which was better for children with epilepsy. PSS were significantly above normal. The functional health and QoL of the children as well as their family stress were found to be positively correlated with increasing age. It is found that epilepsy does not degrade neuromotor development and functional health status of preschool epi-only children, though it has a significant impact on their neurological disability and QoL and the stress level of their families; this impact seems to decrease with age. Copyright © 2016 Elsevier Inc. All rights reserved.

From clinically relevant outcome measures to quality of life in epilepsy: A time trade-off study.

PubMed

de Kinderen, Reina J A; Wijnen, Ben F M; van Breukelen, Gerard; Postulart, Debby; Majoie, Marian H J M; Aldenkamp, Albert P; Evers, Silvia M A A

2016-09-01

A proposed method for bridging the gap between clinically relevant epilepsy outcome measures and quality-adjusted life years is to derive utility scores for epilepsy health states. The aim of this study is to develop such a utility-function and to investigate the impact of the epilepsy outcome measures on utility. Health states, based on clinically important epilepsy attributes (e.g. seizure frequency, seizure severity, side-effects), were valued by a sample of the Dutch population (N=525) based on the time trade-off method. In addition to standard demographics, every participant was asked to rate 10 or 11 different health state scenarios. A multilevel regression analysis was performed to account for the nested structure of the data. Results show that the best health state (no seizures and no side-effects) is estimated at 0.89 and the worst state (seizures type 5 twice a day plus severe side-effects) at 0.22 (scale: 0-1). An increase in seizure frequency, occurrence of side-effects, and seizure severity were all significantly associated with lower utility values. Furthermore, seizure severity has the largest impact on quality of life compared with seizure frequency and side-effects. This study provides a utility-function for transforming clinically relevant epilepsy outcome measures into utility estimates. We advise using our utility-function in economic evaluations, when quality of life is not directly measured in a study and hence, no health state utilities are available, or when there is convincing empirical evidence of the insensitivity of a generic quality-of-life-instrument within epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

Best practice guidelines for the management of women with epilepsy.

PubMed

Crawford, Pamela

2005-01-01

Being a woman with epilepsy is not the same as being a man with epilepsy. Epilepsy affects sexual development, menstrual cycle, aspects of contraception, fertility, and reproduction. MENSTRUAL CYCLE, EPILEPSY, AND FERTILITY: The diagnosis of epilepsy and the use of antiepileptic drugs (AEDs) present women of childbearing age with many problems; both the disease and its treatment can alter the menstrual cycle and fertility. CONTRACEPTION IN EPILEPSY: There are no contraindications to the use of nonhormonal methods of contraception in women with epilepsy (see Table 3). Nonenzyme-inducing AEDs (valproate sodium, benzodiazepines, ethosuximide, and levetiracetam) do not show any interactions with the combined oral contraceptive pill. There are interactions between the COCP and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [doses above 200 mg/day], and oxcarbazepine) and also lamotrigine. SEXUALITY: The majority of women with epilepsy appear to have normal sex lives, although in some women with epilepsy, both the desire and arousal phases may be inhibited. PRECONCEPTION COUNSELING: Preconception counseling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be aware of a number of issues relating to future pregnancy, including methods and consequences of prenatal screening, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labor, breast feeding, and childcare. PREGNANCY: The lowest effective dose of the most appropriate AED should be used, aiming for monotherapy where possible. Recent pregnancy databases have suggested that valproate is significantly more teratogenic than carbamazepine, and the combination of valproate sodium and lamotrigine is particularly teratogenic. Most pregnancies are uneventful in women with epilepsy, and most babies are delivered healthy with no increased risk of obstetric complications in women. BREAST FEEDING: All women with epilepsy should be encouraged to breastfeed their babies. The AED concentration profiled in breast milk follows the plasma concentration curve. The total amount of drug transferred to infants via breast milk is usually much smaller than the amount transferred via the placenta during pregnancy. However, as drug elimination mechanisms are not fully developed in early infancy, repeated administration of a drug such as lamotrigine via breast milk may lead to accumulation in the infant. THE CARE OF CHILDREN OF MOTHERS WITH EPILEPSY: Although there is much anxiety about the possible risks to a child from the mother's epilepsy, there is little published evidence. The risk of the child being harmed depends on the type of seizure and its severity and frequency, and this risk is probably small if time is taken to train mothers and caregivers in safety precautions. MENOPAUSE: During menopause, about 40% of women report worsening of their seizure disorder, 27% improve, and a third had no change. Hormone replacement therapy is significantly associated with an increase in seizure frequency during menopause, and this is more likely in women with a history of catamenial epilepsy. BONE HEALTH: Women with epilepsy are at increased risk of fractures, osteoporosis, and osteomalacia.

Chronic sorrow and coping in families of children with epilepsy.

PubMed

Hobdell, Elizabeth F; Grant, Mitzie L; Valencia, Ignacio; Mare, Jane; Kothare, Sanjeev V; Legido, Agustin; Khurana, Divya S

2007-04-01

Epilepsy, a common problem in child neurology, affects the entire family. There is a potential for such psychosocial consequences as parental chronic sorrow and alterations in coping. In this study, 67 parents completed brief questionnaires about their sorrow and coping styles. Results demonstrated chronic sorrow as measured by the Adapted Burke Questionnaire (10.45 +/- 7.9). Interestingly, the total score was not significantly different between parents of children with refractory and nonrefractory epilepsy or parents of children with comorbid or without comorbid conditions. Selection of the individual item disbelief, however, was significantly increased in parents of children with nonrefractory epilepsy, and selection of the item anger was significantly increased in parents of children with comorbid conditions. Parental coping styles were similar to those reported in the normative data for the instrument used, the Coping Health Inventory for Parents (CHIP). The correlation between chronic sorrow and coping was significant between the grief component of sorrow and Coping Pattern II of the CHIP. Implications for practice include earlier identification of parental feelings of sorrow and coping styles, which may contribute to a positive outcome.

[Prevalence of neurocysticercosis in individuals affected by epilepsy].

PubMed

Palacio, G; Tobón, M E; Mora, O; Sánchez, J L; Jiménez, M; Muñoz, A; Pineda, D; Villa, A; Londoño, A; Buriticá, O; Díaz, H; Acebedo, S; Giraldo, M; Canasteros, I; Tobón, N; Gómez, M E; Arana, A; Uribe, C S; Tsang, V; Pilcher, J; Ahn, L; Rodríguez, M; Hurtado, A; Ceballos, F; Jiménez, I

1997-09-01

In this investigations, was carried out a neurocysticercosis (NC) prevalence study during seven months in the Instituto Neurológico de Antioquia with the purpose of known neurocysticercosis frequency as cause of epilepsy in patients older than ten years that we attended in our institute. Computerized tomographies (CT) were made to 503 patients, with epilepsy, 24.7% of them were CT positive for NC. Cysticercosis enzyme linked immunoelectrotransfer blot (EITB) and enzyme linked immunoabsorbent assay (ELISA) test were made to 178 patients, 19.6% were EITB positive for NC and 5% ELISA positive for NC. Results. From this result it is possible to infer that about 8% of the 503 patients with epilepsy had cysticercosis, according to EITB that is the golden assay for NC. The CT and ELISA test had 94.3% and 27.7% sensitivity, respectively, according to EITB. The specificity of the CT for NC was 49.2% and specificity for ELISA test was 100% as compared to EITB. The multivariate analysis with logistic regression allowed to establish association of positive EITB with factors such as male sex, eating pork, headaches and multiple lesions in CT. Prevention and education actions are necessary for the interruption of the neurocysticercosis transmission chain in order to diminish the high prevalence of epilepsy in the country and its complication and consequences.

Neocortical Temporal Lobe Epilepsy

PubMed Central

Bercovici, Eduard; Kumar, Balagobal Santosh; Mirsattari, Seyed M.

2012-01-01

Complex partial seizures (CPSs) can present with various semiologies, while mesial temporal lobe epilepsy (mTLE) is a well-recognized cause of CPS, neocortical temporal lobe epilepsy (nTLE) albeit being less common is increasingly recognized as separate disease entity. Differentiating the two remains a challenge for epileptologists as many symptoms overlap due to reciprocal connections between the neocortical and the mesial temporal regions. Various studies have attempted to correctly localize the seizure focus in nTLE as patients with this disorder may benefit from surgery. While earlier work predicted poor outcomes in this population, recent work challenges those ideas yielding good outcomes in part due to better localization using improved anatomical and functional techniques. This paper provides a comprehensive review of the diagnostic workup, particularly the application of recent advances in electroencephalography and functional brain imaging, in neocortical temporal lobe epilepsy. PMID:22953057

Functional consequences of hemispherectomy.

PubMed

van Empelen, R; Jennekens-Schinkel, A; Buskens, E; Helders, P J M; van Nieuwenhuizen, O

2004-09-01

Using the International Classification of Functioning Disability and Health (ICF) (WHO, 2001), impairments, activities and social participation are reported in 12 children (mean age at surgery 5.9 years) who were investigated before and three times over a 2-year period after hemispherectomy. Impairments were assessed (i) in terms of seizure frequency (Engel classification) and seizure severity (HASS) and (ii) with respect to muscle strength (MRC), range of motion (JAM score) and muscle tone (modified Ashworth scale). Activities were assessed in terms of gross motor functioning (GMFM) and self-care, mobility and social function (PEDI). Participation was assessed in terms of epilepsy-related restrictions and quantified by means of the Hague Restrictions in Childhood Epilepsy Scale (HARCES). Nine out of 12 children could be classified as free of seizures (Engel class I), and in the remaining three seizure frequency was Engel class III. HASS scores showed maximum improvement in 10 out of 12 children and near-maximum improvement in the two remaining children. Muscle strength and muscle tone on the side of the body contralateral to the hemispherectomy, which were already decreased preoperatively, decreased even further in the first 6 months after surgery, but returned to the presurgical baseline thereafter, except for the distal part of the arm. Range of motion was abnormal prior to operation and remained so after operation. Mean GMFM increase was 20% after 2 years (95% confidence interval 10-33); all five dimensions improved statistically significantly (P < 0.05). Mean PEDI increase was more than 20 scale points (95% confidence interval 10-35); again, all domains improved significantly (P < 0.05). In nearly all children, HARCES scores had normalized 2 years after surgery. In conclusion, decrease of seizure frequency and severity widens the scope of motor and social functioning, which overrides the effects of remaining motor impairments.

Executive Functioning in Childhood Epilepsy: Parent-Report and Cognitive Assessment

ERIC Educational Resources Information Center

Parrish, Joy; Geary, Elizabeth; Jones, Jana; Seth, Raj; Hermann, Bruce; Seidenberg, Michael

2007-01-01

There is considerable interest in the assessment of executive function (EF) in pediatric clinical populations but only a few well-standardized measures exist. We examined EF in 53 children aged 8 to 18 years with recent onset epilepsy (31 males, 22 females) and 50 control children (23 males, 27 females) using the Behavior Rating Inventory of…

Disrupted Structural and Functional Networks and Their Correlation with Alertness in Right Temporal Lobe Epilepsy: A Graph Theory Study.

PubMed

Jiang, Wenyu; Li, Jianping; Chen, Xuemei; Ye, Wei; Zheng, Jinou

2017-01-01

Previous studies have shown that temporal lobe epilepsy (TLE) involves abnormal structural or functional connectivity in specific brain areas. However, limited comprehensive studies have been conducted on TLE associated changes in the topological organization of structural and functional networks. Additionally, epilepsy is associated with impairment in alertness, a fundamental component of attention. In this study, structural networks were constructed using diffusion tensor imaging tractography, and functional networks were obtained from resting-state functional MRI temporal series correlations in 20 right temporal lobe epilepsy (rTLE) patients and 19 healthy controls. Global network properties were computed by graph theoretical analysis, and correlations were assessed between global network properties and alertness. The results from these analyses showed that rTLE patients exhibit abnormal small-world attributes in structural and functional networks. Structural networks shifted toward more regular attributes, but functional networks trended toward more random attributes. After controlling for the influence of the disease duration, negative correlations were found between alertness, small-worldness, and the cluster coefficient. However, alertness did not correlate with either the characteristic path length or global efficiency in rTLE patients. Our findings show that disruptions of the topological construction of brain structural and functional networks as well as small-world property bias are associated with deficits in alertness in rTLE patients. These data suggest that reorganization of brain networks develops as a mechanism to compensate for altered structural and functional brain function during disease progression.

Self-esteem, behavior, and concerns surrounding epilepsy in siblings of children with epilepsy.

PubMed

Mims, J

1997-04-01

Researchers document the emotional impact of epilepsy on the child with seizures. Minimal data are available examining the effects of epilepsy on the siblings of children with seizures. Twenty children whose siblings had either frequent seizures or infrequent seizures were matched by age, gender, and birth order to control subjects with no chronic illness. These three groups were compared. Self-esteem, behavioral and social functioning, and family stress were measured by the Piers-Harris Self-Concept Scale, Child Behavior Checklist, and Family Inventory of Life Events. The siblings of children with epilepsy completed the Sibling Concern About Seizure Scale to define and measure their concerns surrounding epilepsy. There is no statistical difference in self-esteem or social functioning among the three groups. There is a trend toward increased incidence of externalizing behavior in siblings of children with frequent seizures. Data indicate a trend toward siblings of children with frequent seizures having more concerns about epilepsy than siblings of children with infrequent seizures. There is significantly more stress in families of children with frequent seizures compared to families of children with infrequent seizures and families of children with no chronic illness. Although there were no significant differences in the self-esteem, behavior, socialization, and concerns between the siblings in the family when compared to the control group or to each other, there were trends in the results that may be of clinical significance. These issues, along with the level of family stress, should be considered when coordinating and providing care to families of children with intractable epilepsy.

Heredity in epilepsy: neurodevelopment, comorbidity, and the neurological trait.

PubMed

Johnson, Michael R; Shorvon, Simon D

2011-11-01

The genetic bases of common, nonmendelian epilepsy have been difficult to elucidate. In this article, we argue for a new approach to genetic inquiry in epilepsy. In the latter part of the 19th century, epilepsy was universally acknowledged to be part of a wider "neurological trait" that included other neuropsychiatric conditions. In recent years, studies of comorbidity have shown clear links between epilepsy and various neuropsychiatric disorders including psychosis and depression, and genetic studies of copy number variants (CNVs) have shown that in some cases, the same CNV underpins neuropsychiatric illness and epilepsy. Functional annotation analysis of the sets of genes impacted by epilepsy CNVs shows enrichment for genes involved with neural development, with gene ontological (GO) categories including "neurological system process" (P=0.006), "synaptic transmission" (P=0.009), and "learning or memory" (P=0.01). These data support the view that epilepsy and some neuropsychiatric conditions share pathogenic neurodevelopmental pathways, and that epilepsy should be included in the spectrum of neurodevelopmental disorders. Yet, most current genetic research in epilepsy has restricted samples to specific types of epilepsy categorized according to the clinical classification schemes on the basis of seizure type, anatomical location, or epilepsy syndrome. These schemes are, to an extent, arbitrary and do not necessarily align with biological reality. We propose an alternative approach that makes no phenotypic assumptions beyond including epilepsy in the neurodevelopmental spectrum. A "'value-free" strategy of reverse phenotyping may be worth exploring, starting with genetic association and looking backward at the phenotype. Finally, it should be noted that there are societal implications to associating epilepsy with other neuropsychiatric disorders, and it is vital to ensure research in this area does not result in increased stigma for patients with epilepsy. Copyright © 2011 Elsevier Inc. All rights reserved.

Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy.

PubMed

Glennon, Jennifer M; Weiss-Croft, Louise; Harrison, Sue; Cross, J Helen; Boyd, Stewart G; Baldeweg, Torsten

2016-09-01

The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The potential of critical social theory as an educational framework for people with epilepsy.

PubMed

Bennett, Louise; Bergin, Michael; Wells, John S G

2016-01-01

Effective education can support people with epilepsy to develop the attributes and skills required to function as equal partners with clinical service providers, make informed decisions, and competently self-manage their healthcare. However, despite knowledge deficits, unmet information needs, and a poor sense of empowerment, the study of education for people with epilepsy is often neglected and is a poorly understood component of holistic practice within epilepsy healthcare. Historically, the only debate with regard to education and people with epilepsy has been guided either within a positivist or within a constructivist philosophy. We argue that new pedagogies are warranted, recognizing the views of people with epilepsy regarding their illness. Therefore, this paper explores the potential of an educational framework for people with epilepsy based upon critical social theory (CST). By utilizing a CST approach for education, people with epilepsy are engaged with as active 'participants'. This is a key difference that distinguishes CST from other metatheoretical frameworks. It has the potential to support people with epilepsy to acquire the skills and confidence to manage the biopsychosocial challenges associated with their condition. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetics Home Reference: autosomal dominant nocturnal frontal lobe epilepsy

MedlinePlus

... brain are involved in many critical functions, including reasoning, planning, judgment, and problem-solving. It is unclear ... E, Montagna P. Nocturnal frontal lobe epilepsy. A clinical and polygraphic overview of 100 consecutive cases. Brain. ...

The impact of anxiety, seizure severity, executive dysfunction, subjectively perceived psychological deficits, and depression on social function in patients with epilepsy.

PubMed

Kampf, Christina; Walter, Uwe; Rösche, Johannes

2016-04-01

The impact of anxiety, seizure severity, executive dysfunction, subjectively perceived psychological deficits, and depression on social function in patients with epilepsy (PWE) was analyzed. A brief cognitive screening test (EpiTrack) and an estimation of the last 6 months' cumulative seizure severity (Chalfont seizure severity scale) were performed, and questionnaires on subjectively perceived cognitive deficits (c.I.-Skala), anxiety (State-Trait Anxiety Inventory, STAIX1 and STAIX2), depression (Self Rating Depression Scale, SDS), and social function (Soziale Aktivität Selbstbeurteilungsskala, SASS) were completed. Forty PWE (aged 41.8 years, SD 16; 24 female, 16 male) were analyzed. Thirty-eight point 5 percent had a score signifying depression in the SDS; 20% had a pathological result in at least one of the anxiety scores. The ANOVA revealed that only anxiety as a trait symptom (STAIX2) had a significant influence on social function apart from the other factors (p<0.004). Additionally there was a trend for a significant influence of depressive symptoms (SDS) on social functioning (p=0.093). Symptoms of anxiety impair the social function of patients with epilepsy apart from depression, cognitive function, and seizure severity. They should be taken into account in the treatment of patients with epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Low-Dimensional Chaos in an Instance of Epilepsy

NASA Astrophysics Data System (ADS)

Babloyantz, A.; Destexhe, A.

1986-05-01

Using a time series obtained from the electroencephalogram recording of a human epileptic seizure, we show the existence of a chaotic attractor, the latter being the direct consequence of the deterministic nature of brain activity. This result is compared with other attractors seen in normal human brain dynamics. A sudden jump is observed between the dimensionalities of these brain attractors 4.05 ± 0.05 for deep sleep) and the very low dimensionality of the epileptic state (2.05 ± 0.09). The evaluation of the autocorrelation function and of the largest Lyapunov exponent allows us to sharpen further the main features of underlying dynamics. Possible implications in biological and medical research are briefly discussed.

Health-Related Quality of Life and Related Factors in Children and Adolescents With Epilepsy in Iran.

PubMed

Momeni, Maryam; Ghanbari, Atefeh; Bidabadi, Elham; Yousefzadeh-Chabok, Shahrokh

2015-12-01

The effects of epilepsy may disturb the ability of the child and family to function and has detrimental effects on health-related quality of life (HRQOL). We determined HRQOL and related factors in children and adolescents with epilepsy in Iran. This cross-sectional study was performed in a private neurology pediatric clinic in Guilan Province (North of Iran). We evaluated 108 children and adolescents with epilepsy. Data were collected by interview with parents and review of medical records. Generic and specific HRQOL was evaluated by Child Health Questionnaire and QOL in Childhood Epilepsy Questionnaire, respectively. The mean of overall generic HRQOL score was 71.05 ± 11.31. The lowest score was related to parental impact: emotional (52.59 ± 15.49). The average total specific HRQOL score was 71.95 ± 11.16. The lowest score dedicated to general health (51.21 ± 18.25). In multivariate regression analysis, duration of epilepsy (p < .016) was independently associated with generic HRQOL scores. Variables were independently associated with specific HRQOL scores including gender (p < .003), duration of epilepsy (p < .011), and family history of epilepsy (p < .005). We found that epilepsy duration was the strongest predictor of both generic and specific HRQOL in children and adolescents with epilepsy. This will be useful for clinicians in epilepsy management, which will enhance HRQOL.

mTOR: A pathogenic signaling pathway in developmental brain malformations.

PubMed

Crino, Peter B

2011-12-01

The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortical malformations associated with epilepsy and neurobehavioral disabilities. Investigation of mTOR signaling in these disorders provides for the first time exciting future avenues for assessment of biomarkers, patient stratification and prognostic measures as well as the opportunity for targeted therapy to regulate mTOR activity across all age groups. As we learn more about mTOR and its activity in the developing brain, many challenges will arise that must be overcome before widespread clinical therapeutics can be implemented. Copyright © 2011. Published by Elsevier Ltd.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

PubMed

Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

2017-03-01

Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2 = 0.045). In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis. © 2017 by American Journal of Neuroradiology.

Orexin and Epilepsy: Potential Role of REM Sleep.

PubMed

Ng, Marcus C

2017-03-01

Interest in orexin receptor antagonism as a novel mechanism of action against seizures and epilepsy has increased in recent years. Loss of orexinergic activity is associated with rapid eye movement (REM) sleep onset, and REM sleep is generally protective against seizures. This paper discusses the dynamic modulation of seizure threshold by orexin through a postulated "orexi-cortical" axis in which the specific type of orexinergic activity exquisitely regulates sleep-wake states to modify ascending subcortical influences on cortical synchronization with profound subsequent consequences on seizure threshold. This paper also explores the current state of research into experimental orexinergic modulation of seizure threshold and suggests possible future research directions to fully understand the promise and peril of orexinergic manipulation in seizures and epilepsy. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Single photon emission computed tomography (SPECT) in epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leroy, R.F.

1991-12-31

Epilepsy is a common neurologic disorder which has just begun to be studied with single photon emission computerized tomography (SPECT). Epilepsy usually is studied with electroencephalographic (EEG) techniques that demonstrate the physiologic changes that occur during seizures, and with neuroimaging techniques that show the brain structures where seizures originate. Neither method alone has been adequate to describe the pathophysiology of the patient with epilepsy. EEG techniques lack anatomic sensitivity, and there are no structural abnormalities shown by neuroimaging which are specific for epilepsy. Functional imaging (FI) has developed as a physiologic tool with anatomic sensitivity, and SPECT has been promotedmore » as a FI technique because of its potentially wide availability. However, SPECT is early in its development and its clinical utility for epilepsy still has to be demonstrated. To understand this role of SPECT, consideration must be given to the pathophysiology of epilepsy, brain physiology, types of seizure, epileptic syndromes, and the SPECT technique itself. 44 refs., 2 tabs.« less

Neuroimaging correlates of language network impairment and reorganization in temporal lobe epilepsy

PubMed Central

Balter, S.; Lin, G.; Leyden, K.M.; Paul, B.M.; McDonald, C.R.

2016-01-01

Advanced, noninvasive imaging has revolutionized our understanding of language networks in the brain and is reshaping our approach to the presurgical evaluation of patients with epilepsy. Functional magnetic resonance imaging (fMRI) has had the greatest impact, unveiling the complexity of language organization and reorganization in patients with epilepsy both pre- and postoperatively, while volumetric MRI and diffusion tensor imaging have led to a greater appreciation of structural and microstructural correlates of language dysfunction in different epilepsy syndromes. In this article, we review recent literature describing how unimodal and multimodal imaging has advanced our knowledge of language networks and their plasticity in epilepsy, with a focus on the most frequently studied epilepsy syndrome in adults, temporal lobe epilepsy (TLE). We also describe how new analytic techniques (i.e., graph theory) are leading to a refined characterization of abnormal brain connectivity, and how subject-specific imaging profiles combined with clinical data may enhance the prediction of both seizure and language outcomes following surgical interventions. PMID:27393391

Sleep disorders in adults with epilepsy: past, present, and future directions.

PubMed

Grigg-Damberger, Madeleine M; Ralls, Frank

2014-11-01

To summarize recent studies on the complex relationships between sleep disorders, sleep, and epilepsy. Insomnia in adults with epilepsy (AWE) warrants consideration of depression, anxiety, and suicidal ideation. Daytime sleepiness in AWE is more often due to undiagnosed sleep disorders. Sleep deprivation is an important provoker of seizures in juvenile myoclonic epilepsy. Abnormalities in frontal lobe executive function with difficulties making advantageous decisions may explain failure of juvenile myoclonic epilepsy patients to adhere to treatment recommendations and regulate their sleep habits. Sleep architecture in AWE is more likely to be abnormal if seizures are poorly controlled or occur during sleep. Obstructive sleep apnea is much more common in AWE who are man, older, heavier, or whose seizures are poorly controlled. Chronobiology and chronopharmacology of epilepsy is an emerging field worthy of future research and clinical applications. Identifying and treating unrecognized sleep disorders and understanding the impact of circadian rhythms on epilepsy can improve quality of life and seizure control in AWE.

Physical Feature Encoding and Word Recognition Abilities Are Altered in Children with Intractable Epilepsy: Preliminary Neuromagnetic Evidence

PubMed Central

Pardos, Maria; Korostenskaja, Milena; Xiang, Jing; Fujiwara, Hisako; Lee, Ki H.; Horn, Paul S.; Byars, Anna; Vannest, Jennifer; Wang, Yingying; Hemasilpin, Nat; Rose, Douglas F.

2015-01-01

Objective evaluation of language function is critical for children with intractable epilepsy under consideration for epilepsy surgery. The purpose of this preliminary study was to evaluate word recognition in children with intractable epilepsy by using magnetoencephalography (MEG). Ten children with intractable epilepsy (M/F 6/4, mean ± SD 13.4 ± 2.2 years) were matched on age and sex to healthy controls. Common nouns were presented simultaneously from visual and auditory sensory inputs in “match” and “mismatch” conditions. Neuromagnetic responses M1, M2, M3, M4, and M5 with latencies of ~100 ms, ~150 ms, ~250 ms, ~350 ms, and ~450 ms, respectively, elicited during the “match” condition were identified. Compared to healthy children, epilepsy patients had both significantly delayed latency of the M1 and reduced amplitudes of M3 and M5 responses. These results provide neurophysiologic evidence of altered word recognition in children with intractable epilepsy. PMID:26146459

Regional brain volumes and cognition in childhood epilepsy: does size really matter?

PubMed

Zelko, Frank A; Pardoe, Heath R; Blackstone, Sarah R; Jackson, Graeme D; Berg, Anne T

2014-05-01

Recent studies have correlated neurocognitive function and regional brain volumes in children with epilepsy. We tested whether brain volume differences between children with and without epilepsy explained differences in neurocognitive function. The study sample included 108 individuals with uncomplicated non-syndromic epilepsy (NSE) and 36 healthy age- and gender-matched controls. Participants received a standardized cognitive battery. Whole brain T1-weighted MRI was obtained and volumes analyzed with FreeSurfer (TM). Total brain volume (TBV) was significantly smaller in cases. After adjustment for TBV, cases had significantly larger regional grey matter volumes for total, frontal, parietal, and precentral cortex. Cases had poorer performance on neurocognitive indices of intelligence and variability of sustained attention. In cases, TBV showed small associations with intellectual indices of verbal and perceptual ability, working memory, and overall IQ. In controls, TBV showed medium associations with working memory and variability of sustained attention. In both groups, small associations were seen between some TBV-adjusted regional brain volumes and neurocognitive indices, but not in a consistent pattern. Brain volume differences did not account for cognitive differences between the groups. Patients with uncomplicated NSE have smaller brains than controls but areas of relative grey matter enlargement. That this relative regional enlargement occurs in the context of poorer overall neurocognitive functioning suggests that it is not adaptive. However, the lack of consistent associations between case-control differences in brain volumes and cognitive functioning suggests that brain volumes have limited explanatory value for cognitive functioning in childhood epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

Unique and shared areas of cognitive function in children with intractable frontal or temporal lobe epilepsy.

PubMed

Law, Nicole; Widjaja, Elysa; Smith, Mary Lou

2018-03-01

Previous findings have been mixed in terms of identifying a distinct pattern of neuropsychological deficits in children with frontal lobe epilepsy (FLE) and in those with temporal lobe epilepsy (TLE). The current study investigated the neuropsychological similarities and differences across these two pediatric medically intractable localization-related epilepsies. Thirty-eight children with FLE, 20 children with TLE, and 40 healthy children (HC) participated in this study. A comprehensive battery of standardized tests assessed five neuropsychological domains including intelligence, language, memory, executive function, and motor function. A principal component analysis (PCA) was used to distill our neuropsychological measures into latent components to compare between groups. Principal component analysis extracted 5 latent components: executive function (F1), verbal semantics (F2), motor (F3), nonverbal cognition/impulsivity (F4), and verbal cognition/attention (F5). The group with FLE differed from the HC group on F1, F2, F4, and F5, and had worse performance than the group with TLE on F1; the group with TLE had lower performance relative to the HC group on F2. Our findings suggest that, in comparison with neurotypically developing children, children with medically intractable FLE have more widespread neuropsychological impairments than do children with TLE. The differences between the two patient groups were greatest for the factor score most clearly related to executive function. The results provide mixed support for the concept of specificity in neuropsychological dysfunction among different subtypes of localization-related medically intractable childhood epilepsies. Copyright © 2018 Elsevier Inc. All rights reserved.

The influence of folate serum levels on depressive mood and mental processing in patients with epilepsy treated with enzyme-inducing anti-epileptic drugs.

PubMed

Rösche, J; Uhlmann, C; Weber, R; Fröscher, W

2003-04-01

Folate deficiency is common in patients with epilepsy and also occurs in patients with depression or cognitive deficits. This study investigates whether low serum folate levels may contribute to depressive mood and difficulties in mental processing in patients with epilepsy treated with anti-epileptic drugs inducing the cytochrome P450. We analysed the serum folate levels, the score in the Self Rating Depression Scale (SDS) and the results of a bedside test in mental processing in 54 patients with epilepsy. There was a significant negative correlation between the serum folate levels and the score in SDS and significant positive correlations between the score in SDS and the time needed to process an interference task or a letter-reading task. Low serum folate levels may contribute to depressive mood and therefore to difficulties in mental processing. Further studies utilizing total plasma homocysteine as a sensitive measure of functional folate deficiency and more elaborate tests of mental processing are required to elucidate the impact of folate metabolism on depressive mood and cognitive function in patients with epilepsy.

Trends in pediatric epilepsy surgery.

PubMed

Shah, Ritesh; Botre, Abhijit; Udani, Vrajesh

2015-03-01

Epilepsy surgery has become an accepted treatment for drug resistant epilepsy in infants and children. It has gained ground in India over the last decade. Certain epilepsy surgically remediable syndromes have been delineated and should be offered surgery earlier rather than later, especially if cognitive/behavioral development is being compromised. Advances in imaging, particularly in MRI has helped identify surgical candidates. Pre-surgical evaluation includes clinical assessment, structural and functional imaging, inter-ictal EEG, simultaneous video -EEG, with analysis of seizure semiology and ictal EEG and other optional investigations like neuropsychology and other newer imaging techniques. If data are concordant resective surgery is offered, keeping in mind preservation of eloquent cortical areas subserving motor, language and visual functions. In case of discordant data or non-lesional MRI, invasive EEG maybe useful using a two-stage approach. With multi-focal / generalized disease, palliative surgery like corpus callosotomy and vagal nerve stimulation maybe useful. A good outcome is seen in about 2/3rd of patients undergoing resective surgery with a low morbidity and mortality. This review outlines important learning aspects of pediatric epilepsy surgery for the general pediatrician.

Resting-State Functional MR Imaging for Determining Language Laterality in Intractable Epilepsy.

PubMed

DeSalvo, Matthew N; Tanaka, Naoaki; Douw, Linda; Leveroni, Catherine L; Buchbinder, Bradley R; Greve, Douglas N; Stufflebeam, Steven M

2016-10-01

Purpose To measure the accuracy of resting-state functional magnetic resonance (MR) imaging in determining hemispheric language dominance in patients with medically intractable focal epilepsies against the results of an intracarotid amobarbital procedure (IAP). Materials and Methods This study was approved by the institutional review board, and all subjects gave signed informed consent. Data in 23 patients with medically intractable focal epilepsy were retrospectively analyzed. All 23 patients were candidates for epilepsy surgery and underwent both IAP and resting-state functional MR imaging as part of presurgical evaluation. Language dominance was determined from functional MR imaging data by calculating a laterality index (LI) after using independent component analysis. The accuracy of this method was assessed against that of IAP by using a variety of thresholds. Sensitivity and specificity were calculated by using leave-one-out cross validation. Spatial maps of language components were qualitatively compared among each hemispheric language dominance group. Results Measurement of hemispheric language dominance with resting-state functional MR imaging was highly concordant with IAP results, with up to 96% (22 of 23) accuracy, 96% (22 of 23) sensitivity, and 96% (22 of 23) specificity. Composite language component maps in patients with typical language laterality consistently included classic language areas such as the inferior frontal gyrus, the posterior superior temporal gyrus, and the inferior parietal lobule, while those of patients with atypical language laterality also included non-classical language areas such as the superior and middle frontal gyri, the insula, and the occipital cortex. Conclusion Resting-state functional MR imaging can be used to measure language laterality in patients with medically intractable focal epilepsy. (©) RSNA, 2016 Online supplemental material is available for this article.

Resting-State Functional MR Imaging for Determining Language Laterality in Intractable Epilepsy

PubMed Central

Tanaka, Naoaki; Douw, Linda; Leveroni, Catherine L.; Buchbinder, Bradley R.; Greve, Douglas N.; Stufflebeam, Steven M.

2016-01-01

Purpose To measure the accuracy of resting-state functional magnetic resonance (MR) imaging in determining hemispheric language dominance in patients with medically intractable focal epilepsies against the results of an intracarotid amobarbital procedure (IAP). Materials and Methods This study was approved by the institutional review board, and all subjects gave signed informed consent. Data in 23 patients with medically intractable focal epilepsy were retrospectively analyzed. All 23 patients were candidates for epilepsy surgery and underwent both IAP and resting-state functional MR imaging as part of presurgical evaluation. Language dominance was determined from functional MR imaging data by calculating a laterality index (LI) after using independent component analysis. The accuracy of this method was assessed against that of IAP by using a variety of thresholds. Sensitivity and specificity were calculated by using leave-one-out cross validation. Spatial maps of language components were qualitatively compared among each hemispheric language dominance group. Results Measurement of hemispheric language dominance with resting-state functional MR imaging was highly concordant with IAP results, with up to 96% (22 of 23) accuracy, 96% (22 of 23) sensitivity, and 96% (22 of 23) specificity. Composite language component maps in patients with typical language laterality consistently included classic language areas such as the inferior frontal gyrus, the posterior superior temporal gyrus, and the inferior parietal lobule, while those of patients with atypical language laterality also included non-classical language areas such as the superior and middle frontal gyri, the insula, and the occipital cortex. Conclusion Resting-state functional MR imaging can be used to measure language laterality in patients with medically intractable focal epilepsy. © RSNA, 2016 Online supplemental material is available for this article. PMID:27467465

Knowledge about epilepsy in university health students: A multicenter study.

PubMed

Souza, Priscila; Portes, Leslie A; Thomas, Robert K; Bonito, Jorge R; Rua, Marilia; Pacheco, Fabio J; Plaatjes, Phillip; Oliveira, Natalia C

2018-02-01

Even with economic development and improvements in health care around the world, it is estimated that nowadays, 50 million people have epilepsy. It is one of the most prevalent neurological diseases, yet it is still surrounded by prejudice, stigma, lack of awareness, and wrong attitudes of the population towards the disease. The aim of this study was to evaluate and compare the knowledge about epilepsy in health students from different countries: Brazil, Argentina, Portugal, United States, and South Africa. Students were asked to complete a survey regarding knowledge about epilepsy (the Epilepsy Knowledge Questionnaire). One hundred and two students participated, 62.2% of them were female. Portuguese students had significantly higher values than the American ones (p=0.025). Regarding the medical aspects, on average, students hit 63.8% of the questions, and the students from Portugal had significantly higher average than the ones from the United States (p=0.0007). Statements with lower percent of correct answers were about pathophysiology, medication, and treatment of the disease. There were no differences between the scores obtained by the students of each country in the social aspects of the disease. Statements with higher percent of mistakes were about sports practice, labor, proceedings in case of convulsion, and ability to drive vehicles. General knowledge of senior health students about epilepsy was considered low, however, regarding the medical aspects of the disease, students from Brazil and Portugal exhibited a slightly superior knowledge. Changing the way of seeing and treating people with epilepsy brings, as a consequence, increased opportunities for these people in different sectors of society. Copyright © 2017 Elsevier Inc. All rights reserved.

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. Copyright © 2010 Elsevier B.V. All rights reserved.

Basic knowledge of epilepsy among medical students.

PubMed

Tiamkao, Siriporn; Tiamkao, Somsak; Auevitchayapat, Narong; Arunpongpaisal, Suwanna; Chaiyakum, Aporanee; Jitpimolmard, Suthipun; Phuttharak, Warinthorn; Phunikhom, Kutcharin; Saengsuwan M, Jiamjit; Vannaprasaht, Suda

2007-11-01

The medical students' knowledge about basic medical neuroscience in the preclinical level may be fragmented and incomplete. Evaluate the knowledge of students prior to a lecture on epilepsy in clinical level. One hundred ten fourth-year medical students' knowledge was accessed by a self-administered questionnaire. The presented results revealed that 91.8% of respondents knew that epilepsy arose from a transient dysfunction in the brain. Generalized tonic-clonic seizures (GTCs) were the most common type (91.5%) they knew and absence seizures were the least common type (33.6%) they knew. All of them knew that eating pork and punishment of gods did not cause epilepsy. However 50% thought that genetics was a cause and 80.3% did not know that stroke and sleep deprivation (92.7%) cause epilepsy. About treatment and prognosis, only 28.2% of respondents thought epilepsy can be cured and patients should take antiepileptic drugs (AEDs) for seizure free 2-5 years (48.2%), life long (33.6%). They knew that the patients should be prohibited from driving (80%), working on machinery (74.5%), and (27.3%) avoid drinking. However, they knew that the patients could marry (100%), get pregnant (98.2%), and lactate (91.9%). Regarding the first aid management, 50.9% of them recommended that placing a piece of wood between the teeth during a seizure and perform chest compressions (20.0%). Means knowledge scores is about 60%, the highest score is the definition of epilepsy (90.2%) and the lowest is type of seizure (43%). The findings indicated that lecturers should review aspects ofpathophysiology and emphasize on type of seizure, cause, consequences, and prognosis including first-aid management.

Seizure-related factors and non-verbal intelligence in children with epilepsy. A population-based study from Western Norway.

PubMed

Høie, B; Mykletun, A; Sommerfelt, K; Bjørnaes, H; Skeidsvoll, H; Waaler, P E

2005-06-01

To study the relationship between seizure-related factors, non-verbal intelligence, and socio-economic status (SES) in a population-based sample of children with epilepsy. The latest ILAE International classifications of epileptic seizures and syndromes were used to classify seizure types and epileptic syndromes in all 6-12 year old children (N=198) with epilepsy in Hordaland County, Norway. The children had neuropediatric and EEG examinations. Of the 198 patients, demographic characteristics were collected on 183 who participated in psychological studies including Raven matrices. 126 healthy controls underwent the same testing. Severe non-verbal problems (SNVP) were defined as a Raven score at or <10th percentile. Children with epilepsy were highly over-represented in the lowest Raven percentile group, whereas controls were highly over-represented in the higher percentile groups. SNVP were present in 43% of children with epilepsy and 3% of controls. These problems were especially common in children with remote symptomatic epilepsy aetiology, undetermined epilepsy syndromes, myoclonic seizures, early seizure debut, high seizure frequency and in children with polytherapy. Seizure-related characteristics that were not usually associated with SNVP were idiopathic epilepsies, localization related (LR) cryptogenic epilepsies, absence and simple partial seizures, and a late debut of epilepsy. Adjusting for socio-economic status factors did not significantly change results. In childhood epilepsy various seizure-related factors, but not SES factors, were associated with the presence or absence of SNVP. Such deficits may be especially common in children with remote symptomatic epilepsy aetiology and in complex and therapy resistant epilepsies. Low frequencies of SNVP may be found in children with idiopathic and LR cryptogenic epilepsy syndromes, simple partial or absence seizures and a late epilepsy debut. Our study contributes to an overall picture of cognitive function and its relation to central seizure characteristics in a childhood epilepsy population and can be useful for the follow-up team in developing therapy strategies that meet the individual needs of the child with epilepsy.

Sleepiness, On-Task Behavior and Attention in Children with Epilepsy Who Visited a School for Special Education: A Comparative Study

ERIC Educational Resources Information Center

Didden, Robert; de Moor, Jan M. H.; Korzilius, Hubert

2009-01-01

Children with epilepsy are at risk for problems in daytime functioning. We assessed daytime sleepiness, on-task behavior and attention in 17 children (aged between 7 and 11 years) with epilepsy who visited a school for special education and compared these to 17 children from a control group who visited a regular school. Within the group of…

The usefulness of Quality of Life Childhood Epilepsy (QOLCE) questionnaire in evaluating the quality of life of children with epilepsy.

PubMed

Talarska, D

2007-01-01

Evaluation of quality of life has become a frequently used method in treatment effects supervision. Quality of Life Childhood Epilepsy (QOLCE) questionnaire, which is completed by patients' parents, has been prepared for children with epilepsy. It enables to determine the quality of life in children aged 4-18 years. The aim of the study was to show the usefulness of QOLCE questionnaire in evaluating the quality of life of children with epilepsy. 160 epileptic children, aged 8-18 years and their parents were examined in the Chair and Department of Developmental Neurology, K. Marcinkowski University of Medical Sciences in Poznań. QOLCE questionnaire was completed by parents and "Young people and epilepsy" questionnaire was designed for children. Reliability index of the complete questionnaire in own research and in the original amounted to 0.93 Cronbach alpha coefficient. Epileptic, drug-resistant children constituted 28% of the examined group. Parents of children with controlled seizures evaluated children's functioning in analyzed areas of quality of life higher. 1. QOLCE questionnaire is a suitable tool to evaluate the quality of children's and adolescents' life. 2. The most significant differences in functioning of epileptic, drug-resistant patients and those with controlled seizures were observed in areas of cognitive processes and social activity.

Detection of subtle nocturnal motor activity from 3-D accelerometry recordings in epilepsy patients.

PubMed

Nijsen, Tamara M E; Cluitmans, Pierre J M; Arends, Johan B A M; Griep, Paul A M

2007-11-01

This paper presents a first step towards reliable detection of nocturnal epileptic seizures based on 3-D accelerometry (ACM) recordings. The main goal is to distinguish between data with and without subtle nocturnal motor activity, thus reducing the amount of data that needs further (more complex) analysis for seizure detection. From 15 ACM signals (measured on five positions on the body), two features are computed, the variance and the jerk. In the resulting 2-D feature space, a linear threshold function is used for classification. For training and testing, the algorithm ACM data along with video data is used from nocturnal registrations in seven mentally retarded patients with severe epilepsy. Per patient, the algorithm detected 100% of the periods of motor activity that are marked in video recordings and the ACM signals by experts. From all the detections, 43%-89% was correct (mean =65%). We were able to reduce the amount of data that need to be analyzed considerably. The results show that our approach can be used for detection of subtle nocturnal motor activity. Furthermore, our results indicate that our algorithm is robust for fluctuations across patients. Consequently, there is no need for training the algorithm for each new patient.

Amygdala enlargement and emotional responses in (autoimmune) temporal lobe epilepsy.

PubMed

Holtmann, Olga; Schlossmacher, Insa; Moenig, Constanze; Johnen, Andreas; Rutter, Lisa-Marie; Tenberge, Jan-Gerd; Schiffler, Patrick; Everding, Judith; Golombeck, Kristin S; Strippel, Christine; Dik, Andre; Schwindt, Wolfram; Wiendl, Heinz; Meuth, Sven G; Bruchmann, Maximilian; Melzer, Nico; Straube, Thomas

2018-06-22

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.

Epileptogenesis: can the science of epigenetics give us answers?

PubMed

Lubin, Farah D

2012-05-01

Epigenetic mechanisms are regulatory processes that control gene expression changes involved in multiple aspects of neuronal function, including central nervous system development, synaptic plasticity, and memory. Recent evidence indicates that dysregulation of epigenetic mechanisms occurs in several human epilepsy syndromes. Despite this discovery of a potential role for epigenetic mechanisms in epilepsy, few studies have fully explored their contribution to the process of epilepsy development known as epileptogenesis. The purpose of this article is to discuss recent findings suggesting that the process of epileptogenesis may alter the epigenetic landscape, affecting the gene expression patterns observed in epilepsy. Future studies focused on a better characterization of these aberrant epigenetic mechanisms hold the promise of revealing novel treatment options for the prevention and even the reversal of epilepsy.

The role of genetic testing in epilepsy diagnosis and management.

PubMed

Weber, Yvonne G; Biskup, Saskia; Helbig, Katherine L; Von Spiczak, Sarah; Lerche, Holger

2017-08-01

Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. More than 500 epilepsy-associated genes have been described in the literature. Most of these genes play an important role in neuronal excitability, cortical development or synaptic transmission. A growing number of genetic variations have implications on diagnosis and prognostic or therapeutic advice in terms of a personalized medicine. Area covered: The review presents the different forms of genetic epilepsies with respect to their underlying genetic and functional pathophysiology and aims to give advice for recommended genetic testing. Moreover, it discusses ethical and legal guidelines, costs and technical limitations which should be considered. Expert commentary: Genetic testing is an important component in the diagnosis and treatment of many forms of epilepsy.

Mesial frontal lobe epilepsy.

PubMed

Unnwongse, Kanjana; Wehner, Tim; Foldvary-Schaefer, Nancy

2012-10-01

Mesial frontal lobe epilepsies can be divided into epilepsies arising from the anterior cingulate gyrus and those of the supplementary sensorimotor area. They provide diagnostic challenges because they often lack lateralizing or localizing features on clinical semiology and interictal and ictal scalp electroencephalographic (EEG) recordings. A number of unique semiologic features have been described over the last decade in patients with mesial frontal lobe epilepsy (FLE). There are few reports of applying advanced neurophysiologic techniques such as electrical source imaging, magnetoencephalography, EEG/functional magnetic resonance imaging, or analysis of high-frequency oscillations in patients with mesial FLE. Despite these diagnostic challenges, it seems that patients with mesial FLE benefit from epilepsy surgery to the same extent or even better than patients with FLE do, as a whole.

WONOEP appraisal: new genetic approaches to study epilepsy

PubMed Central

Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

2014-01-01

Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non-coding RNAs involved in modifying gene expression following seizures. In addition, genetically-based bioluminescent reporters are providing new opportunities to assess neuronal activity and neurotransmitter levels both in vitro and in vivo in the context of epilepsy. Finally, genetically rederived neurons generated from patient iPS cells and genetically-modified zebrafish have become high-throughput means to investigate disease mechanisms and potential new therapies. Significance Genetics has considerably changed the field of epilepsy research and is paving the way for better diagnosis and therapies for patients with epilepsy. PMID:24965021

Epilepsy Surgery Series: A Study of 502 Consecutive Patients from a Developing Country

PubMed Central

Al-Otaibi, Faisal; Baz, Salah; Althubaiti, Ibrahim; Aldhalaan, Hisham; MacDonald, David; Abalkhail, Tareq; Fiol, Miguel E.; Alyamani, Suad; Chedrawi, Aziza; Leblanc, Frank; Parrent, Andrew; Maclean, Donald; Girvin, John

2014-01-01

Purpose. To review the postoperative seizure outcomes of patients that underwent surgery for epilepsy at King Faisal Specialist Hospital & Research Centre (KFSHRC). Methods. A descriptive retrospective study for 502 patients operated on for medically intractable epilepsy between 1998 and 2012. The surgical outcome was measured using the ILAE criteria. Results. The epilepsy surgery outcome for temporal lobe epilepsy surgery (ILAE classes 1, 2, and 3) at 12, 36, and 60 months is 79.6%, 74.2%, and 67%, respectively. The favorable 12- and 36-month outcomes for frontal lobe epilepsy surgery are 62% and 52%, respectively. For both parietal and occipital epilepsy lobe surgeries the 12- and 36-month outcomes are 67%. For multilobar epilepsy surgery, the 12- and 36-month outcomes are 65% and 50%, respectively. The 12- and 36-month outcomes for functional hemispherectomy epilepsy surgery are 64.2% and 63%, respectively. According to histopathology diagnosis, mesiotemporal sclerosis (MTS) and benign CNS tumors had the best favorable outcome after surgery at 1 year (77.27% and 84.3%, resp.,) and 3 years (76% and 75%, resp.,). The least favorable seizure-free outcome after 3 years occurred in cases with dual pathology (66.6%). Thirty-four epilepsy patients with normal magnetic resonance imaging (MRI) brain scans were surgically treated. The first- and third-year epilepsy surgery outcome of 17 temporal lobe surgeries were (53%) and (47%) seizure-free, respectively. The first- and third-year epilepsy surgery outcomes of 15 extratemporal epilepsy surgeries were (47%) and (33%) seizure-free. Conclusion. The best outcomes are achieved with temporal epilepsy surgery, mesial temporal sclerosis, and benign CNS tumor. The worst outcomes are from multilobar surgery, dual pathology, and normal MRI. PMID:24627805

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Video electroencephalogram telemetry in temporal lobe epilepsy

PubMed Central

Mani, Jayanti

2014-01-01

Temporal lobe epilepsy (TLE) is the most commonly encountered medically refractory epilepsy. It is also the substrate of refractory epilepsy that gives the most gratifying results in any epilepsy surgery program, with a minimum use of resources. Correlation of clinical behavior and the ictal patterns during ictal behavior is mandatory for success at epilepsy surgery. Video electroencephalogram (EEG) telemetry achieves this goal and hence plays a pivotal role in pre-surgical assessment. The role of telemetry is continuously evolving with the advent of digital EEG technology, of high-resolution volumetric magnetic resonance imaging and other functional imaging techniques. Most of surgical selection in patients with TLE can be done with a scalp video EEG monitoring. However, the limitations of the scalp EEG technique demand invasive recordings in a selected group of TLE patients. This subset of the patients can be a challenge to the epileptologist. PMID:24791089

Rational management of epilepsy.

PubMed

Viswanathan, Venkataraman

2014-09-01

Management of epilepsies in children has improved considerably over the last decade, all over the world due to the advances seen in the understanding of the patho-physiology of epileptogenesis, availability of both structural and functional imaging studies along with better quality EEG/video-EEG recordings and the availability of a plethora of newer anti-epileptic drugs which are tailormade to act on specific pathways. In spite of this, there is still a long way to go before one is able to be absolutely rational about which drug to use for which type of epilepsy. There have been a lot of advances in the area of epilepsy surgery and is certainly gaining ground for specific cases. Better understanding of the genetic basis of epilepsies will hopefully lead to a more rational treatment plan in the future. Also, a lot of work needs to be done to dispel various misunderstandings and myths about epilepsy which still exists in our country.

Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy

PubMed Central

Szaflarski, Jerzy P.; Gloss, David; Binder, Jeffrey R.; Gaillard, William D.; Golby, Alexandra J.; Holland, Scott K.; Ojemann, Jeffrey; Spencer, David C.; Swanson, Sara J.; French, Jacqueline A.; Theodore, William H.

2017-01-01

Objective: To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. Methods: An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. Results and recommendations: The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case. PMID:28077494

The Role of Functional Neuroimaging in Pre-Surgical Epilepsy Evaluation

PubMed Central

Pittau, Francesca; Grouiller, Frédéric; Spinelli, Laurent; Seeck, Margitta; Michel, Christoph M.; Vulliemoz, Serge

2014-01-01

The prevalence of epilepsy is about 1% and one-third of cases do not respond to medical treatment. In an eligible subset of patients with drug-resistant epilepsy, surgical resection of the epileptogenic zone is the only treatment that can possibly cure the disease. Non-invasive techniques provide information for the localization of the epileptic focus in the majority of cases, whereas in others invasive procedures are required. In the last years, non-invasive neuroimaging techniques, such as simultaneous recording of functional magnetic resonance imaging and electroencephalogram (EEG-fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), electric and magnetic source imaging (MSI, ESI), spectroscopy (MRS), have proved their usefulness in defining the epileptic focus. The combination of these functional techniques can yield complementary information and their concordance is crucial for guiding clinical decision, namely the planning of invasive EEG recordings or respective surgery. The aim of this review is to present these non-invasive neuroimaging techniques, their potential combination, and their role in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. PMID:24715886

Validation of a screening tool for attention and executive functions (EpiTrack Junior) in children and adolescents with absence epilepsy.

PubMed

Kadish, Navah Ester; Baumann, Matthias; Pietz, Joachim; Schubert-Bast, Susanne; Reuner, Gitta

2013-10-01

Our prospective study aimed at the validation of EpiTrack Junior, a neuropsychological screening tool for attention and executive functions in children with epilepsy. Twenty-two children with absence epilepsy aged 8-17 years underwent comprehensive neuropsychological evaluation including EpiTrack Junior and measures of intelligence, verbal and nonverbal memory, word fluency and visuoconstructive organization. Concurrent and discriminant validity of EpiTrack Junior subtests and total score as well as sensitivity and specificity of the total score were analyzed. EpiTrack Junior total score was impaired in 59% of participants. Concurrent validity was demonstrated in 4/6 subtests and for the total score. Discriminant validity was shown with respect to verbal and nonverbal long-term memory. Sensitivity was higher than specificity and highest for the "working memory index". EpiTrack Junior is recommended as a sensitive and time-efficient screening tool for attention and executive functions in children with epilepsy. Impaired results should be followed up with detailed evaluation including information from the parents and school as well as counseling where indicated. © 2013.

Global development and adaptive behaviour in children with early-onset epilepsy: a population-based case-control study.

PubMed

Reilly, Colin; Atkinson, Patricia; Memon, Ayesha; Jones, Chloe; Dabydeen, Lyvia; Das, Krishna B; Gillberg, Christopher; Neville, Brian G R; Mahoney, J Matthew; Scott, Rod C

2018-06-03

There are limited population-based data on global development and adaptive behaviour in children with early-onset epilepsy. The aims of this study were: (1) to identify the prevalence of deficits in global development and adaptive behaviour experienced by children with early-onset epilepsy; (2) to identify factors associated with such deficits; and (3) to compare the relationship between measures of neurodevelopment in the group with epilepsy to a group without epilepsy who had other neurological or neurodevelopmental difficulties. The Sussex Early Epilepsy and Neurobehaviour study is a prospective, community-based study involving children (1-7y) with epilepsy. We undertook comprehensive psychological assessment with participants, including measures of global development and adaptive behaviour. We compared the children with epilepsy with a sex, age, and developmentally-matched group of children without epilepsy who had neurodevelopmental or neurological difficulties using correlation matrices. Forty-eight children (91% of the eligible population) with epilepsy underwent assessment. Seventy-one per cent of children displayed delayed global development (<2SD) and 56% showed significant deficits (<2SD) in adaptive behaviour. Our analysis revealed that non-white ethnicity and use of polytherapy were independently associated with decreased scores on measures of global development and adaptive behaviour. The correlations between measures of developmental functioning were higher in children with epilepsy than in those without. Children with early-onset epilepsy frequently have difficulties with global development and adaptive behaviour. The higher correlations between neurodevelopmental measures in children with epilepsy suggest that the profile in children with epilepsy is different. This may have significant implications for both neuropathology and interventions. Children with early-onset epilepsy are at significant risk of intellectual disability. Developmental impairment is associated with use of polytherapy but not with any seizure parameters. Developmental profiles in young children with epilepsy differ from other conditions. © 2018 Mac Keith Press.

With or without spikes: localization of focal epileptic activity by simultaneous electroencephalography and functional magnetic resonance imaging

PubMed Central

Grouiller, Frédéric; Thornton, Rachel C.; Groening, Kristina; Spinelli, Laurent; Duncan, John S.; Schaller, Karl; Siniatchkin, Michael; Lemieux, Louis; Seeck, Margitta; Michel, Christoph M.

2011-01-01

In patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordings or surgical resection. Simultaneous electroencephalography and functional magnetic resonance imaging recordings can reveal regions of haemodynamic fluctuations related to epileptic activity and help localize its generators. However, many of these studies (40–70%) remain inconclusive, principally due to the absence of interictal epileptiform discharges during simultaneous recordings, or lack of haemodynamic changes correlated to interictal epileptiform discharges. We investigated whether the presence of epilepsy-specific voltage maps on scalp electroencephalography correlated with haemodynamic changes and could help localize the epileptic focus. In 23 patients with focal epilepsy, we built epilepsy-specific electroencephalographic voltage maps using averaged interictal epileptiform discharges recorded during long-term clinical monitoring outside the scanner and computed the correlation of this map with the electroencephalographic recordings in the scanner for each time frame. The time course of this correlation coefficient was used as a regressor for functional magnetic resonance imaging analysis to map haemodynamic changes related to these epilepsy-specific maps (topography-related haemodynamic changes). The method was first validated in five patients with significant haemodynamic changes correlated to interictal epileptiform discharges on conventional analysis. We then applied the method to 18 patients who had inconclusive simultaneous electroencephalography and functional magnetic resonance imaging studies due to the absence of interictal epileptiform discharges or absence of significant correlated haemodynamic changes. The concordance of the results with subsequent intracranial electroencephalography and/or resection area in patients who were seizure free after surgery was assessed. In the validation group, haemodynamic changes correlated to voltage maps were similar to those obtained with conventional analysis in 5/5 patients. In 14/18 patients (78%) with previously inconclusive studies, scalp maps related to epileptic activity had haemodynamic correlates even when no interictal epileptiform discharges were detected during simultaneous recordings. Haemodynamic changes correlated to voltage maps were spatially concordant with intracranial electroencephalography or with the resection area. We found better concordance in patients with lateral temporal and extratemporal neocortical epilepsy compared to medial/polar temporal lobe epilepsy, probably due to the fact that electroencephalographic voltage maps specific to lateral temporal and extratemporal epileptic activity are more dissimilar to maps of physiological activity. Our approach significantly increases the yield of simultaneous electroencephalography and functional magnetic resonance imaging to localize the epileptic focus non-invasively, allowing better targeting for surgical resection or implantation of intracranial electrode arrays. PMID:21752790

Two Novel Variants Affecting CDKL5 Transcript Associated with Epileptic Encephalopathy.

PubMed

Neupauerová, Jana; Štěrbová, Katalin; Vlčková, Markéta; Sebroňová, Věra; Maříková, Tat'ána; Krůtová, Marcela; David, Staněk; Kršek, Pavel; Žaliová, Markéta; Seeman, Pavel; Laššuthová, Petra

2017-10-01

Variants in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been reported as being etiologically associated with early infantile epileptic encephalopathy type 2 (EIEE2). We report on two patients, a boy and a girl, with EIEE2 that present with early onset epilepsy, hypotonia, severe intellectual disability, and poor eye contact. Massively parallel sequencing (MPS) of a custom-designed gene panel for epilepsy and epileptic encephalopathy containing 112 epilepsy-related genes was performed. Sanger sequencing was used to confirm the novel variants. For confirmation of the functional consequence of an intronic CDKL5 variant in patient 2, an RNA study was done. DNA sequencing revealed de novo variants in CDKL5, a c.2578C>T (p. Gln860*) present in a hemizygous state in a 3-year-old boy, and a potential splice site variant c.463+5G>A in heterozygous state in a 5-year-old girl. Multiple in silico splicing algorithms predicted a highly reduced splice site score for c.463+5G>A. A subsequent mRNA study confirmed an aberrant shorter transcript lacking exon 7. Our data confirmed that variants in the CDKL5 are associated with EIEE2. There is credible evidence that the novel identified variants are pathogenic and, therefore, are likely the cause of the disease in the presented patients. In one of the patients a stop codon variant is predicted to produce a truncated protein, and in the other patient an intronic variant results in aberrant splicing.

Mesial temporal lobe epilepsy lateralization using SPHARM-based features of hippocampus and SVM

NASA Astrophysics Data System (ADS)

Esmaeilzadeh, Mohammad; Soltanian-Zadeh, Hamid; Jafari-Khouzani, Kourosh

2012-02-01

This paper improves the Lateralization (identification of the epileptogenic hippocampus) accuracy in Mesial Temporal Lobe Epilepsy (mTLE). In patients with this kind of epilepsy, usually one of the brain's hippocampi is the focus of the epileptic seizures, and resection of the seizure focus is the ultimate treatment to control or reduce the seizures. Moreover, the epileptogenic hippocampus is prone to shrinkage and deformation; therefore, shape analysis of the hippocampus is advantageous in the preoperative assessment for the Lateralization. The method utilized for shape analysis is the Spherical Harmonics (SPHARM). In this method, the shape of interest is decomposed using a set of bases functions and the obtained coefficients of expansion are the features describing the shape. To perform shape comparison and analysis, some pre- and post-processing steps such as "alignment of different subjects' hippocampi" and the "reduction of feature-space dimension" are required. To this end, first order ellipsoid is used for alignment. For dimension reduction, we propose to keep only the SPHARM coefficients with maximum conformity to the hippocampus shape. Then, using these coefficients of normal and epileptic subjects along with 3D invariants, specific lateralization indices are proposed. Consequently, the 1536 SPHARM coefficients of each subject are summarized into 3 indices, where for each index the negative (positive) value shows that the left (right) hippocampus is deformed (diseased). Employing these indices, the best achieved lateralization accuracy for clustering and classification algorithms are 85% and 92%, respectively. This is a significant improvement compared to the conventional volumetric method.

Depdc5 knockdown causes mTOR-dependent motor hyperactivity in zebrafish.

PubMed

de Calbiac, Hortense; Dabacan, Adriana; Marsan, Elise; Tostivint, Hervé; Devienne, Gabrielle; Ishida, Saeko; Leguern, Eric; Baulac, Stéphanie; Muresan, Raul C; Kabashi, Edor; Ciura, Sorana

2018-05-01

DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling. Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders. In this study, we defined the expression of depdc5 during development and established an epilepsy model with reduced Depdc5 expression. Here we report a zebrafish model of Depdc5 loss-of-function that displays a measurable behavioral phenotype, including hyperkinesia, circular swimming, and increased neuronal activity. These phenotypic features persisted throughout embryonic development and were significantly reduced upon treatment with the mTORC1 inhibitor, rapamycin, as well as overexpression of human WT DEPDC5 transcript. No phenotypic rescue was obtained upon expression of epilepsy-associated DEPDC5 mutations (p.Arg487* and p.Arg485Gln), indicating that these mutations cause a loss of function of the protein. This study demonstrates that Depdc5 knockdown leads to early-onset phenotypic features related to motor and neuronal hyperactivity. Restoration of phenotypic features by WT but not epilepsy-associated Depdc5 mutants, as well as by mTORC1 inhibition confirm the role of Depdc5 in the mTORC1-dependent molecular cascades, defining this pathway as a potential therapeutic target for DEPDC5 -inherited forms of focal epilepsy.

A functional polymorphism of the microRNA-146a gene is associated with susceptibility to drug-resistant epilepsy and seizures frequency.

PubMed

Cui, Lili; Tao, Hua; Wang, Yan; Liu, Zhou; Xu, Zhien; Zhou, Haihong; Cai, Yujie; Yao, Lifen; Chen, Beichu; Liang, Wandong; Liu, Yu; Cheng, Wanwen; Liu, Tingting; Ma, Guoda; Li, You; Zhao, Bin; Li, Keshen

2015-04-01

Epilepsy is the third most common chronic brain disorder and is characterized by an enduring predisposition for seizures. Recently, a growing body of evidence has suggested that microRNA-146a (miR-146a) is upregulated in the brains of epilepsy patients and of mouse models; furthermore, miR-146a may be involved in the development and progression of seizures through the regulation of inflammation and immune responses. In this report, we performed a case-control study to analyze the relationship between the two potentially functional single nucleotide polymorphisms (SNPs) of the miR-146a gene (rs2910464 and rs57095329) and the risk of epilepsy in a Chinese population comprising 249 cases and 249 healthy controls. Our study comprised 249 epilepsy patients and 249 healthy controls in two regions of China. The DNA was genotyped using the ABI PRISM SNapShot method. The statistical analysis was estimated using the chi-square test or Fisher's exact test. Our results indicated a significant association between the rs57095329 SNP of the miR-146a gene and the risk of drug resistant epilepsy (DRE) (genotypes, p = 0.0258 and alleles, p = 0.0108). Moreover, the rs57095329 A allele was found to be associated with a reduced risk of seizures frequency in DRE patients (all p < 0.001). However, the rs2910164 variant was not associated with epilepsy. Our data indicate that the rs57095329 polymorphism in the promoter region of miR-146a is involved in the genetic susceptibility to DRE and the seizures frequency. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Assessment of functional MR imaging in neurosurgical planning.

PubMed

Lee, C C; Ward, H A; Sharbrough, F W; Meyer, F B; Marsh, W R; Raffel, C; So, E L; Cascino, G D; Shin, C; Xu, Y; Riederer, S J; Jack, C R

1999-09-01

Presurgical sensorimotor mapping with functional MR imaging is gaining acceptance in clinical practice; however, to our knowledge, its therapeutic efficacy has not been assessed in a sizable group of patients. Our goal was to identify how preoperative sensorimotor functional studies were used to guide the treatment of neuro-oncologic and epilepsy surgery patients. We retrospectively reviewed the medical records of 46 patients who had undergone preoperative sensorimotor functional MR imaging to document how often and in what ways the imaging studies had influenced their management. Clinical management decisions were grouped into three categories: for assessing the feasibility of surgical resection, for surgical planning, and for selecting patients for invasive functional mapping procedures. Functional MR imaging studies successfully identified the functional central sulcus ipsilateral to the abnormality in 32 of the 46 patients, and these 32 patients are the focus of this report. In epilepsy surgery candidates, the functional MR imaging results were used to determine in part the feasibility of a proposed surgical resection in 70% of patients, to aid in surgical planning in 43%, and to select patients for invasive surgical functional mapping in 52%. In tumor patients, the functional MR imaging results were used to determine in part the feasibility of surgical resection in 55%, to aid in surgical planning in 22%, and to select patients for invasive surgical functional mapping in 78%. Overall, functional MR imaging studies were used in one or more of the three clinical decision-making categories in 89% of tumor patients and 91% of epilepsy surgery patients. Preoperative functional MR imaging is useful to clinicians at three key stages in the preoperative clinical management paradigm of a substantial percentage of patients who are being considered for resective tumor or epilepsy surgery.

Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling.

PubMed

Soriano, Jaymar; Kubo, Takatomi; Inoue, Takao; Kida, Hiroyuki; Yamakawa, Toshitaka; Suzuki, Michiyasu; Ikeda, Kazushi

2017-10-01

Experiments with drug-induced epilepsy in rat brains and epileptic human brain region reveal that focal cooling can suppress epileptic discharges without affecting the brain's normal neurological function. Findings suggest a viable treatment for intractable epilepsy cases via an implantable cooling device. However, precise mechanisms by which cooling suppresses epileptic discharges are still not clearly understood. Cooling experiments in vitro presented evidence of reduction in neurotransmitter release from presynaptic terminals and loss of dendritic spines at post-synaptic terminals offering a possible synaptic mechanism. We show that termination of epileptic discharges is possible by introducing a homogeneous temperature factor in a neural mass model which attenuates the post-synaptic impulse responses of the neuronal populations. This result however may be expected since such attenuation leads to reduced post-synaptic potential and when the effect on inhibitory interneurons is less than on excitatory interneurons, frequency of firing of pyramidal cells is consequently reduced. While this is observed in cooling experiments in vitro, experiments in vivo exhibit persistent discharges during cooling but suppressed in magnitude. This leads us to conjecture that reduction in the frequency of discharges may be compensated through intrinsic excitability mechanisms. Such compensatory mechanism is modelled using a reciprocal temperature factor in the firing response function in the neural mass model. We demonstrate that the complete model can reproduce attenuation of both magnitude and frequency of epileptic discharges during cooling. The compensatory mechanism suggests that cooling lowers the average and the variance of the distribution of threshold potential of firing across the population. Bifurcation study with respect to the temperature parameters of the model reveals how heterogeneous response of epileptic discharges to cooling (termination or suppression only) is exhibited. Possibility of differential temperature effects on post-synaptic potential generation of different populations is also explored.

Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling

PubMed Central

Inoue, Takao; Kida, Hiroyuki; Yamakawa, Toshitaka; Suzuki, Michiyasu

2017-01-01

Experiments with drug-induced epilepsy in rat brains and epileptic human brain region reveal that focal cooling can suppress epileptic discharges without affecting the brain’s normal neurological function. Findings suggest a viable treatment for intractable epilepsy cases via an implantable cooling device. However, precise mechanisms by which cooling suppresses epileptic discharges are still not clearly understood. Cooling experiments in vitro presented evidence of reduction in neurotransmitter release from presynaptic terminals and loss of dendritic spines at post-synaptic terminals offering a possible synaptic mechanism. We show that termination of epileptic discharges is possible by introducing a homogeneous temperature factor in a neural mass model which attenuates the post-synaptic impulse responses of the neuronal populations. This result however may be expected since such attenuation leads to reduced post-synaptic potential and when the effect on inhibitory interneurons is less than on excitatory interneurons, frequency of firing of pyramidal cells is consequently reduced. While this is observed in cooling experiments in vitro, experiments in vivo exhibit persistent discharges during cooling but suppressed in magnitude. This leads us to conjecture that reduction in the frequency of discharges may be compensated through intrinsic excitability mechanisms. Such compensatory mechanism is modelled using a reciprocal temperature factor in the firing response function in the neural mass model. We demonstrate that the complete model can reproduce attenuation of both magnitude and frequency of epileptic discharges during cooling. The compensatory mechanism suggests that cooling lowers the average and the variance of the distribution of threshold potential of firing across the population. Bifurcation study with respect to the temperature parameters of the model reveals how heterogeneous response of epileptic discharges to cooling (termination or suppression only) is exhibited. Possibility of differential temperature effects on post-synaptic potential generation of different populations is also explored. PMID:28981509

Accelerated long-term forgetting in children with idiopathic generalized epilepsy.

PubMed

Gascoigne, Michael B; Barton, Belinda; Webster, Richard; Gill, Deepak; Antony, Jayne; Lah, Suncica Sunny

2012-12-01

The rapid forgetting of information over long (but not short) delays (accelerated long-term forgetting [ALF]) has been associated with temporal lobe epilepsy but not idiopathic generalized epilepsy (IGE). Long-term memory formation (consolidation) is thought to demand an interaction between medial temporal and neocortical networks, which could be disrupted by epilepsy/seizures themselves. The present study investigates whether ALF is present in children with IGE and whether it relates to epilepsy severity. Sixty-one children (20 with IGE and 41 healthy controls [HC]) of comparable age, sex, and parental socioeconomic status completed neuropsychological tests, including a measure of verbal learning and recall after, short (30-min) and long (7-day) delays, and recognition. Epilepsy severity was rated by treating neurologists. A two-way repeated measures analysis of covariance (ANCOVA) found a significant Group x Delay interaction; the children with IGE recalled (and recognized) significantly fewer words after a long, but not short (2- and 30-min) delay relative to the HC children. Moreover, greater epilepsy severity was associated with poorer recognition. This study demonstrates, to our knowledge for the first time, that children with IGE present with ALF, which is related to epilepsy severity. These findings support the notion that epilepsy/seizures themselves may disrupt long-term memory consolidation, which interferes with day-to-day functioning of children with IGE. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Patients with epilepsy and patients with psychogenic non-epileptic seizures: video-EEG, clinical and neuropsychological evaluation.

PubMed

Turner, Katherine; Piazzini, Ada; Chiesa, Valentina; Barbieri, Valentina; Vignoli, Aglaia; Gardella, Elena; Tisi, Giuseppe; Scarone, Silvio; Canevini, Maria Paola; Gambini, Orsola

2011-11-01

The incidence of psychogenic non-epileptic seizures (PNES) is 4.9/100,000/year and it is estimated that about 20-30% of patients referred to tertiary care epilepsy centers for refractory seizures have both epilepsy and PNES. The purpose of our study is to evaluate psychiatric disorders and neuropsychological functions among patients with PNES, patients with epilepsy associated with PNES and patients with epilepsy. We evaluated 66 consecutive in-patients with video-EEG recordings: 21 patients with epilepsy, 22 patients with PNES and 10 patients with epilepsy associated with PNES; 13 patients were excluded (8 because of mental retardation and 5 because they did not present seizures or PNES during the recording period). All patients with PNES had a psychiatric diagnosis (100%) vs. 52% of patients with epilepsy. Cluster B personality disorders were more common in patients with PNES. We observed fewer mood and anxiety disorders in patients with PNES compared with those with epilepsy. We did not find statistically significant differences in neuropsychological profiles among the 3 patient groups. This study can help to contribute to a better understanding of the impact of PNES manifestations, in addition to the occurrence of seizures, in order to provide patients with more appropriate clinical, psychological and social care. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Infections, inflammation and epilepsy

PubMed Central

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

2016-01-01

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

The Combined Burden of Cognitive, Executive Function, and Psychosocial Problems in Children with Epilepsy: A Population-Based Study

ERIC Educational Resources Information Center

Hoie, B.; Sommerfelt, K.; Waaler, P. E.; Alsaker, F. D.; Skeidsvoll, H.; Mykletun, A.

2008-01-01

The combined burden of psychosocial (Achenbach scales), cognitive (Raven matrices), and executive function (EF) problems was studied in a population-based sample of 6- to 12-year-old children with epilepsy (n = 162; 99 males, 63 females) and in an age- and sex-matched control group (n = 107; 62 males, 45 females). Approximately 35% of the children…

Calcified parenchymal central nervous system cysticercosis and clinical outcomes in epilepsy.

PubMed

Leon, Amanda; Saito, Erin K; Mehta, Bijal; McMurtray, Aaron M

2015-02-01

This study aimed to compare clinical outcomes including seizure frequency and psychiatric symptoms between patients with epilepsy with neuroimaging evidence of past brain parenchymal neurocysticercosis infection, patients with other structural brain lesions, and patients without structural neuroimaging abnormalities. The study included retrospective cross-sectional analysis of all patients treated for epilepsy in a community-based adult neurology clinic during a three-month period. A total of 160 patients were included in the analysis, including 63 with neuroimaging findings consistent with past parenchymal neurocysticercosis infection, 55 with structurally normal brain neuroimaging studies, and 42 with other structural brain lesions. No significant differences were detected between groups for either seizure freedom (46.03%, 50.91%, and 47.62%, respectively; p=0.944) or mean seizure frequency per month (mean=2.50, S.D.=8.1; mean=4.83, S.D.=17.64; mean=8.55, S.D.=27.31, respectively; p=0.267). Self-reported depressive symptoms were more prevalent in those with parenchymal neurocysticercosis than in the other groups (p=0.003). No significant differences were detected for prevalence of self-reported anxiety or psychotic symptoms. Calcified parenchymal neurocysticercosis results in refractory epilepsy about as often as other structural brain lesions. Depressive symptoms may be more common among those with epilepsy and calcified parenchymal neurocysticercosis; consequently, screening for depression may be indicated in this population. Published by Elsevier Inc.

Microsurgical techniques in temporal lobe epilepsy.

PubMed

Alonso Vanegas, Mario A; Lew, Sean M; Morino, Michiharu; Sarmento, Stenio A

2017-04-01

Temporal lobe resection is the most prevalent epilepsy surgery procedure. However, there is no consensus on the best surgical approach to treat temporal lobe epilepsy. Complication rates are low and efficacy is very high regarding seizures after such procedures. However, there is still ample controversy regarding the best surgical approach to warrant maximum seizure control with minimal functional deficits. We describe the most frequently used microsurgical techniques for removal of both the lateral and mesial temporal lobe structures in the treatment of medically intractable temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (corticoamygdalohippocampectomy and selective amygdalohippocampectomy). The choice of surgical technique appears to remain a surgeon's preference for the near future. Meticulous surgical technique and thorough three-dimensional microsurgical knowledge are essentials for obtaining the best results. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Determination of hemispheric language dominance in the surgical epilepsy patient: diagnostic properties of functional magnetic resonance imaging.

PubMed

Spritzer, Scott D; Hoerth, Matthew T; Zimmerman, Richard S; Shmookler, Aaron; Hoffman-Snyder, Charlene R; Wellik, Kay E; Demaerschalk, Bart M; Wingerchuk, Dean M

2012-09-01

Presurgical evaluation for refractory epilepsy typically includes assessment of cognitive and language functions. The reference standard for determination of hemispheric language dominance has been the intracarotid amobarbital test (IAT) but functional magnetic resonance imaging (fMRI) is increasingly used. To critically assess current evidence regarding the diagnostic properties of fMRI in comparison with the IAT for determination of hemispheric language dominance. The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy and neurosurgery. A systematic review and meta-analysis that compared the sensitivity and specificity of fMRI to IAT-determined language lateralization was selected for critical appraisal. The review included data from 23 articles (n=442); study methodology varied widely. fMRI was 83.5% sensitive and 88.1% specific for detection of hemispheric language dominance. There are insufficient data to support routine use of fMRI for the purpose of determining hemispheric language dominance in patients with intractable epilepsy. Larger, well-designed studies of fMRI for language and other cognitive outcomes as part of the presurgical and postsurgical evaluation of epilepsy patients are necessary.

Research on psychosocial aspects of epilepsy in Arab countries: a review of literature.

PubMed

Al-Khateeb, Jamal M; Al-Khateeb, Anas J

2014-02-01

This study reviewed research conducted on the psychological aspects of epilepsy in Arab countries. Several databases (Medline, PubMed, Science Direct, Springer Link, and PsycInfo) were searched using the following two sets of search words: (1) Arab, Jordan, Lebanon, United Arab Emirates (UAE), Bahrain, Qatar, Kuwait, Oman, Saudi Arabia, Syria, Iraq, Egypt, Yemen, Tunisia, Libya, Morocco, Algiers, Palestine, Mauritania, Djibouti, Sudan, Comoros, and Somalia; and (2) epilepsy, seizure disorders, and convulsive disorders. Fifty-one studies were conducted in 12 Arab states. Social/emotional, employment, and other problems; knowledge and attitudes; and quality of life (QOL) were the most commonly measured parameters of psychosocial aspects of epilepsy in Arab countries. Results revealed elevated levels of depression and anxiety, a decline in cognitive function, various behavioral problems, sexual dysfunction, and underemployment among persons with epilepsy (PWE). Misconceptions about epilepsy were found to be prevalent. While many studies reported limited knowledge of epilepsy, some studies found an average knowledge. Negative attitudes toward epilepsy were reported in most studies, and moderately positive attitudes were reported in some studies. Finally, PWE showed low overall QOL scores in the majority of studies. © 2013.

Epilepsy, Cognition, and Behavior: The clinical picture

PubMed Central

Berg, Anne T.

2010-01-01

Although epilepsy is defined by the occurrence of spontaneous epileptic seizures, a large body of evidence indicates that epilepsy is linked to a spectrum behavioral, psychiatric, and cognitive disorders as well as to sudden death. Explanations for these associations include: (1) The effects of structural lesions which may impair the functions subserved by the regions of the brain involved in the lesion. (2) The effects of seizure activity which may begin well before a clinical seizure occurs and may persist long after it is over raising questions about what truly constitutes “interictal.” In addition, encephalopathic effects of epilepsy in infancy during critical periods in development may be particularly severe and potentially irreversible. (3) Shared mechanisms underlying seizures as well as these other disorders in the absence of structural lesions or separate diseases of the CNS. Epidemiological and clinical studies demonstrate the elevated risk of cognitive, psychiatric, and behavioral disorders not just during but also prior to the onset of epilepsy (seizures) itself. These may outlast the active phase of epilepsy as well. The mounting evidence argues strongly for the recognition of epilepsy as part of a spectrum of disorders and against the notion that even uncomplicated epilepsy can a priori be considered benign. PMID:21214534

Multivariate trajectories across multiple domains of health-related quality of life in children with new-onset epilepsy.

PubMed

Sajobi, Tolulope T; Wang, Meng; Ferro, Mark A; Brobbey, Anita; Goodwin, Shane; Speechley, Kathy N; Wiebe, Samuel

2017-10-01

The diagnosis of epilepsy in children is known to impact the trajectory of their health-related quality of life (HRQOL) over time. However, there is limited knowledge about variations in longitudinal trajectories across multiple domains of HRQOL. This study aims to characterize the heterogeneity in HRQOL trajectories across multiple HRQOL domains and to evaluate predictors of differences among the identified trajectory groups in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study (HERQULES), a prospective multi-center study of 373 children newly diagnosed with new-onset epilepsy who were followed up over 2years. Child HRQOL and family factors were reported by parents, and clinical characteristics were reported by neurologists. Group-based multi-trajectory modeling was adopted to characterize longitudinal trajectories of HRQOL as measured by the individual domains of cognitive, emotional, physical, and social functioning in the 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Multinomial logistic regression was used to assess potential factors that explain differences among the identified latent trajectory groups. Three distinct HRQOL trajectory subgroups were identified in children with new-onset epilepsy based on HRQOL scores: "High" (44.7%), "Intermediate" (37.0%), and "Low" (18.3%). While most trajectory groups exhibited increasing scores over time on physical and social domains, both flat and declining trajectories were noted on emotional and cognitive domains. Less severe epilepsy, an absence of cognitive and behavioral problems, lower parental depression scores, better family functioning, and fewer family demands were associated with a "Higher" or "Intermediate" HRQOL trajectory. The course of HRQOL over time in children with new-onset epilepsy appears to follow one of three different trajectories. Addressing the clinical and psychosocial determinants identified for each pattern can help clinicians provide more targeted care to these children and their families. Copyright © 2017 Elsevier Inc. All rights reserved.

Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?

PubMed Central

Cardamone, L; Salzberg, MR; O'Brien, TJ; Jones, NC

2013-01-01

There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer (‘second generation’) antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term ‘epileptogenesis’: the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section. PMID:23146067

Antioxidants as a Preventive Treatment for Epileptic Process: A Review of the Current Status

PubMed Central

Martinc, Boštjan; Grabnar, Iztok; Vovk, Tomaž

2014-01-01

Epilepsy is known as one of the most frequent neurological diseases, characterized by an enduring predisposition to generate epileptic seizures. Oxidative stress is believed to directly participate in pathways leading to neurodegeneration, which serves as the most important propagating factor, leading to the epileptic condition and cognitive decline. Moreover, there is also a growing body of evidence showing the disturbance of antioxidant system balance and consequently increased production of reactive species in patients with epilepsy. A meta-analysis, conducted in the present review confirms an association between epilepsy and increased lipid peroxidation. Furthermore, it was also shown that some of the antiepileptic drugs could potentially be responsible for additionally increased lipid peroxidation. Therefore, it is reasonable to propose that during the epileptic process neuroprotective treatment with antioxidants could lead to less sever structural damages, reduced epileptogenesis and milder cognitive deterioration. To evaluate this hypothesis studies investigating the neuroprotective therapeutic potential of various antioxidants in cells, animal seizure models and patients with epilepsy have been reviewed. Numerous beneficial effects of antioxidants on oxidative stress markers and in some cases also neuroprotective effects were observed in animal seizure models. However, despite these encouraging results, till now only a few antioxidants have been further applied to patients with epilepsy as an add-on therapy. Based on the several positive findings in animal models, a strong need for more carefully planned, randomized, double-blind, cross-over, placebo-controlled clinical trials for the evaluation of antioxidants efficacy in patients with epilepsy is warranted. PMID:25977679

Immediate improvement of motor function after epilepsy surgery in congenital hemiparesis.

PubMed

Pascoal, Tharick; Paglioli, Eliseu; Palmini, André; Menezes, Rafael; Staudt, Martin

2013-08-01

Hemispherectomy often leads to a loss of contralateral hand function. In some children with congenital hemiparesis, however, paretic hand function remains unchanged. An immediate improvement of hand function has never been reported. A 17-year-old boy with congenital hemiparesis and therapy-refractory seizures due to a large infarction in the territory of the middle cerebral artery underwent epilepsy surgery. Intraoperatively, electrical cortical stimulation of the affected hemisphere demonstrated preserved motor projections from the sensorimotor cortex to the (contralateral) paretic hand. A frontoparietal resection was performed, which included a complete disconnection of all motor projections originating in the sensorimotor cortex of the affected hemisphere. Surprisingly, the paretic hand showed a significant functional improvement immediately after the operation. This observation demonstrates that, in congenital hemiparesis, crossed motor projections from the affected hemisphere are not always beneficial, but can be dysfunctional, interfering with ipsilateral motor control over the paretic hand by the contralesional hemisphere. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Neurobehavioral consequences of continuous spike and waves during slow sleep (CSWS) in a pediatric population: A pattern of developmental hindrance.

PubMed

De Giorgis, Valentina; Filippini, Melissa; Macasaet, Joyce Ann; Masnada, Silvia; Veggiotti, Pierangelo

2017-09-01

Continuous spike and waves during slow sleep (CSWS) is a typical EEG pattern defined as diffuse, bilateral and recently also unilateral or focal localization spike-wave occurring in slow sleep or non-rapid eye movement sleep. Literature results so far point out a progressive deterioration and decline of intellectual functioning in CSWS patients, i.e. a loss of previously normally acquired skills, as well as persistent neurobehavioral disorders, beyond seizure and EEG control. The objective of this study was to shed light on the neurobehavioral impact of CSWS and to identify the potential clinical risk factors for development. We conducted a retrospective study involving a series of 16 CSWS idiopathic patients age 3-16years, considering the entire duration of epilepsy from the onset to the outcome, i.e. remission of CSWS pattern. All patients were longitudinally assessed taking into account clinical (sex, age at onset, lateralization and localization of epileptiform abnormalities, spike wave index, number of antiepileptic drugs) and behavioral features. Intelligent Quotient (IQ) was measured in the whole sample, whereas visuo-spatial attention, visuo-motor skills, short term memory and academic abilities (reading and writing) were tested in 6 out of 16 patients. Our results showed that the most vulnerable from an intellectual point of view were those children who had an early-onset of CSWS whereas those with later onset resulted less affected (p=0.004). Neuropsychological outcome was better than the behavioral one and the lexical-semantic route in reading and writing resulted more severely affected compared to the phonological route. Cognitive deterioration is one but not the only consequence of CSWS. Especially with respect to verbal skills, CSWS is responsible of a pattern of consequences in terms of developmental hindrance, including slowing of development and stagnation, whereas deterioration is rare. Behavioral and academic problems tend to persist beyond epilepsy resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

The Phe932Ile mutation in KCNT1 channels associated with severe epilepsy, delayed myelination and leukoencephalopathy produces a loss-of-function channel phenotype.

PubMed

Evely, Katherine M; Pryce, Kerri D; Bhattacharjee, Arin

2017-05-20

Sodium-activated potassium (K Na ) channels contribute to firing frequency adaptation and slow after hyperpolarization. The KCNT1 gene (also known as SLACK) encodes a K Na subunit that is expressed throughout the central and peripheral nervous systems. Missense mutations of the SLACK C-terminus have been reported in several patients with rare forms of early onset epilepsy and in some cases severely delayed myelination. To date, such mutations identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), epilepsy of infancy with migrating focal seizures (EIMFS) and Ohtahara syndrome (OS) have been reported to be gain-of-function mutations (Villa and Combi, 2016). An exome sequencing study identified a p.Phe932Ile KCNT1 mutation as the disease-causing change in a child with severe early infantile epileptic encephalopathy and abnormal myelination (Vanderver et al., 2014). We characterized an analogous mutation in the rat Slack channel and unexpectedly found this mutation to produce a loss-of-function phenotype. In an effort to restore current, we tested the known Slack channel opener loxapine. Loxapine exhibited no effect, indicating that this mutation either caused the channel to be insensitive to this established opener or proper translation and trafficking to the membrane was disrupted. Protein analysis confirmed that while total mutant protein did not differ from wild type, membrane expression of the mutant channel was substantially reduced. Although gain-of-function mutations to the Slack channel are linked to epileptic phenotypes, this is the first reported loss-of-function mutation linked to severe epilepsy and delayed myelination. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Ancient Indian concepts about phenomenology, biology, and therapeutics of epilepsy.

PubMed

Arya, Ravindra

2018-01-01

This article discusses etiology, pathogenesis, symptoms, and treatment of epilepsy, as described in Charaka Samhitā (translation: Charaka's Compendium) and Sushruta Samhitā, the two core texts of Ayurveda, an ancient system of medicine. Ayurveda emphasized amnesia and loss of consciousness as core features of epileptic seizures (Sanskrit: apasmar; translation: apa negation, smaran memory) and recognized that seizures occur due to a disturbance in brain function or flow of "humors" to the brain. Semiology of various seizure types was well described. Epilepsy was attributed to both internal and multiple exogenous factors. Treatment of epilepsy with formulations of naturally occurring substances, their compounding and use, is described in remarkable detail. Lifestyle modifications to protect people with epilepsy are also documented. Cognitive comorbidities of epilepsy were recognized. Although none of the Ayurveda formulations have any empirical evidence supporting their safety or efficacy in the treatment of epilepsy, studies are needed to generate relevant evidence, to recognize their hazards, and to integrate traditional and complementary systems of medicine with modern health care in an informed and safe manner.

Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

PubMed

Witcher, Mark R; Ellis, Thomas L

2012-01-01

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

Autistic traits in epilepsy models: Why, when and how?

PubMed

Velíšková, Jana; Silverman, Jill L; Benson, Melissa; Lenck-Santini, Pierre-Pascal

2018-05-18

Autism spectrum disorder (ASD) is a common comorbidity of epilepsy and seizures and/or epileptiform activity are observed in a significant proportion of ASD patients. Current research also implies that autistic traits can be observed to a various degree in mice and rats with seizures. This suggests that there are shared mechanisms in both ASD and epilepsy syndromes. Here, we first review the standard, validated methods used to assess autistic traits in animal models as well as their limitations with regards to epilepsy models. We then discuss two of the potential pathological processes that could be shared between ASD and epilepsy. We first focus on functional implications of neuroinflammation including changes to excitable networks mediated by inflammatory regulators. Finally we examine mechanisms at the cellular and network level involved in neuronal excitability, timing and network coordination that may directly lead to behavioral disturbances present in both epilepsy and ASD. This mini-review summarizes the work first presented at an Investigators Workshop at the 2016 American Epilepsy Society meeting. Copyright © 2018. Published by Elsevier B.V.

[Activation of peripheral T lymphocytes in children with epilepsy and production of cytokines].

PubMed

Yang, Jie; Hu, Chongkang; Jiang, Xun

2016-09-01

Objective To study the state of peripheral T lymphocytes and cytokine levels in children with epilepsy. Methods Twenty children with epilepsy and 20 healthy age-matched children were recruited and their peripheral blood was collected. The activation of T lymphocytes was evaluated by detecting the expressions of CD25, CD69 and cytotoxic T lymphocyte-assicated antigen 4 (CTLA4). The function of T lymphocytes was evaluated by detecting the expressions of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-17A and IL-6. The activation of regulatory T cells (Tregs) was evaluated by detecting the expression of IL-10. Results Children with epilepsy had higher expressions of CD25, CD69 and CTLA-4 in T lymphocytes than the controls did. The expressions of IFN-γ, TNF-α, IL-17A and IL-6 in T lymphocytes of children with epilepsy were higher than those of the controls. Frequency of Tregs producing IL-10 was higher in children with epilepsy as compared with the controls. Conclusion Peripheral T lymphocytes of children with epilepsy are activated and produce cytokines.

Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy.

PubMed

Ribierre, Théo; Deleuze, Charlotte; Bacq, Alexandre; Baldassari, Sara; Marsan, Elise; Chipaux, Mathilde; Muraca, Giuseppe; Roussel, Delphine; Navarro, Vincent; Leguern, Eric; Miles, Richard; Baulac, Stéphanie

2018-04-30

DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch of the mTORC1 pathway. So far, its function in the brain remains largely unknown. Germline loss-of-function mutations in DEPDC5 have emerged as a major cause of familial refractory focal epilepsies, with case reports of sudden unexpected death in epilepsy (SUDEP). Remarkably, a fraction of patients also develop focal cortical dysplasia (FCD), a neurodevelopmental cortical malformation. We therefore hypothesized that a somatic second-hit mutation arising during brain development may support the focal nature of the dysplasia. Here, using postoperative human tissue, we provide the proof of concept that a biallelic 2-hit - brain somatic and germline - mutational mechanism in DEPDC5 causes focal epilepsy with FCD. We discovered a mutation gradient with a higher rate of mosaicism in the seizure-onset zone than in the surrounding epileptogenic zone. Furthermore, we demonstrate the causality of a Depdc5 brain mosaic inactivation using CRISPR-Cas9 editing and in utero electroporation in a mouse model recapitulating focal epilepsy with FCD and SUDEP-like events. We further unveil a key role of Depdc5 in shaping dendrite and spine morphology of excitatory neurons. This study reveals promising therapeutic avenues for treating drug-resistant focal epilepsies with mTORC1-targeting molecules.

Neuroticism in temporal lobe epilepsy: assessment and implications for pre- and postoperative psychosocial adjustment and health-related quality of life.

PubMed

Rose, K J; Derry, P A; McLachlan, R S

1996-05-01

We assessed 77 candidates for epilepsy surgery to determine the association among neuroticism (a dimension of personality characterized by chronic negative emotions and behaviors), psychosocial adjustment as measured by the Washington Psychosocial Seizure Inventory (WPSI), and health-related quality of life (HRQOL) as measured by the Epilepsy Surgery Inventory 55 (ESI-55). Minnesota Multiphasic Personality Inventory 2 (MMPI-2) Neuroticism scale scores were significantly correlated with many domains of patient -perceived psychosocial adjustment and HRQOL regardless of frequency or type of seizures. We then followed 45 of the patients who subsequently underwent epilepsy surgery to determine the influence of neuroticism on postoperative functioning. Two-way analysis of variance (ANOVA) indicated that patients with high preoperative neuroticism had significantly poorer postoperative psychosocial adjustment and HRQOL scores than patients who had low or moderate preoperative neuroticism scores. These results support the validity of the MMPI-2 as a useful measure of neuroticism. Preoperative neuroticism has an important influence on postoperative psychosocial adjustment and HRQOL that is independent of postoperative seizure outcome. Understanding the influence of personality variables, such as neuroticism, on psychosocial functioning both before and after epilepsy surgery is essential in managing intractable seizures.

Emerging roles of Na+/H+ exchangers in epilepsy and developmental brain disorders

PubMed Central

Falgoust, Lindsay; Pan, Jullie W.; Sun, Dandan; Zhang, Zhongling

2016-01-01

Epilepsy is a common central nervous system (CNS) disease characterized by recurrent transient neurological events occurring due to abnormally excessive or synchronous neuronal activity in the brain. The CNS is affected by systemic acid–base disorders, and epileptic seizures are sensitive indicators of underlying imbalances in cellular pH regulation. Na+/H+ exchangers (NHEs) are a family of membrane transporter proteins actively involved in regulating intracellular and organellar pH by extruding H+ in exchange for Na+ influx. Altering NHE function significantly influences neuronal excitability and plays a role in epilepsy. This review gives an overview of pH regulatory mechanisms in the brain with a special focus on the NHE family and the relationship between epilepsy and dysfunction of NHE isoforms. We first discuss how cells translocate acids and bases across the membrane and establish pH homeostasis as a result of the concerted effort of enzymes and ion transporters. We focus on the specific roles of the NHE family by detailing how the loss of NHE1 in two NHE mutant mice results in enhanced neuronal excitability in these animals. Furthermore, we highlight new findings on the link between mutations of NHE6 and NHE9 and developmental brain disorders including epilepsy, autism, and attention deficit hyperactivity disorder (ADHD). These studies demonstrate the importance of NHE proteins in maintaining H+ homeostasis and their intricate roles in the regulation of neuronal function. A better understanding of the mechanisms underlying NHE1, 6, and 9 dysfunctions in epilepsy formation may advance the development of new epilepsy treatment strategies. PMID:26965387

Astrocyte uncoupling as a cause of human temporal lobe epilepsy.

PubMed

Bedner, Peter; Dupper, Alexander; Hüttmann, Kerstin; Müller, Julia; Herde, Michel K; Dublin, Pavel; Deshpande, Tushar; Schramm, Johannes; Häussler, Ute; Haas, Carola A; Henneberger, Christian; Theis, Martin; Steinhäuser, Christian

2015-05-01

Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K(+) concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K(+) buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A review of mobile apps for epilepsy self-management.

PubMed

Escoffery, Cam; McGee, Robin; Bidwell, Jonathan; Sims, Christopher; Thropp, Eliana Kovitch; Frazier, Cherise; Mynatt, Elizabeth D

2018-04-01

Mobile health app developers increasingly are interested in supporting the daily self-care of people with chronic conditions. The purpose of this study was to review mobile applications (apps) to promote epilepsy self-management. It investigates the following: 1) the available mobile apps for epilepsy, 2) how these apps support patient education and self-management (SM), and 3) their usefulness in supporting management of epilepsy. We conducted the review in Fall 2017 and assessed apps on the Apple App Store that related to the terms "epilepsy" and "seizure". Inclusion criteria included apps (adult and pediatric) that, as follows, were: 1) developed for patients or the community; 2) made available in English, and 3) less than $5.00. Exclusion criteria included apps that were designed for dissemination of publications, focused on healthcare providers, or were available in other languages. The search resulted in 149 apps, of which 20 met the selection criteria. A team reviewed each app in terms of three sets of criteria: 1) epilepsy-specific descriptions and SM categories employed by the apps and 2) Mobile App Rating Scale (MARS) subdomain scores for reviewing engagement, functionality, esthetics, and information; and 3) behavioral change techniques. Most apps were for adults and free. Common SM domains for the apps were treatment, seizure tracking, response, and safety. A number of epilepsy apps existed, but many offered similar functionalities and incorporated few SM domains. The findings underline the need for mobile apps to cover broader domains of SM and behavioral change techniques and to be evaluated for outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Emerging roles of Na⁺/H⁺ exchangers in epilepsy and developmental brain disorders.

PubMed

Zhao, Hanshu; Carney, Karen E; Falgoust, Lindsay; Pan, Jullie W; Sun, Dandan; Zhang, Zhongling

2016-01-01

Epilepsy is a common central nervous system (CNS) disease characterized by recurrent transient neurological events occurring due to abnormally excessive or synchronous neuronal activity in the brain. The CNS is affected by systemic acid-base disorders, and epileptic seizures are sensitive indicators of underlying imbalances in cellular pH regulation. Na(+)/H(+) exchangers (NHEs) are a family of membrane transporter proteins actively involved in regulating intracellular and organellar pH by extruding H(+) in exchange for Na(+) influx. Altering NHE function significantly influences neuronal excitability and plays a role in epilepsy. This review gives an overview of pH regulatory mechanisms in the brain with a special focus on the NHE family and the relationship between epilepsy and dysfunction of NHE isoforms. We first discuss how cells translocate acids and bases across the membrane and establish pH homeostasis as a result of the concerted effort of enzymes and ion transporters. We focus on the specific roles of the NHE family by detailing how the loss of NHE1 in two NHE mutant mice results in enhanced neuronal excitability in these animals. Furthermore, we highlight new findings on the link between mutations of NHE6 and NHE9 and developmental brain disorders including epilepsy, autism, and attention deficit hyperactivity disorder (ADHD). These studies demonstrate the importance of NHE proteins in maintaining H(+) homeostasis and their intricate roles in the regulation of neuronal function. A better understanding of the mechanisms underlying NHE1, 6, and 9 dysfunctions in epilepsy formation may advance the development of new epilepsy treatment strategies. Published by Elsevier Ltd.

Engineering Devices to Treat Epilepsy: A Clinical Perspective

DTIC Science & Technology

2001-10-25

Research over the next three decades reinforced the idea that seizures likely spread through discrete, functional neuronal networks [2]. Over the last...15 years, researchers have demonstrated that it is possible to modulate the activity of functional neuronal networks in animal models of epilepsy by...hypothalamus [5], mamillary bodies [6], cerebellum [7], basal ganglia [8], locus ceruleus [9] and the substantia nigra [10]. At the same time some

Imaging structural and functional brain networks in temporal lobe epilepsy.

PubMed

Bernhardt, Boris C; Hong, Seokjun; Bernasconi, Andrea; Bernasconi, Neda

2013-10-01

Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy.

Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

PubMed

Szaflarski, Jerzy P; Gloss, David; Binder, Jeffrey R; Gaillard, William D; Golby, Alexandra J; Holland, Scott K; Ojemann, Jeffrey; Spencer, David C; Swanson, Sara J; French, Jacqueline A; Theodore, William H

2017-01-24

To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case. © 2017 American Academy of Neurology.

Epilepsy and adverse quality of life in surgically resected meningioma.

PubMed

Tanti, M J; Marson, A G; Jenkinson, M D

2017-09-01

Meningiomas are common intracranial tumors, and despite surgery or therapy with anti-epileptic drugs (AEDs), many patients suffer from seizures. Epilepsy has a significant impact on quality of life (QoL) in non-tumor populations, but the impact of epilepsy on QoL in patients with meningioma is unknown. Our aim was to evaluate the impact of epilepsy on QoL in patients that have undergone resection of a benign meningioma. We recruited meningioma patients without epilepsy (n=109), meningioma patients with epilepsy (n=56), and epilepsy patients without meningioma (n=64). QoL was measured with the Short Form 36 version 2 (SF-36), the Functional Assessment of Cancer Therapy (FACT-BR), and the Liverpool Adverse Events Profile (LAEP). Regression analyses identified significant determinants of QoL. Patients with meningioma and epilepsy had poorer QoL scores than meningioma patients without epilepsy in all measures. In FACT-BR, this difference was significant. Multiple regression analyses demonstrated that current AED use had a greater impact on QoL scores than recent seizures. Other variables associated with impaired QoL included depression, unemployment, and meningioma attributed symptoms. Epilepsy has a negative impact on quality of life in patients with benign meningioma. AED use is correlated with impaired QoL and raised LAEP scores, suggesting that AEDs and adverse effects may have led to impaired QoL in our meningioma patients with epilepsy. The severity of epilepsy in our meningioma population was comparatively mild; therefore, a more conservative approach to AED therapy may be indicated in an attempt to minimize adverse effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy.

PubMed

de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Lopim, Glauber Menezes; Vannucci Campos, Diego; Fernandes, Jansen; Cabral, Francisco Romero; Arida, Ricardo Mario

2017-04-01

Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.

Memory in children with epilepsy: a systematic review.

PubMed

Menlove, Leanne; Reilly, Colin

2015-02-01

Research suggests an increased risk for cognitive impairment in childhood epilepsy with memory being one area of cognition most likely to be affected. Understanding the prevalence and predictors of memory difficulties may help improve awareness of the difficulties and allow efficacious supports to be put in place. A systematic review was carried out using the search terms 'memory', 'children' and 'epilepsy' in the database PUBMED. Eighty-eight studies met inclusion criteria. The review focuses on comparisons of memory scores of children with epilepsy and controls, and comparison of memory scores of children with epilepsy to normative scores. Predictors of memory impairment and the effect of surgery on memory functioning are also reviewed. The majority (78%) of studies reviewed revealed that children with epilepsy scored lower than controls and normative scores on measures of memory. Post-surgery, memory scores were reported to improve in 50% of studies. Predictors of memory impairment included a greater number of AEDs used, younger age of onset, increased seizure frequency and longer duration of epilepsy. Children with epilepsy have a high frequency of memory impairments. However, the exact prevalence of difficulties is not clear due to the lack of population-based data. Most studies have not controlled for IQ and thus it is unclear if difficulties are always related to global cognitive difficulties. There is need for future population-based studies and studies focussing on the neurobiology of memory problems in children with epilepsy. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Epilepsy, Anticonvulsants and Cognitive Functions in School Students.

ERIC Educational Resources Information Center

Keister, Douglas Charles

Research is reviewed on epilepsy and findings summarized in terms of intelligence, relationship between etiology and intelligence, seizure frequency, age of onset, duration, premorbid intelligence, and specific psychological defects, electroencephalography (EEG) and IQ, and learning. Among findings noted are that the widespread belief among…

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

PubMed

Caller, Tracie A; Secore, Karen L; Ferguson, Robert J; Roth, Robert M; Alexandre, Faith P; Henegan, Patricia L; Harrington, Jessica J; Jobst, Barbara C

2015-03-01

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial. Copyright © 2015 Elsevier Inc. All rights reserved.

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Jinmei; Wang Xuefeng; Xi Zhiqin

2006-10-06

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in themore » temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.« less

The Impact of a 35-Week Long-Term Exercise Therapy on Psychosocial Health of Children With Benign Epilepsy.

PubMed

Eom, Soyong; Lee, Mi Kyung; Park, Ji-Hye; Lee, Dongpyo; Kang, Hoon-Chul; Lee, Joon Soo; Jeon, Justin Y; Kim, Heung Dong

2016-07-01

The purpose of this study was to evaluate the feasibility of a 35-week exercise program and its efficacy on neurocognitive and psychological variables in children with benign epilepsy with centrotemporal spikes. Ten children with benign epilepsy with centrotemporal spikes (aged 8 to 12 years) completed a 35-week exercise program consisting of supervised sport activities for 5 weeks and home-based exercise program for 30 weeks. The children and their parents participated in neurocognitive and psychological evaluations including measures of attention, executive function, behaviors, and quality of life at baseline and postexercise follow-up at the 35th week. At postintervention evaluation, significant improvements were seen relative to baseline in neurocognitive domains such as psychomotor speed, sustained attention, divided attention, and inhibition-disinhibition ability, and in psychological domains including internalizing behavior problems, general health, and general quality of life. Long-term exercise intervention may have benefits for some aspects of neurocognitive and psychological function in children with benign epilepsy. © The Author(s) 2016.

Reexamining epilepsy-associated stigma: validation of the Stigma Scale of Epilepsy in Zambia.

PubMed

Elafros, Melissa A; Bowles, Ryan P; Atadzhanov, Masharip; Mbewe, Edward; Haworth, Alan; Chomba, Elwyn; Birbeck, Gretchen L

2015-06-01

Epilepsy-associated stigma is an important patient-centered outcome, yet quantification remains challenging. Jacoby's 3-item Stigma Scale is commonly used to assess felt stigma among people with epilepsy (PWE) yet has ceiling effects. The Stigma Scale of Epilepsy (SSE) is a 24-item instrument that measures felt stigma among PWE and stigmatizing attitudes among others. If cross-culturally valid, the SSE may elucidate stigma determinants and provide an outcome measure for interventions. We assessed the properties of the SSE in 102 Zambian PWE using exploratory and confirmatory item response theories and compared the latent traits assessed by the SSE to those assessed by Jacoby's Stigma Scale. Differential item functioning based on forced disclosure of epilepsy was examined. The SSE yielded two latent traits--the first reflected difficulties faced by PWE; the second reflected emotions associated with epilepsy. Jacoby's Stigma Scale was associated only with the first latent trait. Forced disclosure was associated with "worry" and "pity" that were associated with the second latent trait. In Zambian PWE, the SSE captured two latent traits. One trait represents feelings associated with epilepsy, which is theorized as a substantial yet unmeasured part of stigma. The SSE performs well across cultures and may more comprehensively assess felt stigma than other instruments. Further validation is required to determine whether the SSE adequately assesses stigmatizing attitudes among people without epilepsy.

MicroRNA-134 plasma levels before and after treatment with valproic acid for epilepsy patients

PubMed Central

Wang, Xiaofeng; Luo, Yifeng; Liu, Shuangxi; Tan, Liming; Wang, Sanhu; Man, Rongyong

2017-01-01

Background Temporal lobe epilepsy is the second most common neurological disorders characterized by recurrent spontaneous seizures. MicroRNAs play a vital role in regulating synaptic plasticity, brain development and post-transcriptional expression of proteins. In both animal models of epilepsy and human patients, miR-134, a brain-specific microRNA has recently been identified as a potential regulator of epileptogenesis. Methods microRNA identified as targets for the actions of valproic acid (VPA) are known to have important effects in brain function. In this study, 59 new-onset epilepsy patients and 20 controls matched by sex and age were enrolled. Patients with a score < 3 were allocated into the mild group, 3-5 into the moderate group and >5 into the severe group. The plasma miRNA-134 level was quantitatively measured using real-time PCR. Results Plasma miRNA-134 level in new-onset epilepsy patients was significantly up-regulated when compared with that in healthy controls, and then considerably down-regulated after oral intake of valproic acid medication. The up-regulated plasma miRNA-134 levels may be directly associated with the pathophysiology and severity of epilepsy. Conclusion Plasma miRNA-134 in epilepsy may be considered as a potential peripheral biomarker that responds to the incidence of epilepsy and associates with use of anti-epilepsy drugs. PMID:29069823

Sex differences in human epilepsy.

PubMed

Savic, Ivanka

2014-09-01

In the majority of neuropsychiatric conditions, marked gender-based differences have been found in the epidemiology, clinical manifestations, and therapy of disease. Emerging data suggest that gender differences exist also in the epidemiology, and pathophysiology of epilepsy. The present review summarizes the current information regarding gender and epilepsy. These differences are regarded from the perspective of innate sex differences in cerebral morphology, structural and functional connections, and assuming that these differences may render men and women differently vulnerable to epileptogenicity. Copyright © 2014 Elsevier Inc. All rights reserved.

[Autism, epilepsy and tuberous sclerosis complex: a functional model linked to mTOR pathway].

PubMed

García-Peñas, Juan José; Carreras-Sááez, Inmaculada

2013-02-22

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems. Brain disorders are the origin of more frequent and severe problems and include infantile spasms, intractable epilepsy, brain tumors, cognitive disabilities, and autism. TSC1 or TSC2 encoded proteins modulate cell function via the mTOR signaling cascade and serve as keystones in regulating cell growth and proliferation. AIM. To review the etiopathogenic mechanisms and the natural course of the association of autism and epilepsy in TSC. Both the clinical and the neuroimaging findings of TSC, including early onset epilepsy and the localization of cortical tubers in the temporal lobes, and the molecular understanding of the mTOR signaling pathway, not only involved in cell growth, but also in synaptogenesis, synaptic plasticity and neuronal functioning, have suggested a multimodal origin of autism in these patients. A greater understanding of the pathogenetic mechanisms underlying autism in TSC could help in devising targeted and potentially more effective treatment strategies. Antagonism of the mTOR pathway with rapamycin and everolimus may provide new therapeutic options for these TSC patients.

[Peptidergic nootropic therapy in cerebral palsy associated with epilepsy].

PubMed

Kholin, A A; Zavadenko, N N; Il Ina, E S; Kolpakchi, L M; Fedonyuk, I D; Bembeeva, R C; Esipova, E S

To assess the efficacy and safety of сortexin in the treatment of children with cerebral palsy (CP) combined with epilepsy. Eighty-four patients (55 boys and 29 girls), aged from 1 to 11 years, with CP combined with epilepsy received cortexin together with antiepileptic drugs (AEDs). Cortexin was administered in doses of 5-10 mg depending on the patient's age and body weight intramuscularly during hospitalization. Cortexin as add-on to AEDs reduced for more than two times the number of seizures, along with improvement of motor function, in 31 (36.9%) patients. The improvement of motor function, but without a significant decrease in epileptic seizures, was achieved in 15 (17.8%) of the patients. Reduction of epileptic seizures frequency (>2 times), but without a significant effect on motor function, was observed in 14 cases (16.7%). Twenty-three patients (27.4%) did not respond the therapy. The aggravation of epileptic seizures during cortexin therapy was observed in only 1 girl with West syndrome (1.2%), and this was significantly lower than the probability of seizures aggravation on AED. Polypeptide nootropic medication cortexin demonstrated efficacy and safety as adjunctive therapy in children with CP combined with epilepsy.

[Study based on ICA of "dorsal attention network" in patients with temporal lobe epilepsy].

PubMed

Yang, Zhigen; Wang, Huinan; Zhang, Zhiqiang; Zhong, Yuan; Chen, Zhili; Lu, Guangming

2010-02-01

Many functional magnetic resonance imaging (fMRI) studies have revealed the deactivation phenomenon of default mode network in the patients with epilepsy; however, nearly not any of the reports has focused on the dorsal attention network of epilepsy. In this paper, independent component analysis (ICA) was used to isolate the dorsal attention network of 16 patients with temporal lobe epilepsy (TLE) and of 20 healthy normals; and a goodness-of-fit analysis was applied at the individual subject level to choose the interesting component. Intra-group analysis and inter-group analysis were performed. The results indicated that the dorsal attention network included bilateral intraparietal sulcus, middle frontal gyrus, human frontal eye field, posterior lobe of right cerebellum, etc. The TLE group showed decreased functional connectivity in most of the dorsal attention regions with the predominance in the bilateral intraparietal sulcus, middle frontal gyrus, and posterior lobe of right cerebellum. These data suggested that the intrinsic organization of the brain function might be disrupted in TLE. In addition, the decrease of goodness-of-fit scores suggests that activity in the dorsal attention network may ultimately prove a sensitive biomarker for TLE.

Potassium Channels in Epilepsy

PubMed Central

Köhling, Rüdiger; Wolfart, Jakob

2016-01-01

This review attempts to give a concise and up-to-date overview on the role of potassium channels in epilepsies. Their role can be defined from a genetic perspective, focusing on variants and de novo mutations identified in genetic studies or animal models with targeted, specific mutations in genes coding for a member of the large potassium channel family. In these genetic studies, a demonstrated functional link to hyperexcitability often remains elusive. However, their role can also be defined from a functional perspective, based on dynamic, aggravating, or adaptive transcriptional and posttranslational alterations. In these cases, it often remains elusive whether the alteration is causal or merely incidental. With ∼80 potassium channel types, of which ∼10% are known to be associated with epilepsies (in humans) or a seizure phenotype (in animals), if genetically mutated, a comprehensive review is a challenging endeavor. This goal may seem all the more ambitious once the data on posttranslational alterations, found both in human tissue from epilepsy patients and in chronic or acute animal models, are included. We therefore summarize the literature, and expand only on key findings, particularly regarding functional alterations found in patient brain tissue and chronic animal models. PMID:27141079

Loss of Function of KCNC1 is associated with intellectual disability without seizures

PubMed Central

Poirier, Karine; Viot, Géraldine; Lombardi, Laura; Jauny, Clémence; Billuart, Pierre; Bienvenu, Thierry

2017-01-01

p.(Arg320His) mutation in the KCNC1 gene in human 11p15.1 has recently been identified in patients with progressive myoclonus epilepsies, a group of rare inherited disorders manifesting with action myoclonus, myoclonic epilepsy, and ataxia. This KCNC1 variant causes a dominant-negative effect. Here we describe three patients from the same family with intellectual disability and dysmorphic features. The three affected individuals carry a c.1015C>T (p.(Arg339*)) nonsense variant in KCNC1 gene. As previously observed in the mutant mouse carrying a disrupted KCNC1 gene, these findings reveal that individuals with a KCNC1 loss-of-function variant can present intellectual disability without seizure and epilepsy. PMID:28145425

Epilepsy, cognition, and neuropsychiatry (Epilepsy, Brain, and Mind, part 2)

PubMed Central

Korczyn, Amos D.; Schachter, Steven C.; Brodie, Martin J.; Dalal, Sarang S.; Engel, Jerome; Guekht, Alla; Hecimovic, Hrvoje; Jerbi, Karim; Kanner, Andres M.; Landmark, Cecilie Johannessen; Mares, Pavel; Marusic, Petr; Meletti, Stefano; Mula, Marco; Patsalos, Philip N.; Reuber, Markus; Ryvlin, Philippe; Štillová, Klára; Tuchman, Roberto; Rektor, Ivan

2016-01-01

Epilepsy is, of course, not one disease but rather a huge number of disorders that can present with seizures. In common, they all reflect brain dysfunction. Moreover, they can affect the mind and, of course, behavior. While animals too may suffer from epilepsy, as far as we know, the electrical discharges are less likely to affect the mind and behavior, which is not surprising. While the epileptic seizures themselves are episodic, the mental and behavioral changes continue, in many cases, interictally. The episodic mental and behavioral manifestations are more dramatic, while the interictal ones are easier to study with anatomical and functional studies. The following extended summaries complement those presented in Part 1. PMID:23764496

Neuroendocrine considerations in the treatment of men and women with epilepsy

PubMed Central

Harden, Cynthia L; Pennell, Page B

2016-01-01

Complex, multidirectional interactions between hormones, seizures, and the medications used to control them can present a challenge for clinicians treating patients with epilepsy. Many hormones act as neurosteroids, modulating brain excitability via direct binding sites. Thus, changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs. The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning. Knowledge of these complex interactions has increased and can now be incorporated in meaningful treatment approaches for men and women with epilepsy. PMID:23237902

New antiepileptic drug development.

PubMed

Dreifuss, F E

1994-01-01

The development of new antiepileptic drugs is poised on the cusp between empiricism and the rational scientific development of medicaments designed to perform specific neurophysiologic functions in keeping with modern ideas of epilepsy generation and spread. It takes into account the difference between seizures and their underlying disorder known as epilepsies and the fact that, although seizures can be effectively treated with pharmacologic agents, the development of epilepsy requires both a predisposition (which may be innate or preventable) and precipitating factors that determine the timing of the individual seizures. The local membrane phenomena or cellular substrates of epilepsy can be described, as can the process of epileptogenesis. New antiepileptic development can be viewed in the light of these concepts.

Reoperation for refractory epilepsy in childhood: a second chance for selected patients.

PubMed

Ramantani, Georgia; Strobl, Karl; Stathi, Angeliki; Brandt, Armin; Schubert-Bast, Susanne; Wiegand, Gert; Korinthenberg, Rudolf; Stephani, Ulrich; van Velthoven, Vera; Zentner, Josef; Schulze-Bonhage, Andreas; Bast, Thomas

2013-10-01

Reoperations account for >10% in pediatric epilepsy surgery cohorts, and they are especially relevant in young children with catastrophic epilepsy. To determine surgical outcomes and their predictive factors in reoperations for refractory epilepsy in childhood. We retrospectively analyzed presurgical findings, resections, and outcomes of 23 consecutive children who underwent reoperations from 2000 to 2011. Etiology included cortical dysplasia with/without glioneuronal tumor in 19 patients (83%), sole glioneuronal tumor in 2, and tuberous sclerosis and Rasmussen encephalitis in 1 each. The reasons for the failure of the initial surgery were functional considerations in 8 (35%), incorrect delineation of the epileptogenic zone in 8 (35%), and resection not performed as initially planned in 7 (30%) cases. Final procedures included 8 (35%) intralobar, 8 (35%) multilobar resections, and 7 (30%) hemispherotomies. Following reoperations, 14 (61%) patients were seizure free, 6 (26%) showed significant or worthwhile improvement, and 3 (13%) did not respond to surgery. Six of 8 patients who underwent the first resection before the age of 3 years, 6 of 8 whose first resection was limited by functional considerations, and all 7 with hemispherotomy as the final resection achieved seizure freedom after reoperation. Reoperation is particularly beneficial for selected children with refractory epilepsy associated with cortical dysplasia that did not respond to an initial limited and/or early resection but achieved seizure freedom after extensive procedures. When indicated, reoperation should be performed at the youngest possible age to profit from higher functional plasticity in compensating for neurological deficit.

Intellectual and language functions in children of mothers with epilepsy.

PubMed

Thomas, Sanjeev V; Sukumaran, Sajith; Lukose, Neetha; George, Annamma; Sarma, P S

2007-12-01

To compare the intellectual and language functions of children of mothers with epilepsy (CME) with that of controls matched for age and socioeconomic status. Cases were CME, aged six years or more (n = 71), drawn from a prospective cohort in the Kerala Registry of Epilepsy and Pregnancy. Controls were 201 children of parents without epilepsy, matched for age and socioeconomic status. The outcome measures included Indian adaptation of Wechsler Intelligence Scale for children and MLT-a locally developed proficiency test for regional language. All relevant data were abstracted from the registry records. The Full Scale IQ and MLT scores were significantly lower for the cases (87.7 +/- 22.6 and 73.4 +/- 17.3) compared to controls (93.0 +/- 14.4 and 83.2 +/- 11.8). Compared to controls, CME scored poor on all subtests of MLT but their impairment was confined to only some of the subtests of IQ. Maternal education and maternal IQ significantly correlated with low IQ and MLT scores for CME whereas type of epilepsy, seizures during pregnancy or low birth weight did not have any significant association with these outcome measures. Polytherapy and higher dosage of antiepileptic drugs (AEDs) were associated with significant impairment in outcome measures. Infants with low developmental quotient at one year of age continued to have low scores on outcome measures at six years. Low maternal IQ, maternal education, and antenatal AED exposure were associated with significant impairment of intellectual and language functions for CME at six years.

Epilepsy and Mental Retardation: An Overview.

ERIC Educational Resources Information Center

Coulter, David L.

1993-01-01

The comprehensive management of epilepsy in people with mental retardation requires consideration of four aspects of care: diagnosis and classification, anticonvulsant drug treatment, safety and protection from injury, and psychosocial functioning. This paper outlines what is known and unknown in these four areas and introduces articles in this…

Epilepsy Care in Zambia: A Study of Traditional Healers

PubMed Central

Baskind, Roy; Birbeck, Gretchen

2005-01-01

Summary Purpose Most people with epilepsy (PWE) reside in developing countries with limited access to medical care. In sub-Saharan Africa (SSA), traditional healers (THs) play a prominent role in caring for PWE, yet little is known about epilepsy care by THs. We conducted a multimethod, qualitative study to better understand the epilepsy care delivered by THs in Zambia. Methods We conducted focus-group discussions with THs, in-depth semistructured interviews with a well-recognized TH at his place of work, and multiple informal interviews with health-care providers in rural Zambia. Results THs recognize the same symptoms that a neurologist elicits to characterize seizure onset (e.g., olfactory hallucinations, jacksonian march, automatisms). Although THs acknowledge a familial propensity for some seizures and endorse causes of symptomatic epilepsy, they believe witchcraft plays a central, provocative role in most seizures. Treatment is initiated after the first seizure and usually incorporates certain plant and animal products. Patients who do not experience further seizures are considered cured. Those who do not respond to therapy may be referred to other healers. Signs of concomitant systemic illness are the most common reason for referral to a hospital. As a consequence of this work, our local Epilepsy Care Team has developed a more collaborative relationship with THs in the region. Conclusions THs obtain detailed event histories, are treatment focused, and may refer patients who have refractory seizures to therapy to other healers. Under some circumstances, they recognize a role for modern health care and refer patients to the hospital. Given their predominance as care providers for PWE, further understanding of their approach to care is important. Collaborative relationships between physicians and THs are needed if we hope to bridge the treatment gap in SSA. PMID:16026565

The presence of polyglucosan bodies in temporal lobe epilepsy: its role and significance.

PubMed

Abubakr, Abuhuziefa; Wambacq, Ilse; Donahue, John E; Zappulla, Rosario

2005-11-01

Mesial temporal sclerosis (MTS) is an important pathology in temporal lobe epilepsy (TLE) and often associated with good surgical outcome, however prognostic factors for surgical outcome are conflicting. The authors examine seizure outcome after surgery for TLE due to MTS, with focus on the presence of polyglucosan bodies (PGBs), and its relation to the epileptogenic process. Records of 44 consecutive patients with intractable TLE who underwent anterior temporal lobectomy (ATL) at JFK medical center between 1994-2001 were reviewed. Details of clinical, electrophysiological evaluation, and outcome were collected. All slides were reviewed for the presence of MTS. In twenty-one patients with MTS, detailed histology of surgical specimens was reviewed and relative concentration of PGBs was assessed. The postoperative follow-up duration ranges between 28-74 months. Surgical outcome was evaluated according to Engel's classification. Data of fourteen females (mean age 32.8 years) and 7 males (mean age 34.2) were analyzed. PBGs were identified in 10 patients (8 females and 2 males). All 10 patients had good surgical outcome, with 6 patients (60%) being seizure free (class 1) and 4 patients as class 2. While 11 patients (6 males and 5 females) with absent PGB, 72.8% had good surgical outcome. Of these, 7 (63.8%) had class 1, 1 patient had class 2, and 3 patients had class 3&4. Assessing several risk factors, the only significant difference between the two groups was epilepsy duration, which was significantly longer in patients with PGBs (P = 0.011). The histological presence of PGB is associated with long duration of epilepsy and could be the consequence of epilepsy. Despite prolonged duration of epilepsy, the surgical outcome in PGBs +ve is similar to PGBs -ve patients.

Interleukin-1β causes fluoxetine resistance in an animal model of epilepsy-associated depression.

PubMed

Pineda, Eduardo A; Hensler, Julie G; Sankar, Raman; Shin, Don; Burke, Teresa F; Mazarati, Andréy M

2012-04-01

Depression represents a common comorbidity of epilepsy and is frequently resistant to selective serotonin reuptake inhibitors (SSRI). We tested the hypothesis that the SSRI resistance in epilepsy associated depression may be a result of a pathologically enhanced interleukin-1β (IL1-β) signaling, and consequently that the blockade of IL1-β may restore the effectiveness of SSRI. Epilepsy and concurrent depression-like impairments were induced in Wistar rats by pilocarpine status epilepticus (SE). The effects of the 2-week long treatment with fluoxetine, interleukin-1 receptor antagonist (IL-1ra), and their combination were examined using behavioral, biochemical, neuroendocrine, and autoradiographic assays. In post-SE rats, depression-like impairments included behavioral deficits indicative of hopelessness and anhedonia; the hyperactivity of the hypothalamo-pituitary-adrenocortical axis; the diminished serotonin output from raphe nucleus; and the upregulation of presynaptic serotonin 1-A (5-HT1A) receptors. Fluoxetine monotherapy exerted no antidepressant effects, whereas the treatment with IL-1ra led to the complete reversal of anhedonia and to a partial improvement of all other depressive impairments. Combined administration of fluoxetine and IL-1ra completely abolished all hallmarks of epilepsy-associated depressive abnormalities, with the exception of the hyperactivity of the hypothalamo-pituitary-adrenocortical axis, the latter remaining only partially improved. We propose that in certain forms of depression, including but not limited to depression associated with epilepsy, the resistance to SSRI may be driven by the pathologically enhanced interleukin-1β signaling and by the subsequent upregulation of presynaptic 5-HT1A receptors. In such forms of depression, the use of interleukin-1β blockers in conjunction with SSRI may represent an effective therapeutic approach.

Absence epilepsy and the CHD2 gene: an adolescent male with moderate intellectual disability, short-lasting psychoses, and an interstitial deletion in 15q26.1–q26.2

PubMed Central

Verhoeven, Willem MA; Egger, Jos IM; Knegt, Alida C; Zuydam, José; Kleefstra, Tjitske

2016-01-01

Deletions of the 15q26 region encompassing the chromodomain helicase DNA binding domain 2 (CHD2) gene have been associated with intellectual disability, behavioral problems, and several types of epilepsy. Including the cases mentioned in ECARUCA (European cytogeneticists association register of unbalanced chromosome aberrations) and DECIPHER (database of genomic variation and phenotype in humans using ensembl resources), so far, a total of 13 intellectually disabled patients with a genetically proven deletion of the CHD2 gene are described, of whom eleven had a history of severe forms of epilepsy starting from a young age. In this article, a moderately intellectually disabled 15-year-old male with a 15q26.1–q26.2 interstitial deletion is reported, who was referred for analysis of two recent short-lasting psychotic episodes that were nonresponsive to antipsychotic treatment and recurrent disinhibited behaviors since early infancy. Careful interdisciplinary assessment revealed that the psychotic phenomena originated from a previously unrecognized absence epilepsy. Treatment with valproic acid was started which resulted in full remission of psychotic symptoms, and consequently, substantial improvement of behavior. It was concluded that in case of (rare) developmental disorders with genetically proven etiology, a detailed inventory of anamnestic data and description of symptomatology over time may elucidate epilepsy-related psychopathology for which a specific treatment regimen is needed. PMID:27274247

Depression and anxiety during pregnancy and the postpartum period in women with epilepsy: A review of frequency, risks and recommendations for treatment.

PubMed

H Bjørk, Marte; Veiby, Gyri; A Engelsen, Bernt; Gilhus, Nils Erik

2015-05-01

To review available data and provide treatment recommendations concerning peripartum depression, anxiety and fear of birth in women with epilepsy (WWE). The PubMed, the LactMed, the DART and the Cochrane database were searched for original articles concerning psychiatric disease in the peripartum period in WWE. Point prevalence of depression from 2nd trimester to 6 months postpartum ranged from 16 to 35% in women with epilepsy compared to 9-12% in controls. The highest estimates were found early in pregnancy and in the perinatal period. Anxiety symptoms 6 months postpartum were reported by 10 and 5%, respectively. Fear of birth symptoms were increased in primiparous WWE compared to controls. Previous psychiatric disease, sexual/physical abuse, antiepileptic drug (AED) polytherapy, and high seizure frequency emerged as strong risk factors. Depressed WWE rarely used antidepressive medication during pregnancy. No evidence was available concerning treatment effects or impact on the developing child. Peripartum depression is frequent in WWE and seldom medically treated. Health personnel should screen WWE for psychiatric disease and risk factors during pre-pregnancy planning, pregnancy and postpartum follow up. Treatment decisions should rely on efficacy and safety data in peripartum patients without epilepsy and non-pregnant people with epilepsy. Consequences of in utero exposure to AED therapy in combination with antidepressants are not known, and non-pharmacological treatment should be tried first. Copyright © 2015. Published by Elsevier Ltd.

The impact of maternal depressive symptoms on health-related quality of life in children with epilepsy: a prospective study of family environment as mediators and moderators.

PubMed

Ferro, Mark A; Avison, William R; Campbell, M Karen; Speechley, Kathy N

2011-02-01

To examine the impact of maternal depressive symptoms (DS) on health-related quality of life (HRQL) in children with new-onset epilepsy and to identify family factors that moderate and mediate this relationship during the first 24 months after epilepsy diagnosis. A sample of 339 mother-child dyads recruited from pediatric neurologists across Canada in the Health-related Quality of Life in Children with Epilepsy Study. Mothers' and neurologists' reports were collected at four times during the 24-month follow-up. Mothers' DS were measured using the Center for Epidemiological Studies Depression Scale (CES-D) and children's HRQL using the Quality of Life in Childhood Epilepsy (QOLCE). Data were modeled using individual growth curve modeling. Maternal DS were observed to have a negative impact on QOLCE scores at 24 months (β = -0.47, p < 0.0001) and the rate of change in QOLCE scores during follow-up (β = -0.04, p = 0.0250). This relationship was moderated by family resources (β = 0.25, p = 0.0243), and the magnitude of moderation varied over time (β = 0.09, p = 0.0212). Family functioning and demands partially mediated the impact of maternal DS on child HRQL (β = -0.07, p = 0.0007; β = -0.12, p = 0.0006). Maternal DS negatively impact child HRQL in new-onset epilepsy during the first 24 months after diagnosis. This relationship is moderated by family resources and mediated by family functioning and demands. By adopting family centered approaches, health care professionals may be able to intervene at the maternal or family level to promote more positive outcomes in children. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

Molecular Targets for Antiepileptic Drug Development

PubMed Central

Meldrum, Brian S.; Rogawski, Michael A.

2007-01-01

Summary This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the α subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, α2–δ voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ channels and GABAA receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABAB and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current Ih; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na+ channels underlying persistent Na+ currents or GABAA receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies. PMID:17199015

Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.

PubMed

Niesen, Charles E; Xu, Jun; Fan, Xuemo; Li, Xiaojin; Wheeler, Christopher J; Mamelak, Adam N; Wang, Charles

2013-01-01

The molecular mechanism underlying tumor-induced epileptogenesis is poorly understood. Alterations in the peritumoral microenvironment are believed to play a significant role in inducing epileptogenesis. We hypothesize that the change of gene expression in brain peritumoral tissues may contribute to the increased neuronal excitability and epileptogenesis. To identify the genes possibly involved in tumor-induced epilepsy, a genome-wide gene expression profiling was conducted using Affymetrix HG U133 plus 2.0 arrays and RNAs derived from formalin-fixed paraffin embedded (FFPE) peritumoral cortex tissue slides from 5-seizure vs. 5-non-seizure low grade brain tumor patients. We identified many differentially expressed genes (DEGs). Seven dysregulated genes (i.e., C1QB, CALCRL, CCR1, KAL1, SLC1A2, SSTR1 and TYRO3) were validated by qRT-PCR, which showed a high concordance. Principal Component Analysis (PCA) showed that epilepsy subjects were clustered together tightly (except one sample) and were clearly separated from the non-epilepsy subjects. Molecular functional categorization showed that significant portions of the DEGs functioned as receptor activity, molecular binding including enzyme binding and transcription factor binding. Pathway analysis showed these DEGs were mainly enriched in focal adhesion, ECM-receptor interaction, and cell adhesion molecules pathways. In conclusion, our study showed that dysregulation of gene expression in the peritumoral tissues may be one of the major mechanisms of brain tumor induced-epilepsy. However, due to the small sample size of the present study, further validation study is needed. A deeper characterization on the dysregulated genes involved in brain tumor-induced epilepsy may shed some light on the management of epilepsy due to brain tumors.

Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy.

PubMed

Zhao, Junli; Wang, Yi; Xu, Cenglin; Liu, Keyue; Wang, Ying; Chen, Liying; Wu, Xiaohua; Gao, Feng; Guo, Yi; Zhu, Junming; Wang, Shuang; Nishibori, Masahiro; Chen, Zhong

2017-08-01

Brain inflammation is a major factor in epilepsy, and the high mobility group box-1 (HMGB1) protein is known to contribute significantly to the generation of seizures. Here, we investigated the therapeutic potential of an anti-HMGB1 monoclonal antibody (mAb) in epilepsy. anti-HMGB1 mAb attenuated both acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (kainic acid-induced) in a dose-dependent manner. Meanwhile, the anti-HMGB1 mAb also attenuated seizure activities of human brain slices obtained from surgical resection from drug-resistant epilepsy patients. The mAb showed an anti-seizure effect with a long-term manner and appeared to be minimal side effects at even very high dose (no disrupted physical EEG rhythm and no impaired basic physical functions, such as body growth rate and thermoregulation). This anti-seizure effect of mAb results from its inhibition of translocated HMGB1 from nuclei following seizures, and the anti-seizure effect was absent in toll-like receptor 4 knockout (TLR4 -/- ) mice. Interestingly, the anti-HMGB1 mAb also showed a disease-modifying anti-epileptogenetic effect on epileptogenesis after status epileptics, which is indicated by reducing seizure frequency and improving the impaired cognitive function. These results indicate that the anti-HMGB1 mAb should be viewed as a very promising approach for the development of novel therapies to treat refractory epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Emotional well-being in children with epilepsy: Family factors as mediators and moderators.

PubMed

Goodwin, Shane W; Wilk, Piotr; Karen Campbell, M; Speechley, Kathy N

2017-11-01

Our objective was to examine the relationships of factors associated with children's emotional well-being 2 years after diagnosis, and to examine if these relationships are mediated or moderated by family factors. Data came from a multicenter prospective cohort study of children with newly diagnosed epilepsy from across Canada (Health-Related Quality of Life in Children with Epilepsy Study; HERQULES, n = 373). Emotional well-being was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). The relationships between clinical factors, family factors, and emotional well-being were assessed using multiple regression analyses. Family functioning, family stress, and repertoire of resources that the families had to adapt to stressful events were significantly associated with poor emotional well-being 2 years after diagnosis (p < 0.05) in the multivariable analysis. The effect of parental depressive symptoms was partially mediated by family functioning and family stress (p < 0.01 and p = 0.02, respectively). Family resources acted as a moderator in the relationship between severity of epilepsy and emotional well-being (p < 0.05). Based on our findings, efforts to strengthen the family environment may warrant attention. We suggest that clinicians take a family centered care approach by including families in treatment planning. Family centered care has been shown to improve family well-being and coping and in turn may reduce the impact of clinical factors on emotional well-being to improve long-term health-related quality of life. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Cognitive function in Nigerian children with newly diagnosed epilepsy: a preliminary report.

PubMed

Lagunju, Ike Oluwa Abiola; Adeniyi, Yetunde Celia; Olukolade, Gbemi

2016-01-01

Epilepsy has long been associated with cognitive dysfunction and educational underachievement. The purpose of the study was to describe the baseline findings from a larger prospective study. New cases of epilepsy aged 6-16 years seen at a paediatric neurology clinic in Ibadan, Nigeria were evaluated for any evidence of cognitive impairment. Intelligence quotient (IQ) of the participants was measured using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). Scores on cognitive subtests and Full Scale IQ (FSIQ) were computed and association between the subsets scores and seizure variables were calculated. 40 children, 24 males and 16 females were studied and their ages ranged from 6 to 16 years with a mean of 10.8 (SD=3.0) years. Global intellectual functioning as measured by the WISC-IV was in the normal range (FSIQ scores <85) for 52.5% (n = 21) of the participants and the remaining participants (47.5%) scored between the borderline and severe category for intellectual disability. The strongest correlation was between 'caregiver's assessment of school performance' and FSIQ, (r = 0.70; p< 0.001). Age at onset of epilepsy and seizure type had no significant association with scores on the WISC-IV composite scores. There is a high prevalence of significant cognitive dysfunction in Nigerian children with epilepsy, even in the absence of any known brain insult. All children with epilepsy should have routine IQ assessment following diagnosis, in order to allow for early intervention when indicated, and thus, improved outcomes.

Intellectual impairment in patients with epilepsy in Ile-Ife, Nigeria.

PubMed

Sunmonu, T A; Komolafe, M A; Ogunrin, A O; Oladimeji, B Y; Ogunniyi, A

2008-12-01

Epilepsy is the most common non-infectious neurologic disease in developing countries such as Africa, including Nigeria. This study was designed to assess the intellectual performance of patients with epilepsy (PWE) in Nigeria hoping that the result will serve as the basis for educational, vocational, and social counseling. Forty-one PWE were studied along with 41 age-, sex- and education-matched healthy controls. A questionnaire was developed and applied to all subjects and history was taken from patients and eyewitness. The intellectual function of each subject was assessed with the aid of Wechsler Adult Intelligence Scale adapted for Nigerians. All patients subsequently had electroencephalography (EEG) performed and the EEG findings were noted. SPSS statistical package was used to analyze the data. The PWE performed poorly on the verbal IQ, performance IQ, and full scale IQ scores when compared with controls (P < 0.05) and 20% of PWE had mental retardation. Long duration of epilepsy, long duration of antiepileptic drug therapy, younger age at onset of epilepsy, increased frequency of seizures, and low educational status were found to have negative impacts on intellectual performance in PWE (P < 0.05) while seizure types and type of antiepileptic drugs (carbamazepine or phenytoin) did not influence intellectual performance. This study shows that PWE had significant intellectual impairment when compared with controls. In addition, long duration of epilepsy, long duration of AED therapy, earlier age of onset, increased seizure frequency, and low educational status had a negative impact on intellectual functioning in PWE.

Epilepsy Surgery in Pediatric Intractable Epilepsy with Destructive Encephalopathy

PubMed Central

Park, So Young; Kwon, Hye Eun; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Dong Seok; Kim, Heung Dong

2013-01-01

Background and Purpose: The aim of the current study is to review the clinical features, surgery outcomes and parental satisfaction of children with destructive encephalopathy who underwent epilepsy surgery due to medically intractable seizures. Methods: 48 patients who underwent epilepsy surgery from October 2003 to August 2011 at Severance Children’s Hospital have been reviewed. The survey was conducted for functional outcomes and parental satisfaction at least 1 year after the surgery. Results: Epileptic encephalopathy including Lennox-Gastaut syndrome and infantile spasms was more prevalent than symptomatic focal epilepsy. Hypoxic ischemic injury accounted for most of the underlying etiology of the destructive encephalpathy, followed by central nervous system infection and head trauma. 27 patients (56.3%) underwent resective surgery and 21 patients (43.7%) underwent palliative surgery. 16 patients (33.3%) achieved seizure free and 27 parents (87.5%) reported satisfaction with the outcome of their children’s epilepsy surgery. In addition, 14 parents (77.8 %) whose children were not seizure free reported satisfaction with their children’s improvement in cognitive and behavior issues. Conclusions: Epilepsy surgery in destructive encephalopathy was effective for controlling seizures. Parents reported satisfaction not only with the surgical outcomes, but also with improvement of cognitive and behavior issues. PMID:24649473

Stigma and functional disability in relation to marriage and employment in young people with epilepsy in rural Tanzania.

PubMed

Goodall, Jack; Salem, Sabrine; Walker, Richard W; Gray, William K; Burton, Kathryn; Hunter, Ewan; Rogathi, Jane; Shali, Esther; Mohin, Ali; Mushi, Declare; Owens, Stephen

2018-01-01

To assess the impact of childhood epilepsy on social transitioning outcomes for young people with epilepsy (YPWE) living in Tanzania, and to explore influences on these outcomes. At six years from baseline, we followed up 84 YPWE and 79 age- sex- and village- matched controls recruited into a case-control study of childhood epilepsy in rural northern Tanzania. Data were collected from interviews with young people and their carers using a structured questionnaire. Perceived stigma was evaluated using the Kilifi Stigma Score and functional disability using the Barthel Index (BI). The effects of age, gender, functional disability and stigma on selected markers of social transitioning (education, employment and relationships) were estimated using multivariable modelling. Fewer YPWE than controls were in an intimate relationship (42.3% vs. 76.9%) or in education or paid employment (33.3% vs. 91.1%) and they reported elevated perceived stigma scores (27.4% vs. 3.8%). Among YPWE, a positive education or employment outcome was predicted by a lower seizure frequency (adjusted OR 3.79) and a higher BI score (adj. OR 12.12); a positive relationship outcome was predicted by a higher BI score (adj. OR 45.86) and being male (adj. OR 8.55). YPWE were more likely to experience adverse employment, educational and relationship outcomes in the transition to adult life than controls, with the greatest disadvantage experienced by females, those with greater functional disability and those with poorer seizure control. Markers of social transitioning should be included in any prospective evaluation of interventions designed to support these groups. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Brain lateralization and neural plasticity for musical and cognitive abilities in an epileptic musician

PubMed Central

Trujillo-Pozo, Isabel; Martín-Monzón, Isabel; Rodríguez-Romero, Rafael

2013-01-01

The use of intracarotid propofol procedure (IPP) when assessing musical lateralization has not been reported in literature up to now. This procedure (similar to Wada Test) has provided the opportunity to investigate not only lateralization of language and memory functions on epileptic patients but also offers a functional mapping approach with superior spatial and temporal resolution to analyze the lateralization of musical abilities. Findings in literature suggest that musical training modifies functional and structural brain organization. We studied hemispheric lateralization in a professional musician, a 33 years old woman with refractory left medial temporal lobe (MTL) epilepsy (TLE). A longitudinal neuropsychological study was performed over a period of 21 months. Before epilepsy surgery, musical abilities, language and memory were tested during IPP by means of a novel and exhaustive neuropsychological battery focusing on the processing of music. We used a selection of stimuli to analyze listening, score reading, and tempo discrimination. Our results suggested that IPP is an excellent method to determine not only language, semantic, and episodic memory, but also musical dominance in a professional musician who may be candidate for epilepsy surgery. Neuropsychological testing revealed that right hemisphere's patient is involved in semantic and episodic musical memory processes, whereas her score reading and tempo processing require contribution from both hemispheres. At one-year follow-up, outcome was excellent with respect to seizures and professional skills, meanwhile cognitive abilities improved. These findings indicate that IPP helps to predict who might be at risk for postoperative musical, language, and memory deficits after epilepsy surgery. Our research suggests that musical expertise and epilepsy critically modifies long-term memory processes and induces brain structural and functional plasticity. PMID:24367312

Development of the PedsQL™ Epilepsy Module: Focus group and cognitive interviews.

PubMed

Follansbee-Junger, Katherine W; Mann, Krista A; Guilfoyle, Shanna M; Morita, Diego A; Varni, James W; Modi, Avani C

2016-09-01

Youth with epilepsy have impaired health-related quality of life (HRQOL). Existing epilepsy-specific HRQOL measures are limited by not having parallel self- and parent-proxy versions, having a restricted age range, not being inclusive of children with developmental disabilities, or being too lengthy for use in a clinical setting. Generic HRQOL measures do not adequately capture the idiosyncrasies of epilepsy. The purpose of the present study was to develop items and content validity for the PedsQL™ Epilepsy Module. An iterative qualitative process of conducting focus group interviews with families of children with epilepsy, obtaining expert input, and conducting cognitive interviews and debriefing was utilized to develop empirically derived content for the instrument. Eleven health providers with expertise in pediatric epilepsy from across the country provided feedback on the conceptual model and content, including epileptologists, nurse practitioners, social workers, and psychologists. Ten pediatric patients (age 4-16years) with a diagnosis of epilepsy and 11 parents participated in focus groups. Thirteen pediatric patients (age 5-17years) and 17 parents participated in cognitive interviews. Focus groups, expert input, and cognitive debriefing resulted in 6 final domains including restrictions, seizure management, cognitive/executive functioning, social, sleep/fatigue, and mood/behavior. Patient self-report versions ranged from 30 to 33 items and parent proxy-report versions ranged from 26 to 33 items, with the toddler and young child versions having fewer items. Standardized qualitative methodology was employed to develop the items and content for the novel PedsQL™ Epilepsy Module. The PedsQL™ Epilepsy Module has the potential to enhance clinical decision-making in pediatric epilepsy by capturing and monitoring important patient-identified contributors to HRQOL. Copyright © 2016 Elsevier Inc. All rights reserved.

Understanding the pathophysiology of reflex epilepsy using simultaneous EEG-fMRI.

PubMed

Sandhya, Manglore; Bharath, Rose Dawn; Panda, Rajanikant; Chandra, S R; Kumar, Naveen; George, Lija; Thamodharan, A; Gupta, Arun Kumar; Satishchandra, P

2014-03-01

Measuring neuro-haemodynamic correlates in the brain of epilepsy patients using EEG-fMRI has opened new avenues in clinical neuroscience, as these are two complementary methods for understanding brain function. In this study, we investigated three patients with drug-resistant reflex epilepsy using EEG-fMRI. Different types of reflex epilepsy such as eating, startle myoclonus, and hot water epilepsy were included in the study. The analysis of EEG-fMRI data was based on the visual identification of interictal epileptiform discharges on scalp EEG. The convolution of onset time and duration of these epilepsy spikes was estimated, and using these condition-specific effects in a general linear model approach, we evaluated activation of fMRI. Patients with startle myoclonus epilepsy experienced epilepsy in response to sudden sound or touch, in association with increased delta and theta activity with a spike-and-slow-wave pattern of interictal epileptiform discharges on EEG and fronto-parietal network activation pattern on SPECT and EEG-fMRI. Eating epilepsy was triggered by sight or smell of food and fronto-temporal discharges were noted on video-EEG (VEEG). Similarly, fronto-temporo-parietal involvement was noted on SPECT and EEG-fMRI. Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement. SPECT and EEG fMRI revealed a similar fronto-parietal-occipital involvement. From these results, we conclude that continuous EEG recording can improve the modelling of BOLD changes related to interictal epileptic activity and this can thus be used to understand the neuro-haemodynamic substrates involved in reflex epilepsy.

Ictal Cardiac Ryhthym Abnormalities.

PubMed

Ali, Rushna

2016-01-01

Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy.

Topiramate on the quality of life in childhood epilepsy.

PubMed

Jung, Da-Eun; Kim, Heung-Dong; Hur, Yun-Jung; Eom, So-Yong

2011-10-01

This study evaluated the effect of topiramate (TPM) on the quality of life (QOL) in childhood epilepsy, using the Korean quality of life in childhood epilepsy (K-QOLCE) questionnaire. An open label, prospective, observational study of the families of 664 children with epilepsy from 41 centers was conducted. The parents completed the K-QOLCE at the baseline visit and again 6months after starting TPM treatment. The parents reported the seizure frequency at both assessment dates. Statistically significant improvements in all K-QOLCE domains except social functioning were found at 6months after starting TPM treatment from the baseline-scores (P<0.05). However, improved QOL scores were not dependent on the reduction in seizure frequency. TPM significantly improved QOL in children with epilepsy, suggesting its potential clinical benefits. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Epilepsy and the immune system: is there a link?

PubMed

Billiau, An D; Wouters, Carine H; Lagae, Lieven G

2005-01-01

The concept that the immune system plays a role in the epileptogenic process of some epileptic syndromes was first proposed more than 20 years ago. Since then, numerous studies have reported on the existence of a variety of immunological alterations in epileptic patients, on the observation of favourable responses of refractory epilepsy syndromes to immunomodulatory treatment, and on the association of certain well-known immune-mediated disease states with epilepsy. This review comprehensively recapitulates the currently available evidence supporting or arguing against the possible involvement of the immune system in the pathogenesis of certain types of epilepsy. It is concluded that an abundance of facts is in support of this concept and that further studies should be directed at substantiating the pathogenic significance of (auto)immune responses in certain types of epilepsy. Current progress in the functional and molecular immunological research techniques will indisputably contribute to the elucidation of this link.

Causes of learning disability and epilepsy: a review.

PubMed

Prince, Elizabeth; Ring, Howard

2011-04-01

Although the association between learning disability and epilepsy is well known, until relatively recently specific processes underlying this association were relatively poorly understood. However, scientific advances in molecular biology are starting to guide researchers towards descriptions of genetic and pathophysiological processes that may explain why syndromes of epilepsy and learning disability often co-exist. This article will focus largely on three areas of advancing knowledge: insights gained from wider use of genome-wide array comparative genomic hybridization (aCGH), specific insights gained from detailed study of Rett syndrome and the role of abnormalities of astrocytic function in predisposing to both epilepsy and learning disability. The enormous complexity of the biological underpinnings of the co-occurrence of epilepsy and learning disability are becoming apparent. In the future it is likely that research into therapeutic approaches will include, amongst other approaches, investigations of gene structure and expression, the role of astrocytes and the stability of dendritic spines.

The role of interleukin-1 in seizures and epilepsy: a critical review.

PubMed

Rijkers, K; Majoie, H J; Hoogland, G; Kenis, G; De Baets, M; Vles, J S

2009-04-01

Interleukin-1 (IL-1) has a multitude of functions in the central nervous system. Some of them involve mechanisms that are related to epileptogenesis. The role of IL-1 in seizures and epilepsy has been investigated in both patients and animal models. This review aims to synthesize, based on the currently available literature, the consensus role of IL-1 in epilepsy. Three lines of evidence suggest a role for IL-1: brain tissue from epilepsy patients and brain tissue from animal models shows increased IL-1 expression after seizures, and IL-1 has proconvulsive properties when applied exogeneously. However, opposing results have been published as well. More research is needed to fully establish the role of IL-1 in seizure generation and epilepsy, and to explore possible new treatment strategies that are based on interference with intracellular signaling cascades that are initiated when IL-1 binds to its receptor.

[Traumatic brain injuries--forensic and expertise aspects].

PubMed

Vuleković, Petar; Simić, Milan; Misić-Pavkov, Gordana; Cigić, Tomislav; Kojadinović, Zeljko; Dilvesi, Dula

2008-01-01

Traumatic brain injuries have major socio-economic importance due to their frequency, high mortality and serious consequences. According to their nature the consequences of these injuries may be classified as neurological, psychiatric and esthetic. Various lesions of brain structures cause neurological consequences such as disturbance of motor functions, sensibility, coordination or involuntary movements, speech disturbances and other deviations, as well as epilepsy. Psychiatric consequences include cognitive deficit, emotional disturbances and behavior disturbances. CRIMINAL-LEGAL ASPECT OF TRAUMATIC BRAIN INJURIES AND LITIGATION: Criminal-legal aspect of traumatic brain injuries expertise understands the qualification of these injuries as mild, serious and qualified serious body injuries as well as the expertise about the mechanisms of their occurrence. Litigation expertise includes the estimation of pain, fear, diminished, i.e. lost vital activity and disability, esthetic marring, and psychological suffer based on the diminished general vital activity and esthetic marring. Evaluation of consequences of traumatic brain injuries should be performed only when it can be positively confirmed that they are permanent, i.e. at least one year after the injury. Expertise of these injuries is interdisciplinary. Among clinical doctors the most competent medical expert is the one who is in charge for diagnostics and injury treatment, with the recommendation to avoid, if possible, the doctor who conducted treatment. For the estimation of general vital activity, the neurological consequences, pain and esthetic marring expertise, the most competent doctors are neurosurgeon and neurologist. Psychological psychiatric consequences and fear expertise have to be performed by the psychiatrist. Specialists of forensic medicine contribute with knowledge of criminal low and legal expertise.

Helplessness and Resourcefulness in Coping with Epilepsy.

ERIC Educational Resources Information Center

Rosenbaum, Michael; Palmon, Noami

1984-01-01

Tested the hypothesis that psychological adjustment to epilepsy would be a joint function of subjects' (N=50) perceived repertoire of self-control skills and the extent to which they were exposed to uncontrollable seizures. Results showed that high-resourceful epileptics exposed to lower frequencies of seizures coped better with their disability.…

Enhanced astroglial Ca2+ signaling increases excitatory synaptic strength in the epileptic brain.

PubMed

Álvarez-Ferradas, Carla; Morales, Juan Carlos; Wellmann, Mario; Nualart, Francisco; Roncagliolo, Manuel; Fuenzalida, Marco; Bonansco, Christian

2015-09-01

The fine-tuning of synaptic transmission by astrocyte signaling is crucial to CNS physiology. However, how exactly astroglial excitability and gliotransmission are affected in several neuropathologies, including epilepsy, remains unclear. Here, using a chronic model of temporal lobe epilepsy (TLE) in rats, we found that astrocytes from astrogliotic hippocampal slices displayed an augmented incidence of TTX-insensitive spontaneous slow Ca(2+) transients (STs), suggesting a hyperexcitable pattern of astroglial activity. As a consequence, elevated glutamate-mediated gliotransmission, observed as increased slow inward current (SICs) frequency, up-regulates the probability of neurotransmitter release in CA3-CA1 synapses. Selective blockade of spontaneous astroglial Ca(2+) elevations as well as the inhibition of purinergic P2Y1 or mGluR5 receptors relieves the abnormal enhancement of synaptic strength. Moreover, mGluR5 blockade eliminates any synaptic effects induced by P2Y1R inhibition alone, suggesting that the Pr modulation via mGluR occurs downstream of P2Y1R-mediated Ca(2+)-dependent glutamate release from astrocyte. Our findings show that elevated Ca(2+)-dependent glutamate gliotransmission from hyperexcitable astrocytes up-regulates excitatory neurotransmission in epileptic hippocampus, suggesting that gliotransmission should be considered as a novel functional key in a broad spectrum of neuropathological conditions. © 2015 Wiley Periodicals, Inc.

Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency.

PubMed

Almalki, Abdulraheem; Alston, Charlotte L; Parker, Alasdair; Simonic, Ingrid; Mehta, Sarju G; He, Langping; Reza, Mojgan; Oliveira, Jorge M A; Lightowlers, Robert N; McFarland, Robert; Taylor, Robert W; Chrzanowska-Lightowlers, Zofia M A

2014-01-01

Mitochondrial aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in protein synthesis since they charge tRNAs with their cognate amino acids. Mutations in the genes encoding mitochondrial aaRSs have been associated with a wide spectrum of human mitochondrial diseases. Here we report the identification of pathogenic mutations (a partial genomic deletion and a highly conserved p. Asp325Tyr missense variant) in FARS2, the gene encoding mitochondrial phenylalanyl-tRNA synthetase, in a patient with early-onset epilepsy and isolated complex IV deficiency in muscle. The biochemical defect was expressed in myoblasts but not in fibroblasts and associated with decreased steady state levels of COXI and COXII protein and reduced steady state levels of the mt-tRNA(Phe) transcript. Functional analysis of the recombinant mutant p. Asp325Tyr FARS2 protein showed an inability to bind ATP and consequently undetectable aminoacylation activity using either bacterial tRNA or human mt-tRNA(Phe) as substrates. Lentiviral transduction of cells with wildtype FARS2 restored complex IV protein levels, confirming that the p.Asp325Tyr mutation is pathogenic, causing respiratory chain deficiency and neurological deficits on account of defective aminoacylation of mt-tRNA(Phe). © 2013. Published by Elsevier B.V. All rights reserved.

Relationship between social competence and neurocognitive performance in children with epilepsy.

PubMed

Raud, Triin; Kaldoja, Mari-Liis; Kolk, Anneli

2015-11-01

Epilepsy may affect a child's social skills and social cognition. The purpose of the study was to examine associations between sociocognitive skills and neurocognitive performance in children with epilepsy. Thirty-five children with epilepsy between the ages of 7 and 12 years (25 with partial and 10 with generalized epilepsy) and 30 controls participated. Theory of Mind (ToM) tasks, Social Cognition Questionnaire proposed by Saltzman-Benaiah and Lalonde (2007), and Social Skills Rating System were used to assess social competence and sociocognitive skills. Neurocognitive performance was assessed using the NEPSY battery. Children with epilepsy demonstrated more difficulties in understanding false belief (p<.001) and intentional lying (p<.05) and exhibited more behavioral problems (p<.05). Notably, their social skills were at the same level as typically developing peers. Children with epilepsy performed significantly worse in attention, executive, verbal, and fine motor tasks (p<.05). We found positive correlations between the understanding of false belief and in executive (r=.6, p<.05), verbal (r=.45-.49, p<.05), and visuospatial skills (r=.34-.48, p<0.01). Children with generalized epilepsy had more problems in memory tasks (p<.05) and understanding of sarcasm (p<.05) compared with children with partial epilepsy. An age of onset over 9.1 years was positively associated with ToM skills (r=.42, p<.05). In conclusion, better ToM in children with better executive functions, and language and visuospatial skills was revealed. The type of epilepsy and age of onset significantly affected ToM skills. Copyright © 2015 Elsevier Inc. All rights reserved.

Experimental Treatment Options in Absence Epilepsy.

PubMed

Luijtelaar, Gilles van; Zobeiri, Mehrnoush; Lüttjohann, Annika; Depaulis, Antoine

2017-01-01

The benign character of absence epilepsy compared to other genetic generalized epilepsy syndromes has often hampered the search for new treatment options. Absence epilepsy is most often treated with ethosuximide or valproic acid. However, both drugs are not always well tolerated or fail, and seizure freedom for a larger proportion of patients remains to be achieved. The availability of genuine animal models of epilepsy does allow to search for new treatment options not only for absence epilepsy per se but also for other genetic - previously called idiopathic - forms of epilepsy. The recent discovery of a highly excitable cortical zone in these models is considered as a new therapeutic target area. Here, we provide an overview regarding the search for new therapeutical options as has been investigated in the genetic rodent models (mainly WAG/Rij and GAERS) including drugs and whether antiepileptogenesis can be achieved, various types of electrical and optogenetical invasive stimulations, different types of noninvasive stimulation and finally whether absence seizures can be predicted and prevented. Many factors determine either the cortical and or thalamic excitability or the interaction between cortex and thalamus and offer new possibilities for new anti-absence drugs, among others metabotropic glutamatergic positive and negative allosteric modulators. The inhibition of epileptogenesis by various drugs with its widespread consequences seems feasible, although its mechanisms remain obscure and seems different from the antiabsence action. Surgical intervention on the cortical zone initiating seizures, either with radiosurgery using synchrotron- generated microbeams, or ablation techniques might reduce spike-and-wave discharges in the rodent models. High frequency electrical subcortical or cortical stimulation might be a good way to abort ongoing spikeand- wave discharges. In addition, possibilities for prevention with real-time EEG analyses in combination with electrical stimulation could also be a way to fully control these seizures. Although it is obvious that some of these treatment possibilities will not be used for absence epilepsy and/or need to be further developed, all can be considered as proof of principle and provide clear directives for further developments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Imaging structural and functional brain networks in temporal lobe epilepsy

PubMed Central

Bernhardt, Boris C.; Hong, SeokJun; Bernasconi, Andrea; Bernasconi, Neda

2013-01-01

Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy. PMID:24098281

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment.

PubMed

Knopman, Alex A; Wong, Chong H; Stevenson, Richard J; Homewood, Judi; Mohamed, Armin; Somerville, Ernest; Eberl, Stefan; Wen, Lingfeng; Fulham, Michael; Bleasel, Andrew F

2014-08-01

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Nine patients with OLE, ages 8-29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug-refractory epilepsy.

PubMed

Alves, Mariana; Gomez-Villafuertes, Rosa; Delanty, Norman; Farrell, Michael A; O'Brien, Donncha F; Miras-Portugal, Maria Teresa; Hernandez, Miguel Diaz; Henshall, David C; Engel, Tobias

2017-09-01

ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy. Status epilepticus was induced using either intra-amygdala kainic acid or pilocarpine to characterize the acute- and long-term changes in hippocampal P2Y expression. P2Y expression was also investigated in brain tissue from patients with temporal lobe epilepsy. Finally, we analyzed the effects of two specific P2Y agonists, ADP and UTP, on seizure severity and seizure-induced cell death. Both intra-amygdala kainic acid and pilocarpine-induced status epilepticus increased the transcription of the uracil-sensitive P2Y receptors P2ry 2 , P2ry 4 , and P2ry 6 and decreased the transcription of the adenine-sensitive P2Y receptors P2ry 1 , P2ry 12 , P2ry 13 . Protein levels of P2Y 1 , P2Y 2 , P2Y 4 , and P2Y 6 were increased after status epilepticus, whereas P2Y 12 expression was decreased. In the chronic phase, P2ry 1 , P2ry 2 , and P2ry 6 transcription and P2Y 1 , P2Y 2 , and P2Y 12 protein levels were increased with no changes for the other P2Y receptors. In hippocampal samples from patients with temporal lobe epilepsy, P2Y 1 and P2Y 2 protein expression was increased, whereas P2Y 13 levels were lower. Demonstrating a functional contribution of P2Y receptors to seizures, central injection of ADP exacerbated seizure severity, whereas treatment with UTP decreased seizure severity during status epilepticus in mice. The present study is the first to establish the specific hippocampal expression profile and function of the P2Y receptor family after experimental status epilepticus and in human temporal lobe epilepsy and offers potential new targets for seizure control and disease modification. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Decreased number of interneurons and increased seizures in neuropilin 2 deficient mice: Implications for autism and epilepsy

PubMed Central

Gant, John C.; Thibault, Oliver; Blalock, Eric M.; Yang, Jun; Bachstetter, Adam; Kotick, James; Schauwecker, Paula E.; Hauser, Kurt F.; Smith, George M.; Mervis, Ron; Li, YanFang; Barnes, Gregory N.

2010-01-01

Summary Purpose Clinically, perturbations in the semaphorin signaling system have been associated with autism and epilepsy. The semaphorins have been implicated in guidance, migration, differentiation, and synaptic plasticity of neurons. The semaphorin 3F (Sema3F) ligand and its receptor, neuropilin 2 (NPN2) are highly expressed within limbic areas. NPN2 signaling may intimately direct the apposition of presynaptic and postsynaptic locations, facilitating the development and maturity of hippocampal synaptic function. To further understand the role of NPN2 signaling in central nevous system (CNS) plasticity, structural and functional alterations were assessed in NPN2 deficient mice. Methods In NPN2 deficient mice, we measured seizure susceptibility after kainic acid or pentylenetetrazol, neuronal excitability and synaptic throughput in slice preparations, principal and interneuron cell counts with immunocytochemical protocols, synaptosomal protein levels with immunoblots, and dendritic morphology with Golgi-staining. Results NPN2 deficient mice had shorter seizure latencies, increased vulnerability to seizure-related death, were more likely to develop spontaneous recurrent seizure activity after chemical challenge, and had an increased slope on input/output curves. Principal cell counts were unchanged, but GABA, parvalbumin, and neuropeptide Y interneuron cell counts were significantly reduced. Synaptosomal NPN2 protein levels and total number of GABAergic synapses were decreased in a gene dose-dependent fashion. CA1 pyramidal cells showed reduced dendritic length and complexity, as well as an increased number of dendritic spines. Discussion These data suggest the novel hypothesis that the Sema 3F signaling system's role in appropriate placement of subsets of hippocampal interneurons has critical downstream consequences for hippocampal function, resulting in a more seizure susceptible phenotype. PMID:18657176

Global characterization of copy number variants in epilepsy patients from whole genome sequencing

PubMed Central

Meloche, Caroline; Andrade, Danielle M.; Lafreniere, Ron G.; Gravel, Micheline; Spiegelman, Dan; Dionne-Laporte, Alexandre; Boelman, Cyrus; Hamdan, Fadi F.; Michaud, Jacques L.; Rouleau, Guy; Minassian, Berge A.; Bourque, Guillaume; Cossette, Patrick

2018-01-01

Epilepsy will affect nearly 3% of people at some point during their lifetime. Previous copy number variants (CNVs) studies of epilepsy have used array-based technology and were restricted to the detection of large or exonic events. In contrast, whole-genome sequencing (WGS) has the potential to more comprehensively profile CNVs but existing analytic methods suffer from limited accuracy. We show that this is in part due to the non-uniformity of read coverage, even after intra-sample normalization. To improve on this, we developed PopSV, an algorithm that uses multiple samples to control for technical variation and enables the robust detection of CNVs. Using WGS and PopSV, we performed a comprehensive characterization of CNVs in 198 individuals affected with epilepsy and 301 controls. For both large and small variants, we found an enrichment of rare exonic events in epilepsy patients, especially in genes with predicted loss-of-function intolerance. Notably, this genome-wide survey also revealed an enrichment of rare non-coding CNVs near previously known epilepsy genes. This enrichment was strongest for non-coding CNVs located within 100 Kbp of an epilepsy gene and in regions associated with changes in the gene expression, such as expression QTLs or DNase I hypersensitive sites. Finally, we report on 21 potentially damaging events that could be associated with known or new candidate epilepsy genes. Our results suggest that comprehensive sequence-based profiling of CNVs could help explain a larger fraction of epilepsy cases. PMID:29649218

Reexamining epilepsy-associated stigma: validation of the Stigma Scale of Epilepsy in Zambia

PubMed Central

Bowles, Ryan P.; Atadzhanov, Masharip; Mbewe, Edward; Haworth, Alan; Chomba, Elwyn; Birbeck, Gretchen L.

2017-01-01

Purpose Epilepsy-associated stigma is an important patient-centered outcome, yet quantification remains challenging. Jacoby’s 3-item Stigma Scale is commonly used to assess felt stigma among people with epilepsy (PWE) yet has ceiling effects. The Stigma Scale of Epilepsy (SSE) is a 24-item instrument that measures felt stigma among PWE and stigmatizing attitudes among others. If cross-culturally valid, the SSE may elucidate stigma determinants and provide an outcome measure for interventions. Methods We assessed the properties of the SSE in 102 Zambian PWE using exploratory and confirmatory item response theories and compared the latent traits assessed by the SSE to those assessed by Jacoby’s Stigma Scale. Differential item functioning based on forced disclosure of epilepsy was examined. Results The SSE yielded two latent traits—the first reflected difficulties faced by PWE; the second reflected emotions associated with epilepsy. Jacoby’s Stigma Scale was associated only with the first latent trait. Forced disclosure was associated with “worry” and “pity” that were associated with the second latent trait. Conclusions In Zambian PWE, the SSE captured two latent traits. One trait represents feelings associated with epilepsy, which is theorized as a substantial yet unmeasured part of stigma. The SSE performs well across cultures and may more comprehensively assess felt stigma than other instruments. Further validation is required to determine whether the SSE adequately assesses stigmatizing attitudes among people without epilepsy. PMID:25416086

When should temporal-lobe epilepsy be treated surgically?

PubMed

Spencer, Susan S

2002-10-01

Our current knowledge of mesial-temporal-lobe epilepsy (MTLE) is extensive, yet still insufficient to draw final conclusions on the optimal approach to its therapy. MTLE has been well characterised and can usually be identified with noninvasive studies including scalp electroencephalography (EEG) and video monitoring with ictal recording, magnetic resonance imaging, single-photon-emission computed tomography, positron emission tomography, neuropsychological assessment, and historical and clinical data. Sometimes, invasive EEG is needed to confirm mesial-temporal-lobe seizure onset, which, combined with the underlying pathological abnormality (the substrate) of mesial temporal sclerosis (hippocampal neuronal loss and gliosis), defines MTLE. This disorder is the most common refractory partial epilepsy, and also the one most often treated surgically, because medical treatment fails in 75% of cases, and surgical treatment succeeds in a similar percentage. Despite the recent publication of the first randomised trial of surgical treatment for MTLE, questions remain about the neurological consequences of both medical and surgical treatment, the ultimate gains in quality of life parameters, and the precise predictors of success. Long-term follow-up and analyses of multiple factors in large groups of contemporary patient populations will be necessary to fully answer the question, "is temporal lobe epilepsy a surgical disease?" Right now it should be considered one in most cases.

Emotional recognition in depressed epilepsy patients.

PubMed

Brand, Jesse G; Burton, Leslie A; Schaffer, Sarah G; Alper, Kenneth R; Devinsky, Orrin; Barr, William B

2009-07-01

The current study examined the relationship between emotional recognition and depression using the Minnesota Multiphasic Personality Inventory, Second Edition (MMPI-2), in a population with epilepsy. Participants were a mixture of surgical candidates in addition to those receiving neuropsychological testing as part of a comprehensive evaluation. Results suggested that patients with epilepsy reporting increased levels of depression (Scale D) performed better than those patients reporting low levels of depression on an index of simple facial recognition, and depression was associated with poor prosody discrimination. Further, it is notable that more than half of the present sample had significantly elevated Scale D scores. The potential effects of a mood-congruent bias and implications for social functioning in depressed patients with epilepsy are discussed.

"Txt"-induced seizures indicating reading epilepsy in the mobile phone age.

PubMed

Watson, Eloise; Lewis, Jill; Cutfield, Nick

2012-07-01

Reading epilepsy is a rare type of reflex epilepsy. The seizures often comprise facial twitching and alexia, but can be difficult to recognise and mistaken for non-epileptic events. Previous reports have identified reading of printed text, television and computer screens as inducing seizures, but hand-held digital media have not been implicated. We report a 44-year-old woman with difficulty using the text message function of her mobile phone with a long background of unrecognised reading-induced seizures. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-05-03

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.

Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder.

PubMed

Fehr, Stephanie; Wong, Kingsley; Chin, Richard; Williams, Simon; de Klerk, Nick; Forbes, David; Krishnaraj, Rahul; Christodoulou, John; Downs, Jenny; Leonard, Helen

2016-11-22

To investigate seizure outcomes and their relationships to genotype and functional abilities in individuals with the cyclin-dependent kinase-like-5 (CDKL5) disorder. Using the International CDKL5 Disorder Database, we identified 172 cases with a pathogenic CDKL5 mutation. We categorized individual mutations into 4 groups based on predicted structural and functional consequences. Negative binomial regression was used to model the linear association between current seizure rate and mutation group, current level of assistance required to walk 10 steps, and the highest level of expressive communication used to convey refusal or request. All but 3 (169/172) patients had a history of epilepsy. The median age at seizure onset was 6 weeks (range 1 week-1.5 years) and the median seizure rate at ascertainment was 2 per day (range 0-20 per day). After adjusting for walking ability and confounders including use or otherwise of polytherapy, seizure rate was lower in those with truncating mutations between aa172 and aa781 compared to those with no functional protein (incidence rate ratio [IRR] 0.57; 95% confidence interval [CI] 0.35-0.93). Ability to walk and use of spoken language were associated with lower rates of current seizures when compared to those with the least ability after adjusting for genotype (walking: IRR 0.62; 95% CI 0.39-0.99, communication: IRR 0.48; 95% CI 0.23-1.02). At a median age at questionnaire completion of 5 years, those previously treated with corticosteroids had more frequent seizures than those who have never been treated, whether or not there was a history of infantile spasms. Epilepsy is pervasive but not mandatory for the CDKL5 disorder. Genotype and functional abilities were related to seizure frequency, which appears refractory to antiepileptic drugs. © 2016 American Academy of Neurology.

Maternal reactions to a child with epilepsy: Depression, anxiety, parental attitudes and family functions.

PubMed

Pekcanlar Akay, Aynur; Hiz Kurul, Semra; Ozek, Handan; Cengizhan, Sevay; Emiroglu, Neslihan; Ellidokuz, Hulya

2011-08-01

The goal of this study was to investigate how the disease and treatment of epilepsy affected the psychological profile (depression and anxiety) of mothers whose children had epilepsy, as well as these mothers' attitudes towards their children and their family relationships. Both the case and control groups consisted of 50 children and their mothers. All mothers were asked to complete the Beck Depression Inventory, State-Trait Anxiety Inventory, Parental Attitude Research Instrument and Family Assessment Device. Mothers whose children had epilepsy scored significantly higher in depression and state anxiety compared to the mothers of the control group. The mothers of children diagnosed with epilepsy also failed to develop supportive and friendly relationships with their children. In addition, these mothers scored significantly higher in the Attitude of Hostility and Rejection, Marital Discordance and Authoritarian Attitude as compared to the mothers of the control group. This cross-sectional study demonstrated that, for the mothers of children who had epilepsy, the illness might have an adverse effect on their lives and their family relationships. Copyright © 2011 Elsevier B.V. All rights reserved.

Local Functional Connectivity as a Pre-Surgical Tool for Seizure Focus Identification in Non-Lesion, Focal Epilepsy

PubMed Central

Weaver, K. E.; Chaovalitwongse, W. A.; Novotny, E. J.; Poliakov, A.; Grabowski, T. G.; Ojemann, J. G.

2013-01-01

Successful resection of cortical tissue engendering seizure activity is efficacious for the treatment of refractory, focal epilepsy. The pre-operative localization of the seizure focus is therefore critical to yielding positive, post-operative outcomes. In a small proportion of focal epilepsy patients presenting with normal MRI, identification of the seizure focus is significantly more challenging. We examined the capacity of resting state functional MRI (rsfMRI) to identify the seizure focus in a group of four non-lesion, focal (NLF) epilepsy individuals. We predicted that computing patterns of local functional connectivity in and around the epileptogenic zone combined with a specific reference to the corresponding region within the contralateral hemisphere would reliably predict the location of the seizure focus. We first averaged voxel-wise regional homogeneity (ReHo) across regions of interest (ROIs) from a standardized, probabilistic atlas for each NLF subject as well as 16 age- and gender-matched controls. To examine contralateral effects, we computed a ratio of the mean pair-wise correlations of all voxels within a ROI with the corresponding contralateral region (IntraRegional Connectivity – IRC). For each subject, ROIs were ranked (from lowest to highest) on ReHo, IRC, and the mean of the two values. At the group level, we observed a significant decrease in the rank for ROI harboring the seizure focus for the ReHo rankings as well as for the mean rank. At the individual level, the seizure focus ReHo rank was within bottom 10% lowest ranked ROIs for all four NLF epilepsy patients and three out of the four for the IRC rankings. However, when the two ranks were combined (averaging across ReHo and IRC ranks and scalars), the seizure focus ROI was either the lowest or second lowest ranked ROI for three out of the four epilepsy subjects. This suggests that rsfMRI may serve as an adjunct pre-surgical tool, facilitating the identification of the seizure focus in focal epilepsy. PMID:23641233

Cognitive and mood effects of phenobarbital treatment in people with epilepsy in rural China: a prospective study.

PubMed

Ding, Ding; Zhang, Qing; Zhou, Dong; Lin, Weihong; Wu, Qingsheng; Sun, Jixin; Zhao, Qianhua; Yu, Peimin; Wang, Wenzhi; Wu, Jianzhong; Bell, Gail S; Kwan, Patrick; de Boer, Hanneke M; Li, Shichuo; Thompson, Pamela J; Hong, Zhen; Sander, Josemir W

2012-12-01

Phenobarbital is an effective treatment for epilepsy but concerns remain over its potential neurocognitive toxicity. This prospective study evaluated the effects of phenobarbital treatment on cognition and mood in people with epilepsy in rural China. We recruited 144 adults with convulsive seizures and 144 healthy controls from six sites in rural China. People with epilepsy were treated with phenobarbital monotherapy for 12 months. At baseline, and at 3, 6 and 12 months, cases and controls were evaluated with a battery of neuropsychological tests: the Mini-Mental State Examination, the Hamilton Depression Rating Scale, a digit span test, a verbal fluency test, an auditory verbal learning test and a digit cancellation test. Efficacy of phenobarbital treatment was evaluated at the end of follow-up for those with epilepsy. Cognitive test scores and mood ratings were available for 136 (94%) people with epilepsy and 137 (95%) controls at the 12 month follow-up. Both groups showed slightly improved performance on a number of neuropsychological measures. The people with epilepsy showed greater performance gains (p=0.012) in verbal fluency. Nine people with epilepsy complained of memory problems during the treatment period. In this study, phenobarbital was not found to have a major negative impact on cognitive function of people with convulsive seizures and some cognitive gains were observed, possibly due to improved seizure control.

Impaired development of intrinsic connectivity networks in children with medically intractable localization-related epilepsy.

PubMed

Ibrahim, George M; Morgan, Benjamin R; Lee, Wayne; Smith, Mary Lou; Donner, Elizabeth J; Wang, Frank; Beers, Craig A; Federico, Paolo; Taylor, Margot J; Doesburg, Sam M; Rutka, James T; Snead, O Carter

2014-11-01

Typical childhood development is characterized by the emergence of intrinsic connectivity networks (ICNs) by way of internetwork segregation and intranetwork integration. The impact of childhood epilepsy on the maturation of ICNs is, however, poorly understood. The developmental trajectory of ICNs in 26 children (8-17 years) with localization-related epilepsy and 28 propensity-score matched controls was evaluated using graph theoretical analysis of whole brain connectomes from resting-state functional magnetic resonance imaging (fMRI) data. Children with epilepsy demonstrated impaired development of regional hubs in nodes of the salience and default mode networks (DMN). Seed-based connectivity and hierarchical clustering analysis revealed significantly decreased intranetwork connections, and greater internetwork connectivity in children with epilepsy compared to controls. Significant interactions were identified between epilepsy duration and the expected developmental trajectory of ICNs, indicating that prolonged epilepsy may cause progressive alternations in large-scale networks throughout childhood. DMN integration was also associated with better working memory, whereas internetwork segregation was associated with higher full-scale intelligence quotient scores. Furthermore, subgroup analyses revealed the thalamus, hippocampus, and caudate were weaker hubs in children with secondarily generalized seizures, relative to other patient subgroups. Our findings underscore that epilepsy interferes with the developmental trajectory of brain networks underlying cognition, providing evidence supporting the early treatment of affected children. Copyright © 2014 Wiley Periodicals, Inc.

Executive functions and psychiatric symptoms in drug-refractory juvenile myoclonic epilepsy.

PubMed

Walsh, Jordana; Thomas, Rhys H; Church, Carla; Rees, Mark I; Marson, Anthony G; Baker, Gus A

2014-06-01

The pattern of executive dysfunction reported in juvenile myoclonic epilepsy (JME) resembles that of patients with cluster B personality disorders. This study examined whether executive dysfunction and maladaptive behavior reported in patients with JME are related. Sixty patients with drug-refractory JME were administered tests of intellect, memory, and executive dysfunction. Anxiety, depression, personality traits, impact of epilepsy, and perceived cognitive effects of antiepileptic drugs were measured. Half of the cohort exhibited moderate to severe anxiety symptoms. The patients performed most poorly on naming ability and inhibition switching. Duration of epilepsy exacerbated poor performance on inhibition switching. Females presented with pathological scores for neurotic and introvert traits and males for introvert traits. Abnormal personality traits and psychiatric disorders were associated with worse intellectual and executive functioning. People with extreme Eysenck Personality Scale - Brief Version (EPQ-BV) scores demonstrated the greatest level of executive impairment. Furthermore, the same degree of dysfunction was not seen in any individual with unremarkable EPQ-BV scores. This study indicates that specific patterns of executive dysfunction are related to maladaptive behavior in JME. Distinct behavioral patterns may be used to identify functional and anatomical differences between people with JME and for stratification to enable gene discovery. Copyright © 2014. Published by Elsevier Inc.

Specific binding of lacosamide to collapsin response mediator protein 2 (CRMP2) and direct impairment of its canonical function: implications for the therapeutic potential of lacosamide.

PubMed

Wilson, Sarah M; Khanna, Rajesh

2015-04-01

The novel antiepileptic drug lacosamide (LCM; SPM927, Vimpat®) has been heralded as having a dual-mode of action through interactions with both the voltage-gated sodium channel and the neurite outgrowth-promoting collapsin response mediator protein 2 (CRMP2). Lacosamide's ability to dampen neuronal excitability through the voltage-gated sodium channel likely underlies its efficacy in attenuating the symptoms of epilepsy (i.e., seizures). While the role of CRMP2 in epilepsy has not been well studied, given the proposed involvement of circuit reorganization in epileptogenesis, the ability of lacosamide to alter CRMP2 function may prove disease modifying. Recently, however, the validity of lacosamide's interaction with CRMP2 has come under scrutiny. In this review, we address the contradictory reports concerning the binding of lacosamide to CRMP2 as well as the ability of lacosamide to directly impact CRMP2 function. Additionally, we address similarly the contradicting reports regarding the potential disease-modifying effect of lacosamide on the development and progression of epilepsy. As the vast majority of antiepileptic drugs influences only the symptoms of epilepsy, the ability to hinder disease progression would be a major breakthrough in efforts to cure or prevent this debilitating syndrome.

Specific binding of lacosamide to collapsin response mediator protein 2 (CRMP2) and direct impairment of its canonical function: implications for the therapeutic potential of lacosamide

PubMed Central

Wilson, Sarah M.; Khanna, Rajesh

2014-01-01

The novel anti-epileptic drug lacosamide (LCM; SPM927, Vimpat®) has been heralded as having a dual-mode of action through interactions with both the voltage-gated sodium channel and the neurite outgrowth-promoting collapsin response mediator protein 2 (CRMP2). Lacosamide’s ability to dampen neuronal excitability through the voltage-gated sodium channel likely underlies its efficacy in attenuating the symptoms of epilepsy (i.e. seizures). While the role of CRMP2 in epilepsy has not been well-studied, given the proposed involvement of circuit reorganization in epileptogenesis, the ability of lacosamide to alter CRMP2 function may prove disease-modifying. Recently, however, the validity of lacosamide’s interaction with CRMP2 has come under scrutiny. In this review, we address the contradictory reports concerning the binding of lacosamide to CRMP2, as well as, the ability of lacosamide to directly impact CRMP2 function. Additionally, we address similarly contradicting reports regarding the potential disease-modifying effect of lacosamide on the development and progression of epilepsy. As the vast majority of anti-epileptic drugs influence only the symptoms of epilepsy, the ability to hinder disease progression would be a major breakthrough in efforts to cure or prevent this debilitating syndrome. PMID:24944082

Fluoxetine Restores Spatial Learning but Not Accelerated Forgetting in Mesial Temporal Lobe Epilepsy

ERIC Educational Resources Information Center

Barkas, Lisa; Redhead, Edward; Taylor, Matthew; Shtaya, Anan; Hamilton, Derek A.; Gray, William P.

2012-01-01

Learning and memory dysfunction is the most common neuropsychological effect of mesial temporal lobe epilepsy, and because the underlying neurobiology is poorly understood, there are no pharmacological strategies to help restore memory function in these patients. We have demonstrated impairments in the acquisition of an allocentric spatial task,…

Movement of Individuals with Complex Epilepsy from an Institution into the Community: Seizure Control and Functional Outcomes.

ERIC Educational Resources Information Center

Litzinger, M. J.; And Others

1993-01-01

This examination of the successful community placement of 15 medically fragile individuals with profound mental retardation and complex epilepsy found that simplification of anticonvulsants, early intervention for seizures, and improved staff education resulted in fewer seizures, decreases in emergency room visits for status seizures and…

Determining Surgical Candidacy in Temporal Lobe Epilepsy

PubMed Central

Mansouri, Alireza; Fallah, Aria; Valiante, Taufik A.

2012-01-01

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy that is amenable to surgical treatment. In the carefully selected patient, excellent seizure outcome can be achieved with minimal or no side effects from surgery. This may result in improved psychosocial functioning, achieving higher education, and maintaining or gaining employment. The objective of this paper is to discuss the surgical selection process of a patient with TLE. We define what constitutes a patient that has medically refractory TLE, describe the typical history and physical examination, and distinguish between mesial TLE and neocortical TLE. We then review the role of routine (ambulatory/sleep-deprived electroencephalography (EEG), video EEG, magnetic resonance imaging (MRI), neuropsychological testing, and Wada testing) and ancillary preoperative testing (positron emission tomography, single-photon emission computed tomography (SPECT), subtraction ictal SPECT correlated to MRI (SISCOM), magnetoencephalography, magnetic resonance spectroscopy, and functional MRI) in selecting surgical candidates. We describe the surgical options for resective epilepsy surgery in TLE and its commonly associated risks while highlighting some of the controversies. Lastly, we present teaching cases to illustrate the presurgical workup of patients with medically refractory TLE. PMID:22957238

Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy.

PubMed

Prayson, B E; Prayson, R A; Kubu, C S; Bingaman, W; Najm, I M; Busch, R M

2013-09-01

The objective of this retrospective study was to determine if dual pathology [DUAL - focal cortical dysplasia (FCD) and mesial temporal sclerosis (MTS)] in patients with left temporal lobe epilepsy is associated with greater risk for cognitive decline following temporal lobectomy than single pathology (MTS only). Sixty-three adults (Mage=36.5years, female: 52.4%) who underwent left anterior temporal lobectomy for treatment of epilepsy (MTS=28; DUAL=35) completed preoperative and postoperative neuropsychological evaluations. The base rate of dual pathology was 55.5%. Repeated measures ANOVAs yielded significant 2-way interactions (group×time) on most measures of language and memory with generally moderate effect sizes. Specifically, patients with MTS only demonstrated postoperative declines, while those with dual pathology remained unchanged or improved. Results suggest that dual pathology may be associated with better cognitive outcome following epilepsy surgery than MTS alone, possibly reflecting limited functionality of the resected tissue or intrahemispheric reorganization of function in the context of a developmental lesion. Copyright © 2013 Elsevier Inc. All rights reserved.

Cognitive and psychosocial effects of oxcarbazepine monotherapy in newly diagnosed partial epilepsy.

PubMed

Kim, Daeyoung; Seo, Ji-Hye; Joo, Eun Yeon; Lee, Hyang Woon; Shin, Won Chul; Hong, Seung Bong

2014-01-01

The aim of this study was to assess the effects of oxcarbazepine (OXC) on cognition and psychosocial difficulties in patients with new-onset partial epilepsy. Cognitive and psychosocial assessments were performed before and after 6 to 12 months of OXC monotherapy in 52 drug-naive patients (25 women; mean age, 31.1 years; SD, 12.1 years). Cognitive functions were evaluated with well-structured and validated tools. Mood, psychological distress, subjective handicap, and quality of life were also evaluated. Differences between baseline and after-treatment evaluation were compared and adjusted for possible confounders such as age, sex, seizure control, duration of epilepsy, assessment interval, and epileptogenic region. Mean assessment interval was 231.8 (range, 182-348) days, and mean (SD) OXC dose at retest was 693.8 (208.9) mg. The OXC was found to have no significant adverse effect on cognition. Furthermore, OXC monotherapy was not found to affect psychosocial difficulties, including psychological distress and subjective handicap. The results suggest that OXC monotherapy could be used to treat newly diagnosed partial epilepsy without adversely affecting cognitive and psychosocial functions.

Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent

PubMed Central

Farrell, Jordan S; Gaxiola-Valdez, Ismael; Wolff, Marshal D; David, Laurence S; Dika, Haruna I; Geeraert, Bryce L; Rachel Wang, X; Singh, Shaily; Spanswick, Simon C; Dunn, Jeff F; Antle, Michael C; Federico, Paolo; Teskey, G Campbell

2016-01-01

Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable. DOI: http://dx.doi.org/10.7554/eLife.19352.001 PMID:27874832

Genetic and epigenetic mechanisms of epilepsy: a review

PubMed Central

Chen, Tian; Giri, Mohan; Xia, Zhenyi; Subedi, Yadu Nanda; Li, Yan

2017-01-01

Epilepsy is a common episodic neurological disorder or condition characterized by recurrent epileptic seizures, and genetics seems to play a key role in its etiology. Early linkage studies have localized multiple loci that may harbor susceptibility genes to epilepsy, and mutational analyses have detected a number of mutations involved in both ion channel and nonion channel genes in patients with idiopathic epilepsy. Genome-wide studies of epilepsy have found copy number variants at 2q24.2-q24.3, 7q11.22, 15q11.2-q13.3, and 16p13.11-p13.2, some of which disrupt multiple genes, such as NRXN1, AUTS2, NLGN1, CNTNAP2, GRIN2A, PRRT2, NIPA2, and BMP5, implicated for neurodevelopmental disorders, including intellectual disability and autism. Unfortunately, only a few common genetic variants have been associated with epilepsy. Recent exome-sequencing studies have found some genetic mutations, most of which are located in nonion channel genes such as the LGI1, PRRT2, EFHC1, PRICKLE, RBFOX1, and DEPDC5 and in probands with rare forms of familial epilepsy, and some of these genes are involved with the neurodevelopment. Since epigenetics plays a role in neuronal function from embryogenesis and early brain development to tissue-specific gene expression, epigenetic regulation may contribute to the genetic mechanism of neurodevelopment through which a gene and the environment interacting with each other affect the development of epilepsy. This review focused on the analytic tools used to identify epilepsy and then provided a summary of recent linkage and association findings, indicating the existence of novel genes on several chromosomes for further understanding of the biology of epilepsy. PMID:28761347

A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.

PubMed

Amini, Elham; Rezaei, Mohsen; Mohamed Ibrahim, Norlinah; Golpich, Mojtaba; Ghasemi, Rasoul; Mohamed, Zahurin; Raymond, Azman Ali; Dargahi, Leila; Ahmadiani, Abolhassan

2015-08-01

Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.

Reduced Language Connectivity in Pediatric Epilepsy

PubMed Central

Leigh N., Sepeta; Louise J., Croft; Lauren A., Zimmaro; Elizabeth S., Duke; Virginia K., Terwilliger; Benjamin E., Yerys; Xiaozhen., You; Chandan J., Vaidya; William D., Gaillard; Madison M., Berl

2014-01-01

Objective Functional connectivity (FC) among language regions is decreased in adults with epilepsy compared to controls, but less is known about FC in children with epilepsy. We sought to determine if language FC is reduced in pediatric epilepsy, and examined clinical factors that associate with language FC in this population. Methods We assessed FC during an age-adjusted language task in children with left-hemisphere focal epilepsy (n=19) compared to controls (n=19). Time series data were extracted for three left ROIs and their right homologues: inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and Wernicke's area (WA) using SPM8. Associations between FC and factors such as cognitive performance, language dominance, and epilepsy duration were assessed. Results Children with epilepsy showed decreased interhemispheric connectivity compared to controls, particularly between core left language regions (IFG, WA) and their right hemisphere homologues, as well as decreased intrahemispheric right frontal FC. Increased intrahemispheric FC between left IFG and left WA was a positive predictor of language skills overall, and naming ability in particular. FC of language areas was not affected by language dominance, as the effects remained when only examining study participants with left language dominance. Overall FC did not differ according to duration of epilepsy or age of onset. Significance FC during a language task is reduced in children, similar to findings in adults. In specific, children with left focal epilepsy demonstrated decreased interhemispheric FC in temporal and frontal language connections and decreased intrahemispheric right frontal FC. These differences were present near the onset of epilepsy. Greater FC between left language centers is related to better language ability. Our results highlight that connectivity of language areas has a developmental pattern and is related to cognitive ability. PMID:25516399

Unique and shared validity of the "Wechsler logical memory test", the "California verbal learning test", and the "verbal learning and memory test" in patients with epilepsy.

PubMed

Helmstaedter, Christoph; Wietzke, Jennifer; Lutz, Martin T

2009-12-01

This study was set-up to evaluate the construct validity of three verbal memory tests in epilepsy patients. Sixty-one consecutively evaluated patients with temporal lobe epilepsy (TLE) or extra-temporal epilepsy (E-TLE) underwent testing with the verbal learning and memory test (VLMT, the German equivalent of the Rey auditory verbal learning test, RAVLT); the California verbal learning test (CVLT); the logical memory and digit span subtests of the Wechsler memory scale, revised (WMS-R); and testing of intelligence, attention, speech and executive functions. Factor analysis of the memory tests resulted in test-specific rather than test over-spanning factors. Parameters of the CVLT and WMS-R, and to a much lesser degree of the VLMT, were highly correlated with attention, language function and vocabulary. Delayed recall measures of logical memory and the VLMT differentiated TLE from E-TLE. Learning and memory scores off all three tests differentiated mesial temporal sclerosis from other pathologies. A lateralization of the epilepsy was possible only for a subsample of 15 patients with mesial TLE. Although the three tests provide overlapping indicators for a temporal lobe epilepsy or a mesial pathology, they can hardly be taken in exchange. The tests have different demands on semantic processing and memory organization, and they appear differentially sensitive to performance in non-memory domains. The tests capability to lateralize appears to be poor. The findings encourage the further discussion of the dependency of memory outcomes on test selection.

Emotion recognition and social cognition in temporal lobe epilepsy and the effect of epilepsy surgery.

PubMed

Amlerova, Jana; Cavanna, Andrea E; Bradac, Ondrej; Javurkova, Alena; Raudenska, Jaroslava; Marusic, Petr

2014-07-01

The abilities to identify facial expression from another person's face and to attribute mental states to others refer to preserved function of the temporal lobes. In the present study, we set out to evaluate emotion recognition and social cognition in presurgical and postsurgical patients with unilateral refractory temporal lobe epilepsy (TLE). The aim of our study was to investigate the effects of TLE surgery and to identify the main risk factors for impairment in these functions. We recruited 30 patients with TLE for longitudinal data analysis (14 with right-sided and 16 with left-sided TLE) and 74 patients for cross-sectional data analysis (37 with right-sided and 37 with left-sided TLE) plus 20 healthy controls. Besides standard neuropsychological assessment, we administered an analog of the Ekman and Friesen test and the Faux Pas Test to assess emotion recognition and social cognition, respectively. Both emotion recognition and social cognition were impaired in the group of patients with TLE, irrespective of the focus side, compared with healthy controls. The performance in both tests was strongly dependent on the intelligence level. Beyond intelligence level, earlier age at epilepsy onset, longer disease duration, and history of early childhood brain injury predicted social cognition problems in patients with TLE. Epilepsy surgery within the temporal lobe seems to have neutral effect on patients' performances in both domains. However, there are a few individual patients who appear to be at risk of postoperative decline, even when seizure freedom is achieved following epilepsy surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

β1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function

PubMed Central

Kruger, Larisa C.; O'Malley, Heather A.; Hull, Jacob M.; Kleeman, Amanda; Patino, Gustavo A.

2016-01-01

Voltage-gated sodium channel (VGSC) β subunits signal through multiple pathways on multiple time scales. In addition to modulating sodium and potassium currents, β subunits play nonconducting roles as cell adhesion molecules, which allow them to function in cell–cell communication, neuronal migration, neurite outgrowth, neuronal pathfinding, and axonal fasciculation. Mutations in SCN1B, encoding VGSC β1 and β1B, are associated with epilepsy. Autosomal-dominant SCN1B-C121W, the first epilepsy-associated VGSC mutation identified, results in genetic epilepsy with febrile seizures plus (GEFS+). This mutation has been shown to disrupt both the sodium-current-modulatory and cell-adhesive functions of β1 subunits expressed in heterologous systems. The goal of this study was to compare mice heterozygous for Scn1b-C121W (Scn1b+/W) with mice heterozygous for the Scn1b-null allele (Scn1b+/−) to determine whether the C121W mutation results in loss-of-function in vivo. We found that Scn1b+/W mice were more susceptible than Scn1b+/− and Scn1b+/+ mice to hyperthermia-induced convulsions, a model of pediatric febrile seizures. β1-C121W subunits are expressed at the neuronal cell surface in vivo. However, despite this, β1-C121W polypeptides are incompletely glycosylated and do not associate with VGSC α subunits in the brain. β1-C121W subcellular localization is restricted to neuronal cell bodies and is not detected at axon initial segments in the cortex or cerebellum or at optic nerve nodes of Ranvier of Scn1bW/W mice. These data, together with our previous results showing that β1-C121W cannot participate in trans-homophilic cell adhesion, lead to the hypothesis that SCN1B-C121W confers a deleterious gain-of-function in human GEFS+ patients. SIGNIFICANCE STATEMENT The mechanisms underlying genetic epilepsy syndromes are poorly understood. Closing this gap in knowledge is essential to the development of new medicines to treat epilepsy. We have used mouse models to understand the mechanism of a mutation in the sodium channel gene SCN1B linked to genetic epilepsy with febrile seizures plus. We report that sodium channel β1 subunit proteins encoded by this mutant gene are expressed at the surface of neuronal cell bodies; however, they do not associate with the ion channel complex nor are they transported to areas of the axon that are critical for proper neuronal firing. We conclude that this disease-causing mutation is not simply a loss-of-function, but instead results in a deleterious gain-of-function in the brain. PMID:27277800

The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations.

PubMed

Holder, J Lloyd; Quach, Michael M

2016-10-01

The coincidence of autism with epilepsy is 27% in those individuals with intellectual disability. 1 Individuals with loss-of-function mutations in SHANK3 have intellectual disability, autism, and variably, epilepsy. 2-5 The spectrum of seizure semiologies and electroencephalography (EEG) abnormalities has never been investigated in detail. With the recent report that SHANK3 mutations are present in approximately 2% of individuals with moderate to severe intellectual disabilities and 1% of individuals with autism, determining the spectrum of seizure semiologies and electrographic abnormalities will be critical for medical practitioners to appropriately counsel the families of patients with SHANK3 mutations. A retrospective chart review was performed of all individuals treated at the Blue Bird Circle Clinic for Child Neurology who have been identified as having either a chromosome 22q13 microdeletion encompassing SHANK3 or a loss-of-function mutation in SHANK3 identified through whole-exome sequencing. For each subject, the presence or absence of seizures, seizure semiology, frequency, age of onset, and efficacy of therapy were determined. Electroencephalography studies were reviewed by a board certified neurophysiologist. Neuroimaging was reviewed by both a board certified pediatric neuroradiologist and child neurologist. There is a wide spectrum of seizure semiologies, frequencies, and severity in individuals with SHANK3 mutations. There are no specific EEG abnormalities found in our cohort, and EEG abnormalities were present in individuals diagnosed with epilepsy and those without history of a clinical seizure. All individuals with a mutation in SHANK3 should be evaluated for epilepsy due to the high prevalence of seizures in this population. The most common semiology is atypical absence seizure, which can be challenging to identify due to comorbid intellectual disability in individuals with SHANK3 mutations; however, no consistent seizure semiology, neuroimaging findings, or EEG findings were present in the majority of individuals with SHANK3 mutations. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

EEG abnormalities and epilepsy in autistic spectrum disorders: clinical and familial correlates.

PubMed

Ekinci, Ozalp; Arman, Ayşe Rodopman; Işik, Uğur; Bez, Yasin; Berkem, Meral

2010-02-01

Our aim was to examine the characteristics of EEG findings and epilepsy in autistic spectrum disorders (ASD) and the associated clinical and familial risk factors. Fifty-seven children (86% male) with ASD, mean age 82+/-36.2 months, were included in the study. Thirty-nine (68.4%) children had the diagnosis of autism, 15 (26.3%) had Pervasive Developmental Disorder Not Otherwise Specified, and 3 (5.3%) had high-functioning autism. One hour of sleep and/or awake EEG recordings was obtained for each child. All patients were evaluated with respect to clinical and familial characteristics and with the Childhood Autism Rating Scale, the Autism Behavior Checklist, and the Aberrant Behavior Checklist. The frequency of interictal epileptiform EEG abnormalities (IIEAs) was 24.6% (n=14), and the frequency of epilepsy was 14.2% (n=8). IIEAs were associated with a diagnosis of epilepsy (P=0.0001), Childhood Autism Rating Scale Activity scores (P=0.047), and a history of asthma and allergy (P=0.044). Epilepsy was associated with a family history of epilepsy (P=0.049) and psychiatric problems in the mother during pregnancy (P=0.0026). Future studies with larger samples will help to clarify the possible associations of epilepsy/IIEAs with asthma/allergy, hyperactivity, and familial factors in ASD. (c) 2009 Elsevier Inc. All rights reserved.

The Pharmacological Basis of Cannabis Therapy for Epilepsy.

PubMed

Reddy, Doodipala Samba; Golub, Victoria M

2016-04-01

Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Surgical Treatment of Pediatric Epileptic Encephalopathies

PubMed Central

Fridley, J.; Reddy, G.; Curry, D.; Agadi, S.

2013-01-01

Pediatric epileptiform encephalopathies are a group of neurologically devastating disorders related to uncontrolled ictal and interictal epileptic activity, with a poor prognosis. Despite the number of pharmacological options for treatment of epilepsy, many of these patients are drug resistant. For these patients with uncontrolled epilepsy, motor and/or neuropsychological deterioration is common. To prevent these secondary consequences, surgery is often considered as either a curative or a palliative option. Magnetic resonance imaging to look for epileptic lesions that may be surgically treated is an essential part of the workup for these patients. Many surgical procedures for the treatment of epileptiform encephalopathies have been reported in the literature. In this paper the evidence for these procedures for the treatment of pediatric epileptiform encephalopathies is reviewed. PMID:24288601

Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy

PubMed Central

Rudolf, Gabrielle; Lesca, Gaetan; Mehrjouy, Mana M; Labalme, Audrey; Salmi, Manal; Bache, Iben; Bruneau, Nadine; Pendziwiat, Manuela; Fluss, Joel; de Bellescize, Julitta; Scholly, Julia; Møller, Rikke S; Craiu, Dana; Tommerup, Niels; Valenti-Hirsch, Maria Paola; Schluth-Bolard, Caroline; Sloan-Béna, Frédérique; Helbig, Katherine L; Weckhuysen, Sarah; Edery, Patrick; Coulbaut, Safia; Abbas, Mohamed; Scheffer, Ingrid E; Tang, Sha; Myers, Candace T; Stamberger, Hannah; Carvill, Gemma L; Shinde, Deepali N; Mefford, Heather C; Neagu, Elena; Huether, Robert; Lu, Hsiao-Mei; Dica, Alice; Cohen, Julie S; Iliescu, Catrinel; Pomeran, Cristina; Rubenstein, James; Helbig, Ingo; Sanlaville, Damien; Hirsch, Edouard; Szepetowski, Pierre

2016-01-01

Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5–10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures. PMID:27352968

Differences in Memory Functioning between Children with Attention-Deficit/Hyperactivity Disorder and/or Focal Epilepsy

PubMed Central

Lee, Sylvia E.; Kibby, Michelle Y.; Cohen, Morris J.; Stanford, Lisa; Park, Yong; Strickland, Suzanne

2016-01-01

Prior research has shown that attention-deficit/hyperactivity disorder (ADHD) and epilepsy are frequently comorbid and that both disorders are associated with various attention and memory problems. Nonetheless, limited research has been conducted comparing the two disorders in one sample to determine unique versus shared deficits. Hence, we investigated differences in working memory and short-term and delayed recall between children with ADHD, focal epilepsy of mixed foci, comorbid ADHD/epilepsy and controls. Participants were compared on the Core subtests and the Picture Locations subtest of the Children’s Memory Scale (CMS). Results indicated that children with ADHD displayed intact verbal working memory and long-term memory (LTM), as well as intact performance on most aspects of short-term memory (STM). They performed worse than controls on Numbers Forward and Picture Locations, suggesting problems with focused attention and simple span for visual-spatial material. Conversely, children with epilepsy displayed poor focused attention and STM regardless of modality assessed, which affected encoding into LTM. The only loss over time was found for passages (Stories). Working memory was intact. Children with comorbid ADHD/epilepsy displayed focused attention and STM/LTM problems consistent with both disorders, having the lowest scores across the four groups. Hence, focused attention and visual-spatial span appear to be affected in both disorders, whereas additional STM/encoding problems are specific to epilepsy. Children with comorbid ADHD/epilepsy have deficits consistent with both disorders, with slight additive effects. This study suggests that attention and memory testing should be a regular part of the evaluation of children with epilepsy and ADHD. PMID:26156331

[Formula: see text]Differences in memory functioning between children with attention-deficit/hyperactivity disorder and/or focal epilepsy.

PubMed

Lee, Sylvia E; Kibby, Michelle Y; Cohen, Morris J; Stanford, Lisa; Park, Yong; Strickland, Suzanne

2016-01-01

Prior research has shown that attention-deficit/hyperactivity disorder (ADHD) and epilepsy are frequently comorbid and that both disorders are associated with various attention and memory problems. Nonetheless, limited research has been conducted comparing the two disorders in one sample to determine unique versus shared deficits. Hence, we investigated differences in working memory (WM) and short-term and delayed recall between children with ADHD, focal epilepsy of mixed foci, comorbid ADHD/epilepsy and controls. Participants were compared on the Core subtests and the Picture Locations subtest of the Children's Memory Scale (CMS). Results indicated that children with ADHD displayed intact verbal WM and long-term memory (LTM), as well as intact performance on most aspects of short-term memory (STM). They performed worse than controls on Numbers Forward and Picture Locations, suggesting problems with focused attention and simple span for visual-spatial material. Conversely, children with epilepsy displayed poor focused attention and STM regardless of the modality assessed, which affected encoding into LTM. The only loss over time was found for passages (Stories). WM was intact. Children with comorbid ADHD/epilepsy displayed focused attention and STM/LTM problems consistent with both disorders, having the lowest scores across the four groups. Hence, focused attention and visual-spatial span appear to be affected in both disorders, whereas additional STM/encoding problems are specific to epilepsy. Children with comorbid ADHD/epilepsy have deficits consistent with both disorders, with slight additive effects. This study suggests that attention and memory testing should be a regular part of the evaluation of children with epilepsy and ADHD.

Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy

PubMed Central

Sivakumar, Siddharth S.; Namath, Amalia G.; Tuxhorn, Ingrid E.; Lewis, Stephen J.

2016-01-01

We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy. PMID:26888110

Written accounts of living with epilepsy: A thematic analysis.

PubMed

Rawlings, Gregg H; Brown, Ian; Stone, Brendan; Reuber, Markus

2017-07-01

This study examines the subjective experience of living with epilepsy by thematically analyzing participants' written accounts of their condition. Writing is seen as an individual act allowing for private exploration, reflection and expression of thoughts and feelings. Participants (n=20) were recruited from a United Kingdom hospital and from membership-led organizations for individuals living with seizures. Participants were asked to produce four pieces of writing: 1) about their thoughts and feelings about their condition; 2) a letter to their condition; 3) a letter to their younger self; and 4) about a personal value. All writings were analyzed thematically using a theory- and data-driven approach. Five main-themes and 22 sub-themes emerged from the data. Theme 1: 'seizure onset' demonstrated that the development of seizures and subsequent diagnosis was an important event that could change an individuals' identity. Theme 2: 'seizure symptoms' revealed participants externalized their seizures as an intrusive agent with a constant presence in their lives. Theme 3: 'treatment and outcome' reflected medication as an essential means to controlling seizures with subsequent side effects being perceived as a compromise. Theme 4: 'living with epilepsy' explored the consequences of the condition including restrictions and stigma. Theme 5: 'displays of coping' demonstrated that, for the most part, participants were keen to present themselves as living well with epilepsy. The results add to the growing research applying qualitative methodologies to investigate the phenomenology of epilepsy. Qualitative research can improve our understanding and awareness of the condition, as well as inform clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Epilepsy in patients with primary brain tumors: The impact on mood, cognition, and HRQOL.

PubMed

Rahman, Z; Wong, C H; Dexter, M; Olsson, G; Wong, M; Gebsky, V; Nahar, N; Wood, A; Byth, K; King, M; Bleasel, A B

2015-07-01

A primary brain tumor (PBT) is often a fatal disease of the nervous system and has a serious impact on health-related quality of life (HRQOL). Presence of epilepsy and adverse reactions from tumor and epilepsy treatments may cause additional decline in HRQOL. We aimed to study the impact of epileptic seizures on cognition, mood, and HRQOL in patients with brain tumor-related epilepsy. Patients were grouped on an ordinal scale according to epilepsy burden from none to severe based on the presence of epileptic seizures and seizure frequency: L1, no epilepsy; L2, with epilepsy, seizure-free in the last 6 months with antiepileptic drugs; and L3, with epilepsy, at least one seizure in the last 6 months with AEDs. Health-related quality of life was measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Quality of Life in Epilepsy-31 (QOLIE-31) tools, cognition by the Montreal Cognitive Assessment (MoCA) tool and Frontal Assessment Battery (FAB), mood by the Hospital Anxiety and Depression Scale (HADS), activities of daily living (ADLs) by the Barthel Index (BI), and performance status by the Karnofsky Performance Status (KPS) scale in patients with primary brain tumors at least one month following neurosurgery with or without radiotherapy and chemotherapy. Eighty-one patients with a diagnosis of primary brain tumors were recruited. Sixty-eight percent of patients were diagnosed with primary brain tumor-related epilepsy, 50.61% patients had cognitive impairment, 33% had abnormal scores in the anxiety scale, and 34% had abnormal scores in the depression scale. There were no statistically significant differences in these scores among L1, L2, and L3 groups. There were statistically significant differences in duration of disease and KPS and BI scores between L1 and L3 groups. The L3 group has significantly longer duration of disease and scored low in both the BI and KPS scale when compared to the L1 group. All patients with primary brain tumors scored significantly low in FACT-Br 'physical well-being' (PWB) and 'emotional well-being' (EWB) and high in 'social well-being' (SWB) when compared to healthy controls. When scores of each group were individually compared to healthy controls, the L3 group showed the lowest scores in PWB, EWB, and 'functional well-being'. In SWB, L1 and L2 groups showed statistically significantly high scores when compared to normative data. The QOLIE-31 applied to groups with epilepsy showed statistically significantly lower scores in the L3 group when compared to the L2 group in 'cognitive' and 'social functioning' domains. On multivariate analysis, both poor performance status and frequency of seizures were found to be independent risk factors for poor HRQOL when FACT-Br mean scores were compared. Level of seizures was found to be an independent risk factor for poor HRQOL when QOLIE-31 scores were compared between L2 and L3 groups. Presence of brain tumors could be attributed to cognitive impairment irrespective of the presence of epilepsy in our cohort. High seizure burden is an independent risk factor for poor HRQOL in patients with primary brain tumors. The QOLIE-31 is a more sensitive tool than the FACT-Br because of the presence of a seizure-related questionnaire. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Quality of life in children with epilepsy.

PubMed

Aggarwal, Anju; Datta, Varsha; Thakur, L C

2011-11-11

Quality of life was assessed in 108 epileptic children (6-15 years) using a hindi translation of Quality of Life in Children with Epilepsy (QOLCE) questionnaire. The questionnaire consist of 76 items with 16 subscales covering five domains of life: physical function, social function, cognition, emotional and behavioral well being. Overall score was 62.62±21.32. Chronbachs-a for all 13 multi-item subscales was above 0.70, indicating good internal consistency and reliability. Pearson correlation revealed good construct validity. Overall quality of life was affected by age, type of epilepsy, seizure frequency and maternal education (P<0.05). Energy levels, language and attention (P<0.05) were better in older children whereas younger children had better self esteem and lower levels of anxiety. Seizure frequency compromised all fields except stigma, attention, and energy levels (P>0.05).

[Neuropsychological alterations are frequent in rolandic epilepsy and its atypical developments].

PubMed

Pesantez-Rios, G; Martinez-Bermejo, A; Pesantez-Cuesta, G

2016-08-01

Rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes is called benign because its seizures are usually favourable and due to the spontaneous normalisation of the electroencephalogram on reaching puberty. Nevertheless, evidence has been found of the impact on cognitive development with the presence of heterogeneous cognitive deficits, especially related to persistent intercritical discharges during non-REM sleep. The aim of this study is to examine the epileptogenic networks involved in the neuropsychological disorders of this pathology. A common feature of the atypical developments is persistent epileptic activity during slow sleep, which plays an important role in the development of the neurocognitive deficits that are associated to this pathology. Factors such as the age at onset of the epilepsy, the onset of the atypical development, the location of the interictal discharges and the continuous epileptic activity during sleep that persists for more than two years can trigger changes in the functioning of the neurocognitive networks. This may result in deficits in the neuropsychological functions, which may even be irreversible. A close clinical and electroencephalographic follow-up is necessary. Moreover, formal neuropsychological studies must be conducted as of the onset of benign childhood epilepsy with centrotemporal spikes. This is even more necessary in cases in which there is an obvious atypical development in order to detect and prevent the neuropsychological deficits before they establish themselves on a definitive basis.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

[Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

PubMed

Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

2016-01-01

The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

Does ketogenic diet have any negative effect on cardiac systolic and diastolic functions in children with intractable epilepsy?: One-year follow-up results.

PubMed

Ozdemir, Rahmi; Kucuk, Mehmet; Guzel, Orkide; Karadeniz, Cem; Yilmaz, Unsal; Mese, Timur

2016-10-01

The ketogenic diet (KD) has been referred to as an "effective therapy with side effects" for children with intractable epilepsy. Among the most recognized adverse effects, there are cardiac conduction abnormalities, vascular and myocardial dysfunction. However, very limited and controversial data are available regarding the effects of the KD on cardiac functions. We sought to analyze the mid-term effect of ketogenic diet on cardiac functions in patients with intractable epilepsy who received a ketogenic diet for at least 12months using conventional and relatively new imaging techniques. This prospective study included 61 patients with intractable epilepsy who received ketogenic diet for at least 12months. Clinical examinations, serum carnitine and selenium levels as well as electrocardiographic and echocardiographic examinations were scheduled prior to the procedure and at 1, 3, 6 and 12months. We utilized two-dimensional, M-mode, colored Doppler, spectral Doppler and pulsed wave tissue Doppler imaging techniques to investigate ventricular systolic and diastolic functions of this subgroup of patients. In our study, there was no significant difference after 1year of KD therapy compared to baseline values-except a significantly decreased A wave velocity-in terms of pulse wave Doppler echocardiographic measurements of the diastolic function. The tissue Doppler measurements obtained from the lateral wall of tricuspide and mitral annuli were not different at baseline and at month 12 of the treatment, as well. The ketogenic diet appears to have no disturbing effect on ventricular functions in epileptic children in the midterm. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: a case-control study.

PubMed

Coppola, Giangennaro; Natale, Francesco; Torino, Annarita; Capasso, Rosanna; D'Aniello, Alfredo; Pironti, Erica; Santoro, Elena; Calabrò, Raffaele; Verrotti, Alberto

2014-04-01

The present study aimed to assess the impact of the ketogenic diet on arterial morphology and endothelial function of the big vessels of the neck and on cardiac diastolic function, in a cohort of epileptic children and young adults treated with the ketogenic diet. Patients were recruited based on the following inclusion criteria: (1) patients who were or had been on the ketogenic diet for a time period of at least six months. Each patient underwent measurement of carotid intima media thickness, carotid artery stiffness, echocardiography, and diastolic function assessment. Patients with drug resistant epilepsy, matched for number, age and sex and never treated with ketogenic diet, were recruited as controls. The population study was composed by 43 epilepsy patients (23 males), aged between 19 months and 31 years (mean 11 years). Twenty-three patients were or had been treated with ketogenic diet, and 20 had never been on it (control group). Subjects treated with the ketogenic diet had higher arterial stiffness parameters, including AIx and β-index and higher serum levels of cholesterol or triglycerides compared to those who had never been on the diet (control group) (p<0.001). Arterial stiffness is increased in children and young adults treated with the ketogenic diet, before the increase of the intima media thickness. This supports that arterial stiffness is an early marker of vascular damage. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Neuropsychological functioning in children with temporal lobe epilepsy and hippocampal atrophy without mesial temporal sclerosis: a distinct clinical entity?

PubMed

Schmidt, Charlotte S M; Lassonde, Maryse; Gagnon, Louise; Sauerwein, Catherine H; Carmant, Lionel; Major, Philippe; Paquette, Natacha; Lepore, Franco; Gallagher, Anne

2015-03-01

Unilateral hippocampal atrophy (HA) is considered as a precursor of mesial temporal sclerosis (MTS) in some patients with temporal lobe epilepsy. However, in other cases, it has been suggested that HA without MTS may constitute a distinct epileptic entity. Hippocampal atrophy without MTS was defined as HA without T2-weighted hyperintensity, loss of internal architecture, or associated lesion seen on the MRI data. To date, no study has focused on the cognitive pattern of children with epilepsy with HA without MTS. The objectives of the present study were to characterize the cognitive profile of these children and to investigate the presence (or the absence) of material-specific memory deficits in these young patients, as found in patients with MTS. Toward this end, 16 young patients with epilepsy with either left or right HA without MTS completed a set of neuropsychological tests, assessing overall intelligence, verbal memory and nonverbal memory, and some aspects of attention and executive functions. Results showed normal intellectual functioning without specific memory deficits in these patients. Furthermore, comparison between patients with left HA and patients with right HA failed to reveal a material-specific lateralized memory pattern. Instead, attention and executive functions were found to be impaired in most patients. These results suggest that HA may constitute a distinct epileptic entity, and this information may help health-care providers initiate appropriate and timely interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

Practitioner Review: Use of Antiepileptic Drugs in Children

ERIC Educational Resources Information Center

Guerrini, Renzo; Parmeggiani, Lucio

2006-01-01

Background: The aim in treating epilepsy is to minimise or control seizures with full respect of quality-of-life issues, especially of cognitive functions. Optimal treatment first demands a correct recognition of the major type of seizures, followed by a correct diagnosis of the type of epilepsy or of the specific syndrome. Methods: Review of data…

SPECT and fMRI Analysis of Motor and Cognitive Indices of Early Parkinson’s Disease: The Relationship of Striatal Dopamine and Cortical Function

DTIC Science & Technology

2005-09-01

MC. Predicting white matter targets for direct neurostimulation therapy. Epilepsy Research 2010;PMID:20728313. Shukla D, Kaiser CC, Stebbins GT...Predicting white matter targets for direct neurostimulation therapy. Epilepsy Research 2010;PMID:20728313. Shukla D, Kaiser CC, Stebbins GT, Feinstein

Predictors and Course of Medically Intractable Epilepsy in Young Children Presenting Before 36 Months of Age: A Retrospective, Population-Based Study

PubMed Central

Wirrell, Elaine; Wong-Kisiel, Lily; Mandrekar, Jay; Nickels, Katherine

2012-01-01

Purpose To determine the prevalence and identify predictors of medical intractability in children presenting with epilepsy prior to 36 months of age, and to assess the impact of medical intractability on long-term mortality and intellectual function. Methods Children with newly-diagnosed epilepsy prior to 36 months between 1980–2009 while resident in Olmsted County, MN were identified. Medical records were reviewed to collect epilepsy specific variables and long-term outcome data. Medically intractable epilepsy was defined as either (1) seizures greater than every 6 months at final follow-up and failure of two or more antiepileptic drugs for lack of efficacy, or (2) having undergone epilepsy surgery after failure of two or more antiepileptic drugs. Key Findings One hundred and twenty seven children with new-onset epilepsy were identified and followed for a median of 78 months. Medically intractable seizures occurred in 35%, and significant predictors on multivariate analysis were age ≤12 months at diagnosis (odds ratio [OR] 6.76, 95% confidence interval [CI] 2.00, 22.84, p=0.002), developmental delay at initial diagnosis of epilepsy (OR 20.03, 95% CI 3.49, 114.83, p=0.0008 ), neuroimaging abnormality (OR 6.48, 95% CI 1.96, 21.40, p=0.002) and focal slowing on initial EEG (OR 5.33, 95% CI 1.14, 24.88, p=0.03). Medical intractability occurred early in the course in most children, being seen in 61% by one year, and 93% by five years after initial diagnosis. Mortality was higher (20% vs 0%, p<0.001) and intellectual outcome poorer (p<0.001) if epilepsy was medically intractable. Significance One third of children presenting with epilepsy before 36 months will be medically intractable and significant predictors are identified. Medically intractable epilepsy is associated with increased mortality risk and significant intellectual disability. PMID:22738069

Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

PubMed Central

Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.

2015-01-01

Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID:25552301

Women with epilepsy: clinically relevant issues

PubMed Central

Bangar, Santosh; Shastri, Abhishek; El-Sayeh, Hany; Cavanna, Andrea E.

2016-01-01

Summary Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (including bone health), and mental health aspects. Awareness of these gender-specific issues and implementation/adaptation of effective interventions for WWE results in significantly improved health-related quality of life in this patient population. PMID:27678205

A Neuropsychological Profile for Agenesis of the Corpus Callosum? Cognitive, Academic, Executive, Social, and Behavioral Functioning in School-Age Children.

PubMed

Siffredi, Vanessa; Anderson, Vicki; McIlroy, Alissandra; Wood, Amanda G; Leventer, Richard J; Spencer-Smith, Megan M

2018-05-01

Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445-455).

Priorities in pediatric epilepsy research

PubMed Central

Baca, Christine B.; Loddenkemper, Tobias; Vickrey, Barbara G.; Dlugos, Dennis

2013-01-01

The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of patient-centered and patient-driven mandates for developing best practices in care, particularly for epilepsy beginning under age 3 years. The workshop brought together parents, representatives of voluntary advocacy organizations, physicians, allied health professionals, researchers, and administrators to identify priority areas for pediatric epilepsy care and research including implementation and testing of interventions designed to improve care processes and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure control but also behavioral, academic, and social functioning; 2) early and accurate diagnosis and optimal treatment; 3) role and involvement of parents (communication and shared decision-making); and 4) integration of school and community organizations with epilepsy care delivery. Key factors influencing pediatric epilepsy care included the child's impairments and seizure presentation, parents, providers, the health care system, and community systems. Care was represented as a sequential process from initial onset of seizures to referral for comprehensive evaluation when needed. We considered an alternative model in which comprehensive care would be utilized from onset, proactively, rather than reactively after pharmacoresistance became obvious. Barriers, including limited levels of evidence about many aspects of diagnosis and management, access to care—particularly epilepsy specialty and behavioral health care—and implementation, were identified. Progress hinges on coordinated research efforts that systematically address gaps in knowledge and overcoming barriers to access and implementation. The stakes are considerable, and the potential benefits for reduced burden of refractory epilepsy and lifelong disabilities may be enormous. PMID:23966254

Modulation of autonomic activity in neurological conditions: Epilepsy and Tourette Syndrome

PubMed Central

Nagai, Yoko

2015-01-01

This manuscript considers the central but neglected role of the autonomic nervous system in the expression and control of seizures in epilepsy (small) and tics in Tourette Syndrome (TS). In epilepsy, consideration of autonomic involvement is typically confined to differential diagnoses (e.g., syncope), or in relation to Sudden Unexpected Death in Epilepsy (SUDEP). Investigation is more limited in Tourette Syndrome. The role of the autonomic nervous system in the generation and prevention of epileptic seizures is largely overlooked. Emotional stimuli such as anxiety and stress are potent causes of seizures and tic activity in epilepsy and TS, respectively. This manuscript will describe a possible neural mechanism by which afferent autonomic projections linked to cognition and behavior influence central thalamo-cortical regulation, which appears to be an important means for controlling both seizure and tic activity. It also summarizes the link between the integrity of the default mode network and autonomic regulation in patients with epilepsy as well as the link between impaired motor control and autonomic regulation in patients with TS. Two neurological conditions; epilepsy and TS were chosen, as seizures and tics represent parameters that can be easily measured to investigate influences of autonomic functions. The EDA biofeedback approach is anticipated to gain a strong position within the next generation of treatment for epilepsy, as a non-invasive technique with minimal side effects. This approach also takes advantage of the current practical opportunity to utilize growing digital health technology. PMID:26441491

Illness identity in young adults with refractory epilepsy.

PubMed

Luyckx, Koen; Oris, Leen; Raymaekers, Koen; Rassart, Jessica; Moons, Philip; Verdyck, Ludo; Mijnster, Teus; Mark, Ruth E

2018-03-01

Refractory epilepsy is an intrusive condition with important implications for daily functioning in emerging and young adulthood. The present study examined the degree to which refractory epilepsy is integrated in one's identity, and examined how such a sense of illness identity was related to health-related quality of life (HRQOL). A total of 121 18- to 40-year-old patients with refractory epilepsy (56.2% women) completed self-report questionnaires assessing the four illness identity states of acceptance, enrichment, engulfment, and rejection (Illness Identity Questionnaire (IIQ)); HRQOL (Quality of Life in Epilepsy Inventory - 31); and seizure frequency and severity (Liverpool Seizure Severity Scale (LSSS)). Illness identity scores were compared with a sample of 191 patients with a nonneurological chronic disease (congenital heart disease). Hierarchical regression analyses were conducted to assess the predictive value of illness identity for HRQOL when simultaneously controlling for demographic and clinical features. Patients with refractory epilepsy scored higher on rejection and engulfment and lower on acceptance when compared with patients with congenital heart disease. Further, seizure severity and number of medication side-effects were positively related to engulfment and negatively to acceptance. Finally, when simultaneously controlling for various demographic and clinical variables, illness identity significantly predicted HRQOL (with engulfment being the strongest and most consistent predictor). The extent to which patients with refractory epilepsy succeed in integrating their illness into their identity may have important implications for HRQOL. Clinicians should be especially attentive for signs that patients feel engulfed by their epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

Predictors of Trajectories of Epilepsy-Specific Quality of Life among Children Newly Diagnosed with Epilepsy

PubMed Central

Ramsey, Rachelle R.; Loiselle, Kristin; Rausch, Joseph R.; Harrison, Jordan; Modi, Avani C.

2016-01-01

Objective To identify two year trajectories of epilepsy-specific health-related quality of life (HRQOL) among children newly diagnosed with epilepsy and to evaluate the predictive value of a comprehensive set of medical, psychosocial, and family factors. Methods Ninety-four children with epilepsy (8.14 ± 2.37 years of age and 63% male) and their caregivers participated in this study. Caregivers completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE) and measures of psychological and family functioning at one month post-diagnosis. The QOLCE was also given at eight additional time points during the subsequent two years as a part of a large observational study in children with epilepsy. Adherence data was collected via MEMS TrackCaps and medical information was collected through chart review. Results Unique trajectories were identified for the overall QOLCE scale, as well as the subscales. Most trajectory models for the QOLCE subscales contained at least one at-risk trajectory for children, indicating that there is a subgroup of children experiencing poor long-term HRQOL. Health-related quality of life trajectories remained predominantly stable during the two year period following treatment initiation. Number of AEDs, Internalizing Problems, and Externalizing Problems emerged as the most consistent predictors across the HRQOL domains. Significance Medical and psychosocial interventions, such as cognitive-behavioral strategies, should target modifiable factors (e.g., internalizing symptoms, externalizing symptoms, number of AEDs trialed) shortly after diagnosis to improve HRQOL for children with epilepsy over the course of their disease. PMID:26974247

Priorities in pediatric epilepsy research: improving children's futures today.

PubMed

Berg, Anne T; Baca, Christine B; Loddenkemper, Tobias; Vickrey, Barbara G; Dlugos, Dennis

2013-09-24

The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of patient-centered and patient-driven mandates for developing best practices in care, particularly for epilepsy beginning under age 3 years. The workshop brought together parents, representatives of voluntary advocacy organizations, physicians, allied health professionals, researchers, and administrators to identify priority areas for pediatric epilepsy care and research including implementation and testing of interventions designed to improve care processes and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure control but also behavioral, academic, and social functioning; 2) early and accurate diagnosis and optimal treatment; 3) role and involvement of parents (communication and shared decision-making); and 4) integration of school and community organizations with epilepsy care delivery. Key factors influencing pediatric epilepsy care included the child's impairments and seizure presentation, parents, providers, the health care system, and community systems. Care was represented as a sequential process from initial onset of seizures to referral for comprehensive evaluation when needed. We considered an alternative model in which comprehensive care would be utilized from onset, proactively, rather than reactively after pharmacoresistance became obvious. Barriers, including limited levels of evidence about many aspects of diagnosis and management, access to care--particularly epilepsy specialty and behavioral health care--and implementation, were identified. Progress hinges on coordinated research efforts that systematically address gaps in knowledge and overcoming barriers to access and implementation. The stakes are considerable, and the potential benefits for reduced burden of refractory epilepsy and lifelong disabilities may be enormous.

Graph theory and cognition: A complementary avenue for examining neuropsychological status in epilepsy.

PubMed

Garcia-Ramos, Camille; Lin, Jack J; Kellermann, Tanja S; Bonilha, Leonardo; Prabhakaran, Vivek; Hermann, Bruce P

2016-11-01

The recent revision of the classification of the epilepsies released by the ILAE Commission on Classification and Terminology (2005-2009) has been a major development in the field. Papers in this section of the special issue explore the relevance of other techniques to examine, categorize, and classify cognitive and behavioral comorbidities in epilepsy. In this review, we investigate the applicability of graph theory to understand the impact of epilepsy on cognition compared with controls and, then, the patterns of cognitive development in normally developing children which would set the stage for prospective comparisons of children with epilepsy and controls. The overall goal is to examine the potential utility of this analytic tool and approach to conceptualize the cognitive comorbidities in epilepsy. Given that the major cognitive domains representing cognitive function are interdependent, the associations between neuropsychological abilities underlying these domains can be referred to as a cognitive network. Therefore, the architecture of this cognitive network can be quantified and assessed using graph theory methods, rendering a novel approach to the characterization of cognitive status. We first provide fundamental information about graph theory procedures, followed by application of these techniques to cross-sectional analysis of neuropsychological data in children with epilepsy compared with that of controls, concluding with prospective analysis of neuropsychological development in younger and older healthy controls. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of autonomic activity in neurological conditions: Epilepsy and Tourette Syndrome.

PubMed

Nagai, Yoko

2015-01-01

This manuscript considers the central but neglected role of the autonomic nervous system in the expression and control of seizures in epilepsy (small) and tics in Tourette Syndrome (TS). In epilepsy, consideration of autonomic involvement is typically confined to differential diagnoses (e.g., syncope), or in relation to Sudden Unexpected Death in Epilepsy (SUDEP). Investigation is more limited in Tourette Syndrome. The role of the autonomic nervous system in the generation and prevention of epileptic seizures is largely overlooked. Emotional stimuli such as anxiety and stress are potent causes of seizures and tic activity in epilepsy and TS, respectively. This manuscript will describe a possible neural mechanism by which afferent autonomic projections linked to cognition and behavior influence central thalamo-cortical regulation, which appears to be an important means for controlling both seizure and tic activity. It also summarizes the link between the integrity of the default mode network and autonomic regulation in patients with epilepsy as well as the link between impaired motor control and autonomic regulation in patients with TS. Two neurological conditions; epilepsy and TS were chosen, as seizures and tics represent parameters that can be easily measured to investigate influences of autonomic functions. The EDA biofeedback approach is anticipated to gain a strong position within the next generation of treatment for epilepsy, as a non-invasive technique with minimal side effects. This approach also takes advantage of the current practical opportunity to utilize growing digital health technology.

Parental concerns towards children and adolescents with epilepsy in Sri Lanka--Qualitative study.

PubMed

Murugupillai, Roshini; Wanigasinghe, Jithangi; Muniyandi, Ravi; Arambepola, Carukshi

2016-01-01

Social, cultural, psychological and many other factors significantly impact the lives of epileptic children and their families. Parental concerns towards their children are less known in south Asian children with epilepsy. We aimed to identify the parental concerns regarding their children and adolescents with epilepsy in Sri Lanka. We carried out qualitative study in 3 districts of Sri Lanka, comprising 16 in-depth interviews with parents of children and adolescents with epilepsy and 3 focus group discussions with primary caregivers of epileptic children and key informants (schoolteachers, public health staffs). Content analysis of the interview data was performed. Parental concerns were spread among seven themes that emerged from the content analysis. These concerns were about the child's functioning in areas such as physical, behavioural, psychological and social, education, concerns related to anti-epileptic therapy and epilepsy as a disease. Parents were more concerned about their child's safety, educational achievements and future prospects in terms of employment and marriage. Unpredictability of seizures, fear of stigma and unawareness of epilepsy were the main reasons voiced by the parents for having such concerns. Increased concern and perception of vulnerability was seen among parents whose children had epilepsy and co-morbid illness. Parental concerns towards their children and adolescents show a multidimensional construct. Unpredictability of seizures, fear of stigma and unawareness of epilepsy were identified as key influential factors in moulding the parental concerns. Copyright © 2015. Published by Elsevier Ltd.

Provision of sudden unexpected death in epilepsy (SUDEP) information among Malaysian parents of children with epilepsy.

PubMed

Fong, Choong Yi; Lim, Wei Kang; Kong, Ann Nie; Lua, Pei Lin; Ong, Lai Choo

2017-10-01

Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. To date, there is only one published UK study evaluating information provision of SUDEP among parents of children with epilepsy (CWE), and there are no studies published from Asia. Although SUDEP information provision is recommended among parents of CWE, it is uncertain if these recommendations are applicable to Asian countries due to the different cultural attitude towards epilepsy. Our prospective cohort study consisted of multiethnic parents of children with epilepsy (CWE) seen in a tertiary hospital in Malaysia. Information on SUDEP was delivered to parents using an epilepsy educational software program. Participants completed a set of standardized questionnaire and Depression Anxiety Stress Scales-Short Form (DASS-21) immediately after and retested 3-6months after the SUDEP information provision. A total of 127 parents (84 mothers) participated in the study. The CWE consisted of 3 ethnic groups (38% Malay, 30% Chinese, 32% Indian) with a mean age of 9.6years. Majority (70.9%) felt positive after SUDEP information provision, 90.6% wanted SUDEP discussion for themselves with 70.1% wanted SUDEP discussion with their child, and a lower proportion (58.3%) would discuss SUDEP with their child. None of the participants reported increased symptoms of depression, stress or anxiety attributed to SUDEP information provision. Most parents took steps to reduce SUDEP risk, and most parents did not report an impact on their own functioning. However, there was an increase in parental report over time of impact on their child's functioning following SUDEP information (P<0.05). In conclusion, most Malaysian parents of CWE wanted SUDEP information. Following SUDEP information disclosure, majority did not report negative emotions; however, an increase in parents over time reported an impact on their child. Our findings reiterate that provision of SUDEP information should form part of care of CWE and parents should receive ongoing support as they undergo a period of parenting adjustment when dealing with the information provided. Copyright © 2017 Elsevier Inc. All rights reserved.

Validity of the Neurology Quality of Life (Neuro-QoL) Measurement System in Adult Epilepsy

PubMed Central

Victorson, David; Cavazos, Jose E.; Holmes, Gregory L.; Reder, Anthony T.; Wojna, Valerie; Nowinski, Cindy; Miller, Deborah; Buono, Sarah; Mueller, Allison; Moy, Claudia; Cella, David

2014-01-01

Epilepsy is a chronic neurological disorder that results in recurring seizures and can have a significant adverse effect on health related quality of life (HRQL). Neuro-QoL is an NINDS-funded system of patient reported outcome measures for neurology clinical research, which was designed to provide a precise and standardized way to measure HRQL in epilepsy and other neurological disorders. Using mixed-methods and item response theory-based approaches, we developed generic item banks and targeted scales for adults and children with major neurological disorders. This paper provides empirical results from a clinical validation study with a sample of adults diagnosed with epilepsy. One hundred twenty one people diagnosed with epilepsy participated, of which the majority were male (62%), Caucasian (95%), with a mean age of 47.3 (SD=16.9). Baseline assessments included Neuro-QoL short forms and general and external validity measures. Neuro-QoL short forms that are not typically found in other epilepsy-specific HRQL instruments include Stigma, Sleep Disturbance, Emotional and Behavioral Dyscontrol and Positive Affect & Well-being. Neuro-QoL short forms demonstrated adequate reliability (internal consistency range = .86–.96; test-retest range = .57–.89). Pearson correlations (p<.01) between Neuro-QoL forms of emotional distress (Anxiety, Depression, Stigma) and the QOLIE-31 Emotional Well-being Subscale were in the moderate to strong range (r’s = .66, .71 & .53, respectively), as were relations with the PROMIS Global Mental Health subscale (r’s = .59, .74 & .52, respectively). Moderate correlations were observed between Neuro-QoL Social Role Performance and Satisfaction and the QOLIE-31 Social Function (r’s = .58 & .52, respectively). In measuring aspects of physical function, the Neuro-QoL Mobility and Upper Extremity forms demonstrated moderate associations with the PROMIS Global Physical Function Subscale (r’s = .60 & .61, respectively). Neuro-QoL measures of perceived cognitive function (executive function and general concerns) produced moderate to strong correlations with the QOLIE-31 Cognition subscale (r’s = .65 & .75, respectively) and moderate relations with the Liverpool Adverse Events scale (r’s = .51 & .69, respectively). Finally, the Neuro-QoL Fatigue measure demonstrated moderate associations with the QOLIE-31 Energy/Fatigue subscale (r=−.65), Liverpool Adverse Events Scale (r=.69) and the Liverpool Seizure Severity Scale (r=.50). Five Neuro-QoL short forms demonstrated statistically significant responsiveness to change at 5–7 months, including Fatigue, Sleep Disturbance, Depression, Positive Affect & Well-being, and Emotional and Behavioral Dyscontrol. Overall, Neuro-QoL instruments showed good evidence for internal consistency, test-retest reliability, convergent validity and responsiveness to change over several months. These results support the validity of Neuro-QoL to measure HRQL in adults with epilepsy. PMID:24361767

Epilepsy Surgery: An Evidence Summary

PubMed Central

2012-01-01

Background The Medical Advisory Secretariat, the predecessor of Health Quality Ontario, published an evidence-based analysis on functional brain imaging. This analysis highlighted the low uptake of epilepsy surgery in Ontario and internationally. Objective The objective of this analysis was to review the effectiveness of epilepsy surgery at reducing seizure frequency, as well as the safety of epilepsy surgery. Data Sources The literature search included studies published between January 1995 and March 2012. Search terms included epilepsy, surgery, resection, safety, and complications. Review Methods Studies were eligible for inclusion if they included at least 20 patients undergoing surgery; had a comparison group of patients with epilepsy who were not undergoing surgery; and reported follow-up periods of at least 1 year. Outcomes of interest included seizure frequency and complications associated with surgery. Results Six systematic reviews reported pooled seizure-free rates that ranged from 43% to 75%. Two randomized controlled trials compared the effectiveness of epilepsy surgery with no surgery in patients with drug-refractory epilepsy. Both trials reported significant improvements in the seizure frequency in the surgery group compared with the nonsurgery group. Eight retrospective cohort studies reported on the safety of epilepsy surgery. Of the 2,725 patients included in these studies, there were 3 deaths reportedly related to surgery. Other complications included hemiparesis, infection, and visual field defects. The studies had long follow-up periods ranging from a mean of 2 to 7 years. Limitations The most recent randomized controlled trial was stopped early due to slow enrolment rates. Thus results need to be interpreted with caution. Conclusions There is high quality evidence that epilepsy surgery is effective at reducing seizure frequency. Two randomized controlled trials compared surgery to no surgery in patients with drug-refractory epilepsy. Both demonstrated significant reductions in seizure frequency. There are some complications associated with epilepsy surgery. In the published literature identified, we observed a 0.1% mortality rate associated with the surgery. Plain Language Summary About 30% of patients with epilepsy continue to have seizures despite optimal drug treatment. In some of these patients, surgery to control the number of seizures may be an option. Patients are carefully selected based on frequency of seizures, location of seizure in the brain, and type of seizures. There is good evidence to indicate that surgery is an effective and safe option for some patients with drug-refractory epilepsy. PMID:23074427

What graph theory actually tells us about resting state interictal MEG epileptic activity.

PubMed

Niso, Guiomar; Carrasco, Sira; Gudín, María; Maestú, Fernando; Del-Pozo, Francisco; Pereda, Ernesto

2015-01-01

Graph theory provides a useful framework to study functional brain networks from neuroimaging data. In epilepsy research, recent findings suggest that it offers unique insight into the fingerprints of this pathology on brain dynamics. Most studies hitherto have focused on seizure activity during focal epilepsy, but less is known about functional epileptic brain networks during interictal activity in frontal focal and generalized epilepsy. Besides, it is not clear yet which measures are most suitable to characterize these networks. To address these issues, we recorded magnetoencephalographic (MEG) data using two orthogonal planar gradiometers from 45 subjects from three groups (15 healthy controls (7 males, 24 ± 6 years), 15 frontal focal (8 male, 32 ± 16 years) and 15 generalized epileptic (6 male, 27 ± 7 years) patients) during interictal resting state with closed eyes. Then, we estimated the total and relative spectral power of the largest principal component of the gradiometers, and the degree of phase synchronization between each sensor site in the frequency range [0.5-40 Hz]. We further calculated a comprehensive battery of 15 graph-theoretic measures and used the affinity propagation clustering algorithm to elucidate the minimum set of them that fully describe these functional brain networks. The results show that differences in spectral power between the control and the other two groups have a distinctive pattern: generalized epilepsy presents higher total power for all frequencies except the alpha band over a widespread set of sensors; frontal focal epilepsy shows higher relative power in the beta band bilaterally in the fronto-central sensors. Moreover, all network indices can be clustered into three groups, whose exemplars are the global network efficiency, the eccentricity and the synchronizability. Again, the patterns of differences were clear: the brain network of the generalized epilepsy patients presented greater efficiency and lower eccentricity than the control subjects for the high frequency bands, without a clear topography. Besides, the frontal focal epileptic patients showed only reduced eccentricity for the theta band over fronto-temporal and central sensors. These outcomes indicate that functional epileptic brain networks are different to those of healthy subjects during interictal stage at rest, with a unique pattern of dissimilarities for each type of epilepsy. Further, when properly selected, three network indices suffice to provide a comprehensive description of these differences. Yet, since such uniqueness in the pattern of differences is also evident in the power spectrum, we conclude that the added value of the graph theory approach in this context should not be overestimated.

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

PubMed

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; 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

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. 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. 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.

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

Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

PubMed Central

Kundap, Uday P.; Kumari, Yatinesh; Othman, Iekhsan; Shaikh, Mohd. Farooq

2017-01-01

Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs. PMID:28824436

Hyperventilation in Patients With Focal Epilepsy: Electromagnetic Tomography, Functional Connectivity and Graph Theory - A Possible Tool in Epilepsy Diagnosis?

PubMed

Mazzucchi, Edoardo; Vollono, Catello; Losurdo, Anna; Testani, Elisa; Gnoni, Valentina; Di Blasi, Chiara; Giannantoni, Nadia M; Lapenta, Leonardo; Brunetti, Valerio; Della Marca, Giacomo

2017-01-01

Hyperventilation (HV) is a commonly used electroencephalogram activation method. We analyzed EEG recordings in 22 normal subjects and 22 patients with focal epilepsy of unknown cause. We selected segments before (PRE), during (HYPER), and 5 minutes after (POST) HV. To analyze the neural generators of EEG signal, we used standard low-resolution electromagnetic tomography (sLORETA software). We then computed EEG lagged coherence, an index of functional connectivity, between 19 regions of interest. A weighted graph was built for each band in every subject, and characteristic path length (L) and clustering coefficient (C) have been computed. Statistical comparisons were performed by means of analysis of variance (Group X Condition X Band) for mean lagged coherence, L and C. Hyperventilation significantly increases EEG neural generators (P < 0.001); the effect is particularly evident in cingulate cortex. Functional connectivity was increased by HV in delta, theta, alpha, and beta bands in the Epileptic group (P < 0.01) and only in theta band in Control group. Intergroup analysis of mean lagged coherence, C and L, showed significant differences for Group (P < 0.001), Condition (P < 0.001), and Band (P < 0.001). Analysis of variance for L also showed significant interactions: Group X Condition (P = 0.003) and Group X Band (P < 0.001). In our relatively small group of epileptic patients, HV is associated with activation of cingulate cortex; moreover, it modifies brain connectivity. The significant differences in mean lagged coherence, path length, and clustering coefficient permit to hypothesize that this activation method leads to different brain connectivity patterns in patients with epilepsy when compared with normal subjects. If confirmed by other studies involving larger populations, this analysis could become a diagnostic tool in epilepsy.

Innovations in Functional Neurosurgery and Anesthetic Implications.

PubMed

Dunn, Lauren K; Durieux, Marcel E; Elias, W Jeffrey; Nemergut, Edward C; Naik, Bhiken I

2018-01-01

Functional neurosurgery has undergone rapid growth over the last few years fueled by advances in imaging technology and novel treatment modalities. These advances have led to new surgical treatments using minimally invasive and precise techniques for conditions such as Parkinson's disease, essential tremor, epilepsy, and psychiatric disorders. Understanding the goals and technological issues of these procedures is imperative for the anesthesiologist to ensure safe management of patients presenting for functional neurosurgical procedures. In this review, we discuss the advances in neurosurgical techniques for deep brain stimulation, focused ultrasound and minimally invasive laser-based treatment of refractory epilepsy and provide a guideline for anesthesiologists caring for patients undergoing these procedures.

Delineating potential epileptogenic areas utilizing resting functional magnetic resonance imaging (fMRI) in epilepsy patients.

PubMed

Pizarro, Ricardo; Nair, Veena; Meier, Timothy; Holdsworth, Ryan; Tunnell, Evelyn; Rutecki, Paul; Sillay, Karl; Meyerand, Mary E; Prabhakaran, Vivek

2016-08-01

Seizure localization includes neuroimaging like electroencephalogram, and magnetic resonance imaging (MRI) with limited ability to characterize the epileptogenic network. Temporal clustering analysis (TCA) characterizes epileptogenic network congruent with interictal epileptiform discharges by clustering together voxels with transient signals. We generated epileptogenic areas for 12 of 13 epilepsy patients with TCA, congruent with different areas of seizure onset. Resting functional MRI (fMRI) scans are noninvasive, and can be acquired quickly, in patients with different levels of severity and function. Analyzing resting fMRI data using TCA is quick and can complement clinical methods to characterize the epileptogenic network.

Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model.

PubMed

Kilias, Antje; Häussler, Ute; Heining, Katharina; Froriep, Ulrich P; Haas, Carola A; Egert, Ulrich

2018-06-01

Mesial temporal lobe epilepsy is characterized by focal, recurrent spontaneous seizures, sclerosis and granule cell dispersion (GCD) in the hippocampal formation. Changes in theta rhythm properties have been correlated with the severity of hippocampal restructuring and were suggested as a cause of memory deficits accompanying epilepsy. For severe sclerosis, it has even been questioned whether theta band oscillations persist. We asked how theta oscillations change with graded restructuring along the longitudinal hippocampal axis and whether these changes correlate with the overall severity of temporal lobe epilepsy. We recorded local field potentials in the medial entorhinal cortex and along the septo-temporal axis of the dentate gyrus at sites with different degrees of GCD in freely behaving epileptic mice. Theta frequency was decreased at all recording positions throughout the dentate gyrus and in the medial entorhinal cortex, irrespective of the extent of GCD or the rate of severe epileptic events. The frequency reduction by up to 1.7 Hz, corresponding to 1/3 octaves within the theta range, was present during rest, exploration and running. Despite the frequency reduction, theta oscillations remained coherent across the hippocampal formation and were modulated by running speed as in controls. The reduction in theta frequency thus is likely not a consequence of the local restructuring but rather a global phenomenon affecting the hippocampal formation as a whole. © 2018 Wiley Periodicals, Inc.

Pediatric Concerns Due to Expanded Cannabis Use: Unintended Consequences of Legalization.

PubMed

Wang, George Sam

2017-03-01

An "unintended consequence" of marijuana legalization is the impact on the pediatric population. From prenatal exposure to unintentional childhood exposures, through concerns of adolescence abuse and marijuana use for medicinal indications in children, marijuana exposure can affect pediatric patients at every stage in childhood. Regardless of the stage or reason of exposure, concerns exist about short-term and long-term consequences in a child's physical and mental health. The use of cannabidiol (CBD) may have some benefit for the treatment of epilepsy, but emphasis needs to be on rigorous clinical trials to evaluate efficacy and safety. As more states allow both medical and recreational marijuana, availability and prevalence of use will likely increase and more surveillance and research is needed to evaluate the consequences on the pediatric population.

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

PubMed Central

Altmann, Andre; Botía, Juan A; Jahanshad, Neda; Hibar, Derrek P; Absil, Julie; Alhusaini, Saud; Alvim, Marina K M; Auvinen, Pia; Bartolini, Emanuele; Bergo, Felipe P G; Bernardes, Tauana; Blackmon, Karen; Braga, Barbara; Caligiuri, Maria Eugenia; Calvo, Anna; Carr, Sarah J; Chen, Jian; Chen, Shuai; Cherubini, Andrea; David, Philippe; Domin, Martin; Foley, Sonya; França, Wendy; Haaker, Gerrit; Isaev, Dmitry; Keller, Simon S; Kotikalapudi, Raviteja; Kowalczyk, Magdalena A; Kuzniecky, Ruben; Langner, Soenke; Lenge, Matteo; Leyden, Kelly M; Liu, Min; Loi, Richard Q; Martin, Pascal; Mascalchi, Mario; Morita, Marcia E; Pariente, Jose C; Rodríguez-Cruces, Raul; Rummel, Christian; Saavalainen, Taavi; Semmelroch, Mira K; Severino, Mariasavina; Thomas, Rhys H; Tondelli, Manuela; Tortora, Domenico; Vaudano, Anna Elisabetta; Vivash, Lucy; von Podewils, Felix; Wagner, Jan; Weber, Bernd; Yao, Yi; Yasuda, Clarissa L; Zhang, Guohao; Bargalló, Nuria; Bender, Benjamin; Bernasconi, Neda; Bernasconi, Andrea; Bernhardt, Boris C; Blümcke, Ingmar; Carlson, Chad; Cavalleri, Gianpiero L; Cendes, Fernando; Concha, Luis; Delanty, Norman; Depondt, Chantal; Devinsky, Orrin; Doherty, Colin P; Focke, Niels K; Gambardella, Antonio; Guerrini, Renzo; Hamandi, Khalid; Jackson, Graeme D; Kälviäinen, Reetta; Kochunov, Peter; Kwan, Patrick; Labate, Angelo; McDonald, Carrie R; Meletti, Stefano; O'Brien, Terence J; Ourselin, Sebastien; Richardson, Mark P; Striano, Pasquale; Thesen, Thomas; Wiest, Roland; Zhang, Junsong; Vezzani, Annamaria; Ryten, Mina; Thompson, Paul M

2018-01-01

Abstract Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen’s d = −0.24 to −0.73; P < 1.49 × 10−4), and lower thickness in the precentral gyri bilaterally (d = −0.34 to −0.52; P < 4.31 × 10−6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = −1.73 to −1.91, P < 1.4 × 10−19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = −0.36 to −0.52; P < 1.49 × 10−4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = −0.29 to −0.54; P < 1.49 × 10−4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = −0.27 to −0.51; P < 1.49 × 10−4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < −0.0018; P < 1.49 × 10−4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed. PMID:29365066

The Managing Epilepsy Well Network:: Advancing Epilepsy Self-Management.

PubMed

Sajatovic, Martha; Jobst, Barbara C; Shegog, Ross; Bamps, Yvan A; Begley, Charles E; Fraser, Robert T; Johnson, Erica K; Pandey, Dilip K; Quarells, Rakale C; Scal, Peter; Spruill, Tanya M; Thompson, Nancy J; Kobau, Rosemarie

2017-03-01

Epilepsy, a complex spectrum of disorders, affects about 2.9 million people in the U.S. Similar to other chronic disorders, people with epilepsy face challenges related to management of the disorder, its treatment, co-occurring depression, disability, social disadvantages, and stigma. Two national conferences on public health and epilepsy (1997, 2003) and a 2012 IOM report on the public health dimensions of epilepsy highlighted important knowledge gaps and emphasized the need for evidence-based, scalable epilepsy self-management programs. The Centers for Disease Control and Prevention translated recommendations on self-management research and dissemination into an applied research program through the Prevention Research Centers Managing Epilepsy Well (MEW) Network. MEW Network objectives are to advance epilepsy self-management research by developing effective interventions that can be broadly disseminated for use in people's homes, healthcare providers' offices, or in community settings. The aim of this report is to provide an update on the MEW Network research pipeline, which spans efficacy, effectiveness, and dissemination. Many of the interventions use e-health strategies to eliminate barriers to care (e.g., lack of transportation, functional limitations, and stigma). Strengths of this mature research network are the culture of collaboration, community-based partnerships, e-health methods, and its portfolio of prevention activities, which range from efficacy studies engaging hard-to-reach groups, to initiatives focused on provider training and knowledge translation. The MEW Network works with organizations across the country to expand its capacity, help leverage funding and other resources, and enhance the development, dissemination, and sustainability of MEW Network programs and tools. Guided by national initiatives targeting chronic disease or epilepsy burden since 2007, the MEW Network has been responsible for more than 43 scientific journal articles, two study reports, seven book chapters, and 62 presentations and posters. To date, two programs have been adopted and disseminated by the national Epilepsy Foundation, state Epilepsy Foundation affiliates, and other stakeholders. Recent expansion of the MEW Network membership will help to extend future reach and public health impact. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

Managing epilepsy in women of childbearing age.

PubMed

Crawford, Pamela M

2009-01-01

Epilepsy affects the menstrual cycle, aspects of contraception, fertility, pregnancy and bone health in women. It is common for seizure frequency to vary throughout the menstrual cycle. In ovulatory cycles, two peaks can be seen around the time of ovulation and in the few days before menstruation. In anovulatory cycles, there is an increase in seizures during the second half of the menstrual cycle. There is also an increase in polycystic ovaries and hyperandrogenism associated with valproate therapy. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Non-enzyme-inducing antiepileptic drugs (AEDs) [valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine and zonisamide] do not show any interactions with the combined oral contraceptive (OC). There are interactions between the combined OC and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages>200 mg/day], oxcarbazepine) and lamotrigine. Pre-conception counselling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be informed about issues relating to the future pregnancy, including methods and consequences of prenatal screening, fertility, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labour, breast feeding and care of a child. During pregnancy, the lowest effective dose of the most appropriate AED should be used, aiming for monotherapy where possible. Recent pregnancy databases have suggested that valproate is significantly more teratogenic than carbamazepine, and the combination of valproate and lamotrigine is particularly teratogenic. Most pregnancies in women with epilepsy are without complications, and the majority of infants are delivered healthy with no increased risk of obstetric complications in women. There is no medical reason why a woman with epilepsy cannot breastfeed her child. The AED concentration profiled in breast milk follows the plasma concentration curve. The total amount of drug transferred to infants via breast milk is usually much smaller than the amount transferred via the placenta during pregnancy. However, as drug elimination mechanisms are not fully developed in early infancy, repeated administration of a drug such as lamotrigine via breast milk may lead to accumulation in the infant. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis and osteomalacia. No studies have been undertaken looking at preventative therapies for these co-morbidities.

Atypical language laterality is associated with large-scale disruption of network integration in children with intractable focal epilepsy.

PubMed

Ibrahim, George M; Morgan, Benjamin R; Doesburg, Sam M; Taylor, Margot J; Pang, Elizabeth W; Donner, Elizabeth; Go, Cristina Y; Rutka, James T; Snead, O Carter

2015-04-01

Epilepsy is associated with disruption of integration in distributed networks, together with altered localization for functions such as expressive language. The relation between atypical network connectivity and altered localization is unknown. In the current study we tested whether atypical expressive language laterality was associated with the alteration of large-scale network integration in children with medically-intractable localization-related epilepsy (LRE). Twenty-three right-handed children (age range 8-17) with medically-intractable LRE performed a verb generation task in fMRI. Language network activation was identified and the Laterality index (LI) was calculated within the pars triangularis and pars opercularis. Resting-state data from the same cohort were subjected to independent component analysis. Dual regression was used to identify associations between resting-state integration and LI values. Higher positive values of the LI, indicating typical language localization were associated with stronger functional integration of various networks including the default mode network (DMN). The normally symmetric resting-state networks showed a pattern of lateralized connectivity mirroring that of language function. The association between atypical language localization and network integration implies a widespread disruption of neural network development. These findings may inform the interpretation of localization studies by providing novel insights into reorganization of neural networks in epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Left or right? Lateralizing temporal lobe epilepsy by dynamic amygdala fMRI.

PubMed

Ives-Deliperi, Victoria; Butler, James Thomas; Jokeit, Hennric

2017-05-01

In this case series, the findings of 85 functional MRI studies employing a dynamic fearful face paradigm are reported. Previous findings have shown the paradigm to generate bilateral amygdala activations in healthy subjects and unilateral activations in patients with MTLE, in the contralateral hemisphere to seizure origin. Such findings suggest ipsilateral limbic pathology and offer collateral evidence in lateralizing MTLE. The series includes 60 patients with TLE, 12 patients with extra-temporal lobe epilepsy, and 13 healthy controls. Functional MRI studies using a 1.5T scanner were conducted over a three-year period at a single epilepsy center and individual results were compared with EEG findings. In the cohort of unilateral TLE patients, lateralized activations of the amygdala were concordant with EEG findings in 76% of patients (77% lTLE, 74% rTLE). The differences in the mean lateralized indices of the lTLE, rTLE, and healthy control groups were all statistically significant. Lateralized amygdala activations were concordant with EEG findings in only 31% of the 12 patients with extra-temporal lobe epilepsy and bilateral amygdala activations were generated in all but one of the healthy control subjects. This case series further endorses the utility of the dynamic fearful face functional MRI paradigm using the widely available 1.5T as an adjunctive investigation to lateralize TLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Microglia in CNS development: Shaping the brain for the future.

PubMed

Mosser, Coralie-Anne; Baptista, Sofia; Arnoux, Isabelle; Audinat, Etienne

Microglial cells are the resident macrophages of the central nervous system (CNS) and are mainly known for their roles in neuropathologies. However, major recent developments have revealed that these immune cells actively interact with neurons in physiological conditions and can modulate the fate and functions of synapses. Originating from myeloid precursors born in the yolk sac, microglial cells invade the CNS during early embryonic development. As a consequence they can potentially influence neuronal proliferation, migration and differentiation as well as the formation and maturation of neuronal networks, thereby contributing to the entire shaping of the CNS. We review here recent evidence indicating that microglial cells are indeed involved in crucial steps of the CNS development, including neuronal survival and apoptosis, axonal growth, migration of neurons, pruning of supernumerary synapses and functional maturation of developing synapses. We also discuss current hypotheses proposing that diverting microglial cells of their physiological functions, by promoting the expression of an immune phenotype during development, may be central to neurodevelopmental disorders such as autism, schizophrenia and epilepsy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epilepsy surgery in children with drug-resistant epilepsy, a long-term follow-up.

PubMed

Hallböök, T; Tideman, P; Rosén, I; Lundgren, J; Tideman, E

2013-12-01

In this follow-up study, we wanted to present the long-term outcome (5-21 years) in terms of seizure freedom, seizure reduction, and the cognitive development in the first 47 children who underwent epilepsy surgery at the University Hospital in Lund from 1991 to 2007. All children who underwent epilepsy surgery in the southern region of Sweden were assessed for cognitive function before surgery and at follow-up. A review of medical documents for demographic data and seizure-related characteristics was made by retrospectively examining the clinical records. Forty-seven children with a median age at surgery of 8 years (range 0.5-18.7 years) were included. Twenty-three children achieved seizure freedom, six demonstrated >75% improvement in seizure frequency, and none of the children experienced an increase in seizure frequency. Twenty-one children required a reoperation to achieve satisfactory seizure outcomes. Cognitive functional level was preserved, and the majority of patients, 34 (76%), followed their expected cognitive trajectory. The patients who became seizure free significantly improved their cognitive processing speed, even after long-term follow-up. Epilepsy surgery in children offers suitable candidates a good chance of significantly improved outcome and low rates of complications. Several children, however, required a reoperation to achieve satisfactory seizure outcomes. Cognitive level was preserved, and the majority of patients followed their expected cognitive trajectory. Cognitive improvements in processing speed appear to occur in parallel with seizure control and were even more pronounced in subjects with no anti-epilepsy drugs. These improvements persisted even after long-term follow-up. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A neuropsychological assessment, using computerized battery tests (CANTAB), in children with benign rolandic epilepsy before AED therapy.

PubMed

Vinţan, M A; Palade, S; Cristea, A; Benga, I; Muresanu, D F

2012-02-22

Benign rolandic epilepsy (BRE) is a form of partial idiopathic epilepsy according to the International League Against Epilepsy (ILAE) syndromes classification (1989). Recent studies have identified cases of BRE that do not meet the initial definition of 'benign'; these included reports of cases with specific cognitive deficits. It is still a matter of debate, whether these deficits are due to epilepsy per se, to treatment or other associated factors. The aim of this study was to evaluate if BRE children have cognitive deficits at the onset of their seizures, prior to their participation in any anti-epileptic drug therapy (AED). We performed a neuropsychological assessment of 18 BRE children compared with a corresponding age-matched control group. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subjects were at their first neurological evaluation, before any AED therapy. We assessed: visual memory, induction and executive functions. In our group, the BRE children performed comparably with the control children for the induction and executive functions. Substantial differences were identified for the visual memory subtests: PRM percent correct (t = -2.58, p = 0.01) and SRM percent correct (t = -2.73, p = 0.01). Age of seizure onset had a negative impact on the visual memory subtest performances (PRM mean correct latency). We found significant correlations between the different CANTAB subtests results and characteristics of the centrotemporal spikes (CTS). Our results are consistent with the findings of other similar studies. This form of epilepsy is associated with subtle neuropsychological deficits, present at seizure onset. Neuropsychological deficits identified, suggest a more diffuse brain involvement in the epileptiform process.

Memory, Executive Skills, and Psychosocial Phenotype in Children with Pharmacoresponsive Epilepsy: Reactivity to Intervention.

PubMed

Schaffer, Yael; Ben Zeev, Bruria; Cohen, Roni; Shufer, Avinoam; Geva, Ronny

2017-01-01

Recent studies on pharmacoresponsive epilepsies demonstrate specific memory, executive functions (EF), and psychosocial deficits in this group. These deficits are often undertreated, and little is known about the neuropsychological factors that may support moderation of the deficits through intervention. The aim of this study was to explore the effects of a structured cognitive behavioral group intervention on both memory and emotional domains and to evaluate the factors influencing its efficacy. The feasibility study implemented a newly designed intervention for children with pharmacoresponsive epilepsies ( N  = 33, aged 9-14 years, 51% girls), hypothesizing that memory and psychosocial symptoms in children with pharmacoresponsive epilepsies are sensitive to intervention using structured memory and psychosocial modules in a weekly group session setting. Comparable memory and psychosocial assessments were used to evaluate performance at baseline and post-intervention. Results were compared to age- and education-matched healthy controls ( N  = 27, aged 9-14 years). Pre-post-intervention comparisons show improvements in STM ( p  < 0.01, η 2 = 0.358), optimism ( p  < 0.05, η 2 = 0.245), and self-efficacy ( p  < 0.05, η 2 = 0.164). Unique negative relations between memory deficits and psychosocial phenotype were seen in epilepsy patients and not in controls in response to the intervention. EF moderated this intervention effect ( p  < 0.05, η 2 = 0.252), whereas psychosocial status and pharmacological profile did not. Cognitive behavioral therapy focusing on memory and psychosocial perceptions for children with pharmacoresponsive epilepsies seems promising, with greater improvement in memory and psychosocial functioning in children with more affected EF.

Prevalence and Predictors of Long-Term Functional Impairment, Epilepsy, Mortality, and Stroke Recurrence after Childhood Stroke: A Prospective Study of a Chilean Cohort.

PubMed

López-Espejo, Mauricio; Hernández-Chávez, Marta

2017-07-01

To evaluate the prevalence and predictors of long-term impairment, epilepsy, mortality, and recurrences after the first stroke in a cohort of Chilean children. A prospective study involving 98 children who suffered a first stroke and underwent follow-up for at least 3 years in a single center. Functional outcome was measured using the modified Rankin Scale for children. We utilized multivariate logistic regression models to estimate the odds ratios (ORs) for outcomes while adjusting for age, sex, and underlying conditions (significance <.05). Stroke recurrences were present in 18 children and were strongly associated with arteriopathies (OR 8.11; CI 1.5-43). Of 26 children who died during the follow-up period, a significant proportion had a cardiopathy (OR 6.57; CI 1.3-32) or a chronic head and neck disease (OR 41.3; CI 3.5-490). Among 72 survivors (median age 1.49 years; 38 girls; mean follow-up time 4.85 years), 28 presented marked impairment; these children were younger (P = .019) and had more commonly arteriopathies (OR 9.33; CI 1.7-51) and epilepsy (OR 10.5; CI 3.1-36) as compared to survivors without disabilities. Cumulative epilepsy prevalence was 55.6%; children with epilepsy were younger (P = .037) and had more commonly acute symptomatic seizures (OR 12.16; CI 2.93-50.4) as compared to survivors without epilepsy. The prevalence of long-term adverse outcomes after childhood stroke is high and does not differ from other geographical and racial groups. Younger age, acute seizures, and arteriopathies but not sex and other underlying conditions predict adverse outcome following childhood stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Epilepsy following cortical injury: Cellular and molecular mechanisms as targets for potential prophylaxis

PubMed Central

Prince, David A.; Parada, Isabel; Scalise, Karina; Graber, Kevin; Shen, Fran

2009-01-01

Summary The sequelae of traumatic brain injury, including posttraumatic epilepsy, represent a major societal problem. Significant resources are required to develop a better understanding of the underlying pathophysiologic mechanisms as targets for potential prophylactic therapies. Posttraumatic epilepsy undoubtedly involves numerous pathogenic factors that develop more or less in parallel. We have highlighted two potential “prime movers”: disinhibition and development of new functional excitatory connectivity, which occur in a number of animal models and some forms of epilepsy in humans. Previous experiments have shown that tetrodotoxin (TTX) applied to injured cortex during a critical period early after lesion placement can prevent epileptogenesis in the partial cortical (“undercut”) model of posttraumatic epilepsy. Here we show that such treatment markedly attenuates histologic indices of axonal and terminal sprouting and presumably associated aberrant excitatory connectivity. A second finding in the undercut model is a decrease in spontaneous inhibitory events. Current experiments show that this is accompanied by regressive alterations in fast-spiking γ-aminobutyric acid (GABA)ergic interneurons, including shrinkage of dendrites, marked decreases in axonal length, structural changes in inhibitory boutons, and loss of inhibitory synapses on pyramidal cells. Other data support the hypothesis that these anatomic abnormalities may result from loss of trophic support normally provided to interneurons by brain-derived neurotrophic factor (BDNF). Approaches that prevent these two pathophysiologic mechanisms may offer avenues for prophylaxis for posttraumatic epilepsy. However, major issues such as the role of these processes in functional recovery from injury and the timing of the critical period(s) for application of potential therapies in humans are critical and need to be resolved. PMID:19187292

Comparison of Cognitive Impairment between Patients having Epilepsy and Psychogenic Nonepileptic Seizures.

PubMed

Özer Çelik, Ayşegül; Kurt, Pınar; Yener, Görsev; Alkin, Tunç; Öztura, İbrahim; Baklan, Barış

2015-06-01

The aim of this study was to evaluate cognitive impairment in patients having epilepsy or psychogenic nonepileptic seizures (PNESs) using selected neuropsychological tests at different time periods related to the seizure. In this study, selected neurocognitive tests were administered to the patients. Within 24 h, the previously applied neurocognitive tests were repeated within 24 h following the observation of typical seizures when monitoring and normalizing electroencephalography (EEG) activity. Basal neurocognitive tests were also administered to the healthy control group, and repeat neurocognitive evaluation was performed within 24-96 h. The basal neurocognitive evaluation revealed that verbal learning and memory scores as well as Stroop test interference time were significantly lower in the PNES group compared with those in the controls. In the basal cognitive tests administered to the patients with epilepsy, verbal learning and memory scores, long-term memory, and total recognition test scores were significantly lower than those of the controls. Following the repeat cognitive tests, significant progress was found in the verbal categorical fluency score of the PNES group. No significant difference was determined in the epilepsy group. Significant contraction was determined in the Stroop interference time in the control group, but no similar change was recorded in the epilepsy or PNES groups. While memory problems seemed to be most prominent in the assessed patients with epilepsy, attention and executive function problems were more dominant in the patients with PNESs. These findings are probably related to numerous factors such duration of disease, mood disorders, and specific drug use. No deterioration in attention and executive functions was reported in the early post-seizure period in either patient group.

Personalized translational epilepsy research - Novel approaches and future perspectives: Part I: Clinical and network analysis approaches.

PubMed

Rosenow, Felix; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Bauer, Sebastian

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1]. Copyright © 2017 Elsevier Inc. All rights reserved.

Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

PubMed

Bauer, Sebastian; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Rosenow, Felix

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. Copyright © 2017. Published by Elsevier Inc.

Theory of Mind and social competence in children and adolescents with genetic generalised epilepsy (GGE): Relationships to epilepsy severity and anti-epileptic drugs.

PubMed

Stewart, Elizabeth; Catroppa, Cathy; Gill, Deepak; Webster, Richard; Lawson, John; Mandalis, Anna; Sabaz, Mark; Barton, Belinda; Lah, Suncica

2018-06-18

This study aimed to examine Theory of Mind (ToM) and social competence in children and adolescents with genetic generalised epilepsy (GGE), and explore how they relate to neurocognitive and epilepsy variables. Twenty-two children and adolescents with GGE (8-16 years old) and 22 typically developing controls completed two behavioural tasks (faux-pas, strange stories) assessing cognitive and affective ToM, and a battery of standardised neuropsychological tests. Parents completed questionnaires assessing ToM and social competence. Neurologists completed the Global Assessment Severity of Epilepsy (GASE) scale to measure of epilepsy severity. Children and adolescents with GGE were impaired in both cognitive and affective ToM, and had reduced social competence compared to controls, which was not attributable to low intellectual functioning or impaired executive skills (working memory, inhibition). Lower ToM correlated with reduced social competence in children and adolescents with GGE. Clinical variables identified included: (i) higher daily dosage of valproate, which was correlated with reduced affective ToM, (ii) higher daily dosages of ethosuximide and lamotrigine, which were correlated with reduced social competence, and (iii) overall epilepsy severity on the GASE, which was correlated with reduced social competence. Our study revealed cognitive and affective ToM impairments in children and adolescents with GGE, which correlated with everyday social problems. Moreover, higher dosages of commonly prescribed anti-epileptic drugs and overall epilepsy severity were related to ToM impairments and social competence problems. Although preliminary, these findings provide critical information for detection and screening procedures for social difficulties in children and adolescents with GGE, which are currently lacking. Copyright © 2018 British Epilepsy Association. All rights reserved.

Health-related quality of life improvement via telemedicine for epilepsy: printed versus SMS-based education intervention.

PubMed

Lua, Pei Lin; Neni, Widiasmoro Selamat

2013-10-01

Improving health-related quality of life (HRQoL) among people with epilepsy (PWE) has become the focus of various treatment programmes and behavioural interventions which continue to be challenging to both patients and healthcare professionals. To investigate the impact of SMS-based epilepsy education programme on PWE's HRQoL status and to determine the predictors for good HRQoL. Eligible epilepsy out-patients from three public hospitals in East Coast Peninsular Malaysia were randomized into two groups: intervention (IG) and control (CG). Patients in the CG were supplied with only printed epilepsy educational module, while those in the IG additionally received short message service (SMS) from the Mobile Epilepsy Educational System (MEES). The Malay Quality of Life in Epilepsy Inventory-30 (MQOLIE-30) was utilized for HRQoL assessment. Descriptive statistics, paired t test, analysis of covariance and multiple logistic regression were employed for data analyses (SPSS 16). One hundred and forty-four PWE were recruited for the study (age = 30.5 ± 11.8; unmarried = 60.4 %; education level ≤ SPM/Cambridge O' level = 76.4 %; illness duration > 5 years = 51.1 %). After controlling for possible confounders, IG exhibited positive changes in HRQoL profile compared to CG particularly in Seizure Worry, Overall Quality of Life, Emotional Well-Being, Social Functioning and Overall Score (p < 0.05). After adjusting for covariates, being employed and receiving additional SMS-based epilepsy education programme emerged as the significant predictors of good HRQoL among PWE. Receiving continuous SMS-based epilepsy information from the MEES seemed to generate positive impacts on PWE's overall HRQoL. This study has provided a basis for future innovations to inspire efforts in ensuring the welfare and HRQoL of PWE and their families.

Prioritization of Epilepsy Associated Candidate Genes by Convergent Analysis

PubMed Central

Jia, Peilin; Ewers, Jeffrey M.; Zhao, Zhongming

2011-01-01

Background Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research. Methodology/Principal Findings In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways. Conclusions/Significance The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be applied for the study of other complex diseases. PMID:21390307

Prioritization of epilepsy associated candidate genes by convergent analysis.

PubMed

Jia, Peilin; Ewers, Jeffrey M; Zhao, Zhongming

2011-02-24

Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research. In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways. The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be applied for the study of other complex diseases.

Trajectories of health-related quality of life in children with epilepsy: a cohort study.

PubMed

Ferro, Mark A; Camfield, Carol S; Levin, Simon D; Smith, Mary Lou; Wiebe, Samuel; Zou, Guangyong; Speechley, Kathy N

2013-11-01

Little is known about subgroups of children with epilepsy who may experience less favorable outcomes over time. The objectives of this study were to document trajectories of health-related quality of life (HRQL) and to identify predictors of the trajectory group in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study, a prospective multisite study of children 4-12 years old with new-onset epilepsy followed for 24 months. Health-related quality of life was measured using the Quality of Life in Childhood Epilepsy questionnaire. Trajectories of HRQL were investigated using latent class trajectory modeling. Multinomial logistic regression was used to identify child, parent, and family predictors of HRQL trajectories. A total of 374 families responded at baseline and 283 (76%) completed the study. Five HRQL trajectories were observed: low-increasing (4%), moderate-decreasing (12%), moderate-increasing (22%), high-increasing (32%), and high-stable (30%). Many children in the low-increasing, moderate-increasing, high-increasing, and high-stable had clinically meaningful improvements in HRQL: 82%, 47%, 63%, and 44%, respectively. In contrast, the majority of children in the moderate-decreasing group (56%) experienced clinically meaningful declines in their HRQL. Factors predicting trajectories were number of antiepileptic drugs prescribed, presence of comorbid behavior or cognitive problems, parent depression, and family functioning and demands. Results suggested that children with epilepsy are not homogenous but rather consist of groups with different trajectories and unique predictors of HRQL. Problems associated with child behavior and cognition were the strongest predictors identified. Given that several risk factors are modifiable, it is important to examine these as potential targets within a family-centered framework to improve HRQL of children with new-onset epilepsy. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Computer modeling of Epilepsy

PubMed Central

Lytton, William W.

2009-01-01

Preface Epilepsy is a complex set of disorders that can involve many areas of cortex as well as underlying deep brain systems. The myriad manifestations of seizures, as varied as déjà vu and olfactory hallucination, can thereby give researchers insights into regional functions and relations. Epilepsy is also complex genetically and pathophysiologically, involving microscopic (ion channels, synaptic proteins), macroscopic (brain trauma and rewiring) and intermediate changes in a complex interplay of causality. It has long been recognized that computer modeling will be required to disentangle causality, to better understand seizure spread and to understand and eventually predict treatment efficacy. Over the past few years, substantial progress has been made modeling epilepsy at levels ranging from the molecular to the socioeconomic. We review these efforts and connect them to the medical goals of understanding and treating this disorder. PMID:18594562

Factors associated with quality of life in active childhood epilepsy: a population-based study.

PubMed

Reilly, Colin; Atkinson, Patricia; Das, Krishna B; Chin, Richard F M; Aylett, Sarah E; Burch, Victoria; Gillberg, Christopher; Scott, Rod C; Neville, Brian G R

2015-05-01

Improving health-related quality of life (HRQOL), rather than just reducing seizures, should be the principal goal in comprehensive management of childhood epilepsy. There is a lack of population-based data on predictors of HRQOL in childhood epilepsy. The Children with Epilepsy in Sussex Schools (CHESS) study is a prospective, population-based study involving school-aged children (5-15 years) with active epilepsy (on one or more AED and/or had a seizure in the last year) in a defined geographical area in the UK. Eighty-five of 115 (74% of eligible population) children underwent comprehensive psychological assessment including measures of cognition, behaviour, and motor functioning. Parents of the children completed the Quality of Life in Childhood Epilepsy (QOLCE).Clinical data on eligible children was extracted using a standardised pro forma. Linear regression analysis was undertaken to identify factors significantly associated with total Quality of Life in this population. Factors independently significantly associated (p < .05) with total QOLCE scores were seizures before 24 months, cognitive impairment (IQ < 85), anxiety, and parent reported school attendance difficulty. These factors were also significantly associated with total QOLCE when children with IQ < 50 were excluded from analysis. The majority of factors associated with parent reported HRQOL in active childhood epilepsy are related to neurobehavioural and/or psychosocial aspects of the condition. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series.

PubMed

Partemi, Sara; Vidal, Monica Coll; Striano, Pasquale; Campuzano, Oscar; Allegue, Catarina; Pezzella, Marianna; Elia, Maurizio; Parisi, Pasquale; Belcastro, Vincenzo; Casellato, Susanna; Giordano, Lucio; Mastrangelo, Massimo; Pietrafusa, Nicola; Striano, Salvatore; Zara, Federico; Bianchi, Amedeo; Buti, Daniela; La Neve, Angela; Tassinari, Carlo Alberto; Oliva, Antonio; Brugada, Ramon

2015-05-01

Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy.

Behaviour in children with cerebral palsy with and without epilepsy.

PubMed

Carlsson, Malin; Olsson, Ingrid; Hagberg, Gudrun; Beckung, Eva

2008-10-01

The aim of the study was to describe behavioural problems in children with cerebral palsy (CP) with and without epilepsy. The children were sampled from the Western Sweden CP register and were part of a European Union project. The Strength and Difficulties Questionnaire and questions on epilepsy were answered by one parent of each child. Medical records were reviewed. Parents of 83 children (44 males, 39 females) age range participated: 30 at Gross Motor Function Classification System levels I and II, and 53 at levels III to V; 60 had spastic age range 8 to 12 years (bilateral 42, unilateral 18) and 23 dyskinetic CP; 34 children had active epilepsy. The proportion of children with normal behaviour on the total difficulties score (TDS) of the Strength and Difficulties Questionnaire was significantly lower than normative data (57% vs 80%, p<0.001). Parents of 21 children (25%) considered their child's behaviour to be abnormal. Children with CP and epilepsy had a significantly higher median TDS (p=0.03) than seizure-free children. In children with aided or no walking ability, the TDS was significantly higher in those with epilepsy (p=0.04). Parents of 32 children (39%) considered their children's behaviour to have an impact on themselves and others. We conclude that behavioural problems are common in children with CP, and even more when epilepsy is present. Parents identify these problems, and professionals need to address them.

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

2015-08-28

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.

The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR) pathway.

PubMed

Talos, Delia M; Sun, Hongyu; Zhou, Xiangping; Fitzgerald, Erin C; Jackson, Michele C; Klein, Peter M; Lan, Victor J; Joseph, Annelise; Jensen, Frances E

2012-01-01

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures.

The Interaction between Early Life Epilepsy and Autistic-Like Behavioral Consequences: A Role for the Mammalian Target of Rapamycin (mTOR) Pathway

PubMed Central

Fitzgerald, Erin C.; Jackson, Michele C.; Klein, Peter M.; Lan, Victor J.; Joseph, Annelise; Jensen, Frances E.

2012-01-01

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures. PMID:22567115

Advancing epilepsy treatment through personalized genetic zebrafish models.

PubMed

Griffin, A; Krasniak, C; Baraban, S C

2016-01-01

With an increase in the number of disease causing genetic mutations identified from epilepsy cohorts, zebrafish are proving to be an attractive vertebrate model for functional analysis of these allele variants. Not only do zebrafish have conserved gene functions, but larvae harboring mutations in identified human epileptic genes show spontaneous seizure activity and mimic the convulsive behavioral movements observed in humans. With zebrafish being compatible with medium to high-throughput screening, they are also proving to be a unique and powerful system for early preclinical drug screening, including novel target identification, pharmacology, and toxicology. Additionally, with recent advances in genomic engineering technologies, it is now possible to study the precise pathophysiology of patient-specific gene mutations in zebrafish. The following sections highlight how the unique attributes of zebrafish, in combination with genetic modifications, are continuing to transform our understanding of epilepsy and help identify personalized therapeutics for specific patient cohorts. © 2016 Elsevier B.V. All rights reserved.

In search of antiepileptogenic treatments for post-traumatic epilepsy.

PubMed

Saletti, Patricia G; Ali, Idrish; Casillas-Espinosa, Pablo M; Semple, Bridgette D; Lisgaras, Christos; Moshé, Solomon L; Galanopoulou, Aristea S

2018-06-21

Post-traumatic epilepsy (PTE) occurs in 20% of individuals with acquired epilepsy, and can impact significantly the quality of life due to the seizures and other functional or cognitive and behavioral outcomes of the traumatic brain injury (TBI) and PTE. There is no available antiepileptogenic or disease modifying treatment for PTE. Animal models of TBI and PTE have been developed, offering useful insights on the value of inflammatory, neurodegenerative pathways, hemorrhages and iron accumulation, calcium channels and other target pathways that could be used for treatment development. Most of the existing preclinical studies test efficacy towards pathologies of functional recovery after TBI, while a few studies are emerging testing the effects towards induced or spontaneous seizures. Here we review the existing preclinical trials testing new candidate treatments for TBI sequelae and PTE, and discuss future directions for efforts aiming at developing antiepileptogenic and disease-modifying treatments. Copyright © 2018. Published by Elsevier Inc.

The Impact of Sex and Language Dominance on Material-Specific Memory Before and After Left Temporal Lobe Surgery

ERIC Educational Resources Information Center

Helmstaedter, C.; Brosch, T.; Kurthen, M.; Elger, C. E.

2004-01-01

Recent findings raised evidence that in early-onset left temporal lobe epilepsy, women show greater functional plasticity for verbal memory than men. In particular, women with lesion- or epilepsy-driven atypical language dominance show an advantage over men. The question asked in this study was whether there is evidence of sex- and language…

Language dominance in neurologically normal and epilepsy subjects: a functional MRI study.

PubMed

Springer, J A; Binder, J R; Hammeke, T A; Swanson, S J; Frost, J A; Bellgowan, P S; Brewer, C C; Perry, H M; Morris, G L; Mueller, W M

1999-11-01

Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness.